Cardiology

Nordic walking was significantly better at improving functional capacity than were moderate- to vigorous-intensity continuous training and high-intensity interval training (HIIT) in a single-center randomized controlled trial.

Participants who did Nordic walking saw better improvements in functional capacity, measured via the 6-minute walk test distances, than did individuals doing either of the other exercise strategies (interaction effect, P = .010).

amriphoto/E+/Getty Images

From baseline to 26 weeks, the average changes in 6-minute walk test distance were 55.6 m and 59.9 m for moderate- to vigorous-intensity continuous training and HIIT, respectively, but 94.2 m in the Nordic walking group, reported Tasuku Terada, PhD, University of Ottawa Heart Institute, Ontario, and colleagues.

Previous research looked at these results at the end of a 12-week supervised exercise intervention and showed that although all three strategies were safe and had positive effects on physical and mental health in these patients, Nordic walking had a better effect in raising the 6-minute walk test scores than did moderate- to vigorous-intensity continuous training and HIIT, the researchers noted.

“This study is a follow-up on the previous study to show that Nordic walking had greater sustained effects even after the observation phase,” from 12 to 26 weeks, Dr. Terada said in an interview.

“Exercise is a medicine to improve the health of patients, but unfortunately, sometimes it is not as often utilized,” Dr. Terada told this news organization.

Giving patients additional exercise modalities is beneficial because not everyone likes HIIT workouts or long continuous walking, Dr. Terada said. “So, if that’s the case, we can recommend Nordic walking as another type of exercise and expect a similar or good impact in functional capacity.”

The results were published online in the Canadian Journal of Cardiology.

“I think it honestly supports the idea that, as many other studies show, physical activity and exercise improve functional capacity no matter how you measure it and have beneficial effects on mental health and quality of life and particularly depression as well,” Carl “Chip” Lavie, MD, University of Queensland, New Orleans, who coauthored an editorial accompanying the publication, said in an interview.

“Clinicians need to get patients to do the type of exercise that they are going to do. A lot of people ask what’s the best exercise, and the best exercise is one that the person is going to do,” Dr. Lavie said.

Nordic walking is an enhanced form of walking that engages the upper and lower body musculatures, noted Dr. Lavie.

“With regard to Nordic walking, I think that now adds an additional option that many people wouldn’t have thought about. For many of the patients that have issues that are musculoskeletal, issues with posture, gait, or balance, using the poles can be a way to allow them to walk much better and increase their speed, and as they do that, they become fitter,” Dr. Lavie continued.

Moreover, these findings support the use of Nordic walking in cardiac rehabilitation programs, the editorialists noted.
 

Cardiac rehabilitation

The study examined patients with coronary artery disease who underwent cardiac revascularization. They were then referred by their physicians to cardiac rehabilitation.

Participants were randomly assigned to one of the following intervention groups: Nordic walking (n = 30), moderate- to vigorous-intensity continuous training (n = 27), and HIIT (n = 29) for a 12-week period. There was then an additional 14-week observation period after the exercise program. Mean age was 60 years across the intervention groups.

The research team analyzed the extent of participants’ depression with Beck Depression Inventory–II, quality of life with Short Form–36 and HeartQoL, and functional capacity with a 6-minute walk test. They assessed functional capacity, depression, and quality of life at baseline, 12 weeks, and 26 weeks.

Using linear mixed models with extended measures, the study authors evaluated sustained effects, which were between week 12 and week 26, and prolonged effects, which were between baseline and week 26.

From baseline to 26 weeks, participants saw significantly better outcomes in quality of life, depression symptoms, and 6-minute walk test (P < .05).

Physical quality of life and 6-minute walk test distance rose significantly between weeks 12 and 26 (P < .05).

Notably, at week 26, all training groups achieved the minimal clinical threshold difference of 54 m, although participants in the Nordic walking cohort demonstrated significantly greater improvement in outcomes.

Other data indicated the following:

• From baseline to week 12, physical activity levels rose significantly, and this improvement was sustained through the observation period.
• During the observation period, mental component summary significantly declined while physical component summary outcomes improved.
• After completion of cardiac rehabilitation, functional capacity continued to increase significantly.
• Moderate- to vigorous-intensity continuous training, HIIT, and Nordic walking had positive and significant prolonged effects on depression symptoms and general and disease-specific quality of life, with no differences in the extent of improvements between exercise types.

Some limitations of the study include the fact that women comprised a small portion of the study group, which limits the generalizability of these data, the cohort was recruited from a single medical facility, and there was a short follow-up time, the researchers noted.

“Further research is warranted to investigate the efficacy and integration of Nordic walking into home-based exercise after supervised cardiac rehabilitation for maintenance of physical and mental health,” the editorialists concluded.

Dr. Terada, Dr. Lavie, and Dr. Taylor reported no relevant financial relationships.

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

Nordic walking was significantly better at improving functional capacity than were moderate- to vigorous-intensity continuous training and high-intensity interval training (HIIT) in a single-center randomized controlled trial.

Participants who did Nordic walking saw better improvements in functional capacity, measured via the 6-minute walk test distances, than did individuals doing either of the other exercise strategies (interaction effect, P = .010).

amriphoto/E+/Getty Images

From baseline to 26 weeks, the average changes in 6-minute walk test distance were 55.6 m and 59.9 m for moderate- to vigorous-intensity continuous training and HIIT, respectively, but 94.2 m in the Nordic walking group, reported Tasuku Terada, PhD, University of Ottawa Heart Institute, Ontario, and colleagues.

Previous research looked at these results at the end of a 12-week supervised exercise intervention and showed that although all three strategies were safe and had positive effects on physical and mental health in these patients, Nordic walking had a better effect in raising the 6-minute walk test scores than did moderate- to vigorous-intensity continuous training and HIIT, the researchers noted.

“This study is a follow-up on the previous study to show that Nordic walking had greater sustained effects even after the observation phase,” from 12 to 26 weeks, Dr. Terada said in an interview.

“Exercise is a medicine to improve the health of patients, but unfortunately, sometimes it is not as often utilized,” Dr. Terada told this news organization.

Giving patients additional exercise modalities is beneficial because not everyone likes HIIT workouts or long continuous walking, Dr. Terada said. “So, if that’s the case, we can recommend Nordic walking as another type of exercise and expect a similar or good impact in functional capacity.”

The results were published online in the Canadian Journal of Cardiology.

“I think it honestly supports the idea that, as many other studies show, physical activity and exercise improve functional capacity no matter how you measure it and have beneficial effects on mental health and quality of life and particularly depression as well,” Carl “Chip” Lavie, MD, University of Queensland, New Orleans, who coauthored an editorial accompanying the publication, said in an interview.

“Clinicians need to get patients to do the type of exercise that they are going to do. A lot of people ask what’s the best exercise, and the best exercise is one that the person is going to do,” Dr. Lavie said.

Nordic walking is an enhanced form of walking that engages the upper and lower body musculatures, noted Dr. Lavie.

“With regard to Nordic walking, I think that now adds an additional option that many people wouldn’t have thought about. For many of the patients that have issues that are musculoskeletal, issues with posture, gait, or balance, using the poles can be a way to allow them to walk much better and increase their speed, and as they do that, they become fitter,” Dr. Lavie continued.

Moreover, these findings support the use of Nordic walking in cardiac rehabilitation programs, the editorialists noted.
 

Cardiac rehabilitation

The study examined patients with coronary artery disease who underwent cardiac revascularization. They were then referred by their physicians to cardiac rehabilitation.

Participants were randomly assigned to one of the following intervention groups: Nordic walking (n = 30), moderate- to vigorous-intensity continuous training (n = 27), and HIIT (n = 29) for a 12-week period. There was then an additional 14-week observation period after the exercise program. Mean age was 60 years across the intervention groups.

The research team analyzed the extent of participants’ depression with Beck Depression Inventory–II, quality of life with Short Form–36 and HeartQoL, and functional capacity with a 6-minute walk test. They assessed functional capacity, depression, and quality of life at baseline, 12 weeks, and 26 weeks.

Using linear mixed models with extended measures, the study authors evaluated sustained effects, which were between week 12 and week 26, and prolonged effects, which were between baseline and week 26.

From baseline to 26 weeks, participants saw significantly better outcomes in quality of life, depression symptoms, and 6-minute walk test (P < .05).

Physical quality of life and 6-minute walk test distance rose significantly between weeks 12 and 26 (P < .05).

Notably, at week 26, all training groups achieved the minimal clinical threshold difference of 54 m, although participants in the Nordic walking cohort demonstrated significantly greater improvement in outcomes.

Other data indicated the following:

• From baseline to week 12, physical activity levels rose significantly, and this improvement was sustained through the observation period.
• During the observation period, mental component summary significantly declined while physical component summary outcomes improved.
• After completion of cardiac rehabilitation, functional capacity continued to increase significantly.
• Moderate- to vigorous-intensity continuous training, HIIT, and Nordic walking had positive and significant prolonged effects on depression symptoms and general and disease-specific quality of life, with no differences in the extent of improvements between exercise types.

Some limitations of the study include the fact that women comprised a small portion of the study group, which limits the generalizability of these data, the cohort was recruited from a single medical facility, and there was a short follow-up time, the researchers noted.

“Further research is warranted to investigate the efficacy and integration of Nordic walking into home-based exercise after supervised cardiac rehabilitation for maintenance of physical and mental health,” the editorialists concluded.

Dr. Terada, Dr. Lavie, and Dr. Taylor reported no relevant financial relationships.

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

Nordic walking was significantly better at improving functional capacity than were moderate- to vigorous-intensity continuous training and high-intensity interval training (HIIT) in a single-center randomized controlled trial.

Participants who did Nordic walking saw better improvements in functional capacity, measured via the 6-minute walk test distances, than did individuals doing either of the other exercise strategies (interaction effect, P = .010).

amriphoto/E+/Getty Images

From baseline to 26 weeks, the average changes in 6-minute walk test distance were 55.6 m and 59.9 m for moderate- to vigorous-intensity continuous training and HIIT, respectively, but 94.2 m in the Nordic walking group, reported Tasuku Terada, PhD, University of Ottawa Heart Institute, Ontario, and colleagues.

Previous research looked at these results at the end of a 12-week supervised exercise intervention and showed that although all three strategies were safe and had positive effects on physical and mental health in these patients, Nordic walking had a better effect in raising the 6-minute walk test scores than did moderate- to vigorous-intensity continuous training and HIIT, the researchers noted.

“This study is a follow-up on the previous study to show that Nordic walking had greater sustained effects even after the observation phase,” from 12 to 26 weeks, Dr. Terada said in an interview.

“Exercise is a medicine to improve the health of patients, but unfortunately, sometimes it is not as often utilized,” Dr. Terada told this news organization.

Giving patients additional exercise modalities is beneficial because not everyone likes HIIT workouts or long continuous walking, Dr. Terada said. “So, if that’s the case, we can recommend Nordic walking as another type of exercise and expect a similar or good impact in functional capacity.”

The results were published online in the Canadian Journal of Cardiology.

“I think it honestly supports the idea that, as many other studies show, physical activity and exercise improve functional capacity no matter how you measure it and have beneficial effects on mental health and quality of life and particularly depression as well,” Carl “Chip” Lavie, MD, University of Queensland, New Orleans, who coauthored an editorial accompanying the publication, said in an interview.

“Clinicians need to get patients to do the type of exercise that they are going to do. A lot of people ask what’s the best exercise, and the best exercise is one that the person is going to do,” Dr. Lavie said.

Nordic walking is an enhanced form of walking that engages the upper and lower body musculatures, noted Dr. Lavie.

“With regard to Nordic walking, I think that now adds an additional option that many people wouldn’t have thought about. For many of the patients that have issues that are musculoskeletal, issues with posture, gait, or balance, using the poles can be a way to allow them to walk much better and increase their speed, and as they do that, they become fitter,” Dr. Lavie continued.

Moreover, these findings support the use of Nordic walking in cardiac rehabilitation programs, the editorialists noted.
 

Cardiac rehabilitation

The study examined patients with coronary artery disease who underwent cardiac revascularization. They were then referred by their physicians to cardiac rehabilitation.

Participants were randomly assigned to one of the following intervention groups: Nordic walking (n = 30), moderate- to vigorous-intensity continuous training (n = 27), and HIIT (n = 29) for a 12-week period. There was then an additional 14-week observation period after the exercise program. Mean age was 60 years across the intervention groups.

The research team analyzed the extent of participants’ depression with Beck Depression Inventory–II, quality of life with Short Form–36 and HeartQoL, and functional capacity with a 6-minute walk test. They assessed functional capacity, depression, and quality of life at baseline, 12 weeks, and 26 weeks.

Using linear mixed models with extended measures, the study authors evaluated sustained effects, which were between week 12 and week 26, and prolonged effects, which were between baseline and week 26.

From baseline to 26 weeks, participants saw significantly better outcomes in quality of life, depression symptoms, and 6-minute walk test (P < .05).

Physical quality of life and 6-minute walk test distance rose significantly between weeks 12 and 26 (P < .05).

Notably, at week 26, all training groups achieved the minimal clinical threshold difference of 54 m, although participants in the Nordic walking cohort demonstrated significantly greater improvement in outcomes.

Other data indicated the following:

• From baseline to week 12, physical activity levels rose significantly, and this improvement was sustained through the observation period.
• During the observation period, mental component summary significantly declined while physical component summary outcomes improved.
• After completion of cardiac rehabilitation, functional capacity continued to increase significantly.
• Moderate- to vigorous-intensity continuous training, HIIT, and Nordic walking had positive and significant prolonged effects on depression symptoms and general and disease-specific quality of life, with no differences in the extent of improvements between exercise types.

Some limitations of the study include the fact that women comprised a small portion of the study group, which limits the generalizability of these data, the cohort was recruited from a single medical facility, and there was a short follow-up time, the researchers noted.

“Further research is warranted to investigate the efficacy and integration of Nordic walking into home-based exercise after supervised cardiac rehabilitation for maintenance of physical and mental health,” the editorialists concluded.

Dr. Terada, Dr. Lavie, and Dr. Taylor reported no relevant financial relationships.

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

Cardiac rehabilitation (CR) started 2 weeks after sternotomy for a cardiac procedure was noninferior to usual care, in which CR starts 6 weeks after the procedure, with a greater improvement in 6-minute walk test outcomes, a randomized study suggests.

There was no difference in adverse events between groups, although the researchers pointed out that the study was not powered specifically for safety outcomes.

“Cardiac surgical techniques have evolved significantly over the last 60 years, leading to improved survival and shorter hospital stays,” Gordon McGregor, PhD, University of Warwick, Coventry, England, told this news organization. “However, sternal precautions and rehabilitation guidelines have not changed accordingly. There has never been a guideline based on empirical evidence to support rehabilitation professionals working with cardiac surgery patients after median sternotomy.”

“By adopting a progressive individualized approach,” he added, “cardiac surgery sternotomy patients can start cardiac rehabilitation up to 4 weeks earlier than current guidance, and thus potentially complete their recovery sooner.”

