Cardiology

Hypertension is a global problem that affects poorer countries as much as it affects more affluent ones, a new study suggests.

A cross-sectional study of some 1.2 million adults in low- and middle-income countries (LMICs) found that overall, rates of hypertension were similar across all levels of education and wealth.

The one outlier was Southeast Asia. There, higher levels of education and household wealth were associated with a greater prevalence of hypertension, but the absolute difference was small.

However, the authors of the study caution that hypertension may increasingly affect adults in the lowest socioeconomic groups as LMICs develop economically.

The study is published online  in the Journal of the American College of Cardiology.
 

Assumptions about hypertension are wrong

“We found that the differences in hypertension prevalence between education and household wealth groups were small in most low- and middle-income countries, so the frequent assumption that hypertension mostly affects the wealthiest and most educated groups in low-and middle-income countries appears to be largely untenable,” senior author Pascal Geldsetzer, MD, MPH, PhD, assistant professor of medicine at Stanford (Calif.) University, told this news organization.

High blood pressure is sometimes assumed to be a result of “Westernized” lifestyles characterized by a high intake of calorie-dense foods and salt and low physical activity. As a result, the condition is frequently thought of as mainly afflicting wealthier segments of society in LMICs, which may in part be responsible for the low degree of funding and attention that hypertension in LMICs has received thus far, Dr. Geldsetzer said.

Traditionally, other global health issues, particularly HIV, tuberculosis, and malaria, have received the lion’s share of government funding. Hypertension, thought to be a condition affecting more affluent countries because it is associated with obesity and a sedentary lifestyle, was ignored, he said.

Knowing the socioeconomic gradients associated with hypertension in LMICs and how these may change in the future is important for policy makers, Dr. Geldsetzer added.

Led by Tabea K. Kirschbaum, MD, Heidelberg Institute of Global Health, University of Heidelberg, Germany, the researchers examined hypertension prevalence by education and household wealth from 76 LMICs in 1,211,386 participants and assessed whether the effect was modified by the country’s gross domestic product (GDP).

Their analysis included 76 surveys, of which 58 were World Health Organization Stepwise Approach to Surveillance surveys. The median age of the participants was 40 years, and 58.5% were women.

Overall, hypertension prevalence tended to be similar across all educational and household wealth levels and across countries with lower and higher GDPs, although there were some “negligible” country and regional variations.

Treatment rates with blood pressure–lowering drugs for participants who had hypertension were higher in countries with higher GDPs.

Women were more likely to be taking medication than were men.

In some countries, the proportion of individuals taking blood pressure–lowering medication was higher in wealthier households.

In Southeast Asia, however, there was a strong association found between the prevalence of hypertension and higher household wealth levels. Compared with the least wealthy, the risk ratio for the wealthiest was 1.28 (95% confidence interval, 1.22-1.34). A similar association was found for education levels as well.

Education was negatively associated with hypertension in the Eastern Mediterranean. Rates were higher among men than among women.

In an accompanying editorial, Yashashwi Pokharel, MBBS, MSCR, from Wake Forest School of Medicine, Winston-Salem, N.C., and colleagues write:

“Now that we know that hypertension prevalence is not different in the poorest, the least educated, or the least economically developed countries, compared with their wealthier and educated counterparts, we should develop, test, and implement effective strategies to enhance global equity in hypertension care.”

Dr. Pokharel told this news organization that, despite the study’s limitations including heterogeneous data, measurement techniques, and blood pressure monitor use across countries, the signal is loud and clear.

“We urgently need to focus on turning off the faucet by addressing the major determinants of increasing hypertension burden, including the sociocultural and political determinants,” he said. “In this regard, setting funding priorities by donors for hypertension, capacity building, and testing and scaling effective population level hypertension prevention and treatment strategies, developed together with local stakeholders, can have a long-lasting effect. If we perpetuate the neglect, we will ineffectively spend more time mopping up the floor.”

Dr. Geldsetzer is a Chan Zuckerberg Biohub investigator. Dr. Pokharel reports no relevant financial relationships.

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

Hypertension is a global problem that affects poorer countries as much as it affects more affluent ones, a new study suggests.

A cross-sectional study of some 1.2 million adults in low- and middle-income countries (LMICs) found that overall, rates of hypertension were similar across all levels of education and wealth.

The one outlier was Southeast Asia. There, higher levels of education and household wealth were associated with a greater prevalence of hypertension, but the absolute difference was small.

However, the authors of the study caution that hypertension may increasingly affect adults in the lowest socioeconomic groups as LMICs develop economically.

The study is published online  in the Journal of the American College of Cardiology.
 

Assumptions about hypertension are wrong

“We found that the differences in hypertension prevalence between education and household wealth groups were small in most low- and middle-income countries, so the frequent assumption that hypertension mostly affects the wealthiest and most educated groups in low-and middle-income countries appears to be largely untenable,” senior author Pascal Geldsetzer, MD, MPH, PhD, assistant professor of medicine at Stanford (Calif.) University, told this news organization.

High blood pressure is sometimes assumed to be a result of “Westernized” lifestyles characterized by a high intake of calorie-dense foods and salt and low physical activity. As a result, the condition is frequently thought of as mainly afflicting wealthier segments of society in LMICs, which may in part be responsible for the low degree of funding and attention that hypertension in LMICs has received thus far, Dr. Geldsetzer said.

Traditionally, other global health issues, particularly HIV, tuberculosis, and malaria, have received the lion’s share of government funding. Hypertension, thought to be a condition affecting more affluent countries because it is associated with obesity and a sedentary lifestyle, was ignored, he said.

Knowing the socioeconomic gradients associated with hypertension in LMICs and how these may change in the future is important for policy makers, Dr. Geldsetzer added.

Led by Tabea K. Kirschbaum, MD, Heidelberg Institute of Global Health, University of Heidelberg, Germany, the researchers examined hypertension prevalence by education and household wealth from 76 LMICs in 1,211,386 participants and assessed whether the effect was modified by the country’s gross domestic product (GDP).

