Acute Coronary Syndromes

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.

First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.

The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.

The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.

“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
 

Low Prescription Rates

In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.

Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.

The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).

Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.

Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).

“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.

“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.

Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.

The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.

In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.

Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.

“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.

“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
 

‘Concerning’ Data Raise Key Questions

The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.

“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.

“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.

Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.

Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.

Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.

SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.

“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.

“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.

In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”

“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.

None of the studies had commercial funding. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.

First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.

The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.

The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.

“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
 

Low Prescription Rates

In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.

Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.

The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).

Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.

Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).

“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.

“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.

Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.

The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.

In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.

Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.

“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.

“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
 

‘Concerning’ Data Raise Key Questions

The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.

“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.

“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.

Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.

Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.

Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.

SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.

“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.

“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.

In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”

“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.

None of the studies had commercial funding. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.

First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.

The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.

The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.

“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
 

Low Prescription Rates

In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.

Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.

The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).

Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.

Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).

“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.

“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.

Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.

The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.

In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.

Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.

“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.

“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
 

‘Concerning’ Data Raise Key Questions

The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.

“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.

“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.

Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.

Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.

Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.

SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.

“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.

“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.

In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”

“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.

None of the studies had commercial funding. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

While it is increasingly apparent that clonal hematopoiesis of indeterminate potential (CHIP) is associated with conditions that can dramatically affect an individual’s risk for both malignant and cardiovascular diseases, and even death, it has not been clear what to do about it.

Now, researchers at the cutting edge of both oncologic and cardiovascular research are not only defining the prognosis of CHIP with greater granularity but are also finding clues to mitigate the risks.

“It’s a very, very rapidly moving area,” said Christie M. Ballantyne, MD, Director, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, adding that, in many respects, “it’s a totally new area.”
 

CHIP Defined

CHIP was first recognized in the 1990s, when Martin F. Fey, MD, and colleagues from University and Inselspital, Bern, Switzerland, found X-linked inactivation in older women and suggested it was the result of acquired clonality later referred to as being of “indeterminate potential,” although that added syntax is currently a matter of debate.

Further work showed that, while somatic gene mutations occur spontaneously and are an unavoidable consequence of aging, their impact can vary widely.

The majority are “functionally silent,” while others may affect genes crucial to tissue self-renewal and differentiation, Lukasz Gondek, MD, PhD, assistant professor, Johns Hopkins Cellular and Molecular Medicine Program, Baltimore, and colleagues, noted in a recent review.

This results in the outgrowth of affected cells, known as clonal expansion, further dubbed clonal hematopoiesis when it occurs in hematopoietic tissue.

“Even though there’s clonal expansion, there’s no one CHIP,” Dr. Gondek said. “There are different flavors, and it depends on the genes that are mutated in the hematopoietic cells.”

He continued: “The older we get, the more mutations we acquire, and the probability that this mutation will hit the gene that’s responsible for expansion of the clone is higher.”

“That’s why CHIP is very uncommon in people under the age of 40, but it becomes more common in the fifth, sixth, and seventh decade of life and beyond.”

Indeed, it occurs in 10% to 15% of people aged 65 years or older, and in at least 30% of individuals by 80 years of age. In contrast, just 1% of those aged less than 50 years have the condition.

The most commonly affected genes, in around 80% of patients with CHIP, are the epigenetic regulators DNMT3A, TET2, and ASXL1; the DNA damage repair genes PPM1D and TP53; the regulatory tyrosine kinase JAK2; and the messenger RNA spliceosome components SF3B1 and SRSF2.

These mutations can have “two potential consequences,” explained Lachelle D. Weeks, MD, PhD, a hematologist at the Dana-Farber Cancer Institute, Boston.

“One is that there’s a risk of blood cancer development,” as several of the mutations are known drivers of leukemia or myelodysplastic syndromes (MDS).

Although the majority of individuals who acquire clonal hematopoiesis with age will never develop MDS, it nevertheless confers an 11- to 13-fold increased risk or an absolute risk of approximately 0.5%-1.0% per year.

Dr. Weeks continued that “the other side of it, though, is that those cells that have these mutations can also accelerate the risk of developing nonmalignant diseases like cardiovascular disease.”

This, Dr. Gondek explained, is because the mutations will be retained when the stem cells become monocytes or macrophages and, by either silencing or activating individual genes, they can make the cells more pro-inflammatory.

The result is that CHIP is associated with a marked increased risk for arteriosclerotic events such as stroke, myocardial infarction, decompensated heart failure, and cardiogenic shock, and worse outcomes after these events.

Researchers have shown that CHIP-related somatic mutations are associated with a twofold increased risk for coronary heart disease, a more than 2.5-fold increased risk for ischemic stroke, and a fourfold greater risk for myocardial infarction. A study from earlier this year found that CHIP also increases the risk for heart failure with preserved ejection fraction more than twofold.

There is even evidence to suggest that CHIP is associated with more severe acute kidney injury (AKI) and greater post-AKI kidney fibrosis.

The consequence is that individuals with CHIP face a 40% increased risk for all-cause mortality over 8 years.
 

No CHIP Test Yet

All of which has led for some to call for CHIP testing.

However, there are currently no screening programs for CHIP and no plans to introduce any. “So most CHIP is actually being diagnosed incidentally, when patients get genetic testing for some other indication,” said Dr. Weeks.

“The patients that we see in our CHIP clinic at Dana-Farber have genetic testing because they have low blood counts,” she continued, “and somebody’s trying to figure out: Do you have MDS?”

Other patients have genetic testing due to a family history of other cancers, “and so they’re getting hereditary cancer panels to determine if they have Lynch syndrome, or other hereditary syndromes,” which are picking up gene mutations associated with CHIP.

In other cases, study protocols are identifying CHIP “in various research contexts, and then as a follow-up, some of those patients end up with our clinic,” added Dr. Weeks.

Due to the associated risks for CHIP, “obviously everyone wants to know whether they are at risk for hematologic malignancy, or not,” said Dr. Gondek. To those ends, Dr. Weeks and colleagues developed the clonal hematopoiesis risk score (CHRS).

Published by NEJM Evidence in 2023, the score takes a range of predictive variables, such as age, number of mutations and their degree of associated risk, the variant allele fraction, and a series of blood indices to define patients as low-, intermediate-, or high-risk.

“A little over half” of high-risk individuals “will develop a blood cancer” such as MDS or acute myeloid leukemia (AML)” over the next 10 years, Weeks explained, while “for your intermediate risk folks, in that same time period, 7%-8% of them will develop a blood cancer.”

In low-risk individuals, the 10-year risk for MDS or AML is just 1%.

Dr. Weeks noted the “caveat that there are environmental factors or patient-specific issues that might increase your risk that are not considered in the calculator,” such the presence of hereditary cancer syndromes, “or if you’re getting chemotherapy for other cancers.”

From a cardiology point of view, Dr. Ballantyne said that, above all, “cardiologists need to be aware that some of these people are at increased risk for cardiovascular events.” This prompted a team including Dr. Weeks and Dr. Ballantyne to study whether the CHRS can also predict cardiovascular risk.

They found that people designated low-risk on the score faced an 8% increased risk for all-cause mortality vs individuals without CHIP during a median follow-up of 7 years. This rose to a 12% increase in intermediate-risk individuals.

And those deemed high-risk had a 2.5-fold increased risk for early mortality and a threefold higher risk for cardiovascular death.

Dr. Weeks noted: “We have not done a dedicated study to define a cardiovascular disease-specific calculator for CHIP,” but in the meantime, the CHRS is a “very reasonable way to estimate what someone’s risk of progression or adverse events is for cardiovascular disease.”

For clinicians, however, the key question becomes: What can be done to mitigate the risks, particularly in high-risk individuals?

For malignant conditions, the approach is to monitor patients, although “we and other centers are in the process of developing various interventional clinical trials to test various agents on their ability to improve blood counts, as well as to mitigate the risk of progression to overt blood cancer,” said Dr. Weeks.
 

Treat CHIP Like Lipoprotein(a)?

As for cardiovascular risk, Dr. Ballantyne believes that, because CHIP is an unmodifiable risk factor, an example to follow could be lipoprotein(a) (LP[a]).

“We don’t have a therapy specifically to target LP(a) yet, but we do know that the things that benefit in general,” he said, such as “taking a statin, lowering blood pressure into the optimal zone, diet ,and exercise.”

“What we do in our clinic, and what others have been doing,” Dr. Weeks added, “is for every patient who comes in and is diagnosed with CHIP, we are referring them to preventative cardiology for very aggressive preventative management.”

Finally, both Dr. Ballantyne and Dr. Weeks agree that there are many potential innovations on the horizon.

“It’s pretty exciting in terms of beginning to understand some of the links between aging, cardiovascular disease, and cancer that we had not been thinking about,” Dr. Ballantyne said.

On the malignant side, Dr. Weeks is already working on a prospective study to determine how the risks associated with CHIP evolve when patients undergo chemotherapy and radiation for other cancers.

“That will be really exciting and will help us to develop a specific calculator in that context,” she said, adding that a cardiovascular-specific calculator “is also coming down the line.”

Dr. Weeks declared relationships with Abbvie, Vertex, and Sobi. Dr. Ballantyne declared a relationship with Ten Sixteen Bio, and funding from the National Heart, Lung, and Blood Institute. No other relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

While it is increasingly apparent that clonal hematopoiesis of indeterminate potential (CHIP) is associated with conditions that can dramatically affect an individual’s risk for both malignant and cardiovascular diseases, and even death, it has not been clear what to do about it.

Now, researchers at the cutting edge of both oncologic and cardiovascular research are not only defining the prognosis of CHIP with greater granularity but are also finding clues to mitigate the risks.

“It’s a very, very rapidly moving area,” said Christie M. Ballantyne, MD, Director, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, adding that, in many respects, “it’s a totally new area.”
 

CHIP Defined

CHIP was first recognized in the 1990s, when Martin F. Fey, MD, and colleagues from University and Inselspital, Bern, Switzerland, found X-linked inactivation in older women and suggested it was the result of acquired clonality later referred to as being of “indeterminate potential,” although that added syntax is currently a matter of debate.

Further work showed that, while somatic gene mutations occur spontaneously and are an unavoidable consequence of aging, their impact can vary widely.

The majority are “functionally silent,” while others may affect genes crucial to tissue self-renewal and differentiation, Lukasz Gondek, MD, PhD, assistant professor, Johns Hopkins Cellular and Molecular Medicine Program, Baltimore, and colleagues, noted in a recent review.

This results in the outgrowth of affected cells, known as clonal expansion, further dubbed clonal hematopoiesis when it occurs in hematopoietic tissue.

“Even though there’s clonal expansion, there’s no one CHIP,” Dr. Gondek said. “There are different flavors, and it depends on the genes that are mutated in the hematopoietic cells.”

He continued: “The older we get, the more mutations we acquire, and the probability that this mutation will hit the gene that’s responsible for expansion of the clone is higher.”

“That’s why CHIP is very uncommon in people under the age of 40, but it becomes more common in the fifth, sixth, and seventh decade of life and beyond.”

Indeed, it occurs in 10% to 15% of people aged 65 years or older, and in at least 30% of individuals by 80 years of age. In contrast, just 1% of those aged less than 50 years have the condition.

The most commonly affected genes, in around 80% of patients with CHIP, are the epigenetic regulators DNMT3A, TET2, and ASXL1; the DNA damage repair genes PPM1D and TP53; the regulatory tyrosine kinase JAK2; and the messenger RNA spliceosome components SF3B1 and SRSF2.

These mutations can have “two potential consequences,” explained Lachelle D. Weeks, MD, PhD, a hematologist at the Dana-Farber Cancer Institute, Boston.

“One is that there’s a risk of blood cancer development,” as several of the mutations are known drivers of leukemia or myelodysplastic syndromes (MDS).

Although the majority of individuals who acquire clonal hematopoiesis with age will never develop MDS, it nevertheless confers an 11- to 13-fold increased risk or an absolute risk of approximately 0.5%-1.0% per year.