Results of the Early Initiation of Poststernotomy Cardiac Rehabilitation Exercise Training study were published online  in JAMA Cardiology.

In the study, Dr. McGregor and colleagues randomly assigned 158 patients (mean age, 63 years; 84% men) to 8 weeks of 1-hour, twice-weekly supervised CR exercise training starting 2 weeks (early) or 6 weeks (usual care) after sternotomy.

The primary outcome was change in the 6-minute walk test distance from baseline to 10 or 14 weeks after sternotomy, respectively, and 12 months after randomization.

For usual care, training followed British standards: a warm-up with light cardiovascular and mobility exercises; continuous moderate-intensity cardiovascular exercise; a cooldown; functional exercises using resistance machines and free weights; and upper-body exercises designed to prevent sternal and leg wound pain and complications.

There are no specific outpatient CR exercise guidelines for early CR, so study participants followed an individualized exercise program for the first 2-3 weeks after surgery, starting with light mobility and moderate-intensity cardiovascular training when they could do those exercises with minimal discomfort. They then progressed to current British standards, as per usual care.

Forty patients were lost to follow-up, largely because of the pandemic; about half the participants in each group were included in the primary analysis.

Early CR was not inferior to usual care, the authors wrote. The mean change in 6-minute walk distance from baseline to completion of CR was 28 meters greater in the early group than in the usual-care group, and was achieved 4 weeks earlier in the recovery timeline.

Secondary outcomes (functional fitness and quality of life) improved in both groups and between-group differences were not statistically significant, indicating the noninferiority of early CR, the authors noted.
 

Safety not proven

There were more adverse events in the early group than in the usual-care group (58 vs. 46) and more serious adverse events (18 vs. 14), but fewer deaths (1 vs. 2).

Although there was no between-group difference in the likelihood of having an adverse or serious adverse event, Dr. McGregor acknowledged that the study was “not powered specifically for safety outcomes.” He added that “there is the potential to run a very large multination definitive superiority [randomized, controlled trial] with safety as the primary outcome; however, a very large sample would be required.”

Meanwhile, he said, “we can say with some degree of certainty that early CR was likely as safe as usual-care CR. In the United Kingdom, we work closely with the British Association for Cardiovascular Prevention and Rehabilitation and the Association of Chartered Physiotherapists in Cardiovascular Rehabilitation, who will incorporate our findings in their guidelines and training courses.”
 

Questions remain

Asked to comment on the study, John Larry, MD, medical director of cardiology and cardiac rehabilitation at the Ohio State University Wexner Medical Center East Hospital, Columbus, said: “For those under time pressure to return to work, [early CR] could be an advantage to allow more rehab time and improved stamina prior to their return-to-work date.”

That said, he noted, “we typically delay any significant upper-body training activities for 8-10 weeks to avoid impact on healing of the sternum. Thus ... starting sooner would limit the amount of time a patient would have to engage in any upper-body resistance training. Many lose upper body strength after surgery, so this is an important part of the recovery/rehab process.”

Matthew Tomey, MD, director of the cardiac intensive care unit, Mount Sinai Morningside, New York, advised “caution” when interpreting the findings, stating that “there was no evident difference in the primary outcome measure of functional capacity by 14 weeks, and the trial was not designed to directly assess impact on either social functioning or economic productivity.”

“I would be interested to [see] more comprehensive data on safety in a larger, more diverse sample of postoperative patients,” he said, “as well as evidence to indicate clear advantage of an earlier start for patient-centered outcomes specifically after cardiac surgery.

“Perhaps the greatest challenges to full realization of the benefits of CR in practice have been gaps in referral and gaps in enrollment,” he added. “It is incumbent upon us as clinicians to counsel our patients and to provide appropriate referrals.”

The study was supported by the Medical and Life Sciences Research Fund and the Jeremy Pilcher Memorial Fund. No conflicts of interest were reported.

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

Cardiac rehabilitation (CR) started 2 weeks after sternotomy for a cardiac procedure was noninferior to usual care, in which CR starts 6 weeks after the procedure, with a greater improvement in 6-minute walk test outcomes, a randomized study suggests.

There was no difference in adverse events between groups, although the researchers pointed out that the study was not powered specifically for safety outcomes.

“Cardiac surgical techniques have evolved significantly over the last 60 years, leading to improved survival and shorter hospital stays,” Gordon McGregor, PhD, University of Warwick, Coventry, England, told this news organization. “However, sternal precautions and rehabilitation guidelines have not changed accordingly. There has never been a guideline based on empirical evidence to support rehabilitation professionals working with cardiac surgery patients after median sternotomy.”

“By adopting a progressive individualized approach,” he added, “cardiac surgery sternotomy patients can start cardiac rehabilitation up to 4 weeks earlier than current guidance, and thus potentially complete their recovery sooner.”

Results of the Early Initiation of Poststernotomy Cardiac Rehabilitation Exercise Training study were published online  in JAMA Cardiology.

In the study, Dr. McGregor and colleagues randomly assigned 158 patients (mean age, 63 years; 84% men) to 8 weeks of 1-hour, twice-weekly supervised CR exercise training starting 2 weeks (early) or 6 weeks (usual care) after sternotomy.

The primary outcome was change in the 6-minute walk test distance from baseline to 10 or 14 weeks after sternotomy, respectively, and 12 months after randomization.

For usual care, training followed British standards: a warm-up with light cardiovascular and mobility exercises; continuous moderate-intensity cardiovascular exercise; a cooldown; functional exercises using resistance machines and free weights; and upper-body exercises designed to prevent sternal and leg wound pain and complications.

There are no specific outpatient CR exercise guidelines for early CR, so study participants followed an individualized exercise program for the first 2-3 weeks after surgery, starting with light mobility and moderate-intensity cardiovascular training when they could do those exercises with minimal discomfort. They then progressed to current British standards, as per usual care.

Forty patients were lost to follow-up, largely because of the pandemic; about half the participants in each group were included in the primary analysis.

Early CR was not inferior to usual care, the authors wrote. The mean change in 6-minute walk distance from baseline to completion of CR was 28 meters greater in the early group than in the usual-care group, and was achieved 4 weeks earlier in the recovery timeline.

Secondary outcomes (functional fitness and quality of life) improved in both groups and between-group differences were not statistically significant, indicating the noninferiority of early CR, the authors noted.
 

Safety not proven

There were more adverse events in the early group than in the usual-care group (58 vs. 46) and more serious adverse events (18 vs. 14), but fewer deaths (1 vs. 2).

Although there was no between-group difference in the likelihood of having an adverse or serious adverse event, Dr. McGregor acknowledged that the study was “not powered specifically for safety outcomes.” He added that “there is the potential to run a very large multination definitive superiority [randomized, controlled trial] with safety as the primary outcome; however, a very large sample would be required.”

Meanwhile, he said, “we can say with some degree of certainty that early CR was likely as safe as usual-care CR. In the United Kingdom, we work closely with the British Association for Cardiovascular Prevention and Rehabilitation and the Association of Chartered Physiotherapists in Cardiovascular Rehabilitation, who will incorporate our findings in their guidelines and training courses.”
 

Questions remain

Asked to comment on the study, John Larry, MD, medical director of cardiology and cardiac rehabilitation at the Ohio State University Wexner Medical Center East Hospital, Columbus, said: “For those under time pressure to return to work, [early CR] could be an advantage to allow more rehab time and improved stamina prior to their return-to-work date.”

That said, he noted, “we typically delay any significant upper-body training activities for 8-10 weeks to avoid impact on healing of the sternum. Thus ... starting sooner would limit the amount of time a patient would have to engage in any upper-body resistance training. Many lose upper body strength after surgery, so this is an important part of the recovery/rehab process.”

Matthew Tomey, MD, director of the cardiac intensive care unit, Mount Sinai Morningside, New York, advised “caution” when interpreting the findings, stating that “there was no evident difference in the primary outcome measure of functional capacity by 14 weeks, and the trial was not designed to directly assess impact on either social functioning or economic productivity.”

“I would be interested to [see] more comprehensive data on safety in a larger, more diverse sample of postoperative patients,” he said, “as well as evidence to indicate clear advantage of an earlier start for patient-centered outcomes specifically after cardiac surgery.

“Perhaps the greatest challenges to full realization of the benefits of CR in practice have been gaps in referral and gaps in enrollment,” he added. “It is incumbent upon us as clinicians to counsel our patients and to provide appropriate referrals.”

The study was supported by the Medical and Life Sciences Research Fund and the Jeremy Pilcher Memorial Fund. No conflicts of interest were reported.

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

Cardiac rehabilitation (CR) started 2 weeks after sternotomy for a cardiac procedure was noninferior to usual care, in which CR starts 6 weeks after the procedure, with a greater improvement in 6-minute walk test outcomes, a randomized study suggests.

There was no difference in adverse events between groups, although the researchers pointed out that the study was not powered specifically for safety outcomes.

“Cardiac surgical techniques have evolved significantly over the last 60 years, leading to improved survival and shorter hospital stays,” Gordon McGregor, PhD, University of Warwick, Coventry, England, told this news organization. “However, sternal precautions and rehabilitation guidelines have not changed accordingly. There has never been a guideline based on empirical evidence to support rehabilitation professionals working with cardiac surgery patients after median sternotomy.”

“By adopting a progressive individualized approach,” he added, “cardiac surgery sternotomy patients can start cardiac rehabilitation up to 4 weeks earlier than current guidance, and thus potentially complete their recovery sooner.”

Results of the Early Initiation of Poststernotomy Cardiac Rehabilitation Exercise Training study were published online  in JAMA Cardiology.

In the study, Dr. McGregor and colleagues randomly assigned 158 patients (mean age, 63 years; 84% men) to 8 weeks of 1-hour, twice-weekly supervised CR exercise training starting 2 weeks (early) or 6 weeks (usual care) after sternotomy.

The primary outcome was change in the 6-minute walk test distance from baseline to 10 or 14 weeks after sternotomy, respectively, and 12 months after randomization.

For usual care, training followed British standards: a warm-up with light cardiovascular and mobility exercises; continuous moderate-intensity cardiovascular exercise; a cooldown; functional exercises using resistance machines and free weights; and upper-body exercises designed to prevent sternal and leg wound pain and complications.

There are no specific outpatient CR exercise guidelines for early CR, so study participants followed an individualized exercise program for the first 2-3 weeks after surgery, starting with light mobility and moderate-intensity cardiovascular training when they could do those exercises with minimal discomfort. They then progressed to current British standards, as per usual care.

Forty patients were lost to follow-up, largely because of the pandemic; about half the participants in each group were included in the primary analysis.

Early CR was not inferior to usual care, the authors wrote. The mean change in 6-minute walk distance from baseline to completion of CR was 28 meters greater in the early group than in the usual-care group, and was achieved 4 weeks earlier in the recovery timeline.

Secondary outcomes (functional fitness and quality of life) improved in both groups and between-group differences were not statistically significant, indicating the noninferiority of early CR, the authors noted.
 

Safety not proven

There were more adverse events in the early group than in the usual-care group (58 vs. 46) and more serious adverse events (18 vs. 14), but fewer deaths (1 vs. 2).

Although there was no between-group difference in the likelihood of having an adverse or serious adverse event, Dr. McGregor acknowledged that the study was “not powered specifically for safety outcomes.” He added that “there is the potential to run a very large multination definitive superiority [randomized, controlled trial] with safety as the primary outcome; however, a very large sample would be required.”

Meanwhile, he said, “we can say with some degree of certainty that early CR was likely as safe as usual-care CR. In the United Kingdom, we work closely with the British Association for Cardiovascular Prevention and Rehabilitation and the Association of Chartered Physiotherapists in Cardiovascular Rehabilitation, who will incorporate our findings in their guidelines and training courses.”
 

Questions remain

Asked to comment on the study, John Larry, MD, medical director of cardiology and cardiac rehabilitation at the Ohio State University Wexner Medical Center East Hospital, Columbus, said: “For those under time pressure to return to work, [early CR] could be an advantage to allow more rehab time and improved stamina prior to their return-to-work date.”

That said, he noted, “we typically delay any significant upper-body training activities for 8-10 weeks to avoid impact on healing of the sternum. Thus ... starting sooner would limit the amount of time a patient would have to engage in any upper-body resistance training. Many lose upper body strength after surgery, so this is an important part of the recovery/rehab process.”

Matthew Tomey, MD, director of the cardiac intensive care unit, Mount Sinai Morningside, New York, advised “caution” when interpreting the findings, stating that “there was no evident difference in the primary outcome measure of functional capacity by 14 weeks, and the trial was not designed to directly assess impact on either social functioning or economic productivity.”

“I would be interested to [see] more comprehensive data on safety in a larger, more diverse sample of postoperative patients,” he said, “as well as evidence to indicate clear advantage of an earlier start for patient-centered outcomes specifically after cardiac surgery.

“Perhaps the greatest challenges to full realization of the benefits of CR in practice have been gaps in referral and gaps in enrollment,” he added. “It is incumbent upon us as clinicians to counsel our patients and to provide appropriate referrals.”

The study was supported by the Medical and Life Sciences Research Fund and the Jeremy Pilcher Memorial Fund. No conflicts of interest were reported.

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

A higher level of intramuscular fat infiltration in the thighs was associated with a higher risk of developing heart failure in a new study. The association was independent of other cardiometabolic risk factors and measures of adiposity such as body mass index.

The observation raises the possibility of new avenues of research aimed at modifying intramuscular fat levels as a strategy to reduce the risk of developing heart failure.

The study was published online in JACC: Heart Failure.

The authors, led by Kevin Huynh, MD, University of Texas Southwestern Medical Center, Dallas, explained that obesity is a known risk for heart failure, and has been incorporated into risk calculators for heart failure.

However, obesity is a complex and heterogeneous disease with substantial regional variability of adipose deposition in body tissues, they noted. For example, variability in visceral adipose tissue and subcutaneous adipose tissue has been shown to have a differential impact on both cardiovascular risk factors and clinical cardiovascular disease outcomes.

The fat deposition around and within nonadipose tissues (termed “ectopic fat”), such as skeletal muscle, is also a known risk factor for cardiovascular disease, independent of adiposity. However, the impact of peripheral skeletal muscle fat deposition on heart failure risk is not as well studied.

The researchers noted that ectopic fat in skeletal muscle can be measured through imaging and categorized as either intermuscular or intramuscular fat according to the location of muscle fat around or within skeletal muscle, respectively.

The researchers conducted the current study to characterize the association of both intermuscular and intramuscular fat deposition with heart failure risk in a large cohort of older adults.

They used data from 2,399 individuals aged 70-79 years without heart failure at baseline who participated in the Health ABC (Health, Aging and Body Composition) study. Measures of intramuscular and intermuscular fat in the thigh were determined by CT, and the participants were followed for an average of 12 years.

During the follow-up period, there were 485 incident heart failure events. Higher sex-specific tertiles of intramuscular and intermuscular fat were each associated with heart failure risk.

After multivariable adjustment for age, sex, race, education, blood pressure, fasting blood sugar, current smoking, prevalent coronary disease, and creatinine, higher intramuscular fat, but not intermuscular fat, was significantly associated with higher risk for heart failure.

