Lipid Disorders

New research suggests serial coronary CT angiography (CCTA) can provide novel insights into the association between lipoprotein(a) and plaque progression over time in patients with advanced coronary artery disease.

Researchers examined data from 191 individuals with multivessel coronary disease receiving preventive statin (95%) and antiplatelet (100%) therapy in the single-center Scottish DIAMOND trial and compared CCTA at baseline and 12 months available for 160 patients.

As reported in the Journal of the American College of Cardiology, patients with high Lp(a), defined as at least 70 mg/dL, had higher baseline high-density lipoprotein cholesterol and ASSIGN scores than those with low Lp(a) but had comparable coronary artery calcium (CAC) scores and total, calcific, noncalcific, and low-attenuation plaque (LAP) volumes.

At 1 year, however, LAP volume – a marker for necrotic core – increased by 26.2 mm3 in the high-Lp(a) group and decreased by –0.7 mm3 in the low-Lp(a) group (P = .020).

There was no significant difference in change in total, calcific, and noncalcific plaque volumes between groups.

In multivariate linear regression analysis adjusting for body mass index, ASSIGN score, and segment involvement score, LAP volume increased by 10.5% for each 50 mg/dL increment in Lp(a) (P = .034).

“It’s an exciting observation, because we’ve done previous studies where we’ve demonstrated the association of that particular plaque type with future myocardial infarction,” senior author Marc R. Dweck, MD, PhD, University of Amsterdam, told this news organization. “So, you’ve potentially got an explanation for the adverse prognosis associated with high lipoprotein(a) and its link to cardiovascular events and, in particular, myocardial infarction.”

The team’s recent SCOT-HEART analysis found that LAP burden was a stronger predictor of myocardial infarction (MI) than cardiovascular risk scores, stenosis severity, and CAC scoring, with MI risk nearly five-fold higher if LAP was above 4%.

As to why total, calcific, and noncalcific plaque volumes didn’t change significantly on repeat CCTA in the present study, Dr. Dweck said it’s possible that the sample was too small and follow-up too short but also that “total plaque volume is really dominated by the fibrous plaque, which doesn’t appear affected by Lp(a).” Nevertheless, Lp(a)’s effect on low-attenuation plaque was clearly present and supported by the change in fibro-fatty plaque, the next-most unstable plaque type.

At 1 year, fibro-fatty plaque volume was 55.0 mm3 in the high-Lp(a) group versus –25.0 mm3 in the low-Lp(a) group (P = .020).

Lp(a) was associated with fibro-fatty plaque progression in univariate analysis (β = 6.7%; P = .034) and showed a trend in multivariable analysis (β = 6.0%; P = .062).

“This study shows you can track changes in plaque over time and highlight important disease mechanisms and use them to understand the pathology of the disease,” Dr. Dweck said. “I’m very encouraged by this.”

What’s novel in the present study is that “it represents the beginning of our understanding of the role of Lp(a) in plaque progression,” Sotirios Tsimikas, MD, University of California, San Diego, and Jagat Narula, MD, PhD, Icahn School of Medicine at Mount Sinai, New York, say in an accompanying commentary.

They note that prior studies, including the Dallas Heart Study, have struggled to find a strong association between Lp(a) with the extent or progression of CAC, despite elevated Lp(a) and CAC identifying higher-risk patients.

Similarly, a meta-analysis of intravascular ultrasound trials turned up only a 1.2% absolute difference in atheroma volume in patients with elevated Lp(a), and a recent optical coherence tomography study found an association of Lp(a) with thin-cap fibroatheromas but not lipid core.

With just 36 patients with elevated Lp(a), however, the current findings need validation in a larger data set, Dr. Tsimikas and Dr. Narula say.

Although Lp(a) is genetically elevated in about one in five individuals and measurement is recommended in European dyslipidemia guidelines, testing rates are low, in part because the argument has been that there are no Lp(a)-lowering therapies available, Dr. Dweck observed. That may change with the phase 3 cardiovascular outcomes Lp(a)HORIZON trial, which follows strong phase 2 results with the antisense agent AKCEA-APO(a)-LRx and is enrolling patients similar to the current cohort.

“Ultimately it comes down to that fundamental thing, that you need an action once you’ve done the test and then insurers will be happy to pay for it and clinicians will ask for it. That’s why that trial is so important,” Dr. Dweck said.

Dr. Tsimikas and Dr. Narula also point to the eagerly awaited results of that trial, expected in 2025. “A positive trial is likely to lead to additional trials and new drugs that may reinvigorate the use of imaging modalities that could go beyond plaque volume and atherosclerosis to also predict clinically relevant inflammation and atherothrombosis,” they conclude.

Dr. Dweck is supported by the British Heart Foundation and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015; has received speaker fees from Pfizer and Novartis; and has received consultancy fees from Novartis, Jupiter Bioventures, and Silence Therapeutics. Coauthor disclosures are listed in the paper. Dr. Tsimikas has a dual appointment at the University of California, San Diego, (UCSD) and Ionis Pharmaceuticals; is a coinventor and receives royalties from patents owned by UCSD; and is a cofounder and has an equity interest in Oxitope and its affiliates, Kleanthi Diagnostics, and Covicept Therapeutics. Dr. Narula reports having no relevant financial relationships.

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

New research suggests serial coronary CT angiography (CCTA) can provide novel insights into the association between lipoprotein(a) and plaque progression over time in patients with advanced coronary artery disease.

Researchers examined data from 191 individuals with multivessel coronary disease receiving preventive statin (95%) and antiplatelet (100%) therapy in the single-center Scottish DIAMOND trial and compared CCTA at baseline and 12 months available for 160 patients.

As reported in the Journal of the American College of Cardiology, patients with high Lp(a), defined as at least 70 mg/dL, had higher baseline high-density lipoprotein cholesterol and ASSIGN scores than those with low Lp(a) but had comparable coronary artery calcium (CAC) scores and total, calcific, noncalcific, and low-attenuation plaque (LAP) volumes.

At 1 year, however, LAP volume – a marker for necrotic core – increased by 26.2 mm3 in the high-Lp(a) group and decreased by –0.7 mm3 in the low-Lp(a) group (P = .020).

There was no significant difference in change in total, calcific, and noncalcific plaque volumes between groups.

In multivariate linear regression analysis adjusting for body mass index, ASSIGN score, and segment involvement score, LAP volume increased by 10.5% for each 50 mg/dL increment in Lp(a) (P = .034).

“It’s an exciting observation, because we’ve done previous studies where we’ve demonstrated the association of that particular plaque type with future myocardial infarction,” senior author Marc R. Dweck, MD, PhD, University of Amsterdam, told this news organization. “So, you’ve potentially got an explanation for the adverse prognosis associated with high lipoprotein(a) and its link to cardiovascular events and, in particular, myocardial infarction.”

The team’s recent SCOT-HEART analysis found that LAP burden was a stronger predictor of myocardial infarction (MI) than cardiovascular risk scores, stenosis severity, and CAC scoring, with MI risk nearly five-fold higher if LAP was above 4%.

As to why total, calcific, and noncalcific plaque volumes didn’t change significantly on repeat CCTA in the present study, Dr. Dweck said it’s possible that the sample was too small and follow-up too short but also that “total plaque volume is really dominated by the fibrous plaque, which doesn’t appear affected by Lp(a).” Nevertheless, Lp(a)’s effect on low-attenuation plaque was clearly present and supported by the change in fibro-fatty plaque, the next-most unstable plaque type.

At 1 year, fibro-fatty plaque volume was 55.0 mm3 in the high-Lp(a) group versus –25.0 mm3 in the low-Lp(a) group (P = .020).

Lp(a) was associated with fibro-fatty plaque progression in univariate analysis (β = 6.7%; P = .034) and showed a trend in multivariable analysis (β = 6.0%; P = .062).

“This study shows you can track changes in plaque over time and highlight important disease mechanisms and use them to understand the pathology of the disease,” Dr. Dweck said. “I’m very encouraged by this.”

What’s novel in the present study is that “it represents the beginning of our understanding of the role of Lp(a) in plaque progression,” Sotirios Tsimikas, MD, University of California, San Diego, and Jagat Narula, MD, PhD, Icahn School of Medicine at Mount Sinai, New York, say in an accompanying commentary.

They note that prior studies, including the Dallas Heart Study, have struggled to find a strong association between Lp(a) with the extent or progression of CAC, despite elevated Lp(a) and CAC identifying higher-risk patients.

Similarly, a meta-analysis of intravascular ultrasound trials turned up only a 1.2% absolute difference in atheroma volume in patients with elevated Lp(a), and a recent optical coherence tomography study found an association of Lp(a) with thin-cap fibroatheromas but not lipid core.

With just 36 patients with elevated Lp(a), however, the current findings need validation in a larger data set, Dr. Tsimikas and Dr. Narula say.

Although Lp(a) is genetically elevated in about one in five individuals and measurement is recommended in European dyslipidemia guidelines, testing rates are low, in part because the argument has been that there are no Lp(a)-lowering therapies available, Dr. Dweck observed. That may change with the phase 3 cardiovascular outcomes Lp(a)HORIZON trial, which follows strong phase 2 results with the antisense agent AKCEA-APO(a)-LRx and is enrolling patients similar to the current cohort.

“Ultimately it comes down to that fundamental thing, that you need an action once you’ve done the test and then insurers will be happy to pay for it and clinicians will ask for it. That’s why that trial is so important,” Dr. Dweck said.

Dr. Tsimikas and Dr. Narula also point to the eagerly awaited results of that trial, expected in 2025. “A positive trial is likely to lead to additional trials and new drugs that may reinvigorate the use of imaging modalities that could go beyond plaque volume and atherosclerosis to also predict clinically relevant inflammation and atherothrombosis,” they conclude.

Dr. Dweck is supported by the British Heart Foundation and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015; has received speaker fees from Pfizer and Novartis; and has received consultancy fees from Novartis, Jupiter Bioventures, and Silence Therapeutics. Coauthor disclosures are listed in the paper. Dr. Tsimikas has a dual appointment at the University of California, San Diego, (UCSD) and Ionis Pharmaceuticals; is a coinventor and receives royalties from patents owned by UCSD; and is a cofounder and has an equity interest in Oxitope and its affiliates, Kleanthi Diagnostics, and Covicept Therapeutics. Dr. Narula reports having no relevant financial relationships.

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

New research suggests serial coronary CT angiography (CCTA) can provide novel insights into the association between lipoprotein(a) and plaque progression over time in patients with advanced coronary artery disease.

Researchers examined data from 191 individuals with multivessel coronary disease receiving preventive statin (95%) and antiplatelet (100%) therapy in the single-center Scottish DIAMOND trial and compared CCTA at baseline and 12 months available for 160 patients.

As reported in the Journal of the American College of Cardiology, patients with high Lp(a), defined as at least 70 mg/dL, had higher baseline high-density lipoprotein cholesterol and ASSIGN scores than those with low Lp(a) but had comparable coronary artery calcium (CAC) scores and total, calcific, noncalcific, and low-attenuation plaque (LAP) volumes.

At 1 year, however, LAP volume – a marker for necrotic core – increased by 26.2 mm3 in the high-Lp(a) group and decreased by –0.7 mm3 in the low-Lp(a) group (P = .020).

