MDedge Cardiology

Cardiorespiratory fitness emerged as a stronger predictor of all-cause mortality than did any traditional risk factor across the spectrum of age, sex, and race in a modeling study that included more than 750,000 U.S. veterans.

In addition, mortality risk was cut in half if individuals achieved a moderate cardiorespiratory fitness (CRF) level – that is, by meeting the current U.S. physical activity recommendations of 150 minutes per week, the authors note.

Furthermore, contrary to some previous research, “extremely high” fitness was not associated with an increased risk for mortality in the study, published online in the Journal of the American College of Cardiology.

“This study has been 15 years in the making,” lead author Peter Kokkinos, PhD, Rutgers University, New Brunswick, N.J., and the VA Medical Center, Washington, told this news organization. “We waited until we had the computer power and the right people to really assess this. We wanted to be very liberal in excluding patients we thought might contaminate the results, such as those with cardiovascular disease in the 6 months prior to a stress test.”

Figuring the time was right, the team analyzed data from the VA’s Exercise Testing and Health Outcomes Study (ETHOS) on individuals aged 30-95 years who underwent exercise treadmill tests between 1999 and 2020.

After exclusions, 750,302 individuals (from among 822,995) were included: 6.5% were women; 73.7% were White individuals; 19% were African American individuals; 4.7% were Hispanic individuals; and 2.1% were Native American, Asian, or Hawaiian individuals. Septuagenarians made up 14.7% of the cohort, and octogenarians made up 3.6%.

CRF categories for age and sex were determined by the peak metabolic equivalent of task (MET) achieved during the treadmill test. One MET is the energy spent at rest – that is the basal metabolic rate.

Although some physicians may resist putting patients through a stress test, “the amount of information we get from it is incredible,” Dr. Kokkinos noted. “We get blood pressure, we get heart rate, we get a response if you’re not doing exercise. This tells us a lot more than having you sit around so we can measure resting heart rate and blood pressure.”

Lowest mortality at 14.0 METs

During a median follow-up of 10.2 years (7,803,861 person-years), 23% of participants died, for an average of 22.4 events per 1,000 person-years.

Higher exercise capacity was inversely related to mortality risk across the cohort and within each age category. Specifically, every 1 MET increase in exercise capacity yielded an adjusted hazard ratio for mortality of 0.86 (95% confidence interval, 0.85-0.87; P < .001) for the entire cohort and similar HRs by sex and race.

The mortality risk for the least-fit individuals (20th percentile) was fourfold higher than for extremely fit individuals (HR, 4.09; 95% CI, 3.90-4.20), with the lowest mortality risk at about 14.0 METs for both men (HR, 0.24; 95% CI, 0.23-0.25) and women (HR, 0.23; 95% CI, 0.17-0.29). Extremely high CRF did not increase the risk.

In addition, at 20 years of follow-up, about 80% of men and 95% of women in the highest CRF category (98th percentile) were alive vs. less than 40% of men and approximately 75% of women in the least fit CRF category.

“We know CRF declines by 1% per year after age 30,” Dr. Kokkinos said. “But the age-related decline is cut in half if you are fit, meaning that an expected 10% decline over a decade will be only a 5% decline if you stay active. We cannot stop or reverse the decline, but we can kind of put the brakes on, and that’s a reason for clinicians to continue to encourage fitness.” 

Indeed, “improving CRF should be considered a target in CVD prevention, similar to improving lipids, blood sugar, blood pressure, and weight,” Carl J. Lavie, MD, Ochsner Health, New Orleans, and colleagues affirm in a related editorial.
 

‘A difficult battle’

But that may not happen any time soon. “Unfortunately, despite having been recognized in an American Heart Association scientific statement as a clinical vital sign, aerobic fitness is undervalued and underutilized,” Claudio Gil Araújo, MD, PhD, research director of the Exercise Medicine Clinic-CLINIMEX, Rio de Janeiro, told this news organization.

Dr. Araújo led a recent study showing that the ability to stand on one leg for at least 10 seconds is strongly linked to the risk for death over the next 7 years.

Although physicians should be encouraging fitness, he said that “a substantial part of health professionals are physically unfit and feel uncomfortable talking about and prescribing exercise for their patients. Also, physicians tend to be better trained in treating diseases (using medications and/or prescribing procedures) than in preventing diseases by stimulating adoption of healthy habits. So, this a long road and a difficult battle.”

Nonetheless, he added, “Darwin said a long time ago that only the fittest will survive. If Darwin could read this study, he would surely smile.”

No commercial funding or conflicts of interest related to the study were reported. Dr. Lavie previously served as a speaker and consultant for PAI Health on their PAI (Personalized Activity Intelligence) applications.

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

Cardiorespiratory fitness emerged as a stronger predictor of all-cause mortality than did any traditional risk factor across the spectrum of age, sex, and race in a modeling study that included more than 750,000 U.S. veterans.

In addition, mortality risk was cut in half if individuals achieved a moderate cardiorespiratory fitness (CRF) level – that is, by meeting the current U.S. physical activity recommendations of 150 minutes per week, the authors note.

Furthermore, contrary to some previous research, “extremely high” fitness was not associated with an increased risk for mortality in the study, published online in the Journal of the American College of Cardiology.

“This study has been 15 years in the making,” lead author Peter Kokkinos, PhD, Rutgers University, New Brunswick, N.J., and the VA Medical Center, Washington, told this news organization. “We waited until we had the computer power and the right people to really assess this. We wanted to be very liberal in excluding patients we thought might contaminate the results, such as those with cardiovascular disease in the 6 months prior to a stress test.”

Figuring the time was right, the team analyzed data from the VA’s Exercise Testing and Health Outcomes Study (ETHOS) on individuals aged 30-95 years who underwent exercise treadmill tests between 1999 and 2020.

After exclusions, 750,302 individuals (from among 822,995) were included: 6.5% were women; 73.7% were White individuals; 19% were African American individuals; 4.7% were Hispanic individuals; and 2.1% were Native American, Asian, or Hawaiian individuals. Septuagenarians made up 14.7% of the cohort, and octogenarians made up 3.6%.

CRF categories for age and sex were determined by the peak metabolic equivalent of task (MET) achieved during the treadmill test. One MET is the energy spent at rest – that is the basal metabolic rate.

Although some physicians may resist putting patients through a stress test, “the amount of information we get from it is incredible,” Dr. Kokkinos noted. “We get blood pressure, we get heart rate, we get a response if you’re not doing exercise. This tells us a lot more than having you sit around so we can measure resting heart rate and blood pressure.”

Lowest mortality at 14.0 METs

During a median follow-up of 10.2 years (7,803,861 person-years), 23% of participants died, for an average of 22.4 events per 1,000 person-years.

Higher exercise capacity was inversely related to mortality risk across the cohort and within each age category. Specifically, every 1 MET increase in exercise capacity yielded an adjusted hazard ratio for mortality of 0.86 (95% confidence interval, 0.85-0.87; P < .001) for the entire cohort and similar HRs by sex and race.

The mortality risk for the least-fit individuals (20th percentile) was fourfold higher than for extremely fit individuals (HR, 4.09; 95% CI, 3.90-4.20), with the lowest mortality risk at about 14.0 METs for both men (HR, 0.24; 95% CI, 0.23-0.25) and women (HR, 0.23; 95% CI, 0.17-0.29). Extremely high CRF did not increase the risk.

In addition, at 20 years of follow-up, about 80% of men and 95% of women in the highest CRF category (98th percentile) were alive vs. less than 40% of men and approximately 75% of women in the least fit CRF category.

“We know CRF declines by 1% per year after age 30,” Dr. Kokkinos said. “But the age-related decline is cut in half if you are fit, meaning that an expected 10% decline over a decade will be only a 5% decline if you stay active. We cannot stop or reverse the decline, but we can kind of put the brakes on, and that’s a reason for clinicians to continue to encourage fitness.” 

Indeed, “improving CRF should be considered a target in CVD prevention, similar to improving lipids, blood sugar, blood pressure, and weight,” Carl J. Lavie, MD, Ochsner Health, New Orleans, and colleagues affirm in a related editorial.
 

‘A difficult battle’

But that may not happen any time soon. “Unfortunately, despite having been recognized in an American Heart Association scientific statement as a clinical vital sign, aerobic fitness is undervalued and underutilized,” Claudio Gil Araújo, MD, PhD, research director of the Exercise Medicine Clinic-CLINIMEX, Rio de Janeiro, told this news organization.

Dr. Araújo led a recent study showing that the ability to stand on one leg for at least 10 seconds is strongly linked to the risk for death over the next 7 years.

Although physicians should be encouraging fitness, he said that “a substantial part of health professionals are physically unfit and feel uncomfortable talking about and prescribing exercise for their patients. Also, physicians tend to be better trained in treating diseases (using medications and/or prescribing procedures) than in preventing diseases by stimulating adoption of healthy habits. So, this a long road and a difficult battle.”

Nonetheless, he added, “Darwin said a long time ago that only the fittest will survive. If Darwin could read this study, he would surely smile.”

No commercial funding or conflicts of interest related to the study were reported. Dr. Lavie previously served as a speaker and consultant for PAI Health on their PAI (Personalized Activity Intelligence) applications.

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

Cardiorespiratory fitness emerged as a stronger predictor of all-cause mortality than did any traditional risk factor across the spectrum of age, sex, and race in a modeling study that included more than 750,000 U.S. veterans.

In addition, mortality risk was cut in half if individuals achieved a moderate cardiorespiratory fitness (CRF) level – that is, by meeting the current U.S. physical activity recommendations of 150 minutes per week, the authors note.

Furthermore, contrary to some previous research, “extremely high” fitness was not associated with an increased risk for mortality in the study, published online in the Journal of the American College of Cardiology.

“This study has been 15 years in the making,” lead author Peter Kokkinos, PhD, Rutgers University, New Brunswick, N.J., and the VA Medical Center, Washington, told this news organization. “We waited until we had the computer power and the right people to really assess this. We wanted to be very liberal in excluding patients we thought might contaminate the results, such as those with cardiovascular disease in the 6 months prior to a stress test.”

Figuring the time was right, the team analyzed data from the VA’s Exercise Testing and Health Outcomes Study (ETHOS) on individuals aged 30-95 years who underwent exercise treadmill tests between 1999 and 2020.

After exclusions, 750,302 individuals (from among 822,995) were included: 6.5% were women; 73.7% were White individuals; 19% were African American individuals; 4.7% were Hispanic individuals; and 2.1% were Native American, Asian, or Hawaiian individuals. Septuagenarians made up 14.7% of the cohort, and octogenarians made up 3.6%.

CRF categories for age and sex were determined by the peak metabolic equivalent of task (MET) achieved during the treadmill test. One MET is the energy spent at rest – that is the basal metabolic rate.

Although some physicians may resist putting patients through a stress test, “the amount of information we get from it is incredible,” Dr. Kokkinos noted. “We get blood pressure, we get heart rate, we get a response if you’re not doing exercise. This tells us a lot more than having you sit around so we can measure resting heart rate and blood pressure.”

Lowest mortality at 14.0 METs

During a median follow-up of 10.2 years (7,803,861 person-years), 23% of participants died, for an average of 22.4 events per 1,000 person-years.

Higher exercise capacity was inversely related to mortality risk across the cohort and within each age category. Specifically, every 1 MET increase in exercise capacity yielded an adjusted hazard ratio for mortality of 0.86 (95% confidence interval, 0.85-0.87; P < .001) for the entire cohort and similar HRs by sex and race.

The mortality risk for the least-fit individuals (20th percentile) was fourfold higher than for extremely fit individuals (HR, 4.09; 95% CI, 3.90-4.20), with the lowest mortality risk at about 14.0 METs for both men (HR, 0.24; 95% CI, 0.23-0.25) and women (HR, 0.23; 95% CI, 0.17-0.29). Extremely high CRF did not increase the risk.

In addition, at 20 years of follow-up, about 80% of men and 95% of women in the highest CRF category (98th percentile) were alive vs. less than 40% of men and approximately 75% of women in the least fit CRF category.

“We know CRF declines by 1% per year after age 30,” Dr. Kokkinos said. “But the age-related decline is cut in half if you are fit, meaning that an expected 10% decline over a decade will be only a 5% decline if you stay active. We cannot stop or reverse the decline, but we can kind of put the brakes on, and that’s a reason for clinicians to continue to encourage fitness.” 

Indeed, “improving CRF should be considered a target in CVD prevention, similar to improving lipids, blood sugar, blood pressure, and weight,” Carl J. Lavie, MD, Ochsner Health, New Orleans, and colleagues affirm in a related editorial.
 

‘A difficult battle’

But that may not happen any time soon. “Unfortunately, despite having been recognized in an American Heart Association scientific statement as a clinical vital sign, aerobic fitness is undervalued and underutilized,” Claudio Gil Araújo, MD, PhD, research director of the Exercise Medicine Clinic-CLINIMEX, Rio de Janeiro, told this news organization.

Dr. Araújo led a recent study showing that the ability to stand on one leg for at least 10 seconds is strongly linked to the risk for death over the next 7 years.

Although physicians should be encouraging fitness, he said that “a substantial part of health professionals are physically unfit and feel uncomfortable talking about and prescribing exercise for their patients. Also, physicians tend to be better trained in treating diseases (using medications and/or prescribing procedures) than in preventing diseases by stimulating adoption of healthy habits. So, this a long road and a difficult battle.”

Nonetheless, he added, “Darwin said a long time ago that only the fittest will survive. If Darwin could read this study, he would surely smile.”

No commercial funding or conflicts of interest related to the study were reported. Dr. Lavie previously served as a speaker and consultant for PAI Health on their PAI (Personalized Activity Intelligence) applications.

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

The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.

The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.

“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.

“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”

The study was published online in Gut.
 

Risk calculations

NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.

Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.

Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.

The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.

In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.

Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.

The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.

In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.

“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.

“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
 

Future research

Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.

But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.

“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.

Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.

“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”

The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.

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

The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.

The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.

“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.

“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”

The study was published online in Gut.
 

Risk calculations

NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.

Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.

Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.

The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.

In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.

Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.

The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.

In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.

“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.

“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
 

Future research

Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.

But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.

“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.

Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.

“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”

The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.

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

The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.

The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.

“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.

“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”

The study was published online in Gut.
 

Risk calculations

NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.

Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.

Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.

The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.

In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.

Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.

The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.

In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.

“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.

“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
 

Future research

Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.

But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.

“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.

Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.

“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”

The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.

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

Updated clinical practice guidelines for the treatment and prevention of venous thromboembolism for patients with cancer, including those with cancer and COVID-19, have been released by the International Initiative on Thrombosis and Cancer (ITAC), an academic working group of VTE experts.

“Because patients with cancer have a baseline increased risk of VTE, compared with patients without cancer, the combination of both COVID-19 and cancer – and its effect on VTE risk and treatment – is of concern,” said the authors, led by Dominique Farge, MD, PhD, Nord Universite de Paris.

The updated 2022 ITAC guidelines cover new evidence on the treatment and prophylaxis of cancer-associated thrombosis, including for patients with cancer and COVID-19, they added.