Their analysis included 76 surveys, of which 58 were World Health Organization Stepwise Approach to Surveillance surveys. The median age of the participants was 40 years, and 58.5% were women.

Overall, hypertension prevalence tended to be similar across all educational and household wealth levels and across countries with lower and higher GDPs, although there were some “negligible” country and regional variations.

Treatment rates with blood pressure–lowering drugs for participants who had hypertension were higher in countries with higher GDPs.

Women were more likely to be taking medication than were men.

In some countries, the proportion of individuals taking blood pressure–lowering medication was higher in wealthier households.

In Southeast Asia, however, there was a strong association found between the prevalence of hypertension and higher household wealth levels. Compared with the least wealthy, the risk ratio for the wealthiest was 1.28 (95% confidence interval, 1.22-1.34). A similar association was found for education levels as well.

Education was negatively associated with hypertension in the Eastern Mediterranean. Rates were higher among men than among women.

In an accompanying editorial, Yashashwi Pokharel, MBBS, MSCR, from Wake Forest School of Medicine, Winston-Salem, N.C., and colleagues write:

“Now that we know that hypertension prevalence is not different in the poorest, the least educated, or the least economically developed countries, compared with their wealthier and educated counterparts, we should develop, test, and implement effective strategies to enhance global equity in hypertension care.”

Dr. Pokharel told this news organization that, despite the study’s limitations including heterogeneous data, measurement techniques, and blood pressure monitor use across countries, the signal is loud and clear.

“We urgently need to focus on turning off the faucet by addressing the major determinants of increasing hypertension burden, including the sociocultural and political determinants,” he said. “In this regard, setting funding priorities by donors for hypertension, capacity building, and testing and scaling effective population level hypertension prevention and treatment strategies, developed together with local stakeholders, can have a long-lasting effect. If we perpetuate the neglect, we will ineffectively spend more time mopping up the floor.”

Dr. Geldsetzer is a Chan Zuckerberg Biohub investigator. Dr. Pokharel reports no relevant financial relationships.

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

Hypertension is a global problem that affects poorer countries as much as it affects more affluent ones, a new study suggests.

A cross-sectional study of some 1.2 million adults in low- and middle-income countries (LMICs) found that overall, rates of hypertension were similar across all levels of education and wealth.

The one outlier was Southeast Asia. There, higher levels of education and household wealth were associated with a greater prevalence of hypertension, but the absolute difference was small.

However, the authors of the study caution that hypertension may increasingly affect adults in the lowest socioeconomic groups as LMICs develop economically.

The study is published online  in the Journal of the American College of Cardiology.
 

Assumptions about hypertension are wrong

“We found that the differences in hypertension prevalence between education and household wealth groups were small in most low- and middle-income countries, so the frequent assumption that hypertension mostly affects the wealthiest and most educated groups in low-and middle-income countries appears to be largely untenable,” senior author Pascal Geldsetzer, MD, MPH, PhD, assistant professor of medicine at Stanford (Calif.) University, told this news organization.

High blood pressure is sometimes assumed to be a result of “Westernized” lifestyles characterized by a high intake of calorie-dense foods and salt and low physical activity. As a result, the condition is frequently thought of as mainly afflicting wealthier segments of society in LMICs, which may in part be responsible for the low degree of funding and attention that hypertension in LMICs has received thus far, Dr. Geldsetzer said.

Traditionally, other global health issues, particularly HIV, tuberculosis, and malaria, have received the lion’s share of government funding. Hypertension, thought to be a condition affecting more affluent countries because it is associated with obesity and a sedentary lifestyle, was ignored, he said.

Knowing the socioeconomic gradients associated with hypertension in LMICs and how these may change in the future is important for policy makers, Dr. Geldsetzer added.

Led by Tabea K. Kirschbaum, MD, Heidelberg Institute of Global Health, University of Heidelberg, Germany, the researchers examined hypertension prevalence by education and household wealth from 76 LMICs in 1,211,386 participants and assessed whether the effect was modified by the country’s gross domestic product (GDP).

Their analysis included 76 surveys, of which 58 were World Health Organization Stepwise Approach to Surveillance surveys. The median age of the participants was 40 years, and 58.5% were women.

Overall, hypertension prevalence tended to be similar across all educational and household wealth levels and across countries with lower and higher GDPs, although there were some “negligible” country and regional variations.

Treatment rates with blood pressure–lowering drugs for participants who had hypertension were higher in countries with higher GDPs.

Women were more likely to be taking medication than were men.

In some countries, the proportion of individuals taking blood pressure–lowering medication was higher in wealthier households.

In Southeast Asia, however, there was a strong association found between the prevalence of hypertension and higher household wealth levels. Compared with the least wealthy, the risk ratio for the wealthiest was 1.28 (95% confidence interval, 1.22-1.34). A similar association was found for education levels as well.

Education was negatively associated with hypertension in the Eastern Mediterranean. Rates were higher among men than among women.

In an accompanying editorial, Yashashwi Pokharel, MBBS, MSCR, from Wake Forest School of Medicine, Winston-Salem, N.C., and colleagues write:

“Now that we know that hypertension prevalence is not different in the poorest, the least educated, or the least economically developed countries, compared with their wealthier and educated counterparts, we should develop, test, and implement effective strategies to enhance global equity in hypertension care.”

Dr. Pokharel told this news organization that, despite the study’s limitations including heterogeneous data, measurement techniques, and blood pressure monitor use across countries, the signal is loud and clear.

“We urgently need to focus on turning off the faucet by addressing the major determinants of increasing hypertension burden, including the sociocultural and political determinants,” he said. “In this regard, setting funding priorities by donors for hypertension, capacity building, and testing and scaling effective population level hypertension prevention and treatment strategies, developed together with local stakeholders, can have a long-lasting effect. If we perpetuate the neglect, we will ineffectively spend more time mopping up the floor.”

Dr. Geldsetzer is a Chan Zuckerberg Biohub investigator. Dr. Pokharel reports no relevant financial relationships.