There was no significant difference in change in total, calcific, and noncalcific plaque volumes between groups.

In multivariate linear regression analysis adjusting for body mass index, ASSIGN score, and segment involvement score, LAP volume increased by 10.5% for each 50 mg/dL increment in Lp(a) (P = .034).

“It’s an exciting observation, because we’ve done previous studies where we’ve demonstrated the association of that particular plaque type with future myocardial infarction,” senior author Marc R. Dweck, MD, PhD, University of Amsterdam, told this news organization. “So, you’ve potentially got an explanation for the adverse prognosis associated with high lipoprotein(a) and its link to cardiovascular events and, in particular, myocardial infarction.”

The team’s recent SCOT-HEART analysis found that LAP burden was a stronger predictor of myocardial infarction (MI) than cardiovascular risk scores, stenosis severity, and CAC scoring, with MI risk nearly five-fold higher if LAP was above 4%.

As to why total, calcific, and noncalcific plaque volumes didn’t change significantly on repeat CCTA in the present study, Dr. Dweck said it’s possible that the sample was too small and follow-up too short but also that “total plaque volume is really dominated by the fibrous plaque, which doesn’t appear affected by Lp(a).” Nevertheless, Lp(a)’s effect on low-attenuation plaque was clearly present and supported by the change in fibro-fatty plaque, the next-most unstable plaque type.

At 1 year, fibro-fatty plaque volume was 55.0 mm3 in the high-Lp(a) group versus –25.0 mm3 in the low-Lp(a) group (P = .020).

Lp(a) was associated with fibro-fatty plaque progression in univariate analysis (β = 6.7%; P = .034) and showed a trend in multivariable analysis (β = 6.0%; P = .062).

“This study shows you can track changes in plaque over time and highlight important disease mechanisms and use them to understand the pathology of the disease,” Dr. Dweck said. “I’m very encouraged by this.”

What’s novel in the present study is that “it represents the beginning of our understanding of the role of Lp(a) in plaque progression,” Sotirios Tsimikas, MD, University of California, San Diego, and Jagat Narula, MD, PhD, Icahn School of Medicine at Mount Sinai, New York, say in an accompanying commentary.

They note that prior studies, including the Dallas Heart Study, have struggled to find a strong association between Lp(a) with the extent or progression of CAC, despite elevated Lp(a) and CAC identifying higher-risk patients.

Similarly, a meta-analysis of intravascular ultrasound trials turned up only a 1.2% absolute difference in atheroma volume in patients with elevated Lp(a), and a recent optical coherence tomography study found an association of Lp(a) with thin-cap fibroatheromas but not lipid core.

With just 36 patients with elevated Lp(a), however, the current findings need validation in a larger data set, Dr. Tsimikas and Dr. Narula say.

Although Lp(a) is genetically elevated in about one in five individuals and measurement is recommended in European dyslipidemia guidelines, testing rates are low, in part because the argument has been that there are no Lp(a)-lowering therapies available, Dr. Dweck observed. That may change with the phase 3 cardiovascular outcomes Lp(a)HORIZON trial, which follows strong phase 2 results with the antisense agent AKCEA-APO(a)-LRx and is enrolling patients similar to the current cohort.

“Ultimately it comes down to that fundamental thing, that you need an action once you’ve done the test and then insurers will be happy to pay for it and clinicians will ask for it. That’s why that trial is so important,” Dr. Dweck said.

Dr. Tsimikas and Dr. Narula also point to the eagerly awaited results of that trial, expected in 2025. “A positive trial is likely to lead to additional trials and new drugs that may reinvigorate the use of imaging modalities that could go beyond plaque volume and atherosclerosis to also predict clinically relevant inflammation and atherothrombosis,” they conclude.

Dr. Dweck is supported by the British Heart Foundation and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015; has received speaker fees from Pfizer and Novartis; and has received consultancy fees from Novartis, Jupiter Bioventures, and Silence Therapeutics. Coauthor disclosures are listed in the paper. Dr. Tsimikas has a dual appointment at the University of California, San Diego, (UCSD) and Ionis Pharmaceuticals; is a coinventor and receives royalties from patents owned by UCSD; and is a cofounder and has an equity interest in Oxitope and its affiliates, Kleanthi Diagnostics, and Covicept Therapeutics. Dr. Narula reports having no relevant financial relationships.

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

In a meta-analysis of more than 1 million mothers, those who breastfed their children had an 11% to 17% lower risk of developing cardiovascular disease (CVD), coronary heart disease (CHD), or stroke, and of dying from CVD, in later life than mothers who did not.

On average, the women had two children and had breastfed for 15.9 months in total. Longer breastfeeding was associated with greater CV health benefit.

This meta-analysis of eight studies from different countries was published online Jan. 11 in an issue of the Journal of the American Heart Association devoted to the impact of pregnancy on CV health in the mother and child.

Breastfeeding is known to be associated with a lower risk for death from infectious disease and with fewer respiratory infections in babies, the researchers write, but what is less well known is that it is also associated with a reduced risk for breast and ovarian cancer and type 2 diabetes in mothers.

The current study showed a clear association between breastfeeding and reduced risk for CVD in later life, lead author Lena Tschiderer, Dipl.-Ing., PhD, and senior author Peter Willeit, MD, MPhil, PhD, summarized in a joint email to this news organization.

Specifically, mothers who had breastfed their children at any time had an 11% lower risk for CVD, a 14% lower risk for CHD, a 12% lower risk for stroke, and a 17% lower risk of dying from CVD in later life, compared with other mothers.

On the basis of existing evidence, the researchers write, the World Health Organization recommends exclusive breastfeeding until a baby is 6 months old, followed by breastfeeding plus complementary feeding until the baby is 2 years or older.

“We believe that [breastfeeding] benefits for the mother are communicated poorly,” said Dr. Tschiderer and Dr. Willeit, from the University of Innsbruck, Austria.

“Positive effects of breastfeeding on mothers need to be communicated effectively, awareness for breastfeeding recommendations needs to be raised, and interventions to promote and facilitate breastfeeding need to be implemented and reinforced,” the researchers conclude.
 

‘Should not be ignored’

Two cardiologists invited to comment, who were not involved with the research, noted that this study provides insight into an important topic.

“This is yet another body of evidence [and the largest population to date] to show that breastfeeding is protective for women and may show important beneficial effects in terms of CV risk,” Roxana Mehran, MD, said in an email.

“The risk reductions were 11% for CVD events and 14% for CHD events; these are impressive numbers,” said Dr. Mehran, from Icahn School of Medicine at Mount Sinai, New York.

“The caveat,” she said, “is that these are data from several trials, but nonetheless, this is a very important observation that should not be ignored.”

The study did not address the definitive amount of time of breastfeeding and its correlation to the improvement of CVD risk, but it did show that for the lifetime duration, the longer the better.

“The beneficial effects,” she noted, “can be linked to hormones during breastfeeding, as well as weight loss associated with breastfeeding, and resetting the maternal metabolism, as the authors suggest.”

Clinicians and employers “must provide ways to educate women about breastfeeding and make it easy for women who are in the workplace to pump, and to provide them with resources” where possible, Dr. Mehran said.

Michelle O’Donoghue, MD, MPH, noted that over the past several years, there has been intense interest in the possible health benefits of breastfeeding for both mother and child.

There is biologic plausibility for some of the possible maternal benefits because the favorable CV effects of both prolactin and oxytocin are only now being better understood, said Dr. O’Donoghue, from Brigham and Women’s Hospital and Harvard Medical School, Boston.

“The current meta-analysis provides a large dataset that helps support the concept that breastfeeding may offer some cardiovascular benefit for the mother,” she agreed.

“However, ultimately more research will be necessary since this method of combining data across trials relies upon the robustness of the statistical method in each study,” Dr. O’Donoghue said. “I applaud the authors for shining a spotlight on this important topic.”

Although the benefits of breastfeeding appear to continue over time, “it is incredibly difficult for women to continue breastfeeding once they return to work,” she added. “Women in some countries outside the U.S. have an advantage due to longer durations of maternity leave.

“If we want to encourage breastfeeding,” Dr. O’Donoghue stressed, “we need to make sure that we put the right supports in place. Women need protected places to breastfeed in the workplace and places to store their milk. Most importantly, women need to be allowed dedicated time to make it happen.”
 

First large study of CVD in mothers

Emerging individual studies suggest that mothers who breastfeed may have a lower risk for CVD in later life, but studies have been inconsistent, and it is not clear if longer breastfeeding would strengthen this benefit, the authors note.

To examine this, they pooled data from the following eight studies (with study acronym, country, and baseline enrolment dates in brackets): 45&Up (Australia, 2006-2009), China Kadoorie Biobank (CKB, China, 2004-2008), European Prospective Investigation into Cancer and Nutrition (EPIC, multinational, 1992-2000), Gallagher et al. (China, 1989-1991), Nord-Trøndelag Health Survey 2 (HUNT2, Norway, 1995-1997), Japan Public Health Center-based Prospective Study (JPHC, Japan, 1990-1994), Nurses’ Health Study (NHS, U.S., 1986), and the Woman’s Health Initiative (WHI, U.S., 1993-1998).

On average, the women were 51.3 years old (range, 40-65 years) when they enrolled in the study, and they were followed for a median of 10.3 years (range, 7.9-20.9 years, in the individual studies).

On average, they had their first child at age 25 and had two to three children (mean, 2.3); 82% had breastfed at some point (ranging from 58% of women in the two U.S. studies to 97% in CKB and HUNT2).

The women had breastfed for a mean of 7.4 to 18.9 months during their lifetimes (except women in the CKB study, who had breastfed for a median of 24 months).

Among the 1,192,700 women, there were 54,226 incident CVD events, 26,913 incident CHD events, 30,843 incident strokes, and 10,766 deaths from CVD during follow-up.

The researchers acknowledge that study limitations include the fact that there could have been publication bias, since fewer than 10 studies were available for pooling. There was significant between-study heterogeneity for CVD, CHD, and stroke outcomes.

Participant-level data were also lacking, and breastfeeding was self-reported. There may have been unaccounted residual confounding, and the benefits of lifetime breastfeeding that is longer than 2 years are not clear, because few women in this population breastfed that long.

The research was funded by the Austrian Science Fund. The researchers and Dr. Mehran and Dr. O’Donoghue have no relevant financial disclosures.

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

In a meta-analysis of more than 1 million mothers, those who breastfed their children had an 11% to 17% lower risk of developing cardiovascular disease (CVD), coronary heart disease (CHD), or stroke, and of dying from CVD, in later life than mothers who did not.

On average, the women had two children and had breastfed for 15.9 months in total. Longer breastfeeding was associated with greater CV health benefit.

This meta-analysis of eight studies from different countries was published online Jan. 11 in an issue of the Journal of the American Heart Association devoted to the impact of pregnancy on CV health in the mother and child.

Breastfeeding is known to be associated with a lower risk for death from infectious disease and with fewer respiratory infections in babies, the researchers write, but what is less well known is that it is also associated with a reduced risk for breast and ovarian cancer and type 2 diabetes in mothers.

The current study showed a clear association between breastfeeding and reduced risk for CVD in later life, lead author Lena Tschiderer, Dipl.-Ing., PhD, and senior author Peter Willeit, MD, MPhil, PhD, summarized in a joint email to this news organization.