The new guidelines were published online in The Lancet Oncology.

“Cancer-associated VTE remains an important clinical problem, associated with increased morbidity and mortality,” Dr. Farge and colleagues observed.

“The ITAC guidelines’ companion free web-based mobile application will assist the practicing clinician with decision making at various levels to provide optimal care of patients with cancer to treat and prevent VTE,” they emphasized. More information is available at itaccme.com.
 

Cancer patients with COVID

The new section of the guidelines notes that the treatment and prevention of VTE for cancer patients infected with SARS-CoV-2 remain the same as for patients without COVID.

Whether or not cancer patients with COVID-19 are hospitalized, have been discharged, or are ambulatory, they should be assessed for the risk of VTE, as should any other patient. For cancer patients with COVID-19 who are hospitalized, pharmacologic prophylaxis should be given at the same dose and anticoagulant type as for hospitalized cancer patients who do not have COVID-19.

Following discharge, VTE prophylaxis is not advised for cancer patients infected with SARS-CoV-2, and routine primary pharmacologic prophylaxis of VTE for ambulatory patients with COVID-19 is also not recommended, the authors noted.
 

Initial treatment of established VTE

Initial treatment of established VTE for up to 10 days of anticoagulation should include low-molecular-weight heparin (LMWH) when creatinine clearance is at least 30 mL/min.

“A regimen of LMWH, taken once per day, is recommended unless a twice-per-day regimen is required because of patients’ characteristics,” the authors noted. These characteristics include a high risk of bleeding, moderate renal failure, and the need for technical intervention, including surgery.

If a twice-a-day regimen is required, only enoxaparin at a dose of 1 mg/kg twice daily can be used, the authors cautioned.

For patients with a low risk of gastrointestinal or genitourinary bleeding, rivaroxaban (Xarelto) or apixaban (Eliquis) can be given in the first 10 days, as well as edoxaban (Lixiana). The latter should be started after at least 5 days of parenteral anticoagulation, provided creatinine clearance is at least 30 mL/min.

“Unfractionated heparin as well as fondaparinux (GlaxoSmithKline) can be also used for the initial treatment of established VTE when LMWH or direct oral anticoagulants are contraindicated,” Dr. Farge and colleagues wrote.

Thrombolysis can be considered on a case-by-case basis, although physicians must pay attention to specific contraindications, especially bleeding risk.

“In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation,” the authors noted.
 

Maintenance VTE treatment

For maintenance therapy, which the authors define as early maintenance for up to 6 months and long-term maintenance beyond 6 months, they point out that LMWHs are preferred over vitamin K antagonists for the treatment of VTE when the creatinine clearance is again at least 30 mL/min.

Any of the direct oral anticoagulants (DOAs) – edoxaban, rivaroxaban, or apixaban – is also recommended for the same patients, provided there is no risk of inducing a strong drug-drug interaction or GI absorption is impaired.

However, the DOAs should be used with caution for patients with GI malignancies, especially upper GI cancers, because data show there is an increased risk of GI bleeding with both edoxaban and rivaroxaban.

“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer,” the authors wrote.

“After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit-risk ratio,” they added.
 

Treatment of VTE recurrence

The guideline authors explain that three options can be considered in the event of VTE recurrence. These include an increase in the LMWH dose by 20%-25%, or a switch to a DOA, or, if patients are taking a DOA, a switch to an LMWH. If the patient is taking a vitamin K antagonist, it can be switched to either an LMWH or a DOA.

For treatment of catheter-related thrombosis, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place. In this setting, the LMWHs are recommended.

The central venous catheter can be kept in place if it is functional, well positioned, and is not infected, provided there is good resolution of symptoms under close surveillance while anticoagulants are being administered.

In surgically treated patients, the LMWH, given once a day, to patients with a serum creatinine concentration of at least 30 mL/min can be used to prevent VTE. Alternatively, VTE can be prevented by the use low-dose unfractionated heparin, given three times a day.

“Pharmacological prophylaxis should be started 2-12 h preoperatively and continued for at least 7–10 days,” Dr. Farge and colleagues advised. In this setting, there is insufficient evidence to support the use of fondaparinux or a DOA as an alternative to an LMWH for the prophylaxis of postoperative VTE. “Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended,” the authors advised.

Furthermore, extended prophylaxis of at least 4 weeks with LMWH is advised to prevent postoperative VTE after major abdominal or pelvic surgery. Mechanical methods are not recommended except when pharmacologic methods are contraindicated. Inferior vena cava filters are also not recommended for routine prophylaxis.
 

Patients with reduced mobility

For medically treated hospitalized patients with cancer whose mobility is reduced, the authors recommend prophylaxis with either an LMWH or fondaparinux, provided their creatinine clearance is at least 30 mL/min. These patients can also be treated with unfractionated heparin, they add.

In contrast, DOAs are not recommended – at least not routinely – in this setting, the authors cautioned. Primary pharmacologic prophylaxis of VTE with either LMWH or DOAs – either rivaroxaban or apixaban – is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer who are receiving systemic anticancer therapy, provided they are at low risk of bleeding.

However, primary pharmacologic prophylaxis with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer who are undergoing systemic anticancer therapy, even for patients who are at low risk of bleeding.

For ambulatory patients who are receiving systemic anticancer therapy and who are at intermediate risk of VTE, primary prophylaxis with rivaroxaban or apixaban is recommended for those with myeloma who are receiving immunomodulatory therapy plus steroids or other systemic therapies.

In this setting, oral anticoagulants should consist of a vitamin K antagonist, given at low or therapeutic doses, or apixaban, given at prophylactic doses. Alternatively, LMWH, given at prophylactic doses, or low-dose aspirin, given at a dose of 100 mg/day, can be used.
 

Catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. Catheters should be inserted on the right side in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. “In patients requiring central venous catheters, we suggest the use of implanted ports over peripheral inserted central catheter lines,” the authors noted.

The authors described a number of unique situations regarding the treatment of VTE. These situations include patients with a brain tumor, for whom treatment of established VTE should favor either LMWH or a DOA. The authors also recommended the use of LMWH or unfractionated heparin, started postoperatively, for the prevention of VTE for patients undergoing neurosurgery.

In contrast, pharmacologic prophylaxis of VTE in medically treated patients with a brain tumor who are not undergoing neurosurgery is not recommended. “In the presence of severe renal failure...we suggest using unfractionated heparin followed by early vitamin K antagonists (possibly from day 1) or LMWH adjusted to anti-Xa concentration of the treatment of established VTE,” Dr. Farge and colleagues wrote.

Anticoagulant treatment is also recommended for a minimum of 3 months for children with symptomatic catheter-related thrombosis and as long as the central venous catheter is in place. For children with acute lymphoblastic leukemia who are undergoing induction chemotherapy, LMWH is also recommended as thromboprophylaxis.

For children who require a central venous catheter, the authors suggested that physicians use implanted ports over peripherally inserted central lines.

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

Updated clinical practice guidelines for the treatment and prevention of venous thromboembolism for patients with cancer, including those with cancer and COVID-19, have been released by the International Initiative on Thrombosis and Cancer (ITAC), an academic working group of VTE experts.

“Because patients with cancer have a baseline increased risk of VTE, compared with patients without cancer, the combination of both COVID-19 and cancer – and its effect on VTE risk and treatment – is of concern,” said the authors, led by Dominique Farge, MD, PhD, Nord Universite de Paris.

The updated 2022 ITAC guidelines cover new evidence on the treatment and prophylaxis of cancer-associated thrombosis, including for patients with cancer and COVID-19, they added.

The new guidelines were published online in The Lancet Oncology.

“Cancer-associated VTE remains an important clinical problem, associated with increased morbidity and mortality,” Dr. Farge and colleagues observed.

“The ITAC guidelines’ companion free web-based mobile application will assist the practicing clinician with decision making at various levels to provide optimal care of patients with cancer to treat and prevent VTE,” they emphasized. More information is available at itaccme.com.
 

Cancer patients with COVID

The new section of the guidelines notes that the treatment and prevention of VTE for cancer patients infected with SARS-CoV-2 remain the same as for patients without COVID.

Whether or not cancer patients with COVID-19 are hospitalized, have been discharged, or are ambulatory, they should be assessed for the risk of VTE, as should any other patient. For cancer patients with COVID-19 who are hospitalized, pharmacologic prophylaxis should be given at the same dose and anticoagulant type as for hospitalized cancer patients who do not have COVID-19.

Following discharge, VTE prophylaxis is not advised for cancer patients infected with SARS-CoV-2, and routine primary pharmacologic prophylaxis of VTE for ambulatory patients with COVID-19 is also not recommended, the authors noted.
 

Initial treatment of established VTE

Initial treatment of established VTE for up to 10 days of anticoagulation should include low-molecular-weight heparin (LMWH) when creatinine clearance is at least 30 mL/min.

“A regimen of LMWH, taken once per day, is recommended unless a twice-per-day regimen is required because of patients’ characteristics,” the authors noted. These characteristics include a high risk of bleeding, moderate renal failure, and the need for technical intervention, including surgery.

If a twice-a-day regimen is required, only enoxaparin at a dose of 1 mg/kg twice daily can be used, the authors cautioned.

For patients with a low risk of gastrointestinal or genitourinary bleeding, rivaroxaban (Xarelto) or apixaban (Eliquis) can be given in the first 10 days, as well as edoxaban (Lixiana). The latter should be started after at least 5 days of parenteral anticoagulation, provided creatinine clearance is at least 30 mL/min.

“Unfractionated heparin as well as fondaparinux (GlaxoSmithKline) can be also used for the initial treatment of established VTE when LMWH or direct oral anticoagulants are contraindicated,” Dr. Farge and colleagues wrote.

Thrombolysis can be considered on a case-by-case basis, although physicians must pay attention to specific contraindications, especially bleeding risk.

“In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation,” the authors noted.
 

Maintenance VTE treatment

For maintenance therapy, which the authors define as early maintenance for up to 6 months and long-term maintenance beyond 6 months, they point out that LMWHs are preferred over vitamin K antagonists for the treatment of VTE when the creatinine clearance is again at least 30 mL/min.

Any of the direct oral anticoagulants (DOAs) – edoxaban, rivaroxaban, or apixaban – is also recommended for the same patients, provided there is no risk of inducing a strong drug-drug interaction or GI absorption is impaired.

However, the DOAs should be used with caution for patients with GI malignancies, especially upper GI cancers, because data show there is an increased risk of GI bleeding with both edoxaban and rivaroxaban.

“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer,” the authors wrote.

“After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit-risk ratio,” they added.
 

Treatment of VTE recurrence

The guideline authors explain that three options can be considered in the event of VTE recurrence. These include an increase in the LMWH dose by 20%-25%, or a switch to a DOA, or, if patients are taking a DOA, a switch to an LMWH. If the patient is taking a vitamin K antagonist, it can be switched to either an LMWH or a DOA.

For treatment of catheter-related thrombosis, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place. In this setting, the LMWHs are recommended.

The central venous catheter can be kept in place if it is functional, well positioned, and is not infected, provided there is good resolution of symptoms under close surveillance while anticoagulants are being administered.

In surgically treated patients, the LMWH, given once a day, to patients with a serum creatinine concentration of at least 30 mL/min can be used to prevent VTE. Alternatively, VTE can be prevented by the use low-dose unfractionated heparin, given three times a day.

“Pharmacological prophylaxis should be started 2-12 h preoperatively and continued for at least 7–10 days,” Dr. Farge and colleagues advised. In this setting, there is insufficient evidence to support the use of fondaparinux or a DOA as an alternative to an LMWH for the prophylaxis of postoperative VTE. “Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended,” the authors advised.

Furthermore, extended prophylaxis of at least 4 weeks with LMWH is advised to prevent postoperative VTE after major abdominal or pelvic surgery. Mechanical methods are not recommended except when pharmacologic methods are contraindicated. Inferior vena cava filters are also not recommended for routine prophylaxis.
 

Patients with reduced mobility

For medically treated hospitalized patients with cancer whose mobility is reduced, the authors recommend prophylaxis with either an LMWH or fondaparinux, provided their creatinine clearance is at least 30 mL/min. These patients can also be treated with unfractionated heparin, they add.

In contrast, DOAs are not recommended – at least not routinely – in this setting, the authors cautioned. Primary pharmacologic prophylaxis of VTE with either LMWH or DOAs – either rivaroxaban or apixaban – is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer who are receiving systemic anticancer therapy, provided they are at low risk of bleeding.

However, primary pharmacologic prophylaxis with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer who are undergoing systemic anticancer therapy, even for patients who are at low risk of bleeding.

For ambulatory patients who are receiving systemic anticancer therapy and who are at intermediate risk of VTE, primary prophylaxis with rivaroxaban or apixaban is recommended for those with myeloma who are receiving immunomodulatory therapy plus steroids or other systemic therapies.

In this setting, oral anticoagulants should consist of a vitamin K antagonist, given at low or therapeutic doses, or apixaban, given at prophylactic doses. Alternatively, LMWH, given at prophylactic doses, or low-dose aspirin, given at a dose of 100 mg/day, can be used.
 

Catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. Catheters should be inserted on the right side in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. “In patients requiring central venous catheters, we suggest the use of implanted ports over peripheral inserted central catheter lines,” the authors noted.

The authors described a number of unique situations regarding the treatment of VTE. These situations include patients with a brain tumor, for whom treatment of established VTE should favor either LMWH or a DOA. The authors also recommended the use of LMWH or unfractionated heparin, started postoperatively, for the prevention of VTE for patients undergoing neurosurgery.

In contrast, pharmacologic prophylaxis of VTE in medically treated patients with a brain tumor who are not undergoing neurosurgery is not recommended. “In the presence of severe renal failure...we suggest using unfractionated heparin followed by early vitamin K antagonists (possibly from day 1) or LMWH adjusted to anti-Xa concentration of the treatment of established VTE,” Dr. Farge and colleagues wrote.

Anticoagulant treatment is also recommended for a minimum of 3 months for children with symptomatic catheter-related thrombosis and as long as the central venous catheter is in place. For children with acute lymphoblastic leukemia who are undergoing induction chemotherapy, LMWH is also recommended as thromboprophylaxis.

For children who require a central venous catheter, the authors suggested that physicians use implanted ports over peripherally inserted central lines.

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

Updated clinical practice guidelines for the treatment and prevention of venous thromboembolism for patients with cancer, including those with cancer and COVID-19, have been released by the International Initiative on Thrombosis and Cancer (ITAC), an academic working group of VTE experts.

“Because patients with cancer have a baseline increased risk of VTE, compared with patients without cancer, the combination of both COVID-19 and cancer – and its effect on VTE risk and treatment – is of concern,” said the authors, led by Dominique Farge, MD, PhD, Nord Universite de Paris.

The updated 2022 ITAC guidelines cover new evidence on the treatment and prophylaxis of cancer-associated thrombosis, including for patients with cancer and COVID-19, they added.

The new guidelines were published online in The Lancet Oncology.

“Cancer-associated VTE remains an important clinical problem, associated with increased morbidity and mortality,” Dr. Farge and colleagues observed.

