Cardiology

In a case-control study, atherosclerotic risk factors were uncommon in childhood and did not appear to be associated with the pathogenesis of arterial ischemic stroke in children or in early young adulthood.

But by the fourth and fifth decades of life, these risk factors were strongly associated with a significant risk for stroke, heightening that risk almost tenfold.

“While strokes in childhood and very early adulthood are not likely caused by atherosclerotic risk factors, it does look like these risk factors increase throughout early and young adulthood and become significant risk factors for stroke in the 30s and 40s,” lead author Sharon N. Poisson, MD, MAS, associate professor of neurology at the University of Colorado at Denver, Aurora, said in an interview.

The findings were published online in JAMA Neurology.

In this study, the researchers focused on arterial ischemic stroke, not hemorrhagic stroke. “We know that high blood pressure, diabetes, smoking, obesity, all of these are risk factors for ischemic stroke, but what we didn’t know is at what age do those atherosclerotic risk factors actually start to cause stroke,” Dr. Poisson said.

To find out more, she and her team did a case control study of data in the Kaiser Permanente Northern California system, which had been accumulating relevant data over a period of 14 years, from Jan. 1, 2000, through Dec. 31, 2014.

The analysis included 141 children and 455 young adults with arterial ischemic stroke and 1,382 age-matched controls.

The children were divided into two age categories: ages 29 days to 9 years and ages 10-19 years.

In the younger group, there were 69 cases of arterial ischemic stroke. In the older age group, there were 72 cases.

Young adults were divided into three age categories: 20-29 years (n = 71 cases), 30-39 years (144 cases), and 40-49 years (240 cases).

Among pediatric controls, 168 children aged 29 days to 9 years (46.5%) and 196 children aged 10-19 years (53.8%) developed arterial ischemic stroke.

There were 121 cases of ischemic stroke among young adult controls aged 20-29 years, 298 cases among controls aged 30-39 years, and 599 cases in those aged 40-49 years.

Both childhood cases and controls had a low prevalence of documented diagnoses of atherosclerotic risk factors (ARFs). The odds ratio of having any ARFs on arterial ischemic stroke was 1.87 for ages 0-9 years, and 1.00 for ages 10-19.

However, cases rose with age.

The OR was 2.3 for age range 20-29 years, 3.57 for age range 30-39 years, and 4.91 for age range 40-49 years.

The analysis also showed that the OR associated with multiple ARFs was 5.29 for age range 0-9 years, 2.75 for age range 10-19 years, 7.33 for age range 20-29 years, 9.86 for age range 30-39 years, and 9.35 for age range 40-49 years.

Multiple risk factors were rare in children but became more prevalent with each decade of young adult life.

The presumed cause of arterial ischemic stroke was atherosclerosis. Evidence of atherosclerosis was present in 1.4% of those aged 10-19 years, 8.5% of those aged 20-29 years, 21.5% of those aged 30-39 years, and 42.5% of those aged 40-49 years.

“This study tells us that, while stroke in adolescence and very early adulthood may not be caused by atherosclerotic risk factors, starting to accumulate those risk factors early in life clearly increases the risk of stroke in the 30s and 40s. I hope we can get this message across, because the sooner we can treat the risk factors, the better the outcome,” Dr. Poisson said.
 

Prevention starts in childhood

Prevention of cardiovascular disease begins in childhood, which is a paradigm shift from the way cardiovascular disease was thought of a couple of decades ago, noted pediatric cardiologist Guilherme Baptista de Faia, MD, from the Ann & Robert H. Lurie Children’s Hospital in Chicago.

“Our guidelines for risk factor reduction in children aim to address how or when do we screen for these risk factors, how or when do we intervene, and do these interventions impact cardiovascular outcomes later in life? This article is part of the mounting research that aims to understand the relationship between childhood cardiovascular risk factors and early cardiovascular disease,” Dr. Baptista de Faia said.

“There has been an interesting progression in our understanding of the impact of CV risk factors early in life. Large cohorts such as Bogalusa Heart Study, Risk in Young Finns Study, Muscatine Study, the Childhood Determinants of Adult Health, CARDIA, and the International Childhood Cardiovascular Cohorts (i3C) have been instrumental in evaluating this question,” he said.

The knowledge that atherosclerotic risk factors in children can lead to acceleration of atherosclerosis in later life opens the door to preventive medicine, said Dr. Baptista de Faia, who was not part of the study.

“This is where preventive medicine comes in. If we can identify the children at increased risk, can we intervene to improve outcomes later in life?” he said. Familial hypercholesterolemia is “a great example of this. We can screen children early in life, there is an effective treatment, and we know from populations studies that early treatment significantly decreases the risk for cardiovascular disease later in life.”

Dr. Poisson reported that she received grants from the National Institutes of Health during the conduct of this study, which was supported by the NIH.

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

In a case-control study, atherosclerotic risk factors were uncommon in childhood and did not appear to be associated with the pathogenesis of arterial ischemic stroke in children or in early young adulthood.

But by the fourth and fifth decades of life, these risk factors were strongly associated with a significant risk for stroke, heightening that risk almost tenfold.

“While strokes in childhood and very early adulthood are not likely caused by atherosclerotic risk factors, it does look like these risk factors increase throughout early and young adulthood and become significant risk factors for stroke in the 30s and 40s,” lead author Sharon N. Poisson, MD, MAS, associate professor of neurology at the University of Colorado at Denver, Aurora, said in an interview.

The findings were published online in JAMA Neurology.

In this study, the researchers focused on arterial ischemic stroke, not hemorrhagic stroke. “We know that high blood pressure, diabetes, smoking, obesity, all of these are risk factors for ischemic stroke, but what we didn’t know is at what age do those atherosclerotic risk factors actually start to cause stroke,” Dr. Poisson said.

To find out more, she and her team did a case control study of data in the Kaiser Permanente Northern California system, which had been accumulating relevant data over a period of 14 years, from Jan. 1, 2000, through Dec. 31, 2014.

The analysis included 141 children and 455 young adults with arterial ischemic stroke and 1,382 age-matched controls.

The children were divided into two age categories: ages 29 days to 9 years and ages 10-19 years.

In the younger group, there were 69 cases of arterial ischemic stroke. In the older age group, there were 72 cases.

Young adults were divided into three age categories: 20-29 years (n = 71 cases), 30-39 years (144 cases), and 40-49 years (240 cases).

Among pediatric controls, 168 children aged 29 days to 9 years (46.5%) and 196 children aged 10-19 years (53.8%) developed arterial ischemic stroke.

There were 121 cases of ischemic stroke among young adult controls aged 20-29 years, 298 cases among controls aged 30-39 years, and 599 cases in those aged 40-49 years.

Both childhood cases and controls had a low prevalence of documented diagnoses of atherosclerotic risk factors (ARFs). The odds ratio of having any ARFs on arterial ischemic stroke was 1.87 for ages 0-9 years, and 1.00 for ages 10-19.

However, cases rose with age.

The OR was 2.3 for age range 20-29 years, 3.57 for age range 30-39 years, and 4.91 for age range 40-49 years.

The analysis also showed that the OR associated with multiple ARFs was 5.29 for age range 0-9 years, 2.75 for age range 10-19 years, 7.33 for age range 20-29 years, 9.86 for age range 30-39 years, and 9.35 for age range 40-49 years.

Multiple risk factors were rare in children but became more prevalent with each decade of young adult life.

The presumed cause of arterial ischemic stroke was atherosclerosis. Evidence of atherosclerosis was present in 1.4% of those aged 10-19 years, 8.5% of those aged 20-29 years, 21.5% of those aged 30-39 years, and 42.5% of those aged 40-49 years.

“This study tells us that, while stroke in adolescence and very early adulthood may not be caused by atherosclerotic risk factors, starting to accumulate those risk factors early in life clearly increases the risk of stroke in the 30s and 40s. I hope we can get this message across, because the sooner we can treat the risk factors, the better the outcome,” Dr. Poisson said.
 

Prevention starts in childhood

Prevention of cardiovascular disease begins in childhood, which is a paradigm shift from the way cardiovascular disease was thought of a couple of decades ago, noted pediatric cardiologist Guilherme Baptista de Faia, MD, from the Ann & Robert H. Lurie Children’s Hospital in Chicago.

“Our guidelines for risk factor reduction in children aim to address how or when do we screen for these risk factors, how or when do we intervene, and do these interventions impact cardiovascular outcomes later in life? This article is part of the mounting research that aims to understand the relationship between childhood cardiovascular risk factors and early cardiovascular disease,” Dr. Baptista de Faia said.

“There has been an interesting progression in our understanding of the impact of CV risk factors early in life. Large cohorts such as Bogalusa Heart Study, Risk in Young Finns Study, Muscatine Study, the Childhood Determinants of Adult Health, CARDIA, and the International Childhood Cardiovascular Cohorts (i3C) have been instrumental in evaluating this question,” he said.

The knowledge that atherosclerotic risk factors in children can lead to acceleration of atherosclerosis in later life opens the door to preventive medicine, said Dr. Baptista de Faia, who was not part of the study.

“This is where preventive medicine comes in. If we can identify the children at increased risk, can we intervene to improve outcomes later in life?” he said. Familial hypercholesterolemia is “a great example of this. We can screen children early in life, there is an effective treatment, and we know from populations studies that early treatment significantly decreases the risk for cardiovascular disease later in life.”

Dr. Poisson reported that she received grants from the National Institutes of Health during the conduct of this study, which was supported by the NIH.

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

In a case-control study, atherosclerotic risk factors were uncommon in childhood and did not appear to be associated with the pathogenesis of arterial ischemic stroke in children or in early young adulthood.

But by the fourth and fifth decades of life, these risk factors were strongly associated with a significant risk for stroke, heightening that risk almost tenfold.

“While strokes in childhood and very early adulthood are not likely caused by atherosclerotic risk factors, it does look like these risk factors increase throughout early and young adulthood and become significant risk factors for stroke in the 30s and 40s,” lead author Sharon N. Poisson, MD, MAS, associate professor of neurology at the University of Colorado at Denver, Aurora, said in an interview.

The findings were published online in JAMA Neurology.

In this study, the researchers focused on arterial ischemic stroke, not hemorrhagic stroke. “We know that high blood pressure, diabetes, smoking, obesity, all of these are risk factors for ischemic stroke, but what we didn’t know is at what age do those atherosclerotic risk factors actually start to cause stroke,” Dr. Poisson said.

To find out more, she and her team did a case control study of data in the Kaiser Permanente Northern California system, which had been accumulating relevant data over a period of 14 years, from Jan. 1, 2000, through Dec. 31, 2014.

The analysis included 141 children and 455 young adults with arterial ischemic stroke and 1,382 age-matched controls.

The children were divided into two age categories: ages 29 days to 9 years and ages 10-19 years.

In the younger group, there were 69 cases of arterial ischemic stroke. In the older age group, there were 72 cases.

Young adults were divided into three age categories: 20-29 years (n = 71 cases), 30-39 years (144 cases), and 40-49 years (240 cases).

Among pediatric controls, 168 children aged 29 days to 9 years (46.5%) and 196 children aged 10-19 years (53.8%) developed arterial ischemic stroke.

There were 121 cases of ischemic stroke among young adult controls aged 20-29 years, 298 cases among controls aged 30-39 years, and 599 cases in those aged 40-49 years.

Both childhood cases and controls had a low prevalence of documented diagnoses of atherosclerotic risk factors (ARFs). The odds ratio of having any ARFs on arterial ischemic stroke was 1.87 for ages 0-9 years, and 1.00 for ages 10-19.

However, cases rose with age.

The OR was 2.3 for age range 20-29 years, 3.57 for age range 30-39 years, and 4.91 for age range 40-49 years.

The analysis also showed that the OR associated with multiple ARFs was 5.29 for age range 0-9 years, 2.75 for age range 10-19 years, 7.33 for age range 20-29 years, 9.86 for age range 30-39 years, and 9.35 for age range 40-49 years.

Multiple risk factors were rare in children but became more prevalent with each decade of young adult life.