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

The relationship between body mass index (BMI) and all-cause mortality in patients with atrial fibrillation (AFib) is U-shaped, with the risk highest in those who are underweight or severely obese and lowest in patients defined simply as obese, a registry analysis suggests. It also showed a similar relationship between BMI and risk for new or worsening heart failure (HF).

Mortality bottomed out at a BMI of about 30-35 kg/m², which suggests that mild obesity was protective, compared even with “normal-weight” or “overweight” BMI. Still, mortality went up sharply from there with rising BMI.

But higher BMI, a surrogate for obesity, apparently didn’t worsen outcomes by itself. The risk for death from any cause at higher obesity levels was found to depend a lot on related risk factors and comorbidities when the analysis controlled for conditions such as diabetes and hypertension.

The findings suggest an inverse relationship between BMI and all-cause mortality in AFib only for patients with BMI less than about 30. They therefore argue against any “obesity paradox” in AFib that posits consistently better survival with increasing levels of obesity, say researchers, based on their analysis of patients with new-onset AFib in the GARFIELD-AF registry.

“It’s common practice now for clinicians to discuss weight within a clinic setting when they’re talking to their AFib patients,” observed Christian Fielder Camm, BM, BCh, University of Oxford (England), and Royal Berkshire NHS Foundation Trust, Reading, England. So studies suggesting an inverse association between BMI and AFib-related risk can be a concern.

Such studies “seem to suggest that once you’ve got AFib, maintaining a high or very high BMI may in some way be protective – which is contrary to what would seem to make sense and certainly contrary to what our results have shown,” Dr. Camm told this news organization.

“I think that having further evidence now to suggest, actually, that greater BMI is associated with a greater risk of all-cause mortality and heart failure helps reframe that discussion at the physician-patient interaction level more clearly, and ensures that we’re able to talk to our patients appropriately about risks associated with BMI and atrial fibrillation,” said Dr. Camm, who is lead author on the analysis published in Open Heart.

“Obesity is a cause of most cardiovascular diseases, but [these] data would support that being overweight or having mild obesity does not increase the risk,” observed Carl J. Lavie, MD, of the John Ochsner Heart and Vascular Institute, New Orleans, La., and the Ochsner Clinical School at the University of Queensland, Brisbane, Australia.

“At a BMI of 40, it’s very important for them to lose weight for their long-term prognosis,” Dr. Lavie noted, but “at a BMI of 30, the important thing would be to prevent further weight gain. And if they could keep their BMI of 30, they should have a good prognosis. Their prognosis would be particularly good if they didn’t gain weight and put themselves in a more extreme obesity class that is associated with worse risk.”

The current analysis, Dr. Lavie said, “is way better than the AFFIRM study,” which yielded an obesity-paradox report on its patients with AFib about a dozen years ago. “It’s got more data, more numbers, more statistical power,” and breaks BMI into more categories.

That previous analysis based on the influential AFFIRM randomized trial separated its 4,060 patients with AFib into normal (BMI, 18.5-25), overweight (BMI, 25-30), and obese (BMI, > 30) categories, per the convention at the time. It concluded that “obese patients with atrial fibrillation appear to have better long-term outcomes than nonobese patients.”
 

Bleeding risk on oral anticoagulants

Also noteworthy in the current analysis, variation in BMI didn’t seem to affect mortality or risk for major bleeding or nonhemorrhagic stroke according to choice of oral anticoagulant – whether a new oral anticoagulant (NOAC) or a vitamin K antagonist (VKA).

“We saw that even in the obese and extremely obese group, all-cause mortality was lower in the group taking NOACs, compared with taking warfarin,” Dr. Camm observed, “which goes against the idea that we would need any kind of dose adjustments for increased BMI.”

Indeed, the report notes, use of NOACs, compared with VKA, was associated with a 23% drop in risk for death among patients who were either normal weight or overweight and also in those who were obese or extremely obese.

Those findings “are basically saying that the NOACs look better than warfarin regardless of weight,” agreed Dr. Lavie. “The problem is that the study is not very powered.”

Whereas the benefits of NOACs, compared to VKA, seem similar for patients with a BMI of 30 or 34, compared with a BMI of 23, for example, “none of the studies has many people with 50 BMI.” Many clinicians “feel uncomfortable giving the same dose of NOAC to somebody who has a 60 BMI,” he said. At least with warfarin, “you can check the INR [international normalized ratio].”

The current analysis included 40,482 patients with recently diagnosed AFib and at least one other stroke risk factor from among the registry’s more than 50,000 patients from 35 countries, enrolled from 2010 to 2016. They were followed for 2 years.

The 703 patients with BMI under 18.5 at AFib diagnosis were classified per World Health Organization definitions as underweight; the 13,095 with BMI 18.5-25 as normal weight; the 15,043 with BMI 25-30 as overweight; the 7,560 with BMI 30-35 as obese; and the 4,081 with BMI above 35 as extremely obese. Their ages averaged 71 years, and 55.6% were men.
 

BMI effects on different outcomes

Relationships between BMI and all-cause mortality and between BMI and new or worsening HF emerged as U-shaped, the risk climbing with both increasing and decreasing BMI. The nadir BMI for risk was about 30 in the case of mortality and about 25 for new or worsening HF.

The all-cause mortality risk rose by 32% for every 5 BMI points lower than a BMI of 30, and by 16% for every 5 BMI points higher than 30, in a partially adjusted analysis. The risk for new or worsening HF rose significantly with increasing but not decreasing BMI, and the reverse was observed for the endpoint of major bleeding.

The effect of BMI on all-cause mortality was “substantially attenuated” when the analysis was further adjusted with “likely mediators of any association between BMI and outcomes,” including hypertension, diabetes, HF, cerebrovascular events, and history of bleeding, Dr. Camm said.

That blunted BMI-mortality relationship, he said, “suggests that a lot of the effect is mediated through relatively traditional risk factors like hypertension and diabetes.”