“The ITAC guidelines’ companion free web-based mobile application will assist the practicing clinician with decision making at various levels to provide optimal care of patients with cancer to treat and prevent VTE,” they emphasized. More information is available at itaccme.com.
 

Cancer patients with COVID

The new section of the guidelines notes that the treatment and prevention of VTE for cancer patients infected with SARS-CoV-2 remain the same as for patients without COVID.

Whether or not cancer patients with COVID-19 are hospitalized, have been discharged, or are ambulatory, they should be assessed for the risk of VTE, as should any other patient. For cancer patients with COVID-19 who are hospitalized, pharmacologic prophylaxis should be given at the same dose and anticoagulant type as for hospitalized cancer patients who do not have COVID-19.

Following discharge, VTE prophylaxis is not advised for cancer patients infected with SARS-CoV-2, and routine primary pharmacologic prophylaxis of VTE for ambulatory patients with COVID-19 is also not recommended, the authors noted.
 

Initial treatment of established VTE

Initial treatment of established VTE for up to 10 days of anticoagulation should include low-molecular-weight heparin (LMWH) when creatinine clearance is at least 30 mL/min.

“A regimen of LMWH, taken once per day, is recommended unless a twice-per-day regimen is required because of patients’ characteristics,” the authors noted. These characteristics include a high risk of bleeding, moderate renal failure, and the need for technical intervention, including surgery.

If a twice-a-day regimen is required, only enoxaparin at a dose of 1 mg/kg twice daily can be used, the authors cautioned.

For patients with a low risk of gastrointestinal or genitourinary bleeding, rivaroxaban (Xarelto) or apixaban (Eliquis) can be given in the first 10 days, as well as edoxaban (Lixiana). The latter should be started after at least 5 days of parenteral anticoagulation, provided creatinine clearance is at least 30 mL/min.

“Unfractionated heparin as well as fondaparinux (GlaxoSmithKline) can be also used for the initial treatment of established VTE when LMWH or direct oral anticoagulants are contraindicated,” Dr. Farge and colleagues wrote.

Thrombolysis can be considered on a case-by-case basis, although physicians must pay attention to specific contraindications, especially bleeding risk.

“In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation,” the authors noted.
 

Maintenance VTE treatment

For maintenance therapy, which the authors define as early maintenance for up to 6 months and long-term maintenance beyond 6 months, they point out that LMWHs are preferred over vitamin K antagonists for the treatment of VTE when the creatinine clearance is again at least 30 mL/min.

Any of the direct oral anticoagulants (DOAs) – edoxaban, rivaroxaban, or apixaban – is also recommended for the same patients, provided there is no risk of inducing a strong drug-drug interaction or GI absorption is impaired.

However, the DOAs should be used with caution for patients with GI malignancies, especially upper GI cancers, because data show there is an increased risk of GI bleeding with both edoxaban and rivaroxaban.

“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer,” the authors wrote.

“After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit-risk ratio,” they added.
 

Treatment of VTE recurrence

The guideline authors explain that three options can be considered in the event of VTE recurrence. These include an increase in the LMWH dose by 20%-25%, or a switch to a DOA, or, if patients are taking a DOA, a switch to an LMWH. If the patient is taking a vitamin K antagonist, it can be switched to either an LMWH or a DOA.

For treatment of catheter-related thrombosis, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place. In this setting, the LMWHs are recommended.

The central venous catheter can be kept in place if it is functional, well positioned, and is not infected, provided there is good resolution of symptoms under close surveillance while anticoagulants are being administered.

In surgically treated patients, the LMWH, given once a day, to patients with a serum creatinine concentration of at least 30 mL/min can be used to prevent VTE. Alternatively, VTE can be prevented by the use low-dose unfractionated heparin, given three times a day.

“Pharmacological prophylaxis should be started 2-12 h preoperatively and continued for at least 7–10 days,” Dr. Farge and colleagues advised. In this setting, there is insufficient evidence to support the use of fondaparinux or a DOA as an alternative to an LMWH for the prophylaxis of postoperative VTE. “Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended,” the authors advised.

Furthermore, extended prophylaxis of at least 4 weeks with LMWH is advised to prevent postoperative VTE after major abdominal or pelvic surgery. Mechanical methods are not recommended except when pharmacologic methods are contraindicated. Inferior vena cava filters are also not recommended for routine prophylaxis.
 

Patients with reduced mobility

For medically treated hospitalized patients with cancer whose mobility is reduced, the authors recommend prophylaxis with either an LMWH or fondaparinux, provided their creatinine clearance is at least 30 mL/min. These patients can also be treated with unfractionated heparin, they add.

In contrast, DOAs are not recommended – at least not routinely – in this setting, the authors cautioned. Primary pharmacologic prophylaxis of VTE with either LMWH or DOAs – either rivaroxaban or apixaban – is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer who are receiving systemic anticancer therapy, provided they are at low risk of bleeding.

However, primary pharmacologic prophylaxis with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer who are undergoing systemic anticancer therapy, even for patients who are at low risk of bleeding.

For ambulatory patients who are receiving systemic anticancer therapy and who are at intermediate risk of VTE, primary prophylaxis with rivaroxaban or apixaban is recommended for those with myeloma who are receiving immunomodulatory therapy plus steroids or other systemic therapies.

In this setting, oral anticoagulants should consist of a vitamin K antagonist, given at low or therapeutic doses, or apixaban, given at prophylactic doses. Alternatively, LMWH, given at prophylactic doses, or low-dose aspirin, given at a dose of 100 mg/day, can be used.
 

Catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. Catheters should be inserted on the right side in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. “In patients requiring central venous catheters, we suggest the use of implanted ports over peripheral inserted central catheter lines,” the authors noted.

The authors described a number of unique situations regarding the treatment of VTE. These situations include patients with a brain tumor, for whom treatment of established VTE should favor either LMWH or a DOA. The authors also recommended the use of LMWH or unfractionated heparin, started postoperatively, for the prevention of VTE for patients undergoing neurosurgery.

In contrast, pharmacologic prophylaxis of VTE in medically treated patients with a brain tumor who are not undergoing neurosurgery is not recommended. “In the presence of severe renal failure...we suggest using unfractionated heparin followed by early vitamin K antagonists (possibly from day 1) or LMWH adjusted to anti-Xa concentration of the treatment of established VTE,” Dr. Farge and colleagues wrote.

Anticoagulant treatment is also recommended for a minimum of 3 months for children with symptomatic catheter-related thrombosis and as long as the central venous catheter is in place. For children with acute lymphoblastic leukemia who are undergoing induction chemotherapy, LMWH is also recommended as thromboprophylaxis.

For children who require a central venous catheter, the authors suggested that physicians use implanted ports over peripherally inserted central lines.

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

Although cardiovascular disease (CVD) is known to often strike the mortal blow in patients with cancer, a national analysis puts in stark relief the burden of CV-related hospitalizations in this vulnerable population.

Results show that between 2004 and 2017, CV admissions increased 23.2% among patients with a cancer diagnosis, whereas admissions fell 10.9% among those without cancer.

Admissions increased steadily across all cancer types, except prostate cancer, with heart failure being the most common reason for admission.

“Hospital admissions is really important because we know that the size of this group is increasing, given that they live longer and many of the treatments that we offer cause cardiovascular disease or increase the risk of having cardiovascular events. So, from a health care planning perspective, I think it’s really important to see what the burden is likely to be in the next few years,” senior author Mamas Mamas, MD, Keele University, England, told this news organization.

For physicians and the wider population, he said, the findings underscore the need to shift the conversation from saying that patients with cancer are at increased CVD risk to asking how to mitigate this risk. “Because I would say that this increase in cardiovascular admissions, that’s a failure from a preventative perspective.”

The study was published in the European Heart Journal: Quality of Care & Clinical Outcomes.

Individual cancer types

The researchers, led by Ofer Kobo, MD, also with Keele University, used the National Inpatient Sample to identify 42.5 million weighted cases of CV admissions for acute myocardial infarction (AMI), pulmonary embolism, ischemic stroke, heart failure, atrial fibrillation (AFib) or atrial flutter, and intracranial hemorrhage from January 2004 to December 2017. Of these, 1.9 million had a record of cancer.

Patients with cancer were older; had a higher prevalence of valvular disease, anemia, and coagulopathy; and had a lower prevalence of hypertension, diabetes mellitus, and obesity than did patients without cancer.

The most common cancer type was hematologic cancers (26.1%), followed by lung (18.7%), gastrointestinal (12.4%), prostate (11.6%), breast (6.7%), and other in 24.4%.

The admission rate increased across all six admission causes – between 7% for AMI and ischemic stroke and 46% for AFib.

Heart failure was the chief reason for admission among all patients. Annual rates per 100,000 U.S. population increased in patients with cancer (from 13.6 to 16.6; P for trend = .02) and declined in those without (from 352.2 to 349.8; P for trend < .001).

“In the past, patients would be started on medications, and perhaps the importance of monitoring [left ventricular] LV function wasn’t as widely known, whereas now we’re much more aggressive in looking at it and much more aggressive at trying to prevent it,” Dr. Mamas said. “But even with this greater identification and attempting to modify regimens, we’re still getting quite substantial increases in heart failure admissions in this population. And what really surprised me is that it wasn’t just in the breast cancer population, but it was nearly across the board.”

He noted that patients are at highest risk from CV events within the first 2 years of cancer diagnosis. “So that’s really the time where you’ve got to be really aggressive in looking and working up their cardiovascular profile.”

Patients with hematologic cancers (9.7-13.5), lung (7.4-8.9), and gastrointestinal cancer (4.6-6.3) had the highest crude admission rates of CV hospitalizations per 100,000 U.S. population.

The CV admission rate went up from 2.5 to 3.7 per 100,000 U.S. population for breast cancer, and in prostate cancer, the rate dropped from 5.8 to 4.8 per 100,000 U.S. population.

Of note, patients with hematologic cancers also had the highest rate of heart failure hospitalization across all cancer types, which, coupled with their increasing admission rates, likely reflects their exposure to a “constellation of cardiotoxic therapies” as well as pathologic processes related to the cancers themselves, the authors suggest.

In-hospital mortality rates were higher among patients with cancer than those without, ranging from 5% for patients with breast cancer to 9.6% for patients with lung cancer versus 4.2% for those without cancer.

Among patients with cancer, the odds ratio for mortality was highest in those admitted with AFib (4.43), followed by pulmonary embolism (2.36), AMI (2.31), ischemic stroke (2.29), and heart failure (2.24).

In line with prior work and general population trends, in-hospital deaths in primary CV admissions trended lower among patients with cancer over the study period.

Mitigating risk

Commenting on the study, Joerg Herrmann, MD, director of the cardio-oncology clinic at Mayo Clinic, Rochester, Minn., said that the data are “extremely important” because they reflect admissions during a new era of cancer therapy. “Targeted therapies all came out about the turn of the millennium, so we’re not really looking at cancer patients treated with only old and ancient strategies.”

This may be one reason for the increased admissions, but because the study lacked information on specific cancer treatments and the date of cancer diagnosis, it’s not possible to tease out whether the uptick is related to cardiotoxicity or because the oncology outcomes have improved so much that this is a growing population, he said.

One clear implication, however, is that whoever is working on the hospital service will see more patients with a cancer diagnosis, Dr. Herrmann observed.

“Though some may have tried to maybe not get involved with this topic as much, it really calls for some broader scope to get familiar with this very entity,” he said. “And that plays out, in particular, in those patients with a diagnosis of active cancer.”

Dr. Herrmann and colleagues previously reported that patients with active leukemia or lymphoma who were hospitalized with acute coronary syndrome were less likely to receive guideline-directed therapies, even at the Mayo Clinic.

Similarly, a 2020 report by Dr. Mamas and colleagues found that patients with a variety of active cancers derived similar benefit from primary percutaneous coronary intervention for ST-segment–elevation MI as those without cancer but received the treatment less commonly.

Although there’s a greater appreciation that patients with cancer benefit equally from aggressive treatment, much more can be done to mitigate CV risk, Dr. Mamas noted. Valuable coronary information captured by MRI and CT done as part of the cancer investigation is often overlooked. For example, “we know that breast calcification and vascular calcification in the breast are very strong predictors of cardiovascular outcomes and yet people aren’t using this information.”

There are numerous shared risk factors in the development of cancer and coronary artery disease, and patients with cancer often have much worse CV risk profiles but aren’t routinely risk stratified from a CV perspective, he said.

Dr. Mamas said that his team is also studying whether CVD risk prediction tools like the Framingham Risk Score, which were derived from noncancer populations, work as well in patients with cancer. “Often, when you look at the performance of these tools in populations that weren’t covered, they’re much worse.”

“A lot of cancer survivors worry about the recurrence of their cancer and will religiously go and have repeated scans, religiously check themselves, and have all these investigations but don’t think about the actual risk that is greater for them, which is cardiovascular risk,” he said.

The authors report no study funding or relevant financial relationships.

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

Although cardiovascular disease (CVD) is known to often strike the mortal blow in patients with cancer, a national analysis puts in stark relief the burden of CV-related hospitalizations in this vulnerable population.

Results show that between 2004 and 2017, CV admissions increased 23.2% among patients with a cancer diagnosis, whereas admissions fell 10.9% among those without cancer.

Admissions increased steadily across all cancer types, except prostate cancer, with heart failure being the most common reason for admission.

“Hospital admissions is really important because we know that the size of this group is increasing, given that they live longer and many of the treatments that we offer cause cardiovascular disease or increase the risk of having cardiovascular events. So, from a health care planning perspective, I think it’s really important to see what the burden is likely to be in the next few years,” senior author Mamas Mamas, MD, Keele University, England, told this news organization.

For physicians and the wider population, he said, the findings underscore the need to shift the conversation from saying that patients with cancer are at increased CVD risk to asking how to mitigate this risk. “Because I would say that this increase in cardiovascular admissions, that’s a failure from a preventative perspective.”

The study was published in the European Heart Journal: Quality of Care & Clinical Outcomes.

Individual cancer types

The researchers, led by Ofer Kobo, MD, also with Keele University, used the National Inpatient Sample to identify 42.5 million weighted cases of CV admissions for acute myocardial infarction (AMI), pulmonary embolism, ischemic stroke, heart failure, atrial fibrillation (AFib) or atrial flutter, and intracranial hemorrhage from January 2004 to December 2017. Of these, 1.9 million had a record of cancer.

Patients with cancer were older; had a higher prevalence of valvular disease, anemia, and coagulopathy; and had a lower prevalence of hypertension, diabetes mellitus, and obesity than did patients without cancer.

The most common cancer type was hematologic cancers (26.1%), followed by lung (18.7%), gastrointestinal (12.4%), prostate (11.6%), breast (6.7%), and other in 24.4%.

The admission rate increased across all six admission causes – between 7% for AMI and ischemic stroke and 46% for AFib.

Heart failure was the chief reason for admission among all patients. Annual rates per 100,000 U.S. population increased in patients with cancer (from 13.6 to 16.6; P for trend = .02) and declined in those without (from 352.2 to 349.8; P for trend < .001).