The presumed cause of arterial ischemic stroke was atherosclerosis. Evidence of atherosclerosis was present in 1.4% of those aged 10-19 years, 8.5% of those aged 20-29 years, 21.5% of those aged 30-39 years, and 42.5% of those aged 40-49 years.

“This study tells us that, while stroke in adolescence and very early adulthood may not be caused by atherosclerotic risk factors, starting to accumulate those risk factors early in life clearly increases the risk of stroke in the 30s and 40s. I hope we can get this message across, because the sooner we can treat the risk factors, the better the outcome,” Dr. Poisson said.
 

Prevention starts in childhood

Prevention of cardiovascular disease begins in childhood, which is a paradigm shift from the way cardiovascular disease was thought of a couple of decades ago, noted pediatric cardiologist Guilherme Baptista de Faia, MD, from the Ann & Robert H. Lurie Children’s Hospital in Chicago.

“Our guidelines for risk factor reduction in children aim to address how or when do we screen for these risk factors, how or when do we intervene, and do these interventions impact cardiovascular outcomes later in life? This article is part of the mounting research that aims to understand the relationship between childhood cardiovascular risk factors and early cardiovascular disease,” Dr. Baptista de Faia said.

“There has been an interesting progression in our understanding of the impact of CV risk factors early in life. Large cohorts such as Bogalusa Heart Study, Risk in Young Finns Study, Muscatine Study, the Childhood Determinants of Adult Health, CARDIA, and the International Childhood Cardiovascular Cohorts (i3C) have been instrumental in evaluating this question,” he said.

The knowledge that atherosclerotic risk factors in children can lead to acceleration of atherosclerosis in later life opens the door to preventive medicine, said Dr. Baptista de Faia, who was not part of the study.

“This is where preventive medicine comes in. If we can identify the children at increased risk, can we intervene to improve outcomes later in life?” he said. Familial hypercholesterolemia is “a great example of this. We can screen children early in life, there is an effective treatment, and we know from populations studies that early treatment significantly decreases the risk for cardiovascular disease later in life.”

Dr. Poisson reported that she received grants from the National Institutes of Health during the conduct of this study, which was supported by the NIH.

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

Two very different sets of clinical evidence have offered new twists on how nonadherence to cardiovascular medicines not only leads to suboptimal outcomes, but also complicates the data from clinical studies.

One study, a subanalysis of a major trial, outlined how taking more than the assigned therapy – that is, nonadherence by taking too much rather than too little – skewed results. The other was a trial demonstrating that early use of an invasive procedure is not a strategy to compensate for nonadherence to guideline-directed medical therapy (GDMT).

Bruce Jancin/Frontline Medical News

“Both studies provide a fresh reminder that nonadherence is a significant problem in cardiology overall, but also in the trial setting when we are trying to interpret study results,” explained Usam Baber, MD, director of interventional cardiology, University of Oklahoma Health, Oklahoma City, coauthor of an editorial accompanying the two published studies.

Dr. Baber was the first author of a unifying editorial that addressed the issues raised by each. In an interview, Dr. Baber said the studies had unique take-home messages but together highlight important issues of nonadherence.
 

MASTER DAPT: Too much medicine

The subanalysis was performed on data generated by MASTER DAPT, a study evaluating whether a relatively short course of dual-antiplatelet therapy (DAPT) in patients at high risk of bleeding could preserve protection against major adverse cardiovascular events (MACE) while reducing risk of adverse events. The problem was that nonadherence muddied the primary message.

In MASTER DAPT, 1 month of DAPT was compared with a standard therapy of at least 2 additional months of DAPT following revascularization and placement of a biodegradable polymer stent. Enrollment in the study was restricted to those with a high risk of bleeding, the report of the primary results showed.

The major message of MASTER DAPT was that the abbreviated course of DAPT was noninferior for preventing MACE but resulted in lower rates of clinically relevant bleeding in those patients without an indication for oral anticoagulation (OAC). In the subgroup with an indication for OAC, there was no bleeding benefit.

However, when the results were reexamined in the context of adherence, the benefit of the shorter course was found to be underestimated. Relative to 9.4% in the standard-therapy arm, the nonadherence rate in the experimental arm was 20.2%, most of whom did not stop therapy at 1 month. They instead remained on the antiplatelet therapy, failing to adhere to the study protocol.

This form of nonadherence, taking more DAPT than assigned, was particularly common in the group with an indication for oral anticoagulation (OAC). In this group, nearly 25% assigned to an abbreviated course remained on DAPT for more than 6 months.

In the intention-to-treat analysis, there was no difference between abbreviated and standard DAPT for MACE whether or not patients had an indication for OAC. In other words, the new analysis showed a reduced risk of bleeding among all patients, whether taking OAC or not after controlling for nonadherence.

In addition, this MASTER DAPT analysis found that a high proportion of patients taking OAC did not discontinue their single-antiplatelet therapy (SAPT) after 6 months as specified.

When correcting for this failure to adhere to the MASTER DAPT protocol in a patient population at high bleeding risk, the new analysis “suggests for the first time that discontinuation of SAPT at 6 months after percutaneous intervention is associated with less bleeding without an increase in ischemic events,” Marco Valgimigli, MD, PhD, director of clinical research, Inselspital University Hospital, Bern, Switzerland, reported in the Journal of the American College of Cardiology.

The findings “reinforce the importance of accounting and correcting for nonadherence” in order to reduce bias in the assessment of treatment effects, according to Dr. Valgimigli, principal investigator of MASTER DAPT and this substudy.

“The first interesting message from this study is that clinicians are reluctant to stop SAPT in these patients even in the setting of a randomized controlled trial,” Dr. Valgimigli said in an interview.

In addition, this substudy, which was prespecified in the MASTER DAPT protocol and employed “a very sophisticated methodology” to control for the effect of adherence, extends the value of a conservative approach to those who are candidates for OAC.

“The main clinical message is that SAPT needs to be discontinued after 6 months in OAC patients, and clinicians need to stop being reluctant to do so,” Dr. Valgimigli said. The data show “prolongation of SAPT increases bleeding risk without decreasing ischemic risk.”

In evaluating trial relevance, regulators prefer ITT analyses, but Dr. Baber pointed out that these can obscure the evidence of risk or benefit of a per-protocol analysis when patients take their medicine as prescribed.

“The technical message is that, when we are trying to apply results of a clinical trial to daily practice, we must understand nonadherence,” Dr. Baber said.

Dr. Baber pointed out that the lack of adherence in the case of MASTER DAPT appears to relate more to clinicians managing the patients than to the patients themselves, but it still speaks to the importance of understanding the effects of treatment in the context of the medicine rather than adherence to the medicine.

ISCHEMIA: Reconsidering adherence

In the ISCHEMIA trial, the goal was to evaluate whether an early invasive intervention might compensate to at least some degree for the persistent problem of nonadherence.

“If you are managing a patient that you know is at high risk of noncompliance, many clinicians are tempted to perform early revascularization. This was my bias. The thinking is that by offering an invasive therapy we are at least doing something to control their disease,” John A. Spertus, MD, clinical director of outcomes research, St. Luke’s Mid America Heart Institute, Kansas City, Mo., explained in an interview.

The study did not support the hypothesis. Patients with chronic coronary disease were randomized to a strategy of angiography and, if indicated, revascularization, or to receive GDMT alone. The health status was followed with the Seattle Angina Questionnaire (SAQ-7).

At 12 months, patients who were adherent to GDMT had better SAQ-7 scores than those who were nonadherent, regardless of the arm to which they were randomized. Conversely, there was no difference in SAQ-7 scores between the two groups when the nonadherent subgroups in each arm were compared.

“I think these data suggest that an interventional therapy does not absolve clinicians from the responsibility of educating patients about the importance of adhering to GDMT,” Dr. Spertus said.

In ISCHEMIA, 4,480 patients were randomized. At baseline assessment 27.8% were nonadherent to GDMT. The baselines SAQ-7 scores were worse in these patients relative to those who were adherent. At 12 months, nonadherence still correlated with worse SAQ-7 scores.

“These data dispel the belief that we might be benefiting nonadherent patients by moving more quickly to invasive procedures,” Dr. Spertus said.

In cardiovascular disease, particularly heart failure, adherence to GDMT has been associated numerous times with improved quality of life, according to Dr. Baber. However, he said, the ability of invasive procedures to modify the adverse impact of poor adherence to GDMT has not been well studied. This ISCHEMIA subanalysis only reinforces the message that GDMT adherence is a meaningful predictor of improved quality of life.

However, urging clinicians to work with patients to improve adherence is not a novel idea, according to Dr. Baber. The unmet need is effective and reliable strategies.

“There are so many different reasons that patients are nonadherent, so there are limited gains by focusing on just one of the issues,” Dr. Baber said. “I think the answer is a patient-centric approach in which clinicians deal with the specific issues facing the patient in front of them. I think there are data go suggest this yields better results.”

These two very different studies also show that poor adherence is an insidious issue. While the MASTER DAPT data reveal how nonadherence confuse trial data, the ISCHEMIA trial shows that some assumptions about circumventing the effects of nonadherence might not be accurate.

According to Dr. Baber, effective strategies to reduce nonadherence are available, but the problem deserves to be addressed more proactively in clinical trials and in patient care.

Dr. Baber reported financial relationships with AstraZeneca and Amgen. Dr. Spertus has financial relationships with Abbott, Bayer, Bristol-Myers Squibb, Corvia, Janssen, Merck, Novartis, Pfizer and Terumo. Dr. Valgimigli has financial relationships with more than 15 pharmaceutical companies, including Terumo, which provided funding for the MASTER DAPT trial.
 

Two very different sets of clinical evidence have offered new twists on how nonadherence to cardiovascular medicines not only leads to suboptimal outcomes, but also complicates the data from clinical studies.

One study, a subanalysis of a major trial, outlined how taking more than the assigned therapy – that is, nonadherence by taking too much rather than too little – skewed results. The other was a trial demonstrating that early use of an invasive procedure is not a strategy to compensate for nonadherence to guideline-directed medical therapy (GDMT).

Bruce Jancin/Frontline Medical News

“Both studies provide a fresh reminder that nonadherence is a significant problem in cardiology overall, but also in the trial setting when we are trying to interpret study results,” explained Usam Baber, MD, director of interventional cardiology, University of Oklahoma Health, Oklahoma City, coauthor of an editorial accompanying the two published studies.

Dr. Baber was the first author of a unifying editorial that addressed the issues raised by each. In an interview, Dr. Baber said the studies had unique take-home messages but together highlight important issues of nonadherence.
 

MASTER DAPT: Too much medicine

The subanalysis was performed on data generated by MASTER DAPT, a study evaluating whether a relatively short course of dual-antiplatelet therapy (DAPT) in patients at high risk of bleeding could preserve protection against major adverse cardiovascular events (MACE) while reducing risk of adverse events. The problem was that nonadherence muddied the primary message.

In MASTER DAPT, 1 month of DAPT was compared with a standard therapy of at least 2 additional months of DAPT following revascularization and placement of a biodegradable polymer stent. Enrollment in the study was restricted to those with a high risk of bleeding, the report of the primary results showed.

The major message of MASTER DAPT was that the abbreviated course of DAPT was noninferior for preventing MACE but resulted in lower rates of clinically relevant bleeding in those patients without an indication for oral anticoagulation (OAC). In the subgroup with an indication for OAC, there was no bleeding benefit.

However, when the results were reexamined in the context of adherence, the benefit of the shorter course was found to be underestimated. Relative to 9.4% in the standard-therapy arm, the nonadherence rate in the experimental arm was 20.2%, most of whom did not stop therapy at 1 month. They instead remained on the antiplatelet therapy, failing to adhere to the study protocol.

This form of nonadherence, taking more DAPT than assigned, was particularly common in the group with an indication for oral anticoagulation (OAC). In this group, nearly 25% assigned to an abbreviated course remained on DAPT for more than 6 months.

In the intention-to-treat analysis, there was no difference between abbreviated and standard DAPT for MACE whether or not patients had an indication for OAC. In other words, the new analysis showed a reduced risk of bleeding among all patients, whether taking OAC or not after controlling for nonadherence.

In addition, this MASTER DAPT analysis found that a high proportion of patients taking OAC did not discontinue their single-antiplatelet therapy (SAPT) after 6 months as specified.

