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Individuals with type A blood have a 16% higher risk for early onset stroke (EOS) than those with other blood types, new research shows.

Conversely, results from a meta-analysis of nearly 17,000 cases of ischemic stroke in adults younger than 60 years showed that having type O blood reduced the risk for EOS by 12%.

In addition, the associations with risk were significantly stronger in EOS than in those with late-onset stroke (LOS), pointing to a stronger role for prothrombotic factors in younger patients, the researchers noted.

“What this is telling us is that maybe what makes you susceptible to stroke as a young adult is the blood type, which is really giving you a much higher risk of clotting and stroke compared to later onset,” coinvestigator Braxton Mitchell, PhD, professor of medicine and epidemiology and public health at the University of Maryland, Baltimore, said in an interview.

The findings were published online in Neurology.
 

Strong association

The genome-wide association study (GWAS) was done as part of the Genetics of Early Onset Ischemic Stroke Consortium, a collaboration of 48 different studies across North America, Europe, Japan, Pakistan, and Australia. It assessed early onset ischemic stroke in patients aged 18-59 years.

Researchers included data from 16,927 patients with stroke. Of these, 5,825 had a stroke before age 60, defined as early onset. GWAS results were also examined for nearly 600,000 individuals without stroke.

Results showed two genetic variants tied to blood types A and O emerged as highly associated with risk for early stroke.

Researchers found that the protective effects of type O were significantly stronger with EOS vs. LOS (odds ratio [OR], 0.88 vs. 0.96, respectively; P = .001). Likewise, the association between type A and increased EOS risk was significantly stronger than that found in LOS (OR, 1.16 vs. 1.05; P = .005).

Using polygenic risk scores, the investigators also found that the greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared with LOS (P = .008).

Previous studies have shown a link between stroke risk and variants of the ABO gene, which determines blood type. The new analysis suggests that type A and O gene variants represent nearly all of those genetically linked with early stroke, the researchers noted.

While the findings point to blood type as a risk factor for stroke in younger people, Dr. Mitchell cautions that “at the moment, blood group does not have implications for preventive care.”

“The risk of stroke due to blood type is smaller than other risk factors that we know about, like smoking and hypertension,” he said. “I would be much more worried about these other risk factors, especially because those may be modifiable.”

He noted the next step in the study is to assess how blood type interacts with other known risk factors to raise stroke risk.

“There may be a subset of people where, if you have blood type A and you have some of these other risk factors, it’s possible that you may be at particularly high risk,” Dr. Mitchell said.
 

More research needed on younger patients

In an accompanying editorial, Jennifer Juhl Majersik, MD, associate professor of neurology at the University of Utah, Salt Lake City, and Paul Lacaze, PhD, associate professor and head of the public health genomics program at Monash University, Australia, noted that the study fills a gap in stroke research, which often focuses mostly on older individuals.

“In approximately 40% of people with EOS, the stroke is cryptogenic, and there is scant data from clinical trials to guide the selection of preventative strategies in this population, as people with EOS are often excluded from trials,” Dr. Majersik and Dr. Lacaze wrote.

“This work has deepened our understanding of EOS pathophysiology,” they added.

The editorialists noted that future research can build on the results from this analysis, “with the goal of a more precise understanding of stroke pathophysiology, leading to targeted preventative treatments for EOS and a reduction in disability in patients’ most productive years.”

Dr. Mitchell echoed the call for greater inclusion of young patients with stroke in clinical trials.

“As we’re learning, stroke in older folks isn’t the same as stroke in younger people,” he said. “There are many shared risk factors but there are also some that are different ... so there really is a need to include younger people.”

A version of this article first appeared on Medscape.com.

Individuals with type A blood have a 16% higher risk for early onset stroke (EOS) than those with other blood types, new research shows.

Conversely, results from a meta-analysis of nearly 17,000 cases of ischemic stroke in adults younger than 60 years showed that having type O blood reduced the risk for EOS by 12%.

In addition, the associations with risk were significantly stronger in EOS than in those with late-onset stroke (LOS), pointing to a stronger role for prothrombotic factors in younger patients, the researchers noted.

“What this is telling us is that maybe what makes you susceptible to stroke as a young adult is the blood type, which is really giving you a much higher risk of clotting and stroke compared to later onset,” coinvestigator Braxton Mitchell, PhD, professor of medicine and epidemiology and public health at the University of Maryland, Baltimore, said in an interview.

The findings were published online in Neurology.
 

Strong association

The genome-wide association study (GWAS) was done as part of the Genetics of Early Onset Ischemic Stroke Consortium, a collaboration of 48 different studies across North America, Europe, Japan, Pakistan, and Australia. It assessed early onset ischemic stroke in patients aged 18-59 years.

Researchers included data from 16,927 patients with stroke. Of these, 5,825 had a stroke before age 60, defined as early onset. GWAS results were also examined for nearly 600,000 individuals without stroke.

Results showed two genetic variants tied to blood types A and O emerged as highly associated with risk for early stroke.

Researchers found that the protective effects of type O were significantly stronger with EOS vs. LOS (odds ratio [OR], 0.88 vs. 0.96, respectively; P = .001). Likewise, the association between type A and increased EOS risk was significantly stronger than that found in LOS (OR, 1.16 vs. 1.05; P = .005).

Using polygenic risk scores, the investigators also found that the greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared with LOS (P = .008).

Previous studies have shown a link between stroke risk and variants of the ABO gene, which determines blood type. The new analysis suggests that type A and O gene variants represent nearly all of those genetically linked with early stroke, the researchers noted.

While the findings point to blood type as a risk factor for stroke in younger people, Dr. Mitchell cautions that “at the moment, blood group does not have implications for preventive care.”

“The risk of stroke due to blood type is smaller than other risk factors that we know about, like smoking and hypertension,” he said. “I would be much more worried about these other risk factors, especially because those may be modifiable.”

He noted the next step in the study is to assess how blood type interacts with other known risk factors to raise stroke risk.

“There may be a subset of people where, if you have blood type A and you have some of these other risk factors, it’s possible that you may be at particularly high risk,” Dr. Mitchell said.
 

More research needed on younger patients

In an accompanying editorial, Jennifer Juhl Majersik, MD, associate professor of neurology at the University of Utah, Salt Lake City, and Paul Lacaze, PhD, associate professor and head of the public health genomics program at Monash University, Australia, noted that the study fills a gap in stroke research, which often focuses mostly on older individuals.

“In approximately 40% of people with EOS, the stroke is cryptogenic, and there is scant data from clinical trials to guide the selection of preventative strategies in this population, as people with EOS are often excluded from trials,” Dr. Majersik and Dr. Lacaze wrote.

“This work has deepened our understanding of EOS pathophysiology,” they added.

The editorialists noted that future research can build on the results from this analysis, “with the goal of a more precise understanding of stroke pathophysiology, leading to targeted preventative treatments for EOS and a reduction in disability in patients’ most productive years.”

Dr. Mitchell echoed the call for greater inclusion of young patients with stroke in clinical trials.

“As we’re learning, stroke in older folks isn’t the same as stroke in younger people,” he said. “There are many shared risk factors but there are also some that are different ... so there really is a need to include younger people.”

A version of this article first appeared on Medscape.com.

Individuals with type A blood have a 16% higher risk for early onset stroke (EOS) than those with other blood types, new research shows.

Conversely, results from a meta-analysis of nearly 17,000 cases of ischemic stroke in adults younger than 60 years showed that having type O blood reduced the risk for EOS by 12%.

In addition, the associations with risk were significantly stronger in EOS than in those with late-onset stroke (LOS), pointing to a stronger role for prothrombotic factors in younger patients, the researchers noted.

“What this is telling us is that maybe what makes you susceptible to stroke as a young adult is the blood type, which is really giving you a much higher risk of clotting and stroke compared to later onset,” coinvestigator Braxton Mitchell, PhD, professor of medicine and epidemiology and public health at the University of Maryland, Baltimore, said in an interview.

The findings were published online in Neurology.
 

Strong association

The genome-wide association study (GWAS) was done as part of the Genetics of Early Onset Ischemic Stroke Consortium, a collaboration of 48 different studies across North America, Europe, Japan, Pakistan, and Australia. It assessed early onset ischemic stroke in patients aged 18-59 years.

Researchers included data from 16,927 patients with stroke. Of these, 5,825 had a stroke before age 60, defined as early onset. GWAS results were also examined for nearly 600,000 individuals without stroke.

Results showed two genetic variants tied to blood types A and O emerged as highly associated with risk for early stroke.

Researchers found that the protective effects of type O were significantly stronger with EOS vs. LOS (odds ratio [OR], 0.88 vs. 0.96, respectively; P = .001). Likewise, the association between type A and increased EOS risk was significantly stronger than that found in LOS (OR, 1.16 vs. 1.05; P = .005).

Using polygenic risk scores, the investigators also found that the greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared with LOS (P = .008).

Previous studies have shown a link between stroke risk and variants of the ABO gene, which determines blood type. The new analysis suggests that type A and O gene variants represent nearly all of those genetically linked with early stroke, the researchers noted.

While the findings point to blood type as a risk factor for stroke in younger people, Dr. Mitchell cautions that “at the moment, blood group does not have implications for preventive care.”

“The risk of stroke due to blood type is smaller than other risk factors that we know about, like smoking and hypertension,” he said. “I would be much more worried about these other risk factors, especially because those may be modifiable.”

He noted the next step in the study is to assess how blood type interacts with other known risk factors to raise stroke risk.

“There may be a subset of people where, if you have blood type A and you have some of these other risk factors, it’s possible that you may be at particularly high risk,” Dr. Mitchell said.
 

More research needed on younger patients

In an accompanying editorial, Jennifer Juhl Majersik, MD, associate professor of neurology at the University of Utah, Salt Lake City, and Paul Lacaze, PhD, associate professor and head of the public health genomics program at Monash University, Australia, noted that the study fills a gap in stroke research, which often focuses mostly on older individuals.

“In approximately 40% of people with EOS, the stroke is cryptogenic, and there is scant data from clinical trials to guide the selection of preventative strategies in this population, as people with EOS are often excluded from trials,” Dr. Majersik and Dr. Lacaze wrote.

“This work has deepened our understanding of EOS pathophysiology,” they added.

The editorialists noted that future research can build on the results from this analysis, “with the goal of a more precise understanding of stroke pathophysiology, leading to targeted preventative treatments for EOS and a reduction in disability in patients’ most productive years.”

Dr. Mitchell echoed the call for greater inclusion of young patients with stroke in clinical trials.

“As we’re learning, stroke in older folks isn’t the same as stroke in younger people,” he said. “There are many shared risk factors but there are also some that are different ... so there really is a need to include younger people.”

A version of this article first appeared on Medscape.com.

Patients with aortic stenosis (AS) of sufficient severity to portend a high likelihood of early mortality can be detected by an artificial intelligence (AI) algorithm employed in the reading of routine echocardiograms, according to a study that tested this tool in a large national database.

The artificial intelligence decision support algorithm (AI-DSA) “automatically identified patients with moderate to severe forms of AS associated with poor survival if left untreated,” reported Geoffrey A. Strange, PhD, professor, faculty of medicine, University of Sydney.

The AS-DSA was trained not only to recognize adverse changes in aortic valve morphology but to evaluate indices of impaired valve function, including those related to the left ventricle, the left atrium, and pulmonary circulation, according to Dr. Strange.
 

AI algorithm based on more than 800K echos

The training was performed on more than 1 million echocardiograms obtained from 630,000 patients in the National Echo Database (NEDA) of Australia. The testing phase of the study, called AI ENHANCED AS, was carried out on 179,054 individuals from the same database.

In the testing phase, mortality was compared for those determined by AI to have a low probability of clinically significant AS, a moderate to severe AS, or severe AS.

In the nearly 200,000 patients evaluated from the database, the AI-DSA classified 2.5% as having moderate to severe AS and 1.4% as having severe AS. Relative to a 22.9% mortality at 5 years in the low-risk reference group, the rates were 56.2% and 67.9% in the moderate to severe and severe groups, respectively.

When expressed as odds ratios, the mortality risk for the moderate to severe group (OR, 1.8; P < .001) and severe group (HR, 2.8; P < .001) “were about two to three times higher than the low probability group,” Dr. Strange reported.
 

All severe AS by guidelines AI identified

The algorithm picked up all patients identified with severe AS in current guidelines, but it also identified patients “missed by conventional definitions,” Dr. Strange reported.

The findings support the idea “that the AI algorithm could be used in clinical practice to alert physicians to patients who should undergo further investigations to determine if they qualify for aortic valve replacement,” he added.

Missing clinically significant AS is an important clinical problem, according to Catherine Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle.

“We focus on the patients who already have a diagnosis of AS,” she said. “The bigger issue is identification of patients with unknown AS.”

She praised the effort to develop AI that improves detection of AS, but also said that there are immediate steps to improve detection of AS even in the absence of AI support. In addition to the variability in the quality of how echocardiograms are read, she said a substantial proportion of echo reports omit key variables.

“We do not need AI to measure the aortic valve. It is simple to do in clinical practice,” she said. However, studies have repeatedly shown that values, such as maximal aortic jet velocity (Vmax) and the pressure difference across the ventricular septal defect (delta P), are not included. When AS is present, some reports do not include a characterization of the severity.

The AI-DSA described by Dr. Strange takes into account all of these variables along with additional information, but he acknowledged that it does have limitations. For example, the presence of cardiac impairments other than AS will not be included, and these can be relevant to prognostication and treatment.
 

AI does not eliminate clinical decision-making

“This algorithm is definitely not meant to take away from clinical decision-making,” Dr. Strange said, but he argued that there is an unmet need to do better in the detection of AS. He presented data to show that “even moderate AS is not benign” in regard to 5-year outcomes, and he believes AI-DSA can allow clinicians to detect significant disease earlier and intervene in a timelier manner.

“It is time to revisit the practice of watchful waiting and consider more proactive attempts to identify those at risk,” he said.

The next step is to determine if AI-DSA makes a clinical difference,

“Research is now needed to determine if aortic valve replacement in patients identified as being at risk by AI-DSA improves survival and quality of life, particularly in those who do not meet current guideline definitions of clinically significant disease,” he said.

Dr. Strange reports financial relationships with Edwards, Medtronic, Novartis, Pfizer, and Echo IQ, which is developing the artificial algorithm studied in this trial. Dr. Otto reports no relevant conflicts of interest.

Patients with aortic stenosis (AS) of sufficient severity to portend a high likelihood of early mortality can be detected by an artificial intelligence (AI) algorithm employed in the reading of routine echocardiograms, according to a study that tested this tool in a large national database.

The artificial intelligence decision support algorithm (AI-DSA) “automatically identified patients with moderate to severe forms of AS associated with poor survival if left untreated,” reported Geoffrey A. Strange, PhD, professor, faculty of medicine, University of Sydney.

The AS-DSA was trained not only to recognize adverse changes in aortic valve morphology but to evaluate indices of impaired valve function, including those related to the left ventricle, the left atrium, and pulmonary circulation, according to Dr. Strange.
 

AI algorithm based on more than 800K echos

The training was performed on more than 1 million echocardiograms obtained from 630,000 patients in the National Echo Database (NEDA) of Australia. The testing phase of the study, called AI ENHANCED AS, was carried out on 179,054 individuals from the same database.

In the testing phase, mortality was compared for those determined by AI to have a low probability of clinically significant AS, a moderate to severe AS, or severe AS.

In the nearly 200,000 patients evaluated from the database, the AI-DSA classified 2.5% as having moderate to severe AS and 1.4% as having severe AS. Relative to a 22.9% mortality at 5 years in the low-risk reference group, the rates were 56.2% and 67.9% in the moderate to severe and severe groups, respectively.

When expressed as odds ratios, the mortality risk for the moderate to severe group (OR, 1.8; P < .001) and severe group (HR, 2.8; P < .001) “were about two to three times higher than the low probability group,” Dr. Strange reported.
 

All severe AS by guidelines AI identified

The algorithm picked up all patients identified with severe AS in current guidelines, but it also identified patients “missed by conventional definitions,” Dr. Strange reported.

The findings support the idea “that the AI algorithm could be used in clinical practice to alert physicians to patients who should undergo further investigations to determine if they qualify for aortic valve replacement,” he added.

Missing clinically significant AS is an important clinical problem, according to Catherine Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle.

“We focus on the patients who already have a diagnosis of AS,” she said. “The bigger issue is identification of patients with unknown AS.”

She praised the effort to develop AI that improves detection of AS, but also said that there are immediate steps to improve detection of AS even in the absence of AI support. In addition to the variability in the quality of how echocardiograms are read, she said a substantial proportion of echo reports omit key variables.

“We do not need AI to measure the aortic valve. It is simple to do in clinical practice,” she said. However, studies have repeatedly shown that values, such as maximal aortic jet velocity (Vmax) and the pressure difference across the ventricular septal defect (delta P), are not included. When AS is present, some reports do not include a characterization of the severity.

The AI-DSA described by Dr. Strange takes into account all of these variables along with additional information, but he acknowledged that it does have limitations. For example, the presence of cardiac impairments other than AS will not be included, and these can be relevant to prognostication and treatment.
 

AI does not eliminate clinical decision-making

“This algorithm is definitely not meant to take away from clinical decision-making,” Dr. Strange said, but he argued that there is an unmet need to do better in the detection of AS. He presented data to show that “even moderate AS is not benign” in regard to 5-year outcomes, and he believes AI-DSA can allow clinicians to detect significant disease earlier and intervene in a timelier manner.

“It is time to revisit the practice of watchful waiting and consider more proactive attempts to identify those at risk,” he said.

The next step is to determine if AI-DSA makes a clinical difference,

“Research is now needed to determine if aortic valve replacement in patients identified as being at risk by AI-DSA improves survival and quality of life, particularly in those who do not meet current guideline definitions of clinically significant disease,” he said.

Dr. Strange reports financial relationships with Edwards, Medtronic, Novartis, Pfizer, and Echo IQ, which is developing the artificial algorithm studied in this trial. Dr. Otto reports no relevant conflicts of interest.

Patients with aortic stenosis (AS) of sufficient severity to portend a high likelihood of early mortality can be detected by an artificial intelligence (AI) algorithm employed in the reading of routine echocardiograms, according to a study that tested this tool in a large national database.

The artificial intelligence decision support algorithm (AI-DSA) “automatically identified patients with moderate to severe forms of AS associated with poor survival if left untreated,” reported Geoffrey A. Strange, PhD, professor, faculty of medicine, University of Sydney.