Dr. Weeks continued that “the other side of it, though, is that those cells that have these mutations can also accelerate the risk of developing nonmalignant diseases like cardiovascular disease.”

This, Dr. Gondek explained, is because the mutations will be retained when the stem cells become monocytes or macrophages and, by either silencing or activating individual genes, they can make the cells more pro-inflammatory.

The result is that CHIP is associated with a marked increased risk for arteriosclerotic events such as stroke, myocardial infarction, decompensated heart failure, and cardiogenic shock, and worse outcomes after these events.

Researchers have shown that CHIP-related somatic mutations are associated with a twofold increased risk for coronary heart disease, a more than 2.5-fold increased risk for ischemic stroke, and a fourfold greater risk for myocardial infarction. A study from earlier this year found that CHIP also increases the risk for heart failure with preserved ejection fraction more than twofold.

There is even evidence to suggest that CHIP is associated with more severe acute kidney injury (AKI) and greater post-AKI kidney fibrosis.

The consequence is that individuals with CHIP face a 40% increased risk for all-cause mortality over 8 years.
 

No CHIP Test Yet

All of which has led for some to call for CHIP testing.

However, there are currently no screening programs for CHIP and no plans to introduce any. “So most CHIP is actually being diagnosed incidentally, when patients get genetic testing for some other indication,” said Dr. Weeks.

“The patients that we see in our CHIP clinic at Dana-Farber have genetic testing because they have low blood counts,” she continued, “and somebody’s trying to figure out: Do you have MDS?”

Other patients have genetic testing due to a family history of other cancers, “and so they’re getting hereditary cancer panels to determine if they have Lynch syndrome, or other hereditary syndromes,” which are picking up gene mutations associated with CHIP.

In other cases, study protocols are identifying CHIP “in various research contexts, and then as a follow-up, some of those patients end up with our clinic,” added Dr. Weeks.

Due to the associated risks for CHIP, “obviously everyone wants to know whether they are at risk for hematologic malignancy, or not,” said Dr. Gondek. To those ends, Dr. Weeks and colleagues developed the clonal hematopoiesis risk score (CHRS).

Published by NEJM Evidence in 2023, the score takes a range of predictive variables, such as age, number of mutations and their degree of associated risk, the variant allele fraction, and a series of blood indices to define patients as low-, intermediate-, or high-risk.

“A little over half” of high-risk individuals “will develop a blood cancer” such as MDS or acute myeloid leukemia (AML)” over the next 10 years, Weeks explained, while “for your intermediate risk folks, in that same time period, 7%-8% of them will develop a blood cancer.”

In low-risk individuals, the 10-year risk for MDS or AML is just 1%.

Dr. Weeks noted the “caveat that there are environmental factors or patient-specific issues that might increase your risk that are not considered in the calculator,” such the presence of hereditary cancer syndromes, “or if you’re getting chemotherapy for other cancers.”

From a cardiology point of view, Dr. Ballantyne said that, above all, “cardiologists need to be aware that some of these people are at increased risk for cardiovascular events.” This prompted a team including Dr. Weeks and Dr. Ballantyne to study whether the CHRS can also predict cardiovascular risk.

They found that people designated low-risk on the score faced an 8% increased risk for all-cause mortality vs individuals without CHIP during a median follow-up of 7 years. This rose to a 12% increase in intermediate-risk individuals.

And those deemed high-risk had a 2.5-fold increased risk for early mortality and a threefold higher risk for cardiovascular death.

Dr. Weeks noted: “We have not done a dedicated study to define a cardiovascular disease-specific calculator for CHIP,” but in the meantime, the CHRS is a “very reasonable way to estimate what someone’s risk of progression or adverse events is for cardiovascular disease.”

For clinicians, however, the key question becomes: What can be done to mitigate the risks, particularly in high-risk individuals?

For malignant conditions, the approach is to monitor patients, although “we and other centers are in the process of developing various interventional clinical trials to test various agents on their ability to improve blood counts, as well as to mitigate the risk of progression to overt blood cancer,” said Dr. Weeks.
 

Treat CHIP Like Lipoprotein(a)?

As for cardiovascular risk, Dr. Ballantyne believes that, because CHIP is an unmodifiable risk factor, an example to follow could be lipoprotein(a) (LP[a]).

“We don’t have a therapy specifically to target LP(a) yet, but we do know that the things that benefit in general,” he said, such as “taking a statin, lowering blood pressure into the optimal zone, diet ,and exercise.”

“What we do in our clinic, and what others have been doing,” Dr. Weeks added, “is for every patient who comes in and is diagnosed with CHIP, we are referring them to preventative cardiology for very aggressive preventative management.”

Finally, both Dr. Ballantyne and Dr. Weeks agree that there are many potential innovations on the horizon.

“It’s pretty exciting in terms of beginning to understand some of the links between aging, cardiovascular disease, and cancer that we had not been thinking about,” Dr. Ballantyne said.

On the malignant side, Dr. Weeks is already working on a prospective study to determine how the risks associated with CHIP evolve when patients undergo chemotherapy and radiation for other cancers.

“That will be really exciting and will help us to develop a specific calculator in that context,” she said, adding that a cardiovascular-specific calculator “is also coming down the line.”

Dr. Weeks declared relationships with Abbvie, Vertex, and Sobi. Dr. Ballantyne declared a relationship with Ten Sixteen Bio, and funding from the National Heart, Lung, and Blood Institute. No other relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

While it is increasingly apparent that clonal hematopoiesis of indeterminate potential (CHIP) is associated with conditions that can dramatically affect an individual’s risk for both malignant and cardiovascular diseases, and even death, it has not been clear what to do about it.

Now, researchers at the cutting edge of both oncologic and cardiovascular research are not only defining the prognosis of CHIP with greater granularity but are also finding clues to mitigate the risks.

“It’s a very, very rapidly moving area,” said Christie M. Ballantyne, MD, Director, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, adding that, in many respects, “it’s a totally new area.”
 

CHIP Defined

CHIP was first recognized in the 1990s, when Martin F. Fey, MD, and colleagues from University and Inselspital, Bern, Switzerland, found X-linked inactivation in older women and suggested it was the result of acquired clonality later referred to as being of “indeterminate potential,” although that added syntax is currently a matter of debate.

Further work showed that, while somatic gene mutations occur spontaneously and are an unavoidable consequence of aging, their impact can vary widely.

The majority are “functionally silent,” while others may affect genes crucial to tissue self-renewal and differentiation, Lukasz Gondek, MD, PhD, assistant professor, Johns Hopkins Cellular and Molecular Medicine Program, Baltimore, and colleagues, noted in a recent review.

This results in the outgrowth of affected cells, known as clonal expansion, further dubbed clonal hematopoiesis when it occurs in hematopoietic tissue.

“Even though there’s clonal expansion, there’s no one CHIP,” Dr. Gondek said. “There are different flavors, and it depends on the genes that are mutated in the hematopoietic cells.”

He continued: “The older we get, the more mutations we acquire, and the probability that this mutation will hit the gene that’s responsible for expansion of the clone is higher.”

“That’s why CHIP is very uncommon in people under the age of 40, but it becomes more common in the fifth, sixth, and seventh decade of life and beyond.”

Indeed, it occurs in 10% to 15% of people aged 65 years or older, and in at least 30% of individuals by 80 years of age. In contrast, just 1% of those aged less than 50 years have the condition.

The most commonly affected genes, in around 80% of patients with CHIP, are the epigenetic regulators DNMT3A, TET2, and ASXL1; the DNA damage repair genes PPM1D and TP53; the regulatory tyrosine kinase JAK2; and the messenger RNA spliceosome components SF3B1 and SRSF2.

These mutations can have “two potential consequences,” explained Lachelle D. Weeks, MD, PhD, a hematologist at the Dana-Farber Cancer Institute, Boston.

“One is that there’s a risk of blood cancer development,” as several of the mutations are known drivers of leukemia or myelodysplastic syndromes (MDS).

Although the majority of individuals who acquire clonal hematopoiesis with age will never develop MDS, it nevertheless confers an 11- to 13-fold increased risk or an absolute risk of approximately 0.5%-1.0% per year.

Dr. Weeks continued that “the other side of it, though, is that those cells that have these mutations can also accelerate the risk of developing nonmalignant diseases like cardiovascular disease.”

This, Dr. Gondek explained, is because the mutations will be retained when the stem cells become monocytes or macrophages and, by either silencing or activating individual genes, they can make the cells more pro-inflammatory.

The result is that CHIP is associated with a marked increased risk for arteriosclerotic events such as stroke, myocardial infarction, decompensated heart failure, and cardiogenic shock, and worse outcomes after these events.

Researchers have shown that CHIP-related somatic mutations are associated with a twofold increased risk for coronary heart disease, a more than 2.5-fold increased risk for ischemic stroke, and a fourfold greater risk for myocardial infarction. A study from earlier this year found that CHIP also increases the risk for heart failure with preserved ejection fraction more than twofold.

There is even evidence to suggest that CHIP is associated with more severe acute kidney injury (AKI) and greater post-AKI kidney fibrosis.

The consequence is that individuals with CHIP face a 40% increased risk for all-cause mortality over 8 years.
 

No CHIP Test Yet

All of which has led for some to call for CHIP testing.

However, there are currently no screening programs for CHIP and no plans to introduce any. “So most CHIP is actually being diagnosed incidentally, when patients get genetic testing for some other indication,” said Dr. Weeks.

“The patients that we see in our CHIP clinic at Dana-Farber have genetic testing because they have low blood counts,” she continued, “and somebody’s trying to figure out: Do you have MDS?”

Other patients have genetic testing due to a family history of other cancers, “and so they’re getting hereditary cancer panels to determine if they have Lynch syndrome, or other hereditary syndromes,” which are picking up gene mutations associated with CHIP.

In other cases, study protocols are identifying CHIP “in various research contexts, and then as a follow-up, some of those patients end up with our clinic,” added Dr. Weeks.

Due to the associated risks for CHIP, “obviously everyone wants to know whether they are at risk for hematologic malignancy, or not,” said Dr. Gondek. To those ends, Dr. Weeks and colleagues developed the clonal hematopoiesis risk score (CHRS).

Published by NEJM Evidence in 2023, the score takes a range of predictive variables, such as age, number of mutations and their degree of associated risk, the variant allele fraction, and a series of blood indices to define patients as low-, intermediate-, or high-risk.

“A little over half” of high-risk individuals “will develop a blood cancer” such as MDS or acute myeloid leukemia (AML)” over the next 10 years, Weeks explained, while “for your intermediate risk folks, in that same time period, 7%-8% of them will develop a blood cancer.”

In low-risk individuals, the 10-year risk for MDS or AML is just 1%.

Dr. Weeks noted the “caveat that there are environmental factors or patient-specific issues that might increase your risk that are not considered in the calculator,” such the presence of hereditary cancer syndromes, “or if you’re getting chemotherapy for other cancers.”

From a cardiology point of view, Dr. Ballantyne said that, above all, “cardiologists need to be aware that some of these people are at increased risk for cardiovascular events.” This prompted a team including Dr. Weeks and Dr. Ballantyne to study whether the CHRS can also predict cardiovascular risk.

They found that people designated low-risk on the score faced an 8% increased risk for all-cause mortality vs individuals without CHIP during a median follow-up of 7 years. This rose to a 12% increase in intermediate-risk individuals.

And those deemed high-risk had a 2.5-fold increased risk for early mortality and a threefold higher risk for cardiovascular death.

Dr. Weeks noted: “We have not done a dedicated study to define a cardiovascular disease-specific calculator for CHIP,” but in the meantime, the CHRS is a “very reasonable way to estimate what someone’s risk of progression or adverse events is for cardiovascular disease.”

For clinicians, however, the key question becomes: What can be done to mitigate the risks, particularly in high-risk individuals?