The 2010 AFFIRM analysis by BMI, Dr. Lavie noted, “didn’t even look at the underweight; they actually threw them out.” Yet, such patients with AFib, who tend to be extremely frail or have chronic diseases or conditions other than the arrhythmia, are common. A take-home of the current study is that “the underweight with atrial fibrillation have a really bad prognosis.”

That message isn’t heard as much, he observed, “but is as important as saying that BMI 30 has the best prognosis. The worst prognosis is with the underweight or the really extreme obese.”

Dr. Camm discloses research funding from the British Heart Foundation. Disclosures for the other authors are in the report. Dr. Lavie has previously disclosed serving as a speaker and consultant for PAI Health and DSM Nutritional Products and is the author of “The Obesity Paradox: When Thinner Means Sicker and Heavier Means Healthier” (Avery, 2014).

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

The relationship between body mass index (BMI) and all-cause mortality in patients with atrial fibrillation (AFib) is U-shaped, with the risk highest in those who are underweight or severely obese and lowest in patients defined simply as obese, a registry analysis suggests. It also showed a similar relationship between BMI and risk for new or worsening heart failure (HF).

Mortality bottomed out at a BMI of about 30-35 kg/m², which suggests that mild obesity was protective, compared even with “normal-weight” or “overweight” BMI. Still, mortality went up sharply from there with rising BMI.

But higher BMI, a surrogate for obesity, apparently didn’t worsen outcomes by itself. The risk for death from any cause at higher obesity levels was found to depend a lot on related risk factors and comorbidities when the analysis controlled for conditions such as diabetes and hypertension.

The findings suggest an inverse relationship between BMI and all-cause mortality in AFib only for patients with BMI less than about 30. They therefore argue against any “obesity paradox” in AFib that posits consistently better survival with increasing levels of obesity, say researchers, based on their analysis of patients with new-onset AFib in the GARFIELD-AF registry.

“It’s common practice now for clinicians to discuss weight within a clinic setting when they’re talking to their AFib patients,” observed Christian Fielder Camm, BM, BCh, University of Oxford (England), and Royal Berkshire NHS Foundation Trust, Reading, England. So studies suggesting an inverse association between BMI and AFib-related risk can be a concern.

Such studies “seem to suggest that once you’ve got AFib, maintaining a high or very high BMI may in some way be protective – which is contrary to what would seem to make sense and certainly contrary to what our results have shown,” Dr. Camm told this news organization.

“I think that having further evidence now to suggest, actually, that greater BMI is associated with a greater risk of all-cause mortality and heart failure helps reframe that discussion at the physician-patient interaction level more clearly, and ensures that we’re able to talk to our patients appropriately about risks associated with BMI and atrial fibrillation,” said Dr. Camm, who is lead author on the analysis published in Open Heart.

“Obesity is a cause of most cardiovascular diseases, but [these] data would support that being overweight or having mild obesity does not increase the risk,” observed Carl J. Lavie, MD, of the John Ochsner Heart and Vascular Institute, New Orleans, La., and the Ochsner Clinical School at the University of Queensland, Brisbane, Australia.

“At a BMI of 40, it’s very important for them to lose weight for their long-term prognosis,” Dr. Lavie noted, but “at a BMI of 30, the important thing would be to prevent further weight gain. And if they could keep their BMI of 30, they should have a good prognosis. Their prognosis would be particularly good if they didn’t gain weight and put themselves in a more extreme obesity class that is associated with worse risk.”

The current analysis, Dr. Lavie said, “is way better than the AFFIRM study,” which yielded an obesity-paradox report on its patients with AFib about a dozen years ago. “It’s got more data, more numbers, more statistical power,” and breaks BMI into more categories.

That previous analysis based on the influential AFFIRM randomized trial separated its 4,060 patients with AFib into normal (BMI, 18.5-25), overweight (BMI, 25-30), and obese (BMI, > 30) categories, per the convention at the time. It concluded that “obese patients with atrial fibrillation appear to have better long-term outcomes than nonobese patients.”
 

Bleeding risk on oral anticoagulants

Also noteworthy in the current analysis, variation in BMI didn’t seem to affect mortality or risk for major bleeding or nonhemorrhagic stroke according to choice of oral anticoagulant – whether a new oral anticoagulant (NOAC) or a vitamin K antagonist (VKA).

“We saw that even in the obese and extremely obese group, all-cause mortality was lower in the group taking NOACs, compared with taking warfarin,” Dr. Camm observed, “which goes against the idea that we would need any kind of dose adjustments for increased BMI.”

Indeed, the report notes, use of NOACs, compared with VKA, was associated with a 23% drop in risk for death among patients who were either normal weight or overweight and also in those who were obese or extremely obese.

Those findings “are basically saying that the NOACs look better than warfarin regardless of weight,” agreed Dr. Lavie. “The problem is that the study is not very powered.”

Whereas the benefits of NOACs, compared to VKA, seem similar for patients with a BMI of 30 or 34, compared with a BMI of 23, for example, “none of the studies has many people with 50 BMI.” Many clinicians “feel uncomfortable giving the same dose of NOAC to somebody who has a 60 BMI,” he said. At least with warfarin, “you can check the INR [international normalized ratio].”

The current analysis included 40,482 patients with recently diagnosed AFib and at least one other stroke risk factor from among the registry’s more than 50,000 patients from 35 countries, enrolled from 2010 to 2016. They were followed for 2 years.

The 703 patients with BMI under 18.5 at AFib diagnosis were classified per World Health Organization definitions as underweight; the 13,095 with BMI 18.5-25 as normal weight; the 15,043 with BMI 25-30 as overweight; the 7,560 with BMI 30-35 as obese; and the 4,081 with BMI above 35 as extremely obese. Their ages averaged 71 years, and 55.6% were men.
 

BMI effects on different outcomes

Relationships between BMI and all-cause mortality and between BMI and new or worsening HF emerged as U-shaped, the risk climbing with both increasing and decreasing BMI. The nadir BMI for risk was about 30 in the case of mortality and about 25 for new or worsening HF.