Individuals in the highest tertile of intramuscular fat had a 34% increased risk of developing heart failure, compared with those in the lowest tertile. This finding was independent of other cardiometabolic risk factors, measures of adiposity including body mass index and percent fat, muscle strength, and muscle mass.

The association was slightly attenuated when adjusted for inflammatory markers, suggesting that inflammation may be a contributor.

The association between higher intramuscular fat and heart failure appeared specific to higher risk of incident heart failure with reduced ejection fraction, but not with heart failure with preserved ejection fraction.

The researchers noted that skeletal muscle is a pivotal endocrine organ in addition to the role it plays in the production of mechanical power.

They pointed out that there are differences in the biology of intermuscular and intramuscular fat deposition, and that excess intramuscular fat deposition is a result of dysregulated lipid metabolism and is associated with insulin resistance (a known risk factor for the development of heart failure), inflammation, and muscle wasting conditions.

They concluded that, in patients with heart failure, alterations in skeletal muscle function are most likely affected by multiple contributors, including inflammation, oxidative stress, and neurohormonal factors. “As these factors are also implicated in the pathogenesis of heart failure, intramuscular fat deposition may indicate a biological milieu that increases the risk of heart failure.”
 

New approaches to reduce heart failure risk?

In an accompanying editorial, Salvatore Carbone, PhD, Virginia Commonwealth University, Richmond, said the findings of the study are “exceptionally novel,” providing novel evidence that noncardiac body composition compartments, particularly intramuscular adipose tissue, can predict the risk for heart failure in a diverse population of older adults.

He called for further research to understand the mechanisms involved and to assess if this risk factor can be effectively modified to reduce the risk of developing heart failure.

Dr. Carbone reported that intramuscular adipose tissue can be influenced by dietary fat intake and can be worsened by accumulation of saturated fatty acids, which also contribute to insulin resistance.

He noted that saturated fatty acid–induced insulin resistance in the skeletal muscle appears to be mediated by proinflammatory pathways within the skeletal muscle itself, which can be reversed by monounsaturated fatty acids, like oleic acid, that can be found in the largest amount in food like olive oil, canola oil, and avocados, among others.

He added that sodium-glucose transporter 2 inhibitors, drugs used in the treatment of diabetes that have also been shown to prevent heart failure in individuals at risk, can also improve the composition of intramuscular adipose tissue by reducing its content of saturated fatty acids and increase the content of monosaturated fatty acids.

The study results suggest that the quality of intramuscular adipose tissue might also play an important role and could be targeted by therapeutic strategies, he commented.

Dr. Carbone concluded that “studies testing novel modalities of exercise training, intentional weight loss, diet quality improvements with and without weight loss (i.e., increase of dietary monounsaturated fatty acids, such as oleic acid), as well as pharmacological anti-inflammatory strategies should be encouraged in this population to test whether the reduction in intramuscular adipose tissue or improvements of its quality can ultimately reduce the risk for heart failure in this population.”

This research was supported by the National Institute on Aging and the National Institute of Nursing Research. Dr. Huynh and Dr. Carbone disclosed no relevant financial relationships.

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

A higher level of intramuscular fat infiltration in the thighs was associated with a higher risk of developing heart failure in a new study. The association was independent of other cardiometabolic risk factors and measures of adiposity such as body mass index.

The observation raises the possibility of new avenues of research aimed at modifying intramuscular fat levels as a strategy to reduce the risk of developing heart failure.

The study was published online in JACC: Heart Failure.

The authors, led by Kevin Huynh, MD, University of Texas Southwestern Medical Center, Dallas, explained that obesity is a known risk for heart failure, and has been incorporated into risk calculators for heart failure.

However, obesity is a complex and heterogeneous disease with substantial regional variability of adipose deposition in body tissues, they noted. For example, variability in visceral adipose tissue and subcutaneous adipose tissue has been shown to have a differential impact on both cardiovascular risk factors and clinical cardiovascular disease outcomes.

The fat deposition around and within nonadipose tissues (termed “ectopic fat”), such as skeletal muscle, is also a known risk factor for cardiovascular disease, independent of adiposity. However, the impact of peripheral skeletal muscle fat deposition on heart failure risk is not as well studied.

The researchers noted that ectopic fat in skeletal muscle can be measured through imaging and categorized as either intermuscular or intramuscular fat according to the location of muscle fat around or within skeletal muscle, respectively.

The researchers conducted the current study to characterize the association of both intermuscular and intramuscular fat deposition with heart failure risk in a large cohort of older adults.

They used data from 2,399 individuals aged 70-79 years without heart failure at baseline who participated in the Health ABC (Health, Aging and Body Composition) study. Measures of intramuscular and intermuscular fat in the thigh were determined by CT, and the participants were followed for an average of 12 years.

During the follow-up period, there were 485 incident heart failure events. Higher sex-specific tertiles of intramuscular and intermuscular fat were each associated with heart failure risk.

After multivariable adjustment for age, sex, race, education, blood pressure, fasting blood sugar, current smoking, prevalent coronary disease, and creatinine, higher intramuscular fat, but not intermuscular fat, was significantly associated with higher risk for heart failure.

Individuals in the highest tertile of intramuscular fat had a 34% increased risk of developing heart failure, compared with those in the lowest tertile. This finding was independent of other cardiometabolic risk factors, measures of adiposity including body mass index and percent fat, muscle strength, and muscle mass.

The association was slightly attenuated when adjusted for inflammatory markers, suggesting that inflammation may be a contributor.

The association between higher intramuscular fat and heart failure appeared specific to higher risk of incident heart failure with reduced ejection fraction, but not with heart failure with preserved ejection fraction.

The researchers noted that skeletal muscle is a pivotal endocrine organ in addition to the role it plays in the production of mechanical power.

They pointed out that there are differences in the biology of intermuscular and intramuscular fat deposition, and that excess intramuscular fat deposition is a result of dysregulated lipid metabolism and is associated with insulin resistance (a known risk factor for the development of heart failure), inflammation, and muscle wasting conditions.

They concluded that, in patients with heart failure, alterations in skeletal muscle function are most likely affected by multiple contributors, including inflammation, oxidative stress, and neurohormonal factors. “As these factors are also implicated in the pathogenesis of heart failure, intramuscular fat deposition may indicate a biological milieu that increases the risk of heart failure.”
 

New approaches to reduce heart failure risk?

In an accompanying editorial, Salvatore Carbone, PhD, Virginia Commonwealth University, Richmond, said the findings of the study are “exceptionally novel,” providing novel evidence that noncardiac body composition compartments, particularly intramuscular adipose tissue, can predict the risk for heart failure in a diverse population of older adults.

He called for further research to understand the mechanisms involved and to assess if this risk factor can be effectively modified to reduce the risk of developing heart failure.

Dr. Carbone reported that intramuscular adipose tissue can be influenced by dietary fat intake and can be worsened by accumulation of saturated fatty acids, which also contribute to insulin resistance.

He noted that saturated fatty acid–induced insulin resistance in the skeletal muscle appears to be mediated by proinflammatory pathways within the skeletal muscle itself, which can be reversed by monounsaturated fatty acids, like oleic acid, that can be found in the largest amount in food like olive oil, canola oil, and avocados, among others.

He added that sodium-glucose transporter 2 inhibitors, drugs used in the treatment of diabetes that have also been shown to prevent heart failure in individuals at risk, can also improve the composition of intramuscular adipose tissue by reducing its content of saturated fatty acids and increase the content of monosaturated fatty acids.

The study results suggest that the quality of intramuscular adipose tissue might also play an important role and could be targeted by therapeutic strategies, he commented.

Dr. Carbone concluded that “studies testing novel modalities of exercise training, intentional weight loss, diet quality improvements with and without weight loss (i.e., increase of dietary monounsaturated fatty acids, such as oleic acid), as well as pharmacological anti-inflammatory strategies should be encouraged in this population to test whether the reduction in intramuscular adipose tissue or improvements of its quality can ultimately reduce the risk for heart failure in this population.”

This research was supported by the National Institute on Aging and the National Institute of Nursing Research. Dr. Huynh and Dr. Carbone disclosed no relevant financial relationships.

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

A higher level of intramuscular fat infiltration in the thighs was associated with a higher risk of developing heart failure in a new study. The association was independent of other cardiometabolic risk factors and measures of adiposity such as body mass index.

The observation raises the possibility of new avenues of research aimed at modifying intramuscular fat levels as a strategy to reduce the risk of developing heart failure.

The study was published online in JACC: Heart Failure.

The authors, led by Kevin Huynh, MD, University of Texas Southwestern Medical Center, Dallas, explained that obesity is a known risk for heart failure, and has been incorporated into risk calculators for heart failure.

However, obesity is a complex and heterogeneous disease with substantial regional variability of adipose deposition in body tissues, they noted. For example, variability in visceral adipose tissue and subcutaneous adipose tissue has been shown to have a differential impact on both cardiovascular risk factors and clinical cardiovascular disease outcomes.

The fat deposition around and within nonadipose tissues (termed “ectopic fat”), such as skeletal muscle, is also a known risk factor for cardiovascular disease, independent of adiposity. However, the impact of peripheral skeletal muscle fat deposition on heart failure risk is not as well studied.

The researchers noted that ectopic fat in skeletal muscle can be measured through imaging and categorized as either intermuscular or intramuscular fat according to the location of muscle fat around or within skeletal muscle, respectively.

The researchers conducted the current study to characterize the association of both intermuscular and intramuscular fat deposition with heart failure risk in a large cohort of older adults.

They used data from 2,399 individuals aged 70-79 years without heart failure at baseline who participated in the Health ABC (Health, Aging and Body Composition) study. Measures of intramuscular and intermuscular fat in the thigh were determined by CT, and the participants were followed for an average of 12 years.

During the follow-up period, there were 485 incident heart failure events. Higher sex-specific tertiles of intramuscular and intermuscular fat were each associated with heart failure risk.

After multivariable adjustment for age, sex, race, education, blood pressure, fasting blood sugar, current smoking, prevalent coronary disease, and creatinine, higher intramuscular fat, but not intermuscular fat, was significantly associated with higher risk for heart failure.

Individuals in the highest tertile of intramuscular fat had a 34% increased risk of developing heart failure, compared with those in the lowest tertile. This finding was independent of other cardiometabolic risk factors, measures of adiposity including body mass index and percent fat, muscle strength, and muscle mass.

The association was slightly attenuated when adjusted for inflammatory markers, suggesting that inflammation may be a contributor.

The association between higher intramuscular fat and heart failure appeared specific to higher risk of incident heart failure with reduced ejection fraction, but not with heart failure with preserved ejection fraction.

The researchers noted that skeletal muscle is a pivotal endocrine organ in addition to the role it plays in the production of mechanical power.

They pointed out that there are differences in the biology of intermuscular and intramuscular fat deposition, and that excess intramuscular fat deposition is a result of dysregulated lipid metabolism and is associated with insulin resistance (a known risk factor for the development of heart failure), inflammation, and muscle wasting conditions.

They concluded that, in patients with heart failure, alterations in skeletal muscle function are most likely affected by multiple contributors, including inflammation, oxidative stress, and neurohormonal factors. “As these factors are also implicated in the pathogenesis of heart failure, intramuscular fat deposition may indicate a biological milieu that increases the risk of heart failure.”
 

New approaches to reduce heart failure risk?

In an accompanying editorial, Salvatore Carbone, PhD, Virginia Commonwealth University, Richmond, said the findings of the study are “exceptionally novel,” providing novel evidence that noncardiac body composition compartments, particularly intramuscular adipose tissue, can predict the risk for heart failure in a diverse population of older adults.

He called for further research to understand the mechanisms involved and to assess if this risk factor can be effectively modified to reduce the risk of developing heart failure.

Dr. Carbone reported that intramuscular adipose tissue can be influenced by dietary fat intake and can be worsened by accumulation of saturated fatty acids, which also contribute to insulin resistance.

He noted that saturated fatty acid–induced insulin resistance in the skeletal muscle appears to be mediated by proinflammatory pathways within the skeletal muscle itself, which can be reversed by monounsaturated fatty acids, like oleic acid, that can be found in the largest amount in food like olive oil, canola oil, and avocados, among others.

He added that sodium-glucose transporter 2 inhibitors, drugs used in the treatment of diabetes that have also been shown to prevent heart failure in individuals at risk, can also improve the composition of intramuscular adipose tissue by reducing its content of saturated fatty acids and increase the content of monosaturated fatty acids.

The study results suggest that the quality of intramuscular adipose tissue might also play an important role and could be targeted by therapeutic strategies, he commented.

Dr. Carbone concluded that “studies testing novel modalities of exercise training, intentional weight loss, diet quality improvements with and without weight loss (i.e., increase of dietary monounsaturated fatty acids, such as oleic acid), as well as pharmacological anti-inflammatory strategies should be encouraged in this population to test whether the reduction in intramuscular adipose tissue or improvements of its quality can ultimately reduce the risk for heart failure in this population.”

This research was supported by the National Institute on Aging and the National Institute of Nursing Research. Dr. Huynh and Dr. Carbone disclosed no relevant financial relationships.

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

The American College of Cardiology and the American Heart Association have jointly issued a comprehensive set of data standards to help clarify definitions of the cardiovascular (CV) and non-CV complications of COVID-19.

It’s the work of the ACC/AHA Task Force on Clinical Data Standards and has been endorsed by the Heart Failure Society of America and Society for Cardiac Angiography and Interventions.

There is increased importance to understanding the acute and long-term impact of COVID-19 on CV health, the writing group notes. Until now, however, there has not been “clarity or consensus” on definitions of CV conditions related to COVID-19, with different diagnostic terminologies being used for overlapping conditions, such as “myocardial injury,” “myocarditis,” “type Il myocardial infarction,” “stress cardiomyopathy,” and “inflammatory cardiomyopathy,” they point out.

Floaria Bicher/iStock/Getty Images Plus

“We, as a research community, did some things right and some things wrong surrounding the COVID pandemic,” Sandeep Das, MD, MPH, vice chair of the writing group, noted in an interview with this news organization.

“The things that we really did right is that everybody responded with enthusiasm, kind of all hands on deck with a massive crisis response, and that was fantastic,” Dr. Das said.

“However, because of the need to hurry, we didn’t structure and organize in the way that we typically would for something that was sort of a slow burn kind of problem rather than an emergency. One of the consequences of that was fragmentation of how things are collected, reported, et cetera, and that leads to confusion,” he added.

The report was published simultaneously June 23 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.
 

A necessary but not glamorous project

The new data standards for COVID-19 will help standardize definitions and set the framework to capture and better understand how COVID-19 affects CV health.

“It wasn’t exactly a glamorous-type project but, at the same time, it’s super necessary to kind of get everybody on the same page and working together,” Dr. Das said. 

Broad agreement on common vocabulary and definitions will help with efforts to pool or compare data from electronic health records, clinical registries, administrative datasets, and other databases, and determine whether these data apply to clinical practice and research endeavors, the writing group says.