Specifically, mothers who had breastfed their children at any time had an 11% lower risk for CVD, a 14% lower risk for CHD, a 12% lower risk for stroke, and a 17% lower risk of dying from CVD in later life, compared with other mothers.

On the basis of existing evidence, the researchers write, the World Health Organization recommends exclusive breastfeeding until a baby is 6 months old, followed by breastfeeding plus complementary feeding until the baby is 2 years or older.

“We believe that [breastfeeding] benefits for the mother are communicated poorly,” said Dr. Tschiderer and Dr. Willeit, from the University of Innsbruck, Austria.

“Positive effects of breastfeeding on mothers need to be communicated effectively, awareness for breastfeeding recommendations needs to be raised, and interventions to promote and facilitate breastfeeding need to be implemented and reinforced,” the researchers conclude.
 

‘Should not be ignored’

Two cardiologists invited to comment, who were not involved with the research, noted that this study provides insight into an important topic.

“This is yet another body of evidence [and the largest population to date] to show that breastfeeding is protective for women and may show important beneficial effects in terms of CV risk,” Roxana Mehran, MD, said in an email.

“The risk reductions were 11% for CVD events and 14% for CHD events; these are impressive numbers,” said Dr. Mehran, from Icahn School of Medicine at Mount Sinai, New York.

“The caveat,” she said, “is that these are data from several trials, but nonetheless, this is a very important observation that should not be ignored.”

The study did not address the definitive amount of time of breastfeeding and its correlation to the improvement of CVD risk, but it did show that for the lifetime duration, the longer the better.

“The beneficial effects,” she noted, “can be linked to hormones during breastfeeding, as well as weight loss associated with breastfeeding, and resetting the maternal metabolism, as the authors suggest.”

Clinicians and employers “must provide ways to educate women about breastfeeding and make it easy for women who are in the workplace to pump, and to provide them with resources” where possible, Dr. Mehran said.

Michelle O’Donoghue, MD, MPH, noted that over the past several years, there has been intense interest in the possible health benefits of breastfeeding for both mother and child.

There is biologic plausibility for some of the possible maternal benefits because the favorable CV effects of both prolactin and oxytocin are only now being better understood, said Dr. O’Donoghue, from Brigham and Women’s Hospital and Harvard Medical School, Boston.

“The current meta-analysis provides a large dataset that helps support the concept that breastfeeding may offer some cardiovascular benefit for the mother,” she agreed.

“However, ultimately more research will be necessary since this method of combining data across trials relies upon the robustness of the statistical method in each study,” Dr. O’Donoghue said. “I applaud the authors for shining a spotlight on this important topic.”

Although the benefits of breastfeeding appear to continue over time, “it is incredibly difficult for women to continue breastfeeding once they return to work,” she added. “Women in some countries outside the U.S. have an advantage due to longer durations of maternity leave.

“If we want to encourage breastfeeding,” Dr. O’Donoghue stressed, “we need to make sure that we put the right supports in place. Women need protected places to breastfeed in the workplace and places to store their milk. Most importantly, women need to be allowed dedicated time to make it happen.”
 

First large study of CVD in mothers

Emerging individual studies suggest that mothers who breastfeed may have a lower risk for CVD in later life, but studies have been inconsistent, and it is not clear if longer breastfeeding would strengthen this benefit, the authors note.

To examine this, they pooled data from the following eight studies (with study acronym, country, and baseline enrolment dates in brackets): 45&Up (Australia, 2006-2009), China Kadoorie Biobank (CKB, China, 2004-2008), European Prospective Investigation into Cancer and Nutrition (EPIC, multinational, 1992-2000), Gallagher et al. (China, 1989-1991), Nord-Trøndelag Health Survey 2 (HUNT2, Norway, 1995-1997), Japan Public Health Center-based Prospective Study (JPHC, Japan, 1990-1994), Nurses’ Health Study (NHS, U.S., 1986), and the Woman’s Health Initiative (WHI, U.S., 1993-1998).

On average, the women were 51.3 years old (range, 40-65 years) when they enrolled in the study, and they were followed for a median of 10.3 years (range, 7.9-20.9 years, in the individual studies).

On average, they had their first child at age 25 and had two to three children (mean, 2.3); 82% had breastfed at some point (ranging from 58% of women in the two U.S. studies to 97% in CKB and HUNT2).

The women had breastfed for a mean of 7.4 to 18.9 months during their lifetimes (except women in the CKB study, who had breastfed for a median of 24 months).

Among the 1,192,700 women, there were 54,226 incident CVD events, 26,913 incident CHD events, 30,843 incident strokes, and 10,766 deaths from CVD during follow-up.

The researchers acknowledge that study limitations include the fact that there could have been publication bias, since fewer than 10 studies were available for pooling. There was significant between-study heterogeneity for CVD, CHD, and stroke outcomes.

Participant-level data were also lacking, and breastfeeding was self-reported. There may have been unaccounted residual confounding, and the benefits of lifetime breastfeeding that is longer than 2 years are not clear, because few women in this population breastfed that long.

The research was funded by the Austrian Science Fund. The researchers and Dr. Mehran and Dr. O’Donoghue have no relevant financial disclosures.

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

In a meta-analysis of more than 1 million mothers, those who breastfed their children had an 11% to 17% lower risk of developing cardiovascular disease (CVD), coronary heart disease (CHD), or stroke, and of dying from CVD, in later life than mothers who did not.

On average, the women had two children and had breastfed for 15.9 months in total. Longer breastfeeding was associated with greater CV health benefit.

This meta-analysis of eight studies from different countries was published online Jan. 11 in an issue of the Journal of the American Heart Association devoted to the impact of pregnancy on CV health in the mother and child.

Breastfeeding is known to be associated with a lower risk for death from infectious disease and with fewer respiratory infections in babies, the researchers write, but what is less well known is that it is also associated with a reduced risk for breast and ovarian cancer and type 2 diabetes in mothers.

The current study showed a clear association between breastfeeding and reduced risk for CVD in later life, lead author Lena Tschiderer, Dipl.-Ing., PhD, and senior author Peter Willeit, MD, MPhil, PhD, summarized in a joint email to this news organization.

Specifically, mothers who had breastfed their children at any time had an 11% lower risk for CVD, a 14% lower risk for CHD, a 12% lower risk for stroke, and a 17% lower risk of dying from CVD in later life, compared with other mothers.

On the basis of existing evidence, the researchers write, the World Health Organization recommends exclusive breastfeeding until a baby is 6 months old, followed by breastfeeding plus complementary feeding until the baby is 2 years or older.

“We believe that [breastfeeding] benefits for the mother are communicated poorly,” said Dr. Tschiderer and Dr. Willeit, from the University of Innsbruck, Austria.

“Positive effects of breastfeeding on mothers need to be communicated effectively, awareness for breastfeeding recommendations needs to be raised, and interventions to promote and facilitate breastfeeding need to be implemented and reinforced,” the researchers conclude.
 

‘Should not be ignored’

Two cardiologists invited to comment, who were not involved with the research, noted that this study provides insight into an important topic.

“This is yet another body of evidence [and the largest population to date] to show that breastfeeding is protective for women and may show important beneficial effects in terms of CV risk,” Roxana Mehran, MD, said in an email.

“The risk reductions were 11% for CVD events and 14% for CHD events; these are impressive numbers,” said Dr. Mehran, from Icahn School of Medicine at Mount Sinai, New York.

“The caveat,” she said, “is that these are data from several trials, but nonetheless, this is a very important observation that should not be ignored.”

The study did not address the definitive amount of time of breastfeeding and its correlation to the improvement of CVD risk, but it did show that for the lifetime duration, the longer the better.

“The beneficial effects,” she noted, “can be linked to hormones during breastfeeding, as well as weight loss associated with breastfeeding, and resetting the maternal metabolism, as the authors suggest.”

Clinicians and employers “must provide ways to educate women about breastfeeding and make it easy for women who are in the workplace to pump, and to provide them with resources” where possible, Dr. Mehran said.

Michelle O’Donoghue, MD, MPH, noted that over the past several years, there has been intense interest in the possible health benefits of breastfeeding for both mother and child.

There is biologic plausibility for some of the possible maternal benefits because the favorable CV effects of both prolactin and oxytocin are only now being better understood, said Dr. O’Donoghue, from Brigham and Women’s Hospital and Harvard Medical School, Boston.

“The current meta-analysis provides a large dataset that helps support the concept that breastfeeding may offer some cardiovascular benefit for the mother,” she agreed.

“However, ultimately more research will be necessary since this method of combining data across trials relies upon the robustness of the statistical method in each study,” Dr. O’Donoghue said. “I applaud the authors for shining a spotlight on this important topic.”

Although the benefits of breastfeeding appear to continue over time, “it is incredibly difficult for women to continue breastfeeding once they return to work,” she added. “Women in some countries outside the U.S. have an advantage due to longer durations of maternity leave.

“If we want to encourage breastfeeding,” Dr. O’Donoghue stressed, “we need to make sure that we put the right supports in place. Women need protected places to breastfeed in the workplace and places to store their milk. Most importantly, women need to be allowed dedicated time to make it happen.”
 

First large study of CVD in mothers

Emerging individual studies suggest that mothers who breastfeed may have a lower risk for CVD in later life, but studies have been inconsistent, and it is not clear if longer breastfeeding would strengthen this benefit, the authors note.

To examine this, they pooled data from the following eight studies (with study acronym, country, and baseline enrolment dates in brackets): 45&Up (Australia, 2006-2009), China Kadoorie Biobank (CKB, China, 2004-2008), European Prospective Investigation into Cancer and Nutrition (EPIC, multinational, 1992-2000), Gallagher et al. (China, 1989-1991), Nord-Trøndelag Health Survey 2 (HUNT2, Norway, 1995-1997), Japan Public Health Center-based Prospective Study (JPHC, Japan, 1990-1994), Nurses’ Health Study (NHS, U.S., 1986), and the Woman’s Health Initiative (WHI, U.S., 1993-1998).

On average, the women were 51.3 years old (range, 40-65 years) when they enrolled in the study, and they were followed for a median of 10.3 years (range, 7.9-20.9 years, in the individual studies).

On average, they had their first child at age 25 and had two to three children (mean, 2.3); 82% had breastfed at some point (ranging from 58% of women in the two U.S. studies to 97% in CKB and HUNT2).

The women had breastfed for a mean of 7.4 to 18.9 months during their lifetimes (except women in the CKB study, who had breastfed for a median of 24 months).

Among the 1,192,700 women, there were 54,226 incident CVD events, 26,913 incident CHD events, 30,843 incident strokes, and 10,766 deaths from CVD during follow-up.

The researchers acknowledge that study limitations include the fact that there could have been publication bias, since fewer than 10 studies were available for pooling. There was significant between-study heterogeneity for CVD, CHD, and stroke outcomes.

Participant-level data were also lacking, and breastfeeding was self-reported. There may have been unaccounted residual confounding, and the benefits of lifetime breastfeeding that is longer than 2 years are not clear, because few women in this population breastfed that long.

The research was funded by the Austrian Science Fund. The researchers and Dr. Mehran and Dr. O’Donoghue have no relevant financial disclosures.