The all-cause mortality risk rose by 32% for every 5 BMI points lower than a BMI of 30, and by 16% for every 5 BMI points higher than 30, in a partially adjusted analysis. The risk for new or worsening HF rose significantly with increasing but not decreasing BMI, and the reverse was observed for the endpoint of major bleeding.

The effect of BMI on all-cause mortality was “substantially attenuated” when the analysis was further adjusted with “likely mediators of any association between BMI and outcomes,” including hypertension, diabetes, HF, cerebrovascular events, and history of bleeding, Dr. Camm said.

That blunted BMI-mortality relationship, he said, “suggests that a lot of the effect is mediated through relatively traditional risk factors like hypertension and diabetes.”

The 2010 AFFIRM analysis by BMI, Dr. Lavie noted, “didn’t even look at the underweight; they actually threw them out.” Yet, such patients with AFib, who tend to be extremely frail or have chronic diseases or conditions other than the arrhythmia, are common. A take-home of the current study is that “the underweight with atrial fibrillation have a really bad prognosis.”

That message isn’t heard as much, he observed, “but is as important as saying that BMI 30 has the best prognosis. The worst prognosis is with the underweight or the really extreme obese.”

Dr. Camm discloses research funding from the British Heart Foundation. Disclosures for the other authors are in the report. Dr. Lavie has previously disclosed serving as a speaker and consultant for PAI Health and DSM Nutritional Products and is the author of “The Obesity Paradox: When Thinner Means Sicker and Heavier Means Healthier” (Avery, 2014).

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

The relationship between body mass index (BMI) and all-cause mortality in patients with atrial fibrillation (AFib) is U-shaped, with the risk highest in those who are underweight or severely obese and lowest in patients defined simply as obese, a registry analysis suggests. It also showed a similar relationship between BMI and risk for new or worsening heart failure (HF).

Mortality bottomed out at a BMI of about 30-35 kg/m², which suggests that mild obesity was protective, compared even with “normal-weight” or “overweight” BMI. Still, mortality went up sharply from there with rising BMI.

But higher BMI, a surrogate for obesity, apparently didn’t worsen outcomes by itself. The risk for death from any cause at higher obesity levels was found to depend a lot on related risk factors and comorbidities when the analysis controlled for conditions such as diabetes and hypertension.

The findings suggest an inverse relationship between BMI and all-cause mortality in AFib only for patients with BMI less than about 30. They therefore argue against any “obesity paradox” in AFib that posits consistently better survival with increasing levels of obesity, say researchers, based on their analysis of patients with new-onset AFib in the GARFIELD-AF registry.

“It’s common practice now for clinicians to discuss weight within a clinic setting when they’re talking to their AFib patients,” observed Christian Fielder Camm, BM, BCh, University of Oxford (England), and Royal Berkshire NHS Foundation Trust, Reading, England. So studies suggesting an inverse association between BMI and AFib-related risk can be a concern.

Such studies “seem to suggest that once you’ve got AFib, maintaining a high or very high BMI may in some way be protective – which is contrary to what would seem to make sense and certainly contrary to what our results have shown,” Dr. Camm told this news organization.

“I think that having further evidence now to suggest, actually, that greater BMI is associated with a greater risk of all-cause mortality and heart failure helps reframe that discussion at the physician-patient interaction level more clearly, and ensures that we’re able to talk to our patients appropriately about risks associated with BMI and atrial fibrillation,” said Dr. Camm, who is lead author on the analysis published in Open Heart.

“Obesity is a cause of most cardiovascular diseases, but [these] data would support that being overweight or having mild obesity does not increase the risk,” observed Carl J. Lavie, MD, of the John Ochsner Heart and Vascular Institute, New Orleans, La., and the Ochsner Clinical School at the University of Queensland, Brisbane, Australia.

“At a BMI of 40, it’s very important for them to lose weight for their long-term prognosis,” Dr. Lavie noted, but “at a BMI of 30, the important thing would be to prevent further weight gain. And if they could keep their BMI of 30, they should have a good prognosis. Their prognosis would be particularly good if they didn’t gain weight and put themselves in a more extreme obesity class that is associated with worse risk.”

The current analysis, Dr. Lavie said, “is way better than the AFFIRM study,” which yielded an obesity-paradox report on its patients with AFib about a dozen years ago. “It’s got more data, more numbers, more statistical power,” and breaks BMI into more categories.

That previous analysis based on the influential AFFIRM randomized trial separated its 4,060 patients with AFib into normal (BMI, 18.5-25), overweight (BMI, 25-30), and obese (BMI, > 30) categories, per the convention at the time. It concluded that “obese patients with atrial fibrillation appear to have better long-term outcomes than nonobese patients.”
 

Bleeding risk on oral anticoagulants

Also noteworthy in the current analysis, variation in BMI didn’t seem to affect mortality or risk for major bleeding or nonhemorrhagic stroke according to choice of oral anticoagulant – whether a new oral anticoagulant (NOAC) or a vitamin K antagonist (VKA).

“We saw that even in the obese and extremely obese group, all-cause mortality was lower in the group taking NOACs, compared with taking warfarin,” Dr. Camm observed, “which goes against the idea that we would need any kind of dose adjustments for increased BMI.”

Indeed, the report notes, use of NOACs, compared with VKA, was associated with a 23% drop in risk for death among patients who were either normal weight or overweight and also in those who were obese or extremely obese.

Those findings “are basically saying that the NOACs look better than warfarin regardless of weight,” agreed Dr. Lavie. “The problem is that the study is not very powered.”

Whereas the benefits of NOACs, compared to VKA, seem similar for patients with a BMI of 30 or 34, compared with a BMI of 23, for example, “none of the studies has many people with 50 BMI.” Many clinicians “feel uncomfortable giving the same dose of NOAC to somebody who has a 60 BMI,” he said. At least with warfarin, “you can check the INR [international normalized ratio].”

The current analysis included 40,482 patients with recently diagnosed AFib and at least one other stroke risk factor from among the registry’s more than 50,000 patients from 35 countries, enrolled from 2010 to 2016. They were followed for 2 years.