For malignant conditions, the approach is to monitor patients, although “we and other centers are in the process of developing various interventional clinical trials to test various agents on their ability to improve blood counts, as well as to mitigate the risk of progression to overt blood cancer,” said Dr. Weeks.
 

Treat CHIP Like Lipoprotein(a)?

As for cardiovascular risk, Dr. Ballantyne believes that, because CHIP is an unmodifiable risk factor, an example to follow could be lipoprotein(a) (LP[a]).

“We don’t have a therapy specifically to target LP(a) yet, but we do know that the things that benefit in general,” he said, such as “taking a statin, lowering blood pressure into the optimal zone, diet ,and exercise.”

“What we do in our clinic, and what others have been doing,” Dr. Weeks added, “is for every patient who comes in and is diagnosed with CHIP, we are referring them to preventative cardiology for very aggressive preventative management.”

Finally, both Dr. Ballantyne and Dr. Weeks agree that there are many potential innovations on the horizon.

“It’s pretty exciting in terms of beginning to understand some of the links between aging, cardiovascular disease, and cancer that we had not been thinking about,” Dr. Ballantyne said.

On the malignant side, Dr. Weeks is already working on a prospective study to determine how the risks associated with CHIP evolve when patients undergo chemotherapy and radiation for other cancers.

“That will be really exciting and will help us to develop a specific calculator in that context,” she said, adding that a cardiovascular-specific calculator “is also coming down the line.”

Dr. Weeks declared relationships with Abbvie, Vertex, and Sobi. Dr. Ballantyne declared a relationship with Ten Sixteen Bio, and funding from the National Heart, Lung, and Blood Institute. No other relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

A new study raises a cautionary note on time-restricted eating (TRE), a type of intermittent fasting that is gaining popularity.

The observational analysis of over 20,000 US adults showed that those who limited their eating to a period of less than 8 hours per day had a higher risk for cardiovascular mortality compared with peers who ate across the typical 12-16 hours per day. This was the case in the overall sample and in those with cardiovascular disease (CVD) or cancer.

Lead author Victor Wenze Zhong, PhD, cautioned that the findings “require replication and we cannot demonstrate 8-hour TRE causes cardiovascular death in this observational study.

“However, it’s important for patients, particularly those with existing heart conditions or cancer, to be aware of the positive association between an 8-hour eating window and cardiovascular death,” Dr. Zhong, professor and chair, Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China, told this news organization. 

The results (Abstract P192) were presented March 18 at the American Heart Association (AHA) Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions 2024.
 

‘Provocative’ Results 

Short-term randomized controlled trials have suggested that 8-hour TRE may improve cardiometabolic risk profiles, but the potential long-term effects of this eating pattern are unknown. 

The observation that TRE may have short-term benefits but long-term adverse effects is “interesting and provocative” and needs further study, Christopher D. Gardner, PhD, professor of medicine at Stanford University in California, who wasn’t involved in the study, said in a conference statement, and he agreed that much more research is needed. 

The researchers analyzed data on dietary patterns for 20,078 adults (mean age, 48 years; 50% men; 73% non-Hispanic White) who participated in the 2003-2018 National Health and Nutrition Examination Surveys (NHANES). All of them completed two 24-hour dietary recall questionnaires within the first year of enrollment. Deaths through the end of 2019 were determined via the National Death Index.

During a median follow-up of 8 years, there were 2797 deaths due to any cause, including 840 CV deaths and 643 cancer deaths. 

In the overall sample, compared with an eating duration of 12-16 hours, 8-hour TRE was significantly associated with an increased risk for CV mortality (hazard ratio [HR], 1.91; 95% CI, 1.20-3.03).

This association was also observed in adults with CVD (HR, 2.07; 95% CI, 1.14-3.78) and adults with cancer (HR, 3.04; 95% CI, 1.44-6.41). 

Other eating durations were not associated with CV mortality, except for eating duration of 8 to less than 10 hours in people with CVD (HR, 1.66; 95% CI, 1.03-2.67). 

No significant associations were found between eating duration and all-cause or cancer mortality in the overall sample and CVD/cancer subsamples, except that eating duration of more than 16 hours was associated with a lower risk for cancer mortality in people with cancer (HR, 0.47; 95% CI, 0.23-0.95).
 

Quality More Important Than Timing 

Dr. Zhong noted that the study doesn’t address the underlying mechanisms driving the observed association between 8-hour TRE and CV death. 

“However, we did observe that people who restricted eating to a period less than 8 hours per day had less lean muscle mass compared with those with typical eating duration of 12-16 hours. Loss of lean body mass has been linked to higher risk of cardiovascular mortality,” Dr. Zhong said. 

“Based on the evidence as of now, focusing on what people eat appears to be more important than focusing on the time when they eat. There are certain dietary approaches with compelling health benefits to choose, such as DASH diet and Mediterranean diet,” Dr. Zhong said.

Intermittent fasting is “certainly an interesting concept and one on which the potential mechanisms underlying the improvements in short outcome studies and preclinical studies in animals are strongly being pursued,” Sean P. Heffron, MD, cardiologist at the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, New York, who wasn’t involved in the study, told this news organization. 

Dr. Heffron expressed skepticism about the study results calling them “far from complete” and noted that data on diet was based on only 2-day diet records without correction for confounding variables. 

Dr. Heffron also noted that the restricted diet group has more smokers and more men. “I would “strongly anticipate that once appropriate corrections are made, the findings will no longer persist in statistical significance,” Dr. Heffron said.

He emphasized the need for more rigorous research before making clinical recommendations. When patients ask about intermittent fasting, Dr. Heffron said he tells them, “If it works for you, that’s fine,” but he doesn’t provide a recommendation for or against it. 

Funding for the study was provided by the National Key Research and Development Program of China and the National Science Foundation of China. Zhong, Dr. Heffron and Dr. Gardner have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A new study raises a cautionary note on time-restricted eating (TRE), a type of intermittent fasting that is gaining popularity.

The observational analysis of over 20,000 US adults showed that those who limited their eating to a period of less than 8 hours per day had a higher risk for cardiovascular mortality compared with peers who ate across the typical 12-16 hours per day. This was the case in the overall sample and in those with cardiovascular disease (CVD) or cancer.

Lead author Victor Wenze Zhong, PhD, cautioned that the findings “require replication and we cannot demonstrate 8-hour TRE causes cardiovascular death in this observational study.

“However, it’s important for patients, particularly those with existing heart conditions or cancer, to be aware of the positive association between an 8-hour eating window and cardiovascular death,” Dr. Zhong, professor and chair, Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China, told this news organization. 

The results (Abstract P192) were presented March 18 at the American Heart Association (AHA) Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions 2024.
 

‘Provocative’ Results 

Short-term randomized controlled trials have suggested that 8-hour TRE may improve cardiometabolic risk profiles, but the potential long-term effects of this eating pattern are unknown. 

The observation that TRE may have short-term benefits but long-term adverse effects is “interesting and provocative” and needs further study, Christopher D. Gardner, PhD, professor of medicine at Stanford University in California, who wasn’t involved in the study, said in a conference statement, and he agreed that much more research is needed. 

The researchers analyzed data on dietary patterns for 20,078 adults (mean age, 48 years; 50% men; 73% non-Hispanic White) who participated in the 2003-2018 National Health and Nutrition Examination Surveys (NHANES). All of them completed two 24-hour dietary recall questionnaires within the first year of enrollment. Deaths through the end of 2019 were determined via the National Death Index.

During a median follow-up of 8 years, there were 2797 deaths due to any cause, including 840 CV deaths and 643 cancer deaths. 

In the overall sample, compared with an eating duration of 12-16 hours, 8-hour TRE was significantly associated with an increased risk for CV mortality (hazard ratio [HR], 1.91; 95% CI, 1.20-3.03).

This association was also observed in adults with CVD (HR, 2.07; 95% CI, 1.14-3.78) and adults with cancer (HR, 3.04; 95% CI, 1.44-6.41). 

Other eating durations were not associated with CV mortality, except for eating duration of 8 to less than 10 hours in people with CVD (HR, 1.66; 95% CI, 1.03-2.67). 

No significant associations were found between eating duration and all-cause or cancer mortality in the overall sample and CVD/cancer subsamples, except that eating duration of more than 16 hours was associated with a lower risk for cancer mortality in people with cancer (HR, 0.47; 95% CI, 0.23-0.95).
 

Quality More Important Than Timing 

Dr. Zhong noted that the study doesn’t address the underlying mechanisms driving the observed association between 8-hour TRE and CV death. 

“However, we did observe that people who restricted eating to a period less than 8 hours per day had less lean muscle mass compared with those with typical eating duration of 12-16 hours. Loss of lean body mass has been linked to higher risk of cardiovascular mortality,” Dr. Zhong said. 

“Based on the evidence as of now, focusing on what people eat appears to be more important than focusing on the time when they eat. There are certain dietary approaches with compelling health benefits to choose, such as DASH diet and Mediterranean diet,” Dr. Zhong said.

Intermittent fasting is “certainly an interesting concept and one on which the potential mechanisms underlying the improvements in short outcome studies and preclinical studies in animals are strongly being pursued,” Sean P. Heffron, MD, cardiologist at the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, New York, who wasn’t involved in the study, told this news organization. 

Dr. Heffron expressed skepticism about the study results calling them “far from complete” and noted that data on diet was based on only 2-day diet records without correction for confounding variables. 

Dr. Heffron also noted that the restricted diet group has more smokers and more men. “I would “strongly anticipate that once appropriate corrections are made, the findings will no longer persist in statistical significance,” Dr. Heffron said.

He emphasized the need for more rigorous research before making clinical recommendations. When patients ask about intermittent fasting, Dr. Heffron said he tells them, “If it works for you, that’s fine,” but he doesn’t provide a recommendation for or against it. 

Funding for the study was provided by the National Key Research and Development Program of China and the National Science Foundation of China. Zhong, Dr. Heffron and Dr. Gardner have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A new study raises a cautionary note on time-restricted eating (TRE), a type of intermittent fasting that is gaining popularity.

The observational analysis of over 20,000 US adults showed that those who limited their eating to a period of less than 8 hours per day had a higher risk for cardiovascular mortality compared with peers who ate across the typical 12-16 hours per day. This was the case in the overall sample and in those with cardiovascular disease (CVD) or cancer.

Lead author Victor Wenze Zhong, PhD, cautioned that the findings “require replication and we cannot demonstrate 8-hour TRE causes cardiovascular death in this observational study.

“However, it’s important for patients, particularly those with existing heart conditions or cancer, to be aware of the positive association between an 8-hour eating window and cardiovascular death,” Dr. Zhong, professor and chair, Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China, told this news organization. 

The results (Abstract P192) were presented March 18 at the American Heart Association (AHA) Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions 2024.
 

‘Provocative’ Results 

Short-term randomized controlled trials have suggested that 8-hour TRE may improve cardiometabolic risk profiles, but the potential long-term effects of this eating pattern are unknown. 

The observation that TRE may have short-term benefits but long-term adverse effects is “interesting and provocative” and needs further study, Christopher D. Gardner, PhD, professor of medicine at Stanford University in California, who wasn’t involved in the study, said in a conference statement, and he agreed that much more research is needed. 

The researchers analyzed data on dietary patterns for 20,078 adults (mean age, 48 years; 50% men; 73% non-Hispanic White) who participated in the 2003-2018 National Health and Nutrition Examination Surveys (NHANES). All of them completed two 24-hour dietary recall questionnaires within the first year of enrollment. Deaths through the end of 2019 were determined via the National Death Index.

During a median follow-up of 8 years, there were 2797 deaths due to any cause, including 840 CV deaths and 643 cancer deaths. 

In the overall sample, compared with an eating duration of 12-16 hours, 8-hour TRE was significantly associated with an increased risk for CV mortality (hazard ratio [HR], 1.91; 95% CI, 1.20-3.03).