The AS-DSA was trained not only to recognize adverse changes in aortic valve morphology but to evaluate indices of impaired valve function, including those related to the left ventricle, the left atrium, and pulmonary circulation, according to Dr. Strange.
 

AI algorithm based on more than 800K echos

The training was performed on more than 1 million echocardiograms obtained from 630,000 patients in the National Echo Database (NEDA) of Australia. The testing phase of the study, called AI ENHANCED AS, was carried out on 179,054 individuals from the same database.

In the testing phase, mortality was compared for those determined by AI to have a low probability of clinically significant AS, a moderate to severe AS, or severe AS.

In the nearly 200,000 patients evaluated from the database, the AI-DSA classified 2.5% as having moderate to severe AS and 1.4% as having severe AS. Relative to a 22.9% mortality at 5 years in the low-risk reference group, the rates were 56.2% and 67.9% in the moderate to severe and severe groups, respectively.

When expressed as odds ratios, the mortality risk for the moderate to severe group (OR, 1.8; P < .001) and severe group (HR, 2.8; P < .001) “were about two to three times higher than the low probability group,” Dr. Strange reported.
 

All severe AS by guidelines AI identified

The algorithm picked up all patients identified with severe AS in current guidelines, but it also identified patients “missed by conventional definitions,” Dr. Strange reported.

The findings support the idea “that the AI algorithm could be used in clinical practice to alert physicians to patients who should undergo further investigations to determine if they qualify for aortic valve replacement,” he added.

Missing clinically significant AS is an important clinical problem, according to Catherine Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle.

“We focus on the patients who already have a diagnosis of AS,” she said. “The bigger issue is identification of patients with unknown AS.”

She praised the effort to develop AI that improves detection of AS, but also said that there are immediate steps to improve detection of AS even in the absence of AI support. In addition to the variability in the quality of how echocardiograms are read, she said a substantial proportion of echo reports omit key variables.

“We do not need AI to measure the aortic valve. It is simple to do in clinical practice,” she said. However, studies have repeatedly shown that values, such as maximal aortic jet velocity (Vmax) and the pressure difference across the ventricular septal defect (delta P), are not included. When AS is present, some reports do not include a characterization of the severity.

The AI-DSA described by Dr. Strange takes into account all of these variables along with additional information, but he acknowledged that it does have limitations. For example, the presence of cardiac impairments other than AS will not be included, and these can be relevant to prognostication and treatment.
 

AI does not eliminate clinical decision-making

“This algorithm is definitely not meant to take away from clinical decision-making,” Dr. Strange said, but he argued that there is an unmet need to do better in the detection of AS. He presented data to show that “even moderate AS is not benign” in regard to 5-year outcomes, and he believes AI-DSA can allow clinicians to detect significant disease earlier and intervene in a timelier manner.

“It is time to revisit the practice of watchful waiting and consider more proactive attempts to identify those at risk,” he said.

The next step is to determine if AI-DSA makes a clinical difference,

“Research is now needed to determine if aortic valve replacement in patients identified as being at risk by AI-DSA improves survival and quality of life, particularly in those who do not meet current guideline definitions of clinically significant disease,” he said.

Dr. Strange reports financial relationships with Edwards, Medtronic, Novartis, Pfizer, and Echo IQ, which is developing the artificial algorithm studied in this trial. Dr. Otto reports no relevant conflicts of interest.

BARCELONA – Cardiovascular disease risk factors, as well as established disease, in patients undergoing cancer therapy can be safely managed to minimize cancer therapy–related cardiovascular toxicity (CVR-CVT), conclude the first cardio-oncology guidelines from the European Society of Cardiology.

The guidelines were presented at the annual congress of the European Society of Cardiology and published simultaneously in the European Heart Journal.

Guideline cochair Alexander R. Lyon, MD, PhD, told this news organization that the aim of the guideline was to “personalize the decision-making of a patient with cancer who has cardiovascular disease or is at risk of developing it from their treatment ... because it’s not one size fits all.”

A “very strong theme throughout the guideline is risk assessment, and the fact that that risk is dynamic, it can change ... because how you manage someone who’s at high risk is going to be different” than managing someone who is at moderate or low risk, he said.

“We’re doing a lot of surveillance because one of the big advantages of cardio-oncology is we know when someone is about to get treated,” Dr. Lyon, from the National Heart and Lung Institute, Imperial College London, and Cardio-Oncology Service, Royal Brompton Hospital, London, said.

“You don’t know in nature when someone’s going to have an acute myocardial infarction or acute viral myocarditis, but we do know when they’re coming into an oncology clinic to get an infusion of chemotherapy or tablets,” he noted.

The guidelines offer recommendations so that patients can “have their treatment safely and minimize interruptions.”

“We know these cancer therapies work; we’re here to get the best of both worlds” by minimizing cardiotoxicity, Dr. Lyon said.
 

Steady decline in cancer-related mortality

The guidelines note that since the 1990s there has been a “steady decline in cancer-related mortality, mirrored by a steady increase in cancer survival,” and the result is that “treatment-related side effects have gained more significance.”

Dr. Lyon said that between 2011 and 2021, there was a fivefold increase in the number of new referrals of cancer patients with cardiological consequences to his institution.

He said that one of main drivers is modifiable factors, such as smoking, obesity, and inactivity, which increase the risk for both cancer and cardiovascular disease.

“Allied to that, there’s been an improvement in treating cardiovascular diseases in people in their 40s, 50s, and 60s, so they’re surviving their heart failure, myocardial infarction, atrial fibrillation to develop cancers in later life.”

Combined with the aging population, the result is that “not only are many more people being diagnosed with cancer, because they’re living longer, but they have all these pre-existing heart risk factors, whether as confirmed disease or just the risk factors associated with that,” he said.

Another aspect is that many of the newer, targeted cancer therapies confer a cardiovascular risk.

Dr. Lyon said that the “most famous one” is trastuzumab, a monoclonal antibody that is used to treat HER2-positive breast cancer but that also causes left ventricular impairment “in about 15%-20% of the women taking it and can cause severe heart failure if it is missed.”

That, he continued, was the “forerunner of designer, targeted therapies,” and the subsequent “explosion” in the availability of modern cancer therapies has included many that confer cardiac issues.

The final reason for the greater interest in cardio-oncology, Dr. Lyon added, is the increasing awareness in oncology and hematology teams of the potential for cardiac problems among their patients.

“We have been reaching out to our oncology and hematology colleagues over the last 5-10 years to explain we’re here to help. We’re not here to stop their treatments, we’re here to support them.”

Presenting the guidelines, cochair Teresa López-Fernández, MD, cardiology department, La Paz University Hospital, IdiPAZ Research Institute, Madrid, said that the “spectrum of CVR-CVT presentations” includes arterial hypertension, cardiac arrhythmias, coronary artery disease, heart failure, and myocarditis.

She explained that cytotoxic cancer therapies are associated with an increased risk for cardiac toxicity that is most acute during the treatment phase but is not entirely diminished once it is over, then typically accumulates during long-term follow-up.

Crucially, the impact of cancer therapy on cardiovascular risk is dependent on several factors, such as patient age, cancer history, pre-existing cardiovascular risk factors or cardiovascular disease, and previous cardiotoxic cancer therapy.

There are nevertheless a number of potential strategies to reduce the risk for cardiac toxicity, including primary and secondary prevention prior to the start of cancer therapy and early CVR-CVT management during treatment, as well as cardiovascular risk assessment in the first year after treatment completion and cancer-survivorship programs.

To those ends, Dr. López-Fernández said the guidelines incorporate 272 new recommendations that cover the entire cardio-oncology care pathway, beginning with cardiovascular risk stratification before anticancer therapy.

They offer a risk-assessment checklist and make a series of recommendations for patients to be treated with potentially cardiotoxic drugs, such as anthracyclines, as well as recommendations on cardiac imaging.

The guidelines provide a range of recommendations for primary and secondary cancer therapy–related cardiovascular toxicity prevention, including minimization of the use of cardiotoxic drugs and the use of angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta blockers, and statins for primary prevention.

They establish CVR-CVT monitoring protocols across the gamut of cancer therapies, from HER-targeted therapies, through immune checkpoint inhibitors, Bruton tyrosine kinase, CDK4/6, EGFR, VEGF, and ALK inhibitors, and androgen-deprivation and endocrine therapies, to the more novel CAR-T-cell therapies.

A section on radiotherapy-induced cardiovascular toxicity has its own protocol for the establishment of an individual’s mean heart dose of radiation or the amount of radiation exposure to the heart during treatment.

Next, Dr. Lyon looked at recommendations for the management of cardiovascular disease and cancer therapy–related cardiovascular toxicity in patients receiving anticancer treatment.

He underlined that treatment decisions should consider the cancer and cardiovascular symptom burden, the cancer prognosis, the requirements for cancer treatment, including alternative options, drug-drug interactions, and patient preferences.

Dr. Lyon highlighted the algorithms designed to aid the management of cardiac dysfunction related to anthracycline chemotherapy, HER2-targeted therapy, and immune checkpoint inhibitors, as well as QTc-prolonging anticancer drugs.

In the first 12 months after the completions of therapy, there are a number of risk factors for future cardiovascular disease, he continued.

These include high and very high baseline cardiovascular toxicity risk, anticancer treatments known to have a high risk for long-term cardiovascular complications, such as doxorubicin and radiotherapy, and moderate or severe CTR-CVT during anticancer treatment.

Over the long term, the guidelines recommend that surveillance in asymptomatic cancer survivors range from an annual cardiovascular risk assessment in low-risk patients to patient education and cardiovascular risk factor optimization, alongside regular transthoracic echocardiography in high-risk groups.

Finally, Dr. Lyon said the guidelines turn their attention to special populations, such as patients with cardiac masses and tumors, those with carcinoid heart disease, pregnant women receiving cancer therapy, as well as those with cardiac implantable electronic devices undergoing radiotherapy.

The guidelines were developed by the task force on cardio-oncology of the ESC, in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio-Oncology Society. Dr. Lyon declares relationships with Akcea, Takeda Pharmaceuticals, Pfizer, GlaxoSmithKline, AstraZeneca, Novartis, Ferring Pharmaceuticals, Heartfelt Technologies, Brainstorm, and Myocardial Solutions. Dr. López-Fernández declares relationships with Daiichi Sankyo, Almirall Spain, Janssen-Cilag, Bayer, Roche, Philips, and Incyte.

A version of this article first appeared on Medscape.com.

BARCELONA – Cardiovascular disease risk factors, as well as established disease, in patients undergoing cancer therapy can be safely managed to minimize cancer therapy–related cardiovascular toxicity (CVR-CVT), conclude the first cardio-oncology guidelines from the European Society of Cardiology.

The guidelines were presented at the annual congress of the European Society of Cardiology and published simultaneously in the European Heart Journal.

Guideline cochair Alexander R. Lyon, MD, PhD, told this news organization that the aim of the guideline was to “personalize the decision-making of a patient with cancer who has cardiovascular disease or is at risk of developing it from their treatment ... because it’s not one size fits all.”

A “very strong theme throughout the guideline is risk assessment, and the fact that that risk is dynamic, it can change ... because how you manage someone who’s at high risk is going to be different” than managing someone who is at moderate or low risk, he said.

“We’re doing a lot of surveillance because one of the big advantages of cardio-oncology is we know when someone is about to get treated,” Dr. Lyon, from the National Heart and Lung Institute, Imperial College London, and Cardio-Oncology Service, Royal Brompton Hospital, London, said.

“You don’t know in nature when someone’s going to have an acute myocardial infarction or acute viral myocarditis, but we do know when they’re coming into an oncology clinic to get an infusion of chemotherapy or tablets,” he noted.

The guidelines offer recommendations so that patients can “have their treatment safely and minimize interruptions.”

“We know these cancer therapies work; we’re here to get the best of both worlds” by minimizing cardiotoxicity, Dr. Lyon said.
 

Steady decline in cancer-related mortality

The guidelines note that since the 1990s there has been a “steady decline in cancer-related mortality, mirrored by a steady increase in cancer survival,” and the result is that “treatment-related side effects have gained more significance.”

Dr. Lyon said that between 2011 and 2021, there was a fivefold increase in the number of new referrals of cancer patients with cardiological consequences to his institution.

He said that one of main drivers is modifiable factors, such as smoking, obesity, and inactivity, which increase the risk for both cancer and cardiovascular disease.

“Allied to that, there’s been an improvement in treating cardiovascular diseases in people in their 40s, 50s, and 60s, so they’re surviving their heart failure, myocardial infarction, atrial fibrillation to develop cancers in later life.”

Combined with the aging population, the result is that “not only are many more people being diagnosed with cancer, because they’re living longer, but they have all these pre-existing heart risk factors, whether as confirmed disease or just the risk factors associated with that,” he said.

Another aspect is that many of the newer, targeted cancer therapies confer a cardiovascular risk.

Dr. Lyon said that the “most famous one” is trastuzumab, a monoclonal antibody that is used to treat HER2-positive breast cancer but that also causes left ventricular impairment “in about 15%-20% of the women taking it and can cause severe heart failure if it is missed.”

That, he continued, was the “forerunner of designer, targeted therapies,” and the subsequent “explosion” in the availability of modern cancer therapies has included many that confer cardiac issues.

The final reason for the greater interest in cardio-oncology, Dr. Lyon added, is the increasing awareness in oncology and hematology teams of the potential for cardiac problems among their patients.

“We have been reaching out to our oncology and hematology colleagues over the last 5-10 years to explain we’re here to help. We’re not here to stop their treatments, we’re here to support them.”

Presenting the guidelines, cochair Teresa López-Fernández, MD, cardiology department, La Paz University Hospital, IdiPAZ Research Institute, Madrid, said that the “spectrum of CVR-CVT presentations” includes arterial hypertension, cardiac arrhythmias, coronary artery disease, heart failure, and myocarditis.

She explained that cytotoxic cancer therapies are associated with an increased risk for cardiac toxicity that is most acute during the treatment phase but is not entirely diminished once it is over, then typically accumulates during long-term follow-up.

Crucially, the impact of cancer therapy on cardiovascular risk is dependent on several factors, such as patient age, cancer history, pre-existing cardiovascular risk factors or cardiovascular disease, and previous cardiotoxic cancer therapy.

There are nevertheless a number of potential strategies to reduce the risk for cardiac toxicity, including primary and secondary prevention prior to the start of cancer therapy and early CVR-CVT management during treatment, as well as cardiovascular risk assessment in the first year after treatment completion and cancer-survivorship programs.

To those ends, Dr. López-Fernández said the guidelines incorporate 272 new recommendations that cover the entire cardio-oncology care pathway, beginning with cardiovascular risk stratification before anticancer therapy.

They offer a risk-assessment checklist and make a series of recommendations for patients to be treated with potentially cardiotoxic drugs, such as anthracyclines, as well as recommendations on cardiac imaging.

The guidelines provide a range of recommendations for primary and secondary cancer therapy–related cardiovascular toxicity prevention, including minimization of the use of cardiotoxic drugs and the use of angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta blockers, and statins for primary prevention.

They establish CVR-CVT monitoring protocols across the gamut of cancer therapies, from HER-targeted therapies, through immune checkpoint inhibitors, Bruton tyrosine kinase, CDK4/6, EGFR, VEGF, and ALK inhibitors, and androgen-deprivation and endocrine therapies, to the more novel CAR-T-cell therapies.

A section on radiotherapy-induced cardiovascular toxicity has its own protocol for the establishment of an individual’s mean heart dose of radiation or the amount of radiation exposure to the heart during treatment.

Next, Dr. Lyon looked at recommendations for the management of cardiovascular disease and cancer therapy–related cardiovascular toxicity in patients receiving anticancer treatment.

He underlined that treatment decisions should consider the cancer and cardiovascular symptom burden, the cancer prognosis, the requirements for cancer treatment, including alternative options, drug-drug interactions, and patient preferences.

Dr. Lyon highlighted the algorithms designed to aid the management of cardiac dysfunction related to anthracycline chemotherapy, HER2-targeted therapy, and immune checkpoint inhibitors, as well as QTc-prolonging anticancer drugs.

In the first 12 months after the completions of therapy, there are a number of risk factors for future cardiovascular disease, he continued.

These include high and very high baseline cardiovascular toxicity risk, anticancer treatments known to have a high risk for long-term cardiovascular complications, such as doxorubicin and radiotherapy, and moderate or severe CTR-CVT during anticancer treatment.

Over the long term, the guidelines recommend that surveillance in asymptomatic cancer survivors range from an annual cardiovascular risk assessment in low-risk patients to patient education and cardiovascular risk factor optimization, alongside regular transthoracic echocardiography in high-risk groups.

Finally, Dr. Lyon said the guidelines turn their attention to special populations, such as patients with cardiac masses and tumors, those with carcinoid heart disease, pregnant women receiving cancer therapy, as well as those with cardiac implantable electronic devices undergoing radiotherapy.

The guidelines were developed by the task force on cardio-oncology of the ESC, in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio-Oncology Society. Dr. Lyon declares relationships with Akcea, Takeda Pharmaceuticals, Pfizer, GlaxoSmithKline, AstraZeneca, Novartis, Ferring Pharmaceuticals, Heartfelt Technologies, Brainstorm, and Myocardial Solutions. Dr. López-Fernández declares relationships with Daiichi Sankyo, Almirall Spain, Janssen-Cilag, Bayer, Roche, Philips, and Incyte.

A version of this article first appeared on Medscape.com.

BARCELONA – Cardiovascular disease risk factors, as well as established disease, in patients undergoing cancer therapy can be safely managed to minimize cancer therapy–related cardiovascular toxicity (CVR-CVT), conclude the first cardio-oncology guidelines from the European Society of Cardiology.

The guidelines were presented at the annual congress of the European Society of Cardiology and published simultaneously in the European Heart Journal.

Guideline cochair Alexander R. Lyon, MD, PhD, told this news organization that the aim of the guideline was to “personalize the decision-making of a patient with cancer who has cardiovascular disease or is at risk of developing it from their treatment ... because it’s not one size fits all.”

A “very strong theme throughout the guideline is risk assessment, and the fact that that risk is dynamic, it can change ... because how you manage someone who’s at high risk is going to be different” than managing someone who is at moderate or low risk, he said.

“We’re doing a lot of surveillance because one of the big advantages of cardio-oncology is we know when someone is about to get treated,” Dr. Lyon, from the National Heart and Lung Institute, Imperial College London, and Cardio-Oncology Service, Royal Brompton Hospital, London, said.

“You don’t know in nature when someone’s going to have an acute myocardial infarction or acute viral myocarditis, but we do know when they’re coming into an oncology clinic to get an infusion of chemotherapy or tablets,” he noted.