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

Creators of a pilot program that educates preschoolers about good heart health have validated a template for successful early childhood intervention that, they claim, provides a pathway for translating scientific evidence into the community and classroom for educational purposes to encourage long-lasting lifestyle changes.

That validation supports the creators' plans to take the program into more schools.

They reported key lessons in crafting the program, known as the SI! Program (for Salud Integral-Comprehensive Health), online in the Journal of the American College of Cardiology.

Mount Sinai Hospital

“This is a research-based program that uses randomized clinical trial evidence with implementation strategies to design educational health promotion programs,” senior author Valentin Fuster, MD, PhD, founder and trustees chairman of the Foundation for Science, Health, and Education (SHE) based in Barcelona, under whose aegis the SI! Program was implemented, said in an interview. Dr. Fuster is also director of Mount Sinai Heart and physician-in-chief at Mount Sinai Hospital in New York, and general director of the National Center for Cardiovascular Investigation (CNIC) in Madrid, Spain’s equivalent of the National Heart, Lung, and Blood Institute.

“There are specific times in a child’s life when improvements can be made to enhance long-term cardiovascular health status,” said Rodrigo Fernández-Jiménez, MD, PhD, group leader of the cardiovascular health and imaging lab at CNIC and study coauthor. “Our review, and previous studies, suggest that 4-5 years of age is the most favorable time to start a school-based intervention focused on healthy habits.”

A key piece of the SI! Program used a Sesame Street character, known as Dr. Ruster, a Muppet based on Dr. Fuster, to introduce and convey most messages and activities to the preschool children. The program also used a heart-shaped mascot named “Cardio” to teach about healthy behaviors. Other components include video segments, a colorful storybook, an interactive board game, flash cards, and a teacher’s guide. The activities and messages were tailored based on the country in which the program was implemented.
 

A decade of experience

The review evaluated 10 years of experience with the preschool-based program, drawing upon cluster-randomized clinical trials of the program in three countries with different socioeconomic conditions: Colombia, Spain, and the United States. The studies randomized schools to receive the SI! Program for 4 months or to a control group and included more than 3,800 children from 50 schools, along with their parents or caregivers and teachers. The studies found significant increases in preschoolers’ knowledge, attitudes, and habits toward healthy eating and living an active lifestyle. Now, the SI! Program is expanding into more than 250 schools in Spain and more than 40 schools in all five boroughs of New York City.

“This is a multidimensional program,” Dr. Fuster said. The review identified five stages for implementing the program: dissemination; adoption; implementation; evaluation; and institutionalization.

Dissemination involves three substages for intervention: components, design, and strategy. With regard to the components, said Dr. Fuster, “We’re targeting children to educate them in four topics: how the body works; nutritional and dietary requirements; physical activity; and the need to control emotions – to say no in the future when they’re confronted with alcohol, drugs, and tobacco.”

Design involved a multidisciplinary team of experts to develop the intervention, Dr. Fuster said. The strategy itself enlists parents and teachers in the implementation, but goes beyond that. “This is a community,” Dr. Fuster said. Hence, the school environment and classroom itself are also engaged to support the message of the four topics.

Dr. Fuster said future research should look at knowledge, attitude, and habits and biological outcomes in children who’ve been in the SI! Program when they reach adolescence. “Our hypothesis is that we can do this in older children, but when they reach age 10 we want to reintervene in them,” Dr. Fuster said. “Humans need reintervention. Our findings don’t get into sustainability.” He added that further research should also identify socioeconomic factors that influence child health.

Expanding the program across the New York City’s five boroughs “offers a unique opportunity to explore which socioeconomic factors, at both the family and borough level, and may eventually affect children’s health, how they are implicated in the intervention’s effectiveness, and how they can be addressed to reduce the gap in health inequalities,” he said. 

Karalyn Kinsella, MD, a pediatrician affiliated with Yale New Haven (Conn.) Medical Center, noted the program’s multidimensional nature is an important element. “I think what is so important about this intervention is that it is not one single intervention but a curriculum that takes a significant amount of time (up to 50 hours) that allows for repetition of the information, which allows it to become remembered,” she said in an interview. “I also think incorporating families in the intervention is key as that is where change often has to happen.”

While she said the program may provide a template for a mental health curriculum, she added, “My concern is that teachers are already feeling overwhelmed and this may be viewed as another burden.”

The American Heart Association provided funding for the study in the United States. Dr Fernández-Jiménez has received funding from the Fondo de Investigación Sanitaria–Instituto de Salud Carlos III, which is cofunded by the European Regional Development Fund/European Social Fund. Dr. Fuster and Dr. Kinsella have no relevant disclosures.

Creators of a pilot program that educates preschoolers about good heart health have validated a template for successful early childhood intervention that, they claim, provides a pathway for translating scientific evidence into the community and classroom for educational purposes to encourage long-lasting lifestyle changes.

That validation supports the creators' plans to take the program into more schools.

They reported key lessons in crafting the program, known as the SI! Program (for Salud Integral-Comprehensive Health), online in the Journal of the American College of Cardiology.

Mount Sinai Hospital

“This is a research-based program that uses randomized clinical trial evidence with implementation strategies to design educational health promotion programs,” senior author Valentin Fuster, MD, PhD, founder and trustees chairman of the Foundation for Science, Health, and Education (SHE) based in Barcelona, under whose aegis the SI! Program was implemented, said in an interview. Dr. Fuster is also director of Mount Sinai Heart and physician-in-chief at Mount Sinai Hospital in New York, and general director of the National Center for Cardiovascular Investigation (CNIC) in Madrid, Spain’s equivalent of the National Heart, Lung, and Blood Institute.

“There are specific times in a child’s life when improvements can be made to enhance long-term cardiovascular health status,” said Rodrigo Fernández-Jiménez, MD, PhD, group leader of the cardiovascular health and imaging lab at CNIC and study coauthor. “Our review, and previous studies, suggest that 4-5 years of age is the most favorable time to start a school-based intervention focused on healthy habits.”

A key piece of the SI! Program used a Sesame Street character, known as Dr. Ruster, a Muppet based on Dr. Fuster, to introduce and convey most messages and activities to the preschool children. The program also used a heart-shaped mascot named “Cardio” to teach about healthy behaviors. Other components include video segments, a colorful storybook, an interactive board game, flash cards, and a teacher’s guide. The activities and messages were tailored based on the country in which the program was implemented.
 

A decade of experience

The review evaluated 10 years of experience with the preschool-based program, drawing upon cluster-randomized clinical trials of the program in three countries with different socioeconomic conditions: Colombia, Spain, and the United States. The studies randomized schools to receive the SI! Program for 4 months or to a control group and included more than 3,800 children from 50 schools, along with their parents or caregivers and teachers. The studies found significant increases in preschoolers’ knowledge, attitudes, and habits toward healthy eating and living an active lifestyle. Now, the SI! Program is expanding into more than 250 schools in Spain and more than 40 schools in all five boroughs of New York City.

“This is a multidimensional program,” Dr. Fuster said. The review identified five stages for implementing the program: dissemination; adoption; implementation; evaluation; and institutionalization.

Dissemination involves three substages for intervention: components, design, and strategy. With regard to the components, said Dr. Fuster, “We’re targeting children to educate them in four topics: how the body works; nutritional and dietary requirements; physical activity; and the need to control emotions – to say no in the future when they’re confronted with alcohol, drugs, and tobacco.”

Design involved a multidisciplinary team of experts to develop the intervention, Dr. Fuster said. The strategy itself enlists parents and teachers in the implementation, but goes beyond that. “This is a community,” Dr. Fuster said. Hence, the school environment and classroom itself are also engaged to support the message of the four topics.

Dr. Fuster said future research should look at knowledge, attitude, and habits and biological outcomes in children who’ve been in the SI! Program when they reach adolescence. “Our hypothesis is that we can do this in older children, but when they reach age 10 we want to reintervene in them,” Dr. Fuster said. “Humans need reintervention. Our findings don’t get into sustainability.” He added that further research should also identify socioeconomic factors that influence child health.

Expanding the program across the New York City’s five boroughs “offers a unique opportunity to explore which socioeconomic factors, at both the family and borough level, and may eventually affect children’s health, how they are implicated in the intervention’s effectiveness, and how they can be addressed to reduce the gap in health inequalities,” he said. 

Karalyn Kinsella, MD, a pediatrician affiliated with Yale New Haven (Conn.) Medical Center, noted the program’s multidimensional nature is an important element. “I think what is so important about this intervention is that it is not one single intervention but a curriculum that takes a significant amount of time (up to 50 hours) that allows for repetition of the information, which allows it to become remembered,” she said in an interview. “I also think incorporating families in the intervention is key as that is where change often has to happen.”

While she said the program may provide a template for a mental health curriculum, she added, “My concern is that teachers are already feeling overwhelmed and this may be viewed as another burden.”

The American Heart Association provided funding for the study in the United States. Dr Fernández-Jiménez has received funding from the Fondo de Investigación Sanitaria–Instituto de Salud Carlos III, which is cofunded by the European Regional Development Fund/European Social Fund. Dr. Fuster and Dr. Kinsella have no relevant disclosures.

Creators of a pilot program that educates preschoolers about good heart health have validated a template for successful early childhood intervention that, they claim, provides a pathway for translating scientific evidence into the community and classroom for educational purposes to encourage long-lasting lifestyle changes.

That validation supports the creators' plans to take the program into more schools.

They reported key lessons in crafting the program, known as the SI! Program (for Salud Integral-Comprehensive Health), online in the Journal of the American College of Cardiology.

Mount Sinai Hospital

“This is a research-based program that uses randomized clinical trial evidence with implementation strategies to design educational health promotion programs,” senior author Valentin Fuster, MD, PhD, founder and trustees chairman of the Foundation for Science, Health, and Education (SHE) based in Barcelona, under whose aegis the SI! Program was implemented, said in an interview. Dr. Fuster is also director of Mount Sinai Heart and physician-in-chief at Mount Sinai Hospital in New York, and general director of the National Center for Cardiovascular Investigation (CNIC) in Madrid, Spain’s equivalent of the National Heart, Lung, and Blood Institute.

“There are specific times in a child’s life when improvements can be made to enhance long-term cardiovascular health status,” said Rodrigo Fernández-Jiménez, MD, PhD, group leader of the cardiovascular health and imaging lab at CNIC and study coauthor. “Our review, and previous studies, suggest that 4-5 years of age is the most favorable time to start a school-based intervention focused on healthy habits.”

A key piece of the SI! Program used a Sesame Street character, known as Dr. Ruster, a Muppet based on Dr. Fuster, to introduce and convey most messages and activities to the preschool children. The program also used a heart-shaped mascot named “Cardio” to teach about healthy behaviors. Other components include video segments, a colorful storybook, an interactive board game, flash cards, and a teacher’s guide. The activities and messages were tailored based on the country in which the program was implemented.
 

A decade of experience

The review evaluated 10 years of experience with the preschool-based program, drawing upon cluster-randomized clinical trials of the program in three countries with different socioeconomic conditions: Colombia, Spain, and the United States. The studies randomized schools to receive the SI! Program for 4 months or to a control group and included more than 3,800 children from 50 schools, along with their parents or caregivers and teachers. The studies found significant increases in preschoolers’ knowledge, attitudes, and habits toward healthy eating and living an active lifestyle. Now, the SI! Program is expanding into more than 250 schools in Spain and more than 40 schools in all five boroughs of New York City.