This association was also observed in adults with CVD (HR, 2.07; 95% CI, 1.14-3.78) and adults with cancer (HR, 3.04; 95% CI, 1.44-6.41). 

Other eating durations were not associated with CV mortality, except for eating duration of 8 to less than 10 hours in people with CVD (HR, 1.66; 95% CI, 1.03-2.67). 

No significant associations were found between eating duration and all-cause or cancer mortality in the overall sample and CVD/cancer subsamples, except that eating duration of more than 16 hours was associated with a lower risk for cancer mortality in people with cancer (HR, 0.47; 95% CI, 0.23-0.95).
 

Quality More Important Than Timing 

Dr. Zhong noted that the study doesn’t address the underlying mechanisms driving the observed association between 8-hour TRE and CV death. 

“However, we did observe that people who restricted eating to a period less than 8 hours per day had less lean muscle mass compared with those with typical eating duration of 12-16 hours. Loss of lean body mass has been linked to higher risk of cardiovascular mortality,” Dr. Zhong said. 

“Based on the evidence as of now, focusing on what people eat appears to be more important than focusing on the time when they eat. There are certain dietary approaches with compelling health benefits to choose, such as DASH diet and Mediterranean diet,” Dr. Zhong said.

Intermittent fasting is “certainly an interesting concept and one on which the potential mechanisms underlying the improvements in short outcome studies and preclinical studies in animals are strongly being pursued,” Sean P. Heffron, MD, cardiologist at the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, New York, who wasn’t involved in the study, told this news organization. 

Dr. Heffron expressed skepticism about the study results calling them “far from complete” and noted that data on diet was based on only 2-day diet records without correction for confounding variables. 

Dr. Heffron also noted that the restricted diet group has more smokers and more men. “I would “strongly anticipate that once appropriate corrections are made, the findings will no longer persist in statistical significance,” Dr. Heffron said.

He emphasized the need for more rigorous research before making clinical recommendations. When patients ask about intermittent fasting, Dr. Heffron said he tells them, “If it works for you, that’s fine,” but he doesn’t provide a recommendation for or against it. 

Funding for the study was provided by the National Key Research and Development Program of China and the National Science Foundation of China. Zhong, Dr. Heffron and Dr. Gardner have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

TOPLINE:

Depression is linked to a significantly increased risk for cardiovascular disease (CVD), particularly in women, new data from a large retrospective cohort study show. Researchers suggest that screening and treating patients for depression may lead to a decreased incidence of CVD.

METHODOLOGY:

• Researchers analyzed health insurance claims from more than 4 million Japanese patients filed between 2005 and 2022.
• Participants were 18-75 (median age, 44) without a history of CVD or stroke, heart failure, or atrial fibrillation.
• Investigators followed participants for a mean period of 2.5-3.5 years to observe the number of CVD events in those who had a diagnosis of depression.
• During the follow-up period, there were 119,000 CVD events in men (14 per 10,000 person-years) and 61,800 CVD events in women (111 per 10,000 person-years).

TAKEAWAY:

• Compared with women without depression, those with depression had a 64% higher risk for CVD (hazard ratio [HR], 1.64), while men with depression had a 39% higher risk for CVD vs their counterparts without depression (HR, 1.39; P < .001).
• This association was significant even after controlling for various factors such as body mass index, diabetes, smoking, alcohol consumption, and physical inactivity.
• Investigators offered several theories about the increased risk for CVD in women with depression, including how depression during hormonal shifts can contribute to a greater impact on cardiovascular health.

IN PRACTICE:

“Healthcare professionals must recognize the important role of depression in the development of CVD and emphasize the importance of a comprehensive, patient-centered approach to its prevention and management,” study author Hidehiro Kaneko, MD, said in a press release. “Assessing the risk of CVD in depressed patients and treating and preventing depression may lead to a decrease of CVD cases.”

SOURCE:

Keitaro Senoo, MD, of the Kyoto Prefectural University of Medicine, Kyoto, Japan, led the study, which was published online on March 12 in JACC: Asia.

LIMITATIONS:

The study is observational, so causality between depression and subsequent CVD events cannot be established. In addition, depression severity is unknown.

DISCLOSURES:

The study was funded by the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science, and Technology, Japan. There were no disclosures reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Depression is linked to a significantly increased risk for cardiovascular disease (CVD), particularly in women, new data from a large retrospective cohort study show. Researchers suggest that screening and treating patients for depression may lead to a decreased incidence of CVD.

METHODOLOGY:

• Researchers analyzed health insurance claims from more than 4 million Japanese patients filed between 2005 and 2022.
• Participants were 18-75 (median age, 44) without a history of CVD or stroke, heart failure, or atrial fibrillation.
• Investigators followed participants for a mean period of 2.5-3.5 years to observe the number of CVD events in those who had a diagnosis of depression.
• During the follow-up period, there were 119,000 CVD events in men (14 per 10,000 person-years) and 61,800 CVD events in women (111 per 10,000 person-years).

TAKEAWAY:

• Compared with women without depression, those with depression had a 64% higher risk for CVD (hazard ratio [HR], 1.64), while men with depression had a 39% higher risk for CVD vs their counterparts without depression (HR, 1.39; P < .001).
• This association was significant even after controlling for various factors such as body mass index, diabetes, smoking, alcohol consumption, and physical inactivity.
• Investigators offered several theories about the increased risk for CVD in women with depression, including how depression during hormonal shifts can contribute to a greater impact on cardiovascular health.

IN PRACTICE:

“Healthcare professionals must recognize the important role of depression in the development of CVD and emphasize the importance of a comprehensive, patient-centered approach to its prevention and management,” study author Hidehiro Kaneko, MD, said in a press release. “Assessing the risk of CVD in depressed patients and treating and preventing depression may lead to a decrease of CVD cases.”

SOURCE:

Keitaro Senoo, MD, of the Kyoto Prefectural University of Medicine, Kyoto, Japan, led the study, which was published online on March 12 in JACC: Asia.

LIMITATIONS:

The study is observational, so causality between depression and subsequent CVD events cannot be established. In addition, depression severity is unknown.

DISCLOSURES:

The study was funded by the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science, and Technology, Japan. There were no disclosures reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Depression is linked to a significantly increased risk for cardiovascular disease (CVD), particularly in women, new data from a large retrospective cohort study show. Researchers suggest that screening and treating patients for depression may lead to a decreased incidence of CVD.

METHODOLOGY:

• Researchers analyzed health insurance claims from more than 4 million Japanese patients filed between 2005 and 2022.
• Participants were 18-75 (median age, 44) without a history of CVD or stroke, heart failure, or atrial fibrillation.
• Investigators followed participants for a mean period of 2.5-3.5 years to observe the number of CVD events in those who had a diagnosis of depression.
• During the follow-up period, there were 119,000 CVD events in men (14 per 10,000 person-years) and 61,800 CVD events in women (111 per 10,000 person-years).

TAKEAWAY:

• Compared with women without depression, those with depression had a 64% higher risk for CVD (hazard ratio [HR], 1.64), while men with depression had a 39% higher risk for CVD vs their counterparts without depression (HR, 1.39; P < .001).
• This association was significant even after controlling for various factors such as body mass index, diabetes, smoking, alcohol consumption, and physical inactivity.
• Investigators offered several theories about the increased risk for CVD in women with depression, including how depression during hormonal shifts can contribute to a greater impact on cardiovascular health.

IN PRACTICE:

“Healthcare professionals must recognize the important role of depression in the development of CVD and emphasize the importance of a comprehensive, patient-centered approach to its prevention and management,” study author Hidehiro Kaneko, MD, said in a press release. “Assessing the risk of CVD in depressed patients and treating and preventing depression may lead to a decrease of CVD cases.”

SOURCE:

Keitaro Senoo, MD, of the Kyoto Prefectural University of Medicine, Kyoto, Japan, led the study, which was published online on March 12 in JACC: Asia.

LIMITATIONS:

The study is observational, so causality between depression and subsequent CVD events cannot be established. In addition, depression severity is unknown.

DISCLOSURES:

The study was funded by the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science, and Technology, Japan. There were no disclosures reported.

A version of this article appeared on Medscape.com.

Silence Therapeutics shared positive topline 36-week data from its ongoing phase 2 study of zerlasiran, a long-acting agent directed at lowering Lp(a) levels. 

In a statement, the company said the study shows a highly significant reduction from baseline in Lp(a) levels with zerlasiran compared with placebo at 36 weeks, the primary endpoint.

Zerlasiran (formerly known as SLN360), is a short interfering RNA (siRNA) agent, or “ gene silencing” therapy. It binds to and temporarily blocks the action of the LPA gene which encodes for apolipoprotein(a), a dominant and a rate-limiting component in the hepatic synthesis of the Lp(a) particle.

A previous phase 1 study showed that single subcutaneous doses of the drug, ranging from 30 mg to 600 mg, produced a dose-dependent reduction in Lp(a) plasma levels at 45-60 days.

The current double-blind placebo-controlled phase 2 trial — known as ALPACAR-360 — enrolled 178 patients at high risk for atherosclerotic cardiovascular events who had elevated levels of Lp(a), ie, ≥ 125 nmol/L (median baseline Lp(a) was approximately 215 nmol/L). They were randomized to zerlasiran or placebo. 

Zerlasiran was administered at 300 mg subcutaneously every 16 or 24 weeks or at 450 mg every 24 weeks. 

Results reported by the company show a median percentage reduction in Lp(a) of ≥ 90% for both doses at week 36, with no new safety concerns identified during this treatment period.

The 60-week study is ongoing, and secondary endpoints, including change in Lp(a) from baseline to 48 weeks (end of treatment period) and 60 weeks (end of study) and potential effects on other lipids/lipoproteins, will be evaluated.

Silence says it plans to report topline 48-week data from the ALPACAR-360 study in the second quarter of this year.

Elevated levels of Lp(a) represent a genetic risk factor for cardiovascular disease, which is believed to affect approximately 20% of the population. Although there are currently no approved Lp(a)-lowering therapies, several drug candidates are in late-stage clinical testing.

A version of this article appeared on Medscape.com.

Silence Therapeutics shared positive topline 36-week data from its ongoing phase 2 study of zerlasiran, a long-acting agent directed at lowering Lp(a) levels. 

In a statement, the company said the study shows a highly significant reduction from baseline in Lp(a) levels with zerlasiran compared with placebo at 36 weeks, the primary endpoint.

Zerlasiran (formerly known as SLN360), is a short interfering RNA (siRNA) agent, or “ gene silencing” therapy. It binds to and temporarily blocks the action of the LPA gene which encodes for apolipoprotein(a), a dominant and a rate-limiting component in the hepatic synthesis of the Lp(a) particle.

A previous phase 1 study showed that single subcutaneous doses of the drug, ranging from 30 mg to 600 mg, produced a dose-dependent reduction in Lp(a) plasma levels at 45-60 days.

The current double-blind placebo-controlled phase 2 trial — known as ALPACAR-360 — enrolled 178 patients at high risk for atherosclerotic cardiovascular events who had elevated levels of Lp(a), ie, ≥ 125 nmol/L (median baseline Lp(a) was approximately 215 nmol/L). They were randomized to zerlasiran or placebo. 

Zerlasiran was administered at 300 mg subcutaneously every 16 or 24 weeks or at 450 mg every 24 weeks. 

Results reported by the company show a median percentage reduction in Lp(a) of ≥ 90% for both doses at week 36, with no new safety concerns identified during this treatment period.

The 60-week study is ongoing, and secondary endpoints, including change in Lp(a) from baseline to 48 weeks (end of treatment period) and 60 weeks (end of study) and potential effects on other lipids/lipoproteins, will be evaluated.

Silence says it plans to report topline 48-week data from the ALPACAR-360 study in the second quarter of this year.

Elevated levels of Lp(a) represent a genetic risk factor for cardiovascular disease, which is believed to affect approximately 20% of the population. Although there are currently no approved Lp(a)-lowering therapies, several drug candidates are in late-stage clinical testing.