The guidelines offer recommendations so that patients can “have their treatment safely and minimize interruptions.”

“We know these cancer therapies work; we’re here to get the best of both worlds” by minimizing cardiotoxicity, Dr. Lyon said.
 

Steady decline in cancer-related mortality

The guidelines note that since the 1990s there has been a “steady decline in cancer-related mortality, mirrored by a steady increase in cancer survival,” and the result is that “treatment-related side effects have gained more significance.”

Dr. Lyon said that between 2011 and 2021, there was a fivefold increase in the number of new referrals of cancer patients with cardiological consequences to his institution.

He said that one of main drivers is modifiable factors, such as smoking, obesity, and inactivity, which increase the risk for both cancer and cardiovascular disease.

“Allied to that, there’s been an improvement in treating cardiovascular diseases in people in their 40s, 50s, and 60s, so they’re surviving their heart failure, myocardial infarction, atrial fibrillation to develop cancers in later life.”

Combined with the aging population, the result is that “not only are many more people being diagnosed with cancer, because they’re living longer, but they have all these pre-existing heart risk factors, whether as confirmed disease or just the risk factors associated with that,” he said.

Another aspect is that many of the newer, targeted cancer therapies confer a cardiovascular risk.

Dr. Lyon said that the “most famous one” is trastuzumab, a monoclonal antibody that is used to treat HER2-positive breast cancer but that also causes left ventricular impairment “in about 15%-20% of the women taking it and can cause severe heart failure if it is missed.”

That, he continued, was the “forerunner of designer, targeted therapies,” and the subsequent “explosion” in the availability of modern cancer therapies has included many that confer cardiac issues.

The final reason for the greater interest in cardio-oncology, Dr. Lyon added, is the increasing awareness in oncology and hematology teams of the potential for cardiac problems among their patients.

“We have been reaching out to our oncology and hematology colleagues over the last 5-10 years to explain we’re here to help. We’re not here to stop their treatments, we’re here to support them.”

Presenting the guidelines, cochair Teresa López-Fernández, MD, cardiology department, La Paz University Hospital, IdiPAZ Research Institute, Madrid, said that the “spectrum of CVR-CVT presentations” includes arterial hypertension, cardiac arrhythmias, coronary artery disease, heart failure, and myocarditis.

She explained that cytotoxic cancer therapies are associated with an increased risk for cardiac toxicity that is most acute during the treatment phase but is not entirely diminished once it is over, then typically accumulates during long-term follow-up.

Crucially, the impact of cancer therapy on cardiovascular risk is dependent on several factors, such as patient age, cancer history, pre-existing cardiovascular risk factors or cardiovascular disease, and previous cardiotoxic cancer therapy.

There are nevertheless a number of potential strategies to reduce the risk for cardiac toxicity, including primary and secondary prevention prior to the start of cancer therapy and early CVR-CVT management during treatment, as well as cardiovascular risk assessment in the first year after treatment completion and cancer-survivorship programs.

To those ends, Dr. López-Fernández said the guidelines incorporate 272 new recommendations that cover the entire cardio-oncology care pathway, beginning with cardiovascular risk stratification before anticancer therapy.

They offer a risk-assessment checklist and make a series of recommendations for patients to be treated with potentially cardiotoxic drugs, such as anthracyclines, as well as recommendations on cardiac imaging.

The guidelines provide a range of recommendations for primary and secondary cancer therapy–related cardiovascular toxicity prevention, including minimization of the use of cardiotoxic drugs and the use of angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta blockers, and statins for primary prevention.

They establish CVR-CVT monitoring protocols across the gamut of cancer therapies, from HER-targeted therapies, through immune checkpoint inhibitors, Bruton tyrosine kinase, CDK4/6, EGFR, VEGF, and ALK inhibitors, and androgen-deprivation and endocrine therapies, to the more novel CAR-T-cell therapies.

A section on radiotherapy-induced cardiovascular toxicity has its own protocol for the establishment of an individual’s mean heart dose of radiation or the amount of radiation exposure to the heart during treatment.

Next, Dr. Lyon looked at recommendations for the management of cardiovascular disease and cancer therapy–related cardiovascular toxicity in patients receiving anticancer treatment.

He underlined that treatment decisions should consider the cancer and cardiovascular symptom burden, the cancer prognosis, the requirements for cancer treatment, including alternative options, drug-drug interactions, and patient preferences.

Dr. Lyon highlighted the algorithms designed to aid the management of cardiac dysfunction related to anthracycline chemotherapy, HER2-targeted therapy, and immune checkpoint inhibitors, as well as QTc-prolonging anticancer drugs.

In the first 12 months after the completions of therapy, there are a number of risk factors for future cardiovascular disease, he continued.

These include high and very high baseline cardiovascular toxicity risk, anticancer treatments known to have a high risk for long-term cardiovascular complications, such as doxorubicin and radiotherapy, and moderate or severe CTR-CVT during anticancer treatment.

Over the long term, the guidelines recommend that surveillance in asymptomatic cancer survivors range from an annual cardiovascular risk assessment in low-risk patients to patient education and cardiovascular risk factor optimization, alongside regular transthoracic echocardiography in high-risk groups.

Finally, Dr. Lyon said the guidelines turn their attention to special populations, such as patients with cardiac masses and tumors, those with carcinoid heart disease, pregnant women receiving cancer therapy, as well as those with cardiac implantable electronic devices undergoing radiotherapy.

The guidelines were developed by the task force on cardio-oncology of the ESC, in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio-Oncology Society. Dr. Lyon declares relationships with Akcea, Takeda Pharmaceuticals, Pfizer, GlaxoSmithKline, AstraZeneca, Novartis, Ferring Pharmaceuticals, Heartfelt Technologies, Brainstorm, and Myocardial Solutions. Dr. López-Fernández declares relationships with Daiichi Sankyo, Almirall Spain, Janssen-Cilag, Bayer, Roche, Philips, and Incyte.

A version of this article first appeared on Medscape.com.

The kids aren’t alright (at identifying fake news online)

If there’s one thing today’s teenagers are good at, it’s the Internet. What with their TokTiks, Fortnights, and memes whose lifespans are measured in milliseconds, it’s only natural that a contingent of people who have never known a world where the Internet wasn’t omnipresent would be highly skilled at navigating the dense, labyrinthine virtual world and the many falsehoods contained within.

Ladies and gentlemen, we’ve been duped, bamboozled, and smeckledorfed. New research from Slovakia suggests the opposite, in fact: Teenagers are just as bad as the rest of us, if not worse, at distinguishing between fake and real online health messaging.

monkeybusinessimages/iStock/Getty Images Plus

For the study, 300 teenagers aged 16-19 years old were shown a group of messages about the health-promoting effects of fruits and vegetables; these messages were either false, true and neutral, or true with some sort of editing (a clickbait title or grammar mistakes) to mask their trustworthiness. Just under half of the subjects identified and trusted the true neutral messages over fake messages, while 41% couldn’t tell the difference and 11% trusted the fake messages more. In addition, they couldn’t tell the difference between fake and true messages when the content seemed plausible.

In a bit of good news, teenagers were just as likely to trust the edited true messages as the true neutral ones, except in instances when the edited message had a clickbait title. They were much less likely to trust those.

Based on their subjects’ rather poor performance, the study authors suggested teenagers go through health literacy and media literacy training, as well as develop their analytical and scientific reasoning. The LOTME staff rather suspects the study authors have never met a teenager. The only thing teenagers are going to get out of health literacy training is fodder for memes to put up on Myspace. Myspace is still a thing, right? We’re not old, we swear.
 

Can a computer help deliver babies?

Delivering babies can be a complicated business. Most doctors and midwives rely on their years of experience and training to make certain decisions for mothers in labor, but an artificial intelligence (AI) algorithm could make the entire process easier and safer.

©Paul Hakimata/thinkstockphotos.com

Researchers from the Mayo Clinic recently reported that using an AI to analyze women’s labor patterns was very successful in determining whether a vaginal or cesarean delivery was appropriate.

They examined over 700 factors and over 66,000 deliveries from the National Institute of Child Health and Human Development’s multicenter Consortium on Safe Labor database to produce a risk-prediction model that may “provide an alternative to conventional labor charts and promote individualization of clinical decisions using baseline and labor characteristics of each patient,” they said in a written statement from the clinic.

It is hoped that the AI will reduce the risk of possible complications and the costs associated with maternal mortality. The AI also could be a significant tool for doctors and midwives in rural areas to determine when a patient needs to be moved to a location with a higher level of care.

“We believe the algorithm will work in real time, meaning every input of new data during an expectant woman’s labor automatically recalculates the risk of adverse outcome,” said senior author Abimbola Famuyide, MD, of the Mayo Clinic.

If it all works out, many lives and dollars could be saved, thanks to science.
 

Democracy, meet COVID-19

Everywhere you look, it seems, someone is trying to keep someone else from doing something: Don’t carry a gun. Don’t get an abortion. Don’t drive so fast. Don’t inhale that whipped cream. Don’t get a vaccine. Don’t put that in your mouth.

One of the biggies these days is voting rights. Some people are trying to prevent other people from voting. But why? Well, turns out that turnout can be bad for your health … at least during a worldwide pandemic event.

mohamed mahmoud hassan

The evidence for that claim comes from researchers who examined the Italian national constitutional referendum conducted in September 2020 along with elections for assembly representatives in 7 of the country’s 20 regions and for mayors in about 12% of municipalities. The combination mattered: Voter turnout was higher in the municipalities that voted for both the referendum and local elections (69%), compared with municipalities voting only for the referendum (47%), the investigators reported in the Journal of Economic Behavior & Organization.

Also occurring in September of 2020 was, as we mentioned, a worldwide pandemic event. You may have heard about it.

The investigators considered the differences in election turnout between the various municipalities and compared them with new weekly COVID-19 infections at the municipality level. “Our model shows that something as fundamental as casting a vote can come at a cost,” investigator Giuseppe Moscelli, PhD, of the University of Surrey (England) said in a written statement.

What was the cost? Each 1% increase in turnout, they found, amounted to an average 1.1% increase in COVID infections after the elections.

See? More people voting means more COVID, which is bad. Which brings us to today’s lesson in people preventing other people from doing something. Don’t let COVID win. Stay in your house and never come out. And get that smeckledorf out of your mouth. You don’t know where it’s been.

The kids aren’t alright (at identifying fake news online)

If there’s one thing today’s teenagers are good at, it’s the Internet. What with their TokTiks, Fortnights, and memes whose lifespans are measured in milliseconds, it’s only natural that a contingent of people who have never known a world where the Internet wasn’t omnipresent would be highly skilled at navigating the dense, labyrinthine virtual world and the many falsehoods contained within.

Ladies and gentlemen, we’ve been duped, bamboozled, and smeckledorfed. New research from Slovakia suggests the opposite, in fact: Teenagers are just as bad as the rest of us, if not worse, at distinguishing between fake and real online health messaging.

monkeybusinessimages/iStock/Getty Images Plus

For the study, 300 teenagers aged 16-19 years old were shown a group of messages about the health-promoting effects of fruits and vegetables; these messages were either false, true and neutral, or true with some sort of editing (a clickbait title or grammar mistakes) to mask their trustworthiness. Just under half of the subjects identified and trusted the true neutral messages over fake messages, while 41% couldn’t tell the difference and 11% trusted the fake messages more. In addition, they couldn’t tell the difference between fake and true messages when the content seemed plausible.

In a bit of good news, teenagers were just as likely to trust the edited true messages as the true neutral ones, except in instances when the edited message had a clickbait title. They were much less likely to trust those.

Based on their subjects’ rather poor performance, the study authors suggested teenagers go through health literacy and media literacy training, as well as develop their analytical and scientific reasoning. The LOTME staff rather suspects the study authors have never met a teenager. The only thing teenagers are going to get out of health literacy training is fodder for memes to put up on Myspace. Myspace is still a thing, right? We’re not old, we swear.
 

Can a computer help deliver babies?

Delivering babies can be a complicated business. Most doctors and midwives rely on their years of experience and training to make certain decisions for mothers in labor, but an artificial intelligence (AI) algorithm could make the entire process easier and safer.

©Paul Hakimata/thinkstockphotos.com

Researchers from the Mayo Clinic recently reported that using an AI to analyze women’s labor patterns was very successful in determining whether a vaginal or cesarean delivery was appropriate.

They examined over 700 factors and over 66,000 deliveries from the National Institute of Child Health and Human Development’s multicenter Consortium on Safe Labor database to produce a risk-prediction model that may “provide an alternative to conventional labor charts and promote individualization of clinical decisions using baseline and labor characteristics of each patient,” they said in a written statement from the clinic.

It is hoped that the AI will reduce the risk of possible complications and the costs associated with maternal mortality. The AI also could be a significant tool for doctors and midwives in rural areas to determine when a patient needs to be moved to a location with a higher level of care.

“We believe the algorithm will work in real time, meaning every input of new data during an expectant woman’s labor automatically recalculates the risk of adverse outcome,” said senior author Abimbola Famuyide, MD, of the Mayo Clinic.

If it all works out, many lives and dollars could be saved, thanks to science.
 

Democracy, meet COVID-19

Everywhere you look, it seems, someone is trying to keep someone else from doing something: Don’t carry a gun. Don’t get an abortion. Don’t drive so fast. Don’t inhale that whipped cream. Don’t get a vaccine. Don’t put that in your mouth.

One of the biggies these days is voting rights. Some people are trying to prevent other people from voting. But why? Well, turns out that turnout can be bad for your health … at least during a worldwide pandemic event.

mohamed mahmoud hassan

The evidence for that claim comes from researchers who examined the Italian national constitutional referendum conducted in September 2020 along with elections for assembly representatives in 7 of the country’s 20 regions and for mayors in about 12% of municipalities. The combination mattered: Voter turnout was higher in the municipalities that voted for both the referendum and local elections (69%), compared with municipalities voting only for the referendum (47%), the investigators reported in the Journal of Economic Behavior & Organization.

Also occurring in September of 2020 was, as we mentioned, a worldwide pandemic event. You may have heard about it.

The investigators considered the differences in election turnout between the various municipalities and compared them with new weekly COVID-19 infections at the municipality level. “Our model shows that something as fundamental as casting a vote can come at a cost,” investigator Giuseppe Moscelli, PhD, of the University of Surrey (England) said in a written statement.

What was the cost? Each 1% increase in turnout, they found, amounted to an average 1.1% increase in COVID infections after the elections.

See? More people voting means more COVID, which is bad. Which brings us to today’s lesson in people preventing other people from doing something. Don’t let COVID win. Stay in your house and never come out. And get that smeckledorf out of your mouth. You don’t know where it’s been.

The kids aren’t alright (at identifying fake news online)

If there’s one thing today’s teenagers are good at, it’s the Internet. What with their TokTiks, Fortnights, and memes whose lifespans are measured in milliseconds, it’s only natural that a contingent of people who have never known a world where the Internet wasn’t omnipresent would be highly skilled at navigating the dense, labyrinthine virtual world and the many falsehoods contained within.

Ladies and gentlemen, we’ve been duped, bamboozled, and smeckledorfed. New research from Slovakia suggests the opposite, in fact: Teenagers are just as bad as the rest of us, if not worse, at distinguishing between fake and real online health messaging.

monkeybusinessimages/iStock/Getty Images Plus

For the study, 300 teenagers aged 16-19 years old were shown a group of messages about the health-promoting effects of fruits and vegetables; these messages were either false, true and neutral, or true with some sort of editing (a clickbait title or grammar mistakes) to mask their trustworthiness. Just under half of the subjects identified and trusted the true neutral messages over fake messages, while 41% couldn’t tell the difference and 11% trusted the fake messages more. In addition, they couldn’t tell the difference between fake and true messages when the content seemed plausible.

In a bit of good news, teenagers were just as likely to trust the edited true messages as the true neutral ones, except in instances when the edited message had a clickbait title. They were much less likely to trust those.

Based on their subjects’ rather poor performance, the study authors suggested teenagers go through health literacy and media literacy training, as well as develop their analytical and scientific reasoning. The LOTME staff rather suspects the study authors have never met a teenager. The only thing teenagers are going to get out of health literacy training is fodder for memes to put up on Myspace. Myspace is still a thing, right? We’re not old, we swear.
 

Can a computer help deliver babies?

Delivering babies can be a complicated business. Most doctors and midwives rely on their years of experience and training to make certain decisions for mothers in labor, but an artificial intelligence (AI) algorithm could make the entire process easier and safer.

©Paul Hakimata/thinkstockphotos.com

Researchers from the Mayo Clinic recently reported that using an AI to analyze women’s labor patterns was very successful in determining whether a vaginal or cesarean delivery was appropriate.

They examined over 700 factors and over 66,000 deliveries from the National Institute of Child Health and Human Development’s multicenter Consortium on Safe Labor database to produce a risk-prediction model that may “provide an alternative to conventional labor charts and promote individualization of clinical decisions using baseline and labor characteristics of each patient,” they said in a written statement from the clinic.

It is hoped that the AI will reduce the risk of possible complications and the costs associated with maternal mortality. The AI also could be a significant tool for doctors and midwives in rural areas to determine when a patient needs to be moved to a location with a higher level of care.

“We believe the algorithm will work in real time, meaning every input of new data during an expectant woman’s labor automatically recalculates the risk of adverse outcome,” said senior author Abimbola Famuyide, MD, of the Mayo Clinic.

If it all works out, many lives and dollars could be saved, thanks to science.
 

Democracy, meet COVID-19

Everywhere you look, it seems, someone is trying to keep someone else from doing something: Don’t carry a gun. Don’t get an abortion. Don’t drive so fast. Don’t inhale that whipped cream. Don’t get a vaccine. Don’t put that in your mouth.

One of the biggies these days is voting rights. Some people are trying to prevent other people from voting. But why? Well, turns out that turnout can be bad for your health … at least during a worldwide pandemic event.

mohamed mahmoud hassan

The evidence for that claim comes from researchers who examined the Italian national constitutional referendum conducted in September 2020 along with elections for assembly representatives in 7 of the country’s 20 regions and for mayors in about 12% of municipalities. The combination mattered: Voter turnout was higher in the municipalities that voted for both the referendum and local elections (69%), compared with municipalities voting only for the referendum (47%), the investigators reported in the Journal of Economic Behavior & Organization.

Also occurring in September of 2020 was, as we mentioned, a worldwide pandemic event. You may have heard about it.