When correcting for this failure to adhere to the MASTER DAPT protocol in a patient population at high bleeding risk, the new analysis “suggests for the first time that discontinuation of SAPT at 6 months after percutaneous intervention is associated with less bleeding without an increase in ischemic events,” Marco Valgimigli, MD, PhD, director of clinical research, Inselspital University Hospital, Bern, Switzerland, reported in the Journal of the American College of Cardiology.

The findings “reinforce the importance of accounting and correcting for nonadherence” in order to reduce bias in the assessment of treatment effects, according to Dr. Valgimigli, principal investigator of MASTER DAPT and this substudy.

“The first interesting message from this study is that clinicians are reluctant to stop SAPT in these patients even in the setting of a randomized controlled trial,” Dr. Valgimigli said in an interview.

In addition, this substudy, which was prespecified in the MASTER DAPT protocol and employed “a very sophisticated methodology” to control for the effect of adherence, extends the value of a conservative approach to those who are candidates for OAC.

“The main clinical message is that SAPT needs to be discontinued after 6 months in OAC patients, and clinicians need to stop being reluctant to do so,” Dr. Valgimigli said. The data show “prolongation of SAPT increases bleeding risk without decreasing ischemic risk.”

In evaluating trial relevance, regulators prefer ITT analyses, but Dr. Baber pointed out that these can obscure the evidence of risk or benefit of a per-protocol analysis when patients take their medicine as prescribed.

“The technical message is that, when we are trying to apply results of a clinical trial to daily practice, we must understand nonadherence,” Dr. Baber said.

Dr. Baber pointed out that the lack of adherence in the case of MASTER DAPT appears to relate more to clinicians managing the patients than to the patients themselves, but it still speaks to the importance of understanding the effects of treatment in the context of the medicine rather than adherence to the medicine.

ISCHEMIA: Reconsidering adherence

In the ISCHEMIA trial, the goal was to evaluate whether an early invasive intervention might compensate to at least some degree for the persistent problem of nonadherence.

“If you are managing a patient that you know is at high risk of noncompliance, many clinicians are tempted to perform early revascularization. This was my bias. The thinking is that by offering an invasive therapy we are at least doing something to control their disease,” John A. Spertus, MD, clinical director of outcomes research, St. Luke’s Mid America Heart Institute, Kansas City, Mo., explained in an interview.

The study did not support the hypothesis. Patients with chronic coronary disease were randomized to a strategy of angiography and, if indicated, revascularization, or to receive GDMT alone. The health status was followed with the Seattle Angina Questionnaire (SAQ-7).

At 12 months, patients who were adherent to GDMT had better SAQ-7 scores than those who were nonadherent, regardless of the arm to which they were randomized. Conversely, there was no difference in SAQ-7 scores between the two groups when the nonadherent subgroups in each arm were compared.

“I think these data suggest that an interventional therapy does not absolve clinicians from the responsibility of educating patients about the importance of adhering to GDMT,” Dr. Spertus said.

In ISCHEMIA, 4,480 patients were randomized. At baseline assessment 27.8% were nonadherent to GDMT. The baselines SAQ-7 scores were worse in these patients relative to those who were adherent. At 12 months, nonadherence still correlated with worse SAQ-7 scores.

“These data dispel the belief that we might be benefiting nonadherent patients by moving more quickly to invasive procedures,” Dr. Spertus said.

In cardiovascular disease, particularly heart failure, adherence to GDMT has been associated numerous times with improved quality of life, according to Dr. Baber. However, he said, the ability of invasive procedures to modify the adverse impact of poor adherence to GDMT has not been well studied. This ISCHEMIA subanalysis only reinforces the message that GDMT adherence is a meaningful predictor of improved quality of life.

However, urging clinicians to work with patients to improve adherence is not a novel idea, according to Dr. Baber. The unmet need is effective and reliable strategies.

“There are so many different reasons that patients are nonadherent, so there are limited gains by focusing on just one of the issues,” Dr. Baber said. “I think the answer is a patient-centric approach in which clinicians deal with the specific issues facing the patient in front of them. I think there are data go suggest this yields better results.”

These two very different studies also show that poor adherence is an insidious issue. While the MASTER DAPT data reveal how nonadherence confuse trial data, the ISCHEMIA trial shows that some assumptions about circumventing the effects of nonadherence might not be accurate.

According to Dr. Baber, effective strategies to reduce nonadherence are available, but the problem deserves to be addressed more proactively in clinical trials and in patient care.

Dr. Baber reported financial relationships with AstraZeneca and Amgen. Dr. Spertus has financial relationships with Abbott, Bayer, Bristol-Myers Squibb, Corvia, Janssen, Merck, Novartis, Pfizer and Terumo. Dr. Valgimigli has financial relationships with more than 15 pharmaceutical companies, including Terumo, which provided funding for the MASTER DAPT trial.
 

Two very different sets of clinical evidence have offered new twists on how nonadherence to cardiovascular medicines not only leads to suboptimal outcomes, but also complicates the data from clinical studies.

One study, a subanalysis of a major trial, outlined how taking more than the assigned therapy – that is, nonadherence by taking too much rather than too little – skewed results. The other was a trial demonstrating that early use of an invasive procedure is not a strategy to compensate for nonadherence to guideline-directed medical therapy (GDMT).

Bruce Jancin/Frontline Medical News

“Both studies provide a fresh reminder that nonadherence is a significant problem in cardiology overall, but also in the trial setting when we are trying to interpret study results,” explained Usam Baber, MD, director of interventional cardiology, University of Oklahoma Health, Oklahoma City, coauthor of an editorial accompanying the two published studies.

Dr. Baber was the first author of a unifying editorial that addressed the issues raised by each. In an interview, Dr. Baber said the studies had unique take-home messages but together highlight important issues of nonadherence.
 

MASTER DAPT: Too much medicine

The subanalysis was performed on data generated by MASTER DAPT, a study evaluating whether a relatively short course of dual-antiplatelet therapy (DAPT) in patients at high risk of bleeding could preserve protection against major adverse cardiovascular events (MACE) while reducing risk of adverse events. The problem was that nonadherence muddied the primary message.

In MASTER DAPT, 1 month of DAPT was compared with a standard therapy of at least 2 additional months of DAPT following revascularization and placement of a biodegradable polymer stent. Enrollment in the study was restricted to those with a high risk of bleeding, the report of the primary results showed.

The major message of MASTER DAPT was that the abbreviated course of DAPT was noninferior for preventing MACE but resulted in lower rates of clinically relevant bleeding in those patients without an indication for oral anticoagulation (OAC). In the subgroup with an indication for OAC, there was no bleeding benefit.

However, when the results were reexamined in the context of adherence, the benefit of the shorter course was found to be underestimated. Relative to 9.4% in the standard-therapy arm, the nonadherence rate in the experimental arm was 20.2%, most of whom did not stop therapy at 1 month. They instead remained on the antiplatelet therapy, failing to adhere to the study protocol.

This form of nonadherence, taking more DAPT than assigned, was particularly common in the group with an indication for oral anticoagulation (OAC). In this group, nearly 25% assigned to an abbreviated course remained on DAPT for more than 6 months.

In the intention-to-treat analysis, there was no difference between abbreviated and standard DAPT for MACE whether or not patients had an indication for OAC. In other words, the new analysis showed a reduced risk of bleeding among all patients, whether taking OAC or not after controlling for nonadherence.

In addition, this MASTER DAPT analysis found that a high proportion of patients taking OAC did not discontinue their single-antiplatelet therapy (SAPT) after 6 months as specified.

When correcting for this failure to adhere to the MASTER DAPT protocol in a patient population at high bleeding risk, the new analysis “suggests for the first time that discontinuation of SAPT at 6 months after percutaneous intervention is associated with less bleeding without an increase in ischemic events,” Marco Valgimigli, MD, PhD, director of clinical research, Inselspital University Hospital, Bern, Switzerland, reported in the Journal of the American College of Cardiology.

The findings “reinforce the importance of accounting and correcting for nonadherence” in order to reduce bias in the assessment of treatment effects, according to Dr. Valgimigli, principal investigator of MASTER DAPT and this substudy.

“The first interesting message from this study is that clinicians are reluctant to stop SAPT in these patients even in the setting of a randomized controlled trial,” Dr. Valgimigli said in an interview.

In addition, this substudy, which was prespecified in the MASTER DAPT protocol and employed “a very sophisticated methodology” to control for the effect of adherence, extends the value of a conservative approach to those who are candidates for OAC.

“The main clinical message is that SAPT needs to be discontinued after 6 months in OAC patients, and clinicians need to stop being reluctant to do so,” Dr. Valgimigli said. The data show “prolongation of SAPT increases bleeding risk without decreasing ischemic risk.”

In evaluating trial relevance, regulators prefer ITT analyses, but Dr. Baber pointed out that these can obscure the evidence of risk or benefit of a per-protocol analysis when patients take their medicine as prescribed.

“The technical message is that, when we are trying to apply results of a clinical trial to daily practice, we must understand nonadherence,” Dr. Baber said.

Dr. Baber pointed out that the lack of adherence in the case of MASTER DAPT appears to relate more to clinicians managing the patients than to the patients themselves, but it still speaks to the importance of understanding the effects of treatment in the context of the medicine rather than adherence to the medicine.

ISCHEMIA: Reconsidering adherence

In the ISCHEMIA trial, the goal was to evaluate whether an early invasive intervention might compensate to at least some degree for the persistent problem of nonadherence.

“If you are managing a patient that you know is at high risk of noncompliance, many clinicians are tempted to perform early revascularization. This was my bias. The thinking is that by offering an invasive therapy we are at least doing something to control their disease,” John A. Spertus, MD, clinical director of outcomes research, St. Luke’s Mid America Heart Institute, Kansas City, Mo., explained in an interview.

The study did not support the hypothesis. Patients with chronic coronary disease were randomized to a strategy of angiography and, if indicated, revascularization, or to receive GDMT alone. The health status was followed with the Seattle Angina Questionnaire (SAQ-7).

At 12 months, patients who were adherent to GDMT had better SAQ-7 scores than those who were nonadherent, regardless of the arm to which they were randomized. Conversely, there was no difference in SAQ-7 scores between the two groups when the nonadherent subgroups in each arm were compared.

“I think these data suggest that an interventional therapy does not absolve clinicians from the responsibility of educating patients about the importance of adhering to GDMT,” Dr. Spertus said.

In ISCHEMIA, 4,480 patients were randomized. At baseline assessment 27.8% were nonadherent to GDMT. The baselines SAQ-7 scores were worse in these patients relative to those who were adherent. At 12 months, nonadherence still correlated with worse SAQ-7 scores.

“These data dispel the belief that we might be benefiting nonadherent patients by moving more quickly to invasive procedures,” Dr. Spertus said.

In cardiovascular disease, particularly heart failure, adherence to GDMT has been associated numerous times with improved quality of life, according to Dr. Baber. However, he said, the ability of invasive procedures to modify the adverse impact of poor adherence to GDMT has not been well studied. This ISCHEMIA subanalysis only reinforces the message that GDMT adherence is a meaningful predictor of improved quality of life.

However, urging clinicians to work with patients to improve adherence is not a novel idea, according to Dr. Baber. The unmet need is effective and reliable strategies.

“There are so many different reasons that patients are nonadherent, so there are limited gains by focusing on just one of the issues,” Dr. Baber said. “I think the answer is a patient-centric approach in which clinicians deal with the specific issues facing the patient in front of them. I think there are data go suggest this yields better results.”

These two very different studies also show that poor adherence is an insidious issue. While the MASTER DAPT data reveal how nonadherence confuse trial data, the ISCHEMIA trial shows that some assumptions about circumventing the effects of nonadherence might not be accurate.

According to Dr. Baber, effective strategies to reduce nonadherence are available, but the problem deserves to be addressed more proactively in clinical trials and in patient care.

Dr. Baber reported financial relationships with AstraZeneca and Amgen. Dr. Spertus has financial relationships with Abbott, Bayer, Bristol-Myers Squibb, Corvia, Janssen, Merck, Novartis, Pfizer and Terumo. Dr. Valgimigli has financial relationships with more than 15 pharmaceutical companies, including Terumo, which provided funding for the MASTER DAPT trial.
 