They considered data elements relevant to the full range of care provided to COVID-19 patients in all care settings. Among the key items included in the document are:

• Case definitions for confirmed, probable, and suspected acute COVID-19, as well as postacute sequelae of COVID-19.
• Definitions for acute CV complications related to COVID-19, including acute myocardial injury, heart failure, shock, arrhythmia, thromboembolic complications, and .
• Data elements related to COVID-19 vaccination status, comorbidities, and preexisting CV conditions.
• Definitions for postacute CV sequelae of SARS-CoV-2 infection and long-term CV complications of COVID-19.
• Data elements for CV mortality during acute COVID-19.
• Data elements for non-CV complications to help document severity of illness and other competing diagnoses and complications that might affect CV outcomes.
• A list of symptoms and signs related to COVID-19 and CV complications.
• Data elements for diagnostic and therapeutic strategies for COVID-19 and CV conditions.
• A discussion of advanced therapies, including , extracorporeal membrane oxygenation, and end-of-life management strategies.

These data standards will be useful for researchers, registry developers, and clinicians, and they are proposed as a framework for ICD-10 code development of COVID-19–related CV conditions, the writing group says.

The standards are also of “great importance” to patients, clinicians, investigators, scientists, administrators, public health officials, policymakers, and payers, the group says.

Dr. Das said that, although there is no formal plan in place to update the document, he could see sections that might be refined.

“For example, there’s a nice long list of all the various variants, and unfortunately, I suspect that that is going to change and evolve over time,” Dr. Das told this news organization.

“We tried very hard not to include things like specifying specific treatments so we didn’t get proscriptive. We wanted to make it descriptive, so hopefully it will stand the test of time pretty well,” he added.

This research had no commercial funding. The writing group has no relevant disclosures.

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

The American College of Cardiology and the American Heart Association have jointly issued a comprehensive set of data standards to help clarify definitions of the cardiovascular (CV) and non-CV complications of COVID-19.

It’s the work of the ACC/AHA Task Force on Clinical Data Standards and has been endorsed by the Heart Failure Society of America and Society for Cardiac Angiography and Interventions.

There is increased importance to understanding the acute and long-term impact of COVID-19 on CV health, the writing group notes. Until now, however, there has not been “clarity or consensus” on definitions of CV conditions related to COVID-19, with different diagnostic terminologies being used for overlapping conditions, such as “myocardial injury,” “myocarditis,” “type Il myocardial infarction,” “stress cardiomyopathy,” and “inflammatory cardiomyopathy,” they point out.

Floaria Bicher/iStock/Getty Images Plus

“We, as a research community, did some things right and some things wrong surrounding the COVID pandemic,” Sandeep Das, MD, MPH, vice chair of the writing group, noted in an interview with this news organization.

“The things that we really did right is that everybody responded with enthusiasm, kind of all hands on deck with a massive crisis response, and that was fantastic,” Dr. Das said.

“However, because of the need to hurry, we didn’t structure and organize in the way that we typically would for something that was sort of a slow burn kind of problem rather than an emergency. One of the consequences of that was fragmentation of how things are collected, reported, et cetera, and that leads to confusion,” he added.

The report was published simultaneously June 23 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.
 

A necessary but not glamorous project

The new data standards for COVID-19 will help standardize definitions and set the framework to capture and better understand how COVID-19 affects CV health.

“It wasn’t exactly a glamorous-type project but, at the same time, it’s super necessary to kind of get everybody on the same page and working together,” Dr. Das said. 

Broad agreement on common vocabulary and definitions will help with efforts to pool or compare data from electronic health records, clinical registries, administrative datasets, and other databases, and determine whether these data apply to clinical practice and research endeavors, the writing group says.

They considered data elements relevant to the full range of care provided to COVID-19 patients in all care settings. Among the key items included in the document are:

• Case definitions for confirmed, probable, and suspected acute COVID-19, as well as postacute sequelae of COVID-19.
• Definitions for acute CV complications related to COVID-19, including acute myocardial injury, heart failure, shock, arrhythmia, thromboembolic complications, and .
• Data elements related to COVID-19 vaccination status, comorbidities, and preexisting CV conditions.
• Definitions for postacute CV sequelae of SARS-CoV-2 infection and long-term CV complications of COVID-19.
• Data elements for CV mortality during acute COVID-19.
• Data elements for non-CV complications to help document severity of illness and other competing diagnoses and complications that might affect CV outcomes.
• A list of symptoms and signs related to COVID-19 and CV complications.
• Data elements for diagnostic and therapeutic strategies for COVID-19 and CV conditions.
• A discussion of advanced therapies, including , extracorporeal membrane oxygenation, and end-of-life management strategies.

These data standards will be useful for researchers, registry developers, and clinicians, and they are proposed as a framework for ICD-10 code development of COVID-19–related CV conditions, the writing group says.

The standards are also of “great importance” to patients, clinicians, investigators, scientists, administrators, public health officials, policymakers, and payers, the group says.

Dr. Das said that, although there is no formal plan in place to update the document, he could see sections that might be refined.

“For example, there’s a nice long list of all the various variants, and unfortunately, I suspect that that is going to change and evolve over time,” Dr. Das told this news organization.

“We tried very hard not to include things like specifying specific treatments so we didn’t get proscriptive. We wanted to make it descriptive, so hopefully it will stand the test of time pretty well,” he added.

This research had no commercial funding. The writing group has no relevant disclosures.

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

The American College of Cardiology and the American Heart Association have jointly issued a comprehensive set of data standards to help clarify definitions of the cardiovascular (CV) and non-CV complications of COVID-19.

It’s the work of the ACC/AHA Task Force on Clinical Data Standards and has been endorsed by the Heart Failure Society of America and Society for Cardiac Angiography and Interventions.

There is increased importance to understanding the acute and long-term impact of COVID-19 on CV health, the writing group notes. Until now, however, there has not been “clarity or consensus” on definitions of CV conditions related to COVID-19, with different diagnostic terminologies being used for overlapping conditions, such as “myocardial injury,” “myocarditis,” “type Il myocardial infarction,” “stress cardiomyopathy,” and “inflammatory cardiomyopathy,” they point out.

Floaria Bicher/iStock/Getty Images Plus

“We, as a research community, did some things right and some things wrong surrounding the COVID pandemic,” Sandeep Das, MD, MPH, vice chair of the writing group, noted in an interview with this news organization.

“The things that we really did right is that everybody responded with enthusiasm, kind of all hands on deck with a massive crisis response, and that was fantastic,” Dr. Das said.

“However, because of the need to hurry, we didn’t structure and organize in the way that we typically would for something that was sort of a slow burn kind of problem rather than an emergency. One of the consequences of that was fragmentation of how things are collected, reported, et cetera, and that leads to confusion,” he added.

The report was published simultaneously June 23 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.
 

A necessary but not glamorous project

The new data standards for COVID-19 will help standardize definitions and set the framework to capture and better understand how COVID-19 affects CV health.

“It wasn’t exactly a glamorous-type project but, at the same time, it’s super necessary to kind of get everybody on the same page and working together,” Dr. Das said. 

Broad agreement on common vocabulary and definitions will help with efforts to pool or compare data from electronic health records, clinical registries, administrative datasets, and other databases, and determine whether these data apply to clinical practice and research endeavors, the writing group says.

They considered data elements relevant to the full range of care provided to COVID-19 patients in all care settings. Among the key items included in the document are:

• Case definitions for confirmed, probable, and suspected acute COVID-19, as well as postacute sequelae of COVID-19.
• Definitions for acute CV complications related to COVID-19, including acute myocardial injury, heart failure, shock, arrhythmia, thromboembolic complications, and .
• Data elements related to COVID-19 vaccination status, comorbidities, and preexisting CV conditions.
• Definitions for postacute CV sequelae of SARS-CoV-2 infection and long-term CV complications of COVID-19.
• Data elements for CV mortality during acute COVID-19.
• Data elements for non-CV complications to help document severity of illness and other competing diagnoses and complications that might affect CV outcomes.
• A list of symptoms and signs related to COVID-19 and CV complications.
• Data elements for diagnostic and therapeutic strategies for COVID-19 and CV conditions.
• A discussion of advanced therapies, including , extracorporeal membrane oxygenation, and end-of-life management strategies.

These data standards will be useful for researchers, registry developers, and clinicians, and they are proposed as a framework for ICD-10 code development of COVID-19–related CV conditions, the writing group says.

The standards are also of “great importance” to patients, clinicians, investigators, scientists, administrators, public health officials, policymakers, and payers, the group says.

Dr. Das said that, although there is no formal plan in place to update the document, he could see sections that might be refined.

“For example, there’s a nice long list of all the various variants, and unfortunately, I suspect that that is going to change and evolve over time,” Dr. Das told this news organization.

“We tried very hard not to include things like specifying specific treatments so we didn’t get proscriptive. We wanted to make it descriptive, so hopefully it will stand the test of time pretty well,” he added.

This research had no commercial funding. The writing group has no relevant disclosures.

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

Pregnancy termination for medical reasons had been part of the fabric of everyday health care in the United States since the Supreme Court’s 1973 Roe v. Wade decision, which the current high court overturned in a ruling announced on June 24.

That means many clinicians across specialties are entering uncharted territory with the country’s new patchwork of abortion legality. Some specialties, cardiology among them, may feel the impact more than others.

javi_indy/ Thinkstock

“Unfortunately,” Dr. Haythe said, “many of the states that are going to make or have made abortion illegal are not providing that kind of preconception counseling or good prenatal care to women.”

Cardiologists can provide such counseling to their female patients of childbearing age who have high-risk cardiac conditions, “but not everybody knows that they have a heart problem when they get pregnant, and not everybody is getting screened for heart problems when they’re of childbearing age,” Dr. Haythe said.

“Sometimes it’s not clear whether the problems could have been picked up until a woman is pregnant and has started to have symptoms.” For example, “a lot of women with poor access to health care have rheumatic heart disease. They may have no idea that they have severe aortic stenosis, and it’s not until their second trimester that they start to feel really short of breath.” Often that can be treated in the cath lab, “but again, that’s putting the woman and the baby at risk.”

Cardiologists in states where abortion is illegal will still present the option to their patients with high-risk pregnancies, noted Dr. Haythe. But the conversation may sound something like, “you are at very high risk, termination of the pregnancy takes that risk away, but you’ll have to find a state where it’s legal to do that.”

Dr. Park said such a situation, when abortion is recommended but locally unavailable, is much like any other in cardiology for which the patient may want a second opinion. If a center “doesn’t have the capability or the technology to offer a certain treatment, the patient can opt to seek another opinion at another center,” she said. “Patients will often travel out of state to get the care they need.”

A requirement for out-of-state travel to obtain abortions is likely to worsen socioeconomic disparities in health care, Dr. Bond observed, “because we know that those who are low-income won’t be able to afford that travel.”

Dr. Bond is cosignatory on a statement from the Association of Black Cardiologists (ABC) responding to the high court’s ruling in Dobbs v. Jackson. “This decision will isolate the poor, socioeconomically disadvantaged, and minority populations specifically, widening the already large gaps in health care for our most vulnerable communities,” it states.

“The loss of broad protections supporting the medical and often lifesaving procedure of abortions is likely to have a real impact on the maternal mortality rate, especially in those with congenital and/or acquired cardiovascular conditions where evidence-based guidelines advise at times on termination of such high-risk pregnancies.”

The ABC, it states, “believes that every woman, and every person, should be afforded the right to safe, accessible, legal, timely, patient-centered, equitable, and affordable health care.”

The American College of Cardiology (ACC) released a statement on the matter June 24, signed by its president, Edward T.A. Fry, MD, along with five former ACC presidents. “While the ACC has no official policy on abortion, clinical practice guidelines and other clinical guidance tools address the dangers of pregnancy in certain patient populations at higher risk of death or serious cardiac events.”

The college, it states, is “deeply concerned about the potential implications of the Supreme Court decision regarding Roe vs. Wade on the ability of patients and clinicians to engage in important shared discussions about maternal health, or to remove previously available health care options.”

Dr. Bond proposed that a “vocal stance” from medical societies involved in women’s health, “perhaps even a collective stance from our cardiovascular societies and our obstetrics societies,” would also perhaps reach “the masses of doctors in private practice who are dealing with these patients.”

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

Pregnancy termination for medical reasons had been part of the fabric of everyday health care in the United States since the Supreme Court’s 1973 Roe v. Wade decision, which the current high court overturned in a ruling announced on June 24.

That means many clinicians across specialties are entering uncharted territory with the country’s new patchwork of abortion legality. Some specialties, cardiology among them, may feel the impact more than others.

javi_indy/ Thinkstock

“Unfortunately,” Dr. Haythe said, “many of the states that are going to make or have made abortion illegal are not providing that kind of preconception counseling or good prenatal care to women.”

Cardiologists can provide such counseling to their female patients of childbearing age who have high-risk cardiac conditions, “but not everybody knows that they have a heart problem when they get pregnant, and not everybody is getting screened for heart problems when they’re of childbearing age,” Dr. Haythe said.

“Sometimes it’s not clear whether the problems could have been picked up until a woman is pregnant and has started to have symptoms.” For example, “a lot of women with poor access to health care have rheumatic heart disease. They may have no idea that they have severe aortic stenosis, and it’s not until their second trimester that they start to feel really short of breath.” Often that can be treated in the cath lab, “but again, that’s putting the woman and the baby at risk.”

Cardiologists in states where abortion is illegal will still present the option to their patients with high-risk pregnancies, noted Dr. Haythe. But the conversation may sound something like, “you are at very high risk, termination of the pregnancy takes that risk away, but you’ll have to find a state where it’s legal to do that.”

Dr. Park said such a situation, when abortion is recommended but locally unavailable, is much like any other in cardiology for which the patient may want a second opinion. If a center “doesn’t have the capability or the technology to offer a certain treatment, the patient can opt to seek another opinion at another center,” she said. “Patients will often travel out of state to get the care they need.”

A requirement for out-of-state travel to obtain abortions is likely to worsen socioeconomic disparities in health care, Dr. Bond observed, “because we know that those who are low-income won’t be able to afford that travel.”

Dr. Bond is cosignatory on a statement from the Association of Black Cardiologists (ABC) responding to the high court’s ruling in Dobbs v. Jackson. “This decision will isolate the poor, socioeconomically disadvantaged, and minority populations specifically, widening the already large gaps in health care for our most vulnerable communities,” it states.

“The loss of broad protections supporting the medical and often lifesaving procedure of abortions is likely to have a real impact on the maternal mortality rate, especially in those with congenital and/or acquired cardiovascular conditions where evidence-based guidelines advise at times on termination of such high-risk pregnancies.”

The ABC, it states, “believes that every woman, and every person, should be afforded the right to safe, accessible, legal, timely, patient-centered, equitable, and affordable health care.”

The American College of Cardiology (ACC) released a statement on the matter June 24, signed by its president, Edward T.A. Fry, MD, along with five former ACC presidents. “While the ACC has no official policy on abortion, clinical practice guidelines and other clinical guidance tools address the dangers of pregnancy in certain patient populations at higher risk of death or serious cardiac events.”