The investigators considered the differences in election turnout between the various municipalities and compared them with new weekly COVID-19 infections at the municipality level. “Our model shows that something as fundamental as casting a vote can come at a cost,” investigator Giuseppe Moscelli, PhD, of the University of Surrey (England) said in a written statement.

What was the cost? Each 1% increase in turnout, they found, amounted to an average 1.1% increase in COVID infections after the elections.

See? More people voting means more COVID, which is bad. Which brings us to today’s lesson in people preventing other people from doing something. Don’t let COVID win. Stay in your house and never come out. And get that smeckledorf out of your mouth. You don’t know where it’s been.

In the vast majority of people who experience muscle pain or weakness while taking a statin, those symptoms are not related to the statin, a new individual patient data meta-analysis of randomized controlled trials shows.

The Cholesterol Trialists Collaboration meta-analysis examined 19 large randomized double-blind trials that compared statin therapy with placebo and involved almost 124,000 patients.

RogerAshford/Thinkstock

“Our results show that, in people who experience muscle symptoms in the first year of taking a statin, those symptoms are actually due to the statin in only 1 of 15 of those people. For the other 14 of the 15 people who experience muscle symptoms in the first year of taking a statin, that muscle pain is not due to the statin,” lead investigator Colin Baigent, MD, said.

After the first year, there was no difference in muscle symptoms between patients taking a statin or those taking placebo.

Dr. Baigent, who is director of the Population Health Research Unit at the University of Oxford (England), presented the data on Aug. 29 at the European Society of Cardiology 2022 Congress.

It was also simultaneously published online in The Lancet. 

Dr. Baigent explained that statins very rarely cause serious muscle adverse effects with biochemical evidence of cellular damage, such as myopathy (which occurs in less than 1 in 10,000 patients per year) and rhabdomyolysis (which occurs in about 0.2 per 10,000 patients per year).

The effect of statins on other less serious muscle symptoms without biochemical evidence of cellular damage is less clear, but misinformation about the risks have arisen from nonrandomized studies, with social media and press reports suggesting that the risk for muscle symptoms with statins is extremely common, Dr. Baigent said.  

In response to this, the Cholesterol Trialists Collaboration put together a new program of data collection, validation, and analysis to provide reliable information from large double-blind randomized trials that are free from bias and confounding.

“Overall, when we look at all these data, we find there is about a 3% relative increase in the risks of experiencing muscle pain or weakness with a statin versus with placebo,” Dr. Baigent reported.

Muscle pain or weakness was reported by 16,835 of 62,028 patients taking a statin, (27.1%), compared with 16,446 of 61,912 patients taking placebo (26.6%), for a rate ratio of 1.03 (95% confidence interval, 1.01-1.06).

In absolute terms, the results show a rate of 166 reports of muscle symptoms per 1,000 patient-years in those taking a statin, compared with 155 per 1,000-patient-years in those taking placebo in the first year. This gives a rate ratio of 1.07 and an excess of 11 cases of muscle pain or weakness per 1,000 patients in the first year of statin therapy. 

“The very small excess of muscle symptoms in the statin patients were generally mild, with most patients able to continue treatment,” Dr. Baigent added. 

After the first year, the rate of muscle pain or weakness was exactly the same in the statin and placebo groups, at 50 per 1,000 patient-years.

“Therefore, for the vast majority of people who experience muscle pain or weakness on a statin, those symptoms are not due to the statin itself. It is due to something else, which could be ageing, thyroid disease, or exercise,” Dr. Baigent said. “After the first year of taking a statin, there is no excess risk of muscle pain or weakness at all.”

“To summarize, the excess risk of muscle pain or weakness with statin use is tiny, and almost nonexistent after the first year,” he added.

“Muscle pain is very common in the general population, and it was very common in both patients taking a statin and those given placebo in these randomized trials. We can only detect a difference by looking at all the data combined in this enormous study. And we now know for sure that over 90% of cases of muscle symptoms experienced by people taking a statin are not due to the statin.”

The researchers also looked at statin intensity and found that the more intense statins tend to cause slightly more muscle pain. “There was also some evidence, although this was not very clear, that the muscle pain with the more intensive statins may persist for longer than 1 year,” Dr. Baigent said.

But in terms of different moderate-intensity and high-intensity statins, there was no evidence of differences in muscle pain between the individual statin brands, he added.
 

Better patient information needed

Dr. Baigent called for better information in statin package inserts about the real risk for muscle symptoms with these drugs.

“We need to do a better job of communicating the real risk of muscle symptom to patients who are taking statins and to their doctors. At the moment, doctors often stop statins if patients complain of muscle pain, but our data show that in 14 out of 15 times, they would be wrong for doing that. Stopping the statin is nearly always a mistake,” he commented.

“At present, the package inserts include a whole load of rubbish from observational studies, which are completely unreliable,” he added. “This is of no value to patients. They go through this information and find several symptoms they are experiencing, which they attribute to the drugs. We really need to divide up the information into the evidence that we really know for sure and then the more speculative stuff.”

Dr. Baigent also highlighted the large benefits of statins, compared with the small risk for muscle symptoms.

“While statins may cause 11 patients per 1,000 to experience some mild muscle pain in the first year of taking these drugs, and this was reduced to none in subsequent years, statins, when used for the primary prevention of cardiovascular disease, prevent 25 cardiovascular events per 1,000 patients every year they are taken. And for secondary prevention this rises to 50 events prevented per 1,000 patients each year,” he noted.  

The individual participant data meta-analysis involved 23 trials with information on almost 155,000 patients. All trials included at least 1,000 patients and at least 2 years of scheduled treatment. Adverse-event data were collected for all individual participants in 19 large randomized double-blind trials comparing statin therapy with placebo (123,940 patients) and in four randomized double-blind trials comparing more-intensive with less-intensive statin therapy (30,724 patients).

In the four trials of more-intensive versus less-intensive statin therapy, high-intensity regimens (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily) resulted in a larger relative increase in the rate of muscle pain or weakness than moderate-intensity regimens, with rate ratios of 1.08 (95% CI, 1.04-1.13) and 1.02 (95% CI, 1.00-1.05), respectively.
 

‘Reassuring information’

Discussant of the study at the ESC Hotline session, Erin Bohula, MD, Brigham and Women’s Hospital, Boston, said this new analysis had many strengths and used a rigorous approach to look at the issue of muscle symptoms with statins.

She pointed out some challenges, including the fact that the definition of adverse muscle events has changed over time and differed in the various trials, with heterogeneous data capture across trials. “So, this was a Herculean task to harmonize this very complicated dataset.”

Dr. Bohula concluded: “I think this is a very significant undertaking, resulting in a rich dataset that enhances our understanding of muscle symptoms related to statin use. The take-home for me is that muscle symptoms are a common complaint in the general population but are very rarely attributable to statins. This is very reassuring to me, and I hope it is reassuring to patients and can help us encourage them with adherence, given the clear cardiovascular benefits of statins.”

Chair of the ESC Hotline session at which the study was presented, Gabriel Steg, MD, Hôpital Bichat, Paris, asked whether some statin patients who experienced muscle symptoms with the drugs in active run-in periods in the trials may have been excluded from the main trials, so that this information might not have been captured, but Dr. Baigent replied that they also examined those data, which had been accounted for in the analysis.

“That’s really good news,” Dr. Steg commented. “This study is going to be one more tool in our response to statin skeptics and I think, as such, this work is a really a service to public health.”

The meta-analysis was funded by the British Heart Foundation, the U.K. Medical Research Council, and the Australian National Health and Medical Research Council.

A version of this article first appeared on Medscape.com.

In the vast majority of people who experience muscle pain or weakness while taking a statin, those symptoms are not related to the statin, a new individual patient data meta-analysis of randomized controlled trials shows.

The Cholesterol Trialists Collaboration meta-analysis examined 19 large randomized double-blind trials that compared statin therapy with placebo and involved almost 124,000 patients.

RogerAshford/Thinkstock

“Our results show that, in people who experience muscle symptoms in the first year of taking a statin, those symptoms are actually due to the statin in only 1 of 15 of those people. For the other 14 of the 15 people who experience muscle symptoms in the first year of taking a statin, that muscle pain is not due to the statin,” lead investigator Colin Baigent, MD, said.

After the first year, there was no difference in muscle symptoms between patients taking a statin or those taking placebo.

Dr. Baigent, who is director of the Population Health Research Unit at the University of Oxford (England), presented the data on Aug. 29 at the European Society of Cardiology 2022 Congress.

It was also simultaneously published online in The Lancet. 

Dr. Baigent explained that statins very rarely cause serious muscle adverse effects with biochemical evidence of cellular damage, such as myopathy (which occurs in less than 1 in 10,000 patients per year) and rhabdomyolysis (which occurs in about 0.2 per 10,000 patients per year).

The effect of statins on other less serious muscle symptoms without biochemical evidence of cellular damage is less clear, but misinformation about the risks have arisen from nonrandomized studies, with social media and press reports suggesting that the risk for muscle symptoms with statins is extremely common, Dr. Baigent said.  

In response to this, the Cholesterol Trialists Collaboration put together a new program of data collection, validation, and analysis to provide reliable information from large double-blind randomized trials that are free from bias and confounding.

“Overall, when we look at all these data, we find there is about a 3% relative increase in the risks of experiencing muscle pain or weakness with a statin versus with placebo,” Dr. Baigent reported.

Muscle pain or weakness was reported by 16,835 of 62,028 patients taking a statin, (27.1%), compared with 16,446 of 61,912 patients taking placebo (26.6%), for a rate ratio of 1.03 (95% confidence interval, 1.01-1.06).

In absolute terms, the results show a rate of 166 reports of muscle symptoms per 1,000 patient-years in those taking a statin, compared with 155 per 1,000-patient-years in those taking placebo in the first year. This gives a rate ratio of 1.07 and an excess of 11 cases of muscle pain or weakness per 1,000 patients in the first year of statin therapy. 

“The very small excess of muscle symptoms in the statin patients were generally mild, with most patients able to continue treatment,” Dr. Baigent added. 

After the first year, the rate of muscle pain or weakness was exactly the same in the statin and placebo groups, at 50 per 1,000 patient-years.

“Therefore, for the vast majority of people who experience muscle pain or weakness on a statin, those symptoms are not due to the statin itself. It is due to something else, which could be ageing, thyroid disease, or exercise,” Dr. Baigent said. “After the first year of taking a statin, there is no excess risk of muscle pain or weakness at all.”

“To summarize, the excess risk of muscle pain or weakness with statin use is tiny, and almost nonexistent after the first year,” he added.

“Muscle pain is very common in the general population, and it was very common in both patients taking a statin and those given placebo in these randomized trials. We can only detect a difference by looking at all the data combined in this enormous study. And we now know for sure that over 90% of cases of muscle symptoms experienced by people taking a statin are not due to the statin.”

The researchers also looked at statin intensity and found that the more intense statins tend to cause slightly more muscle pain. “There was also some evidence, although this was not very clear, that the muscle pain with the more intensive statins may persist for longer than 1 year,” Dr. Baigent said.

But in terms of different moderate-intensity and high-intensity statins, there was no evidence of differences in muscle pain between the individual statin brands, he added.
 

Better patient information needed

Dr. Baigent called for better information in statin package inserts about the real risk for muscle symptoms with these drugs.

“We need to do a better job of communicating the real risk of muscle symptom to patients who are taking statins and to their doctors. At the moment, doctors often stop statins if patients complain of muscle pain, but our data show that in 14 out of 15 times, they would be wrong for doing that. Stopping the statin is nearly always a mistake,” he commented.

“At present, the package inserts include a whole load of rubbish from observational studies, which are completely unreliable,” he added. “This is of no value to patients. They go through this information and find several symptoms they are experiencing, which they attribute to the drugs. We really need to divide up the information into the evidence that we really know for sure and then the more speculative stuff.”

Dr. Baigent also highlighted the large benefits of statins, compared with the small risk for muscle symptoms.

“While statins may cause 11 patients per 1,000 to experience some mild muscle pain in the first year of taking these drugs, and this was reduced to none in subsequent years, statins, when used for the primary prevention of cardiovascular disease, prevent 25 cardiovascular events per 1,000 patients every year they are taken. And for secondary prevention this rises to 50 events prevented per 1,000 patients each year,” he noted.  

The individual participant data meta-analysis involved 23 trials with information on almost 155,000 patients. All trials included at least 1,000 patients and at least 2 years of scheduled treatment. Adverse-event data were collected for all individual participants in 19 large randomized double-blind trials comparing statin therapy with placebo (123,940 patients) and in four randomized double-blind trials comparing more-intensive with less-intensive statin therapy (30,724 patients).

In the four trials of more-intensive versus less-intensive statin therapy, high-intensity regimens (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily) resulted in a larger relative increase in the rate of muscle pain or weakness than moderate-intensity regimens, with rate ratios of 1.08 (95% CI, 1.04-1.13) and 1.02 (95% CI, 1.00-1.05), respectively.
 

‘Reassuring information’

Discussant of the study at the ESC Hotline session, Erin Bohula, MD, Brigham and Women’s Hospital, Boston, said this new analysis had many strengths and used a rigorous approach to look at the issue of muscle symptoms with statins.

She pointed out some challenges, including the fact that the definition of adverse muscle events has changed over time and differed in the various trials, with heterogeneous data capture across trials. “So, this was a Herculean task to harmonize this very complicated dataset.”

Dr. Bohula concluded: “I think this is a very significant undertaking, resulting in a rich dataset that enhances our understanding of muscle symptoms related to statin use. The take-home for me is that muscle symptoms are a common complaint in the general population but are very rarely attributable to statins. This is very reassuring to me, and I hope it is reassuring to patients and can help us encourage them with adherence, given the clear cardiovascular benefits of statins.”

Chair of the ESC Hotline session at which the study was presented, Gabriel Steg, MD, Hôpital Bichat, Paris, asked whether some statin patients who experienced muscle symptoms with the drugs in active run-in periods in the trials may have been excluded from the main trials, so that this information might not have been captured, but Dr. Baigent replied that they also examined those data, which had been accounted for in the analysis.

“That’s really good news,” Dr. Steg commented. “This study is going to be one more tool in our response to statin skeptics and I think, as such, this work is a really a service to public health.”

The meta-analysis was funded by the British Heart Foundation, the U.K. Medical Research Council, and the Australian National Health and Medical Research Council.

A version of this article first appeared on Medscape.com.

In the vast majority of people who experience muscle pain or weakness while taking a statin, those symptoms are not related to the statin, a new individual patient data meta-analysis of randomized controlled trials shows.

The Cholesterol Trialists Collaboration meta-analysis examined 19 large randomized double-blind trials that compared statin therapy with placebo and involved almost 124,000 patients.

RogerAshford/Thinkstock

“Our results show that, in people who experience muscle symptoms in the first year of taking a statin, those symptoms are actually due to the statin in only 1 of 15 of those people. For the other 14 of the 15 people who experience muscle symptoms in the first year of taking a statin, that muscle pain is not due to the statin,” lead investigator Colin Baigent, MD, said.

After the first year, there was no difference in muscle symptoms between patients taking a statin or those taking placebo.

Dr. Baigent, who is director of the Population Health Research Unit at the University of Oxford (England), presented the data on Aug. 29 at the European Society of Cardiology 2022 Congress.

It was also simultaneously published online in The Lancet. 

Dr. Baigent explained that statins very rarely cause serious muscle adverse effects with biochemical evidence of cellular damage, such as myopathy (which occurs in less than 1 in 10,000 patients per year) and rhabdomyolysis (which occurs in about 0.2 per 10,000 patients per year).

The effect of statins on other less serious muscle symptoms without biochemical evidence of cellular damage is less clear, but misinformation about the risks have arisen from nonrandomized studies, with social media and press reports suggesting that the risk for muscle symptoms with statins is extremely common, Dr. Baigent said.  

In response to this, the Cholesterol Trialists Collaboration put together a new program of data collection, validation, and analysis to provide reliable information from large double-blind randomized trials that are free from bias and confounding.

“Overall, when we look at all these data, we find there is about a 3% relative increase in the risks of experiencing muscle pain or weakness with a statin versus with placebo,” Dr. Baigent reported.

Muscle pain or weakness was reported by 16,835 of 62,028 patients taking a statin, (27.1%), compared with 16,446 of 61,912 patients taking placebo (26.6%), for a rate ratio of 1.03 (95% confidence interval, 1.01-1.06).

In absolute terms, the results show a rate of 166 reports of muscle symptoms per 1,000 patient-years in those taking a statin, compared with 155 per 1,000-patient-years in those taking placebo in the first year. This gives a rate ratio of 1.07 and an excess of 11 cases of muscle pain or weakness per 1,000 patients in the first year of statin therapy. 

“The very small excess of muscle symptoms in the statin patients were generally mild, with most patients able to continue treatment,” Dr. Baigent added. 

After the first year, the rate of muscle pain or weakness was exactly the same in the statin and placebo groups, at 50 per 1,000 patient-years.

“Therefore, for the vast majority of people who experience muscle pain or weakness on a statin, those symptoms are not due to the statin itself. It is due to something else, which could be ageing, thyroid disease, or exercise,” Dr. Baigent said. “After the first year of taking a statin, there is no excess risk of muscle pain or weakness at all.”

“To summarize, the excess risk of muscle pain or weakness with statin use is tiny, and almost nonexistent after the first year,” he added.

“Muscle pain is very common in the general population, and it was very common in both patients taking a statin and those given placebo in these randomized trials. We can only detect a difference by looking at all the data combined in this enormous study. And we now know for sure that over 90% of cases of muscle symptoms experienced by people taking a statin are not due to the statin.”

The researchers also looked at statin intensity and found that the more intense statins tend to cause slightly more muscle pain. “There was also some evidence, although this was not very clear, that the muscle pain with the more intensive statins may persist for longer than 1 year,” Dr. Baigent said.

But in terms of different moderate-intensity and high-intensity statins, there was no evidence of differences in muscle pain between the individual statin brands, he added.
 

Better patient information needed

Dr. Baigent called for better information in statin package inserts about the real risk for muscle symptoms with these drugs.

“We need to do a better job of communicating the real risk of muscle symptom to patients who are taking statins and to their doctors. At the moment, doctors often stop statins if patients complain of muscle pain, but our data show that in 14 out of 15 times, they would be wrong for doing that. Stopping the statin is nearly always a mistake,” he commented.

“At present, the package inserts include a whole load of rubbish from observational studies, which are completely unreliable,” he added. “This is of no value to patients. They go through this information and find several symptoms they are experiencing, which they attribute to the drugs. We really need to divide up the information into the evidence that we really know for sure and then the more speculative stuff.”