The connection between red meat and atherosclerotic cardiovascular disease has been well established, but newly reported findings indicate that metabolites in the gut microbiome may explain that relationship more than cholesterol and blood pressure.

“Eating more meat, especially red meat and processed meats, is associated with a higher risk of cardiovascular disease, even later in life,” co–lead study author Meng Wang, PhD, said in an interview.

The study, from a large community-based cohort of older people, included 3,931 U.S. participants aged 65 and older in the Cardiovascular Health Study (CHS). It found that gut microbiota–generated metabolites of dietary L-carnitine, including trimethylamine N-oxide (TMAO), have a role in the association between unprocessed red meat intake and incident ASCVD.

“TMAO-related metabolites produced by our gut microbes as well as blood-glucose and insulin homeostasis and systematic inflammation appeared to explain much of the association, more so than blood cholesterol or blood pressure,” added Dr. Wang, of the Friedman School of Nutrition Science and Policy at Tufts University, Boston.

Dr. Wang said this study was unique because it focused specifically on older adults; the average participant age was 72.9 years. “Older adults are at the highest risk of CVD, and for them adequate intake of protein may help to offset aging-related loss of muscle mass and strength,” she said. However, the study population was largely white (88%), so, she said, the results may not be generalizable to populations that are younger or of different nationalities and races.

The researchers performed a multivariable analysis that showed that participants who had higher intakes of unprocessed red meat, total meat, and total animal source foods (ASF) had higher hazard ratios of ASCVD risk. The study had a median follow-up of 12.5 years. It divided the study population into five quintiles based on how much unprocessed red met they consumed at baseline and analyzed dietary exposure in the differences between the midpoints of the first and fifth quintiles.

Earlier studies of meat intake and CVD risk focused mostly on saturated fat and blood cholesterol, Dr. Wang added. “But our findings suggest that other components in red meat, such as L-carnitine and heme iron, might play a more important role than saturated fat,” she said.

camij/thinkstockphotos.com

Higher intake of unprocessed red meat was linked to a 15% higher incidence of ASCVD per interquintile range (hazard ratio, 1.15; 95% confidence interval, 1.01-1.30; P = .031). Total meat intake, defined as unprocessed plus processed red meat, was tied to a 22% higher incidence of ASCVD (HR, 1.22; CI, 1.07-1.39; P = .004).

The study found no significant association between fish, poultry, or egg intake and incident ASCVD, but found total ASF intake had an 18% higher risk (HR, 1.18; CI, 1.03–1.34; P = .016).
 

Explaining the red meat–CVD connection

“The more novel part of our study is about the mediation analysis,” Dr. Wang said. “It helps explain why meat intake was associated with a higher risk of CVD. We identified several biological pathways, including the novel one through TMAO-related metabolites produced by the gut microbiome.”

Three gut microbiota–generated metabolites of L-carnitine – TMAO, gamma-butyrobetaine, and crotonobetaine – seem to partly explain the association between unprocessed red meat intake and incident ASCVD, the study reported.

The study found 3.92 excess ASCVD events per 1,000 person years associated with each interquintile range of higher unprocessed red meat intake; 10.6% of them were attributed to plasma levels of the three L-carnitine metabolites (95% CI, 1.0-114.5).

In this study, neither blood cholesterol nor blood pressure levels seemed to explain the elevated risk of ASCVD associated with meat intake, but blood glucose and insulin did, with mediation proportions of 26.1% and 11.8%, respectively.

Study strengths are its size and its general population cohort with well-measured CVD risk factors, Dr. Wang pointed out. All participants were free of clinically diagnosed CVD at enrollment, which minimized selection bias and reverse causation, she said. However, she acknowledged that the use of self-reported diet intake data, along with the largely white population, constitute limitations.

“Our study findings need to be confirmed in different populations and more research efforts are needed to better understand the health effects of some of the components in red meat, such as L-carnitine and heme iron,” Dr. Wang said.

“This study is interesting in that it doesn’t just ask the question, ‘Is eating red meat associated with coronary disease and atherosclerotic disease?’ but it tells what the mechanism is,” Robert Vogel, MD, professor at University of Colorado at Denver, Aurora, said in an interview.

The association between red meat and ASCVD is “an established science,” he said. “Where this study adds to the literature is that it suggests that elevated LDL cholesterol or blood pressure, things – especially the former – that are thought to be associated with coronary disease, may or may not be the mechanism.” He cautioned, however, “this is all associative data.”

The study “produces incremental knowledge for the association between eating red met and atherosclerosis, but it does not establish causality,” Dr. Vogel added.

Dr. Wang has no relevant disclosures. Dr. Vogel is a consultant to the Pritikin Longevity Center in Miami.

The connection between red meat and atherosclerotic cardiovascular disease has been well established, but newly reported findings indicate that metabolites in the gut microbiome may explain that relationship more than cholesterol and blood pressure.

“Eating more meat, especially red meat and processed meats, is associated with a higher risk of cardiovascular disease, even later in life,” co–lead study author Meng Wang, PhD, said in an interview.

The study, from a large community-based cohort of older people, included 3,931 U.S. participants aged 65 and older in the Cardiovascular Health Study (CHS). It found that gut microbiota–generated metabolites of dietary L-carnitine, including trimethylamine N-oxide (TMAO), have a role in the association between unprocessed red meat intake and incident ASCVD.

“TMAO-related metabolites produced by our gut microbes as well as blood-glucose and insulin homeostasis and systematic inflammation appeared to explain much of the association, more so than blood cholesterol or blood pressure,” added Dr. Wang, of the Friedman School of Nutrition Science and Policy at Tufts University, Boston.

Dr. Wang said this study was unique because it focused specifically on older adults; the average participant age was 72.9 years. “Older adults are at the highest risk of CVD, and for them adequate intake of protein may help to offset aging-related loss of muscle mass and strength,” she said. However, the study population was largely white (88%), so, she said, the results may not be generalizable to populations that are younger or of different nationalities and races.

The researchers performed a multivariable analysis that showed that participants who had higher intakes of unprocessed red meat, total meat, and total animal source foods (ASF) had higher hazard ratios of ASCVD risk. The study had a median follow-up of 12.5 years. It divided the study population into five quintiles based on how much unprocessed red met they consumed at baseline and analyzed dietary exposure in the differences between the midpoints of the first and fifth quintiles.

Earlier studies of meat intake and CVD risk focused mostly on saturated fat and blood cholesterol, Dr. Wang added. “But our findings suggest that other components in red meat, such as L-carnitine and heme iron, might play a more important role than saturated fat,” she said.

camij/thinkstockphotos.com

Higher intake of unprocessed red meat was linked to a 15% higher incidence of ASCVD per interquintile range (hazard ratio, 1.15; 95% confidence interval, 1.01-1.30; P = .031). Total meat intake, defined as unprocessed plus processed red meat, was tied to a 22% higher incidence of ASCVD (HR, 1.22; CI, 1.07-1.39; P = .004).

The study found no significant association between fish, poultry, or egg intake and incident ASCVD, but found total ASF intake had an 18% higher risk (HR, 1.18; CI, 1.03–1.34; P = .016).
 

Explaining the red meat–CVD connection

“The more novel part of our study is about the mediation analysis,” Dr. Wang said. “It helps explain why meat intake was associated with a higher risk of CVD. We identified several biological pathways, including the novel one through TMAO-related metabolites produced by the gut microbiome.”

Three gut microbiota–generated metabolites of L-carnitine – TMAO, gamma-butyrobetaine, and crotonobetaine – seem to partly explain the association between unprocessed red meat intake and incident ASCVD, the study reported.

The study found 3.92 excess ASCVD events per 1,000 person years associated with each interquintile range of higher unprocessed red meat intake; 10.6% of them were attributed to plasma levels of the three L-carnitine metabolites (95% CI, 1.0-114.5).

In this study, neither blood cholesterol nor blood pressure levels seemed to explain the elevated risk of ASCVD associated with meat intake, but blood glucose and insulin did, with mediation proportions of 26.1% and 11.8%, respectively.

Study strengths are its size and its general population cohort with well-measured CVD risk factors, Dr. Wang pointed out. All participants were free of clinically diagnosed CVD at enrollment, which minimized selection bias and reverse causation, she said. However, she acknowledged that the use of self-reported diet intake data, along with the largely white population, constitute limitations.

“Our study findings need to be confirmed in different populations and more research efforts are needed to better understand the health effects of some of the components in red meat, such as L-carnitine and heme iron,” Dr. Wang said.

“This study is interesting in that it doesn’t just ask the question, ‘Is eating red meat associated with coronary disease and atherosclerotic disease?’ but it tells what the mechanism is,” Robert Vogel, MD, professor at University of Colorado at Denver, Aurora, said in an interview.

The association between red meat and ASCVD is “an established science,” he said. “Where this study adds to the literature is that it suggests that elevated LDL cholesterol or blood pressure, things – especially the former – that are thought to be associated with coronary disease, may or may not be the mechanism.” He cautioned, however, “this is all associative data.”

The study “produces incremental knowledge for the association between eating red met and atherosclerosis, but it does not establish causality,” Dr. Vogel added.

Dr. Wang has no relevant disclosures. Dr. Vogel is a consultant to the Pritikin Longevity Center in Miami.

The connection between red meat and atherosclerotic cardiovascular disease has been well established, but newly reported findings indicate that metabolites in the gut microbiome may explain that relationship more than cholesterol and blood pressure.

“Eating more meat, especially red meat and processed meats, is associated with a higher risk of cardiovascular disease, even later in life,” co–lead study author Meng Wang, PhD, said in an interview.

The study, from a large community-based cohort of older people, included 3,931 U.S. participants aged 65 and older in the Cardiovascular Health Study (CHS). It found that gut microbiota–generated metabolites of dietary L-carnitine, including trimethylamine N-oxide (TMAO), have a role in the association between unprocessed red meat intake and incident ASCVD.

“TMAO-related metabolites produced by our gut microbes as well as blood-glucose and insulin homeostasis and systematic inflammation appeared to explain much of the association, more so than blood cholesterol or blood pressure,” added Dr. Wang, of the Friedman School of Nutrition Science and Policy at Tufts University, Boston.

Dr. Wang said this study was unique because it focused specifically on older adults; the average participant age was 72.9 years. “Older adults are at the highest risk of CVD, and for them adequate intake of protein may help to offset aging-related loss of muscle mass and strength,” she said. However, the study population was largely white (88%), so, she said, the results may not be generalizable to populations that are younger or of different nationalities and races.

The researchers performed a multivariable analysis that showed that participants who had higher intakes of unprocessed red meat, total meat, and total animal source foods (ASF) had higher hazard ratios of ASCVD risk. The study had a median follow-up of 12.5 years. It divided the study population into five quintiles based on how much unprocessed red met they consumed at baseline and analyzed dietary exposure in the differences between the midpoints of the first and fifth quintiles.

Earlier studies of meat intake and CVD risk focused mostly on saturated fat and blood cholesterol, Dr. Wang added. “But our findings suggest that other components in red meat, such as L-carnitine and heme iron, might play a more important role than saturated fat,” she said.

camij/thinkstockphotos.com

Higher intake of unprocessed red meat was linked to a 15% higher incidence of ASCVD per interquintile range (hazard ratio, 1.15; 95% confidence interval, 1.01-1.30; P = .031). Total meat intake, defined as unprocessed plus processed red meat, was tied to a 22% higher incidence of ASCVD (HR, 1.22; CI, 1.07-1.39; P = .004).

The study found no significant association between fish, poultry, or egg intake and incident ASCVD, but found total ASF intake had an 18% higher risk (HR, 1.18; CI, 1.03–1.34; P = .016).
 

Explaining the red meat–CVD connection

“The more novel part of our study is about the mediation analysis,” Dr. Wang said. “It helps explain why meat intake was associated with a higher risk of CVD. We identified several biological pathways, including the novel one through TMAO-related metabolites produced by the gut microbiome.”