“In the past, patients would be started on medications, and perhaps the importance of monitoring [left ventricular] LV function wasn’t as widely known, whereas now we’re much more aggressive in looking at it and much more aggressive at trying to prevent it,” Dr. Mamas said. “But even with this greater identification and attempting to modify regimens, we’re still getting quite substantial increases in heart failure admissions in this population. And what really surprised me is that it wasn’t just in the breast cancer population, but it was nearly across the board.”

He noted that patients are at highest risk from CV events within the first 2 years of cancer diagnosis. “So that’s really the time where you’ve got to be really aggressive in looking and working up their cardiovascular profile.”

Patients with hematologic cancers (9.7-13.5), lung (7.4-8.9), and gastrointestinal cancer (4.6-6.3) had the highest crude admission rates of CV hospitalizations per 100,000 U.S. population.

The CV admission rate went up from 2.5 to 3.7 per 100,000 U.S. population for breast cancer, and in prostate cancer, the rate dropped from 5.8 to 4.8 per 100,000 U.S. population.

Of note, patients with hematologic cancers also had the highest rate of heart failure hospitalization across all cancer types, which, coupled with their increasing admission rates, likely reflects their exposure to a “constellation of cardiotoxic therapies” as well as pathologic processes related to the cancers themselves, the authors suggest.

In-hospital mortality rates were higher among patients with cancer than those without, ranging from 5% for patients with breast cancer to 9.6% for patients with lung cancer versus 4.2% for those without cancer.

Among patients with cancer, the odds ratio for mortality was highest in those admitted with AFib (4.43), followed by pulmonary embolism (2.36), AMI (2.31), ischemic stroke (2.29), and heart failure (2.24).

In line with prior work and general population trends, in-hospital deaths in primary CV admissions trended lower among patients with cancer over the study period.

Mitigating risk

Commenting on the study, Joerg Herrmann, MD, director of the cardio-oncology clinic at Mayo Clinic, Rochester, Minn., said that the data are “extremely important” because they reflect admissions during a new era of cancer therapy. “Targeted therapies all came out about the turn of the millennium, so we’re not really looking at cancer patients treated with only old and ancient strategies.”

This may be one reason for the increased admissions, but because the study lacked information on specific cancer treatments and the date of cancer diagnosis, it’s not possible to tease out whether the uptick is related to cardiotoxicity or because the oncology outcomes have improved so much that this is a growing population, he said.

One clear implication, however, is that whoever is working on the hospital service will see more patients with a cancer diagnosis, Dr. Herrmann observed.

“Though some may have tried to maybe not get involved with this topic as much, it really calls for some broader scope to get familiar with this very entity,” he said. “And that plays out, in particular, in those patients with a diagnosis of active cancer.”

Dr. Herrmann and colleagues previously reported that patients with active leukemia or lymphoma who were hospitalized with acute coronary syndrome were less likely to receive guideline-directed therapies, even at the Mayo Clinic.

Similarly, a 2020 report by Dr. Mamas and colleagues found that patients with a variety of active cancers derived similar benefit from primary percutaneous coronary intervention for ST-segment–elevation MI as those without cancer but received the treatment less commonly.

Although there’s a greater appreciation that patients with cancer benefit equally from aggressive treatment, much more can be done to mitigate CV risk, Dr. Mamas noted. Valuable coronary information captured by MRI and CT done as part of the cancer investigation is often overlooked. For example, “we know that breast calcification and vascular calcification in the breast are very strong predictors of cardiovascular outcomes and yet people aren’t using this information.”

There are numerous shared risk factors in the development of cancer and coronary artery disease, and patients with cancer often have much worse CV risk profiles but aren’t routinely risk stratified from a CV perspective, he said.

Dr. Mamas said that his team is also studying whether CVD risk prediction tools like the Framingham Risk Score, which were derived from noncancer populations, work as well in patients with cancer. “Often, when you look at the performance of these tools in populations that weren’t covered, they’re much worse.”

“A lot of cancer survivors worry about the recurrence of their cancer and will religiously go and have repeated scans, religiously check themselves, and have all these investigations but don’t think about the actual risk that is greater for them, which is cardiovascular risk,” he said.

The authors report no study funding or relevant financial relationships.

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

Although cardiovascular disease (CVD) is known to often strike the mortal blow in patients with cancer, a national analysis puts in stark relief the burden of CV-related hospitalizations in this vulnerable population.

Results show that between 2004 and 2017, CV admissions increased 23.2% among patients with a cancer diagnosis, whereas admissions fell 10.9% among those without cancer.

Admissions increased steadily across all cancer types, except prostate cancer, with heart failure being the most common reason for admission.

“Hospital admissions is really important because we know that the size of this group is increasing, given that they live longer and many of the treatments that we offer cause cardiovascular disease or increase the risk of having cardiovascular events. So, from a health care planning perspective, I think it’s really important to see what the burden is likely to be in the next few years,” senior author Mamas Mamas, MD, Keele University, England, told this news organization.

For physicians and the wider population, he said, the findings underscore the need to shift the conversation from saying that patients with cancer are at increased CVD risk to asking how to mitigate this risk. “Because I would say that this increase in cardiovascular admissions, that’s a failure from a preventative perspective.”

The study was published in the European Heart Journal: Quality of Care & Clinical Outcomes.

Individual cancer types

The researchers, led by Ofer Kobo, MD, also with Keele University, used the National Inpatient Sample to identify 42.5 million weighted cases of CV admissions for acute myocardial infarction (AMI), pulmonary embolism, ischemic stroke, heart failure, atrial fibrillation (AFib) or atrial flutter, and intracranial hemorrhage from January 2004 to December 2017. Of these, 1.9 million had a record of cancer.

Patients with cancer were older; had a higher prevalence of valvular disease, anemia, and coagulopathy; and had a lower prevalence of hypertension, diabetes mellitus, and obesity than did patients without cancer.

The most common cancer type was hematologic cancers (26.1%), followed by lung (18.7%), gastrointestinal (12.4%), prostate (11.6%), breast (6.7%), and other in 24.4%.

The admission rate increased across all six admission causes – between 7% for AMI and ischemic stroke and 46% for AFib.

Heart failure was the chief reason for admission among all patients. Annual rates per 100,000 U.S. population increased in patients with cancer (from 13.6 to 16.6; P for trend = .02) and declined in those without (from 352.2 to 349.8; P for trend < .001).

“In the past, patients would be started on medications, and perhaps the importance of monitoring [left ventricular] LV function wasn’t as widely known, whereas now we’re much more aggressive in looking at it and much more aggressive at trying to prevent it,” Dr. Mamas said. “But even with this greater identification and attempting to modify regimens, we’re still getting quite substantial increases in heart failure admissions in this population. And what really surprised me is that it wasn’t just in the breast cancer population, but it was nearly across the board.”

He noted that patients are at highest risk from CV events within the first 2 years of cancer diagnosis. “So that’s really the time where you’ve got to be really aggressive in looking and working up their cardiovascular profile.”

Patients with hematologic cancers (9.7-13.5), lung (7.4-8.9), and gastrointestinal cancer (4.6-6.3) had the highest crude admission rates of CV hospitalizations per 100,000 U.S. population.

The CV admission rate went up from 2.5 to 3.7 per 100,000 U.S. population for breast cancer, and in prostate cancer, the rate dropped from 5.8 to 4.8 per 100,000 U.S. population.

Of note, patients with hematologic cancers also had the highest rate of heart failure hospitalization across all cancer types, which, coupled with their increasing admission rates, likely reflects their exposure to a “constellation of cardiotoxic therapies” as well as pathologic processes related to the cancers themselves, the authors suggest.

In-hospital mortality rates were higher among patients with cancer than those without, ranging from 5% for patients with breast cancer to 9.6% for patients with lung cancer versus 4.2% for those without cancer.

Among patients with cancer, the odds ratio for mortality was highest in those admitted with AFib (4.43), followed by pulmonary embolism (2.36), AMI (2.31), ischemic stroke (2.29), and heart failure (2.24).

In line with prior work and general population trends, in-hospital deaths in primary CV admissions trended lower among patients with cancer over the study period.

Mitigating risk

Commenting on the study, Joerg Herrmann, MD, director of the cardio-oncology clinic at Mayo Clinic, Rochester, Minn., said that the data are “extremely important” because they reflect admissions during a new era of cancer therapy. “Targeted therapies all came out about the turn of the millennium, so we’re not really looking at cancer patients treated with only old and ancient strategies.”

This may be one reason for the increased admissions, but because the study lacked information on specific cancer treatments and the date of cancer diagnosis, it’s not possible to tease out whether the uptick is related to cardiotoxicity or because the oncology outcomes have improved so much that this is a growing population, he said.

One clear implication, however, is that whoever is working on the hospital service will see more patients with a cancer diagnosis, Dr. Herrmann observed.

“Though some may have tried to maybe not get involved with this topic as much, it really calls for some broader scope to get familiar with this very entity,” he said. “And that plays out, in particular, in those patients with a diagnosis of active cancer.”

Dr. Herrmann and colleagues previously reported that patients with active leukemia or lymphoma who were hospitalized with acute coronary syndrome were less likely to receive guideline-directed therapies, even at the Mayo Clinic.

Similarly, a 2020 report by Dr. Mamas and colleagues found that patients with a variety of active cancers derived similar benefit from primary percutaneous coronary intervention for ST-segment–elevation MI as those without cancer but received the treatment less commonly.

Although there’s a greater appreciation that patients with cancer benefit equally from aggressive treatment, much more can be done to mitigate CV risk, Dr. Mamas noted. Valuable coronary information captured by MRI and CT done as part of the cancer investigation is often overlooked. For example, “we know that breast calcification and vascular calcification in the breast are very strong predictors of cardiovascular outcomes and yet people aren’t using this information.”

There are numerous shared risk factors in the development of cancer and coronary artery disease, and patients with cancer often have much worse CV risk profiles but aren’t routinely risk stratified from a CV perspective, he said.

Dr. Mamas said that his team is also studying whether CVD risk prediction tools like the Framingham Risk Score, which were derived from noncancer populations, work as well in patients with cancer. “Often, when you look at the performance of these tools in populations that weren’t covered, they’re much worse.”

“A lot of cancer survivors worry about the recurrence of their cancer and will religiously go and have repeated scans, religiously check themselves, and have all these investigations but don’t think about the actual risk that is greater for them, which is cardiovascular risk,” he said.

The authors report no study funding or relevant financial relationships.

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

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

PCSK9 inhibitors, which are among the most effective therapies for reducing LDL cholesterol (LDL-C), are associated with a neutral effect on cognitive function, according to a genetics-based Mendelian randomization study intended to sort out through the complexity of confounders.

The same study linked HMG-Co A reductase inhibitors (statins) with the potential for modest adverse neurocognitive effects, although these are likely to be outweighed by cardiovascular benefits, according to a collaborating team of investigators from the U.S. National Institutes of Health and the University of Oxford (England).

For clinicians and patients who continue to harbor concerns that cognitive function is threatened by very low LDL-C, this novel approach to evaluating risk is “reassuring,” according to the authors.

Early in clinical testing of PCSK9 inhibitors, a potential signal for adverse effects on cognitive function was reported but unconfirmed. This signal raised concern that extremely low levels of LDL-C, such as < 25 mg/dL, achieved with PCSK9 inhibitors might pose a risk to neurocognitive function.

Of several factors that provided a basis for concern, the PCSK9 enzyme is known to participate in brain development, according to the authors of this newly published study.
 

Mendelian randomization addresses complex issue

The objective of this Mendelian randomization analysis was to evaluate the relationship of PCSK9 inhibitors and statins on long-term neurocognitive function. Used previously to address other clinical issues, a drug-effect Mendelian randomization analysis evaluates genetic variants to determine whether there is a causal relationship between a risk, which in this case was lipid-lowering drugs, to a specific outcome, which was cognitive performance.

By looking directly at genetic variants that simulate the pharmacological inhibition of drug gene targets, the bias of confounders of clinical effects, such as baseline cognitive function, are avoided, according to the authors.

The message from this drug-effect Mendelian analysis was simple, according to the senior author of the study, Falk W. Lohoff, MD, chief of the section on clinical genomics and experimental therapeutics, National Institute of Alcohol Abuse and Alcoholism.

“Based on our data, we do not see a significant cognitive risk profile with PCSK9 inhibition associated with low LDL-C,” Dr. Lohoff said in an interview. He cautioned that “future long-term clinical studies are needed to confirm the absence of this effect,” but he and his coauthors noted that these data concur with the clinical studies.

From genome-wide association studies, single-nucleotide polymorphisms in PCSK9 and HMG-Co A reductase were extracted from a sample of more than 700,000 individuals of predominantly European ancestry. In the analysis, the investigators evaluated whether inhibition of PCSK9 or HMG-Co A reductase had an effect on seven clinical outcomes that relate to neurocognitive function, including memory, verbal intelligence, and reaction time, as well as biomarkers of cognitive function, such as cortical surface area.

The genetic effect of PCSK9 inhibition was “null for every cognitive-related outcome evaluated,” the investigators reported. The genetic effect of HMG-Co A reductase inhibition had a statistically significant but modest effect on cognitive performance (P = .03) and cortical surface area (P = .03). While the impact of HMG-Co A reductase inhibition on reaction time was stronger on a statistical basis (P = .0002), the investigators reported that it translated into a decrease of only 0.067 milliseconds per 38.7 mg/dL. They characterized this as a “small impact” unlikely to outweigh clinical benefits.

In an editorial that accompanied publication of this study, Brian A. Ference, MD, MPhil, provided context for the suitability of a Mendelian randomization analysis to address this or other questions regarding the impact of lipid-lowering therapies on clinical outcomes, and he ultimately concurred with the major conclusions

Ultimately, this analysis is consistent with other evidence that PCSK9 inhibition does not pose a risk of impaired cognitive function, he wrote. For statins, he concluded that this study “does not provide compelling evidence” to challenge their current clinical use.


 

Data do not support low LDL-C as cognitive risk factor

Moreover, this study – as well as other evidence – argues strongly against very low levels of LDL-C, regardless of how they are achieved, as a risk factor for diminished cognitive function, Dr. Ference, director of research in the division of translational therapeutics, University of Cambridge (England), said in an interview.

“There is no evidence from Mendelian randomization studies that lifelong exposure to lower LDL-C increases the risk of cognitive impairment,” he said. “This is true when evaluating lifelong exposure to lower LDL-C due to genetic variants in a wide variety of different genes or the genes that encode the target PCKS9 inhibitors, statins, or other lipid-lowering therapies.”

In other words, this study “adds to the accumulating evidence” that LDL-C lowering by itself does not contribute to an adverse impact on cognitive function despite persistent concern. This should not be surprising. Dr. Ference emphasized that there has never been strong evidence for an association.

“As I point out in the editorial, there is no biologically plausible mechanism by which reducing peripheral LDL-C should impact neurological function in any way, because the therapies do not cross the blood brain barrier, and because the nervous system produces its own cholesterol to maintain the integrity of membranes in nervous system cells,” he explained.