The 703 patients with BMI under 18.5 at AFib diagnosis were classified per World Health Organization definitions as underweight; the 13,095 with BMI 18.5-25 as normal weight; the 15,043 with BMI 25-30 as overweight; the 7,560 with BMI 30-35 as obese; and the 4,081 with BMI above 35 as extremely obese. Their ages averaged 71 years, and 55.6% were men.
 

BMI effects on different outcomes

Relationships between BMI and all-cause mortality and between BMI and new or worsening HF emerged as U-shaped, the risk climbing with both increasing and decreasing BMI. The nadir BMI for risk was about 30 in the case of mortality and about 25 for new or worsening HF.

The all-cause mortality risk rose by 32% for every 5 BMI points lower than a BMI of 30, and by 16% for every 5 BMI points higher than 30, in a partially adjusted analysis. The risk for new or worsening HF rose significantly with increasing but not decreasing BMI, and the reverse was observed for the endpoint of major bleeding.

The effect of BMI on all-cause mortality was “substantially attenuated” when the analysis was further adjusted with “likely mediators of any association between BMI and outcomes,” including hypertension, diabetes, HF, cerebrovascular events, and history of bleeding, Dr. Camm said.

That blunted BMI-mortality relationship, he said, “suggests that a lot of the effect is mediated through relatively traditional risk factors like hypertension and diabetes.”

The 2010 AFFIRM analysis by BMI, Dr. Lavie noted, “didn’t even look at the underweight; they actually threw them out.” Yet, such patients with AFib, who tend to be extremely frail or have chronic diseases or conditions other than the arrhythmia, are common. A take-home of the current study is that “the underweight with atrial fibrillation have a really bad prognosis.”

That message isn’t heard as much, he observed, “but is as important as saying that BMI 30 has the best prognosis. The worst prognosis is with the underweight or the really extreme obese.”

Dr. Camm discloses research funding from the British Heart Foundation. Disclosures for the other authors are in the report. Dr. Lavie has previously disclosed serving as a speaker and consultant for PAI Health and DSM Nutritional Products and is the author of “The Obesity Paradox: When Thinner Means Sicker and Heavier Means Healthier” (Avery, 2014).

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

Here’s another vote for less screen time. Using a smartphone application to track blood pressure won’t lead to any greater reduction in BP than self-monitoring the old-fashioned way, a new study finds.

“By itself, standard self-measured blood pressure (SMBP) has minimal effect on BP control,” wrote lead author Mark J. Pletcher, MD, of the University of California, San Francisco, and colleagues in JAMA Internal Medicine. “To improve BP control, SMBP must be accompanied by patient feedback, counseling, or other cointerventions, and the BP-lowering effects of SMBP appear to be proportional to the intensity of the cointervention.”

While this is known, higher-intensity cointerventions demand both money and time, prompting development of new devices that link with smartphone apps, they continued.

In the prospective randomized trial, patients with hypertension were randomly assigned to self-measure their blood pressure using a standard device that paired with a connected smartphone application or to self-measure their blood pressure with a standard device alone. Both groups achieved about an 11 mm Hg reduction in systolic BP over 6 months, reported similar levels of satisfaction with the monitoring process, and shared their readings with their physicians with similar frequency.

Methods

Dr. Pletcher and colleagues enrolled 2,101 adults who self-reported a systolic BP greater than 145 mm Hg and expressed a commitment to reduce their BP by at least 10 points in their trial. The participants, who were generally middle-aged or older, were randomized in a 1:1 ratio to monitor their BP using standard SMBP or “enhanced” SMBP. The standard group used the OMRON BP monitor alone, while the enhanced group used the same BP monitor coupled with the OMRON Connect smartphone app.

After 6 months of follow-up for each patient, mean BP reduction from baseline in the standard group was 10.6 mm Hg, compared with 10.7 mm Hg in the enhanced group, a nonsignificant difference (P = .81). While slightly more patients in the enhanced group achieved a BP lower than 140/90 mm Hg (32% vs. 29%; odds ratio, 1.17; 95% confidence interval, 1.01-1.34), this trend did not extend below the 130/80 mm Hg threshold.

Other secondary outcomes were also similar between groups. For example, 70% of participants in the enhanced group said they would recommend their SMBP process to a friend, compared with 69% of participants who followed the standard monitoring approach. The smartphone app had little impact on sharing readings with physicians, either, based on a 44% share rate in the enhanced group versus 48% in the standard group (P = .22).

“Enhanced SMBP does not provide any additional reduction in BP,” the investigators concluded.

New devices that link with smartphone apps, like the one used in this trial, “transmit BP measurements via wireless connection to the patient’s smartphone, where they are processed in a smartphone application to support tracking, visualization, interpretation, reminders to measure BP and/or take medications; recommendations for lifestyle interventions, medication adherence, or to discuss their BP with their clinician; and communications (for example, emailing a summary to a family member or clinician),” the researchers explained. While these devices are “only slightly more expensive than standard SMBP devices,” their relative efficacy over standard SMBP is “unclear.”

Findings can likely be extrapolated to other apps

Although the trial evaluated just one smartphone app, Dr. Pletcher suggested that the findings can likely be extrapolated to other apps.

“Most basic BP-tracking apps have some version or subset of the same essential functionality,” he said, in an interview. “My guess is that apps that meet this description without some substantially different technology or feature would likely show the same basic results as we did.”

Making a similar remark, Matthew Jung, MD, of Keck Medicine of USC, Los Angeles, stated that the findings can be “reasonably extrapolated” to other BP-tracking apps with similar functionality “if we put aside the study’s issues with power.”

When it comes to smartphone apps, active engagement is needed to achieve greater impacts on blood pressure, Dr. Pletcher said, but “there is so much competition for people’s attention on their phone that it is hard to maintain active engagement with any health-related app for long.”

Still, Dr. Pletcher hasn’t given up on biometric apps, noting that “with the right technology and connectivity and user experience (for both patient and clinician), they still could be game-changing for managing chronic conditions like hypertension.”