A version of this article appeared on Medscape.com.

Silence Therapeutics shared positive topline 36-week data from its ongoing phase 2 study of zerlasiran, a long-acting agent directed at lowering Lp(a) levels. 

In a statement, the company said the study shows a highly significant reduction from baseline in Lp(a) levels with zerlasiran compared with placebo at 36 weeks, the primary endpoint.

Zerlasiran (formerly known as SLN360), is a short interfering RNA (siRNA) agent, or “ gene silencing” therapy. It binds to and temporarily blocks the action of the LPA gene which encodes for apolipoprotein(a), a dominant and a rate-limiting component in the hepatic synthesis of the Lp(a) particle.

A previous phase 1 study showed that single subcutaneous doses of the drug, ranging from 30 mg to 600 mg, produced a dose-dependent reduction in Lp(a) plasma levels at 45-60 days.

The current double-blind placebo-controlled phase 2 trial — known as ALPACAR-360 — enrolled 178 patients at high risk for atherosclerotic cardiovascular events who had elevated levels of Lp(a), ie, ≥ 125 nmol/L (median baseline Lp(a) was approximately 215 nmol/L). They were randomized to zerlasiran or placebo. 

Zerlasiran was administered at 300 mg subcutaneously every 16 or 24 weeks or at 450 mg every 24 weeks. 

Results reported by the company show a median percentage reduction in Lp(a) of ≥ 90% for both doses at week 36, with no new safety concerns identified during this treatment period.

The 60-week study is ongoing, and secondary endpoints, including change in Lp(a) from baseline to 48 weeks (end of treatment period) and 60 weeks (end of study) and potential effects on other lipids/lipoproteins, will be evaluated.

Silence says it plans to report topline 48-week data from the ALPACAR-360 study in the second quarter of this year.

Elevated levels of Lp(a) represent a genetic risk factor for cardiovascular disease, which is believed to affect approximately 20% of the population. Although there are currently no approved Lp(a)-lowering therapies, several drug candidates are in late-stage clinical testing.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher dietary niacin intake is associated with a lower risk for all-cause mortality among people with metabolic dysfunction-associated steatotic liver disease (MASLD), but there is no connection between niacin consumption and cardiovascular disease (CVD) mortality, a recent study suggested.

METHODOLOGY:

• Researchers analyzed data from the National Health and Nutrition Examination Survey (2003-2018) for 4315 adults with MASLD (mean age, 52.5 years; 55%, men; 67%, non-Hispanic White).
• Dietary niacin intake levels were based on two 24-hour dietary recall interviews to report the types and quantities of foods that participants consumed in the 24 hours prior to the interviews.
• Participants were categorized by tertile of dietary niacin intake: Tertile 1 (n = 1440), < 18.4 mg; tertile 2 (n = 1441), 18.5-26.6 mg; and tertile 3 (n = 1434), > 26.7 mg.

TAKEAWAY:

• During a median follow-up of 8.8 years, 566 deaths occurred, of which 197 were attributed to CVD.
• Compared with participants with a niacin intake of 18.4 mg or lower (the lowest tertile), the multivariable-adjusted hazard ratios (HRs) for participants with a niacin intake of 26.7 mg or higher (the highest tertile) were 0.70 for all-cause mortality and 0.65 for CVD mortality.
• For the subgroup with diabetes compared with the reference group (the first tertile), the HR of all-cause mortality in the third tertile was 0.82.
• When the subgroup without diabetes was compared with the reference group, the HR of all-cause mortality in the third tertile was 0.58, suggesting a significant interaction between niacin and diabetes with the risk of all-cause mortality.
• An inverse association between dietary niacin intake and all-cause mortality was seen in sensitivity analyses, when excluding a participant who died within 2 years of follow-up.

IN PRACTICE:

“Higher dietary niacin intake was associated with a lower risk of all-cause mortality,” but not CVD, among individuals with MASLD, and “the dose-response association…needs to be further investigated to determine optimal intake level,” the authors wrote.

SOURCE:

The study, led by Jie Pan, MD, Sun Yat-sen University, Guangzhou, China, was published online in JAMA Network Open.

LIMITATIONS:

Physical activity data were missing and could not be adjusted for. The National Death Index used by the researchers has only “modest” ability to accurately classify CVD mortality, and the dietary data were subject to recall bias.

DISCLOSURES:

One author was supported by a grant from the National Nature Science Foundation of China. No other conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher dietary niacin intake is associated with a lower risk for all-cause mortality among people with metabolic dysfunction-associated steatotic liver disease (MASLD), but there is no connection between niacin consumption and cardiovascular disease (CVD) mortality, a recent study suggested.

METHODOLOGY:

• Researchers analyzed data from the National Health and Nutrition Examination Survey (2003-2018) for 4315 adults with MASLD (mean age, 52.5 years; 55%, men; 67%, non-Hispanic White).
• Dietary niacin intake levels were based on two 24-hour dietary recall interviews to report the types and quantities of foods that participants consumed in the 24 hours prior to the interviews.
• Participants were categorized by tertile of dietary niacin intake: Tertile 1 (n = 1440), < 18.4 mg; tertile 2 (n = 1441), 18.5-26.6 mg; and tertile 3 (n = 1434), > 26.7 mg.

TAKEAWAY:

• During a median follow-up of 8.8 years, 566 deaths occurred, of which 197 were attributed to CVD.
• Compared with participants with a niacin intake of 18.4 mg or lower (the lowest tertile), the multivariable-adjusted hazard ratios (HRs) for participants with a niacin intake of 26.7 mg or higher (the highest tertile) were 0.70 for all-cause mortality and 0.65 for CVD mortality.
• For the subgroup with diabetes compared with the reference group (the first tertile), the HR of all-cause mortality in the third tertile was 0.82.
• When the subgroup without diabetes was compared with the reference group, the HR of all-cause mortality in the third tertile was 0.58, suggesting a significant interaction between niacin and diabetes with the risk of all-cause mortality.
• An inverse association between dietary niacin intake and all-cause mortality was seen in sensitivity analyses, when excluding a participant who died within 2 years of follow-up.

IN PRACTICE:

“Higher dietary niacin intake was associated with a lower risk of all-cause mortality,” but not CVD, among individuals with MASLD, and “the dose-response association…needs to be further investigated to determine optimal intake level,” the authors wrote.

SOURCE:

The study, led by Jie Pan, MD, Sun Yat-sen University, Guangzhou, China, was published online in JAMA Network Open.

LIMITATIONS:

Physical activity data were missing and could not be adjusted for. The National Death Index used by the researchers has only “modest” ability to accurately classify CVD mortality, and the dietary data were subject to recall bias.

DISCLOSURES:

One author was supported by a grant from the National Nature Science Foundation of China. No other conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher dietary niacin intake is associated with a lower risk for all-cause mortality among people with metabolic dysfunction-associated steatotic liver disease (MASLD), but there is no connection between niacin consumption and cardiovascular disease (CVD) mortality, a recent study suggested.

METHODOLOGY:

• Researchers analyzed data from the National Health and Nutrition Examination Survey (2003-2018) for 4315 adults with MASLD (mean age, 52.5 years; 55%, men; 67%, non-Hispanic White).
• Dietary niacin intake levels were based on two 24-hour dietary recall interviews to report the types and quantities of foods that participants consumed in the 24 hours prior to the interviews.
• Participants were categorized by tertile of dietary niacin intake: Tertile 1 (n = 1440), < 18.4 mg; tertile 2 (n = 1441), 18.5-26.6 mg; and tertile 3 (n = 1434), > 26.7 mg.

TAKEAWAY:

• During a median follow-up of 8.8 years, 566 deaths occurred, of which 197 were attributed to CVD.
• Compared with participants with a niacin intake of 18.4 mg or lower (the lowest tertile), the multivariable-adjusted hazard ratios (HRs) for participants with a niacin intake of 26.7 mg or higher (the highest tertile) were 0.70 for all-cause mortality and 0.65 for CVD mortality.
• For the subgroup with diabetes compared with the reference group (the first tertile), the HR of all-cause mortality in the third tertile was 0.82.
• When the subgroup without diabetes was compared with the reference group, the HR of all-cause mortality in the third tertile was 0.58, suggesting a significant interaction between niacin and diabetes with the risk of all-cause mortality.
• An inverse association between dietary niacin intake and all-cause mortality was seen in sensitivity analyses, when excluding a participant who died within 2 years of follow-up.

IN PRACTICE:

“Higher dietary niacin intake was associated with a lower risk of all-cause mortality,” but not CVD, among individuals with MASLD, and “the dose-response association…needs to be further investigated to determine optimal intake level,” the authors wrote.

SOURCE:

The study, led by Jie Pan, MD, Sun Yat-sen University, Guangzhou, China, was published online in JAMA Network Open.

LIMITATIONS:

Physical activity data were missing and could not be adjusted for. The National Death Index used by the researchers has only “modest” ability to accurately classify CVD mortality, and the dietary data were subject to recall bias.

DISCLOSURES:

One author was supported by a grant from the National Nature Science Foundation of China. No other conflicts of interest were reported.

A version of this article appeared on Medscape.com.

Snoring is a common disorder that affects 20%-40% of the general population. The mechanism of snoring is the vibration of anatomical structures in the pharyngeal airways. The flutter of the soft palate explains the harsh aspect of the snoring sound, which occurs during natural sleep or drug-induced sleep. The presentation of snoring may vary throughout the night or between nights, with a subjective, and therefore inconsistent, assessment of its loudness.

Objective evaluation of snoring is important for clinical decision-making and predicting the effect of therapeutic interventions. It also provides information regarding the site and degree of upper airway obstruction. Snoring is one of the main features of sleep-disordered breathing, including hypopnea events, which reflect partial upper airway obstruction.

Obstructive sleep apnea (OSA) is characterized by episodes of complete (apnea) or partial (hypopnea) collapse of the upper airways with associated oxygen desaturation or awakening from sleep. Most patients with OSA snore loudly almost every night. However, in the Sleep Heart Health Study, one-third of participants with OSA reported no snoring, while one-third of snoring participants did not meet the criteria for OSA. Therefore, subjective assessments of snoring (self-reported) may not be sufficiently reliable to assess its potential impact on cardiovascular (CV) health outcomes.
 

CV Effects

OSA has been hypothesized as a modifiable risk factor for CV diseases (CVD), including hypertension, coronary artery disease (CAD), atrial fibrillation, heart failure, and stroke, primarily because of the results of traditional observational studies. Snoring is reported as a symptom of the early stage of OSA and has also been associated with a higher risk for CVD. However, establishing causality based on observational studies is difficult because of residual confounding from unknown or unmeasured factors and reverse causality (i.e., the scenario in which CVD increases the risk for OSA or snoring). A Mendelian randomization study, using the natural random allocation of genetic variants as instruments capable of producing results analogous to those of randomized controlled trials, suggested that OSA and snoring increase the risk for hypertension and CAD, with associations partly driven by body mass index (BMI). Conversely, no evidence was found that CVD causally influenced OSA or snoring.

Snoring has been associated with multiple subclinical markers of CV pathology, including high blood pressure, and loud snoring can interfere with restorative sleep and contribute to the risk for hypertension and other adverse outcomes in snorers. However, evidence on the associations between snoring and CV health outcomes remains limited and is primarily based on subjective assessments of snoring or small clinical samples with objective assessments of snoring for only 1 night.
 

Snoring and Hypertension

A study of 12,287 middle-aged patients (age, 50 years) who were predominantly males (88%) and generally overweight (BMI, 28 kg/m²) determined the prevalence of snoring and its association with the prevalence of hypertension using objective evaluation of snoring over multiple nights and multiple daytime blood pressure measurements. The findings included the following observations:

An increase in snoring duration was associated with a 3-mmHg increase in systolic (SBP) and a 4 mmHg increase in diastolic blood pressure (DBP) in patients with frequent and regular snoring, compared with those with infrequent snoring, regardless of age, BMI, sex, and estimated apnea/hypopnea index.