Dr. Lohoff reports no potential conflicts of interest. Dr. Ference has financial relationships with numerous pharmaceutical companies including those that make lipid-lowering therapies.

PCSK9 inhibitors, which are among the most effective therapies for reducing LDL cholesterol (LDL-C), are associated with a neutral effect on cognitive function, according to a genetics-based Mendelian randomization study intended to sort out through the complexity of confounders.

The same study linked HMG-Co A reductase inhibitors (statins) with the potential for modest adverse neurocognitive effects, although these are likely to be outweighed by cardiovascular benefits, according to a collaborating team of investigators from the U.S. National Institutes of Health and the University of Oxford (England).

For clinicians and patients who continue to harbor concerns that cognitive function is threatened by very low LDL-C, this novel approach to evaluating risk is “reassuring,” according to the authors.

Early in clinical testing of PCSK9 inhibitors, a potential signal for adverse effects on cognitive function was reported but unconfirmed. This signal raised concern that extremely low levels of LDL-C, such as < 25 mg/dL, achieved with PCSK9 inhibitors might pose a risk to neurocognitive function.

Of several factors that provided a basis for concern, the PCSK9 enzyme is known to participate in brain development, according to the authors of this newly published study.
 

Mendelian randomization addresses complex issue

The objective of this Mendelian randomization analysis was to evaluate the relationship of PCSK9 inhibitors and statins on long-term neurocognitive function. Used previously to address other clinical issues, a drug-effect Mendelian randomization analysis evaluates genetic variants to determine whether there is a causal relationship between a risk, which in this case was lipid-lowering drugs, to a specific outcome, which was cognitive performance.

By looking directly at genetic variants that simulate the pharmacological inhibition of drug gene targets, the bias of confounders of clinical effects, such as baseline cognitive function, are avoided, according to the authors.

The message from this drug-effect Mendelian analysis was simple, according to the senior author of the study, Falk W. Lohoff, MD, chief of the section on clinical genomics and experimental therapeutics, National Institute of Alcohol Abuse and Alcoholism.

“Based on our data, we do not see a significant cognitive risk profile with PCSK9 inhibition associated with low LDL-C,” Dr. Lohoff said in an interview. He cautioned that “future long-term clinical studies are needed to confirm the absence of this effect,” but he and his coauthors noted that these data concur with the clinical studies.

From genome-wide association studies, single-nucleotide polymorphisms in PCSK9 and HMG-Co A reductase were extracted from a sample of more than 700,000 individuals of predominantly European ancestry. In the analysis, the investigators evaluated whether inhibition of PCSK9 or HMG-Co A reductase had an effect on seven clinical outcomes that relate to neurocognitive function, including memory, verbal intelligence, and reaction time, as well as biomarkers of cognitive function, such as cortical surface area.

The genetic effect of PCSK9 inhibition was “null for every cognitive-related outcome evaluated,” the investigators reported. The genetic effect of HMG-Co A reductase inhibition had a statistically significant but modest effect on cognitive performance (P = .03) and cortical surface area (P = .03). While the impact of HMG-Co A reductase inhibition on reaction time was stronger on a statistical basis (P = .0002), the investigators reported that it translated into a decrease of only 0.067 milliseconds per 38.7 mg/dL. They characterized this as a “small impact” unlikely to outweigh clinical benefits.

In an editorial that accompanied publication of this study, Brian A. Ference, MD, MPhil, provided context for the suitability of a Mendelian randomization analysis to address this or other questions regarding the impact of lipid-lowering therapies on clinical outcomes, and he ultimately concurred with the major conclusions

Ultimately, this analysis is consistent with other evidence that PCSK9 inhibition does not pose a risk of impaired cognitive function, he wrote. For statins, he concluded that this study “does not provide compelling evidence” to challenge their current clinical use.


 

Data do not support low LDL-C as cognitive risk factor

Moreover, this study – as well as other evidence – argues strongly against very low levels of LDL-C, regardless of how they are achieved, as a risk factor for diminished cognitive function, Dr. Ference, director of research in the division of translational therapeutics, University of Cambridge (England), said in an interview.

“There is no evidence from Mendelian randomization studies that lifelong exposure to lower LDL-C increases the risk of cognitive impairment,” he said. “This is true when evaluating lifelong exposure to lower LDL-C due to genetic variants in a wide variety of different genes or the genes that encode the target PCKS9 inhibitors, statins, or other lipid-lowering therapies.”

In other words, this study “adds to the accumulating evidence” that LDL-C lowering by itself does not contribute to an adverse impact on cognitive function despite persistent concern. This should not be surprising. Dr. Ference emphasized that there has never been strong evidence for an association.

“As I point out in the editorial, there is no biologically plausible mechanism by which reducing peripheral LDL-C should impact neurological function in any way, because the therapies do not cross the blood brain barrier, and because the nervous system produces its own cholesterol to maintain the integrity of membranes in nervous system cells,” he explained.

Dr. Lohoff reports no potential conflicts of interest. Dr. Ference has financial relationships with numerous pharmaceutical companies including those that make lipid-lowering therapies.

PCSK9 inhibitors, which are among the most effective therapies for reducing LDL cholesterol (LDL-C), are associated with a neutral effect on cognitive function, according to a genetics-based Mendelian randomization study intended to sort out through the complexity of confounders.

The same study linked HMG-Co A reductase inhibitors (statins) with the potential for modest adverse neurocognitive effects, although these are likely to be outweighed by cardiovascular benefits, according to a collaborating team of investigators from the U.S. National Institutes of Health and the University of Oxford (England).

For clinicians and patients who continue to harbor concerns that cognitive function is threatened by very low LDL-C, this novel approach to evaluating risk is “reassuring,” according to the authors.

Early in clinical testing of PCSK9 inhibitors, a potential signal for adverse effects on cognitive function was reported but unconfirmed. This signal raised concern that extremely low levels of LDL-C, such as < 25 mg/dL, achieved with PCSK9 inhibitors might pose a risk to neurocognitive function.

Of several factors that provided a basis for concern, the PCSK9 enzyme is known to participate in brain development, according to the authors of this newly published study.
 

Mendelian randomization addresses complex issue

The objective of this Mendelian randomization analysis was to evaluate the relationship of PCSK9 inhibitors and statins on long-term neurocognitive function. Used previously to address other clinical issues, a drug-effect Mendelian randomization analysis evaluates genetic variants to determine whether there is a causal relationship between a risk, which in this case was lipid-lowering drugs, to a specific outcome, which was cognitive performance.

By looking directly at genetic variants that simulate the pharmacological inhibition of drug gene targets, the bias of confounders of clinical effects, such as baseline cognitive function, are avoided, according to the authors.

The message from this drug-effect Mendelian analysis was simple, according to the senior author of the study, Falk W. Lohoff, MD, chief of the section on clinical genomics and experimental therapeutics, National Institute of Alcohol Abuse and Alcoholism.

“Based on our data, we do not see a significant cognitive risk profile with PCSK9 inhibition associated with low LDL-C,” Dr. Lohoff said in an interview. He cautioned that “future long-term clinical studies are needed to confirm the absence of this effect,” but he and his coauthors noted that these data concur with the clinical studies.

From genome-wide association studies, single-nucleotide polymorphisms in PCSK9 and HMG-Co A reductase were extracted from a sample of more than 700,000 individuals of predominantly European ancestry. In the analysis, the investigators evaluated whether inhibition of PCSK9 or HMG-Co A reductase had an effect on seven clinical outcomes that relate to neurocognitive function, including memory, verbal intelligence, and reaction time, as well as biomarkers of cognitive function, such as cortical surface area.

The genetic effect of PCSK9 inhibition was “null for every cognitive-related outcome evaluated,” the investigators reported. The genetic effect of HMG-Co A reductase inhibition had a statistically significant but modest effect on cognitive performance (P = .03) and cortical surface area (P = .03). While the impact of HMG-Co A reductase inhibition on reaction time was stronger on a statistical basis (P = .0002), the investigators reported that it translated into a decrease of only 0.067 milliseconds per 38.7 mg/dL. They characterized this as a “small impact” unlikely to outweigh clinical benefits.

In an editorial that accompanied publication of this study, Brian A. Ference, MD, MPhil, provided context for the suitability of a Mendelian randomization analysis to address this or other questions regarding the impact of lipid-lowering therapies on clinical outcomes, and he ultimately concurred with the major conclusions

Ultimately, this analysis is consistent with other evidence that PCSK9 inhibition does not pose a risk of impaired cognitive function, he wrote. For statins, he concluded that this study “does not provide compelling evidence” to challenge their current clinical use.


 

Data do not support low LDL-C as cognitive risk factor

Moreover, this study – as well as other evidence – argues strongly against very low levels of LDL-C, regardless of how they are achieved, as a risk factor for diminished cognitive function, Dr. Ference, director of research in the division of translational therapeutics, University of Cambridge (England), said in an interview.

“There is no evidence from Mendelian randomization studies that lifelong exposure to lower LDL-C increases the risk of cognitive impairment,” he said. “This is true when evaluating lifelong exposure to lower LDL-C due to genetic variants in a wide variety of different genes or the genes that encode the target PCKS9 inhibitors, statins, or other lipid-lowering therapies.”

In other words, this study “adds to the accumulating evidence” that LDL-C lowering by itself does not contribute to an adverse impact on cognitive function despite persistent concern. This should not be surprising. Dr. Ference emphasized that there has never been strong evidence for an association.

“As I point out in the editorial, there is no biologically plausible mechanism by which reducing peripheral LDL-C should impact neurological function in any way, because the therapies do not cross the blood brain barrier, and because the nervous system produces its own cholesterol to maintain the integrity of membranes in nervous system cells,” he explained.

Dr. Lohoff reports no potential conflicts of interest. Dr. Ference has financial relationships with numerous pharmaceutical companies including those that make lipid-lowering therapies.

People with elevated levels of protein prostasin seem to have a higher risk of developing diabetes and dying from cancer, according to a large, prospective, population-based study. The finding may provide new insights into why people with diabetes have an increased risk of cancer.

The study claims to be the first to investigate the link between plasma prostasin levels and cancer mortality, the study authors wrote in Diabetologia. The study analyzed plasma prostasin samples from 4,297 older adults (average age, 57.5 years) from the Malmö (Sweden) Diet and Cancer Study Cardiovascular Cohort.

“This study from the general population shows that prostasin, a protein that could be measured in blood, is associated with increased risk of developing diabetes,” senior author Gunnar Engström, MD, PhD, professor of epidemiology at Lund University in Malmö, Sweden, said in a comment. “Furthermore, it was associated with increased risk of death from cancer, especially in individuals with elevated glucose levels in the prediabetic range.

“The relationship between diabetes and cancer is poorly understood,” Dr. Engström said. “To our knowledge, this is the first big population study of prostasin and risk of diabetes.”

He noted previous studies have found a relationship between prostasin and cancer outcomes. “Prostasin could be a possible shared link between  the two diseases and the results could help us understand why individuals with diabetes have increased risk of cancer.”

Patients in the study were assigned to quartiles based on prostasin levels. Those in the highest quartile had almost twice the risk of prevalent diabetes than did those in the lowest quartile (adjusted odds ratio, 1.95; 95% confidence interval, 1.39-2.76; P < .0001).

During the follow-up periods of 21.9 years for diabetes and 23.5 years for cancer, on average, 702 participants developed diabetes and 651 died from cancer. Again, the analysis found a significantly higher adjusted hazard ratio for participants in the fourth quartile: about 75% higher for diabetes (HR, 1.76; 95% CI, 1.41-2.19; P < .0001), and, after multivariable analysis, about 40% higher for death from cancer (HR, 1.43; 95% CI, 1.14-1.8; P = .0008).
 

Potential diabetes-cancer ‘interaction’

The study also identified what it called “a significant interaction” between prostasin and fasting blood glucose for cancer mortality risk (P = .022). In patients with impaired fasting blood glucose levels at baseline, the risk for cancer mortality was about 50% greater with each standard deviation increase in prostasin (HR, 1.52; 95% CI, 1.07-2.16; P = .019). Those with normal fasting blood glucose at baseline had a significantly lower risk with each SD increase in prostasin (HR, 1.11; 95% CI, 1.01-1.21; P = .025).

Further research is needed to validate the potential of prostasin as a biomarker for diabetes and cancer risks, Dr. Engström said. “The results need to be replicated in other studies. A study of cancer mortality in a big cohort of diabetes patients would be of great interest. We also need to examine whether prostasin is causally related to cancer and/or diabetes, or whether prostasin could act as a valuable risk marker in clinical settings. If causal, there could a possible molecular target for treatment.”

He added: “Biomarkers of diabetes and cancer are of great interest in the era of personalized medicine, both for disease prevention and for treatment of those with established disease.”

Li-Mei Chen, MD, PhD, a research associate professor at the University of Central Florida, Orlando, has studied the role of prostasin in epidemiology. She noted that one of the challenges of using prostasin in clinical or research settings is the lack of a standardized assay, which the Malmö study acknowledged. Dr. Engström and colleagues wrote that “prostasin levels were measured in arbitrary units (NPX values), and thus could not be compared directly with absolute values.”

Dr. Chen pointed out that the study reported a lower range of 0.24 pg/mL and an upper range of 7,800 pg/mL.

This means that, “in different groups that measure prostasin, the absolute quantity could have a difference in the thousands or tens of thousands,” she said. “That makes the judgment difficult of whether for this person you have a high level of prostasin in the blood and the other one you don’t if the difference is over a thousandfold.”

The Malmö study used the Proseek Multiplex Oncology I panel to determine plasma prostasin concentration, but Dr. Chen noted that she couldn’t find any data validating the panel for measuring prostasin. “It’s really hard for me to say whether this is of value or not because if the method that generated the data is not verified by another method, you don’t really know what you’re measuring.

“If the data are questionable, it’s really hard to say whether it means whether it’s a marker for cancer or diabetes,” Dr. Chen added. “That’s the biggest question I have, but actually the authors realize that.”

Dr. Engström confirmed that, “if prostasin is used to identify patients with increased risk of diabetes and cancer mortality, we also need to develop standardized assays for clinical use.”

Dr. Engström and coauthors had no disclosures. The study received funding from the Swedish Heart Lung Foundation, the National Natural Science Foundation of China, and the Natural Science Foundation of Jiangsu Province. The Malmö Diet and Cancer study received grants from the Swedish Cancer Society, the Swedish Medical Research Council, AFA Insurance, the Albert Påhlsson and Gunnar Nilsson Foundations, Malmö City Council, and Lund University. Dr. Chen had no relevant disclosures.
 

People with elevated levels of protein prostasin seem to have a higher risk of developing diabetes and dying from cancer, according to a large, prospective, population-based study. The finding may provide new insights into why people with diabetes have an increased risk of cancer.

The study claims to be the first to investigate the link between plasma prostasin levels and cancer mortality, the study authors wrote in Diabetologia. The study analyzed plasma prostasin samples from 4,297 older adults (average age, 57.5 years) from the Malmö (Sweden) Diet and Cancer Study Cardiovascular Cohort.