Three gut microbiota–generated metabolites of L-carnitine – TMAO, gamma-butyrobetaine, and crotonobetaine – seem to partly explain the association between unprocessed red meat intake and incident ASCVD, the study reported.

The study found 3.92 excess ASCVD events per 1,000 person years associated with each interquintile range of higher unprocessed red meat intake; 10.6% of them were attributed to plasma levels of the three L-carnitine metabolites (95% CI, 1.0-114.5).

In this study, neither blood cholesterol nor blood pressure levels seemed to explain the elevated risk of ASCVD associated with meat intake, but blood glucose and insulin did, with mediation proportions of 26.1% and 11.8%, respectively.

Study strengths are its size and its general population cohort with well-measured CVD risk factors, Dr. Wang pointed out. All participants were free of clinically diagnosed CVD at enrollment, which minimized selection bias and reverse causation, she said. However, she acknowledged that the use of self-reported diet intake data, along with the largely white population, constitute limitations.

“Our study findings need to be confirmed in different populations and more research efforts are needed to better understand the health effects of some of the components in red meat, such as L-carnitine and heme iron,” Dr. Wang said.

“This study is interesting in that it doesn’t just ask the question, ‘Is eating red meat associated with coronary disease and atherosclerotic disease?’ but it tells what the mechanism is,” Robert Vogel, MD, professor at University of Colorado at Denver, Aurora, said in an interview.

The association between red meat and ASCVD is “an established science,” he said. “Where this study adds to the literature is that it suggests that elevated LDL cholesterol or blood pressure, things – especially the former – that are thought to be associated with coronary disease, may or may not be the mechanism.” He cautioned, however, “this is all associative data.”

The study “produces incremental knowledge for the association between eating red met and atherosclerosis, but it does not establish causality,” Dr. Vogel added.

Dr. Wang has no relevant disclosures. Dr. Vogel is a consultant to the Pritikin Longevity Center in Miami.

Early improvement of left ventricular ejection fraction (LVEF) after transcatheter aortic valve replacement (TAVR) is associated with improved all-cause and cardiac death at 5 years in patients with severe aortic stenosis and LVEF less than 50%, new research shows.

Further analyses revealed a significant interaction by sex, with the mortality benefit largely in women.

“It’s absolutely fascinating,” senior author Sammy Elmariah, MD, Massachusetts General Hospital, Boston, said of the finding. “We know that women are more likely to have concentric hypertrophy, that they have lesser degrees of fibrosis, and smaller ventricles, and, of course, they’re in general less affected by coronary artery disease and MIs [myocardial infarctions]. All of those things in my mind, at least that’s what I assumed ahead of time, would make it more likely for women’s hearts to recover.”

“But that’s actually not what we found,” he continued. “We didn’t see a difference between the sexes in terms of likelihood of recovery. But what we saw is that the survival benefit, that associates with improvement in EF, was almost completely driven by women. So women really seem to be reaping that benefit in a manner that is unique and very different from what we saw in men.”

Dr. Elmariah noted that the reason for this benefit is unclear but points to the differences in biology for LV remodeling. “Clearly there are several details there that warrant further attention and more research.”

Suzanne J. Baron, MD, director of interventional cardiology research at Lahey Hospital and Medical Center, Burlington, Mass., said in an email that the finding of a substantial long-term survival benefit was “a bit surprising.”

Several studies have suggested that women may derive a greater benefit from TAVR versus surgical aortic valve replacement, and meta-analyses have demonstrated short and intermediate-term survival after TAVR is better in women, compared with in men, she pointed out. However, the mediating mechanism for this finding has never been clearly elucidated.

“Certainly, the sex differences in LVEF improvement after TAVR observed in this study, which could be related to sex differences in LV remodeling and LV mass regression, may now give us a clue as to why these sex-specific survival differences after TAVR persist,” Dr. Baron said.
 

More data amassed

Previous research in smaller cohorts with follow-up out to 1 year have shown an association between early LVEF improvement after TAVR and better survival. This includes a 2013 study by the investigators in high-risk patients in PARTNER-1 and a separate 2016 study in patients in the CoreValve extreme and high surgical risk trials.

Now, with longer follow-up amassed, the investigators examined data from 659 high- or intermediate-risk patients with severe stenosis and LVEF less than 50% who underwent transfemoral TAVR in the PARTNER 1, 2, and S3 trials and registries between July 2007 and April 2015.

Their mean age was 82.4 years, 71% were men, and 89.7% were White individuals. During the study period, 55.6% of the cohort died.

As reported in JAMA Cardiology, 32.8% of patients had early LVEF improvement, defined as an increase of at least 10% percentage points at 30 days after TAVR (mean change, 16.4%).

This compares with about 50%-60% of patients in the earlier studies, likely owing to the relatively higher baseline LVEF, especially in the intermediate-risk cohort, the authors suggested.

Independent predictors of lower likelihood of early LVEF improvement were previous MI, diabetes, cancer, higher baseline LVEF, larger LV end-diastolic diameter, and larger aortic valve area (AVA), whereas higher body mass index and higher stroke volume index predicted greater likelihood of LV recovery.

At 5 years, patients with versus without improved early LV improvement had lower risks of all-cause death (50.0% vs. 58.4%; P = .04) and cardiac death (29.5% vs. 38.1%; P = .05).

In multivariable analyses, each 5%-point increase in LVEF after TAVR was associated with a 6% lower risk of all-cause death (hazard ratio [HR], 0.94; P = .04) and 10% lower risk of cardiac death (HR, 0.90; P = .02).

Restricted cubic spline analysis demonstrated an inflection point above a 10% change in LVEF beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement.

There were no significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire score at 5 years in patients with and without early LVEF improvement.

“I think what this really gets to is what is the reason behind the LV dysfunction in the first place,” said Dr. Elmariah, soon to be joining the University of California, San Francisco. “We know that TAVR cures aortic stenosis, so if the LV dysfunction is primarily related to the valve itself, hopefully those patients are going to recover.”

On the other hand, if the patient has LV dysfunction because of a prior myocardial infarction or cardiomyopathy and then developed aortic stenosis, “you can treat the aortic stenosis but the heart is still diseased from whatever process was affecting it previously and so it’s not likely to recover in those scenarios,” he added.

The results can be used for counseling patients and highlight the need to optimize goal-directed medical therapy in those with valvular heart disease, Dr. Elmariah suggested.

“Often, patients with aortic stenosis are on miniscule doses of many of the heart failure agents because people are worried about the hemodynamic consequences and they’re worried that patients won’t tolerate these medications,” he said. “But it’s very important for us to aggressively try to treat the heart failure that is affecting these patients in order to hopefully increase the chances that their left ventricles will recover and, hopefully, that they will have improved survival.”

Dr. Baron said that “this study clearly demonstrates that patients with reduced LVEF and severe aortic stenosis can benefit from TAVR and that early improvement in LVEF is an important prognostic marker for this population.”

In Dr. Baron and colleagues’ earlier analysis of 11,000 patients who underwent TAVR as part of the transcatheter valve therapy registry, only low aortic valve gradient but not LV dysfunction was associated with higher adjusted 1-year mortality. Asked about the finding, she noted that patients were evaluated based on LV function at baseline and not for a difference in outcomes based on LVEF improvement after TAVR.

“As such, I think that these two studies are actually complementary,” Dr. Baron said. “Together, they suggest that a low LVEF should not preclude a patient from receiving TAVR and if the patient does experience a 10% increase in LVEF after TAVR, then their 5-year prognosis is improved.”

Dr. Elmariah reports grants from the American Heart Association, National Institutes of Health, Edwards Lifesciences, Medtronic, and Svelte Medical and has received consulting fees from Medtronic and AstraZeneca. Coauthor disclosures are listed in the paper. The PARTNER trials and registries and this analysis were supported by Edwards Lifesciences. Edwards was involved in the design and conduct of the study including collection, management, analysis, and interpretation of the data. Dr. Baron reports receiving research grant funding from Abiomed and Boston Scientific; consulting/medical advisory board fees from Boston Scientific, Shockwave and Biotronik; and speaking honoraria from Medtronic and Zoll.

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

Early improvement of left ventricular ejection fraction (LVEF) after transcatheter aortic valve replacement (TAVR) is associated with improved all-cause and cardiac death at 5 years in patients with severe aortic stenosis and LVEF less than 50%, new research shows.

Further analyses revealed a significant interaction by sex, with the mortality benefit largely in women.

“It’s absolutely fascinating,” senior author Sammy Elmariah, MD, Massachusetts General Hospital, Boston, said of the finding. “We know that women are more likely to have concentric hypertrophy, that they have lesser degrees of fibrosis, and smaller ventricles, and, of course, they’re in general less affected by coronary artery disease and MIs [myocardial infarctions]. All of those things in my mind, at least that’s what I assumed ahead of time, would make it more likely for women’s hearts to recover.”

“But that’s actually not what we found,” he continued. “We didn’t see a difference between the sexes in terms of likelihood of recovery. But what we saw is that the survival benefit, that associates with improvement in EF, was almost completely driven by women. So women really seem to be reaping that benefit in a manner that is unique and very different from what we saw in men.”

Dr. Elmariah noted that the reason for this benefit is unclear but points to the differences in biology for LV remodeling. “Clearly there are several details there that warrant further attention and more research.”

Suzanne J. Baron, MD, director of interventional cardiology research at Lahey Hospital and Medical Center, Burlington, Mass., said in an email that the finding of a substantial long-term survival benefit was “a bit surprising.”

Several studies have suggested that women may derive a greater benefit from TAVR versus surgical aortic valve replacement, and meta-analyses have demonstrated short and intermediate-term survival after TAVR is better in women, compared with in men, she pointed out. However, the mediating mechanism for this finding has never been clearly elucidated.

“Certainly, the sex differences in LVEF improvement after TAVR observed in this study, which could be related to sex differences in LV remodeling and LV mass regression, may now give us a clue as to why these sex-specific survival differences after TAVR persist,” Dr. Baron said.
 

More data amassed

Previous research in smaller cohorts with follow-up out to 1 year have shown an association between early LVEF improvement after TAVR and better survival. This includes a 2013 study by the investigators in high-risk patients in PARTNER-1 and a separate 2016 study in patients in the CoreValve extreme and high surgical risk trials.

Now, with longer follow-up amassed, the investigators examined data from 659 high- or intermediate-risk patients with severe stenosis and LVEF less than 50% who underwent transfemoral TAVR in the PARTNER 1, 2, and S3 trials and registries between July 2007 and April 2015.

Their mean age was 82.4 years, 71% were men, and 89.7% were White individuals. During the study period, 55.6% of the cohort died.

As reported in JAMA Cardiology, 32.8% of patients had early LVEF improvement, defined as an increase of at least 10% percentage points at 30 days after TAVR (mean change, 16.4%).

This compares with about 50%-60% of patients in the earlier studies, likely owing to the relatively higher baseline LVEF, especially in the intermediate-risk cohort, the authors suggested.

Independent predictors of lower likelihood of early LVEF improvement were previous MI, diabetes, cancer, higher baseline LVEF, larger LV end-diastolic diameter, and larger aortic valve area (AVA), whereas higher body mass index and higher stroke volume index predicted greater likelihood of LV recovery.

At 5 years, patients with versus without improved early LV improvement had lower risks of all-cause death (50.0% vs. 58.4%; P = .04) and cardiac death (29.5% vs. 38.1%; P = .05).

In multivariable analyses, each 5%-point increase in LVEF after TAVR was associated with a 6% lower risk of all-cause death (hazard ratio [HR], 0.94; P = .04) and 10% lower risk of cardiac death (HR, 0.90; P = .02).

Restricted cubic spline analysis demonstrated an inflection point above a 10% change in LVEF beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement.

There were no significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire score at 5 years in patients with and without early LVEF improvement.

“I think what this really gets to is what is the reason behind the LV dysfunction in the first place,” said Dr. Elmariah, soon to be joining the University of California, San Francisco. “We know that TAVR cures aortic stenosis, so if the LV dysfunction is primarily related to the valve itself, hopefully those patients are going to recover.”