To this end, he and his colleagues are exploring technologies to passively monitor health-related measurements like BP, potentially sidestepping the pitfall of active engagement.

Dr. Jung said the study is noteworthy for several reasons, including its large size, similar level of comfort with technology reported by both groups, and representation of Black and Hispanic participants, who accounted for almost one-third of the population.
 

Study limitations

Dr. Jung pointed out several study limitations, including the lack of standardized measurement of BP, which left more than one-third of patients unevaluated via chart review, as well as gaps in usage data, such as that one-third of the participants never confirmed receipt of a device, and less than half of the enhanced group reported using the smartphone application.

These limitations “may have detracted from its ability to identify the true efficacy of an enhanced app-based BP tracking device,” he said. “In contrast, each of these issues also helped us get a better picture for how well these devices may work in the real world.”

Dr. Jung also commented on the duration of the study, noting that only 10 weeks passed, on average, from baseline to follow-up BP measurement, which “may not have been sufficient for a possible difference between enhanced and standard BP monitoring to become noticeable.”

“This may be especially important when taking into consideration the time required to mail the devices out to patients, for patients to become familiar with usage of the devices, and for them to start using the devices in a meaningful way,” he added.

The study was supported the Patient-Centered Outcomes Research Institute, the American Medical Association, and the American Heart Association. The investigators disclosed additional relationships with Pfizer, Bristol Myers Squibb, and Novartis. Dr. Jung, who was not involved in the study, disclosed no relevant conflicts of interest.

Here’s another vote for less screen time. Using a smartphone application to track blood pressure won’t lead to any greater reduction in BP than self-monitoring the old-fashioned way, a new study finds.

“By itself, standard self-measured blood pressure (SMBP) has minimal effect on BP control,” wrote lead author Mark J. Pletcher, MD, of the University of California, San Francisco, and colleagues in JAMA Internal Medicine. “To improve BP control, SMBP must be accompanied by patient feedback, counseling, or other cointerventions, and the BP-lowering effects of SMBP appear to be proportional to the intensity of the cointervention.”

While this is known, higher-intensity cointerventions demand both money and time, prompting development of new devices that link with smartphone apps, they continued.

In the prospective randomized trial, patients with hypertension were randomly assigned to self-measure their blood pressure using a standard device that paired with a connected smartphone application or to self-measure their blood pressure with a standard device alone. Both groups achieved about an 11 mm Hg reduction in systolic BP over 6 months, reported similar levels of satisfaction with the monitoring process, and shared their readings with their physicians with similar frequency.

Methods

Dr. Pletcher and colleagues enrolled 2,101 adults who self-reported a systolic BP greater than 145 mm Hg and expressed a commitment to reduce their BP by at least 10 points in their trial. The participants, who were generally middle-aged or older, were randomized in a 1:1 ratio to monitor their BP using standard SMBP or “enhanced” SMBP. The standard group used the OMRON BP monitor alone, while the enhanced group used the same BP monitor coupled with the OMRON Connect smartphone app.

After 6 months of follow-up for each patient, mean BP reduction from baseline in the standard group was 10.6 mm Hg, compared with 10.7 mm Hg in the enhanced group, a nonsignificant difference (P = .81). While slightly more patients in the enhanced group achieved a BP lower than 140/90 mm Hg (32% vs. 29%; odds ratio, 1.17; 95% confidence interval, 1.01-1.34), this trend did not extend below the 130/80 mm Hg threshold.

Other secondary outcomes were also similar between groups. For example, 70% of participants in the enhanced group said they would recommend their SMBP process to a friend, compared with 69% of participants who followed the standard monitoring approach. The smartphone app had little impact on sharing readings with physicians, either, based on a 44% share rate in the enhanced group versus 48% in the standard group (P = .22).

“Enhanced SMBP does not provide any additional reduction in BP,” the investigators concluded.

New devices that link with smartphone apps, like the one used in this trial, “transmit BP measurements via wireless connection to the patient’s smartphone, where they are processed in a smartphone application to support tracking, visualization, interpretation, reminders to measure BP and/or take medications; recommendations for lifestyle interventions, medication adherence, or to discuss their BP with their clinician; and communications (for example, emailing a summary to a family member or clinician),” the researchers explained. While these devices are “only slightly more expensive than standard SMBP devices,” their relative efficacy over standard SMBP is “unclear.”

Findings can likely be extrapolated to other apps

Although the trial evaluated just one smartphone app, Dr. Pletcher suggested that the findings can likely be extrapolated to other apps.

“Most basic BP-tracking apps have some version or subset of the same essential functionality,” he said, in an interview. “My guess is that apps that meet this description without some substantially different technology or feature would likely show the same basic results as we did.”

Making a similar remark, Matthew Jung, MD, of Keck Medicine of USC, Los Angeles, stated that the findings can be “reasonably extrapolated” to other BP-tracking apps with similar functionality “if we put aside the study’s issues with power.”

When it comes to smartphone apps, active engagement is needed to achieve greater impacts on blood pressure, Dr. Pletcher said, but “there is so much competition for people’s attention on their phone that it is hard to maintain active engagement with any health-related app for long.”

Still, Dr. Pletcher hasn’t given up on biometric apps, noting that “with the right technology and connectivity and user experience (for both patient and clinician), they still could be game-changing for managing chronic conditions like hypertension.”

To this end, he and his colleagues are exploring technologies to passively monitor health-related measurements like BP, potentially sidestepping the pitfall of active engagement.

Dr. Jung said the study is noteworthy for several reasons, including its large size, similar level of comfort with technology reported by both groups, and representation of Black and Hispanic participants, who accounted for almost one-third of the population.
 

Study limitations

Dr. Jung pointed out several study limitations, including the lack of standardized measurement of BP, which left more than one-third of patients unevaluated via chart review, as well as gaps in usage data, such as that one-third of the participants never confirmed receipt of a device, and less than half of the enhanced group reported using the smartphone application.

These limitations “may have detracted from its ability to identify the true efficacy of an enhanced app-based BP tracking device,” he said. “In contrast, each of these issues also helped us get a better picture for how well these devices may work in the real world.”