“This study from the general population shows that prostasin, a protein that could be measured in blood, is associated with increased risk of developing diabetes,” senior author Gunnar Engström, MD, PhD, professor of epidemiology at Lund University in Malmö, Sweden, said in a comment. “Furthermore, it was associated with increased risk of death from cancer, especially in individuals with elevated glucose levels in the prediabetic range.

“The relationship between diabetes and cancer is poorly understood,” Dr. Engström said. “To our knowledge, this is the first big population study of prostasin and risk of diabetes.”

He noted previous studies have found a relationship between prostasin and cancer outcomes. “Prostasin could be a possible shared link between  the two diseases and the results could help us understand why individuals with diabetes have increased risk of cancer.”

Patients in the study were assigned to quartiles based on prostasin levels. Those in the highest quartile had almost twice the risk of prevalent diabetes than did those in the lowest quartile (adjusted odds ratio, 1.95; 95% confidence interval, 1.39-2.76; P < .0001).

During the follow-up periods of 21.9 years for diabetes and 23.5 years for cancer, on average, 702 participants developed diabetes and 651 died from cancer. Again, the analysis found a significantly higher adjusted hazard ratio for participants in the fourth quartile: about 75% higher for diabetes (HR, 1.76; 95% CI, 1.41-2.19; P < .0001), and, after multivariable analysis, about 40% higher for death from cancer (HR, 1.43; 95% CI, 1.14-1.8; P = .0008).
 

Potential diabetes-cancer ‘interaction’

The study also identified what it called “a significant interaction” between prostasin and fasting blood glucose for cancer mortality risk (P = .022). In patients with impaired fasting blood glucose levels at baseline, the risk for cancer mortality was about 50% greater with each standard deviation increase in prostasin (HR, 1.52; 95% CI, 1.07-2.16; P = .019). Those with normal fasting blood glucose at baseline had a significantly lower risk with each SD increase in prostasin (HR, 1.11; 95% CI, 1.01-1.21; P = .025).

Further research is needed to validate the potential of prostasin as a biomarker for diabetes and cancer risks, Dr. Engström said. “The results need to be replicated in other studies. A study of cancer mortality in a big cohort of diabetes patients would be of great interest. We also need to examine whether prostasin is causally related to cancer and/or diabetes, or whether prostasin could act as a valuable risk marker in clinical settings. If causal, there could a possible molecular target for treatment.”

He added: “Biomarkers of diabetes and cancer are of great interest in the era of personalized medicine, both for disease prevention and for treatment of those with established disease.”

Li-Mei Chen, MD, PhD, a research associate professor at the University of Central Florida, Orlando, has studied the role of prostasin in epidemiology. She noted that one of the challenges of using prostasin in clinical or research settings is the lack of a standardized assay, which the Malmö study acknowledged. Dr. Engström and colleagues wrote that “prostasin levels were measured in arbitrary units (NPX values), and thus could not be compared directly with absolute values.”

Dr. Chen pointed out that the study reported a lower range of 0.24 pg/mL and an upper range of 7,800 pg/mL.

This means that, “in different groups that measure prostasin, the absolute quantity could have a difference in the thousands or tens of thousands,” she said. “That makes the judgment difficult of whether for this person you have a high level of prostasin in the blood and the other one you don’t if the difference is over a thousandfold.”

The Malmö study used the Proseek Multiplex Oncology I panel to determine plasma prostasin concentration, but Dr. Chen noted that she couldn’t find any data validating the panel for measuring prostasin. “It’s really hard for me to say whether this is of value or not because if the method that generated the data is not verified by another method, you don’t really know what you’re measuring.

“If the data are questionable, it’s really hard to say whether it means whether it’s a marker for cancer or diabetes,” Dr. Chen added. “That’s the biggest question I have, but actually the authors realize that.”

Dr. Engström confirmed that, “if prostasin is used to identify patients with increased risk of diabetes and cancer mortality, we also need to develop standardized assays for clinical use.”

Dr. Engström and coauthors had no disclosures. The study received funding from the Swedish Heart Lung Foundation, the National Natural Science Foundation of China, and the Natural Science Foundation of Jiangsu Province. The Malmö Diet and Cancer study received grants from the Swedish Cancer Society, the Swedish Medical Research Council, AFA Insurance, the Albert Påhlsson and Gunnar Nilsson Foundations, Malmö City Council, and Lund University. Dr. Chen had no relevant disclosures.
 

People with elevated levels of protein prostasin seem to have a higher risk of developing diabetes and dying from cancer, according to a large, prospective, population-based study. The finding may provide new insights into why people with diabetes have an increased risk of cancer.

The study claims to be the first to investigate the link between plasma prostasin levels and cancer mortality, the study authors wrote in Diabetologia. The study analyzed plasma prostasin samples from 4,297 older adults (average age, 57.5 years) from the Malmö (Sweden) Diet and Cancer Study Cardiovascular Cohort.

“This study from the general population shows that prostasin, a protein that could be measured in blood, is associated with increased risk of developing diabetes,” senior author Gunnar Engström, MD, PhD, professor of epidemiology at Lund University in Malmö, Sweden, said in a comment. “Furthermore, it was associated with increased risk of death from cancer, especially in individuals with elevated glucose levels in the prediabetic range.

“The relationship between diabetes and cancer is poorly understood,” Dr. Engström said. “To our knowledge, this is the first big population study of prostasin and risk of diabetes.”

He noted previous studies have found a relationship between prostasin and cancer outcomes. “Prostasin could be a possible shared link between  the two diseases and the results could help us understand why individuals with diabetes have increased risk of cancer.”

Patients in the study were assigned to quartiles based on prostasin levels. Those in the highest quartile had almost twice the risk of prevalent diabetes than did those in the lowest quartile (adjusted odds ratio, 1.95; 95% confidence interval, 1.39-2.76; P < .0001).

During the follow-up periods of 21.9 years for diabetes and 23.5 years for cancer, on average, 702 participants developed diabetes and 651 died from cancer. Again, the analysis found a significantly higher adjusted hazard ratio for participants in the fourth quartile: about 75% higher for diabetes (HR, 1.76; 95% CI, 1.41-2.19; P < .0001), and, after multivariable analysis, about 40% higher for death from cancer (HR, 1.43; 95% CI, 1.14-1.8; P = .0008).
 

Potential diabetes-cancer ‘interaction’

The study also identified what it called “a significant interaction” between prostasin and fasting blood glucose for cancer mortality risk (P = .022). In patients with impaired fasting blood glucose levels at baseline, the risk for cancer mortality was about 50% greater with each standard deviation increase in prostasin (HR, 1.52; 95% CI, 1.07-2.16; P = .019). Those with normal fasting blood glucose at baseline had a significantly lower risk with each SD increase in prostasin (HR, 1.11; 95% CI, 1.01-1.21; P = .025).

Further research is needed to validate the potential of prostasin as a biomarker for diabetes and cancer risks, Dr. Engström said. “The results need to be replicated in other studies. A study of cancer mortality in a big cohort of diabetes patients would be of great interest. We also need to examine whether prostasin is causally related to cancer and/or diabetes, or whether prostasin could act as a valuable risk marker in clinical settings. If causal, there could a possible molecular target for treatment.”

He added: “Biomarkers of diabetes and cancer are of great interest in the era of personalized medicine, both for disease prevention and for treatment of those with established disease.”

Li-Mei Chen, MD, PhD, a research associate professor at the University of Central Florida, Orlando, has studied the role of prostasin in epidemiology. She noted that one of the challenges of using prostasin in clinical or research settings is the lack of a standardized assay, which the Malmö study acknowledged. Dr. Engström and colleagues wrote that “prostasin levels were measured in arbitrary units (NPX values), and thus could not be compared directly with absolute values.”

Dr. Chen pointed out that the study reported a lower range of 0.24 pg/mL and an upper range of 7,800 pg/mL.

This means that, “in different groups that measure prostasin, the absolute quantity could have a difference in the thousands or tens of thousands,” she said. “That makes the judgment difficult of whether for this person you have a high level of prostasin in the blood and the other one you don’t if the difference is over a thousandfold.”

The Malmö study used the Proseek Multiplex Oncology I panel to determine plasma prostasin concentration, but Dr. Chen noted that she couldn’t find any data validating the panel for measuring prostasin. “It’s really hard for me to say whether this is of value or not because if the method that generated the data is not verified by another method, you don’t really know what you’re measuring.

“If the data are questionable, it’s really hard to say whether it means whether it’s a marker for cancer or diabetes,” Dr. Chen added. “That’s the biggest question I have, but actually the authors realize that.”

Dr. Engström confirmed that, “if prostasin is used to identify patients with increased risk of diabetes and cancer mortality, we also need to develop standardized assays for clinical use.”

Dr. Engström and coauthors had no disclosures. The study received funding from the Swedish Heart Lung Foundation, the National Natural Science Foundation of China, and the Natural Science Foundation of Jiangsu Province. The Malmö Diet and Cancer study received grants from the Swedish Cancer Society, the Swedish Medical Research Council, AFA Insurance, the Albert Påhlsson and Gunnar Nilsson Foundations, Malmö City Council, and Lund University. Dr. Chen had no relevant disclosures.
 

People who are socially isolated or lonely have an increased risk for myocardial infarction, stroke, and death, independent of other factors, the American Heart Association concludes in a new scientific statement.

More than 4 decades of research have “clearly demonstrated that social isolation and loneliness are both associated with adverse health outcomes,” writing group chair Crystal Wiley Cené, MD, University of California San Diego Health, said in a news release.

“Given the prevalence of social disconnectedness across the United States, the public health impact is quite significant,” Dr. Cené added.

The writing group says more research is needed to develop, implement, and test interventions to improve cardiovascular (CV) and brain health in people who are socially isolated or lonely.

The scientific statement was published online in the Journal of the American Heart Association.
 

Common and potentially deadly

Social isolation is defined as having infrequent in-person contact with people and loneliness is when a person feels he or she is alone or has less connection with others than desired.

It’s estimated that one-quarter of community-dwelling Americans 65 years and older are socially isolated, with even more experiencing loneliness.

The problem is not limited to older adults, however. Research suggests that younger adults also experience social isolation and loneliness, which might be attributed to more social media use and less frequent in-person activities.

Dr. Cené and colleagues reviewed observational and intervention research on social isolation published through July 2021 to examine the impact of social isolation and loneliness on CV and brain health.

The evidence is most consistent for a direct association between social isolation, loneliness, and death from coronary heart disease (CHD) and stroke, they reported.

For example, one meta-analysis of 19 studies showed that social isolation and loneliness increase the risk for CHD by 29%; most of these studies focused on acute MI and/or CHD death as the measure of CHD.

A meta-analysis of eight longitudinal observational studies showed social isolation and loneliness were associated with a 32% increased risk for stroke, after adjustment for age, sex, and socioeconomic status.

The literature also suggests social isolation and loneliness are associated with worse prognoses in adults with existing CHD or history of stroke.

One systematic review showed that socially isolated people with CHD had a two- to threefold increase in illness and death over 6 years, independent of cardiac risk factors.

Other research suggests that socially isolated adults with three or fewer social contacts per month have a 40% increased risk for recurrent stroke or MI.

There are fewer and less robust data on the association between social isolation and loneliness with heart failure (HF), dementia, and cognitive impairment, the writing group noted.

It’s also unclear whether actually being isolated (social isolation) or feeling isolated (loneliness) matters most for cardiovascular and brain health, because only a few studies have examined both in the same sample, they pointed out.

However, a study published in Neurology in June showed that older adults who reported feeling socially isolated had worse cognitive function at baseline than did those who did not report social isolation, and were 26% more likely to have dementia at follow-up, as reported by this news organization.
 

Urgent need for interventions

“There is an urgent need to develop, implement, and evaluate programs and strategies to reduce the negative effects of social isolation and loneliness on cardiovascular and brain health, particularly for at-risk populations,” Dr. Cené said in the news release. 

She encourages clinicians to ask patients about their social life and whether they are satisfied with their level of interactions with friends and family, and to be prepared to refer patients who are socially isolated or lonely, especially those with a history of CHD or stroke, to community resources to help them connect with others.

Fitness programs and recreational activities at senior centers, as well as interventions that address negative thoughts of self-worth and other negative thinking, have shown promise in reducing isolation and loneliness, the writing group said.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Social Determinants of Health Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Stroke Council.

This research had no commercial funding. Members of the writing group have disclosed no relevant conflicts of interest.

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

People who are socially isolated or lonely have an increased risk for myocardial infarction, stroke, and death, independent of other factors, the American Heart Association concludes in a new scientific statement.

More than 4 decades of research have “clearly demonstrated that social isolation and loneliness are both associated with adverse health outcomes,” writing group chair Crystal Wiley Cené, MD, University of California San Diego Health, said in a news release.

“Given the prevalence of social disconnectedness across the United States, the public health impact is quite significant,” Dr. Cené added.

The writing group says more research is needed to develop, implement, and test interventions to improve cardiovascular (CV) and brain health in people who are socially isolated or lonely.

The scientific statement was published online in the Journal of the American Heart Association.
 

Common and potentially deadly

Social isolation is defined as having infrequent in-person contact with people and loneliness is when a person feels he or she is alone or has less connection with others than desired.

It’s estimated that one-quarter of community-dwelling Americans 65 years and older are socially isolated, with even more experiencing loneliness.

The problem is not limited to older adults, however. Research suggests that younger adults also experience social isolation and loneliness, which might be attributed to more social media use and less frequent in-person activities.

Dr. Cené and colleagues reviewed observational and intervention research on social isolation published through July 2021 to examine the impact of social isolation and loneliness on CV and brain health.

The evidence is most consistent for a direct association between social isolation, loneliness, and death from coronary heart disease (CHD) and stroke, they reported.

For example, one meta-analysis of 19 studies showed that social isolation and loneliness increase the risk for CHD by 29%; most of these studies focused on acute MI and/or CHD death as the measure of CHD.

A meta-analysis of eight longitudinal observational studies showed social isolation and loneliness were associated with a 32% increased risk for stroke, after adjustment for age, sex, and socioeconomic status.

The literature also suggests social isolation and loneliness are associated with worse prognoses in adults with existing CHD or history of stroke.

One systematic review showed that socially isolated people with CHD had a two- to threefold increase in illness and death over 6 years, independent of cardiac risk factors.

Other research suggests that socially isolated adults with three or fewer social contacts per month have a 40% increased risk for recurrent stroke or MI.

There are fewer and less robust data on the association between social isolation and loneliness with heart failure (HF), dementia, and cognitive impairment, the writing group noted.

It’s also unclear whether actually being isolated (social isolation) or feeling isolated (loneliness) matters most for cardiovascular and brain health, because only a few studies have examined both in the same sample, they pointed out.

However, a study published in Neurology in June showed that older adults who reported feeling socially isolated had worse cognitive function at baseline than did those who did not report social isolation, and were 26% more likely to have dementia at follow-up, as reported by this news organization.
 