Dr. Baigent also highlighted the large benefits of statins, compared with the small risk for muscle symptoms.

“While statins may cause 11 patients per 1,000 to experience some mild muscle pain in the first year of taking these drugs, and this was reduced to none in subsequent years, statins, when used for the primary prevention of cardiovascular disease, prevent 25 cardiovascular events per 1,000 patients every year they are taken. And for secondary prevention this rises to 50 events prevented per 1,000 patients each year,” he noted.  

The individual participant data meta-analysis involved 23 trials with information on almost 155,000 patients. All trials included at least 1,000 patients and at least 2 years of scheduled treatment. Adverse-event data were collected for all individual participants in 19 large randomized double-blind trials comparing statin therapy with placebo (123,940 patients) and in four randomized double-blind trials comparing more-intensive with less-intensive statin therapy (30,724 patients).

In the four trials of more-intensive versus less-intensive statin therapy, high-intensity regimens (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily) resulted in a larger relative increase in the rate of muscle pain or weakness than moderate-intensity regimens, with rate ratios of 1.08 (95% CI, 1.04-1.13) and 1.02 (95% CI, 1.00-1.05), respectively.
 

‘Reassuring information’

Discussant of the study at the ESC Hotline session, Erin Bohula, MD, Brigham and Women’s Hospital, Boston, said this new analysis had many strengths and used a rigorous approach to look at the issue of muscle symptoms with statins.

She pointed out some challenges, including the fact that the definition of adverse muscle events has changed over time and differed in the various trials, with heterogeneous data capture across trials. “So, this was a Herculean task to harmonize this very complicated dataset.”

Dr. Bohula concluded: “I think this is a very significant undertaking, resulting in a rich dataset that enhances our understanding of muscle symptoms related to statin use. The take-home for me is that muscle symptoms are a common complaint in the general population but are very rarely attributable to statins. This is very reassuring to me, and I hope it is reassuring to patients and can help us encourage them with adherence, given the clear cardiovascular benefits of statins.”

Chair of the ESC Hotline session at which the study was presented, Gabriel Steg, MD, Hôpital Bichat, Paris, asked whether some statin patients who experienced muscle symptoms with the drugs in active run-in periods in the trials may have been excluded from the main trials, so that this information might not have been captured, but Dr. Baigent replied that they also examined those data, which had been accounted for in the analysis.

“That’s really good news,” Dr. Steg commented. “This study is going to be one more tool in our response to statin skeptics and I think, as such, this work is a really a service to public health.”

The meta-analysis was funded by the British Heart Foundation, the U.K. Medical Research Council, and the Australian National Health and Medical Research Council.

A version of this article first appeared on Medscape.com.

Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.

In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.

Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).

The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.

The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.

Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.

With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.

FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.

Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).

At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).

Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).

Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.

When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.

“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”

Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.

Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).

“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.

Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
 

Translating the benefits

Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.

“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.

The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.

Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”

With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.

“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”

In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”

Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.

Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”

The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.

A version of this article first appeared on Medscape.com.

Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.

In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.

Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).

The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.

The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.

Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.

With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.

FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.

Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).

At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).

Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).

Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.

When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.

“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”

Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.

Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).

“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.

Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
 

Translating the benefits

Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.

“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.

The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.

Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”

With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.

“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”

In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”

Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.

Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”

The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.

A version of this article first appeared on Medscape.com.

Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.

In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.

Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).

The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.

The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.

Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.

With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.

FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.

Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).

At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).

Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).

Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.

When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.

“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”

Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.

Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).

“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.

Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
 

Translating the benefits

Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.

“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.

The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.

Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”

With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.

“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”

In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”

Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.

Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”

The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.

A version of this article first appeared on Medscape.com.

Beta-blockers have long been recommended to prevent aortic dissection associated with Marfan syndrome despite limited evidence, but a new analysis also supports a benefit from angiotensin receptors blockers (ARBs) and further suggests that beta-blockers and ARBs exert independent effects.

For the endpoint of inhibition of growth of the aortic root, “there is no evidence of any interaction between the effects of ARBs with beta-blockers, and so we think that the treatment effects are likely to be additive,” reported Alex Pitcher, BMBCh, DPhil, Oxford (England) University Hospitals, NHS Trust.

Based on these data, Dr. Pitcher recommended considering ARBs and beta-blockers together soon after the diagnosis of Marfan syndrome. This includes young children.

“We think that medical treatments can delay surgery and dissection substantially if given for a number of years,” he added.

In this study, undertaken by the Marfan Treatment Trialists (MTT) collaboration, data were available from 1,442 Marfan syndrome patients participating in seven treatment trials. The primary outcome was aortic root enlargement, a predictor of life-threatening aortic dissection and rupture. Rather than a meta-analysis of the pooled data, the meta-analysis was conducted with individual patient data that involved collaboration with the original trialists.

Four of the studies with 746 patients compared ARBs to placebo or a control medication. A second group of three trials with 766 patients compared ARBs to beta-blockers.

From the two sets of data, a calculation of the effect of beta-blockers was indirectly estimated.
 

ARBs slow annualized aortic growth rate significantly

In the first set of trials, the analysis showed a significantly slower annualized aortic root growth rate for those treated with ARBs relative to controls (0.07 vs. 0.13), producing a statistically significant absolute difference (0.7%; P = .01) in favor of the ARB.

“In other words, the rate of growth was nearly double in the control arm,” Dr. Pitcher said.

In the three trials comparing ARBs to beta-blockers, the annualized growth rate among those taking an ARB was similar (0.8%) to that seen in the previous set of controlled trials. This rate of annualized growth was not significantly different from the 0.11% annualized rate of growth in patients receiving beta-blockers. When an analysis of the impact of beta-blockers was conducted by indirectly evaluating the change in growth relative to controls, the estimated impact was an annualized growth rate of 0.9% (P = .042).

A second set of data provided the basis for suggesting that the effects of beta ARBs and beta-blockers are independent and potentially additive.

“We were able to look at subgroups of patients in the ARB trials that were broken down by whether they were or were not on beta-blockers at baseline, and so by doing able to estimate independent effects,” Dr. Pitcher said. The lack of any interactions led Dr. Pitcher to conclude that benefits are likely additive.

Of patients genotyped in the ARB studies, more than 80% had the FBN1 pathogenic variant of Marfan syndrome. When the data were analyzed by subgroups, including age or blood pressure, there were no differences in treatment effect except for those with the FBN1 mutation in whom the benefit of ARB therapy was greater relative to those without.

As FBN1 is one of the most common genetic signatures of Marfan syndrome, the “greater effect of ARBs in this group makes it more plausible that the effect is real,” Dr. Pitcher said.
 

Results could change treatment guidelines

Current guidelines recommend beta-blockers in Marfan syndrome prior to a dilatation size of 4.5 to 5 cm when surgery is indicated, according to Dr. Pitcher, but he said these data might change guidelines. While reinforcing the benefit of beta-blockers, this analysis suggests ARBs should also be considered, possibly in combination with beta-blockers.

“What I hope this meta-analysis does is add substantially to the certainty with which physicians can discuss treatments with patients.”

As for the mechanism, it is reasonable to speculate the antihypertensive effect of both medications is relevant, but each has plausible independent activities that might contribute to modifying aortic growth, according to Roland R.J. van Kimmenade, MD, PhD, a specialist in aortic diseases and heart failure at Raboud University Medical Center, Nijmegan, the Netherlands.

Citing several studies, he suggested that the benefit of beta-blockers could also stem from their ability to reduce heart rate and aortic stiffness while ARBs are likely to inhibit the interaction between the renin-angiotensin system (RAS) and TGF-beta pathway. Each of these might participate in risk of aortic root growth, according to Dr. van Kimmenade, who was invited by ESC to discuss this study.

On the basis of these data as well as past studies, he agreed that the combination of beta-blockers and ARBs might not just be additive but “even a little bit synergistic.”

While Dr. Pitcher suggested that the evidence supports starting both beta-blockers and ARBs soon after the diagnosis, Dr. van Kimmenade said, “I don’t like using beta-blockers in young patients, but ARBs are now shown to be an excellent alternative.”

Ultimately, “the prescription pencil will not replace the surgical knife” in a disease that is likely to eventually require surgery to prevent life-threatening events, according to Dr. van Kimmenade, but he agreed that these data provide more certainty about the value of beta-blockers and ARBs for slowing progression.

Dr. Pitcher reports no potential conflicts of interest. Dr. van Kimmenade has financial relationships with Bayer and Novartis.

Beta-blockers have long been recommended to prevent aortic dissection associated with Marfan syndrome despite limited evidence, but a new analysis also supports a benefit from angiotensin receptors blockers (ARBs) and further suggests that beta-blockers and ARBs exert independent effects.

For the endpoint of inhibition of growth of the aortic root, “there is no evidence of any interaction between the effects of ARBs with beta-blockers, and so we think that the treatment effects are likely to be additive,” reported Alex Pitcher, BMBCh, DPhil, Oxford (England) University Hospitals, NHS Trust.

Based on these data, Dr. Pitcher recommended considering ARBs and beta-blockers together soon after the diagnosis of Marfan syndrome. This includes young children.

“We think that medical treatments can delay surgery and dissection substantially if given for a number of years,” he added.

In this study, undertaken by the Marfan Treatment Trialists (MTT) collaboration, data were available from 1,442 Marfan syndrome patients participating in seven treatment trials. The primary outcome was aortic root enlargement, a predictor of life-threatening aortic dissection and rupture. Rather than a meta-analysis of the pooled data, the meta-analysis was conducted with individual patient data that involved collaboration with the original trialists.

Four of the studies with 746 patients compared ARBs to placebo or a control medication. A second group of three trials with 766 patients compared ARBs to beta-blockers.

From the two sets of data, a calculation of the effect of beta-blockers was indirectly estimated.
 

ARBs slow annualized aortic growth rate significantly

In the first set of trials, the analysis showed a significantly slower annualized aortic root growth rate for those treated with ARBs relative to controls (0.07 vs. 0.13), producing a statistically significant absolute difference (0.7%; P = .01) in favor of the ARB.

“In other words, the rate of growth was nearly double in the control arm,” Dr. Pitcher said.

In the three trials comparing ARBs to beta-blockers, the annualized growth rate among those taking an ARB was similar (0.8%) to that seen in the previous set of controlled trials. This rate of annualized growth was not significantly different from the 0.11% annualized rate of growth in patients receiving beta-blockers. When an analysis of the impact of beta-blockers was conducted by indirectly evaluating the change in growth relative to controls, the estimated impact was an annualized growth rate of 0.9% (P = .042).

A second set of data provided the basis for suggesting that the effects of beta ARBs and beta-blockers are independent and potentially additive.

“We were able to look at subgroups of patients in the ARB trials that were broken down by whether they were or were not on beta-blockers at baseline, and so by doing able to estimate independent effects,” Dr. Pitcher said. The lack of any interactions led Dr. Pitcher to conclude that benefits are likely additive.

Of patients genotyped in the ARB studies, more than 80% had the FBN1 pathogenic variant of Marfan syndrome. When the data were analyzed by subgroups, including age or blood pressure, there were no differences in treatment effect except for those with the FBN1 mutation in whom the benefit of ARB therapy was greater relative to those without.

As FBN1 is one of the most common genetic signatures of Marfan syndrome, the “greater effect of ARBs in this group makes it more plausible that the effect is real,” Dr. Pitcher said.
 

Results could change treatment guidelines

Current guidelines recommend beta-blockers in Marfan syndrome prior to a dilatation size of 4.5 to 5 cm when surgery is indicated, according to Dr. Pitcher, but he said these data might change guidelines. While reinforcing the benefit of beta-blockers, this analysis suggests ARBs should also be considered, possibly in combination with beta-blockers.

“What I hope this meta-analysis does is add substantially to the certainty with which physicians can discuss treatments with patients.”

As for the mechanism, it is reasonable to speculate the antihypertensive effect of both medications is relevant, but each has plausible independent activities that might contribute to modifying aortic growth, according to Roland R.J. van Kimmenade, MD, PhD, a specialist in aortic diseases and heart failure at Raboud University Medical Center, Nijmegan, the Netherlands.

Citing several studies, he suggested that the benefit of beta-blockers could also stem from their ability to reduce heart rate and aortic stiffness while ARBs are likely to inhibit the interaction between the renin-angiotensin system (RAS) and TGF-beta pathway. Each of these might participate in risk of aortic root growth, according to Dr. van Kimmenade, who was invited by ESC to discuss this study.

On the basis of these data as well as past studies, he agreed that the combination of beta-blockers and ARBs might not just be additive but “even a little bit synergistic.”

While Dr. Pitcher suggested that the evidence supports starting both beta-blockers and ARBs soon after the diagnosis, Dr. van Kimmenade said, “I don’t like using beta-blockers in young patients, but ARBs are now shown to be an excellent alternative.”

Ultimately, “the prescription pencil will not replace the surgical knife” in a disease that is likely to eventually require surgery to prevent life-threatening events, according to Dr. van Kimmenade, but he agreed that these data provide more certainty about the value of beta-blockers and ARBs for slowing progression.

Dr. Pitcher reports no potential conflicts of interest. Dr. van Kimmenade has financial relationships with Bayer and Novartis.

Beta-blockers have long been recommended to prevent aortic dissection associated with Marfan syndrome despite limited evidence, but a new analysis also supports a benefit from angiotensin receptors blockers (ARBs) and further suggests that beta-blockers and ARBs exert independent effects.

For the endpoint of inhibition of growth of the aortic root, “there is no evidence of any interaction between the effects of ARBs with beta-blockers, and so we think that the treatment effects are likely to be additive,” reported Alex Pitcher, BMBCh, DPhil, Oxford (England) University Hospitals, NHS Trust.

Based on these data, Dr. Pitcher recommended considering ARBs and beta-blockers together soon after the diagnosis of Marfan syndrome. This includes young children.

“We think that medical treatments can delay surgery and dissection substantially if given for a number of years,” he added.

In this study, undertaken by the Marfan Treatment Trialists (MTT) collaboration, data were available from 1,442 Marfan syndrome patients participating in seven treatment trials. The primary outcome was aortic root enlargement, a predictor of life-threatening aortic dissection and rupture. Rather than a meta-analysis of the pooled data, the meta-analysis was conducted with individual patient data that involved collaboration with the original trialists.

Four of the studies with 746 patients compared ARBs to placebo or a control medication. A second group of three trials with 766 patients compared ARBs to beta-blockers.

From the two sets of data, a calculation of the effect of beta-blockers was indirectly estimated.
 

ARBs slow annualized aortic growth rate significantly

In the first set of trials, the analysis showed a significantly slower annualized aortic root growth rate for those treated with ARBs relative to controls (0.07 vs. 0.13), producing a statistically significant absolute difference (0.7%; P = .01) in favor of the ARB.

“In other words, the rate of growth was nearly double in the control arm,” Dr. Pitcher said.

In the three trials comparing ARBs to beta-blockers, the annualized growth rate among those taking an ARB was similar (0.8%) to that seen in the previous set of controlled trials. This rate of annualized growth was not significantly different from the 0.11% annualized rate of growth in patients receiving beta-blockers. When an analysis of the impact of beta-blockers was conducted by indirectly evaluating the change in growth relative to controls, the estimated impact was an annualized growth rate of 0.9% (P = .042).

A second set of data provided the basis for suggesting that the effects of beta ARBs and beta-blockers are independent and potentially additive.

“We were able to look at subgroups of patients in the ARB trials that were broken down by whether they were or were not on beta-blockers at baseline, and so by doing able to estimate independent effects,” Dr. Pitcher said. The lack of any interactions led Dr. Pitcher to conclude that benefits are likely additive.

Of patients genotyped in the ARB studies, more than 80% had the FBN1 pathogenic variant of Marfan syndrome. When the data were analyzed by subgroups, including age or blood pressure, there were no differences in treatment effect except for those with the FBN1 mutation in whom the benefit of ARB therapy was greater relative to those without.

As FBN1 is one of the most common genetic signatures of Marfan syndrome, the “greater effect of ARBs in this group makes it more plausible that the effect is real,” Dr. Pitcher said.
 

Results could change treatment guidelines

Current guidelines recommend beta-blockers in Marfan syndrome prior to a dilatation size of 4.5 to 5 cm when surgery is indicated, according to Dr. Pitcher, but he said these data might change guidelines. While reinforcing the benefit of beta-blockers, this analysis suggests ARBs should also be considered, possibly in combination with beta-blockers.

“What I hope this meta-analysis does is add substantially to the certainty with which physicians can discuss treatments with patients.”

As for the mechanism, it is reasonable to speculate the antihypertensive effect of both medications is relevant, but each has plausible independent activities that might contribute to modifying aortic growth, according to Roland R.J. van Kimmenade, MD, PhD, a specialist in aortic diseases and heart failure at Raboud University Medical Center, Nijmegan, the Netherlands.

Citing several studies, he suggested that the benefit of beta-blockers could also stem from their ability to reduce heart rate and aortic stiffness while ARBs are likely to inhibit the interaction between the renin-angiotensin system (RAS) and TGF-beta pathway. Each of these might participate in risk of aortic root growth, according to Dr. van Kimmenade, who was invited by ESC to discuss this study.

On the basis of these data as well as past studies, he agreed that the combination of beta-blockers and ARBs might not just be additive but “even a little bit synergistic.”

While Dr. Pitcher suggested that the evidence supports starting both beta-blockers and ARBs soon after the diagnosis, Dr. van Kimmenade said, “I don’t like using beta-blockers in young patients, but ARBs are now shown to be an excellent alternative.”

Ultimately, “the prescription pencil will not replace the surgical knife” in a disease that is likely to eventually require surgery to prevent life-threatening events, according to Dr. van Kimmenade, but he agreed that these data provide more certainty about the value of beta-blockers and ARBs for slowing progression.

Dr. Pitcher reports no potential conflicts of interest. Dr. van Kimmenade has financial relationships with Bayer and Novartis.

New research is suggesting that there are “meaningful” associations between higher dietary intake of omega-3 fatty acids and lower risk for depressive episodes.

In a longitudinal study of more than 13,000 participants, consumption of omega-3 fatty acids (total and subtypes) was associated with a 2%-65% reduction in the risk for depressive episodes in patients with depressive episodes at baseline.

In addition, consumption of total fatty acids and alpha-linolenic acid was associated with a reduced risk for incident depressive episodes (9% and 29%, respectively).

“Our results showed an important protective effect from the consumption of omega-3,” Maria de Jesus Mendes da Fonseca, University of the State of Rio de Janeiro, and colleagues write.

The findings were published online in Nutrients.
 