The college, it states, is “deeply concerned about the potential implications of the Supreme Court decision regarding Roe vs. Wade on the ability of patients and clinicians to engage in important shared discussions about maternal health, or to remove previously available health care options.”

Dr. Bond proposed that a “vocal stance” from medical societies involved in women’s health, “perhaps even a collective stance from our cardiovascular societies and our obstetrics societies,” would also perhaps reach “the masses of doctors in private practice who are dealing with these patients.”

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

Pregnancy termination for medical reasons had been part of the fabric of everyday health care in the United States since the Supreme Court’s 1973 Roe v. Wade decision, which the current high court overturned in a ruling announced on June 24.

That means many clinicians across specialties are entering uncharted territory with the country’s new patchwork of abortion legality. Some specialties, cardiology among them, may feel the impact more than others.

javi_indy/ Thinkstock

“Unfortunately,” Dr. Haythe said, “many of the states that are going to make or have made abortion illegal are not providing that kind of preconception counseling or good prenatal care to women.”

Cardiologists can provide such counseling to their female patients of childbearing age who have high-risk cardiac conditions, “but not everybody knows that they have a heart problem when they get pregnant, and not everybody is getting screened for heart problems when they’re of childbearing age,” Dr. Haythe said.

“Sometimes it’s not clear whether the problems could have been picked up until a woman is pregnant and has started to have symptoms.” For example, “a lot of women with poor access to health care have rheumatic heart disease. They may have no idea that they have severe aortic stenosis, and it’s not until their second trimester that they start to feel really short of breath.” Often that can be treated in the cath lab, “but again, that’s putting the woman and the baby at risk.”

Cardiologists in states where abortion is illegal will still present the option to their patients with high-risk pregnancies, noted Dr. Haythe. But the conversation may sound something like, “you are at very high risk, termination of the pregnancy takes that risk away, but you’ll have to find a state where it’s legal to do that.”

Dr. Park said such a situation, when abortion is recommended but locally unavailable, is much like any other in cardiology for which the patient may want a second opinion. If a center “doesn’t have the capability or the technology to offer a certain treatment, the patient can opt to seek another opinion at another center,” she said. “Patients will often travel out of state to get the care they need.”

A requirement for out-of-state travel to obtain abortions is likely to worsen socioeconomic disparities in health care, Dr. Bond observed, “because we know that those who are low-income won’t be able to afford that travel.”

Dr. Bond is cosignatory on a statement from the Association of Black Cardiologists (ABC) responding to the high court’s ruling in Dobbs v. Jackson. “This decision will isolate the poor, socioeconomically disadvantaged, and minority populations specifically, widening the already large gaps in health care for our most vulnerable communities,” it states.

“The loss of broad protections supporting the medical and often lifesaving procedure of abortions is likely to have a real impact on the maternal mortality rate, especially in those with congenital and/or acquired cardiovascular conditions where evidence-based guidelines advise at times on termination of such high-risk pregnancies.”

The ABC, it states, “believes that every woman, and every person, should be afforded the right to safe, accessible, legal, timely, patient-centered, equitable, and affordable health care.”

The American College of Cardiology (ACC) released a statement on the matter June 24, signed by its president, Edward T.A. Fry, MD, along with five former ACC presidents. “While the ACC has no official policy on abortion, clinical practice guidelines and other clinical guidance tools address the dangers of pregnancy in certain patient populations at higher risk of death or serious cardiac events.”

The college, it states, is “deeply concerned about the potential implications of the Supreme Court decision regarding Roe vs. Wade on the ability of patients and clinicians to engage in important shared discussions about maternal health, or to remove previously available health care options.”

Dr. Bond proposed that a “vocal stance” from medical societies involved in women’s health, “perhaps even a collective stance from our cardiovascular societies and our obstetrics societies,” would also perhaps reach “the masses of doctors in private practice who are dealing with these patients.”

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

Hydroxychloroquine should be initiated with caution in older patients with rheumatoid arthritis who also have heart failure or are at risk for it, say the authors of a study suggesting that the drug could increase their risk for major adverse cardiovascular events (MACE), compared with methotrexate.

A cohort study published online in the Journal of the American College of Cardiology looked at outcomes in 54,462 patients with RA aged 65 years or older and not previously treated with disease-modifying antirheumatic drugs. Half were initiated on methotrexate and half on hydroxychloroquine, making 27,231 propensity-matched pairs.

Across the entire cohort, hydroxychloroquine was not associated with a higher risk for sudden cardiac arrest, ventricular arrhythmia, or MACE, compared with methotrexate. When broken down into individual cardiovascular events, the data suggested a statistically significant 17% increase in the risk for cardiovascular mortality and 10% increase in all-cause mortality with hydroxychloroquine, although there were no differences in the risks for myocardial infarction or stroke.

However, a subgroup analysis revealed a significant 30% increase in the risk for MACE among patients starting hydroxychloroquine who also had a history of heart failure, compared with patients taking methotrexate. The researchers found no difference between the two drugs in patients without a history of heart failure. The study also suggested an overall 41% increase in the risk for hospitalization with heart failure with hydroxychloroquine, regardless of heart failure history.

Hydroxychloroquine was also associated with a 34% increase in the risk for cardiovascular mortality, a 22% increase in the risk for all-cause mortality, and a 74% increase in the risk for MI.

The lead author of the study, Elvira D’Andrea, MD, PhD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, said that hydroxychloroquine is used as a first-line treatment for RA, but there was limited evidence on its cardiovascular risks. The pandemic in particular shined a spotlight on these concerns and prompted the researchers to extend their original prepandemic study to encompass additional cardiovascular outcomes.

“The emerging concerns on its cardiovascular safety in early 2020 has led the rheumatological community, and patients regularly taking hydroxychloroquine for rheumatoid arthritis, to confusion,” Dr. D’Andrea said in an interview.

She advised that clinicians be cautious when initiating hydroxychloroquine in older patients with existing heart failure or who have risk factors for it. “Although heart failure is a known concern for hydroxychloroquine use, these findings helped to clarify the relationship between the use of hydroxychloroquine or methotrexate and heart failure. Clinicians should pay careful attention to clinical manifestations of cardiomyopathy or heart failure in older patients with rheumatoid arthritis treated with hydroxychloroquine.”

Hydroxychloroquine is associated with cardiotoxicity, particularly cardiomyopathy, which may help precipitate MACE or heart failure exacerbations in patients who already have deterioration of their cardiac tissue, the authors suggested.

Short follow-up period leaves risk attribution under question

In an accompanying editorial, Elizabeth Blair Solow, MD, and Bonnie L. Bermas, MD, of the University of Texas Southwestern Medical Center, Dallas, commented that the lack of an increased risk for arrhythmic events or MACE in the overall cohort taking hydroxychloroquine was reassuring. They also suggested the subgroup analysis findings among patients with preexisting heart failure were still “exploratory and hypothesis-generating” and should be interpreted with caution.

They noted that the follow-up time of the study was relatively short – a median of 209 days – given that hydroxychloroquine does not reach a steady-state level for 6 months.

“Evidence to date suggests cardiomyopathy from HCQ [hydroxychloroquine] takes years to develop, many months beyond the exposures described here, bringing into question as to whether HCQ itself increased HF hospitalizations,” the editorialists wrote.

The editorial also raised the question of whether the association observed in the study was related to a possible cardioprotective effect of methotrexate, given that previous studies have suggested this effect in older patients with RA.

The study authors did an exploratory analysis comparing hydroxychloroquine with sulfasalazine, which appeared to support their main findings of a possible cardiovascular effect of hydroxychloroquine. However, they qualified this by pointing out that the analysis involved small numbers of patients.

Senior investigator Seoyoung C. Kim, MD, ScD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, also noted that the study only looked at outcomes in patients aged 65 years and older.

“It would be clinically important to further examine the cardiovascular safety of hydroxychloroquine versus methotrexate in a younger population with rheumatic conditions,” she said.

The study was supported by the National Institutes of Health, Brigham and Women’s Hospital, and Harvard Medical School. Four authors declared unrelated research grants from the pharmaceutical sector, with one also declaring stock options and consulting work with the pharmaceutical sector. No other conflicts of interest were declared.

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

Hydroxychloroquine should be initiated with caution in older patients with rheumatoid arthritis who also have heart failure or are at risk for it, say the authors of a study suggesting that the drug could increase their risk for major adverse cardiovascular events (MACE), compared with methotrexate.

A cohort study published online in the Journal of the American College of Cardiology looked at outcomes in 54,462 patients with RA aged 65 years or older and not previously treated with disease-modifying antirheumatic drugs. Half were initiated on methotrexate and half on hydroxychloroquine, making 27,231 propensity-matched pairs.

Across the entire cohort, hydroxychloroquine was not associated with a higher risk for sudden cardiac arrest, ventricular arrhythmia, or MACE, compared with methotrexate. When broken down into individual cardiovascular events, the data suggested a statistically significant 17% increase in the risk for cardiovascular mortality and 10% increase in all-cause mortality with hydroxychloroquine, although there were no differences in the risks for myocardial infarction or stroke.

However, a subgroup analysis revealed a significant 30% increase in the risk for MACE among patients starting hydroxychloroquine who also had a history of heart failure, compared with patients taking methotrexate. The researchers found no difference between the two drugs in patients without a history of heart failure. The study also suggested an overall 41% increase in the risk for hospitalization with heart failure with hydroxychloroquine, regardless of heart failure history.

Hydroxychloroquine was also associated with a 34% increase in the risk for cardiovascular mortality, a 22% increase in the risk for all-cause mortality, and a 74% increase in the risk for MI.

The lead author of the study, Elvira D’Andrea, MD, PhD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, said that hydroxychloroquine is used as a first-line treatment for RA, but there was limited evidence on its cardiovascular risks. The pandemic in particular shined a spotlight on these concerns and prompted the researchers to extend their original prepandemic study to encompass additional cardiovascular outcomes.

“The emerging concerns on its cardiovascular safety in early 2020 has led the rheumatological community, and patients regularly taking hydroxychloroquine for rheumatoid arthritis, to confusion,” Dr. D’Andrea said in an interview.

She advised that clinicians be cautious when initiating hydroxychloroquine in older patients with existing heart failure or who have risk factors for it. “Although heart failure is a known concern for hydroxychloroquine use, these findings helped to clarify the relationship between the use of hydroxychloroquine or methotrexate and heart failure. Clinicians should pay careful attention to clinical manifestations of cardiomyopathy or heart failure in older patients with rheumatoid arthritis treated with hydroxychloroquine.”

Hydroxychloroquine is associated with cardiotoxicity, particularly cardiomyopathy, which may help precipitate MACE or heart failure exacerbations in patients who already have deterioration of their cardiac tissue, the authors suggested.

Short follow-up period leaves risk attribution under question

In an accompanying editorial, Elizabeth Blair Solow, MD, and Bonnie L. Bermas, MD, of the University of Texas Southwestern Medical Center, Dallas, commented that the lack of an increased risk for arrhythmic events or MACE in the overall cohort taking hydroxychloroquine was reassuring. They also suggested the subgroup analysis findings among patients with preexisting heart failure were still “exploratory and hypothesis-generating” and should be interpreted with caution.

They noted that the follow-up time of the study was relatively short – a median of 209 days – given that hydroxychloroquine does not reach a steady-state level for 6 months.

“Evidence to date suggests cardiomyopathy from HCQ [hydroxychloroquine] takes years to develop, many months beyond the exposures described here, bringing into question as to whether HCQ itself increased HF hospitalizations,” the editorialists wrote.

The editorial also raised the question of whether the association observed in the study was related to a possible cardioprotective effect of methotrexate, given that previous studies have suggested this effect in older patients with RA.

The study authors did an exploratory analysis comparing hydroxychloroquine with sulfasalazine, which appeared to support their main findings of a possible cardiovascular effect of hydroxychloroquine. However, they qualified this by pointing out that the analysis involved small numbers of patients.

Senior investigator Seoyoung C. Kim, MD, ScD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, also noted that the study only looked at outcomes in patients aged 65 years and older.

“It would be clinically important to further examine the cardiovascular safety of hydroxychloroquine versus methotrexate in a younger population with rheumatic conditions,” she said.

The study was supported by the National Institutes of Health, Brigham and Women’s Hospital, and Harvard Medical School. Four authors declared unrelated research grants from the pharmaceutical sector, with one also declaring stock options and consulting work with the pharmaceutical sector. No other conflicts of interest were declared.

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

Hydroxychloroquine should be initiated with caution in older patients with rheumatoid arthritis who also have heart failure or are at risk for it, say the authors of a study suggesting that the drug could increase their risk for major adverse cardiovascular events (MACE), compared with methotrexate.

A cohort study published online in the Journal of the American College of Cardiology looked at outcomes in 54,462 patients with RA aged 65 years or older and not previously treated with disease-modifying antirheumatic drugs. Half were initiated on methotrexate and half on hydroxychloroquine, making 27,231 propensity-matched pairs.

Across the entire cohort, hydroxychloroquine was not associated with a higher risk for sudden cardiac arrest, ventricular arrhythmia, or MACE, compared with methotrexate. When broken down into individual cardiovascular events, the data suggested a statistically significant 17% increase in the risk for cardiovascular mortality and 10% increase in all-cause mortality with hydroxychloroquine, although there were no differences in the risks for myocardial infarction or stroke.

However, a subgroup analysis revealed a significant 30% increase in the risk for MACE among patients starting hydroxychloroquine who also had a history of heart failure, compared with patients taking methotrexate. The researchers found no difference between the two drugs in patients without a history of heart failure. The study also suggested an overall 41% increase in the risk for hospitalization with heart failure with hydroxychloroquine, regardless of heart failure history.

Hydroxychloroquine was also associated with a 34% increase in the risk for cardiovascular mortality, a 22% increase in the risk for all-cause mortality, and a 74% increase in the risk for MI.

The lead author of the study, Elvira D’Andrea, MD, PhD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, said that hydroxychloroquine is used as a first-line treatment for RA, but there was limited evidence on its cardiovascular risks. The pandemic in particular shined a spotlight on these concerns and prompted the researchers to extend their original prepandemic study to encompass additional cardiovascular outcomes.

“The emerging concerns on its cardiovascular safety in early 2020 has led the rheumatological community, and patients regularly taking hydroxychloroquine for rheumatoid arthritis, to confusion,” Dr. D’Andrea said in an interview.

She advised that clinicians be cautious when initiating hydroxychloroquine in older patients with existing heart failure or who have risk factors for it. “Although heart failure is a known concern for hydroxychloroquine use, these findings helped to clarify the relationship between the use of hydroxychloroquine or methotrexate and heart failure. Clinicians should pay careful attention to clinical manifestations of cardiomyopathy or heart failure in older patients with rheumatoid arthritis treated with hydroxychloroquine.”

Hydroxychloroquine is associated with cardiotoxicity, particularly cardiomyopathy, which may help precipitate MACE or heart failure exacerbations in patients who already have deterioration of their cardiac tissue, the authors suggested.