“This is a multidimensional program,” Dr. Fuster said. The review identified five stages for implementing the program: dissemination; adoption; implementation; evaluation; and institutionalization.

Dissemination involves three substages for intervention: components, design, and strategy. With regard to the components, said Dr. Fuster, “We’re targeting children to educate them in four topics: how the body works; nutritional and dietary requirements; physical activity; and the need to control emotions – to say no in the future when they’re confronted with alcohol, drugs, and tobacco.”

Design involved a multidisciplinary team of experts to develop the intervention, Dr. Fuster said. The strategy itself enlists parents and teachers in the implementation, but goes beyond that. “This is a community,” Dr. Fuster said. Hence, the school environment and classroom itself are also engaged to support the message of the four topics.

Dr. Fuster said future research should look at knowledge, attitude, and habits and biological outcomes in children who’ve been in the SI! Program when they reach adolescence. “Our hypothesis is that we can do this in older children, but when they reach age 10 we want to reintervene in them,” Dr. Fuster said. “Humans need reintervention. Our findings don’t get into sustainability.” He added that further research should also identify socioeconomic factors that influence child health.

Expanding the program across the New York City’s five boroughs “offers a unique opportunity to explore which socioeconomic factors, at both the family and borough level, and may eventually affect children’s health, how they are implicated in the intervention’s effectiveness, and how they can be addressed to reduce the gap in health inequalities,” he said. 

Karalyn Kinsella, MD, a pediatrician affiliated with Yale New Haven (Conn.) Medical Center, noted the program’s multidimensional nature is an important element. “I think what is so important about this intervention is that it is not one single intervention but a curriculum that takes a significant amount of time (up to 50 hours) that allows for repetition of the information, which allows it to become remembered,” she said in an interview. “I also think incorporating families in the intervention is key as that is where change often has to happen.”

While she said the program may provide a template for a mental health curriculum, she added, “My concern is that teachers are already feeling overwhelmed and this may be viewed as another burden.”

The American Heart Association provided funding for the study in the United States. Dr Fernández-Jiménez has received funding from the Fondo de Investigación Sanitaria–Instituto de Salud Carlos III, which is cofunded by the European Regional Development Fund/European Social Fund. Dr. Fuster and Dr. Kinsella have no relevant disclosures.

A study showing that once-weekly subcutaneous semaglutide 2.4 mg (Wegovy, Novo Nordisk) produces greater long-term weight loss than once-daily injected liraglutide 3.0 mg (Saxenda, Novo Nordisk) among adults with overweight or obesity without diabetes has now been published.

The data, previously reported at Obesity Week 2021, were published online Jan. 11 in JAMA.

The findings are from the phase 3 Semaglutide Treatment Effect in People with Obesity (STEP) 8 trial by Domenica M. Rubino, MD, of the Washington Center for Weight Management and Research, Arlington, Virginia, and colleagues.

Semaglutide and liraglutide, subcutaneously injectable glucagon-like peptide-1 (GLP-1) agonists, were both first approved for the treatment of type 2 diabetes in the United States and elsewhere, but are now also approved, in different doses, for chronic weight management and in people with obesity or overweight and comorbidities. A phase 2 trial demonstrated that once-daily semaglutide 0.4 mg produced significantly more weight loss than liraglutide 3.0 mg.

“Semaglutide and liraglutide induce weight loss by lowering energy intake. However, the reduction in caloric intake versus placebo appears to be larger with semaglutide (35%) than liraglutide (approximately 16%),” say Dr. Rubino and colleagues.

“Semaglutide has also been associated with reductions in food cravings, which is less evident with liraglutide, suggesting different mechanisms of energy intake regulation,” they add.   

Novo Nordisk has recently reported that there may be supply problems with Wegovy, as a contract manufacturer that fills syringes for pens to inject the drug temporarily halted deliveries and manufacturing after issues related to good manufacturing practice.

The company is also developing an oral form of semaglutide for weight loss. The oral form has already been approved in doses of 7 or 14 mg/day for the treatment of type 2 diabetes in the United States as Rybelsus.

Individualize treatment for those with obesity

STEP 8 was a randomized, open-label, 68-week phase 3b trial of 338 adults randomized to once-weekly semaglutide 2.4 mg (n = 126), once-daily liraglutide 3.0 mg (n = 127), or matched injected placebo (n = 85) for 68 weeks, all provided with counseling on diet and physical activity.  

The primary outcome – estimated mean change in body weight at week 68 – was –15.8% with semaglutide versus –6.4% with liraglutide, a significant difference (P < .001). The proportions of patients achieving loss of body weight of 10%, 15%, or 20% were 70.9%, 55.6%, and 38.5% with semaglutide versus 25.6%, 12.0%, and 6.0% with liraglutide, respectively.

Significantly greater reductions were also seen at 68 weeks for weekly semaglutide versus daily liraglutide in absolute body weight, waist circumference, diastolic blood pressure, total cholesterol, very low-density cholesterol, triglycerides, A1c, fasting plasma glucose, and C-reactive protein. Differences in systolic blood pressure, LDL and HDL cholesterol, free fatty acids, and fasting serum insulin did not achieve significance.

Overall, 19.8% of patients permanently discontinued treatment, with the most discontinuations in the liraglutide group (27.6%), followed by placebo (17.6%) and semaglutide (3.5%). Time to first and permanent discontinuation were shorter with liraglutide than with semaglutide or placebo.

Adverse events were reported by 95.2% of patients with semaglutide, 96.1% with liraglutide, and 95.3% with placebo. Gastrointestinal disorders were the most common with the two active drugs, reported by 84.1% with semaglutide and 82.7% with liraglutide versus 55.3% with placebo.

Most side effects were mild to moderate and resolved without treatment discontinuation. Severe gastrointestinal adverse events were reported by only 3.2%, 2.4%, and 3.5% of patients with semaglutide, liraglutide, and placebo, respectively.

“This trial found weight loss with semaglutide was significantly greater than with liraglutide. However, the variability in treatment response means an individual’s tolerance and sensitivity to a specific treatment is important for obesity management,” the researchers observe.

“Therefore, having multiple antiobesity medications proven to lower body weight through different mechanisms, with different adverse effect profiles and dosing regimens, can only benefit clinicians and patients,” they conclude.

The trial was funded by Novo Nordisk. Dr. Rubino has reported being a clinical investigator for Boehringer Ingelheim, AstraZeneca, and Novo Nordisk; receiving honoraria from WebMD; receiving speaker fees, consulting fees, scientific advisory fees, and honoraria from Novo Nordisk; receiving grants from SARL and personal fees from Medscape, PeerView, and the Endocrine Society; and being a shareholder in Novo Nordisk.

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

A study showing that once-weekly subcutaneous semaglutide 2.4 mg (Wegovy, Novo Nordisk) produces greater long-term weight loss than once-daily injected liraglutide 3.0 mg (Saxenda, Novo Nordisk) among adults with overweight or obesity without diabetes has now been published.

The data, previously reported at Obesity Week 2021, were published online Jan. 11 in JAMA.

The findings are from the phase 3 Semaglutide Treatment Effect in People with Obesity (STEP) 8 trial by Domenica M. Rubino, MD, of the Washington Center for Weight Management and Research, Arlington, Virginia, and colleagues.

Semaglutide and liraglutide, subcutaneously injectable glucagon-like peptide-1 (GLP-1) agonists, were both first approved for the treatment of type 2 diabetes in the United States and elsewhere, but are now also approved, in different doses, for chronic weight management and in people with obesity or overweight and comorbidities. A phase 2 trial demonstrated that once-daily semaglutide 0.4 mg produced significantly more weight loss than liraglutide 3.0 mg.

“Semaglutide and liraglutide induce weight loss by lowering energy intake. However, the reduction in caloric intake versus placebo appears to be larger with semaglutide (35%) than liraglutide (approximately 16%),” say Dr. Rubino and colleagues.

“Semaglutide has also been associated with reductions in food cravings, which is less evident with liraglutide, suggesting different mechanisms of energy intake regulation,” they add.   

Novo Nordisk has recently reported that there may be supply problems with Wegovy, as a contract manufacturer that fills syringes for pens to inject the drug temporarily halted deliveries and manufacturing after issues related to good manufacturing practice.

The company is also developing an oral form of semaglutide for weight loss. The oral form has already been approved in doses of 7 or 14 mg/day for the treatment of type 2 diabetes in the United States as Rybelsus.

Individualize treatment for those with obesity

STEP 8 was a randomized, open-label, 68-week phase 3b trial of 338 adults randomized to once-weekly semaglutide 2.4 mg (n = 126), once-daily liraglutide 3.0 mg (n = 127), or matched injected placebo (n = 85) for 68 weeks, all provided with counseling on diet and physical activity.  

The primary outcome – estimated mean change in body weight at week 68 – was –15.8% with semaglutide versus –6.4% with liraglutide, a significant difference (P < .001). The proportions of patients achieving loss of body weight of 10%, 15%, or 20% were 70.9%, 55.6%, and 38.5% with semaglutide versus 25.6%, 12.0%, and 6.0% with liraglutide, respectively.

Significantly greater reductions were also seen at 68 weeks for weekly semaglutide versus daily liraglutide in absolute body weight, waist circumference, diastolic blood pressure, total cholesterol, very low-density cholesterol, triglycerides, A1c, fasting plasma glucose, and C-reactive protein. Differences in systolic blood pressure, LDL and HDL cholesterol, free fatty acids, and fasting serum insulin did not achieve significance.

Overall, 19.8% of patients permanently discontinued treatment, with the most discontinuations in the liraglutide group (27.6%), followed by placebo (17.6%) and semaglutide (3.5%). Time to first and permanent discontinuation were shorter with liraglutide than with semaglutide or placebo.

Adverse events were reported by 95.2% of patients with semaglutide, 96.1% with liraglutide, and 95.3% with placebo. Gastrointestinal disorders were the most common with the two active drugs, reported by 84.1% with semaglutide and 82.7% with liraglutide versus 55.3% with placebo.

Most side effects were mild to moderate and resolved without treatment discontinuation. Severe gastrointestinal adverse events were reported by only 3.2%, 2.4%, and 3.5% of patients with semaglutide, liraglutide, and placebo, respectively.

“This trial found weight loss with semaglutide was significantly greater than with liraglutide. However, the variability in treatment response means an individual’s tolerance and sensitivity to a specific treatment is important for obesity management,” the researchers observe.

“Therefore, having multiple antiobesity medications proven to lower body weight through different mechanisms, with different adverse effect profiles and dosing regimens, can only benefit clinicians and patients,” they conclude.

The trial was funded by Novo Nordisk. Dr. Rubino has reported being a clinical investigator for Boehringer Ingelheim, AstraZeneca, and Novo Nordisk; receiving honoraria from WebMD; receiving speaker fees, consulting fees, scientific advisory fees, and honoraria from Novo Nordisk; receiving grants from SARL and personal fees from Medscape, PeerView, and the Endocrine Society; and being a shareholder in Novo Nordisk.