Mixed bag of studies

Epidemiologic evidence suggests that deficient dietary omega-3 intake is a modifiable risk factor for depression and that individuals with low consumption of omega-3 food sources have more depressive symptoms.

However, the results are inconsistent, and few longitudinal studies have addressed this association, the investigators note.

The new analysis included 13,879 adults (aged 39-65 years or older) participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) from 2008 to 2014.

Data on depressive episodes were obtained with the Clinical Interview Schedule Revised (CIS-R), and food consumption was measured with the Food Frequency Questionnaire (FFQ).

The target dietary components were total polyunsaturated fatty acids (PUFA) and the omega-3 fatty acids: alpha-linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA).

The majority of participants had adequate dietary intake of omega-3 fatty acids, and none was taking omega-3 supplements.

In the fully adjusted model, consumption of fatty acids from the omega-3 family had a protective effect against maintenance of depressive episodes, showing “important associations, although the significance levels are borderline, possibly due to the sample size,” the researchers report.

In regard to onset of depressive episodes, estimates from the fully adjusted model suggest that a higher consumption of omega-3 acids (total and subtypes) is associated with lower risk for depressive episodes – with significant associations for omega-3 and alpha-linolenic acid.

The investigators note that strengths of the study include “its originality, as it is the first to assess associations between maintenance and incidence of depressive episodes and consumption of omega-3, besides the use of data from the ELSA-Brasil Study, with rigorous data collection protocols and reliable and validated instruments, thus guaranteeing the quality of the sample and the data.”

A study limitation, however, was that the ELSA-Brasil sample consists only of public employees, with the potential for a selection bias such as healthy worker phenomenon, the researchers note. Another was the use of the FFQ, which may underestimate daily intake of foods and depends on individual participant recall – all of which could possibly lead to a differential classification bias.
 

Interpret cautiously

Commenting on the study, David Mischoulon, MD, PhD, professor of psychiatry, Harvard Medical School, and director of the depression clinical and research program at Massachusetts General Hospital, both in Boston, said that data on omega-3s in depression are “very mixed.”

“A lot of the studies don’t necessarily agree with each other. Certainly, in studies that try to seek an association between omega-3 use and depression, it’s always complicated because it can be difficult to control for all variables that could be contributing to the result that you get,” said Dr. Mischoulon, who is also a member of the Anxiety and Depression Association of America and was not involved in the research.

A caveat to the current study was that diet was assessed only at baseline, “so we don’t really know whether there were any substantial dietary changes over time, he noted.

He also cautioned that it is hard to draw any firm conclusions from this type of study.

“In general, in studies with a large sample, which this study has, it’s easier to find statistically significant differences. But you need to ask yourself: Does it really matter? Is it enough to have a clinical impact and make a difference?” Dr. Mischoulon said.

The ELSA-Brasil study was funded by the Brazilian Ministry of Science, Technology, and Innovation and by the Ministry of Health. The investigators have reported no relevant financial relationships. Dr. Mischoulon has received research support from Nordic Naturals and heckel medizintechnik GmbH and honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy. He also works with the MGH Clinical Trials Network and Institute, which has received research funding from multiple pharmaceutical companies and the National Institute of Mental Health.

A version of this article first appeared on Medscape.com.

New research is suggesting that there are “meaningful” associations between higher dietary intake of omega-3 fatty acids and lower risk for depressive episodes.

In a longitudinal study of more than 13,000 participants, consumption of omega-3 fatty acids (total and subtypes) was associated with a 2%-65% reduction in the risk for depressive episodes in patients with depressive episodes at baseline.

In addition, consumption of total fatty acids and alpha-linolenic acid was associated with a reduced risk for incident depressive episodes (9% and 29%, respectively).

“Our results showed an important protective effect from the consumption of omega-3,” Maria de Jesus Mendes da Fonseca, University of the State of Rio de Janeiro, and colleagues write.

The findings were published online in Nutrients.
 

Mixed bag of studies

Epidemiologic evidence suggests that deficient dietary omega-3 intake is a modifiable risk factor for depression and that individuals with low consumption of omega-3 food sources have more depressive symptoms.

However, the results are inconsistent, and few longitudinal studies have addressed this association, the investigators note.

The new analysis included 13,879 adults (aged 39-65 years or older) participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) from 2008 to 2014.

Data on depressive episodes were obtained with the Clinical Interview Schedule Revised (CIS-R), and food consumption was measured with the Food Frequency Questionnaire (FFQ).

The target dietary components were total polyunsaturated fatty acids (PUFA) and the omega-3 fatty acids: alpha-linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA).

The majority of participants had adequate dietary intake of omega-3 fatty acids, and none was taking omega-3 supplements.

In the fully adjusted model, consumption of fatty acids from the omega-3 family had a protective effect against maintenance of depressive episodes, showing “important associations, although the significance levels are borderline, possibly due to the sample size,” the researchers report.

In regard to onset of depressive episodes, estimates from the fully adjusted model suggest that a higher consumption of omega-3 acids (total and subtypes) is associated with lower risk for depressive episodes – with significant associations for omega-3 and alpha-linolenic acid.

The investigators note that strengths of the study include “its originality, as it is the first to assess associations between maintenance and incidence of depressive episodes and consumption of omega-3, besides the use of data from the ELSA-Brasil Study, with rigorous data collection protocols and reliable and validated instruments, thus guaranteeing the quality of the sample and the data.”

A study limitation, however, was that the ELSA-Brasil sample consists only of public employees, with the potential for a selection bias such as healthy worker phenomenon, the researchers note. Another was the use of the FFQ, which may underestimate daily intake of foods and depends on individual participant recall – all of which could possibly lead to a differential classification bias.
 

Interpret cautiously

Commenting on the study, David Mischoulon, MD, PhD, professor of psychiatry, Harvard Medical School, and director of the depression clinical and research program at Massachusetts General Hospital, both in Boston, said that data on omega-3s in depression are “very mixed.”

“A lot of the studies don’t necessarily agree with each other. Certainly, in studies that try to seek an association between omega-3 use and depression, it’s always complicated because it can be difficult to control for all variables that could be contributing to the result that you get,” said Dr. Mischoulon, who is also a member of the Anxiety and Depression Association of America and was not involved in the research.

A caveat to the current study was that diet was assessed only at baseline, “so we don’t really know whether there were any substantial dietary changes over time, he noted.

He also cautioned that it is hard to draw any firm conclusions from this type of study.

“In general, in studies with a large sample, which this study has, it’s easier to find statistically significant differences. But you need to ask yourself: Does it really matter? Is it enough to have a clinical impact and make a difference?” Dr. Mischoulon said.

The ELSA-Brasil study was funded by the Brazilian Ministry of Science, Technology, and Innovation and by the Ministry of Health. The investigators have reported no relevant financial relationships. Dr. Mischoulon has received research support from Nordic Naturals and heckel medizintechnik GmbH and honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy. He also works with the MGH Clinical Trials Network and Institute, which has received research funding from multiple pharmaceutical companies and the National Institute of Mental Health.

A version of this article first appeared on Medscape.com.

New research is suggesting that there are “meaningful” associations between higher dietary intake of omega-3 fatty acids and lower risk for depressive episodes.

In a longitudinal study of more than 13,000 participants, consumption of omega-3 fatty acids (total and subtypes) was associated with a 2%-65% reduction in the risk for depressive episodes in patients with depressive episodes at baseline.

In addition, consumption of total fatty acids and alpha-linolenic acid was associated with a reduced risk for incident depressive episodes (9% and 29%, respectively).

“Our results showed an important protective effect from the consumption of omega-3,” Maria de Jesus Mendes da Fonseca, University of the State of Rio de Janeiro, and colleagues write.

The findings were published online in Nutrients.
 

Mixed bag of studies

Epidemiologic evidence suggests that deficient dietary omega-3 intake is a modifiable risk factor for depression and that individuals with low consumption of omega-3 food sources have more depressive symptoms.

However, the results are inconsistent, and few longitudinal studies have addressed this association, the investigators note.

The new analysis included 13,879 adults (aged 39-65 years or older) participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) from 2008 to 2014.

Data on depressive episodes were obtained with the Clinical Interview Schedule Revised (CIS-R), and food consumption was measured with the Food Frequency Questionnaire (FFQ).

The target dietary components were total polyunsaturated fatty acids (PUFA) and the omega-3 fatty acids: alpha-linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA).

The majority of participants had adequate dietary intake of omega-3 fatty acids, and none was taking omega-3 supplements.

In the fully adjusted model, consumption of fatty acids from the omega-3 family had a protective effect against maintenance of depressive episodes, showing “important associations, although the significance levels are borderline, possibly due to the sample size,” the researchers report.

In regard to onset of depressive episodes, estimates from the fully adjusted model suggest that a higher consumption of omega-3 acids (total and subtypes) is associated with lower risk for depressive episodes – with significant associations for omega-3 and alpha-linolenic acid.

The investigators note that strengths of the study include “its originality, as it is the first to assess associations between maintenance and incidence of depressive episodes and consumption of omega-3, besides the use of data from the ELSA-Brasil Study, with rigorous data collection protocols and reliable and validated instruments, thus guaranteeing the quality of the sample and the data.”

A study limitation, however, was that the ELSA-Brasil sample consists only of public employees, with the potential for a selection bias such as healthy worker phenomenon, the researchers note. Another was the use of the FFQ, which may underestimate daily intake of foods and depends on individual participant recall – all of which could possibly lead to a differential classification bias.
 

Interpret cautiously

Commenting on the study, David Mischoulon, MD, PhD, professor of psychiatry, Harvard Medical School, and director of the depression clinical and research program at Massachusetts General Hospital, both in Boston, said that data on omega-3s in depression are “very mixed.”

“A lot of the studies don’t necessarily agree with each other. Certainly, in studies that try to seek an association between omega-3 use and depression, it’s always complicated because it can be difficult to control for all variables that could be contributing to the result that you get,” said Dr. Mischoulon, who is also a member of the Anxiety and Depression Association of America and was not involved in the research.

A caveat to the current study was that diet was assessed only at baseline, “so we don’t really know whether there were any substantial dietary changes over time, he noted.

He also cautioned that it is hard to draw any firm conclusions from this type of study.

“In general, in studies with a large sample, which this study has, it’s easier to find statistically significant differences. But you need to ask yourself: Does it really matter? Is it enough to have a clinical impact and make a difference?” Dr. Mischoulon said.

The ELSA-Brasil study was funded by the Brazilian Ministry of Science, Technology, and Innovation and by the Ministry of Health. The investigators have reported no relevant financial relationships. Dr. Mischoulon has received research support from Nordic Naturals and heckel medizintechnik GmbH and honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy. He also works with the MGH Clinical Trials Network and Institute, which has received research funding from multiple pharmaceutical companies and the National Institute of Mental Health.

A version of this article first appeared on Medscape.com.

Drinking tea has several reported health benefits, but most studies have been conducted in regions where green tea predominates. New data from Britain – where there is a strong tradition of ‘afternoon tea’ – now shows that black tea is also associated with health benefits.

The findings come from a prospective study of nearly 500,000 participants in the UK Biobank cohort, among whom drinking black tea was common. They suggest that drinking black tea may be associated with a moderately lower all-cause mortality risk, and the risk was lowest among those drinking two or more cups of tea per day.

The study was published online in Annals of Internal Medicine.

During a median follow-up of 11.2 years, those who drank at least two cups of tea each day had a lower all-cause mortality risk, reported Maki Inoue-Choi, PhD, and colleagues from the National Cancer Institute in Bethesda, Md.  

After multivariate adjustment, the hazard ratios for death among tea drinkers, compared with no tea intake, were similar across intake levels: 0.95 for daily intake of up to 1 cup, 0.87 for 2-3 cups, 0.88 for 4-5 cups, 0.88 for 6-7 cups, 0.91 for 8-9 cups, and 0.89 for 10 or more cups.

Drinking tea also showed an inverse association with mortality from cardiovascular disease (adjusted HRs ranging from 0.98 to 0.76), ischemic heart disease (aHRs ranging from 1.03 to 0.74), and stroke (aHRs ranging from 0.92 to 0.48 ), However, the researchers added that “no clear trend was seen for cancer or respiratory disease mortality, with associations among higher intake categories tending toward the null.”

There is “no clear answer” as to why no association was observed between tea consumption and cancer mortality in the current study, Dr. Inoue-Choi said at a press briefing. Notably, the effects were apparent regardless of whether milk or sugar was added to tea, tea temperature, or genetic variations in caffeine metabolism among participants.

She and her colleagues controlled for these factors, as well as numerous others that could confound the results, including coffee consumption and baseline health and demographic characteristics..

The study subjects were 498,043 adults with a mean baseline age of 56.5 years. About 85% reported drinking tea, 90% reported drinking black tea, and most drank two to three cups (29%), four to five cups (26%), or six to seven cups (12%) per day.

A limitation of the study is the lack of information on certain aspects of tea intake, such as portion size and tea strength, the authors noted.

Tea is among the most frequently consumed beverages worldwide, and studies from places where green tea is popular, like China and Japan, have demonstrated health benefits. Data from places where black tea is more commonly consumed have been lacking and have provided conflicting results, Dr. Inoue-Choi said.

 A presumed mechanism of action related to tea consumption is reduced oxidative stress and inflammation thanks to "polyphenols and flavonoids, namely catechins and their oxidated products," the authors explained. Oxidative stress and inflammation may promote carcinogenesis; therefore, reducing oxidative stress and inflammation may improve endothelial function, they added.

“While these findings may offer reassurance to tea drinkers, they do not indicate that people should start drinking tea or change their tea consumption for health benefits,” Dr. Inoue-Choi said, explaining that “the results need to be replicated in future studies and extended in other diverse populations.”

This study was funded by the National Cancer Institute Intramural Research Program and the NCI division of cancer epidemiology & genetics. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This article was updated 8/31/22.

Drinking tea has several reported health benefits, but most studies have been conducted in regions where green tea predominates. New data from Britain – where there is a strong tradition of ‘afternoon tea’ – now shows that black tea is also associated with health benefits.

The findings come from a prospective study of nearly 500,000 participants in the UK Biobank cohort, among whom drinking black tea was common. They suggest that drinking black tea may be associated with a moderately lower all-cause mortality risk, and the risk was lowest among those drinking two or more cups of tea per day.

The study was published online in Annals of Internal Medicine.

During a median follow-up of 11.2 years, those who drank at least two cups of tea each day had a lower all-cause mortality risk, reported Maki Inoue-Choi, PhD, and colleagues from the National Cancer Institute in Bethesda, Md.  

After multivariate adjustment, the hazard ratios for death among tea drinkers, compared with no tea intake, were similar across intake levels: 0.95 for daily intake of up to 1 cup, 0.87 for 2-3 cups, 0.88 for 4-5 cups, 0.88 for 6-7 cups, 0.91 for 8-9 cups, and 0.89 for 10 or more cups.

Drinking tea also showed an inverse association with mortality from cardiovascular disease (adjusted HRs ranging from 0.98 to 0.76), ischemic heart disease (aHRs ranging from 1.03 to 0.74), and stroke (aHRs ranging from 0.92 to 0.48 ), However, the researchers added that “no clear trend was seen for cancer or respiratory disease mortality, with associations among higher intake categories tending toward the null.”

There is “no clear answer” as to why no association was observed between tea consumption and cancer mortality in the current study, Dr. Inoue-Choi said at a press briefing. Notably, the effects were apparent regardless of whether milk or sugar was added to tea, tea temperature, or genetic variations in caffeine metabolism among participants.

She and her colleagues controlled for these factors, as well as numerous others that could confound the results, including coffee consumption and baseline health and demographic characteristics..

The study subjects were 498,043 adults with a mean baseline age of 56.5 years. About 85% reported drinking tea, 90% reported drinking black tea, and most drank two to three cups (29%), four to five cups (26%), or six to seven cups (12%) per day.

A limitation of the study is the lack of information on certain aspects of tea intake, such as portion size and tea strength, the authors noted.

Tea is among the most frequently consumed beverages worldwide, and studies from places where green tea is popular, like China and Japan, have demonstrated health benefits. Data from places where black tea is more commonly consumed have been lacking and have provided conflicting results, Dr. Inoue-Choi said.

 A presumed mechanism of action related to tea consumption is reduced oxidative stress and inflammation thanks to "polyphenols and flavonoids, namely catechins and their oxidated products," the authors explained. Oxidative stress and inflammation may promote carcinogenesis; therefore, reducing oxidative stress and inflammation may improve endothelial function, they added.

“While these findings may offer reassurance to tea drinkers, they do not indicate that people should start drinking tea or change their tea consumption for health benefits,” Dr. Inoue-Choi said, explaining that “the results need to be replicated in future studies and extended in other diverse populations.”

This study was funded by the National Cancer Institute Intramural Research Program and the NCI division of cancer epidemiology & genetics. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This article was updated 8/31/22.

Drinking tea has several reported health benefits, but most studies have been conducted in regions where green tea predominates. New data from Britain – where there is a strong tradition of ‘afternoon tea’ – now shows that black tea is also associated with health benefits.

The findings come from a prospective study of nearly 500,000 participants in the UK Biobank cohort, among whom drinking black tea was common. They suggest that drinking black tea may be associated with a moderately lower all-cause mortality risk, and the risk was lowest among those drinking two or more cups of tea per day.

The study was published online in Annals of Internal Medicine.

During a median follow-up of 11.2 years, those who drank at least two cups of tea each day had a lower all-cause mortality risk, reported Maki Inoue-Choi, PhD, and colleagues from the National Cancer Institute in Bethesda, Md.  

After multivariate adjustment, the hazard ratios for death among tea drinkers, compared with no tea intake, were similar across intake levels: 0.95 for daily intake of up to 1 cup, 0.87 for 2-3 cups, 0.88 for 4-5 cups, 0.88 for 6-7 cups, 0.91 for 8-9 cups, and 0.89 for 10 or more cups.

Drinking tea also showed an inverse association with mortality from cardiovascular disease (adjusted HRs ranging from 0.98 to 0.76), ischemic heart disease (aHRs ranging from 1.03 to 0.74), and stroke (aHRs ranging from 0.92 to 0.48 ), However, the researchers added that “no clear trend was seen for cancer or respiratory disease mortality, with associations among higher intake categories tending toward the null.”

There is “no clear answer” as to why no association was observed between tea consumption and cancer mortality in the current study, Dr. Inoue-Choi said at a press briefing. Notably, the effects were apparent regardless of whether milk or sugar was added to tea, tea temperature, or genetic variations in caffeine metabolism among participants.