On the other hand, if the patient has LV dysfunction because of a prior myocardial infarction or cardiomyopathy and then developed aortic stenosis, “you can treat the aortic stenosis but the heart is still diseased from whatever process was affecting it previously and so it’s not likely to recover in those scenarios,” he added.

The results can be used for counseling patients and highlight the need to optimize goal-directed medical therapy in those with valvular heart disease, Dr. Elmariah suggested.

“Often, patients with aortic stenosis are on miniscule doses of many of the heart failure agents because people are worried about the hemodynamic consequences and they’re worried that patients won’t tolerate these medications,” he said. “But it’s very important for us to aggressively try to treat the heart failure that is affecting these patients in order to hopefully increase the chances that their left ventricles will recover and, hopefully, that they will have improved survival.”

Dr. Baron said that “this study clearly demonstrates that patients with reduced LVEF and severe aortic stenosis can benefit from TAVR and that early improvement in LVEF is an important prognostic marker for this population.”

In Dr. Baron and colleagues’ earlier analysis of 11,000 patients who underwent TAVR as part of the transcatheter valve therapy registry, only low aortic valve gradient but not LV dysfunction was associated with higher adjusted 1-year mortality. Asked about the finding, she noted that patients were evaluated based on LV function at baseline and not for a difference in outcomes based on LVEF improvement after TAVR.

“As such, I think that these two studies are actually complementary,” Dr. Baron said. “Together, they suggest that a low LVEF should not preclude a patient from receiving TAVR and if the patient does experience a 10% increase in LVEF after TAVR, then their 5-year prognosis is improved.”

Dr. Elmariah reports grants from the American Heart Association, National Institutes of Health, Edwards Lifesciences, Medtronic, and Svelte Medical and has received consulting fees from Medtronic and AstraZeneca. Coauthor disclosures are listed in the paper. The PARTNER trials and registries and this analysis were supported by Edwards Lifesciences. Edwards was involved in the design and conduct of the study including collection, management, analysis, and interpretation of the data. Dr. Baron reports receiving research grant funding from Abiomed and Boston Scientific; consulting/medical advisory board fees from Boston Scientific, Shockwave and Biotronik; and speaking honoraria from Medtronic and Zoll.

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

Early improvement of left ventricular ejection fraction (LVEF) after transcatheter aortic valve replacement (TAVR) is associated with improved all-cause and cardiac death at 5 years in patients with severe aortic stenosis and LVEF less than 50%, new research shows.

Further analyses revealed a significant interaction by sex, with the mortality benefit largely in women.

“It’s absolutely fascinating,” senior author Sammy Elmariah, MD, Massachusetts General Hospital, Boston, said of the finding. “We know that women are more likely to have concentric hypertrophy, that they have lesser degrees of fibrosis, and smaller ventricles, and, of course, they’re in general less affected by coronary artery disease and MIs [myocardial infarctions]. All of those things in my mind, at least that’s what I assumed ahead of time, would make it more likely for women’s hearts to recover.”

“But that’s actually not what we found,” he continued. “We didn’t see a difference between the sexes in terms of likelihood of recovery. But what we saw is that the survival benefit, that associates with improvement in EF, was almost completely driven by women. So women really seem to be reaping that benefit in a manner that is unique and very different from what we saw in men.”

Dr. Elmariah noted that the reason for this benefit is unclear but points to the differences in biology for LV remodeling. “Clearly there are several details there that warrant further attention and more research.”

Suzanne J. Baron, MD, director of interventional cardiology research at Lahey Hospital and Medical Center, Burlington, Mass., said in an email that the finding of a substantial long-term survival benefit was “a bit surprising.”

Several studies have suggested that women may derive a greater benefit from TAVR versus surgical aortic valve replacement, and meta-analyses have demonstrated short and intermediate-term survival after TAVR is better in women, compared with in men, she pointed out. However, the mediating mechanism for this finding has never been clearly elucidated.

“Certainly, the sex differences in LVEF improvement after TAVR observed in this study, which could be related to sex differences in LV remodeling and LV mass regression, may now give us a clue as to why these sex-specific survival differences after TAVR persist,” Dr. Baron said.
 

More data amassed

Previous research in smaller cohorts with follow-up out to 1 year have shown an association between early LVEF improvement after TAVR and better survival. This includes a 2013 study by the investigators in high-risk patients in PARTNER-1 and a separate 2016 study in patients in the CoreValve extreme and high surgical risk trials.

Now, with longer follow-up amassed, the investigators examined data from 659 high- or intermediate-risk patients with severe stenosis and LVEF less than 50% who underwent transfemoral TAVR in the PARTNER 1, 2, and S3 trials and registries between July 2007 and April 2015.

Their mean age was 82.4 years, 71% were men, and 89.7% were White individuals. During the study period, 55.6% of the cohort died.

As reported in JAMA Cardiology, 32.8% of patients had early LVEF improvement, defined as an increase of at least 10% percentage points at 30 days after TAVR (mean change, 16.4%).

This compares with about 50%-60% of patients in the earlier studies, likely owing to the relatively higher baseline LVEF, especially in the intermediate-risk cohort, the authors suggested.

Independent predictors of lower likelihood of early LVEF improvement were previous MI, diabetes, cancer, higher baseline LVEF, larger LV end-diastolic diameter, and larger aortic valve area (AVA), whereas higher body mass index and higher stroke volume index predicted greater likelihood of LV recovery.

At 5 years, patients with versus without improved early LV improvement had lower risks of all-cause death (50.0% vs. 58.4%; P = .04) and cardiac death (29.5% vs. 38.1%; P = .05).

In multivariable analyses, each 5%-point increase in LVEF after TAVR was associated with a 6% lower risk of all-cause death (hazard ratio [HR], 0.94; P = .04) and 10% lower risk of cardiac death (HR, 0.90; P = .02).

Restricted cubic spline analysis demonstrated an inflection point above a 10% change in LVEF beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement.

There were no significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire score at 5 years in patients with and without early LVEF improvement.

“I think what this really gets to is what is the reason behind the LV dysfunction in the first place,” said Dr. Elmariah, soon to be joining the University of California, San Francisco. “We know that TAVR cures aortic stenosis, so if the LV dysfunction is primarily related to the valve itself, hopefully those patients are going to recover.”

On the other hand, if the patient has LV dysfunction because of a prior myocardial infarction or cardiomyopathy and then developed aortic stenosis, “you can treat the aortic stenosis but the heart is still diseased from whatever process was affecting it previously and so it’s not likely to recover in those scenarios,” he added.

The results can be used for counseling patients and highlight the need to optimize goal-directed medical therapy in those with valvular heart disease, Dr. Elmariah suggested.

“Often, patients with aortic stenosis are on miniscule doses of many of the heart failure agents because people are worried about the hemodynamic consequences and they’re worried that patients won’t tolerate these medications,” he said. “But it’s very important for us to aggressively try to treat the heart failure that is affecting these patients in order to hopefully increase the chances that their left ventricles will recover and, hopefully, that they will have improved survival.”

Dr. Baron said that “this study clearly demonstrates that patients with reduced LVEF and severe aortic stenosis can benefit from TAVR and that early improvement in LVEF is an important prognostic marker for this population.”

In Dr. Baron and colleagues’ earlier analysis of 11,000 patients who underwent TAVR as part of the transcatheter valve therapy registry, only low aortic valve gradient but not LV dysfunction was associated with higher adjusted 1-year mortality. Asked about the finding, she noted that patients were evaluated based on LV function at baseline and not for a difference in outcomes based on LVEF improvement after TAVR.

“As such, I think that these two studies are actually complementary,” Dr. Baron said. “Together, they suggest that a low LVEF should not preclude a patient from receiving TAVR and if the patient does experience a 10% increase in LVEF after TAVR, then their 5-year prognosis is improved.”

Dr. Elmariah reports grants from the American Heart Association, National Institutes of Health, Edwards Lifesciences, Medtronic, and Svelte Medical and has received consulting fees from Medtronic and AstraZeneca. Coauthor disclosures are listed in the paper. The PARTNER trials and registries and this analysis were supported by Edwards Lifesciences. Edwards was involved in the design and conduct of the study including collection, management, analysis, and interpretation of the data. Dr. Baron reports receiving research grant funding from Abiomed and Boston Scientific; consulting/medical advisory board fees from Boston Scientific, Shockwave and Biotronik; and speaking honoraria from Medtronic and Zoll.

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

Screening for atrial fibrillation with wearable devices is cost effective, when compared with either no screening or screening using traditional methods, a new study concludes.

“Undiagnosed atrial fibrillation (AFib) is an important cause of stroke. Screening for AFib using wrist-worn wearable devices may prevent strokes, but their cost effectiveness is unknown,” write Wanyi Chen, PhD, from Massachusetts General Hospital, Boston, and colleagues, in JAMA Health Forum.

The investigators used a microsimulation decision-analytic model to evaluate the cost effectiveness of these devices to screen for undiagnosed AFib.

The model comprised 30 million simulated individuals with an age, sex, and comorbidity profile matching the United States population aged 65 years or older.

The model looked at eight AFib screening strategies: six using wrist-worn wearable devices (either watch or band photoplethysmography with or without watch or band electrocardiography) and two using traditional modalities (that is, pulse palpation and 12-lead electrocardiogram) versus no screening.

The primary outcome was the incremental cost effectiveness ratio, defined as U.S. dollars per quality-adjusted life-year (QALY). Secondary outcomes included rates of stroke and major bleeding.

In the model, the mean age was 72.5 years and 50% were women.

All 6 screening strategies using wrist-worn wearable devices were estimated to be more cost effective than no screening. The model showed that the range of QALYs gained, compared with no screening, was 226 to 957 per 100,000 individuals.

The wrist-worn devices were also associated with greater relative benefit than screening using traditional modalities, as the range of QALYs gained, compared with no screening, was –116 to 93 per 100,000 individuals.

Compared with no screening, screening with wrist-worn wearable devices was associated with a reduction in stroke incidence by 20 to 23 per 100,000 person-years but an increase in major bleeding by 20 to 44 per 100,000 person years.

Overall, the preferred strategy for screening was wearable photoplethysmography, followed by wearable electrocardiography with patch monitor confirmation. This strategy had an incremental cost effectiveness ratio of $57,894 per QALY, “meeting the acceptability threshold of $100,000 per QALY,” the authors write.

The cost effectiveness of screening was consistent across multiple clinically relevant scenarios, including screening a general population aged 50 years or older with risk factors for stroke, the authors report.

“When deployed within specific AFib screening pathways, wearable devices are likely to be an important component of cost-effective AFib screening,” the investigators conclude.

Study based on modeled data

“This study is the first simulation of various screening strategies for atrial fibrillation using wearable devices and suggests that wearable devices, in particular wrist-worn wearables, in an elderly population, [are] estimated to be cost-effective,” Emma Svennberg, MD, PhD, from the Karolinska University Hospital, Stockholm, told this news organization.

“I find this study interesting, as the adoption of wearables amongst individuals is high and increasing, hence many wearers will screen themselves for arrhythmias (even if health care recommendations are discordant), and the potential costs for society have been unknown,” said Dr. Svennberg, who was not part of this study.

“Of course, no study is without its flaws, and here one must note that the study is based on modeled data alone and not RCTs of the wearable screening strategies ... hence true clinical outcome data is missing,” Dr. Svennberg added.

The large STROKESTOP study, on which she was the lead investigator, “presented data based on true clinical outcomes at ESC 2021 (European Society of Cardiology) and showed cost effectiveness,” Dr. Svennberg said.

The study authors report financial relationships with Bristol Myers Squibb, Fitbit, Medtronic, Pfizer, UpToDate, American Heart Association, IBM, Bayer AG, Novartis, MyoKardia, Boehringer Ingelheim, Heart Rhythm Society, Avania Consulting, Apple, Premier, the National Institutes of Health, Invitae, Blackstone Life Sciences, Flatiron, and Value Analytics Labs. Dr. Svennberg reports no relevant financial relationships.

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

Screening for atrial fibrillation with wearable devices is cost effective, when compared with either no screening or screening using traditional methods, a new study concludes.