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

A study showing that once-weekly subcutaneous semaglutide 2.4 mg (Wegovy, Novo Nordisk) produces greater long-term weight loss than once-daily injected liraglutide 3.0 mg (Saxenda, Novo Nordisk) among adults with overweight or obesity without diabetes has now been published.

The data, previously reported at Obesity Week 2021, were published online Jan. 11 in JAMA.

The findings are from the phase 3 Semaglutide Treatment Effect in People with Obesity (STEP) 8 trial by Domenica M. Rubino, MD, of the Washington Center for Weight Management and Research, Arlington, Virginia, and colleagues.

Semaglutide and liraglutide, subcutaneously injectable glucagon-like peptide-1 (GLP-1) agonists, were both first approved for the treatment of type 2 diabetes in the United States and elsewhere, but are now also approved, in different doses, for chronic weight management and in people with obesity or overweight and comorbidities. A phase 2 trial demonstrated that once-daily semaglutide 0.4 mg produced significantly more weight loss than liraglutide 3.0 mg.

“Semaglutide and liraglutide induce weight loss by lowering energy intake. However, the reduction in caloric intake versus placebo appears to be larger with semaglutide (35%) than liraglutide (approximately 16%),” say Dr. Rubino and colleagues.

“Semaglutide has also been associated with reductions in food cravings, which is less evident with liraglutide, suggesting different mechanisms of energy intake regulation,” they add.   

Novo Nordisk has recently reported that there may be supply problems with Wegovy, as a contract manufacturer that fills syringes for pens to inject the drug temporarily halted deliveries and manufacturing after issues related to good manufacturing practice.

The company is also developing an oral form of semaglutide for weight loss. The oral form has already been approved in doses of 7 or 14 mg/day for the treatment of type 2 diabetes in the United States as Rybelsus.

Individualize treatment for those with obesity

STEP 8 was a randomized, open-label, 68-week phase 3b trial of 338 adults randomized to once-weekly semaglutide 2.4 mg (n = 126), once-daily liraglutide 3.0 mg (n = 127), or matched injected placebo (n = 85) for 68 weeks, all provided with counseling on diet and physical activity.  

The primary outcome – estimated mean change in body weight at week 68 – was –15.8% with semaglutide versus –6.4% with liraglutide, a significant difference (P < .001). The proportions of patients achieving loss of body weight of 10%, 15%, or 20% were 70.9%, 55.6%, and 38.5% with semaglutide versus 25.6%, 12.0%, and 6.0% with liraglutide, respectively.

Significantly greater reductions were also seen at 68 weeks for weekly semaglutide versus daily liraglutide in absolute body weight, waist circumference, diastolic blood pressure, total cholesterol, very low-density cholesterol, triglycerides, A1c, fasting plasma glucose, and C-reactive protein. Differences in systolic blood pressure, LDL and HDL cholesterol, free fatty acids, and fasting serum insulin did not achieve significance.

Overall, 19.8% of patients permanently discontinued treatment, with the most discontinuations in the liraglutide group (27.6%), followed by placebo (17.6%) and semaglutide (3.5%). Time to first and permanent discontinuation were shorter with liraglutide than with semaglutide or placebo.

Adverse events were reported by 95.2% of patients with semaglutide, 96.1% with liraglutide, and 95.3% with placebo. Gastrointestinal disorders were the most common with the two active drugs, reported by 84.1% with semaglutide and 82.7% with liraglutide versus 55.3% with placebo.

Most side effects were mild to moderate and resolved without treatment discontinuation. Severe gastrointestinal adverse events were reported by only 3.2%, 2.4%, and 3.5% of patients with semaglutide, liraglutide, and placebo, respectively.

“This trial found weight loss with semaglutide was significantly greater than with liraglutide. However, the variability in treatment response means an individual’s tolerance and sensitivity to a specific treatment is important for obesity management,” the researchers observe.

“Therefore, having multiple antiobesity medications proven to lower body weight through different mechanisms, with different adverse effect profiles and dosing regimens, can only benefit clinicians and patients,” they conclude.

The trial was funded by Novo Nordisk. Dr. Rubino has reported being a clinical investigator for Boehringer Ingelheim, AstraZeneca, and Novo Nordisk; receiving honoraria from WebMD; receiving speaker fees, consulting fees, scientific advisory fees, and honoraria from Novo Nordisk; receiving grants from SARL and personal fees from Medscape, PeerView, and the Endocrine Society; and being a shareholder in Novo Nordisk.

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

Whenever I get a new patient with type 2 diabetes, who is generally on metformin, one of the very first questions they ask me is, “Can I get off my medication?” Everybody, it seems, who gets diabetes wants to not have diabetes.

So, what does this really mean? What does this mean to me as a clinician? And what does this mean to my patients? The American Diabetes Association recently came out with a consensus statement that defines and interprets the definition of remission in people with type 2 diabetes. Basically, if the hemoglobin A1c is less than 6.5% without diabetes medications for at least 3 months, that’s considered remission.

There are other considerations, such as metabolic surgery, that can lead to remission. But again, such patients should be 3 months post surgery and at least 3 months off diabetes medication. As for a lifestyle intervention, the authors state that remission really happens within about 6 months.

That leads me to wonder: What is remission? Remission really means temporary recovery, so it doesn’t mean a cure. Now, I’m not against curing diabetes. In fact, I’m all for it. But when somebody gets diabetes – and honestly, it doesn’t matter whether it’s type 1 or type 2 – the first thing I think of, and I think the first thing that my patients are taught, is how important it is to have a healthy lifestyle. This healthy lifestyle isn’t just for people with diabetes; it largely means the healthy lifestyle that all of us should follow, one where we eat fewer simple carbs, less processed food, more vegetables, more lean proteins and meats – all of the things that we know we should do. And all of the things that keep us healthy. To some degree, I don’t think you can ever get “remission” from diabetes, because if having diabetes points an individual toward having a healthier lifestyle, I think that’s great.

I think people should exercise more. When it comes to treating diabetes, exercise is key. When you think about obesity, we want to help people who are overweight or obese lose weight as part of their treatment for diabetes. And that doesn’t go away, either.

So, no, people who are diagnosed with diabetes don’t really go into remission if they keep their same old habits and don’t lose weight and don’t exercise. But many people with diabetes can get off medication if they do those things.

However, it’s not true for everybody, and I don’t want people to get unrealistic expectations because I think there are probably about a thousand different subtypes of type 2 diabetes. And I’ve definitely seen people who are lean with type 2 diabetes who don’t respond as well to a lifestyle intervention, or people who are more insulin deficient, who also need medication.

I think it’s really important to frame the expectation that, if remission means going back to the way it was before, when they didn’t have to think about what they ate or whether or not they exercised, that’s not going to happen. I think diabetes should really be a wake-up call that people need to be healthier in terms of their lifestyle habits.

The issue of medication is really an individual one, and I think we need to help patients look for what’s best for the individual, what their targets are, what their goals are. But we also have to think that diabetes isn’t just about glucose.

So remission in terms of the ADA’s definition looks at glucose, but I look at more than glucose. You have to look at lipids and blood pressure. And, as I mentioned earlier, you have to look at whether or not a person has preexisting cardiovascular disease or has the presence of microvascular complications that need to be screened for and treated.

I actually think that, in some ways, the diagnosis of diabetes is helpful simply because it helps put people on a better path to health. I don’t want people to think that remission means that they can go back to unhealthy habits. I really encourage all people to live a healthier lifestyle, and if it leads to improvements in glucose levels and getting off medication, I think that’s wonderful and a worthy goal. But remember, health and meeting one’s targets remain key in the treatment of type 2 diabetes.
 

Dr. Peters is a professor in the department of clinical medicine at the University of Southern California, Los Angeles. She reported serving on the advisory board or speakers’ bureau of Medscape and several pharmaceutical companies, and has received research support from Dexcom, MannKind, and AstraZeneca. This perspective and an accompanying video first appeared on Medscape.com.

Whenever I get a new patient with type 2 diabetes, who is generally on metformin, one of the very first questions they ask me is, “Can I get off my medication?” Everybody, it seems, who gets diabetes wants to not have diabetes.

So, what does this really mean? What does this mean to me as a clinician? And what does this mean to my patients? The American Diabetes Association recently came out with a consensus statement that defines and interprets the definition of remission in people with type 2 diabetes. Basically, if the hemoglobin A1c is less than 6.5% without diabetes medications for at least 3 months, that’s considered remission.

There are other considerations, such as metabolic surgery, that can lead to remission. But again, such patients should be 3 months post surgery and at least 3 months off diabetes medication. As for a lifestyle intervention, the authors state that remission really happens within about 6 months.

That leads me to wonder: What is remission? Remission really means temporary recovery, so it doesn’t mean a cure. Now, I’m not against curing diabetes. In fact, I’m all for it. But when somebody gets diabetes – and honestly, it doesn’t matter whether it’s type 1 or type 2 – the first thing I think of, and I think the first thing that my patients are taught, is how important it is to have a healthy lifestyle. This healthy lifestyle isn’t just for people with diabetes; it largely means the healthy lifestyle that all of us should follow, one where we eat fewer simple carbs, less processed food, more vegetables, more lean proteins and meats – all of the things that we know we should do. And all of the things that keep us healthy. To some degree, I don’t think you can ever get “remission” from diabetes, because if having diabetes points an individual toward having a healthier lifestyle, I think that’s great.

I think people should exercise more. When it comes to treating diabetes, exercise is key. When you think about obesity, we want to help people who are overweight or obese lose weight as part of their treatment for diabetes. And that doesn’t go away, either.

So, no, people who are diagnosed with diabetes don’t really go into remission if they keep their same old habits and don’t lose weight and don’t exercise. But many people with diabetes can get off medication if they do those things.

However, it’s not true for everybody, and I don’t want people to get unrealistic expectations because I think there are probably about a thousand different subtypes of type 2 diabetes. And I’ve definitely seen people who are lean with type 2 diabetes who don’t respond as well to a lifestyle intervention, or people who are more insulin deficient, who also need medication.

I think it’s really important to frame the expectation that, if remission means going back to the way it was before, when they didn’t have to think about what they ate or whether or not they exercised, that’s not going to happen. I think diabetes should really be a wake-up call that people need to be healthier in terms of their lifestyle habits.

The issue of medication is really an individual one, and I think we need to help patients look for what’s best for the individual, what their targets are, what their goals are. But we also have to think that diabetes isn’t just about glucose.

So remission in terms of the ADA’s definition looks at glucose, but I look at more than glucose. You have to look at lipids and blood pressure. And, as I mentioned earlier, you have to look at whether or not a person has preexisting cardiovascular disease or has the presence of microvascular complications that need to be screened for and treated.

I actually think that, in some ways, the diagnosis of diabetes is helpful simply because it helps put people on a better path to health. I don’t want people to think that remission means that they can go back to unhealthy habits. I really encourage all people to live a healthier lifestyle, and if it leads to improvements in glucose levels and getting off medication, I think that’s wonderful and a worthy goal. But remember, health and meeting one’s targets remain key in the treatment of type 2 diabetes.
 