Short follow-up period leaves risk attribution under question

In an accompanying editorial, Elizabeth Blair Solow, MD, and Bonnie L. Bermas, MD, of the University of Texas Southwestern Medical Center, Dallas, commented that the lack of an increased risk for arrhythmic events or MACE in the overall cohort taking hydroxychloroquine was reassuring. They also suggested the subgroup analysis findings among patients with preexisting heart failure were still “exploratory and hypothesis-generating” and should be interpreted with caution.

They noted that the follow-up time of the study was relatively short – a median of 209 days – given that hydroxychloroquine does not reach a steady-state level for 6 months.

“Evidence to date suggests cardiomyopathy from HCQ [hydroxychloroquine] takes years to develop, many months beyond the exposures described here, bringing into question as to whether HCQ itself increased HF hospitalizations,” the editorialists wrote.

The editorial also raised the question of whether the association observed in the study was related to a possible cardioprotective effect of methotrexate, given that previous studies have suggested this effect in older patients with RA.

The study authors did an exploratory analysis comparing hydroxychloroquine with sulfasalazine, which appeared to support their main findings of a possible cardiovascular effect of hydroxychloroquine. However, they qualified this by pointing out that the analysis involved small numbers of patients.

Senior investigator Seoyoung C. Kim, MD, ScD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, also noted that the study only looked at outcomes in patients aged 65 years and older.

“It would be clinically important to further examine the cardiovascular safety of hydroxychloroquine versus methotrexate in a younger population with rheumatic conditions,” she said.

The study was supported by the National Institutes of Health, Brigham and Women’s Hospital, and Harvard Medical School. Four authors declared unrelated research grants from the pharmaceutical sector, with one also declaring stock options and consulting work with the pharmaceutical sector. No other conflicts of interest were declared.

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

It’s a given that the case of David Bennett, Sr, and his transplanted, genetically modified porcine heart will have a lot to teach, and the peer-reviewed publication this week lends welcome authority to some of its earliest lessons.

Mr. Bennett lived for 2 months after receiving the heart in the pioneering surgery, and the new case report compiles the available clinical, anatomic, and histologic evidence and other potential clues to the underlying cause or causes of death.

It also describes a mystery that came to light at autopsy: a grossly enlarged heart attributable to pervasive interstitial edema, and at the cellular level, a peculiar pattern of myocardial damage that included microvascular deterioration and, potentially as a result, cellular necrosis, according to the new report.

The myocardium itself was described as “thickened and stiff,” consistent with the “diastolic heart failure” that characterized Mr. Bennett’s final 10 days and the likely convergence of several underlying processes. Missing, however, was any conventional sign of graft rejection as it is understood clinically or in animal models, the report states.

If a form of tissue rejection was the cause of graft failure, any implicating cellular evidence may simply have been unrecognizable, given the unprecedented nature of the first pig-to-human heart transplantation, the donor animal’s multiple anti-inflammatory gene deletions, and partly investigational immunosuppression regimen, speculated Bartley P. Griffith, MD, University of Maryland, College Park.

“I’m betting against it being a fulminant rejection,” he told this news organization, “because we saw nothing like the [characteristic] platelet deposition or thrombosis of the capillaries.”

Dr. Griffith, who performed the xenotransplant surgery and led Mr. Bennett’s postoperative care, is lead author on the case report published in the New England Journal of Medicine. “Additional studies are underway to characterize the pathophysiologic mechanisms that resulted in this damage,” the report states.

The report builds on recent meeting presentations on the case, which, as previously reported, gave cursory details regarding the organ damage and other clinical developments during and after the surgery, including evidence that the transplanted heart contained porcine cytomegalovirus (PCMV).

Similar details also appeared in a third-person account based in part on personal communication with Dr. Griffith. The cardiac XTx review that focused on this University of Maryland experience was published June 15 in JACC: Basic to Translational Science, with lead author Jacinthe Boulet, MD, CM, Brigham and Women’s Hospital Heart, Boston.

“The question of how to move XTx forward remains uncertain, and appropriate selection of patients for experimental XTx will be one of the most important challenges to be addressed. The first issue we must contend with is whether we are ready to move to the next XTx in a human. We strongly believe this to be the case,” the review states. “Once early experience is gained, with successive iterations of XTx, the bar for success can be raised with maturation of the technology.”

Evidence has so far not implicated several other potential mechanisms underlying the graft failure that had been the focus of early speculations. For example, the transplanted pig heart was infected with PCMV, as previously reported. Mr. Bennett showed traces of PCMV DNA in his circulation, but no actual virus in his native cells. Still, PCMV remains a suspect.

Mr. Bennett also received intravenous immunoglobulin (IVIG) on several occasions to fight rejection, and also severe infections, including a nasty episode of sepsis. A reaction to the IVIG, derived from pooled donor antibodies, could potentially have caused the unusual myocardial damage seen by the University of Maryland team, Dr. Griffith observed. Alternatively, the damage might have been partly related to the patient’s overall severely diminished condition even before the transplant surgery or his rocky postoperative clinical course.

Indeed, Mr. Bennett’s condition worsened dramatically on postoperative day 50, and echocardiography showed a striking degree of myocardial wall thickening and heart enlargement, determined to be from edema. “The heart got amazingly stiff but maintained a systolic function that wasn›t too terrible, even to the very end. But his heart seemed as though it had swollen overnight,” Dr. Griffith said. “We had never seen that type of process, the suddenness of this swelling, in our nonhuman primate studies.”

The damage to the heart muscle appeared irreversible, based on myocardial biopsy results, so the decision was made to withdraw life support 60 days after the transplant surgery, the report notes.

Among the experience’s apparent lessons for future cardiac xenotransplantation, Dr. Griffith said, would be to select patients for the surgery who are in a bit more robust condition than Mr. Bennett was, who are perhaps ambulatory, not sarcopenic, and not recently on prolonged mechanical circulatory support. “We’re going to try to pick a patient who, on the front end, is less critically ill but who is just as likely not to benefit from continued medical therapy” and who isn’t a candidate for conventional heart transplantation, he said.

Because of universal efforts to manage conditions like diabetes, hypertension, and vascular disease in the population, and “because these conditions cause many of the cases of organ failure and fuel demand for transplantation, one might wonder whether the advances reported by Dr. Griffith and colleagues presage a decreasing demand for organ transplantation,” speculates an accompanying editorialfrom Jeffrey L. Platt, MD, and Marilia Cascalho, MD, PhD, University of Michigan, Ann Arbor.

“We think the answer is no. Since aging is associated with progressive decline in the function of the heart, kidneys, and other organs, advances that extend life expectancy will ultimately increase the prevalence of organ failure and potentially the demand for transplantation.”

The donor pig was developed and provided by Revivicor, and the investigational KPL-404 antibody drug used in the experience was provided by Kiniksa. Other disclosures for the case report and editorial from Dr. Platt and Dr. Cascalho are available at NEJM.com. Dr. Boulet reports no relevant relationships; disclosures for the other authors are in their report.

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

It’s a given that the case of David Bennett, Sr, and his transplanted, genetically modified porcine heart will have a lot to teach, and the peer-reviewed publication this week lends welcome authority to some of its earliest lessons.

Mr. Bennett lived for 2 months after receiving the heart in the pioneering surgery, and the new case report compiles the available clinical, anatomic, and histologic evidence and other potential clues to the underlying cause or causes of death.

It also describes a mystery that came to light at autopsy: a grossly enlarged heart attributable to pervasive interstitial edema, and at the cellular level, a peculiar pattern of myocardial damage that included microvascular deterioration and, potentially as a result, cellular necrosis, according to the new report.

The myocardium itself was described as “thickened and stiff,” consistent with the “diastolic heart failure” that characterized Mr. Bennett’s final 10 days and the likely convergence of several underlying processes. Missing, however, was any conventional sign of graft rejection as it is understood clinically or in animal models, the report states.

If a form of tissue rejection was the cause of graft failure, any implicating cellular evidence may simply have been unrecognizable, given the unprecedented nature of the first pig-to-human heart transplantation, the donor animal’s multiple anti-inflammatory gene deletions, and partly investigational immunosuppression regimen, speculated Bartley P. Griffith, MD, University of Maryland, College Park.

“I’m betting against it being a fulminant rejection,” he told this news organization, “because we saw nothing like the [characteristic] platelet deposition or thrombosis of the capillaries.”

Dr. Griffith, who performed the xenotransplant surgery and led Mr. Bennett’s postoperative care, is lead author on the case report published in the New England Journal of Medicine. “Additional studies are underway to characterize the pathophysiologic mechanisms that resulted in this damage,” the report states.

The report builds on recent meeting presentations on the case, which, as previously reported, gave cursory details regarding the organ damage and other clinical developments during and after the surgery, including evidence that the transplanted heart contained porcine cytomegalovirus (PCMV).

Similar details also appeared in a third-person account based in part on personal communication with Dr. Griffith. The cardiac XTx review that focused on this University of Maryland experience was published June 15 in JACC: Basic to Translational Science, with lead author Jacinthe Boulet, MD, CM, Brigham and Women’s Hospital Heart, Boston.

“The question of how to move XTx forward remains uncertain, and appropriate selection of patients for experimental XTx will be one of the most important challenges to be addressed. The first issue we must contend with is whether we are ready to move to the next XTx in a human. We strongly believe this to be the case,” the review states. “Once early experience is gained, with successive iterations of XTx, the bar for success can be raised with maturation of the technology.”

Evidence has so far not implicated several other potential mechanisms underlying the graft failure that had been the focus of early speculations. For example, the transplanted pig heart was infected with PCMV, as previously reported. Mr. Bennett showed traces of PCMV DNA in his circulation, but no actual virus in his native cells. Still, PCMV remains a suspect.

Mr. Bennett also received intravenous immunoglobulin (IVIG) on several occasions to fight rejection, and also severe infections, including a nasty episode of sepsis. A reaction to the IVIG, derived from pooled donor antibodies, could potentially have caused the unusual myocardial damage seen by the University of Maryland team, Dr. Griffith observed. Alternatively, the damage might have been partly related to the patient’s overall severely diminished condition even before the transplant surgery or his rocky postoperative clinical course.

Indeed, Mr. Bennett’s condition worsened dramatically on postoperative day 50, and echocardiography showed a striking degree of myocardial wall thickening and heart enlargement, determined to be from edema. “The heart got amazingly stiff but maintained a systolic function that wasn›t too terrible, even to the very end. But his heart seemed as though it had swollen overnight,” Dr. Griffith said. “We had never seen that type of process, the suddenness of this swelling, in our nonhuman primate studies.”

The damage to the heart muscle appeared irreversible, based on myocardial biopsy results, so the decision was made to withdraw life support 60 days after the transplant surgery, the report notes.

Among the experience’s apparent lessons for future cardiac xenotransplantation, Dr. Griffith said, would be to select patients for the surgery who are in a bit more robust condition than Mr. Bennett was, who are perhaps ambulatory, not sarcopenic, and not recently on prolonged mechanical circulatory support. “We’re going to try to pick a patient who, on the front end, is less critically ill but who is just as likely not to benefit from continued medical therapy” and who isn’t a candidate for conventional heart transplantation, he said.

Because of universal efforts to manage conditions like diabetes, hypertension, and vascular disease in the population, and “because these conditions cause many of the cases of organ failure and fuel demand for transplantation, one might wonder whether the advances reported by Dr. Griffith and colleagues presage a decreasing demand for organ transplantation,” speculates an accompanying editorialfrom Jeffrey L. Platt, MD, and Marilia Cascalho, MD, PhD, University of Michigan, Ann Arbor.

“We think the answer is no. Since aging is associated with progressive decline in the function of the heart, kidneys, and other organs, advances that extend life expectancy will ultimately increase the prevalence of organ failure and potentially the demand for transplantation.”

The donor pig was developed and provided by Revivicor, and the investigational KPL-404 antibody drug used in the experience was provided by Kiniksa. Other disclosures for the case report and editorial from Dr. Platt and Dr. Cascalho are available at NEJM.com. Dr. Boulet reports no relevant relationships; disclosures for the other authors are in their report.

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

It’s a given that the case of David Bennett, Sr, and his transplanted, genetically modified porcine heart will have a lot to teach, and the peer-reviewed publication this week lends welcome authority to some of its earliest lessons.

Mr. Bennett lived for 2 months after receiving the heart in the pioneering surgery, and the new case report compiles the available clinical, anatomic, and histologic evidence and other potential clues to the underlying cause or causes of death.

It also describes a mystery that came to light at autopsy: a grossly enlarged heart attributable to pervasive interstitial edema, and at the cellular level, a peculiar pattern of myocardial damage that included microvascular deterioration and, potentially as a result, cellular necrosis, according to the new report.

The myocardium itself was described as “thickened and stiff,” consistent with the “diastolic heart failure” that characterized Mr. Bennett’s final 10 days and the likely convergence of several underlying processes. Missing, however, was any conventional sign of graft rejection as it is understood clinically or in animal models, the report states.

If a form of tissue rejection was the cause of graft failure, any implicating cellular evidence may simply have been unrecognizable, given the unprecedented nature of the first pig-to-human heart transplantation, the donor animal’s multiple anti-inflammatory gene deletions, and partly investigational immunosuppression regimen, speculated Bartley P. Griffith, MD, University of Maryland, College Park.

“I’m betting against it being a fulminant rejection,” he told this news organization, “because we saw nothing like the [characteristic] platelet deposition or thrombosis of the capillaries.”

Dr. Griffith, who performed the xenotransplant surgery and led Mr. Bennett’s postoperative care, is lead author on the case report published in the New England Journal of Medicine. “Additional studies are underway to characterize the pathophysiologic mechanisms that resulted in this damage,” the report states.

The report builds on recent meeting presentations on the case, which, as previously reported, gave cursory details regarding the organ damage and other clinical developments during and after the surgery, including evidence that the transplanted heart contained porcine cytomegalovirus (PCMV).

Similar details also appeared in a third-person account based in part on personal communication with Dr. Griffith. The cardiac XTx review that focused on this University of Maryland experience was published June 15 in JACC: Basic to Translational Science, with lead author Jacinthe Boulet, MD, CM, Brigham and Women’s Hospital Heart, Boston.

“The question of how to move XTx forward remains uncertain, and appropriate selection of patients for experimental XTx will be one of the most important challenges to be addressed. The first issue we must contend with is whether we are ready to move to the next XTx in a human. We strongly believe this to be the case,” the review states. “Once early experience is gained, with successive iterations of XTx, the bar for success can be raised with maturation of the technology.”

Evidence has so far not implicated several other potential mechanisms underlying the graft failure that had been the focus of early speculations. For example, the transplanted pig heart was infected with PCMV, as previously reported. Mr. Bennett showed traces of PCMV DNA in his circulation, but no actual virus in his native cells. Still, PCMV remains a suspect.

Mr. Bennett also received intravenous immunoglobulin (IVIG) on several occasions to fight rejection, and also severe infections, including a nasty episode of sepsis. A reaction to the IVIG, derived from pooled donor antibodies, could potentially have caused the unusual myocardial damage seen by the University of Maryland team, Dr. Griffith observed. Alternatively, the damage might have been partly related to the patient’s overall severely diminished condition even before the transplant surgery or his rocky postoperative clinical course.