She and her colleagues controlled for these factors, as well as numerous others that could confound the results, including coffee consumption and baseline health and demographic characteristics..

The study subjects were 498,043 adults with a mean baseline age of 56.5 years. About 85% reported drinking tea, 90% reported drinking black tea, and most drank two to three cups (29%), four to five cups (26%), or six to seven cups (12%) per day.

A limitation of the study is the lack of information on certain aspects of tea intake, such as portion size and tea strength, the authors noted.

Tea is among the most frequently consumed beverages worldwide, and studies from places where green tea is popular, like China and Japan, have demonstrated health benefits. Data from places where black tea is more commonly consumed have been lacking and have provided conflicting results, Dr. Inoue-Choi said.

 A presumed mechanism of action related to tea consumption is reduced oxidative stress and inflammation thanks to "polyphenols and flavonoids, namely catechins and their oxidated products," the authors explained. Oxidative stress and inflammation may promote carcinogenesis; therefore, reducing oxidative stress and inflammation may improve endothelial function, they added.

“While these findings may offer reassurance to tea drinkers, they do not indicate that people should start drinking tea or change their tea consumption for health benefits,” Dr. Inoue-Choi said, explaining that “the results need to be replicated in future studies and extended in other diverse populations.”

This study was funded by the National Cancer Institute Intramural Research Program and the NCI division of cancer epidemiology & genetics. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This article was updated 8/31/22.

Early in 2020, Anne Peters, MD, caught COVID-19. The author of Medscape’s “Peters on Diabetes” column was sick in March 2020 before state-mandated lockdowns, and well before there were any vaccines.

She remembers sitting in a small exam room with two patients who had flown to her Los Angeles office from New York. The elderly couple had hearing difficulties, so Dr. Peters sat close to them, putting on a continuous glucose monitor. “At that time, we didn’t think of COVID-19 as being in L.A.,” Dr. Peters recalled, “so I think we were not terribly consistent at mask-wearing due to the need to educate.”

“Several days later, I got COVID, but I didn’t know I had COVID per se. I felt crappy, had a terrible sore throat, lost my sense of taste and smell [which was not yet described as a COVID symptom], was completely exhausted, but had no fever or cough, which were the only criteria for getting COVID tested at the time. I didn’t know I had been exposed until 2 weeks later, when the patient’s assistant returned the sensor warning us to ‘be careful’ with it because the patient and his wife were recovering from COVID.”

That early battle with COVID-19 was just the beginning of what would become a 2-year struggle, including familial loss amid her own health problems and concerns about the under-resourced patients she cares for. Here, she shares her journey through the pandemic with this news organization.
 

Question: Thanks for talking to us. Let’s discuss your journey over these past 2.5 years.

Answer: Everybody has their own COVID story because we all went through this together. Some of us have worse COVID stories, and some of us have better ones, but all have been impacted.

I’m not a sick person. I’m a very healthy person but COVID made me so unwell for 2 years. The brain fog and fatigue were nothing compared to the autonomic neuropathy that affected my heart. It was really limiting for me. And I still don’t know the long-term implications, looking 20-30 years from now.
 

Q: When you initially had COVID, what were your symptoms? What was the impact?

A: I had all the symptoms of COVID, except for a cough and fever. I lost my sense of taste and smell. I had a horrible headache, a sore throat, and I was exhausted. I couldn’t get tested because I didn’t have the right symptoms.

Despite being sick, I never stopped working but just switched to telemedicine. I also took my regular monthly trip to our cabin in Montana. I unknowingly flew on a plane with COVID. I wore a well-fitted N95 mask, so I don’t think I gave anybody COVID. I didn’t give COVID to my partner, Eric, which is hard to believe as – at 77 – he’s older than me. He has diabetes, heart disease, and every other high-risk characteristic. If he’d gotten COVID back then, it would have been terrible, as there were no treatments, but luckily he didn’t get it.
 

Q: When were you officially diagnosed?

A: Two or 3 months after I thought I might have had COVID, I checked my antibodies, which tested strongly positive for a prior COVID infection. That was when I knew all the symptoms I’d had were due to the disease.

Q: Not only were you dealing with your own illness, but also that of those close to you. Can you talk about that?

A: In April 2020, my mother who was in her 90s and otherwise healthy except for dementia, got COVID. She could have gotten it from me. I visited often but wore a mask. She had all the horrible pulmonary symptoms. In her advance directive, she didn’t want to be hospitalized so I kept her in her home. She died from COVID in her own bed. It was fairly brutal, but at least I kept her where she felt comforted.

My 91-year-old dad was living in a different residential facility. Throughout COVID he had become very depressed because his social patterns had changed. Prior to COVID, they all ate together, but during the pandemic they were unable to. He missed his social connections, disliked being isolated in his room, hated everyone in masks.

He was a bit demented, but not so much that he couldn’t communicate with me or remember where his grandson was going to law school. I wasn’t allowed inside the facility, which was hard on him. I hadn’t told him his wife died because the hospice social workers advised me that I shouldn’t give him news that he couldn’t process readily until I could spend time with him. Unfortunately, that time never came. In December 2020, he got COVID. One of the people in that facility had gone to the hospital, came back, and tested negative, but actually had COVID and gave it to my dad. The guy who gave it to my dad didn’t die but my dad was terribly ill. He died 2 weeks short of getting his vaccine. He was coherent enough to have a conversation. I asked him: ‘Do you want to go to the hospital?’ And he said: ‘No, because it would be too scary,’ since he couldn’t be with me. I put him on hospice and held his hand as he died from pulmonary COVID, which was awful. I couldn’t give him enough morphine or valium to ease his breathing. But his last words to me were “I love you,” and at the very end he seemed peaceful, which was a blessing.

I got an autopsy, because he wanted one. Nothing else was wrong with him other than COVID. It destroyed his lungs. The rest of him was fine – no heart disease, cancer, or anything else. He died of COVID-19, the same as my mother.

That same week, my aunt, my only surviving older relative, who was in Des Moines, Iowa, died of COVID-19. All three family members died before the vaccine came out.

It was hard to lose my parents. I’m the only surviving child because my sister died in her 20s. It’s not been an easy pandemic. But what pandemic is easy? I just happened to have lost more people than most. Ironically, my grandfather was one of the legionnaires at the Bellevue-Stratford Hotel in Philadelphia in 1976 and died of Legionnaire’s disease before we knew what was causing the outbreak.
 

Q: Were you still struggling with COVID?

A: COVID impacted my whole body. I lost a lot of weight. I didn’t want to eat, and my gastrointestinal system was not happy. It took a while for my sense of taste and smell to come back. Nothing tasted good. I’m not a foodie; I don’t really care about food. We could get takeout or whatever, but none of it appealed to me. I’m not so sure it was a taste thing, I just didn’t feel like eating.

I didn’t realize I had “brain fog” per se, because I felt stressed and overwhelmed by the pandemic and my patients’ concerns. But one day, about 3 months after I had developed COVID, I woke up without the fog. Which made me aware that I hadn’t been feeling right up until that point.

The worst symptoms, however, were cardiac. I noticed also immediately that my heart rate went up very quickly with minimal exertion. My pulse has always been in the 55-60 bpm range, and suddenly just walking across a room made it go up to over 140 bpm. If I did any aerobic activity, it went up over 160 and would be associated with dyspnea and chest pain. I believed these were all post-COVID symptoms and felt validated when reports of others having similar issues were published in the literature.

Q: Did you continue seeing patients?

A: Yes, of course. Patients never needed their doctors more. In East L.A., where patients don’t have easy access to telemedicine, I kept going into clinic throughout the pandemic. In the more affluent Westside of Los Angeles, we switched to telemedicine, which was quite effective for most. However, because diabetes was associated with an increased risk of hospitalization and death from COVID, my patients were understandably afraid. I’ve never been busier, but (like all health care providers), I became more of a COVID provider than a diabetologist.

Q: Do you feel your battle with COVID impacted your work?

A: It didn’t affect me at work. If I was sitting still, I was fine. Sitting at home at a desk, I didn’t notice any symptoms. But as a habitual stair-user, I would be gasping for breath in the stairwell because I couldn’t go up the stairs to my office as I once could.

I think you empathize more with people who had COVID (when you’ve had it yourself). There was such a huge patient burden. And I think that’s been the thing that’s affected health care providers the most – no matter what specialty we’re in – that nobody has answers.
 

Q: What happened after you had your vaccine?

A: The vaccine itself was fine. I didn’t have any reaction to the first two doses. But the first booster made my cardiac issues worse.

By this point, my cardiac problems stopped me from exercising. I even went to the ER with chest pain once because I was having palpitations and chest pressure caused by simply taking my morning shower. Fortunately, I wasn’t having an MI, but I certainly wasn’t “normal.”

My measure of my fitness is the cross-country skiing trail I use in Montana. I know exactly how far I can ski. Usually I can do the loop in 35 minutes. After COVID, I lasted 10 minutes. I would be tachycardic, short of breath with chest pain radiating down my left arm. I would rest and try to keep going. But with each rest period, I only got worse. I would be laying in the snow and strangers would ask if I needed help.
 

Q: What helped you?

A: I’ve read a lot about long COVID and have tried to learn from the experts. Of course, I never went to a doctor directly, although I did ask colleagues for advice. What I learned was to never push myself. I forced myself to create an exercise schedule where I only exercised three times a week with rest days in between. When exercising, the second my heart rate went above 140 bpm, I stopped until I could get it back down. I would push against this new limit, even though my limit was low.

Additionally, I worked on my breathing patterns and did meditative breathing for 10 minutes twice daily using a commercially available app.

Although progress was slow, I did improve, and by June 2022, I seemed back to normal. I was not as fit as I was prior to COVID and needed to improve, but the tachycardic response to exercise and cardiac symptoms were gone. I felt like my normal self. Normal enough to go on a spot packing trip in the Sierras in August. (Horses carried us and a mule carried the gear over the 12,000-foot pass into the mountains, and then left my friend and me high in the Sierras for a week.) We were camped above 10,000 feet and every day hiked up to another high mountain lake where we fly-fished for trout that we ate for dinner. The hikes were a challenge, but not abnormally so. Not as they would have been while I had long COVID.
 

Q: What is the current atmosphere in your clinic?

A: COVID is much milder now in my vaccinated patients, but I feel most health care providers are exhausted. Many of my staff left when COVID hit because they didn’t want to keep working. It made practicing medicine exhausting. There’s been a shortage of nurses, a shortage of everything. We’ve been required to do a whole lot more than we ever did before. It’s much harder to be a doctor. This pandemic is the first time I’ve ever thought of quitting. Granted, I lost my whole family, or at least the older generation, but it’s just been almost overwhelming.

On the plus side, almost every one of my patients has been vaccinated, because early on, people would ask: “Do you trust this vaccine?” I would reply: “I saw my parents die from COVID when they weren’t vaccinated, so you’re getting vaccinated. This is real and the vaccines help.” It made me very good at convincing people to get vaccines because I knew what it was like to see someone dying from COVID up close.
 

Q: What advice do you have for those struggling with the COVID pandemic?

A: People need to decide what their own risk is for getting sick and how many times they want to get COVID. At this point, I want people to go out, but safely. In the beginning, when my patients said, “can I go visit my granddaughter?” I said, “no,” but that was before we had the vaccine. Now I feel it is safe to go out using common sense. I still have my patients wear masks on planes. I still have patients try to eat outside as much as possible. And I tell people to take the precautions that make sense, but I tell them to go out and do things because life is short.

I had a patient in his 70s who has many risk factors like heart disease and diabetes. His granddaughter’s Bat Mitzvah in Florida was coming up. He asked: “Can I go?” I told him “Yes,” but to be safe – to wear an N95 mask on the plane and at the event, and stay in his own hotel room, rather than with the whole family. I said, “You need to do this.” Earlier in the pandemic, I saw people who literally died from loneliness and isolation.

He and his wife flew there. He sent me a picture of himself with his granddaughter. When he returned, he showed me a handwritten note from her that said, “I love you so much. Everyone else canceled, which made me cry. You’re the only one who came. You have no idea how much this meant to me.”

He’s back in L.A., and he didn’t get COVID. He said, “It was the best thing I’ve done in years.” That’s what I need to help people with, navigating this world with COVID and assessing risks and benefits. As with all of medicine, my advice is individualized. My advice changes based on the major circulating variant and the rates of the virus in the population, as well as the risk factors of the individual.
 

Q: What are you doing now?

A: I’m trying to avoid getting COVID again, or another booster. I could get pre-exposure monoclonal antibodies but am waiting to do anything further until I see what happens over the fall and winter. I still wear a mask inside but now do a mix of in-person and telemedicine visits. I still try to go to outdoor restaurants, which is easy in California. But I’m flying to see my son in New York and plan to go to Europe this fall for a meeting. I also go to my cabin in Montana every month to get my “dose” of the wilderness. Overall, I travel for conferences and speaking engagements much less because I have learned the joy of staying home.

Thinking back on my life as a doctor, my career began as an intern at Stanford rotating through Ward 5B, the AIDS unit at San Francisco General Hospital, and will likely end with COVID. In spite of all our medical advances, my generation of physicians, much as many generations before us, has a front-row seat to the vulnerability of humans to infectious diseases and how far we still need to go to protect our patients from communicable illness.

A version of this article first appeared on Medscape.com.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts; three books on diabetes; and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.

Early in 2020, Anne Peters, MD, caught COVID-19. The author of Medscape’s “Peters on Diabetes” column was sick in March 2020 before state-mandated lockdowns, and well before there were any vaccines.

She remembers sitting in a small exam room with two patients who had flown to her Los Angeles office from New York. The elderly couple had hearing difficulties, so Dr. Peters sat close to them, putting on a continuous glucose monitor. “At that time, we didn’t think of COVID-19 as being in L.A.,” Dr. Peters recalled, “so I think we were not terribly consistent at mask-wearing due to the need to educate.”

“Several days later, I got COVID, but I didn’t know I had COVID per se. I felt crappy, had a terrible sore throat, lost my sense of taste and smell [which was not yet described as a COVID symptom], was completely exhausted, but had no fever or cough, which were the only criteria for getting COVID tested at the time. I didn’t know I had been exposed until 2 weeks later, when the patient’s assistant returned the sensor warning us to ‘be careful’ with it because the patient and his wife were recovering from COVID.”

That early battle with COVID-19 was just the beginning of what would become a 2-year struggle, including familial loss amid her own health problems and concerns about the under-resourced patients she cares for. Here, she shares her journey through the pandemic with this news organization.
 

Question: Thanks for talking to us. Let’s discuss your journey over these past 2.5 years.

Answer: Everybody has their own COVID story because we all went through this together. Some of us have worse COVID stories, and some of us have better ones, but all have been impacted.

I’m not a sick person. I’m a very healthy person but COVID made me so unwell for 2 years. The brain fog and fatigue were nothing compared to the autonomic neuropathy that affected my heart. It was really limiting for me. And I still don’t know the long-term implications, looking 20-30 years from now.
 

Q: When you initially had COVID, what were your symptoms? What was the impact?

A: I had all the symptoms of COVID, except for a cough and fever. I lost my sense of taste and smell. I had a horrible headache, a sore throat, and I was exhausted. I couldn’t get tested because I didn’t have the right symptoms.

Despite being sick, I never stopped working but just switched to telemedicine. I also took my regular monthly trip to our cabin in Montana. I unknowingly flew on a plane with COVID. I wore a well-fitted N95 mask, so I don’t think I gave anybody COVID. I didn’t give COVID to my partner, Eric, which is hard to believe as – at 77 – he’s older than me. He has diabetes, heart disease, and every other high-risk characteristic. If he’d gotten COVID back then, it would have been terrible, as there were no treatments, but luckily he didn’t get it.
 

Q: When were you officially diagnosed?

A: Two or 3 months after I thought I might have had COVID, I checked my antibodies, which tested strongly positive for a prior COVID infection. That was when I knew all the symptoms I’d had were due to the disease.

Q: Not only were you dealing with your own illness, but also that of those close to you. Can you talk about that?

A: In April 2020, my mother who was in her 90s and otherwise healthy except for dementia, got COVID. She could have gotten it from me. I visited often but wore a mask. She had all the horrible pulmonary symptoms. In her advance directive, she didn’t want to be hospitalized so I kept her in her home. She died from COVID in her own bed. It was fairly brutal, but at least I kept her where she felt comforted.

My 91-year-old dad was living in a different residential facility. Throughout COVID he had become very depressed because his social patterns had changed. Prior to COVID, they all ate together, but during the pandemic they were unable to. He missed his social connections, disliked being isolated in his room, hated everyone in masks.

He was a bit demented, but not so much that he couldn’t communicate with me or remember where his grandson was going to law school. I wasn’t allowed inside the facility, which was hard on him. I hadn’t told him his wife died because the hospice social workers advised me that I shouldn’t give him news that he couldn’t process readily until I could spend time with him. Unfortunately, that time never came. In December 2020, he got COVID. One of the people in that facility had gone to the hospital, came back, and tested negative, but actually had COVID and gave it to my dad. The guy who gave it to my dad didn’t die but my dad was terribly ill. He died 2 weeks short of getting his vaccine. He was coherent enough to have a conversation. I asked him: ‘Do you want to go to the hospital?’ And he said: ‘No, because it would be too scary,’ since he couldn’t be with me. I put him on hospice and held his hand as he died from pulmonary COVID, which was awful. I couldn’t give him enough morphine or valium to ease his breathing. But his last words to me were “I love you,” and at the very end he seemed peaceful, which was a blessing.

I got an autopsy, because he wanted one. Nothing else was wrong with him other than COVID. It destroyed his lungs. The rest of him was fine – no heart disease, cancer, or anything else. He died of COVID-19, the same as my mother.

That same week, my aunt, my only surviving older relative, who was in Des Moines, Iowa, died of COVID-19. All three family members died before the vaccine came out.

It was hard to lose my parents. I’m the only surviving child because my sister died in her 20s. It’s not been an easy pandemic. But what pandemic is easy? I just happened to have lost more people than most. Ironically, my grandfather was one of the legionnaires at the Bellevue-Stratford Hotel in Philadelphia in 1976 and died of Legionnaire’s disease before we knew what was causing the outbreak.
 

Q: Were you still struggling with COVID?

A: COVID impacted my whole body. I lost a lot of weight. I didn’t want to eat, and my gastrointestinal system was not happy. It took a while for my sense of taste and smell to come back. Nothing tasted good. I’m not a foodie; I don’t really care about food. We could get takeout or whatever, but none of it appealed to me. I’m not so sure it was a taste thing, I just didn’t feel like eating.