“Undiagnosed atrial fibrillation (AFib) is an important cause of stroke. Screening for AFib using wrist-worn wearable devices may prevent strokes, but their cost effectiveness is unknown,” write Wanyi Chen, PhD, from Massachusetts General Hospital, Boston, and colleagues, in JAMA Health Forum.

The investigators used a microsimulation decision-analytic model to evaluate the cost effectiveness of these devices to screen for undiagnosed AFib.

The model comprised 30 million simulated individuals with an age, sex, and comorbidity profile matching the United States population aged 65 years or older.

The model looked at eight AFib screening strategies: six using wrist-worn wearable devices (either watch or band photoplethysmography with or without watch or band electrocardiography) and two using traditional modalities (that is, pulse palpation and 12-lead electrocardiogram) versus no screening.

The primary outcome was the incremental cost effectiveness ratio, defined as U.S. dollars per quality-adjusted life-year (QALY). Secondary outcomes included rates of stroke and major bleeding.

In the model, the mean age was 72.5 years and 50% were women.

All 6 screening strategies using wrist-worn wearable devices were estimated to be more cost effective than no screening. The model showed that the range of QALYs gained, compared with no screening, was 226 to 957 per 100,000 individuals.

The wrist-worn devices were also associated with greater relative benefit than screening using traditional modalities, as the range of QALYs gained, compared with no screening, was –116 to 93 per 100,000 individuals.

Compared with no screening, screening with wrist-worn wearable devices was associated with a reduction in stroke incidence by 20 to 23 per 100,000 person-years but an increase in major bleeding by 20 to 44 per 100,000 person years.

Overall, the preferred strategy for screening was wearable photoplethysmography, followed by wearable electrocardiography with patch monitor confirmation. This strategy had an incremental cost effectiveness ratio of $57,894 per QALY, “meeting the acceptability threshold of $100,000 per QALY,” the authors write.

The cost effectiveness of screening was consistent across multiple clinically relevant scenarios, including screening a general population aged 50 years or older with risk factors for stroke, the authors report.

“When deployed within specific AFib screening pathways, wearable devices are likely to be an important component of cost-effective AFib screening,” the investigators conclude.

Study based on modeled data

“This study is the first simulation of various screening strategies for atrial fibrillation using wearable devices and suggests that wearable devices, in particular wrist-worn wearables, in an elderly population, [are] estimated to be cost-effective,” Emma Svennberg, MD, PhD, from the Karolinska University Hospital, Stockholm, told this news organization.

“I find this study interesting, as the adoption of wearables amongst individuals is high and increasing, hence many wearers will screen themselves for arrhythmias (even if health care recommendations are discordant), and the potential costs for society have been unknown,” said Dr. Svennberg, who was not part of this study.

“Of course, no study is without its flaws, and here one must note that the study is based on modeled data alone and not RCTs of the wearable screening strategies ... hence true clinical outcome data is missing,” Dr. Svennberg added.

The large STROKESTOP study, on which she was the lead investigator, “presented data based on true clinical outcomes at ESC 2021 (European Society of Cardiology) and showed cost effectiveness,” Dr. Svennberg said.

The study authors report financial relationships with Bristol Myers Squibb, Fitbit, Medtronic, Pfizer, UpToDate, American Heart Association, IBM, Bayer AG, Novartis, MyoKardia, Boehringer Ingelheim, Heart Rhythm Society, Avania Consulting, Apple, Premier, the National Institutes of Health, Invitae, Blackstone Life Sciences, Flatiron, and Value Analytics Labs. Dr. Svennberg reports no relevant financial relationships.

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

Screening for atrial fibrillation with wearable devices is cost effective, when compared with either no screening or screening using traditional methods, a new study concludes.

“Undiagnosed atrial fibrillation (AFib) is an important cause of stroke. Screening for AFib using wrist-worn wearable devices may prevent strokes, but their cost effectiveness is unknown,” write Wanyi Chen, PhD, from Massachusetts General Hospital, Boston, and colleagues, in JAMA Health Forum.

The investigators used a microsimulation decision-analytic model to evaluate the cost effectiveness of these devices to screen for undiagnosed AFib.

The model comprised 30 million simulated individuals with an age, sex, and comorbidity profile matching the United States population aged 65 years or older.

The model looked at eight AFib screening strategies: six using wrist-worn wearable devices (either watch or band photoplethysmography with or without watch or band electrocardiography) and two using traditional modalities (that is, pulse palpation and 12-lead electrocardiogram) versus no screening.

The primary outcome was the incremental cost effectiveness ratio, defined as U.S. dollars per quality-adjusted life-year (QALY). Secondary outcomes included rates of stroke and major bleeding.

In the model, the mean age was 72.5 years and 50% were women.

All 6 screening strategies using wrist-worn wearable devices were estimated to be more cost effective than no screening. The model showed that the range of QALYs gained, compared with no screening, was 226 to 957 per 100,000 individuals.

The wrist-worn devices were also associated with greater relative benefit than screening using traditional modalities, as the range of QALYs gained, compared with no screening, was –116 to 93 per 100,000 individuals.

Compared with no screening, screening with wrist-worn wearable devices was associated with a reduction in stroke incidence by 20 to 23 per 100,000 person-years but an increase in major bleeding by 20 to 44 per 100,000 person years.

Overall, the preferred strategy for screening was wearable photoplethysmography, followed by wearable electrocardiography with patch monitor confirmation. This strategy had an incremental cost effectiveness ratio of $57,894 per QALY, “meeting the acceptability threshold of $100,000 per QALY,” the authors write.

The cost effectiveness of screening was consistent across multiple clinically relevant scenarios, including screening a general population aged 50 years or older with risk factors for stroke, the authors report.

“When deployed within specific AFib screening pathways, wearable devices are likely to be an important component of cost-effective AFib screening,” the investigators conclude.

Study based on modeled data

“This study is the first simulation of various screening strategies for atrial fibrillation using wearable devices and suggests that wearable devices, in particular wrist-worn wearables, in an elderly population, [are] estimated to be cost-effective,” Emma Svennberg, MD, PhD, from the Karolinska University Hospital, Stockholm, told this news organization.

“I find this study interesting, as the adoption of wearables amongst individuals is high and increasing, hence many wearers will screen themselves for arrhythmias (even if health care recommendations are discordant), and the potential costs for society have been unknown,” said Dr. Svennberg, who was not part of this study.

“Of course, no study is without its flaws, and here one must note that the study is based on modeled data alone and not RCTs of the wearable screening strategies ... hence true clinical outcome data is missing,” Dr. Svennberg added.

The large STROKESTOP study, on which she was the lead investigator, “presented data based on true clinical outcomes at ESC 2021 (European Society of Cardiology) and showed cost effectiveness,” Dr. Svennberg said.

The study authors report financial relationships with Bristol Myers Squibb, Fitbit, Medtronic, Pfizer, UpToDate, American Heart Association, IBM, Bayer AG, Novartis, MyoKardia, Boehringer Ingelheim, Heart Rhythm Society, Avania Consulting, Apple, Premier, the National Institutes of Health, Invitae, Blackstone Life Sciences, Flatiron, and Value Analytics Labs. Dr. Svennberg reports no relevant financial relationships.

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

Dietary salt substitutes not only lower blood pressure but also have a clear impact on hard clinical endpoints, lowering the risk of myocardial infarction (MI), stroke, and death from all causes and cardiovascular disease (CVD), a meta-analysis shows.

jirkaejc/Getty Images

The blood pressure–mediated protective effects of salt substitutes on CVD and death are likely to apply to the roughly 1.28 billion people around the world who have high blood pressure, the researchers say.

“These findings are unlikely to reflect the play of chance and support the adoption of salt substitutes in clinical practice and public health policy as a strategy to reduce dietary sodium intake, increase dietary potassium intake, lower blood pressure, and prevent major cardiovascular events,” they write.

The study was published online  in Heart.
 

Strong support for landmark study

In salt substitutes, a proportion of sodium chloride is replaced with potassium chloride. They are known to help lower blood pressure, but less is known about their impact on hard clinical endpoints, Maoyi Tian, PhD, with Harbin Medical University, China, and the George Institute for Global Health, Sydney, and colleagues note in their article.

In the landmark Salt Substitute and Stroke Study (SSaSS), salt substitutes cut the risk of MI, stroke, and early death, as reported previously by this news organization.

But SSaSS was conducted in China, and it was unclear whether these benefits would apply to people in other parts of the world.

To investigate, Dr. Tian and colleagues pooled data from 21 relevant parallel-group, step-wedge, or cluster randomized controlled trials published through August 2021, with 31,949 participants. The trials were conducted in Europe, the Western Pacific Region, the Americas, and South East Asia and reported the effect of a salt substitute on blood pressure or clinical outcomes.

A meta-analysis of blood pressure data from 19 trials that included 29,528 participants showed that salt substitutes lowered systolic blood pressure (SBP) by 4.61 mm Hg (95% confidence interval, −6.07 to −3.14) and diastolic blood pressure (DBP) by 1.61 mm Hg (95% CI, −2.42 to −0.79).

The proportion of sodium chloride in the salt substitutes varied from 33% to 75%; the proportion of potassium ranged from 25% to 65%.

Each 10% lower proportion of sodium chloride in the salt substitute was associated with a 1.53 mm Hg (95% CI, −3.02 to −0.03; P = .045) greater reduction in SBP and a 0.95 mm Hg (95% CI, −1.78 to −0.12; P = .025) greater reduction in DBP.

Reductions in blood pressure appeared consistent, irrespective of country, age, sex, history of high blood pressure, weight, baseline blood pressure, and baseline levels of urinary sodium and potassium.

Clear benefit on hard outcomes

Pooled data on clinical outcomes from five trials that included 24,306 participants, mostly from the SSaSS, showed clear protective effects of salt substitutes on total mortality (risk ratio, 0.89; 95% CI, 0.85-0.94), CV mortality (RR, 0.87; 95% CI, 0.81-0.94), and CV events (RR, 0.89; 95% CI, 0.85-0.94).

Dr. Tian and colleagues say that “broader population use of salt substitute is supported by the absence of any detectable adverse effect of salt substitutes on hyperkalemia in this review.”

They note, however, that all of the trials took “pragmatic steps to exclude participants at elevated risk of hyperkalemia, seeking to exclude those with chronic kidney disease or using medications that elevate serum potassium.”

Offering perspective on the study, Harlan Krumholz, MD, with Yale New Haven Hospital and Yale School of Medicine, both in New Haven, Conn., said it provides “useful information by bringing together the trial evidence on salt substitutes. The evidence is dominated by the SSaSS, but the others add context.”

Dr. Krumholz said that at this point, he thinks salt substitutes “could be included in recommendations to patients.”

“SSaSS was conducted in villages in China, so that is where the evidence is strongest and most relevant, but this is a low-cost and seemingly safe strategy that could be tried by anyone without contraindications, such as kidney disease or taking a potassium-sparing medication or potassium supplement,” Dr. Krumholz told this news organization.

Johanna Contreras, MD, heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, agrees that in the absence of contraindications, salt substitutes should be recommended.

“Americans put salt on everything and don’t even think about it. The salt substitutes are very helpful,” Dr. Contreras said in an interview.

“People who don’t have high blood pressure should limit salt intake, because what we have seen is that if you have high blood pressure in your family – even if you don’t have high blood pressure in your 20s or 30s – you’re likely to develop high blood pressure,” Dr. Contreras said.

“Therefore, it’s wise early on to start protecting yourself and using low salt and salt substitutes,” she added.

The study had no specific funding. Dr. Tian, Dr. Krumholz, and Dr. Contreras have disclosed no relevant financial relationships.

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

Dietary salt substitutes not only lower blood pressure but also have a clear impact on hard clinical endpoints, lowering the risk of myocardial infarction (MI), stroke, and death from all causes and cardiovascular disease (CVD), a meta-analysis shows.

jirkaejc/Getty Images

The blood pressure–mediated protective effects of salt substitutes on CVD and death are likely to apply to the roughly 1.28 billion people around the world who have high blood pressure, the researchers say.

“These findings are unlikely to reflect the play of chance and support the adoption of salt substitutes in clinical practice and public health policy as a strategy to reduce dietary sodium intake, increase dietary potassium intake, lower blood pressure, and prevent major cardiovascular events,” they write.