Indeed, Mr. Bennett’s condition worsened dramatically on postoperative day 50, and echocardiography showed a striking degree of myocardial wall thickening and heart enlargement, determined to be from edema. “The heart got amazingly stiff but maintained a systolic function that wasn›t too terrible, even to the very end. But his heart seemed as though it had swollen overnight,” Dr. Griffith said. “We had never seen that type of process, the suddenness of this swelling, in our nonhuman primate studies.”

The damage to the heart muscle appeared irreversible, based on myocardial biopsy results, so the decision was made to withdraw life support 60 days after the transplant surgery, the report notes.

Among the experience’s apparent lessons for future cardiac xenotransplantation, Dr. Griffith said, would be to select patients for the surgery who are in a bit more robust condition than Mr. Bennett was, who are perhaps ambulatory, not sarcopenic, and not recently on prolonged mechanical circulatory support. “We’re going to try to pick a patient who, on the front end, is less critically ill but who is just as likely not to benefit from continued medical therapy” and who isn’t a candidate for conventional heart transplantation, he said.

Because of universal efforts to manage conditions like diabetes, hypertension, and vascular disease in the population, and “because these conditions cause many of the cases of organ failure and fuel demand for transplantation, one might wonder whether the advances reported by Dr. Griffith and colleagues presage a decreasing demand for organ transplantation,” speculates an accompanying editorialfrom Jeffrey L. Platt, MD, and Marilia Cascalho, MD, PhD, University of Michigan, Ann Arbor.

“We think the answer is no. Since aging is associated with progressive decline in the function of the heart, kidneys, and other organs, advances that extend life expectancy will ultimately increase the prevalence of organ failure and potentially the demand for transplantation.”

The donor pig was developed and provided by Revivicor, and the investigational KPL-404 antibody drug used in the experience was provided by Kiniksa. Other disclosures for the case report and editorial from Dr. Platt and Dr. Cascalho are available at NEJM.com. Dr. Boulet reports no relevant relationships; disclosures for the other authors are in their report.

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

Infertility, pregnancy loss, and stillbirth increased women’s later risk of both nonfatal and fatal stroke, based on data from more than 600,000 women.

“To date, multiple studies have generated an expanding body of evidence on the association between pregnancy complications (e.g., gestational diabetes and preeclampsia) and the long-term risk of stroke, but studies on associations with infertility, miscarriage, or stillbirth have produced mixed evidence,” Chen Liang, a PhD candidate at the University of Queensland, Brisbane, Australia, and colleagues wrote.

In a study published in the BMJ, the researchers reviewed data from eight observational cohort studies across seven countries (Australia, China, Japan, the Netherlands, Sweden, the United Kingdom, and the United States). The participants were part of the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium established in 2021. Most observational studies included in the analysis began between 1990 and 2000.

The study population included 618,851 women aged 32-73 years at baseline for whom data on infertility, miscarriage, or stillbirth, were available. The primary outcome was the association of infertility, recurrent miscarriage, and stillbirth with risk of first fatal or nonfatal stroke, and the results were further stratified by subtype. Stroke was identified through self-reports, linked hospital data, national patient registers, or death registry data. Baseline was defined as the first incidence of infertility, miscarriage, or stillbirth. The exception was the National Survey of Health and Development, a British birth cohort started in 1946, that collected data retrospectively.

The median follow-up period was 13 years for nonfatal stroke and 9.4 years for fatal stroke.

Overall, 17.2%, 16.6%, and 4.6% of the women experienced infertility, miscarriage, and stillbirth, respectively.

Women with a history of infertility had a significantly higher nonfatal stroke risk, compared with those without infertility (hazard ratio, 1.14). Further analysis by stroke subtypes showed an increased association between miscarriage and ischemic stroke (HR, 1.15).

Those with a history of miscarriage also had an increased risk of nonfatal stroke, compared with those without miscarriages (HR, 1.11). In the miscarriage group, the risk of stroke increased with the number of miscarriages, with adjusted HRs of 1.07, 1.12, and 1.35 for women with one, two, and three or more miscarriages, respectively. When stratified by stroke subtype, women with three or more miscarriages were more likely than women with no miscarriages to experience ischemic and hemorrhagic nonfatal strokes.

Associations were similar between miscarriage history and fatal stroke risk. Women with one, two, and three or more miscarriages had increased risk of fatal stroke, compared with those with no miscarriages (aHR, 1.08, 1.26, and 1.82, respectively, and women with three or more miscarriages had a higher risk of ischemic and hemorrhagic stroke (aHR, 1.83 and 1.84, respectively).

Women with a history of stillbirth had an approximately 31% increased risk of nonfatal stroke, compared with those with no history of stillbirth, with aHRs similar for single and recurrent stillbirths (1.32 and 1.29, respectively). Ischemic nonfatal stroke risk was higher in women with any stillbirth, compared with those without stillbirth (aHR, 1.77). Fatal stroke risk also was higher in women with any stillbirth, compared with those without, and this risk increased with the number of stillbirths (HR, 0.97 and HR, 1.26 for those with one stillbirth and two or more, respectively).

“The increased risk of stroke associated with infertility or recurrent stillbirths was mainly driven by a single subtype of stroke (nonfatal ischemic stroke or fatal hemorrhagic stroke, respectively), whereas the risk of stroke associated with recurrent miscarriages was driven by both subtypes,” the researchers wrote.

The researchers cited endothelial dysfunction as a potential underlying mechanism for increased stroke risk associated with pregnancy complications. “Endothelial dysfunction might lead to pregnancy loss through placentation-related defects, persist after a complicated pregnancy, and contribute to the development of stroke through reduced vasodilation, proinflammatory status, and prothrombic properties,” and that history of recurrent pregnancy loss might be a female-specific risk factor for stroke.

To mitigate this risk, they advised early monitoring of women with a history of recurrent miscarriages and stillbirths for stroke risk factors such as high blood pressure, blood sugar levels, and lipid levels.

The study findings were limited by several factors including the use of questionnaires to collect information on infertility, miscarriage, and stillbirth, and the potential variation in definitions of infertility, miscarriage, and stillbirth across the included studies, and a lack of data on the effect of different causes or treatments based on reproductive histories, the researchers noted. Other limitations include incomplete data on stroke subtypes and inability to adjust for all covariates such as thyroid disorders and endometriosis. However, the results were strengthened by the large study size and geographically and racially diverse population, extend the current knowledge on associations between infertility, miscarriage, and stillbirth with stroke, and highlight the need for more research on underlying mechanisms.
 

Data support gender-specific stroke risk stratification

“Studies that seek to understand gender differences and disparities in adverse outcomes, such as stroke risk, are extremely important given that women historically were excluded from research studies,” Catherine M. Albright, MD, of the University of Washington, Seattle, said in an interview. “By doing these studies, we are able to better risk stratify people in order to better predict and modify risks,” added Dr. Albright, who was not involved in the current study.

“It is well known than adverse pregnancy outcomes such as hypertension in pregnancy, fetal growth restriction, and preterm birth, lead to increased risk of cardiovascular disease and stroke later in life, so the general findings of an association between other adverse reproductive and pregnancy outcomes leads to increased stroke risk are not surprising,” she said.

“The take-home message is that outcomes for pregnancy really do provide a window to future health,” said Dr. Albright. “For clinicians, especially non-ob.gyns., knowing a complete pregnancy history for any new patient is important and can help risk-stratify patients, especially as we continue to gain knowledge like what is shown in this study.”

However, “this study did not evaluate why individual patients may have had infertility, recurrent pregnancy loss, or stillbirth, so research to look further into this association to determine if there is an underlying medical condition that could be treated and therefore possibly reduce both pregnancy complications and future stroke risks would be important,” Dr. Albright noted.

The study was supported by the Australian National Health and Medical Research Council Centres of Research Excellence; one corresponding author was supported by an Australian National Health and Medical Research Council Investigator grant. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Infertility, pregnancy loss, and stillbirth increased women’s later risk of both nonfatal and fatal stroke, based on data from more than 600,000 women.

“To date, multiple studies have generated an expanding body of evidence on the association between pregnancy complications (e.g., gestational diabetes and preeclampsia) and the long-term risk of stroke, but studies on associations with infertility, miscarriage, or stillbirth have produced mixed evidence,” Chen Liang, a PhD candidate at the University of Queensland, Brisbane, Australia, and colleagues wrote.

In a study published in the BMJ, the researchers reviewed data from eight observational cohort studies across seven countries (Australia, China, Japan, the Netherlands, Sweden, the United Kingdom, and the United States). The participants were part of the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium established in 2021. Most observational studies included in the analysis began between 1990 and 2000.

The study population included 618,851 women aged 32-73 years at baseline for whom data on infertility, miscarriage, or stillbirth, were available. The primary outcome was the association of infertility, recurrent miscarriage, and stillbirth with risk of first fatal or nonfatal stroke, and the results were further stratified by subtype. Stroke was identified through self-reports, linked hospital data, national patient registers, or death registry data. Baseline was defined as the first incidence of infertility, miscarriage, or stillbirth. The exception was the National Survey of Health and Development, a British birth cohort started in 1946, that collected data retrospectively.

The median follow-up period was 13 years for nonfatal stroke and 9.4 years for fatal stroke.

Overall, 17.2%, 16.6%, and 4.6% of the women experienced infertility, miscarriage, and stillbirth, respectively.

Women with a history of infertility had a significantly higher nonfatal stroke risk, compared with those without infertility (hazard ratio, 1.14). Further analysis by stroke subtypes showed an increased association between miscarriage and ischemic stroke (HR, 1.15).

Those with a history of miscarriage also had an increased risk of nonfatal stroke, compared with those without miscarriages (HR, 1.11). In the miscarriage group, the risk of stroke increased with the number of miscarriages, with adjusted HRs of 1.07, 1.12, and 1.35 for women with one, two, and three or more miscarriages, respectively. When stratified by stroke subtype, women with three or more miscarriages were more likely than women with no miscarriages to experience ischemic and hemorrhagic nonfatal strokes.

Associations were similar between miscarriage history and fatal stroke risk. Women with one, two, and three or more miscarriages had increased risk of fatal stroke, compared with those with no miscarriages (aHR, 1.08, 1.26, and 1.82, respectively, and women with three or more miscarriages had a higher risk of ischemic and hemorrhagic stroke (aHR, 1.83 and 1.84, respectively).

Women with a history of stillbirth had an approximately 31% increased risk of nonfatal stroke, compared with those with no history of stillbirth, with aHRs similar for single and recurrent stillbirths (1.32 and 1.29, respectively). Ischemic nonfatal stroke risk was higher in women with any stillbirth, compared with those without stillbirth (aHR, 1.77). Fatal stroke risk also was higher in women with any stillbirth, compared with those without, and this risk increased with the number of stillbirths (HR, 0.97 and HR, 1.26 for those with one stillbirth and two or more, respectively).

“The increased risk of stroke associated with infertility or recurrent stillbirths was mainly driven by a single subtype of stroke (nonfatal ischemic stroke or fatal hemorrhagic stroke, respectively), whereas the risk of stroke associated with recurrent miscarriages was driven by both subtypes,” the researchers wrote.

The researchers cited endothelial dysfunction as a potential underlying mechanism for increased stroke risk associated with pregnancy complications. “Endothelial dysfunction might lead to pregnancy loss through placentation-related defects, persist after a complicated pregnancy, and contribute to the development of stroke through reduced vasodilation, proinflammatory status, and prothrombic properties,” and that history of recurrent pregnancy loss might be a female-specific risk factor for stroke.

To mitigate this risk, they advised early monitoring of women with a history of recurrent miscarriages and stillbirths for stroke risk factors such as high blood pressure, blood sugar levels, and lipid levels.

The study findings were limited by several factors including the use of questionnaires to collect information on infertility, miscarriage, and stillbirth, and the potential variation in definitions of infertility, miscarriage, and stillbirth across the included studies, and a lack of data on the effect of different causes or treatments based on reproductive histories, the researchers noted. Other limitations include incomplete data on stroke subtypes and inability to adjust for all covariates such as thyroid disorders and endometriosis. However, the results were strengthened by the large study size and geographically and racially diverse population, extend the current knowledge on associations between infertility, miscarriage, and stillbirth with stroke, and highlight the need for more research on underlying mechanisms.
 

Data support gender-specific stroke risk stratification

“Studies that seek to understand gender differences and disparities in adverse outcomes, such as stroke risk, are extremely important given that women historically were excluded from research studies,” Catherine M. Albright, MD, of the University of Washington, Seattle, said in an interview. “By doing these studies, we are able to better risk stratify people in order to better predict and modify risks,” added Dr. Albright, who was not involved in the current study.

“It is well known than adverse pregnancy outcomes such as hypertension in pregnancy, fetal growth restriction, and preterm birth, lead to increased risk of cardiovascular disease and stroke later in life, so the general findings of an association between other adverse reproductive and pregnancy outcomes leads to increased stroke risk are not surprising,” she said.

“The take-home message is that outcomes for pregnancy really do provide a window to future health,” said Dr. Albright. “For clinicians, especially non-ob.gyns., knowing a complete pregnancy history for any new patient is important and can help risk-stratify patients, especially as we continue to gain knowledge like what is shown in this study.”

However, “this study did not evaluate why individual patients may have had infertility, recurrent pregnancy loss, or stillbirth, so research to look further into this association to determine if there is an underlying medical condition that could be treated and therefore possibly reduce both pregnancy complications and future stroke risks would be important,” Dr. Albright noted.

The study was supported by the Australian National Health and Medical Research Council Centres of Research Excellence; one corresponding author was supported by an Australian National Health and Medical Research Council Investigator grant. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Infertility, pregnancy loss, and stillbirth increased women’s later risk of both nonfatal and fatal stroke, based on data from more than 600,000 women.

“To date, multiple studies have generated an expanding body of evidence on the association between pregnancy complications (e.g., gestational diabetes and preeclampsia) and the long-term risk of stroke, but studies on associations with infertility, miscarriage, or stillbirth have produced mixed evidence,” Chen Liang, a PhD candidate at the University of Queensland, Brisbane, Australia, and colleagues wrote.

In a study published in the BMJ, the researchers reviewed data from eight observational cohort studies across seven countries (Australia, China, Japan, the Netherlands, Sweden, the United Kingdom, and the United States). The participants were part of the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium established in 2021. Most observational studies included in the analysis began between 1990 and 2000.

The study population included 618,851 women aged 32-73 years at baseline for whom data on infertility, miscarriage, or stillbirth, were available. The primary outcome was the association of infertility, recurrent miscarriage, and stillbirth with risk of first fatal or nonfatal stroke, and the results were further stratified by subtype. Stroke was identified through self-reports, linked hospital data, national patient registers, or death registry data. Baseline was defined as the first incidence of infertility, miscarriage, or stillbirth. The exception was the National Survey of Health and Development, a British birth cohort started in 1946, that collected data retrospectively.

The median follow-up period was 13 years for nonfatal stroke and 9.4 years for fatal stroke.