I didn’t realize I had “brain fog” per se, because I felt stressed and overwhelmed by the pandemic and my patients’ concerns. But one day, about 3 months after I had developed COVID, I woke up without the fog. Which made me aware that I hadn’t been feeling right up until that point.

The worst symptoms, however, were cardiac. I noticed also immediately that my heart rate went up very quickly with minimal exertion. My pulse has always been in the 55-60 bpm range, and suddenly just walking across a room made it go up to over 140 bpm. If I did any aerobic activity, it went up over 160 and would be associated with dyspnea and chest pain. I believed these were all post-COVID symptoms and felt validated when reports of others having similar issues were published in the literature.

Q: Did you continue seeing patients?

A: Yes, of course. Patients never needed their doctors more. In East L.A., where patients don’t have easy access to telemedicine, I kept going into clinic throughout the pandemic. In the more affluent Westside of Los Angeles, we switched to telemedicine, which was quite effective for most. However, because diabetes was associated with an increased risk of hospitalization and death from COVID, my patients were understandably afraid. I’ve never been busier, but (like all health care providers), I became more of a COVID provider than a diabetologist.

Q: Do you feel your battle with COVID impacted your work?

A: It didn’t affect me at work. If I was sitting still, I was fine. Sitting at home at a desk, I didn’t notice any symptoms. But as a habitual stair-user, I would be gasping for breath in the stairwell because I couldn’t go up the stairs to my office as I once could.

I think you empathize more with people who had COVID (when you’ve had it yourself). There was such a huge patient burden. And I think that’s been the thing that’s affected health care providers the most – no matter what specialty we’re in – that nobody has answers.
 

Q: What happened after you had your vaccine?

A: The vaccine itself was fine. I didn’t have any reaction to the first two doses. But the first booster made my cardiac issues worse.

By this point, my cardiac problems stopped me from exercising. I even went to the ER with chest pain once because I was having palpitations and chest pressure caused by simply taking my morning shower. Fortunately, I wasn’t having an MI, but I certainly wasn’t “normal.”

My measure of my fitness is the cross-country skiing trail I use in Montana. I know exactly how far I can ski. Usually I can do the loop in 35 minutes. After COVID, I lasted 10 minutes. I would be tachycardic, short of breath with chest pain radiating down my left arm. I would rest and try to keep going. But with each rest period, I only got worse. I would be laying in the snow and strangers would ask if I needed help.
 

Q: What helped you?

A: I’ve read a lot about long COVID and have tried to learn from the experts. Of course, I never went to a doctor directly, although I did ask colleagues for advice. What I learned was to never push myself. I forced myself to create an exercise schedule where I only exercised three times a week with rest days in between. When exercising, the second my heart rate went above 140 bpm, I stopped until I could get it back down. I would push against this new limit, even though my limit was low.

Additionally, I worked on my breathing patterns and did meditative breathing for 10 minutes twice daily using a commercially available app.

Although progress was slow, I did improve, and by June 2022, I seemed back to normal. I was not as fit as I was prior to COVID and needed to improve, but the tachycardic response to exercise and cardiac symptoms were gone. I felt like my normal self. Normal enough to go on a spot packing trip in the Sierras in August. (Horses carried us and a mule carried the gear over the 12,000-foot pass into the mountains, and then left my friend and me high in the Sierras for a week.) We were camped above 10,000 feet and every day hiked up to another high mountain lake where we fly-fished for trout that we ate for dinner. The hikes were a challenge, but not abnormally so. Not as they would have been while I had long COVID.
 

Q: What is the current atmosphere in your clinic?

A: COVID is much milder now in my vaccinated patients, but I feel most health care providers are exhausted. Many of my staff left when COVID hit because they didn’t want to keep working. It made practicing medicine exhausting. There’s been a shortage of nurses, a shortage of everything. We’ve been required to do a whole lot more than we ever did before. It’s much harder to be a doctor. This pandemic is the first time I’ve ever thought of quitting. Granted, I lost my whole family, or at least the older generation, but it’s just been almost overwhelming.

On the plus side, almost every one of my patients has been vaccinated, because early on, people would ask: “Do you trust this vaccine?” I would reply: “I saw my parents die from COVID when they weren’t vaccinated, so you’re getting vaccinated. This is real and the vaccines help.” It made me very good at convincing people to get vaccines because I knew what it was like to see someone dying from COVID up close.
 

Q: What advice do you have for those struggling with the COVID pandemic?

A: People need to decide what their own risk is for getting sick and how many times they want to get COVID. At this point, I want people to go out, but safely. In the beginning, when my patients said, “can I go visit my granddaughter?” I said, “no,” but that was before we had the vaccine. Now I feel it is safe to go out using common sense. I still have my patients wear masks on planes. I still have patients try to eat outside as much as possible. And I tell people to take the precautions that make sense, but I tell them to go out and do things because life is short.

I had a patient in his 70s who has many risk factors like heart disease and diabetes. His granddaughter’s Bat Mitzvah in Florida was coming up. He asked: “Can I go?” I told him “Yes,” but to be safe – to wear an N95 mask on the plane and at the event, and stay in his own hotel room, rather than with the whole family. I said, “You need to do this.” Earlier in the pandemic, I saw people who literally died from loneliness and isolation.

He and his wife flew there. He sent me a picture of himself with his granddaughter. When he returned, he showed me a handwritten note from her that said, “I love you so much. Everyone else canceled, which made me cry. You’re the only one who came. You have no idea how much this meant to me.”

He’s back in L.A., and he didn’t get COVID. He said, “It was the best thing I’ve done in years.” That’s what I need to help people with, navigating this world with COVID and assessing risks and benefits. As with all of medicine, my advice is individualized. My advice changes based on the major circulating variant and the rates of the virus in the population, as well as the risk factors of the individual.
 

Q: What are you doing now?

A: I’m trying to avoid getting COVID again, or another booster. I could get pre-exposure monoclonal antibodies but am waiting to do anything further until I see what happens over the fall and winter. I still wear a mask inside but now do a mix of in-person and telemedicine visits. I still try to go to outdoor restaurants, which is easy in California. But I’m flying to see my son in New York and plan to go to Europe this fall for a meeting. I also go to my cabin in Montana every month to get my “dose” of the wilderness. Overall, I travel for conferences and speaking engagements much less because I have learned the joy of staying home.

Thinking back on my life as a doctor, my career began as an intern at Stanford rotating through Ward 5B, the AIDS unit at San Francisco General Hospital, and will likely end with COVID. In spite of all our medical advances, my generation of physicians, much as many generations before us, has a front-row seat to the vulnerability of humans to infectious diseases and how far we still need to go to protect our patients from communicable illness.

A version of this article first appeared on Medscape.com.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts; three books on diabetes; and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.

Early in 2020, Anne Peters, MD, caught COVID-19. The author of Medscape’s “Peters on Diabetes” column was sick in March 2020 before state-mandated lockdowns, and well before there were any vaccines.

She remembers sitting in a small exam room with two patients who had flown to her Los Angeles office from New York. The elderly couple had hearing difficulties, so Dr. Peters sat close to them, putting on a continuous glucose monitor. “At that time, we didn’t think of COVID-19 as being in L.A.,” Dr. Peters recalled, “so I think we were not terribly consistent at mask-wearing due to the need to educate.”

“Several days later, I got COVID, but I didn’t know I had COVID per se. I felt crappy, had a terrible sore throat, lost my sense of taste and smell [which was not yet described as a COVID symptom], was completely exhausted, but had no fever or cough, which were the only criteria for getting COVID tested at the time. I didn’t know I had been exposed until 2 weeks later, when the patient’s assistant returned the sensor warning us to ‘be careful’ with it because the patient and his wife were recovering from COVID.”

That early battle with COVID-19 was just the beginning of what would become a 2-year struggle, including familial loss amid her own health problems and concerns about the under-resourced patients she cares for. Here, she shares her journey through the pandemic with this news organization.
 

Question: Thanks for talking to us. Let’s discuss your journey over these past 2.5 years.

Answer: Everybody has their own COVID story because we all went through this together. Some of us have worse COVID stories, and some of us have better ones, but all have been impacted.

I’m not a sick person. I’m a very healthy person but COVID made me so unwell for 2 years. The brain fog and fatigue were nothing compared to the autonomic neuropathy that affected my heart. It was really limiting for me. And I still don’t know the long-term implications, looking 20-30 years from now.
 

Q: When you initially had COVID, what were your symptoms? What was the impact?

A: I had all the symptoms of COVID, except for a cough and fever. I lost my sense of taste and smell. I had a horrible headache, a sore throat, and I was exhausted. I couldn’t get tested because I didn’t have the right symptoms.

Despite being sick, I never stopped working but just switched to telemedicine. I also took my regular monthly trip to our cabin in Montana. I unknowingly flew on a plane with COVID. I wore a well-fitted N95 mask, so I don’t think I gave anybody COVID. I didn’t give COVID to my partner, Eric, which is hard to believe as – at 77 – he’s older than me. He has diabetes, heart disease, and every other high-risk characteristic. If he’d gotten COVID back then, it would have been terrible, as there were no treatments, but luckily he didn’t get it.
 

Q: When were you officially diagnosed?

A: Two or 3 months after I thought I might have had COVID, I checked my antibodies, which tested strongly positive for a prior COVID infection. That was when I knew all the symptoms I’d had were due to the disease.

Q: Not only were you dealing with your own illness, but also that of those close to you. Can you talk about that?

A: In April 2020, my mother who was in her 90s and otherwise healthy except for dementia, got COVID. She could have gotten it from me. I visited often but wore a mask. She had all the horrible pulmonary symptoms. In her advance directive, she didn’t want to be hospitalized so I kept her in her home. She died from COVID in her own bed. It was fairly brutal, but at least I kept her where she felt comforted.

My 91-year-old dad was living in a different residential facility. Throughout COVID he had become very depressed because his social patterns had changed. Prior to COVID, they all ate together, but during the pandemic they were unable to. He missed his social connections, disliked being isolated in his room, hated everyone in masks.

He was a bit demented, but not so much that he couldn’t communicate with me or remember where his grandson was going to law school. I wasn’t allowed inside the facility, which was hard on him. I hadn’t told him his wife died because the hospice social workers advised me that I shouldn’t give him news that he couldn’t process readily until I could spend time with him. Unfortunately, that time never came. In December 2020, he got COVID. One of the people in that facility had gone to the hospital, came back, and tested negative, but actually had COVID and gave it to my dad. The guy who gave it to my dad didn’t die but my dad was terribly ill. He died 2 weeks short of getting his vaccine. He was coherent enough to have a conversation. I asked him: ‘Do you want to go to the hospital?’ And he said: ‘No, because it would be too scary,’ since he couldn’t be with me. I put him on hospice and held his hand as he died from pulmonary COVID, which was awful. I couldn’t give him enough morphine or valium to ease his breathing. But his last words to me were “I love you,” and at the very end he seemed peaceful, which was a blessing.

I got an autopsy, because he wanted one. Nothing else was wrong with him other than COVID. It destroyed his lungs. The rest of him was fine – no heart disease, cancer, or anything else. He died of COVID-19, the same as my mother.

That same week, my aunt, my only surviving older relative, who was in Des Moines, Iowa, died of COVID-19. All three family members died before the vaccine came out.

It was hard to lose my parents. I’m the only surviving child because my sister died in her 20s. It’s not been an easy pandemic. But what pandemic is easy? I just happened to have lost more people than most. Ironically, my grandfather was one of the legionnaires at the Bellevue-Stratford Hotel in Philadelphia in 1976 and died of Legionnaire’s disease before we knew what was causing the outbreak.
 

Q: Were you still struggling with COVID?

A: COVID impacted my whole body. I lost a lot of weight. I didn’t want to eat, and my gastrointestinal system was not happy. It took a while for my sense of taste and smell to come back. Nothing tasted good. I’m not a foodie; I don’t really care about food. We could get takeout or whatever, but none of it appealed to me. I’m not so sure it was a taste thing, I just didn’t feel like eating.

I didn’t realize I had “brain fog” per se, because I felt stressed and overwhelmed by the pandemic and my patients’ concerns. But one day, about 3 months after I had developed COVID, I woke up without the fog. Which made me aware that I hadn’t been feeling right up until that point.

The worst symptoms, however, were cardiac. I noticed also immediately that my heart rate went up very quickly with minimal exertion. My pulse has always been in the 55-60 bpm range, and suddenly just walking across a room made it go up to over 140 bpm. If I did any aerobic activity, it went up over 160 and would be associated with dyspnea and chest pain. I believed these were all post-COVID symptoms and felt validated when reports of others having similar issues were published in the literature.

Q: Did you continue seeing patients?

A: Yes, of course. Patients never needed their doctors more. In East L.A., where patients don’t have easy access to telemedicine, I kept going into clinic throughout the pandemic. In the more affluent Westside of Los Angeles, we switched to telemedicine, which was quite effective for most. However, because diabetes was associated with an increased risk of hospitalization and death from COVID, my patients were understandably afraid. I’ve never been busier, but (like all health care providers), I became more of a COVID provider than a diabetologist.

Q: Do you feel your battle with COVID impacted your work?

A: It didn’t affect me at work. If I was sitting still, I was fine. Sitting at home at a desk, I didn’t notice any symptoms. But as a habitual stair-user, I would be gasping for breath in the stairwell because I couldn’t go up the stairs to my office as I once could.

I think you empathize more with people who had COVID (when you’ve had it yourself). There was such a huge patient burden. And I think that’s been the thing that’s affected health care providers the most – no matter what specialty we’re in – that nobody has answers.
 

Q: What happened after you had your vaccine?

A: The vaccine itself was fine. I didn’t have any reaction to the first two doses. But the first booster made my cardiac issues worse.

By this point, my cardiac problems stopped me from exercising. I even went to the ER with chest pain once because I was having palpitations and chest pressure caused by simply taking my morning shower. Fortunately, I wasn’t having an MI, but I certainly wasn’t “normal.”

My measure of my fitness is the cross-country skiing trail I use in Montana. I know exactly how far I can ski. Usually I can do the loop in 35 minutes. After COVID, I lasted 10 minutes. I would be tachycardic, short of breath with chest pain radiating down my left arm. I would rest and try to keep going. But with each rest period, I only got worse. I would be laying in the snow and strangers would ask if I needed help.
 

Q: What helped you?

A: I’ve read a lot about long COVID and have tried to learn from the experts. Of course, I never went to a doctor directly, although I did ask colleagues for advice. What I learned was to never push myself. I forced myself to create an exercise schedule where I only exercised three times a week with rest days in between. When exercising, the second my heart rate went above 140 bpm, I stopped until I could get it back down. I would push against this new limit, even though my limit was low.

Additionally, I worked on my breathing patterns and did meditative breathing for 10 minutes twice daily using a commercially available app.

Although progress was slow, I did improve, and by June 2022, I seemed back to normal. I was not as fit as I was prior to COVID and needed to improve, but the tachycardic response to exercise and cardiac symptoms were gone. I felt like my normal self. Normal enough to go on a spot packing trip in the Sierras in August. (Horses carried us and a mule carried the gear over the 12,000-foot pass into the mountains, and then left my friend and me high in the Sierras for a week.) We were camped above 10,000 feet and every day hiked up to another high mountain lake where we fly-fished for trout that we ate for dinner. The hikes were a challenge, but not abnormally so. Not as they would have been while I had long COVID.
 

Q: What is the current atmosphere in your clinic?

A: COVID is much milder now in my vaccinated patients, but I feel most health care providers are exhausted. Many of my staff left when COVID hit because they didn’t want to keep working. It made practicing medicine exhausting. There’s been a shortage of nurses, a shortage of everything. We’ve been required to do a whole lot more than we ever did before. It’s much harder to be a doctor. This pandemic is the first time I’ve ever thought of quitting. Granted, I lost my whole family, or at least the older generation, but it’s just been almost overwhelming.

On the plus side, almost every one of my patients has been vaccinated, because early on, people would ask: “Do you trust this vaccine?” I would reply: “I saw my parents die from COVID when they weren’t vaccinated, so you’re getting vaccinated. This is real and the vaccines help.” It made me very good at convincing people to get vaccines because I knew what it was like to see someone dying from COVID up close.
 

Q: What advice do you have for those struggling with the COVID pandemic?

A: People need to decide what their own risk is for getting sick and how many times they want to get COVID. At this point, I want people to go out, but safely. In the beginning, when my patients said, “can I go visit my granddaughter?” I said, “no,” but that was before we had the vaccine. Now I feel it is safe to go out using common sense. I still have my patients wear masks on planes. I still have patients try to eat outside as much as possible. And I tell people to take the precautions that make sense, but I tell them to go out and do things because life is short.

I had a patient in his 70s who has many risk factors like heart disease and diabetes. His granddaughter’s Bat Mitzvah in Florida was coming up. He asked: “Can I go?” I told him “Yes,” but to be safe – to wear an N95 mask on the plane and at the event, and stay in his own hotel room, rather than with the whole family. I said, “You need to do this.” Earlier in the pandemic, I saw people who literally died from loneliness and isolation.

He and his wife flew there. He sent me a picture of himself with his granddaughter. When he returned, he showed me a handwritten note from her that said, “I love you so much. Everyone else canceled, which made me cry. You’re the only one who came. You have no idea how much this meant to me.”

He’s back in L.A., and he didn’t get COVID. He said, “It was the best thing I’ve done in years.” That’s what I need to help people with, navigating this world with COVID and assessing risks and benefits. As with all of medicine, my advice is individualized. My advice changes based on the major circulating variant and the rates of the virus in the population, as well as the risk factors of the individual.
 

Q: What are you doing now?

A: I’m trying to avoid getting COVID again, or another booster. I could get pre-exposure monoclonal antibodies but am waiting to do anything further until I see what happens over the fall and winter. I still wear a mask inside but now do a mix of in-person and telemedicine visits. I still try to go to outdoor restaurants, which is easy in California. But I’m flying to see my son in New York and plan to go to Europe this fall for a meeting. I also go to my cabin in Montana every month to get my “dose” of the wilderness. Overall, I travel for conferences and speaking engagements much less because I have learned the joy of staying home.

Thinking back on my life as a doctor, my career began as an intern at Stanford rotating through Ward 5B, the AIDS unit at San Francisco General Hospital, and will likely end with COVID. In spite of all our medical advances, my generation of physicians, much as many generations before us, has a front-row seat to the vulnerability of humans to infectious diseases and how far we still need to go to protect our patients from communicable illness.

A version of this article first appeared on Medscape.com.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts; three books on diabetes; and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.