The association between severe OSA alone and blood pressure had an effect size similar to that of the association between snoring alone and blood pressure. In a model where OSA severity was classified and snoring duration was stratified into quartiles, severe OSA without snoring was associated with 3.6 mmHg higher SBP and 3.5 mmHg higher DBP, compared with the absence of snoring or OSA. Participants without OSA but with intense snoring (4th quartile) had 3.8 mmHg higher SBP and 4.5 mmHg higher DBP compared with participants without nighttime apnea or snoring.

Snoring was significantly associated with uncontrolled hypertension. There was a 20% increase in the probability of uncontrolled hypertension in subjects aged > 50 years with obesity and a 98% increase in subjects aged ≤ 50 years with normal BMI.

Duration of snoring was associated with an 87% increase in the likelihood of uncontrolled hypertension.
 

Implications for Practice

This study indicates that 15% of a predominantly overweight male population snore for > 20% of the night and about 10% of these subjects without nighttime apnea snore for > 12% of the night.

Regular nighttime snoring is associated with elevated blood pressure and uncontrolled hypertension, regardless of the presence or severity of OSA.

Physicians must be aware of the potential consequences of snoring on the risk for hypertension, and these results highlight the need to consider snoring in clinical care and in the management of sleep problems, especially in the context of managing arterial hypertension.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Snoring is a common disorder that affects 20%-40% of the general population. The mechanism of snoring is the vibration of anatomical structures in the pharyngeal airways. The flutter of the soft palate explains the harsh aspect of the snoring sound, which occurs during natural sleep or drug-induced sleep. The presentation of snoring may vary throughout the night or between nights, with a subjective, and therefore inconsistent, assessment of its loudness.

Objective evaluation of snoring is important for clinical decision-making and predicting the effect of therapeutic interventions. It also provides information regarding the site and degree of upper airway obstruction. Snoring is one of the main features of sleep-disordered breathing, including hypopnea events, which reflect partial upper airway obstruction.

Obstructive sleep apnea (OSA) is characterized by episodes of complete (apnea) or partial (hypopnea) collapse of the upper airways with associated oxygen desaturation or awakening from sleep. Most patients with OSA snore loudly almost every night. However, in the Sleep Heart Health Study, one-third of participants with OSA reported no snoring, while one-third of snoring participants did not meet the criteria for OSA. Therefore, subjective assessments of snoring (self-reported) may not be sufficiently reliable to assess its potential impact on cardiovascular (CV) health outcomes.
 

CV Effects

OSA has been hypothesized as a modifiable risk factor for CV diseases (CVD), including hypertension, coronary artery disease (CAD), atrial fibrillation, heart failure, and stroke, primarily because of the results of traditional observational studies. Snoring is reported as a symptom of the early stage of OSA and has also been associated with a higher risk for CVD. However, establishing causality based on observational studies is difficult because of residual confounding from unknown or unmeasured factors and reverse causality (i.e., the scenario in which CVD increases the risk for OSA or snoring). A Mendelian randomization study, using the natural random allocation of genetic variants as instruments capable of producing results analogous to those of randomized controlled trials, suggested that OSA and snoring increase the risk for hypertension and CAD, with associations partly driven by body mass index (BMI). Conversely, no evidence was found that CVD causally influenced OSA or snoring.

Snoring has been associated with multiple subclinical markers of CV pathology, including high blood pressure, and loud snoring can interfere with restorative sleep and contribute to the risk for hypertension and other adverse outcomes in snorers. However, evidence on the associations between snoring and CV health outcomes remains limited and is primarily based on subjective assessments of snoring or small clinical samples with objective assessments of snoring for only 1 night.
 

Snoring and Hypertension

A study of 12,287 middle-aged patients (age, 50 years) who were predominantly males (88%) and generally overweight (BMI, 28 kg/m²) determined the prevalence of snoring and its association with the prevalence of hypertension using objective evaluation of snoring over multiple nights and multiple daytime blood pressure measurements. The findings included the following observations:

An increase in snoring duration was associated with a 3-mmHg increase in systolic (SBP) and a 4 mmHg increase in diastolic blood pressure (DBP) in patients with frequent and regular snoring, compared with those with infrequent snoring, regardless of age, BMI, sex, and estimated apnea/hypopnea index.

The association between severe OSA alone and blood pressure had an effect size similar to that of the association between snoring alone and blood pressure. In a model where OSA severity was classified and snoring duration was stratified into quartiles, severe OSA without snoring was associated with 3.6 mmHg higher SBP and 3.5 mmHg higher DBP, compared with the absence of snoring or OSA. Participants without OSA but with intense snoring (4th quartile) had 3.8 mmHg higher SBP and 4.5 mmHg higher DBP compared with participants without nighttime apnea or snoring.

Snoring was significantly associated with uncontrolled hypertension. There was a 20% increase in the probability of uncontrolled hypertension in subjects aged > 50 years with obesity and a 98% increase in subjects aged ≤ 50 years with normal BMI.

Duration of snoring was associated with an 87% increase in the likelihood of uncontrolled hypertension.
 

Implications for Practice

This study indicates that 15% of a predominantly overweight male population snore for > 20% of the night and about 10% of these subjects without nighttime apnea snore for > 12% of the night.

Regular nighttime snoring is associated with elevated blood pressure and uncontrolled hypertension, regardless of the presence or severity of OSA.

Physicians must be aware of the potential consequences of snoring on the risk for hypertension, and these results highlight the need to consider snoring in clinical care and in the management of sleep problems, especially in the context of managing arterial hypertension.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Snoring is a common disorder that affects 20%-40% of the general population. The mechanism of snoring is the vibration of anatomical structures in the pharyngeal airways. The flutter of the soft palate explains the harsh aspect of the snoring sound, which occurs during natural sleep or drug-induced sleep. The presentation of snoring may vary throughout the night or between nights, with a subjective, and therefore inconsistent, assessment of its loudness.

Objective evaluation of snoring is important for clinical decision-making and predicting the effect of therapeutic interventions. It also provides information regarding the site and degree of upper airway obstruction. Snoring is one of the main features of sleep-disordered breathing, including hypopnea events, which reflect partial upper airway obstruction.

Obstructive sleep apnea (OSA) is characterized by episodes of complete (apnea) or partial (hypopnea) collapse of the upper airways with associated oxygen desaturation or awakening from sleep. Most patients with OSA snore loudly almost every night. However, in the Sleep Heart Health Study, one-third of participants with OSA reported no snoring, while one-third of snoring participants did not meet the criteria for OSA. Therefore, subjective assessments of snoring (self-reported) may not be sufficiently reliable to assess its potential impact on cardiovascular (CV) health outcomes.
 

CV Effects

OSA has been hypothesized as a modifiable risk factor for CV diseases (CVD), including hypertension, coronary artery disease (CAD), atrial fibrillation, heart failure, and stroke, primarily because of the results of traditional observational studies. Snoring is reported as a symptom of the early stage of OSA and has also been associated with a higher risk for CVD. However, establishing causality based on observational studies is difficult because of residual confounding from unknown or unmeasured factors and reverse causality (i.e., the scenario in which CVD increases the risk for OSA or snoring). A Mendelian randomization study, using the natural random allocation of genetic variants as instruments capable of producing results analogous to those of randomized controlled trials, suggested that OSA and snoring increase the risk for hypertension and CAD, with associations partly driven by body mass index (BMI). Conversely, no evidence was found that CVD causally influenced OSA or snoring.

Snoring has been associated with multiple subclinical markers of CV pathology, including high blood pressure, and loud snoring can interfere with restorative sleep and contribute to the risk for hypertension and other adverse outcomes in snorers. However, evidence on the associations between snoring and CV health outcomes remains limited and is primarily based on subjective assessments of snoring or small clinical samples with objective assessments of snoring for only 1 night.
 

Snoring and Hypertension

A study of 12,287 middle-aged patients (age, 50 years) who were predominantly males (88%) and generally overweight (BMI, 28 kg/m²) determined the prevalence of snoring and its association with the prevalence of hypertension using objective evaluation of snoring over multiple nights and multiple daytime blood pressure measurements. The findings included the following observations:

An increase in snoring duration was associated with a 3-mmHg increase in systolic (SBP) and a 4 mmHg increase in diastolic blood pressure (DBP) in patients with frequent and regular snoring, compared with those with infrequent snoring, regardless of age, BMI, sex, and estimated apnea/hypopnea index.

The association between severe OSA alone and blood pressure had an effect size similar to that of the association between snoring alone and blood pressure. In a model where OSA severity was classified and snoring duration was stratified into quartiles, severe OSA without snoring was associated with 3.6 mmHg higher SBP and 3.5 mmHg higher DBP, compared with the absence of snoring or OSA. Participants without OSA but with intense snoring (4th quartile) had 3.8 mmHg higher SBP and 4.5 mmHg higher DBP compared with participants without nighttime apnea or snoring.

Snoring was significantly associated with uncontrolled hypertension. There was a 20% increase in the probability of uncontrolled hypertension in subjects aged > 50 years with obesity and a 98% increase in subjects aged ≤ 50 years with normal BMI.

Duration of snoring was associated with an 87% increase in the likelihood of uncontrolled hypertension.
 

Implications for Practice

This study indicates that 15% of a predominantly overweight male population snore for > 20% of the night and about 10% of these subjects without nighttime apnea snore for > 12% of the night.

Regular nighttime snoring is associated with elevated blood pressure and uncontrolled hypertension, regardless of the presence or severity of OSA.

Physicians must be aware of the potential consequences of snoring on the risk for hypertension, and these results highlight the need to consider snoring in clinical care and in the management of sleep problems, especially in the context of managing arterial hypertension.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

According to a new study, patients found to have microplastics and nanoplastics in their carotid artery plaque had a higher risk for death or major cardiovascular events compared with patients who had plaques where particles were not found.

This is the first study to show plastic particles are present in atheroma plaques, but the most important finding is that this was related to a four times higher risk for cardiovascular events, study coauthor Antonio Ceriello, MD, IRCCS MultiMedica, Milan, told this news organization. 

“I believe we have demonstrated that plastics are a new risk factor for cardiovascular disease,” he added. And while plastics may have made our lives easier in many respects, it appears that the price we are paying for that is a shortening of our lives. That is not a good balance.”

The trial involved 304 patients undergoing carotid endarterectomy for asymptomatic carotid artery disease, whose excised plaque specimens were analyzed for the presence of microplastics and nanoplastics, ultimately found in almost 60% of patients. 

After a mean follow-up of 34 months, patients in whom microplastics and nanoplastics were detected within the atheroma had a 4.5 times higher risk for the composite endpoint of all cause death, myocardial infarction, or stroke than those in whom these substances were not detected (hazard ratio, 4.53; 95% CI, 2.00-10.27; P < .001).

The study, led by Raffaele Marfella, MD, University of Campania Luigi Vanvitelli, Naples, Italy, was published in The New England Journal of Medicine on March 7, 2024.

The researchers say the study does not prove causality, and many other unmeasured confounding factors could have contributed to the findings. 

However, Dr. Ceriello noted that many important risk factors such as diabetes, hypertension, and dyslipidemia, were controlled for. 

“In this study, all the patients involved were at high risk of cardiovascular events and they were well treated with statins and antithrombotics, so the relationship between the presence of plastic particles in plaque and cardiovascular events is seen on top of good preventive therapy,” he said. 

“While we cannot say for sure that we have shown a causal relationship, we found a large effect and there is a great deal of literature than supports this. We know that plastic particles can penetrate cells and act at the mitochondrial level to increase free radical production and produce chronic inflammation which is the basis for atherosclerosis,” Dr. Ceriello added. 

He believes there is only one approach to addressing this issue, and that is to reduce the amount of plastic in the environment. 