Dr. Jung also commented on the duration of the study, noting that only 10 weeks passed, on average, from baseline to follow-up BP measurement, which “may not have been sufficient for a possible difference between enhanced and standard BP monitoring to become noticeable.”

“This may be especially important when taking into consideration the time required to mail the devices out to patients, for patients to become familiar with usage of the devices, and for them to start using the devices in a meaningful way,” he added.

The study was supported the Patient-Centered Outcomes Research Institute, the American Medical Association, and the American Heart Association. The investigators disclosed additional relationships with Pfizer, Bristol Myers Squibb, and Novartis. Dr. Jung, who was not involved in the study, disclosed no relevant conflicts of interest.

Here’s another vote for less screen time. Using a smartphone application to track blood pressure won’t lead to any greater reduction in BP than self-monitoring the old-fashioned way, a new study finds.

“By itself, standard self-measured blood pressure (SMBP) has minimal effect on BP control,” wrote lead author Mark J. Pletcher, MD, of the University of California, San Francisco, and colleagues in JAMA Internal Medicine. “To improve BP control, SMBP must be accompanied by patient feedback, counseling, or other cointerventions, and the BP-lowering effects of SMBP appear to be proportional to the intensity of the cointervention.”

While this is known, higher-intensity cointerventions demand both money and time, prompting development of new devices that link with smartphone apps, they continued.

In the prospective randomized trial, patients with hypertension were randomly assigned to self-measure their blood pressure using a standard device that paired with a connected smartphone application or to self-measure their blood pressure with a standard device alone. Both groups achieved about an 11 mm Hg reduction in systolic BP over 6 months, reported similar levels of satisfaction with the monitoring process, and shared their readings with their physicians with similar frequency.

Methods

Dr. Pletcher and colleagues enrolled 2,101 adults who self-reported a systolic BP greater than 145 mm Hg and expressed a commitment to reduce their BP by at least 10 points in their trial. The participants, who were generally middle-aged or older, were randomized in a 1:1 ratio to monitor their BP using standard SMBP or “enhanced” SMBP. The standard group used the OMRON BP monitor alone, while the enhanced group used the same BP monitor coupled with the OMRON Connect smartphone app.

After 6 months of follow-up for each patient, mean BP reduction from baseline in the standard group was 10.6 mm Hg, compared with 10.7 mm Hg in the enhanced group, a nonsignificant difference (P = .81). While slightly more patients in the enhanced group achieved a BP lower than 140/90 mm Hg (32% vs. 29%; odds ratio, 1.17; 95% confidence interval, 1.01-1.34), this trend did not extend below the 130/80 mm Hg threshold.

Other secondary outcomes were also similar between groups. For example, 70% of participants in the enhanced group said they would recommend their SMBP process to a friend, compared with 69% of participants who followed the standard monitoring approach. The smartphone app had little impact on sharing readings with physicians, either, based on a 44% share rate in the enhanced group versus 48% in the standard group (P = .22).

“Enhanced SMBP does not provide any additional reduction in BP,” the investigators concluded.

New devices that link with smartphone apps, like the one used in this trial, “transmit BP measurements via wireless connection to the patient’s smartphone, where they are processed in a smartphone application to support tracking, visualization, interpretation, reminders to measure BP and/or take medications; recommendations for lifestyle interventions, medication adherence, or to discuss their BP with their clinician; and communications (for example, emailing a summary to a family member or clinician),” the researchers explained. While these devices are “only slightly more expensive than standard SMBP devices,” their relative efficacy over standard SMBP is “unclear.”

Findings can likely be extrapolated to other apps

Although the trial evaluated just one smartphone app, Dr. Pletcher suggested that the findings can likely be extrapolated to other apps.

“Most basic BP-tracking apps have some version or subset of the same essential functionality,” he said, in an interview. “My guess is that apps that meet this description without some substantially different technology or feature would likely show the same basic results as we did.”

Making a similar remark, Matthew Jung, MD, of Keck Medicine of USC, Los Angeles, stated that the findings can be “reasonably extrapolated” to other BP-tracking apps with similar functionality “if we put aside the study’s issues with power.”

When it comes to smartphone apps, active engagement is needed to achieve greater impacts on blood pressure, Dr. Pletcher said, but “there is so much competition for people’s attention on their phone that it is hard to maintain active engagement with any health-related app for long.”

Still, Dr. Pletcher hasn’t given up on biometric apps, noting that “with the right technology and connectivity and user experience (for both patient and clinician), they still could be game-changing for managing chronic conditions like hypertension.”

To this end, he and his colleagues are exploring technologies to passively monitor health-related measurements like BP, potentially sidestepping the pitfall of active engagement.

Dr. Jung said the study is noteworthy for several reasons, including its large size, similar level of comfort with technology reported by both groups, and representation of Black and Hispanic participants, who accounted for almost one-third of the population.
 

Study limitations

Dr. Jung pointed out several study limitations, including the lack of standardized measurement of BP, which left more than one-third of patients unevaluated via chart review, as well as gaps in usage data, such as that one-third of the participants never confirmed receipt of a device, and less than half of the enhanced group reported using the smartphone application.

These limitations “may have detracted from its ability to identify the true efficacy of an enhanced app-based BP tracking device,” he said. “In contrast, each of these issues also helped us get a better picture for how well these devices may work in the real world.”

Dr. Jung also commented on the duration of the study, noting that only 10 weeks passed, on average, from baseline to follow-up BP measurement, which “may not have been sufficient for a possible difference between enhanced and standard BP monitoring to become noticeable.”

“This may be especially important when taking into consideration the time required to mail the devices out to patients, for patients to become familiar with usage of the devices, and for them to start using the devices in a meaningful way,” he added.

The study was supported the Patient-Centered Outcomes Research Institute, the American Medical Association, and the American Heart Association. The investigators disclosed additional relationships with Pfizer, Bristol Myers Squibb, and Novartis. Dr. Jung, who was not involved in the study, disclosed no relevant conflicts of interest.

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