The study was published online  in Heart.
 

Strong support for landmark study

In salt substitutes, a proportion of sodium chloride is replaced with potassium chloride. They are known to help lower blood pressure, but less is known about their impact on hard clinical endpoints, Maoyi Tian, PhD, with Harbin Medical University, China, and the George Institute for Global Health, Sydney, and colleagues note in their article.

In the landmark Salt Substitute and Stroke Study (SSaSS), salt substitutes cut the risk of MI, stroke, and early death, as reported previously by this news organization.

But SSaSS was conducted in China, and it was unclear whether these benefits would apply to people in other parts of the world.

To investigate, Dr. Tian and colleagues pooled data from 21 relevant parallel-group, step-wedge, or cluster randomized controlled trials published through August 2021, with 31,949 participants. The trials were conducted in Europe, the Western Pacific Region, the Americas, and South East Asia and reported the effect of a salt substitute on blood pressure or clinical outcomes.

A meta-analysis of blood pressure data from 19 trials that included 29,528 participants showed that salt substitutes lowered systolic blood pressure (SBP) by 4.61 mm Hg (95% confidence interval, −6.07 to −3.14) and diastolic blood pressure (DBP) by 1.61 mm Hg (95% CI, −2.42 to −0.79).

The proportion of sodium chloride in the salt substitutes varied from 33% to 75%; the proportion of potassium ranged from 25% to 65%.

Each 10% lower proportion of sodium chloride in the salt substitute was associated with a 1.53 mm Hg (95% CI, −3.02 to −0.03; P = .045) greater reduction in SBP and a 0.95 mm Hg (95% CI, −1.78 to −0.12; P = .025) greater reduction in DBP.

Reductions in blood pressure appeared consistent, irrespective of country, age, sex, history of high blood pressure, weight, baseline blood pressure, and baseline levels of urinary sodium and potassium.

Clear benefit on hard outcomes

Pooled data on clinical outcomes from five trials that included 24,306 participants, mostly from the SSaSS, showed clear protective effects of salt substitutes on total mortality (risk ratio, 0.89; 95% CI, 0.85-0.94), CV mortality (RR, 0.87; 95% CI, 0.81-0.94), and CV events (RR, 0.89; 95% CI, 0.85-0.94).

Dr. Tian and colleagues say that “broader population use of salt substitute is supported by the absence of any detectable adverse effect of salt substitutes on hyperkalemia in this review.”

They note, however, that all of the trials took “pragmatic steps to exclude participants at elevated risk of hyperkalemia, seeking to exclude those with chronic kidney disease or using medications that elevate serum potassium.”

Offering perspective on the study, Harlan Krumholz, MD, with Yale New Haven Hospital and Yale School of Medicine, both in New Haven, Conn., said it provides “useful information by bringing together the trial evidence on salt substitutes. The evidence is dominated by the SSaSS, but the others add context.”

Dr. Krumholz said that at this point, he thinks salt substitutes “could be included in recommendations to patients.”

“SSaSS was conducted in villages in China, so that is where the evidence is strongest and most relevant, but this is a low-cost and seemingly safe strategy that could be tried by anyone without contraindications, such as kidney disease or taking a potassium-sparing medication or potassium supplement,” Dr. Krumholz told this news organization.

Johanna Contreras, MD, heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, agrees that in the absence of contraindications, salt substitutes should be recommended.

“Americans put salt on everything and don’t even think about it. The salt substitutes are very helpful,” Dr. Contreras said in an interview.

“People who don’t have high blood pressure should limit salt intake, because what we have seen is that if you have high blood pressure in your family – even if you don’t have high blood pressure in your 20s or 30s – you’re likely to develop high blood pressure,” Dr. Contreras said.

“Therefore, it’s wise early on to start protecting yourself and using low salt and salt substitutes,” she added.

The study had no specific funding. Dr. Tian, Dr. Krumholz, and Dr. Contreras have disclosed no relevant financial relationships.

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

Dietary salt substitutes not only lower blood pressure but also have a clear impact on hard clinical endpoints, lowering the risk of myocardial infarction (MI), stroke, and death from all causes and cardiovascular disease (CVD), a meta-analysis shows.

jirkaejc/Getty Images

The blood pressure–mediated protective effects of salt substitutes on CVD and death are likely to apply to the roughly 1.28 billion people around the world who have high blood pressure, the researchers say.

“These findings are unlikely to reflect the play of chance and support the adoption of salt substitutes in clinical practice and public health policy as a strategy to reduce dietary sodium intake, increase dietary potassium intake, lower blood pressure, and prevent major cardiovascular events,” they write.

The study was published online  in Heart.
 

Strong support for landmark study

In salt substitutes, a proportion of sodium chloride is replaced with potassium chloride. They are known to help lower blood pressure, but less is known about their impact on hard clinical endpoints, Maoyi Tian, PhD, with Harbin Medical University, China, and the George Institute for Global Health, Sydney, and colleagues note in their article.

In the landmark Salt Substitute and Stroke Study (SSaSS), salt substitutes cut the risk of MI, stroke, and early death, as reported previously by this news organization.

But SSaSS was conducted in China, and it was unclear whether these benefits would apply to people in other parts of the world.

To investigate, Dr. Tian and colleagues pooled data from 21 relevant parallel-group, step-wedge, or cluster randomized controlled trials published through August 2021, with 31,949 participants. The trials were conducted in Europe, the Western Pacific Region, the Americas, and South East Asia and reported the effect of a salt substitute on blood pressure or clinical outcomes.

A meta-analysis of blood pressure data from 19 trials that included 29,528 participants showed that salt substitutes lowered systolic blood pressure (SBP) by 4.61 mm Hg (95% confidence interval, −6.07 to −3.14) and diastolic blood pressure (DBP) by 1.61 mm Hg (95% CI, −2.42 to −0.79).

The proportion of sodium chloride in the salt substitutes varied from 33% to 75%; the proportion of potassium ranged from 25% to 65%.

Each 10% lower proportion of sodium chloride in the salt substitute was associated with a 1.53 mm Hg (95% CI, −3.02 to −0.03; P = .045) greater reduction in SBP and a 0.95 mm Hg (95% CI, −1.78 to −0.12; P = .025) greater reduction in DBP.

Reductions in blood pressure appeared consistent, irrespective of country, age, sex, history of high blood pressure, weight, baseline blood pressure, and baseline levels of urinary sodium and potassium.

Clear benefit on hard outcomes

Pooled data on clinical outcomes from five trials that included 24,306 participants, mostly from the SSaSS, showed clear protective effects of salt substitutes on total mortality (risk ratio, 0.89; 95% CI, 0.85-0.94), CV mortality (RR, 0.87; 95% CI, 0.81-0.94), and CV events (RR, 0.89; 95% CI, 0.85-0.94).

Dr. Tian and colleagues say that “broader population use of salt substitute is supported by the absence of any detectable adverse effect of salt substitutes on hyperkalemia in this review.”

They note, however, that all of the trials took “pragmatic steps to exclude participants at elevated risk of hyperkalemia, seeking to exclude those with chronic kidney disease or using medications that elevate serum potassium.”

Offering perspective on the study, Harlan Krumholz, MD, with Yale New Haven Hospital and Yale School of Medicine, both in New Haven, Conn., said it provides “useful information by bringing together the trial evidence on salt substitutes. The evidence is dominated by the SSaSS, but the others add context.”

Dr. Krumholz said that at this point, he thinks salt substitutes “could be included in recommendations to patients.”

“SSaSS was conducted in villages in China, so that is where the evidence is strongest and most relevant, but this is a low-cost and seemingly safe strategy that could be tried by anyone without contraindications, such as kidney disease or taking a potassium-sparing medication or potassium supplement,” Dr. Krumholz told this news organization.

Johanna Contreras, MD, heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, agrees that in the absence of contraindications, salt substitutes should be recommended.

“Americans put salt on everything and don’t even think about it. The salt substitutes are very helpful,” Dr. Contreras said in an interview.

“People who don’t have high blood pressure should limit salt intake, because what we have seen is that if you have high blood pressure in your family – even if you don’t have high blood pressure in your 20s or 30s – you’re likely to develop high blood pressure,” Dr. Contreras said.

“Therefore, it’s wise early on to start protecting yourself and using low salt and salt substitutes,” she added.

The study had no specific funding. Dr. Tian, Dr. Krumholz, and Dr. Contreras have disclosed no relevant financial relationships.

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

Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner highlighting the latest research and study outcomes related to the health of veteran and active-duty populations. 

In this issue:

• Vaccinations
• Mental Health and Related Disorders
• LGBTQ+ Veterans
• Military Sexual Trauma
• Sleep Disorders
• Respiratory Illnesses
• HIV Care in the VA
• Rheumatologic Diseases
• The Cancer-Obesity Connection
• Skin Health for Active-Duty Personnel
• Contraception
• Chronic Kidney Disease
• Cardiovascular Diseases
• Neurologic Disorders
• Hearing, Vision, and Balance

Federal Practitioner would like to thank the following experts for their review of content and helpful guidance in developing this issue: 

Kelvin N.V. Bush, MD, FACC, CCDS; Sonya Borrero, MD, MS; Kenneth L. Cameron, PhD, MPH, ATC, FNATA; Jason DeViva, PhD; Ellen Lockard Edens, MD; Leonard E. Egede, MD, MS; Amy Justice, MD, PhD; Stephanie Knudson, MD; Willis H. Lyford, MD; Sarah O. Meadows, PhD; Tamara Schult, PhD, MPH; Eric L. Singman, MD, PhD; Art Wallace, MD, PhD; Elizabeth Waterhouse, MD, FAAN

Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner highlighting the latest research and study outcomes related to the health of veteran and active-duty populations. 

In this issue:

• Vaccinations
• Mental Health and Related Disorders
• LGBTQ+ Veterans
• Military Sexual Trauma
• Sleep Disorders
• Respiratory Illnesses
• HIV Care in the VA
• Rheumatologic Diseases
• The Cancer-Obesity Connection
• Skin Health for Active-Duty Personnel
• Contraception
• Chronic Kidney Disease
• Cardiovascular Diseases
• Neurologic Disorders
• Hearing, Vision, and Balance

Federal Practitioner would like to thank the following experts for their review of content and helpful guidance in developing this issue: 

Kelvin N.V. Bush, MD, FACC, CCDS; Sonya Borrero, MD, MS; Kenneth L. Cameron, PhD, MPH, ATC, FNATA; Jason DeViva, PhD; Ellen Lockard Edens, MD; Leonard E. Egede, MD, MS; Amy Justice, MD, PhD; Stephanie Knudson, MD; Willis H. Lyford, MD; Sarah O. Meadows, PhD; Tamara Schult, PhD, MPH; Eric L. Singman, MD, PhD; Art Wallace, MD, PhD; Elizabeth Waterhouse, MD, FAAN

Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner highlighting the latest research and study outcomes related to the health of veteran and active-duty populations. 

In this issue:

• Vaccinations
• Mental Health and Related Disorders
• LGBTQ+ Veterans
• Military Sexual Trauma
• Sleep Disorders
• Respiratory Illnesses
• HIV Care in the VA
• Rheumatologic Diseases
• The Cancer-Obesity Connection
• Skin Health for Active-Duty Personnel
• Contraception
• Chronic Kidney Disease
• Cardiovascular Diseases
• Neurologic Disorders
• Hearing, Vision, and Balance

Federal Practitioner would like to thank the following experts for their review of content and helpful guidance in developing this issue: 

Kelvin N.V. Bush, MD, FACC, CCDS; Sonya Borrero, MD, MS; Kenneth L. Cameron, PhD, MPH, ATC, FNATA; Jason DeViva, PhD; Ellen Lockard Edens, MD; Leonard E. Egede, MD, MS; Amy Justice, MD, PhD; Stephanie Knudson, MD; Willis H. Lyford, MD; Sarah O. Meadows, PhD; Tamara Schult, PhD, MPH; Eric L. Singman, MD, PhD; Art Wallace, MD, PhD; Elizabeth Waterhouse, MD, FAAN

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.

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.