Urgent need for interventions

“There is an urgent need to develop, implement, and evaluate programs and strategies to reduce the negative effects of social isolation and loneliness on cardiovascular and brain health, particularly for at-risk populations,” Dr. Cené said in the news release. 

She encourages clinicians to ask patients about their social life and whether they are satisfied with their level of interactions with friends and family, and to be prepared to refer patients who are socially isolated or lonely, especially those with a history of CHD or stroke, to community resources to help them connect with others.

Fitness programs and recreational activities at senior centers, as well as interventions that address negative thoughts of self-worth and other negative thinking, have shown promise in reducing isolation and loneliness, the writing group said.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Social Determinants of Health Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Stroke Council.

This research had no commercial funding. Members of the writing group have disclosed no relevant conflicts of interest.

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

People who are socially isolated or lonely have an increased risk for myocardial infarction, stroke, and death, independent of other factors, the American Heart Association concludes in a new scientific statement.

More than 4 decades of research have “clearly demonstrated that social isolation and loneliness are both associated with adverse health outcomes,” writing group chair Crystal Wiley Cené, MD, University of California San Diego Health, said in a news release.

“Given the prevalence of social disconnectedness across the United States, the public health impact is quite significant,” Dr. Cené added.

The writing group says more research is needed to develop, implement, and test interventions to improve cardiovascular (CV) and brain health in people who are socially isolated or lonely.

The scientific statement was published online in the Journal of the American Heart Association.
 

Common and potentially deadly

Social isolation is defined as having infrequent in-person contact with people and loneliness is when a person feels he or she is alone or has less connection with others than desired.

It’s estimated that one-quarter of community-dwelling Americans 65 years and older are socially isolated, with even more experiencing loneliness.

The problem is not limited to older adults, however. Research suggests that younger adults also experience social isolation and loneliness, which might be attributed to more social media use and less frequent in-person activities.

Dr. Cené and colleagues reviewed observational and intervention research on social isolation published through July 2021 to examine the impact of social isolation and loneliness on CV and brain health.

The evidence is most consistent for a direct association between social isolation, loneliness, and death from coronary heart disease (CHD) and stroke, they reported.

For example, one meta-analysis of 19 studies showed that social isolation and loneliness increase the risk for CHD by 29%; most of these studies focused on acute MI and/or CHD death as the measure of CHD.

A meta-analysis of eight longitudinal observational studies showed social isolation and loneliness were associated with a 32% increased risk for stroke, after adjustment for age, sex, and socioeconomic status.

The literature also suggests social isolation and loneliness are associated with worse prognoses in adults with existing CHD or history of stroke.

One systematic review showed that socially isolated people with CHD had a two- to threefold increase in illness and death over 6 years, independent of cardiac risk factors.

Other research suggests that socially isolated adults with three or fewer social contacts per month have a 40% increased risk for recurrent stroke or MI.

There are fewer and less robust data on the association between social isolation and loneliness with heart failure (HF), dementia, and cognitive impairment, the writing group noted.

It’s also unclear whether actually being isolated (social isolation) or feeling isolated (loneliness) matters most for cardiovascular and brain health, because only a few studies have examined both in the same sample, they pointed out.

However, a study published in Neurology in June showed that older adults who reported feeling socially isolated had worse cognitive function at baseline than did those who did not report social isolation, and were 26% more likely to have dementia at follow-up, as reported by this news organization.
 

Urgent need for interventions

“There is an urgent need to develop, implement, and evaluate programs and strategies to reduce the negative effects of social isolation and loneliness on cardiovascular and brain health, particularly for at-risk populations,” Dr. Cené said in the news release. 

She encourages clinicians to ask patients about their social life and whether they are satisfied with their level of interactions with friends and family, and to be prepared to refer patients who are socially isolated or lonely, especially those with a history of CHD or stroke, to community resources to help them connect with others.

Fitness programs and recreational activities at senior centers, as well as interventions that address negative thoughts of self-worth and other negative thinking, have shown promise in reducing isolation and loneliness, the writing group said.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Social Determinants of Health Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Stroke Council.

This research had no commercial funding. Members of the writing group have disclosed no relevant conflicts of interest.

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

Patients who take beta-blockers or antiplatelet agents are lowering their risk for cardiovascular events, but the protection may fall short for those who spend time outdoors on hot summer days, hints a limited analysis published as a letter in Nature Cardiovascular Research.

Patients taking either a beta-blocker or antiplatelet, or both medications together, appeared at elevated risk for nonfatal acute MI specifically on days when the weather turned hot, suggests the registry cohort study that covered 14 years of clinical and meteorologic data.

rottadana/Thinkstock

“The take-away message is not that patients should stop using these two medications, by no means. We’re raising cautions for patients taking them, to watch out for themselves during high-heat days,” lead author Kai Chen, PhD, Yale University, New Haven, Conn., said in an interview.

“We’re not giving the message that these drugs have harmful effects” because the nature of the links between the medications and MI in the study, with its potential for confounding, remain unknown, said Dr. Chen, from the department of environmental health sciences and Yale Center on Climate Change and Health.

For example, patients who take beta-blockers or antiplatelets tend to be sicker than patients not on the drugs, which could make heat-related MI more likely, and the drugs wrongly appear to be culprits, he observed. The analysis contained signals that could support either scenario.

The study is based on cases of nonfatal MI in Augsburg, Germany, that are part of the MONICA-KORA MI registry. The odds of a heat-related nonfatal MI, it suggests, were increased 63% among patients taking antiplatelets and by 65% among those on beta-blockers, compared with those not on these drugs. The odds went up by 75% among those on both drug classes, but the risks weren’t raised in patients not taking them.
 

Rising heat-related MI

Chen said analysis was inspired by a 2019 report – also based on MONICA-KORA, from many of the same authors and using similar methods to track events by daily air temperature – that showed a rising trend for heat-related MI and declining rate for MI related to cold weather from 1987 to 2014. A next step, he figured, would be to determine whether the MI risk trends were associated with any cardiovascular medications.

The current study’s signal of risk related to antiplatelets and beta-blockers did not emerge for ACE inhibitors, calcium-channel blockers, or diuretics. Statins showed a link to increased nonfatal MI risk, but solely among participants aged younger than 60 years, who were also far less likely to have pre-existing coronary heart disease (CHD). He and his colleagues chose not to highlight that finding, Dr. Chen said, because the age subgroup analysis was grossly underpowered.

The overall analysis involved 2,494 cases of nonfatal MI that occurred during the warmer months – May to September – from 2001 to 2014. It was limited to nonfatal cases – those with at least a month of survival after hospital admission – because of insufficient data on medication use associated with fatal MIs, the report states.

Nonfatal MIs were defined as heat-related if they struck on days reaching the 95th percentile for temperature across the 14 years, in this case 24.2 °C (about 75.6 °F), relative to the average temperature of lowest nonfatal MI risk across the cohort, 7.5 °C (about 45.5 °F).

Patients served as both cases and their own controls, in that air temperature exposures on the day of their MI (case day) were compared with the remaining same days of the week in the same calendar month (control days). That approach, the report stated, “automatically controls for long-term time trends, seasonality, day of the week, and time-invariant confounders (for example, pre-existing cardiovascular disease).”

The odds ratio for heat-related MI for patients on antiplatelets was 1.63 (95% confidence interval, 1.07-2.46), and for antiplatelet nonusers was 0.94 (95% CI, 0.68-1.29). The difference between the two ratios was significant (P = .04).

The corresponding OR for patients taking beta-blockers was 1.65 (95% CI, 1.11-2.45), and for nonusers of beta-blockers was 0.90 (95% CI, 0.64-1.26). Again, the OR difference was significant (P = .02).

The ORs for users of both medication classes and nonusers of either med class, respectively, were 1.75 (95% CI, 1.12-2.73) and 0.84 (95% CI, 0.59-1.19). The latter OR was significantly lower than former (P = .01).

In a sign that antiplatelet and beta-blocker use might have been just a marker for sicker patients who were more vulnerable to heat-related MI, Chen said, the nonfatal MI risk was significantly elevated (OR, 2.17; 95% CI, 1.40-3.38) among patients with pre-existing CHD, but not among those free of pre-existing CHD (OR, 0.88; 95% CI, 0.65-1.20); the odds difference was P < .01.

That signal of confounding by indication is somewhat countered, the report states, by variations in nonfatal MI risk by age group. The increased chances of an event seen overall in relation to beta-blockers and antiplatelets were more pronounced among the 39% of patients aged 25-59 years (P < .01). That’s in spite that group’s lower CHD prevalence. The risk elevation solely among the older patients was attenuated and rendered nonsignificant, even with their greater CHD burden, the report noted.

The report speculates on a potential mechanism by which beta-blockers, at least, might conceivably raise the risk for heat-related MI. “Beta-receptor blockers inhibit skin vasodilation, resulting in reduced heat dissipation through convection and, at the same time, could intensify the blood-pressure-lowering effect of other antihypertensive drugs, which then could lead to syncope.”

Beta-blockers, Dr. Chen said, “can mechanistically make people more vulnerable to heat. That’s one potential explanation. Or it could be that these people taking the medications are just sicker. Whatever the reasons, the phenomenon we observed is that these patients taking these two medications are at higher risk during high-temperature days.”

Dr. Chen and the other authors declare no competing interests.

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

Patients who take beta-blockers or antiplatelet agents are lowering their risk for cardiovascular events, but the protection may fall short for those who spend time outdoors on hot summer days, hints a limited analysis published as a letter in Nature Cardiovascular Research.

Patients taking either a beta-blocker or antiplatelet, or both medications together, appeared at elevated risk for nonfatal acute MI specifically on days when the weather turned hot, suggests the registry cohort study that covered 14 years of clinical and meteorologic data.

rottadana/Thinkstock

“The take-away message is not that patients should stop using these two medications, by no means. We’re raising cautions for patients taking them, to watch out for themselves during high-heat days,” lead author Kai Chen, PhD, Yale University, New Haven, Conn., said in an interview.

“We’re not giving the message that these drugs have harmful effects” because the nature of the links between the medications and MI in the study, with its potential for confounding, remain unknown, said Dr. Chen, from the department of environmental health sciences and Yale Center on Climate Change and Health.

For example, patients who take beta-blockers or antiplatelets tend to be sicker than patients not on the drugs, which could make heat-related MI more likely, and the drugs wrongly appear to be culprits, he observed. The analysis contained signals that could support either scenario.

The study is based on cases of nonfatal MI in Augsburg, Germany, that are part of the MONICA-KORA MI registry. The odds of a heat-related nonfatal MI, it suggests, were increased 63% among patients taking antiplatelets and by 65% among those on beta-blockers, compared with those not on these drugs. The odds went up by 75% among those on both drug classes, but the risks weren’t raised in patients not taking them.
 

Rising heat-related MI

Chen said analysis was inspired by a 2019 report – also based on MONICA-KORA, from many of the same authors and using similar methods to track events by daily air temperature – that showed a rising trend for heat-related MI and declining rate for MI related to cold weather from 1987 to 2014. A next step, he figured, would be to determine whether the MI risk trends were associated with any cardiovascular medications.

The current study’s signal of risk related to antiplatelets and beta-blockers did not emerge for ACE inhibitors, calcium-channel blockers, or diuretics. Statins showed a link to increased nonfatal MI risk, but solely among participants aged younger than 60 years, who were also far less likely to have pre-existing coronary heart disease (CHD). He and his colleagues chose not to highlight that finding, Dr. Chen said, because the age subgroup analysis was grossly underpowered.

The overall analysis involved 2,494 cases of nonfatal MI that occurred during the warmer months – May to September – from 2001 to 2014. It was limited to nonfatal cases – those with at least a month of survival after hospital admission – because of insufficient data on medication use associated with fatal MIs, the report states.

Nonfatal MIs were defined as heat-related if they struck on days reaching the 95th percentile for temperature across the 14 years, in this case 24.2 °C (about 75.6 °F), relative to the average temperature of lowest nonfatal MI risk across the cohort, 7.5 °C (about 45.5 °F).

Patients served as both cases and their own controls, in that air temperature exposures on the day of their MI (case day) were compared with the remaining same days of the week in the same calendar month (control days). That approach, the report stated, “automatically controls for long-term time trends, seasonality, day of the week, and time-invariant confounders (for example, pre-existing cardiovascular disease).”

The odds ratio for heat-related MI for patients on antiplatelets was 1.63 (95% confidence interval, 1.07-2.46), and for antiplatelet nonusers was 0.94 (95% CI, 0.68-1.29). The difference between the two ratios was significant (P = .04).

The corresponding OR for patients taking beta-blockers was 1.65 (95% CI, 1.11-2.45), and for nonusers of beta-blockers was 0.90 (95% CI, 0.64-1.26). Again, the OR difference was significant (P = .02).

The ORs for users of both medication classes and nonusers of either med class, respectively, were 1.75 (95% CI, 1.12-2.73) and 0.84 (95% CI, 0.59-1.19). The latter OR was significantly lower than former (P = .01).

In a sign that antiplatelet and beta-blocker use might have been just a marker for sicker patients who were more vulnerable to heat-related MI, Chen said, the nonfatal MI risk was significantly elevated (OR, 2.17; 95% CI, 1.40-3.38) among patients with pre-existing CHD, but not among those free of pre-existing CHD (OR, 0.88; 95% CI, 0.65-1.20); the odds difference was P < .01.

That signal of confounding by indication is somewhat countered, the report states, by variations in nonfatal MI risk by age group. The increased chances of an event seen overall in relation to beta-blockers and antiplatelets were more pronounced among the 39% of patients aged 25-59 years (P < .01). That’s in spite that group’s lower CHD prevalence. The risk elevation solely among the older patients was attenuated and rendered nonsignificant, even with their greater CHD burden, the report noted.

The report speculates on a potential mechanism by which beta-blockers, at least, might conceivably raise the risk for heat-related MI. “Beta-receptor blockers inhibit skin vasodilation, resulting in reduced heat dissipation through convection and, at the same time, could intensify the blood-pressure-lowering effect of other antihypertensive drugs, which then could lead to syncope.”

Beta-blockers, Dr. Chen said, “can mechanistically make people more vulnerable to heat. That’s one potential explanation. Or it could be that these people taking the medications are just sicker. Whatever the reasons, the phenomenon we observed is that these patients taking these two medications are at higher risk during high-temperature days.”

Dr. Chen and the other authors declare no competing interests.

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

Patients who take beta-blockers or antiplatelet agents are lowering their risk for cardiovascular events, but the protection may fall short for those who spend time outdoors on hot summer days, hints a limited analysis published as a letter in Nature Cardiovascular Research.

Patients taking either a beta-blocker or antiplatelet, or both medications together, appeared at elevated risk for nonfatal acute MI specifically on days when the weather turned hot, suggests the registry cohort study that covered 14 years of clinical and meteorologic data.

rottadana/Thinkstock

“The take-away message is not that patients should stop using these two medications, by no means. We’re raising cautions for patients taking them, to watch out for themselves during high-heat days,” lead author Kai Chen, PhD, Yale University, New Haven, Conn., said in an interview.