Dr. Peters is a professor in the department of clinical medicine at the University of Southern California, Los Angeles. She reported serving on the advisory board or speakers’ bureau of Medscape and several pharmaceutical companies, and has received research support from Dexcom, MannKind, and AstraZeneca. This perspective and an accompanying video first appeared on Medscape.com.

Whenever I get a new patient with type 2 diabetes, who is generally on metformin, one of the very first questions they ask me is, “Can I get off my medication?” Everybody, it seems, who gets diabetes wants to not have diabetes.

So, what does this really mean? What does this mean to me as a clinician? And what does this mean to my patients? The American Diabetes Association recently came out with a consensus statement that defines and interprets the definition of remission in people with type 2 diabetes. Basically, if the hemoglobin A1c is less than 6.5% without diabetes medications for at least 3 months, that’s considered remission.

There are other considerations, such as metabolic surgery, that can lead to remission. But again, such patients should be 3 months post surgery and at least 3 months off diabetes medication. As for a lifestyle intervention, the authors state that remission really happens within about 6 months.

That leads me to wonder: What is remission? Remission really means temporary recovery, so it doesn’t mean a cure. Now, I’m not against curing diabetes. In fact, I’m all for it. But when somebody gets diabetes – and honestly, it doesn’t matter whether it’s type 1 or type 2 – the first thing I think of, and I think the first thing that my patients are taught, is how important it is to have a healthy lifestyle. This healthy lifestyle isn’t just for people with diabetes; it largely means the healthy lifestyle that all of us should follow, one where we eat fewer simple carbs, less processed food, more vegetables, more lean proteins and meats – all of the things that we know we should do. And all of the things that keep us healthy. To some degree, I don’t think you can ever get “remission” from diabetes, because if having diabetes points an individual toward having a healthier lifestyle, I think that’s great.

I think people should exercise more. When it comes to treating diabetes, exercise is key. When you think about obesity, we want to help people who are overweight or obese lose weight as part of their treatment for diabetes. And that doesn’t go away, either.

So, no, people who are diagnosed with diabetes don’t really go into remission if they keep their same old habits and don’t lose weight and don’t exercise. But many people with diabetes can get off medication if they do those things.

However, it’s not true for everybody, and I don’t want people to get unrealistic expectations because I think there are probably about a thousand different subtypes of type 2 diabetes. And I’ve definitely seen people who are lean with type 2 diabetes who don’t respond as well to a lifestyle intervention, or people who are more insulin deficient, who also need medication.

I think it’s really important to frame the expectation that, if remission means going back to the way it was before, when they didn’t have to think about what they ate or whether or not they exercised, that’s not going to happen. I think diabetes should really be a wake-up call that people need to be healthier in terms of their lifestyle habits.

The issue of medication is really an individual one, and I think we need to help patients look for what’s best for the individual, what their targets are, what their goals are. But we also have to think that diabetes isn’t just about glucose.

So remission in terms of the ADA’s definition looks at glucose, but I look at more than glucose. You have to look at lipids and blood pressure. And, as I mentioned earlier, you have to look at whether or not a person has preexisting cardiovascular disease or has the presence of microvascular complications that need to be screened for and treated.

I actually think that, in some ways, the diagnosis of diabetes is helpful simply because it helps put people on a better path to health. I don’t want people to think that remission means that they can go back to unhealthy habits. I really encourage all people to live a healthier lifestyle, and if it leads to improvements in glucose levels and getting off medication, I think that’s wonderful and a worthy goal. But remember, health and meeting one’s targets remain key in the treatment of type 2 diabetes.
 

Dr. Peters is a professor in the department of clinical medicine at the University of Southern California, Los Angeles. She reported serving on the advisory board or speakers’ bureau of Medscape and several pharmaceutical companies, and has received research support from Dexcom, MannKind, and AstraZeneca. This perspective and an accompanying video first appeared on Medscape.com.

In an observational study of more than 90,000 U.S. health care professionals, consuming even a small amount of olive oil was associated with reduced total mortality.

Compared with men and women who rarely or never consumed olive oil (the lowest intake), those who consumed greater than 0.5 tablespoon/day or more than 7 g/day (the highest intake) had a 19% lower mortality risk over a 28-year follow-up, starting from an average age of 56 years.

Moreover, compared with those with the lowest olive oil intake, those with the highest intake had a 19% lower cardiovascular disease (CVD) mortality, a 17% lower risk of dying from cancer, a 29% lower risk of dying from neurodegenerative disease, and an 18% lower risk of dying from respiratory disease during follow-up.

masa44/iStock/Getty Images

The researchers estimate that replacing 10 g/day of margarine, butter, mayonnaise, or dairy fat with the same amount of olive oil is associated with an 8%-34% lower risk of death from various causes.

The study by Marta Guasch-Ferré, PhD, and colleagues was published online Jan. 10 in the Journal of the American College of Cardiology.
 

Results support plant-based dietary fat recommendations

“Our results support current dietary recommendations to increase the intake of olive oil and other unsaturated vegetable oils in place of other fats to improve overall health and longevity,” the researchers summarize.

However, “I wouldn’t say that olive oil is the only way to help you live longer,” Dr. Guasch-Ferré, a senior research scientist in the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, cautioned in an interview with this news organization.

“Other things are very important, such as not smoking, doing physical activity, etc., but one recommendation could be to try to eat more plant-based food including olive oil and healthy fat,” she added, and to use it for cooking, salad dressing, and baking, and substitute it for saturated fat or animal fat, especially for cooking.

The study suggests that people should “consume a more plant-based diet and prioritize fatty acids such as olive oil because they have a better nutritional composition (high in phenols and antioxidants), instead of using butter or margarines or other animal fats that have been shown to have detrimental effects for health,” she added, which is consistent with recommendations in the Dietary Guidelines for Americans.

“That said,” Dr. Guasch-Ferré summarized, “replication is needed in other cohorts and populations to see if the results are similar.”

In an accompanying editorial, Susanna C. Larsson, PhD, writes that “this was a well-designed study, with long-term follow-up and repeated measurements of dietary intake and other risk factors for diseases.”

“However, the difference in olive oil consumption between those with the highest and those with the lowest/no olive oil consumption was very low (0.5 tablespoon) and a [12%] reduced mortality risk was observed already at a much lower intake (0.5 teaspoon, about 1.5 g/day) of olive oil,” she noted in an email to this news organization.

“It’s a bit hard to believe that such a small amount could have an independent effect on mortality risk,” Dr. Larsson, associate professor of epidemiology at the Karolinska Institutet, Stockholm, cautioned.

Like Dr. Guasch-Ferré, she noted that “just adding one or two teaspoons of olive oil to the diet each day will likely not change the risk of mortality.”

Rather, “people may need to make larger changes in the whole diet, not focus on fat only. An overall healthier diet, rich in nonrefined plant-based foods (vegetables, whole grains, nuts), low/no intake of processed foods, and a switch to healthier fat (eg, olive oil) is needed.”

Importantly, “this study cannot say anything about causality, that is, whether it’s olive oil specifically that reduces mortality risk or if there are many other beneficial factors that act together to reduce mortality rate among those with high olive oil consumption.”

The researchers acknowledge this observational study limitation and that the findings may not be generalizable to other populations.
 

Novel findings regarding Alzheimer’s and respiratory disease

Dr. Larsson highlights two novel findings of this study.

First, it showed a 27% reduction in risk of dementia-related mortality for those in the highest versus lowest category of olive oil consumption. “Considering the lack of preventive strategies for Alzheimer’s disease and the high morbidity and mortality related to this disease, this finding, if confirmed, is of great public health importance,” she said.

Second, the study reported an inverse association of olive oil consumption with risk of respiratory disease mortality. “Because residual confounding from smoking cannot be ruled out,” Dr. Larsson said, “this finding is tentative and requires confirmation in a study that is less susceptible to confounding, such as a randomized trial.”

And although the current study and previous studies have found that consumption of olive oil may have health benefits, she identified several remaining questions.

“Are the associations causal or spurious?” she noted. Is olive oil consumption protective for certain cardiovascular diseases like stroke or atrial fibrillation only, as has been shown in other studies, or also for other major diseases and causes of death, she added. What is the amount of olive oil required for a protective effect?

Further, is the potential effect related to monounsaturated fatty acids (MUFAs) or phenolic compounds; that is, “is the protective effect confined to polyphenol-rich extra-virgin olive oil or are refined olive oil and other vegetable oils as beneficial? More research is needed to address these questions,” she concludes.

“Further studies are needed,” the researchers agree, “to confirm the association of olive oil consumption with reduced mortality, clarify the mechanisms responsible, and quantify the dose/volume boundaries around this effect.”  
 

Virgin olive oil has more polyphenols

Olive oil, a key component of the Mediterranean diet, is high in MUFAs, especially oleic acid, as well as vitamin E and polyphenols, which contribute to its anti-inflammatory and antioxidant properties, the researchers explain.

Virgin olive oil, produced by mechanically pressing ripe olives, contains multiple bioactive and antioxidant components and has an acidity of less than 1.5%. And extra-virgin olive oil is produced the same way but has a higher quality, more intense taste, and lower acidity (less than 1%).

Refined or processed olive oil contains less phytochemicals, as some are lost during processing; it usually contains more than 80% refined oil, plus virgin oil added back to enhance flavor, and may also be labeled “pure” or “light.” However, refined olive oil “still has a good amount of healthy fatty acids but less bioactive compounds,” Dr. Guasch-Ferré noted.

Until now, no large prospective study has examined the link between olive oil intake and all-cause and cause-specific mortality in a U.S. population, where olive oil consumption is limited, compared with Mediterranean countries.

The researchers identified 60,582 women in the Nurses’ Health Study and 31,801 men in the Health Professionals Follow-up Study who were free of CVD or cancer in 1990, the first year that food frequency questionnaires in these studies asked about olive oil.

Participants replied to questionnaires every 4 years that asked about use of olive oil (for salad dressing, baking, frying, sautéing, and spreading on bread), other vegetable oils (for example, corn, safflower, soybean, canola oil), margarine, butter, and dairy fat. The researchers averaged the consumption of these fats during the follow-up years.

From 1990 to 2019, the average consumption of olive oil increased from 1.6 g/day to 4 g/day. Margarine in the 1990s contained saturated fat and trans fats, whereas more recently margarine contains beneficial olive oil or vegetable fat, Dr. Guasch-Ferré noted.

Baseline olive oil consumption in this U.S. population “differed remarkably” from that in the Spanish population in the PREDIMED (Prevención con Dieta Mediterránea) trial, which was, on average, 20-22 g/day of extra-virgin olive oil and 16-18 g/day of refined/mixed olive oil, Larsson pointed out.

Because olive oil consumption was so low in this U.S. study, the researchers did not distinguish between virgin/extra-virgin olive oil and refined/processed olive oil.

The participants were almost all White (99%) and were generally healthier than the average U.S. population; on average, they had a body mass index of 25.3-25.8 kg/m² and ate 4.8-7.2 fruits and vegetables/day.

Those with the highest olive oil consumption were more physically active, had a healthier diet, were more likely to have Southern European or Mediterranean ancestry, and were less likely to smoke.

During 28 years of follow-up, 36,856 participants died. The researchers classified the deaths into five categories: CVD, cancer, neurodegenerative disease (including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis), respiratory disease (such as chronic obstructive pulmonary disease), and all other causes (including suicide, injury, infections, diabetes, and kidney disease).