“Plastic is everywhere — in water pipes, in the ocean. We are hoping that this study will increase the push for government to act on this. This is even more important for the long-term health of our children, who will be exposed to high levels of plastics for the whole of their lives,” he said. 
 

‘Strongly Suggestive of a Causal Relationship’

Commenting for this news organization, Philip J. Landrigan, MD, author of an editorial accompanying publication of the study in the NEJM, described the link as “strongly suggestive.”

“Because this was just a single observational study, it doesn’t prove cause and effect, but I think this is strongly suggestive of a causal relationship,” he said. “While there may be some other confounding factors at play, it is hard for me to imagine that these could account for a hazard ratio of 4.5 — that is a large and alarming increase in just 3 years.”

Dr. Landrigan, who is director of the Program for Global Public Health and the Common Good, Boston College, points out that although it is not known what other exposures may have contributed to the adverse outcomes in patients in this study, the finding of microplastics and nanoplastics in plaque tissue is itself a breakthrough discovery that raises a series of urgent questions. These include: “Should exposure to microplastics and nanoplastics be considered a cardiovascular risk factor? What organs in addition to the heart may be at risk? How can we reduce exposure?”

Dr. Landrigan said he was not surprised that plastic particles had been found in carotid plaques. “Previous studies have found microplastics in other tissues including the lungs, colon and placenta. Now they have turned up in the vessel wall,” he said. “But what is really striking about this study is that it suggests the presence of these plastic particles is causing serious harm.”

He says this should be a wake-up call. “It is telling us that we need to worry about the amount of plastic in our environment. And it is not something that’s going to be a problem down the line — it is affecting us now.” 

Dr. Landrigan explained that plastic particles are taken into the body predominantly by ingestion, which could include drinking from plastic bottles or eating food wrapped in plastic. He said it is particularly damaging to use plastic containers to heat food in the microwave, as heating plastic up drives particles into the food. “That will really increase exposure.” 

He noted that plastics are often already in the food itself, especially seafood. 

“Plastics are dumped in the ocean, they break down and get picked up by the fish. Especially if you eat fish at the top of the food chain like tuna, or if you eat oysters or mussels that are filter feeders, you are more likely to ingest microplastics.” 

Dr. Landrigan said he would not advise against eating fish in general, however. “Maybe tuna or other predatory fish may be an issue, but fish in general are good for us, and fish like salmon which have a mainly vegetarian diet are probably safer in this regard.”

The other route is inhalation, with these small plastic particles being widely present in the air, from sources such as vehicle tires becoming abraded from running along the highway.

While it is impossible to avoid taking in plastic completely, Dr. Landrigan says individuals can make efforts to reduce their exposure. 

“People can make intelligent choices in their homes about what they purchase for themselves and their families, and they can act in their local environments and workplace to try and reduce plastics.”

He noted that 40% of all plastic currently being made is single use plastic, and that percentage is growing, with global production of plastic on track to double by 2040 and triple by 2060, and most of this rapid growth being single use plastic. 

“We are all members of the broader society, and we need to become educated about the plastic situation and lobby our elected officials to come up with a good strong legally binding treaty that will place a cap on plastic production,” Dr. Landrigan said. 
 

A version of this article appeared on Medscape.com.

According to a new study, patients found to have microplastics and nanoplastics in their carotid artery plaque had a higher risk for death or major cardiovascular events compared with patients who had plaques where particles were not found.

This is the first study to show plastic particles are present in atheroma plaques, but the most important finding is that this was related to a four times higher risk for cardiovascular events, study coauthor Antonio Ceriello, MD, IRCCS MultiMedica, Milan, told this news organization. 

“I believe we have demonstrated that plastics are a new risk factor for cardiovascular disease,” he added. And while plastics may have made our lives easier in many respects, it appears that the price we are paying for that is a shortening of our lives. That is not a good balance.”

The trial involved 304 patients undergoing carotid endarterectomy for asymptomatic carotid artery disease, whose excised plaque specimens were analyzed for the presence of microplastics and nanoplastics, ultimately found in almost 60% of patients. 

After a mean follow-up of 34 months, patients in whom microplastics and nanoplastics were detected within the atheroma had a 4.5 times higher risk for the composite endpoint of all cause death, myocardial infarction, or stroke than those in whom these substances were not detected (hazard ratio, 4.53; 95% CI, 2.00-10.27; P < .001).

The study, led by Raffaele Marfella, MD, University of Campania Luigi Vanvitelli, Naples, Italy, was published in The New England Journal of Medicine on March 7, 2024.

The researchers say the study does not prove causality, and many other unmeasured confounding factors could have contributed to the findings. 

However, Dr. Ceriello noted that many important risk factors such as diabetes, hypertension, and dyslipidemia, were controlled for. 

“In this study, all the patients involved were at high risk of cardiovascular events and they were well treated with statins and antithrombotics, so the relationship between the presence of plastic particles in plaque and cardiovascular events is seen on top of good preventive therapy,” he said. 

“While we cannot say for sure that we have shown a causal relationship, we found a large effect and there is a great deal of literature than supports this. We know that plastic particles can penetrate cells and act at the mitochondrial level to increase free radical production and produce chronic inflammation which is the basis for atherosclerosis,” Dr. Ceriello added. 

He believes there is only one approach to addressing this issue, and that is to reduce the amount of plastic in the environment. 

“Plastic is everywhere — in water pipes, in the ocean. We are hoping that this study will increase the push for government to act on this. This is even more important for the long-term health of our children, who will be exposed to high levels of plastics for the whole of their lives,” he said. 
 

‘Strongly Suggestive of a Causal Relationship’

Commenting for this news organization, Philip J. Landrigan, MD, author of an editorial accompanying publication of the study in the NEJM, described the link as “strongly suggestive.”

“Because this was just a single observational study, it doesn’t prove cause and effect, but I think this is strongly suggestive of a causal relationship,” he said. “While there may be some other confounding factors at play, it is hard for me to imagine that these could account for a hazard ratio of 4.5 — that is a large and alarming increase in just 3 years.”

Dr. Landrigan, who is director of the Program for Global Public Health and the Common Good, Boston College, points out that although it is not known what other exposures may have contributed to the adverse outcomes in patients in this study, the finding of microplastics and nanoplastics in plaque tissue is itself a breakthrough discovery that raises a series of urgent questions. These include: “Should exposure to microplastics and nanoplastics be considered a cardiovascular risk factor? What organs in addition to the heart may be at risk? How can we reduce exposure?”

Dr. Landrigan said he was not surprised that plastic particles had been found in carotid plaques. “Previous studies have found microplastics in other tissues including the lungs, colon and placenta. Now they have turned up in the vessel wall,” he said. “But what is really striking about this study is that it suggests the presence of these plastic particles is causing serious harm.”

He says this should be a wake-up call. “It is telling us that we need to worry about the amount of plastic in our environment. And it is not something that’s going to be a problem down the line — it is affecting us now.” 

Dr. Landrigan explained that plastic particles are taken into the body predominantly by ingestion, which could include drinking from plastic bottles or eating food wrapped in plastic. He said it is particularly damaging to use plastic containers to heat food in the microwave, as heating plastic up drives particles into the food. “That will really increase exposure.” 

He noted that plastics are often already in the food itself, especially seafood. 

“Plastics are dumped in the ocean, they break down and get picked up by the fish. Especially if you eat fish at the top of the food chain like tuna, or if you eat oysters or mussels that are filter feeders, you are more likely to ingest microplastics.” 

Dr. Landrigan said he would not advise against eating fish in general, however. “Maybe tuna or other predatory fish may be an issue, but fish in general are good for us, and fish like salmon which have a mainly vegetarian diet are probably safer in this regard.”

The other route is inhalation, with these small plastic particles being widely present in the air, from sources such as vehicle tires becoming abraded from running along the highway.

While it is impossible to avoid taking in plastic completely, Dr. Landrigan says individuals can make efforts to reduce their exposure. 

“People can make intelligent choices in their homes about what they purchase for themselves and their families, and they can act in their local environments and workplace to try and reduce plastics.”

He noted that 40% of all plastic currently being made is single use plastic, and that percentage is growing, with global production of plastic on track to double by 2040 and triple by 2060, and most of this rapid growth being single use plastic. 

“We are all members of the broader society, and we need to become educated about the plastic situation and lobby our elected officials to come up with a good strong legally binding treaty that will place a cap on plastic production,” Dr. Landrigan said. 
 

A version of this article appeared on Medscape.com.

According to a new study, patients found to have microplastics and nanoplastics in their carotid artery plaque had a higher risk for death or major cardiovascular events compared with patients who had plaques where particles were not found.

This is the first study to show plastic particles are present in atheroma plaques, but the most important finding is that this was related to a four times higher risk for cardiovascular events, study coauthor Antonio Ceriello, MD, IRCCS MultiMedica, Milan, told this news organization. 

“I believe we have demonstrated that plastics are a new risk factor for cardiovascular disease,” he added. And while plastics may have made our lives easier in many respects, it appears that the price we are paying for that is a shortening of our lives. That is not a good balance.”

The trial involved 304 patients undergoing carotid endarterectomy for asymptomatic carotid artery disease, whose excised plaque specimens were analyzed for the presence of microplastics and nanoplastics, ultimately found in almost 60% of patients. 

After a mean follow-up of 34 months, patients in whom microplastics and nanoplastics were detected within the atheroma had a 4.5 times higher risk for the composite endpoint of all cause death, myocardial infarction, or stroke than those in whom these substances were not detected (hazard ratio, 4.53; 95% CI, 2.00-10.27; P < .001).

The study, led by Raffaele Marfella, MD, University of Campania Luigi Vanvitelli, Naples, Italy, was published in The New England Journal of Medicine on March 7, 2024.

The researchers say the study does not prove causality, and many other unmeasured confounding factors could have contributed to the findings. 

However, Dr. Ceriello noted that many important risk factors such as diabetes, hypertension, and dyslipidemia, were controlled for. 

“In this study, all the patients involved were at high risk of cardiovascular events and they were well treated with statins and antithrombotics, so the relationship between the presence of plastic particles in plaque and cardiovascular events is seen on top of good preventive therapy,” he said. 

“While we cannot say for sure that we have shown a causal relationship, we found a large effect and there is a great deal of literature than supports this. We know that plastic particles can penetrate cells and act at the mitochondrial level to increase free radical production and produce chronic inflammation which is the basis for atherosclerosis,” Dr. Ceriello added. 

He believes there is only one approach to addressing this issue, and that is to reduce the amount of plastic in the environment. 

“Plastic is everywhere — in water pipes, in the ocean. We are hoping that this study will increase the push for government to act on this. This is even more important for the long-term health of our children, who will be exposed to high levels of plastics for the whole of their lives,” he said. 
 

‘Strongly Suggestive of a Causal Relationship’

Commenting for this news organization, Philip J. Landrigan, MD, author of an editorial accompanying publication of the study in the NEJM, described the link as “strongly suggestive.”

“Because this was just a single observational study, it doesn’t prove cause and effect, but I think this is strongly suggestive of a causal relationship,” he said. “While there may be some other confounding factors at play, it is hard for me to imagine that these could account for a hazard ratio of 4.5 — that is a large and alarming increase in just 3 years.”

Dr. Landrigan, who is director of the Program for Global Public Health and the Common Good, Boston College, points out that although it is not known what other exposures may have contributed to the adverse outcomes in patients in this study, the finding of microplastics and nanoplastics in plaque tissue is itself a breakthrough discovery that raises a series of urgent questions. These include: “Should exposure to microplastics and nanoplastics be considered a cardiovascular risk factor? What organs in addition to the heart may be at risk? How can we reduce exposure?”

Dr. Landrigan said he was not surprised that plastic particles had been found in carotid plaques. “Previous studies have found microplastics in other tissues including the lungs, colon and placenta. Now they have turned up in the vessel wall,” he said. “But what is really striking about this study is that it suggests the presence of these plastic particles is causing serious harm.”