“We’re not giving the message that these drugs have harmful effects” because the nature of the links between the medications and MI in the study, with its potential for confounding, remain unknown, said Dr. Chen, from the department of environmental health sciences and Yale Center on Climate Change and Health.

For example, patients who take beta-blockers or antiplatelets tend to be sicker than patients not on the drugs, which could make heat-related MI more likely, and the drugs wrongly appear to be culprits, he observed. The analysis contained signals that could support either scenario.

The study is based on cases of nonfatal MI in Augsburg, Germany, that are part of the MONICA-KORA MI registry. The odds of a heat-related nonfatal MI, it suggests, were increased 63% among patients taking antiplatelets and by 65% among those on beta-blockers, compared with those not on these drugs. The odds went up by 75% among those on both drug classes, but the risks weren’t raised in patients not taking them.
 

Rising heat-related MI

Chen said analysis was inspired by a 2019 report – also based on MONICA-KORA, from many of the same authors and using similar methods to track events by daily air temperature – that showed a rising trend for heat-related MI and declining rate for MI related to cold weather from 1987 to 2014. A next step, he figured, would be to determine whether the MI risk trends were associated with any cardiovascular medications.

The current study’s signal of risk related to antiplatelets and beta-blockers did not emerge for ACE inhibitors, calcium-channel blockers, or diuretics. Statins showed a link to increased nonfatal MI risk, but solely among participants aged younger than 60 years, who were also far less likely to have pre-existing coronary heart disease (CHD). He and his colleagues chose not to highlight that finding, Dr. Chen said, because the age subgroup analysis was grossly underpowered.

The overall analysis involved 2,494 cases of nonfatal MI that occurred during the warmer months – May to September – from 2001 to 2014. It was limited to nonfatal cases – those with at least a month of survival after hospital admission – because of insufficient data on medication use associated with fatal MIs, the report states.

Nonfatal MIs were defined as heat-related if they struck on days reaching the 95th percentile for temperature across the 14 years, in this case 24.2 °C (about 75.6 °F), relative to the average temperature of lowest nonfatal MI risk across the cohort, 7.5 °C (about 45.5 °F).

Patients served as both cases and their own controls, in that air temperature exposures on the day of their MI (case day) were compared with the remaining same days of the week in the same calendar month (control days). That approach, the report stated, “automatically controls for long-term time trends, seasonality, day of the week, and time-invariant confounders (for example, pre-existing cardiovascular disease).”

The odds ratio for heat-related MI for patients on antiplatelets was 1.63 (95% confidence interval, 1.07-2.46), and for antiplatelet nonusers was 0.94 (95% CI, 0.68-1.29). The difference between the two ratios was significant (P = .04).

The corresponding OR for patients taking beta-blockers was 1.65 (95% CI, 1.11-2.45), and for nonusers of beta-blockers was 0.90 (95% CI, 0.64-1.26). Again, the OR difference was significant (P = .02).

The ORs for users of both medication classes and nonusers of either med class, respectively, were 1.75 (95% CI, 1.12-2.73) and 0.84 (95% CI, 0.59-1.19). The latter OR was significantly lower than former (P = .01).

In a sign that antiplatelet and beta-blocker use might have been just a marker for sicker patients who were more vulnerable to heat-related MI, Chen said, the nonfatal MI risk was significantly elevated (OR, 2.17; 95% CI, 1.40-3.38) among patients with pre-existing CHD, but not among those free of pre-existing CHD (OR, 0.88; 95% CI, 0.65-1.20); the odds difference was P < .01.

That signal of confounding by indication is somewhat countered, the report states, by variations in nonfatal MI risk by age group. The increased chances of an event seen overall in relation to beta-blockers and antiplatelets were more pronounced among the 39% of patients aged 25-59 years (P < .01). That’s in spite that group’s lower CHD prevalence. The risk elevation solely among the older patients was attenuated and rendered nonsignificant, even with their greater CHD burden, the report noted.

The report speculates on a potential mechanism by which beta-blockers, at least, might conceivably raise the risk for heat-related MI. “Beta-receptor blockers inhibit skin vasodilation, resulting in reduced heat dissipation through convection and, at the same time, could intensify the blood-pressure-lowering effect of other antihypertensive drugs, which then could lead to syncope.”

Beta-blockers, Dr. Chen said, “can mechanistically make people more vulnerable to heat. That’s one potential explanation. Or it could be that these people taking the medications are just sicker. Whatever the reasons, the phenomenon we observed is that these patients taking these two medications are at higher risk during high-temperature days.”

Dr. Chen and the other authors declare no competing interests.

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

Researchers published the study covered in this summary on researchsquare.com as a preprint that has not yet been peer reviewed.

Key takeaways

• In Japanese adults with type 1 diabetes insulin-pump treatment (continuous subcutaneous insulin infusion) and higher problem-solving perception appear protective against impaired awareness of hypoglycemia (IAH), while diabetic peripheral neuropathy (DPN) is associated with increased risk.
• Diabetes distress and fear of hypoglycemia are common in people with IAH.

Why this matters

• Adults with type 1 diabetes and IAH have a reduced ability to perceive hypoglycemic symptoms and are at risk of severe hypoglycemic events because they are unable to take immediate corrective action.
• This is the first study to identify protective factors and risk factors of IAH in Japanese adults with type 1 diabetes.
• People with IAH may plan to loosen tight glucose management and intentionally omit insulin injection to prevent severe hypoglycemia.
• The information in this report may help improve the management of people with problematic hypoglycemia, the authors suggested. Treatment with an insulin pump and structured education aimed at improving problem-solving skills may be useful interventions for adults with type 1 diabetes and IAH, they suggested.

Study design

• The study involved a cross-sectional analysis of 288 Japanese adults with type 1 diabetes who averaged 50 years old, had diabetes for an average of about 18 years, had an average hemoglobin A1c at baseline of 7.7%, and included about 37% men and 63% women.
• The cohort included 55 people with IAH (19%) and 233 with no impairment of their hypoglycemia awareness, based on their score on the .

Key results

• DPN was significantly more prevalent in the IAH group than in the control group (12.0% vs. 26.5%). A logistic regression analysis showed that the odds ratio for DPN was 2.63-fold higher among people with IAH, compared with those without IAH, but there were no differences in other complications or by HbA1c levels.
• Treatment with continuous subcutaneous insulin therapy (an insulin pump) was significantly less prevalent in the IAH group, compared with those without IAH (23.6% vs 39.5%), with an adjusted odds ratio of 0.48. The two subgroups showed no differences in use of continuous glucose monitoring, used by 56% of the people in each of the two subgroups.
• The two subgroups showed no differences in their healthy lifestyle score, sleep debt, or rates of excessive drinking.
• Mean autonomic symptom scores for both sweating and shaking were significantly reduced in the IAH group, but no between-group differences appeared for palpations or hunger.
• All mean neuroglycopenic symptom scores were significantly lower in those without IAH, including confusion and speech difficulty.
• Scores for measures of diabetes distress and for the worry component of the fear of hypoglycemia were significantly higher in the IAH group, but there were no differences in other psychological measures.
• Higher were significantly associated with decreased IAH risk with a calculated odds ratio of 0.54, but other aspects of hypoglycemia problem-solving such as detection control, goal setting, and strategy evaluation showed no significant links.

Limitations

• The study used a cross-sectional design, which is not suited to making causal inferences.
• The authors characterized DPN as either present or absent. They did not evaluate or analyze the severity of peripheral neuropathy.
• The authors evaluated diabetic cardiac autonomic neuropathy (DCAN) by a person’s coefficient of variation of R-R intervals, and definitive diagnosis of DCAN required at least two positive results on a cardiac autonomic test. More vigorous evaluation using a more definitive assessment of DCAN is needed to relate DCAN and IAH status.

Disclosures

• The study received no commercial funding.
• The authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, “Protective and risk factors of impaired awareness of hypoglycemia in patients with type 1 diabetes: a cross- sectional analysis of baseline data from the PR-IAH study,” written by researchers at several hospitals in Japan, all affiliated with the National Hospital Organization, on Research Square. The study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com.

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

Researchers published the study covered in this summary on researchsquare.com as a preprint that has not yet been peer reviewed.

Key takeaways

• In Japanese adults with type 1 diabetes insulin-pump treatment (continuous subcutaneous insulin infusion) and higher problem-solving perception appear protective against impaired awareness of hypoglycemia (IAH), while diabetic peripheral neuropathy (DPN) is associated with increased risk.
• Diabetes distress and fear of hypoglycemia are common in people with IAH.

Why this matters

• Adults with type 1 diabetes and IAH have a reduced ability to perceive hypoglycemic symptoms and are at risk of severe hypoglycemic events because they are unable to take immediate corrective action.
• This is the first study to identify protective factors and risk factors of IAH in Japanese adults with type 1 diabetes.
• People with IAH may plan to loosen tight glucose management and intentionally omit insulin injection to prevent severe hypoglycemia.
• The information in this report may help improve the management of people with problematic hypoglycemia, the authors suggested. Treatment with an insulin pump and structured education aimed at improving problem-solving skills may be useful interventions for adults with type 1 diabetes and IAH, they suggested.

Study design

• The study involved a cross-sectional analysis of 288 Japanese adults with type 1 diabetes who averaged 50 years old, had diabetes for an average of about 18 years, had an average hemoglobin A1c at baseline of 7.7%, and included about 37% men and 63% women.
• The cohort included 55 people with IAH (19%) and 233 with no impairment of their hypoglycemia awareness, based on their score on the .

Key results

• DPN was significantly more prevalent in the IAH group than in the control group (12.0% vs. 26.5%). A logistic regression analysis showed that the odds ratio for DPN was 2.63-fold higher among people with IAH, compared with those without IAH, but there were no differences in other complications or by HbA1c levels.
• Treatment with continuous subcutaneous insulin therapy (an insulin pump) was significantly less prevalent in the IAH group, compared with those without IAH (23.6% vs 39.5%), with an adjusted odds ratio of 0.48. The two subgroups showed no differences in use of continuous glucose monitoring, used by 56% of the people in each of the two subgroups.
• The two subgroups showed no differences in their healthy lifestyle score, sleep debt, or rates of excessive drinking.
• Mean autonomic symptom scores for both sweating and shaking were significantly reduced in the IAH group, but no between-group differences appeared for palpations or hunger.
• All mean neuroglycopenic symptom scores were significantly lower in those without IAH, including confusion and speech difficulty.
• Scores for measures of diabetes distress and for the worry component of the fear of hypoglycemia were significantly higher in the IAH group, but there were no differences in other psychological measures.
• Higher were significantly associated with decreased IAH risk with a calculated odds ratio of 0.54, but other aspects of hypoglycemia problem-solving such as detection control, goal setting, and strategy evaluation showed no significant links.

Limitations

• The study used a cross-sectional design, which is not suited to making causal inferences.
• The authors characterized DPN as either present or absent. They did not evaluate or analyze the severity of peripheral neuropathy.
• The authors evaluated diabetic cardiac autonomic neuropathy (DCAN) by a person’s coefficient of variation of R-R intervals, and definitive diagnosis of DCAN required at least two positive results on a cardiac autonomic test. More vigorous evaluation using a more definitive assessment of DCAN is needed to relate DCAN and IAH status.

Disclosures

• The study received no commercial funding.
• The authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, “Protective and risk factors of impaired awareness of hypoglycemia in patients with type 1 diabetes: a cross- sectional analysis of baseline data from the PR-IAH study,” written by researchers at several hospitals in Japan, all affiliated with the National Hospital Organization, on Research Square. The study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com.

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

Researchers published the study covered in this summary on researchsquare.com as a preprint that has not yet been peer reviewed.

Key takeaways

• In Japanese adults with type 1 diabetes insulin-pump treatment (continuous subcutaneous insulin infusion) and higher problem-solving perception appear protective against impaired awareness of hypoglycemia (IAH), while diabetic peripheral neuropathy (DPN) is associated with increased risk.
• Diabetes distress and fear of hypoglycemia are common in people with IAH.

Why this matters

• Adults with type 1 diabetes and IAH have a reduced ability to perceive hypoglycemic symptoms and are at risk of severe hypoglycemic events because they are unable to take immediate corrective action.
• This is the first study to identify protective factors and risk factors of IAH in Japanese adults with type 1 diabetes.
• People with IAH may plan to loosen tight glucose management and intentionally omit insulin injection to prevent severe hypoglycemia.
• The information in this report may help improve the management of people with problematic hypoglycemia, the authors suggested. Treatment with an insulin pump and structured education aimed at improving problem-solving skills may be useful interventions for adults with type 1 diabetes and IAH, they suggested.

Study design

• The study involved a cross-sectional analysis of 288 Japanese adults with type 1 diabetes who averaged 50 years old, had diabetes for an average of about 18 years, had an average hemoglobin A1c at baseline of 7.7%, and included about 37% men and 63% women.
• The cohort included 55 people with IAH (19%) and 233 with no impairment of their hypoglycemia awareness, based on their score on the .

Key results

• DPN was significantly more prevalent in the IAH group than in the control group (12.0% vs. 26.5%). A logistic regression analysis showed that the odds ratio for DPN was 2.63-fold higher among people with IAH, compared with those without IAH, but there were no differences in other complications or by HbA1c levels.
• Treatment with continuous subcutaneous insulin therapy (an insulin pump) was significantly less prevalent in the IAH group, compared with those without IAH (23.6% vs 39.5%), with an adjusted odds ratio of 0.48. The two subgroups showed no differences in use of continuous glucose monitoring, used by 56% of the people in each of the two subgroups.
• The two subgroups showed no differences in their healthy lifestyle score, sleep debt, or rates of excessive drinking.
• Mean autonomic symptom scores for both sweating and shaking were significantly reduced in the IAH group, but no between-group differences appeared for palpations or hunger.
• All mean neuroglycopenic symptom scores were significantly lower in those without IAH, including confusion and speech difficulty.
• Scores for measures of diabetes distress and for the worry component of the fear of hypoglycemia were significantly higher in the IAH group, but there were no differences in other psychological measures.
• Higher were significantly associated with decreased IAH risk with a calculated odds ratio of 0.54, but other aspects of hypoglycemia problem-solving such as detection control, goal setting, and strategy evaluation showed no significant links.

Limitations

• The study used a cross-sectional design, which is not suited to making causal inferences.
• The authors characterized DPN as either present or absent. They did not evaluate or analyze the severity of peripheral neuropathy.
• The authors evaluated diabetic cardiac autonomic neuropathy (DCAN) by a person’s coefficient of variation of R-R intervals, and definitive diagnosis of DCAN required at least two positive results on a cardiac autonomic test. More vigorous evaluation using a more definitive assessment of DCAN is needed to relate DCAN and IAH status.

Disclosures

• The study received no commercial funding.
• The authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, “Protective and risk factors of impaired awareness of hypoglycemia in patients with type 1 diabetes: a cross- sectional analysis of baseline data from the PR-IAH study,” written by researchers at several hospitals in Japan, all affiliated with the National Hospital Organization, on Research Square. The study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com.

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