Overall, 17.2%, 16.6%, and 4.6% of the women experienced infertility, miscarriage, and stillbirth, respectively.

Women with a history of infertility had a significantly higher nonfatal stroke risk, compared with those without infertility (hazard ratio, 1.14). Further analysis by stroke subtypes showed an increased association between miscarriage and ischemic stroke (HR, 1.15).

Those with a history of miscarriage also had an increased risk of nonfatal stroke, compared with those without miscarriages (HR, 1.11). In the miscarriage group, the risk of stroke increased with the number of miscarriages, with adjusted HRs of 1.07, 1.12, and 1.35 for women with one, two, and three or more miscarriages, respectively. When stratified by stroke subtype, women with three or more miscarriages were more likely than women with no miscarriages to experience ischemic and hemorrhagic nonfatal strokes.

Associations were similar between miscarriage history and fatal stroke risk. Women with one, two, and three or more miscarriages had increased risk of fatal stroke, compared with those with no miscarriages (aHR, 1.08, 1.26, and 1.82, respectively, and women with three or more miscarriages had a higher risk of ischemic and hemorrhagic stroke (aHR, 1.83 and 1.84, respectively).

Women with a history of stillbirth had an approximately 31% increased risk of nonfatal stroke, compared with those with no history of stillbirth, with aHRs similar for single and recurrent stillbirths (1.32 and 1.29, respectively). Ischemic nonfatal stroke risk was higher in women with any stillbirth, compared with those without stillbirth (aHR, 1.77). Fatal stroke risk also was higher in women with any stillbirth, compared with those without, and this risk increased with the number of stillbirths (HR, 0.97 and HR, 1.26 for those with one stillbirth and two or more, respectively).

“The increased risk of stroke associated with infertility or recurrent stillbirths was mainly driven by a single subtype of stroke (nonfatal ischemic stroke or fatal hemorrhagic stroke, respectively), whereas the risk of stroke associated with recurrent miscarriages was driven by both subtypes,” the researchers wrote.

The researchers cited endothelial dysfunction as a potential underlying mechanism for increased stroke risk associated with pregnancy complications. “Endothelial dysfunction might lead to pregnancy loss through placentation-related defects, persist after a complicated pregnancy, and contribute to the development of stroke through reduced vasodilation, proinflammatory status, and prothrombic properties,” and that history of recurrent pregnancy loss might be a female-specific risk factor for stroke.

To mitigate this risk, they advised early monitoring of women with a history of recurrent miscarriages and stillbirths for stroke risk factors such as high blood pressure, blood sugar levels, and lipid levels.

The study findings were limited by several factors including the use of questionnaires to collect information on infertility, miscarriage, and stillbirth, and the potential variation in definitions of infertility, miscarriage, and stillbirth across the included studies, and a lack of data on the effect of different causes or treatments based on reproductive histories, the researchers noted. Other limitations include incomplete data on stroke subtypes and inability to adjust for all covariates such as thyroid disorders and endometriosis. However, the results were strengthened by the large study size and geographically and racially diverse population, extend the current knowledge on associations between infertility, miscarriage, and stillbirth with stroke, and highlight the need for more research on underlying mechanisms.
 

Data support gender-specific stroke risk stratification

“Studies that seek to understand gender differences and disparities in adverse outcomes, such as stroke risk, are extremely important given that women historically were excluded from research studies,” Catherine M. Albright, MD, of the University of Washington, Seattle, said in an interview. “By doing these studies, we are able to better risk stratify people in order to better predict and modify risks,” added Dr. Albright, who was not involved in the current study.

“It is well known than adverse pregnancy outcomes such as hypertension in pregnancy, fetal growth restriction, and preterm birth, lead to increased risk of cardiovascular disease and stroke later in life, so the general findings of an association between other adverse reproductive and pregnancy outcomes leads to increased stroke risk are not surprising,” she said.

“The take-home message is that outcomes for pregnancy really do provide a window to future health,” said Dr. Albright. “For clinicians, especially non-ob.gyns., knowing a complete pregnancy history for any new patient is important and can help risk-stratify patients, especially as we continue to gain knowledge like what is shown in this study.”

However, “this study did not evaluate why individual patients may have had infertility, recurrent pregnancy loss, or stillbirth, so research to look further into this association to determine if there is an underlying medical condition that could be treated and therefore possibly reduce both pregnancy complications and future stroke risks would be important,” Dr. Albright noted.

The study was supported by the Australian National Health and Medical Research Council Centres of Research Excellence; one corresponding author was supported by an Australian National Health and Medical Research Council Investigator grant. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the U.S. Preventive Services Task Force concludes.

However, there are two vitamins – vitamin E and beta-carotene – that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos.

sodapix/thinkstockphotos.com

These are the main findings of the USPSTF’s final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. The statement was published in JAMA.

“This is essentially the same recommendation that the task force made in 2014,” USPSTF member John Wong, MD, professor of medicine at Tufts University, Boston, said in an interview.

“We recognize that over half of people in the U.S. take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer,” Dr. Wong explained.

“We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking,” he noted.

Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Dr. Wong explained.

“While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E,” he said.

The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized, controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force noted.

“Apart from beta-carotene and vitamin E, after reviewing 84 studies – including 78 randomized controlled trials – in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don’t know whether people should take vitamins or not, and we need more research,” Dr. Wong added.

On the use of a multivitamin supplement, Dr. Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.

However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.

“The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn’t really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in U.S. male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins,” Dr. Wong explained.

But he noted that the task force did not find any significant harms from taking multivitamins.

“There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn’t find sufficient evidence to be able to make a recommendation,” he said.

Asked what he would say to all the people currently taking multivitamins, Dr. Wong responded that he would advise them to have a conversation with a trusted health care professional about their particular circumstances.

“Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency,” he commented.
 

‘Any benefit likely to be small’

In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD; Natalie Cameron, MD; and Jeffrey Linder, MD – all from Northwestern University, Chicago – noted that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.

The editorialists pointed out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.

They gave an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5-10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).

“In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed,” they said.

The editorialists recommended that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.

However, they added that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.

The editorialists suggested that, rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.
 

Possible benefit for older adults?

Commenting on the USPSTF statement, JoAnn Manson, MD, chief, division of preventive medicine, Brigham and Women’s Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.

“The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing,” she said. “Although it’s easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can’t be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods.”

However, Dr. Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.

She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.  

“The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality,” she noted. “Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults,” Dr. Manson said.

“Many people view multivitamins as a form of insurance, as a way to hedge their bets,” she added. “Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it’s important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day.”

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

There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the U.S. Preventive Services Task Force concludes.

However, there are two vitamins – vitamin E and beta-carotene – that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos.

sodapix/thinkstockphotos.com

These are the main findings of the USPSTF’s final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. The statement was published in JAMA.

“This is essentially the same recommendation that the task force made in 2014,” USPSTF member John Wong, MD, professor of medicine at Tufts University, Boston, said in an interview.

“We recognize that over half of people in the U.S. take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer,” Dr. Wong explained.

“We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking,” he noted.

Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Dr. Wong explained.

“While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E,” he said.

The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized, controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force noted.

“Apart from beta-carotene and vitamin E, after reviewing 84 studies – including 78 randomized controlled trials – in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don’t know whether people should take vitamins or not, and we need more research,” Dr. Wong added.

On the use of a multivitamin supplement, Dr. Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.

However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.

“The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn’t really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in U.S. male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins,” Dr. Wong explained.

But he noted that the task force did not find any significant harms from taking multivitamins.

“There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn’t find sufficient evidence to be able to make a recommendation,” he said.

Asked what he would say to all the people currently taking multivitamins, Dr. Wong responded that he would advise them to have a conversation with a trusted health care professional about their particular circumstances.

“Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency,” he commented.
 

‘Any benefit likely to be small’

In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD; Natalie Cameron, MD; and Jeffrey Linder, MD – all from Northwestern University, Chicago – noted that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.

The editorialists pointed out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.

They gave an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5-10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).

“In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed,” they said.

The editorialists recommended that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.

However, they added that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.

The editorialists suggested that, rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.
 

Possible benefit for older adults?

Commenting on the USPSTF statement, JoAnn Manson, MD, chief, division of preventive medicine, Brigham and Women’s Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.

“The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing,” she said. “Although it’s easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can’t be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods.”

However, Dr. Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.

She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.  

“The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality,” she noted. “Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults,” Dr. Manson said.

“Many people view multivitamins as a form of insurance, as a way to hedge their bets,” she added. “Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it’s important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day.”

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

There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the U.S. Preventive Services Task Force concludes.

However, there are two vitamins – vitamin E and beta-carotene – that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos.

sodapix/thinkstockphotos.com

These are the main findings of the USPSTF’s final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. The statement was published in JAMA.

“This is essentially the same recommendation that the task force made in 2014,” USPSTF member John Wong, MD, professor of medicine at Tufts University, Boston, said in an interview.

“We recognize that over half of people in the U.S. take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer,” Dr. Wong explained.

“We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking,” he noted.

Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Dr. Wong explained.

“While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E,” he said.

The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized, controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force noted.

“Apart from beta-carotene and vitamin E, after reviewing 84 studies – including 78 randomized controlled trials – in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don’t know whether people should take vitamins or not, and we need more research,” Dr. Wong added.

On the use of a multivitamin supplement, Dr. Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.

However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.

“The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn’t really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in U.S. male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins,” Dr. Wong explained.

But he noted that the task force did not find any significant harms from taking multivitamins.

“There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn’t find sufficient evidence to be able to make a recommendation,” he said.

Asked what he would say to all the people currently taking multivitamins, Dr. Wong responded that he would advise them to have a conversation with a trusted health care professional about their particular circumstances.

“Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency,” he commented.
 

‘Any benefit likely to be small’

In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD; Natalie Cameron, MD; and Jeffrey Linder, MD – all from Northwestern University, Chicago – noted that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.

The editorialists pointed out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.

They gave an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5-10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).

“In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed,” they said.

The editorialists recommended that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.

However, they added that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.

The editorialists suggested that, rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.
 

Possible benefit for older adults?

Commenting on the USPSTF statement, JoAnn Manson, MD, chief, division of preventive medicine, Brigham and Women’s Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.

“The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing,” she said. “Although it’s easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can’t be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods.”

However, Dr. Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.

She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.  

“The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality,” she noted. “Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults,” Dr. Manson said.

“Many people view multivitamins as a form of insurance, as a way to hedge their bets,” she added. “Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it’s important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day.”

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

Medtronic is recalling a single lot of HeartWare Ventricular Assist Device (HVAD) System batteries because of welding defects that may cause separation of the two cell battery packs used to power the system, according to an alert on the Food and Drug Administration website.

“The welding defect may cause the battery to malfunction and no longer provide power or prevent the battery from holding a full charge or properly recharging,” the FDA said.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The agency has identified this as a class I recall, the most serious type because of the potential for serious injury or death.

Medtronic reports one death associated with this recall and two complaints in the affected lot.

Back in April, as reported by this news organization, Medtronic alerted providers that patients implanted with the Medtronic HVAD System who develop pump thrombosis could have a welding defect in the internal pump that causes the pump to malfunction.

The batteries from the recalled lot have a model number of 1650DE, were manufactured from April 13 to 19, 2021 and distributed from April 20 to July 19, 2021. The recall affects a total of 429 devices.

On May 5, 2022, Medtronic sent an urgent medical device correction notice to customers asking them to identify and quarantine all affected batteries and notify affected patients. The notice includes a patient template to help communicate directly with patients.

It also includes a customer confirmation form to initiate an exchange. The completed form should be returned to rs.cfqfca@medtronic.com.

Medtronic is replacing the affected batteries with new product and has implemented actions to improve control of the welding process.

The Medtronic HVAD System was approved as a bridge to heart transplantation in 2012. Since then, it’s been fraught with problems.

Earlier in June, the company announced it was stopping all sales of the device and advised physicians to stop implanting it, as reported by this news organization.

Problems related to the Medtronic HVAD System should be reported to the FDA’s MedWatch program.

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

Medtronic is recalling a single lot of HeartWare Ventricular Assist Device (HVAD) System batteries because of welding defects that may cause separation of the two cell battery packs used to power the system, according to an alert on the Food and Drug Administration website.

“The welding defect may cause the battery to malfunction and no longer provide power or prevent the battery from holding a full charge or properly recharging,” the FDA said.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The agency has identified this as a class I recall, the most serious type because of the potential for serious injury or death.

Medtronic reports one death associated with this recall and two complaints in the affected lot.

Back in April, as reported by this news organization, Medtronic alerted providers that patients implanted with the Medtronic HVAD System who develop pump thrombosis could have a welding defect in the internal pump that causes the pump to malfunction.

The batteries from the recalled lot have a model number of 1650DE, were manufactured from April 13 to 19, 2021 and distributed from April 20 to July 19, 2021. The recall affects a total of 429 devices.

On May 5, 2022, Medtronic sent an urgent medical device correction notice to customers asking them to identify and quarantine all affected batteries and notify affected patients. The notice includes a patient template to help communicate directly with patients.

It also includes a customer confirmation form to initiate an exchange. The completed form should be returned to rs.cfqfca@medtronic.com.

Medtronic is replacing the affected batteries with new product and has implemented actions to improve control of the welding process.

The Medtronic HVAD System was approved as a bridge to heart transplantation in 2012. Since then, it’s been fraught with problems.

Earlier in June, the company announced it was stopping all sales of the device and advised physicians to stop implanting it, as reported by this news organization.

Problems related to the Medtronic HVAD System should be reported to the FDA’s MedWatch program.

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

Medtronic is recalling a single lot of HeartWare Ventricular Assist Device (HVAD) System batteries because of welding defects that may cause separation of the two cell battery packs used to power the system, according to an alert on the Food and Drug Administration website.

“The welding defect may cause the battery to malfunction and no longer provide power or prevent the battery from holding a full charge or properly recharging,” the FDA said.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The agency has identified this as a class I recall, the most serious type because of the potential for serious injury or death.

Medtronic reports one death associated with this recall and two complaints in the affected lot.

Back in April, as reported by this news organization, Medtronic alerted providers that patients implanted with the Medtronic HVAD System who develop pump thrombosis could have a welding defect in the internal pump that causes the pump to malfunction.

The batteries from the recalled lot have a model number of 1650DE, were manufactured from April 13 to 19, 2021 and distributed from April 20 to July 19, 2021. The recall affects a total of 429 devices.

On May 5, 2022, Medtronic sent an urgent medical device correction notice to customers asking them to identify and quarantine all affected batteries and notify affected patients. The notice includes a patient template to help communicate directly with patients.

It also includes a customer confirmation form to initiate an exchange. The completed form should be returned to rs.cfqfca@medtronic.com.

Medtronic is replacing the affected batteries with new product and has implemented actions to improve control of the welding process.

The Medtronic HVAD System was approved as a bridge to heart transplantation in 2012. Since then, it’s been fraught with problems.

Earlier in June, the company announced it was stopping all sales of the device and advised physicians to stop implanting it, as reported by this news organization.

Problems related to the Medtronic HVAD System should be reported to the FDA’s MedWatch program.

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