He says this should be a wake-up call. “It is telling us that we need to worry about the amount of plastic in our environment. And it is not something that’s going to be a problem down the line — it is affecting us now.” 

Dr. Landrigan explained that plastic particles are taken into the body predominantly by ingestion, which could include drinking from plastic bottles or eating food wrapped in plastic. He said it is particularly damaging to use plastic containers to heat food in the microwave, as heating plastic up drives particles into the food. “That will really increase exposure.” 

He noted that plastics are often already in the food itself, especially seafood. 

“Plastics are dumped in the ocean, they break down and get picked up by the fish. Especially if you eat fish at the top of the food chain like tuna, or if you eat oysters or mussels that are filter feeders, you are more likely to ingest microplastics.” 

Dr. Landrigan said he would not advise against eating fish in general, however. “Maybe tuna or other predatory fish may be an issue, but fish in general are good for us, and fish like salmon which have a mainly vegetarian diet are probably safer in this regard.”

The other route is inhalation, with these small plastic particles being widely present in the air, from sources such as vehicle tires becoming abraded from running along the highway.

While it is impossible to avoid taking in plastic completely, Dr. Landrigan says individuals can make efforts to reduce their exposure. 

“People can make intelligent choices in their homes about what they purchase for themselves and their families, and they can act in their local environments and workplace to try and reduce plastics.”

He noted that 40% of all plastic currently being made is single use plastic, and that percentage is growing, with global production of plastic on track to double by 2040 and triple by 2060, and most of this rapid growth being single use plastic. 

“We are all members of the broader society, and we need to become educated about the plastic situation and lobby our elected officials to come up with a good strong legally binding treaty that will place a cap on plastic production,” Dr. Landrigan said. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Metformin cuts the risk for diabetic nephropathy (DN) and major kidney and cardiovascular events in patients with newly diagnosed type 2 diabetes (T2D) across various renal function states.

METHODOLOGY:

Metformin is a first-line treatment in US and South Korean T2D management guidelines, except for patients with advanced chronic kidney disease (CKD) (stage, ≥ 4; estimated glomerular filtration rate [eGFR], < 30).

The study used data from the databases of three tertiary hospitals in South Korea to assess the effect of metformin on long-term renal and cardiovascular outcomes across various renal function states in patients with newly diagnosed T2D.

Four groups of treatment-control comparative cohorts were identified at each hospital: Patients who had not yet developed DN at T2D diagnosis (mean age in treatment and control cohorts, 61-65 years) and those with reduced renal function (CKD stages 3A, 3B, and 4).

Patients who continuously received metformin after T2D diagnosis and beyond the observation period were 1:1 propensity score matched with controls who were prescribed oral hypoglycemic agents other than metformin.

Primary outcomes were net major adverse cardiovascular events including strokes (MACEs) or in-hospital death and a composite of major adverse kidney events (MAKEs) or in-hospital death.

TAKEAWAY:

Among patients without DN at T2D diagnosis, the continuous use of metformin vs other oral hypoglycemic agents was associated with a lower risk for:

Overt DN (incidence rate ratio [IRR], 0.82; 95% CI, 0.71-0.95),

MACEs (IRR, 0.76; 95% CI, 0.64-0.92), and

MAKEs (IRR, 0.45; 95% CI, 0.33-0.62).

Compared with non-metformin or discontinued metformin use, the continuous use of metformin was associated with a lower risk for MACE across CKD stages 3A (IRR, 0.70; 95% CI, 0.57-0.87), 3B (IRR, 0.83; 95% CI, 0.74-0.93), and 4 (IRR, 0.71; 95% CI, 0.60-0.85).

Similarly, the risk for MAKE was lower among continuous metformin users than in nonusers or discontinuous metformin users across CKD stage 3A (IRR, 0.39; 95% CI, 0.35-0.43), 3B (IRR, 0.44; 95% CI, 0.40-0.48), and 4 (IRR, 0.45; 95% CI, 0.39-0.51).

IN PRACTICE:

“The significance of the current study is highlighted by its integration of real-world clinical data, which encompasses patients diagnosed with CDK4 [eGRF, 15-29 mL/min/1.73 m2], a group currently considered contraindicated,” the authors wrote.

SOURCE:

The study, led by Yongjin Yi, MD, PhD, Department of Internal Medicine, Dankook University College of Medicine, Cheonan-si, Republic of Korea, was published in Scientific Reports.

LIMITATIONS:

There may be a possibility of selection bias because of the retrospective and observational nature of this study. Despite achieving a 1:1 propensity score matching to address the confounding factors, some variables, such as serum albumin and A1c levels, remained unbalanced after matching. The paper did not include observation length or patient numbers, but in response to an email query from Medscape, Yi notes that in one hospital, the mean duration of observation for the control and treatment groups was about 6.5 years, and the total number in the treatment groups across data from three hospitals was 11,675, with the same number of matched controls.

DISCLOSURES:

This study was supported by a Young Investigator Research Grant from the Korean Society of Nephrology, a grant from the Seoul National University Bundang Hospital Research Fund, and the Bio&Medical Technology Development Program of the National Research Foundation funded by the Korean government. The authors disclosed no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Metformin cuts the risk for diabetic nephropathy (DN) and major kidney and cardiovascular events in patients with newly diagnosed type 2 diabetes (T2D) across various renal function states.

METHODOLOGY:

Metformin is a first-line treatment in US and South Korean T2D management guidelines, except for patients with advanced chronic kidney disease (CKD) (stage, ≥ 4; estimated glomerular filtration rate [eGFR], < 30).

The study used data from the databases of three tertiary hospitals in South Korea to assess the effect of metformin on long-term renal and cardiovascular outcomes across various renal function states in patients with newly diagnosed T2D.

Four groups of treatment-control comparative cohorts were identified at each hospital: Patients who had not yet developed DN at T2D diagnosis (mean age in treatment and control cohorts, 61-65 years) and those with reduced renal function (CKD stages 3A, 3B, and 4).

Patients who continuously received metformin after T2D diagnosis and beyond the observation period were 1:1 propensity score matched with controls who were prescribed oral hypoglycemic agents other than metformin.

Primary outcomes were net major adverse cardiovascular events including strokes (MACEs) or in-hospital death and a composite of major adverse kidney events (MAKEs) or in-hospital death.

TAKEAWAY:

Among patients without DN at T2D diagnosis, the continuous use of metformin vs other oral hypoglycemic agents was associated with a lower risk for:

Overt DN (incidence rate ratio [IRR], 0.82; 95% CI, 0.71-0.95),

MACEs (IRR, 0.76; 95% CI, 0.64-0.92), and

MAKEs (IRR, 0.45; 95% CI, 0.33-0.62).

Compared with non-metformin or discontinued metformin use, the continuous use of metformin was associated with a lower risk for MACE across CKD stages 3A (IRR, 0.70; 95% CI, 0.57-0.87), 3B (IRR, 0.83; 95% CI, 0.74-0.93), and 4 (IRR, 0.71; 95% CI, 0.60-0.85).

Similarly, the risk for MAKE was lower among continuous metformin users than in nonusers or discontinuous metformin users across CKD stage 3A (IRR, 0.39; 95% CI, 0.35-0.43), 3B (IRR, 0.44; 95% CI, 0.40-0.48), and 4 (IRR, 0.45; 95% CI, 0.39-0.51).

IN PRACTICE:

“The significance of the current study is highlighted by its integration of real-world clinical data, which encompasses patients diagnosed with CDK4 [eGRF, 15-29 mL/min/1.73 m2], a group currently considered contraindicated,” the authors wrote.

SOURCE:

The study, led by Yongjin Yi, MD, PhD, Department of Internal Medicine, Dankook University College of Medicine, Cheonan-si, Republic of Korea, was published in Scientific Reports.

LIMITATIONS:

There may be a possibility of selection bias because of the retrospective and observational nature of this study. Despite achieving a 1:1 propensity score matching to address the confounding factors, some variables, such as serum albumin and A1c levels, remained unbalanced after matching. The paper did not include observation length or patient numbers, but in response to an email query from Medscape, Yi notes that in one hospital, the mean duration of observation for the control and treatment groups was about 6.5 years, and the total number in the treatment groups across data from three hospitals was 11,675, with the same number of matched controls.

DISCLOSURES:

This study was supported by a Young Investigator Research Grant from the Korean Society of Nephrology, a grant from the Seoul National University Bundang Hospital Research Fund, and the Bio&Medical Technology Development Program of the National Research Foundation funded by the Korean government. The authors disclosed no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Metformin cuts the risk for diabetic nephropathy (DN) and major kidney and cardiovascular events in patients with newly diagnosed type 2 diabetes (T2D) across various renal function states.

METHODOLOGY:

Metformin is a first-line treatment in US and South Korean T2D management guidelines, except for patients with advanced chronic kidney disease (CKD) (stage, ≥ 4; estimated glomerular filtration rate [eGFR], < 30).

The study used data from the databases of three tertiary hospitals in South Korea to assess the effect of metformin on long-term renal and cardiovascular outcomes across various renal function states in patients with newly diagnosed T2D.

Four groups of treatment-control comparative cohorts were identified at each hospital: Patients who had not yet developed DN at T2D diagnosis (mean age in treatment and control cohorts, 61-65 years) and those with reduced renal function (CKD stages 3A, 3B, and 4).

Patients who continuously received metformin after T2D diagnosis and beyond the observation period were 1:1 propensity score matched with controls who were prescribed oral hypoglycemic agents other than metformin.

Primary outcomes were net major adverse cardiovascular events including strokes (MACEs) or in-hospital death and a composite of major adverse kidney events (MAKEs) or in-hospital death.

TAKEAWAY:

Among patients without DN at T2D diagnosis, the continuous use of metformin vs other oral hypoglycemic agents was associated with a lower risk for:

Overt DN (incidence rate ratio [IRR], 0.82; 95% CI, 0.71-0.95),

MACEs (IRR, 0.76; 95% CI, 0.64-0.92), and

MAKEs (IRR, 0.45; 95% CI, 0.33-0.62).

Compared with non-metformin or discontinued metformin use, the continuous use of metformin was associated with a lower risk for MACE across CKD stages 3A (IRR, 0.70; 95% CI, 0.57-0.87), 3B (IRR, 0.83; 95% CI, 0.74-0.93), and 4 (IRR, 0.71; 95% CI, 0.60-0.85).

Similarly, the risk for MAKE was lower among continuous metformin users than in nonusers or discontinuous metformin users across CKD stage 3A (IRR, 0.39; 95% CI, 0.35-0.43), 3B (IRR, 0.44; 95% CI, 0.40-0.48), and 4 (IRR, 0.45; 95% CI, 0.39-0.51).

IN PRACTICE:

“The significance of the current study is highlighted by its integration of real-world clinical data, which encompasses patients diagnosed with CDK4 [eGRF, 15-29 mL/min/1.73 m2], a group currently considered contraindicated,” the authors wrote.

SOURCE:

The study, led by Yongjin Yi, MD, PhD, Department of Internal Medicine, Dankook University College of Medicine, Cheonan-si, Republic of Korea, was published in Scientific Reports.

LIMITATIONS:

There may be a possibility of selection bias because of the retrospective and observational nature of this study. Despite achieving a 1:1 propensity score matching to address the confounding factors, some variables, such as serum albumin and A1c levels, remained unbalanced after matching. The paper did not include observation length or patient numbers, but in response to an email query from Medscape, Yi notes that in one hospital, the mean duration of observation for the control and treatment groups was about 6.5 years, and the total number in the treatment groups across data from three hospitals was 11,675, with the same number of matched controls.

DISCLOSURES:

This study was supported by a Young Investigator Research Grant from the Korean Society of Nephrology, a grant from the Seoul National University Bundang Hospital Research Fund, and the Bio&Medical Technology Development Program of the National Research Foundation funded by the Korean government. The authors disclosed no competing interests.

A version of this article appeared on Medscape.com.