After adjusting for multiple confounders, compared with participants who rarely or never consumed olive oil, those in the highest quartile for olive oil consumption had a decreased risk of death from all causes (hazard ratio, 0.81; 95% confidence interval, 0.78 - 0.84) and from CVD (HR, 0.81; 95% CI, 0.75-0.87), cancer (HR, 0.83; 95% CI, 0.78-0.89), neurodegenerative disease (HR, 0.71; 95% CI, 0.64-0.78), and respiratory disease (HR, 0.82; 95% CI, 0.72-0.93). 

There was no decrease in mortality in models where the researchers substituted olive oil for vegetable oil, suggesting that vegetable oils may provide similar health benefits as olive oil.

The research was supported by grants from the National Institutes of Health. Dr. Guasch-Ferré was supported by the American Diabetes Association. Coauthor Salas-Salvadó is partially supported by the Catalan Institution for Research and Advanced Studies and received the virgin olive oil that was used in the PREDIMED and PREDIMED-Plus studies from the Patrimonio Communal Olivalero and Hojiblanca (Málaga, Spain). The other study authors and Dr. Larsson have reported no relevant financial relationships.

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

In an observational study of more than 90,000 U.S. health care professionals, consuming even a small amount of olive oil was associated with reduced total mortality.

Compared with men and women who rarely or never consumed olive oil (the lowest intake), those who consumed greater than 0.5 tablespoon/day or more than 7 g/day (the highest intake) had a 19% lower mortality risk over a 28-year follow-up, starting from an average age of 56 years.

Moreover, compared with those with the lowest olive oil intake, those with the highest intake had a 19% lower cardiovascular disease (CVD) mortality, a 17% lower risk of dying from cancer, a 29% lower risk of dying from neurodegenerative disease, and an 18% lower risk of dying from respiratory disease during follow-up.

masa44/iStock/Getty Images

The researchers estimate that replacing 10 g/day of margarine, butter, mayonnaise, or dairy fat with the same amount of olive oil is associated with an 8%-34% lower risk of death from various causes.

The study by Marta Guasch-Ferré, PhD, and colleagues was published online Jan. 10 in the Journal of the American College of Cardiology.
 

Results support plant-based dietary fat recommendations

“Our results support current dietary recommendations to increase the intake of olive oil and other unsaturated vegetable oils in place of other fats to improve overall health and longevity,” the researchers summarize.

However, “I wouldn’t say that olive oil is the only way to help you live longer,” Dr. Guasch-Ferré, a senior research scientist in the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, cautioned in an interview with this news organization.

“Other things are very important, such as not smoking, doing physical activity, etc., but one recommendation could be to try to eat more plant-based food including olive oil and healthy fat,” she added, and to use it for cooking, salad dressing, and baking, and substitute it for saturated fat or animal fat, especially for cooking.

The study suggests that people should “consume a more plant-based diet and prioritize fatty acids such as olive oil because they have a better nutritional composition (high in phenols and antioxidants), instead of using butter or margarines or other animal fats that have been shown to have detrimental effects for health,” she added, which is consistent with recommendations in the Dietary Guidelines for Americans.

“That said,” Dr. Guasch-Ferré summarized, “replication is needed in other cohorts and populations to see if the results are similar.”

In an accompanying editorial, Susanna C. Larsson, PhD, writes that “this was a well-designed study, with long-term follow-up and repeated measurements of dietary intake and other risk factors for diseases.”

“However, the difference in olive oil consumption between those with the highest and those with the lowest/no olive oil consumption was very low (0.5 tablespoon) and a [12%] reduced mortality risk was observed already at a much lower intake (0.5 teaspoon, about 1.5 g/day) of olive oil,” she noted in an email to this news organization.

“It’s a bit hard to believe that such a small amount could have an independent effect on mortality risk,” Dr. Larsson, associate professor of epidemiology at the Karolinska Institutet, Stockholm, cautioned.

Like Dr. Guasch-Ferré, she noted that “just adding one or two teaspoons of olive oil to the diet each day will likely not change the risk of mortality.”

Rather, “people may need to make larger changes in the whole diet, not focus on fat only. An overall healthier diet, rich in nonrefined plant-based foods (vegetables, whole grains, nuts), low/no intake of processed foods, and a switch to healthier fat (eg, olive oil) is needed.”

Importantly, “this study cannot say anything about causality, that is, whether it’s olive oil specifically that reduces mortality risk or if there are many other beneficial factors that act together to reduce mortality rate among those with high olive oil consumption.”

The researchers acknowledge this observational study limitation and that the findings may not be generalizable to other populations.
 

Novel findings regarding Alzheimer’s and respiratory disease

Dr. Larsson highlights two novel findings of this study.

First, it showed a 27% reduction in risk of dementia-related mortality for those in the highest versus lowest category of olive oil consumption. “Considering the lack of preventive strategies for Alzheimer’s disease and the high morbidity and mortality related to this disease, this finding, if confirmed, is of great public health importance,” she said.

Second, the study reported an inverse association of olive oil consumption with risk of respiratory disease mortality. “Because residual confounding from smoking cannot be ruled out,” Dr. Larsson said, “this finding is tentative and requires confirmation in a study that is less susceptible to confounding, such as a randomized trial.”

And although the current study and previous studies have found that consumption of olive oil may have health benefits, she identified several remaining questions.

“Are the associations causal or spurious?” she noted. Is olive oil consumption protective for certain cardiovascular diseases like stroke or atrial fibrillation only, as has been shown in other studies, or also for other major diseases and causes of death, she added. What is the amount of olive oil required for a protective effect?

Further, is the potential effect related to monounsaturated fatty acids (MUFAs) or phenolic compounds; that is, “is the protective effect confined to polyphenol-rich extra-virgin olive oil or are refined olive oil and other vegetable oils as beneficial? More research is needed to address these questions,” she concludes.

“Further studies are needed,” the researchers agree, “to confirm the association of olive oil consumption with reduced mortality, clarify the mechanisms responsible, and quantify the dose/volume boundaries around this effect.”  
 

Virgin olive oil has more polyphenols

Olive oil, a key component of the Mediterranean diet, is high in MUFAs, especially oleic acid, as well as vitamin E and polyphenols, which contribute to its anti-inflammatory and antioxidant properties, the researchers explain.

Virgin olive oil, produced by mechanically pressing ripe olives, contains multiple bioactive and antioxidant components and has an acidity of less than 1.5%. And extra-virgin olive oil is produced the same way but has a higher quality, more intense taste, and lower acidity (less than 1%).

Refined or processed olive oil contains less phytochemicals, as some are lost during processing; it usually contains more than 80% refined oil, plus virgin oil added back to enhance flavor, and may also be labeled “pure” or “light.” However, refined olive oil “still has a good amount of healthy fatty acids but less bioactive compounds,” Dr. Guasch-Ferré noted.

Until now, no large prospective study has examined the link between olive oil intake and all-cause and cause-specific mortality in a U.S. population, where olive oil consumption is limited, compared with Mediterranean countries.

The researchers identified 60,582 women in the Nurses’ Health Study and 31,801 men in the Health Professionals Follow-up Study who were free of CVD or cancer in 1990, the first year that food frequency questionnaires in these studies asked about olive oil.

Participants replied to questionnaires every 4 years that asked about use of olive oil (for salad dressing, baking, frying, sautéing, and spreading on bread), other vegetable oils (for example, corn, safflower, soybean, canola oil), margarine, butter, and dairy fat. The researchers averaged the consumption of these fats during the follow-up years.

From 1990 to 2019, the average consumption of olive oil increased from 1.6 g/day to 4 g/day. Margarine in the 1990s contained saturated fat and trans fats, whereas more recently margarine contains beneficial olive oil or vegetable fat, Dr. Guasch-Ferré noted.

Baseline olive oil consumption in this U.S. population “differed remarkably” from that in the Spanish population in the PREDIMED (Prevención con Dieta Mediterránea) trial, which was, on average, 20-22 g/day of extra-virgin olive oil and 16-18 g/day of refined/mixed olive oil, Larsson pointed out.

Because olive oil consumption was so low in this U.S. study, the researchers did not distinguish between virgin/extra-virgin olive oil and refined/processed olive oil.

The participants were almost all White (99%) and were generally healthier than the average U.S. population; on average, they had a body mass index of 25.3-25.8 kg/m² and ate 4.8-7.2 fruits and vegetables/day.

Those with the highest olive oil consumption were more physically active, had a healthier diet, were more likely to have Southern European or Mediterranean ancestry, and were less likely to smoke.

During 28 years of follow-up, 36,856 participants died. The researchers classified the deaths into five categories: CVD, cancer, neurodegenerative disease (including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis), respiratory disease (such as chronic obstructive pulmonary disease), and all other causes (including suicide, injury, infections, diabetes, and kidney disease).

After adjusting for multiple confounders, compared with participants who rarely or never consumed olive oil, those in the highest quartile for olive oil consumption had a decreased risk of death from all causes (hazard ratio, 0.81; 95% confidence interval, 0.78 - 0.84) and from CVD (HR, 0.81; 95% CI, 0.75-0.87), cancer (HR, 0.83; 95% CI, 0.78-0.89), neurodegenerative disease (HR, 0.71; 95% CI, 0.64-0.78), and respiratory disease (HR, 0.82; 95% CI, 0.72-0.93). 

There was no decrease in mortality in models where the researchers substituted olive oil for vegetable oil, suggesting that vegetable oils may provide similar health benefits as olive oil.

The research was supported by grants from the National Institutes of Health. Dr. Guasch-Ferré was supported by the American Diabetes Association. Coauthor Salas-Salvadó is partially supported by the Catalan Institution for Research and Advanced Studies and received the virgin olive oil that was used in the PREDIMED and PREDIMED-Plus studies from the Patrimonio Communal Olivalero and Hojiblanca (Málaga, Spain). The other study authors and Dr. Larsson have reported no relevant financial relationships.

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

In an observational study of more than 90,000 U.S. health care professionals, consuming even a small amount of olive oil was associated with reduced total mortality.

Compared with men and women who rarely or never consumed olive oil (the lowest intake), those who consumed greater than 0.5 tablespoon/day or more than 7 g/day (the highest intake) had a 19% lower mortality risk over a 28-year follow-up, starting from an average age of 56 years.

Moreover, compared with those with the lowest olive oil intake, those with the highest intake had a 19% lower cardiovascular disease (CVD) mortality, a 17% lower risk of dying from cancer, a 29% lower risk of dying from neurodegenerative disease, and an 18% lower risk of dying from respiratory disease during follow-up.

masa44/iStock/Getty Images

The researchers estimate that replacing 10 g/day of margarine, butter, mayonnaise, or dairy fat with the same amount of olive oil is associated with an 8%-34% lower risk of death from various causes.

The study by Marta Guasch-Ferré, PhD, and colleagues was published online Jan. 10 in the Journal of the American College of Cardiology.
 

Results support plant-based dietary fat recommendations

“Our results support current dietary recommendations to increase the intake of olive oil and other unsaturated vegetable oils in place of other fats to improve overall health and longevity,” the researchers summarize.

However, “I wouldn’t say that olive oil is the only way to help you live longer,” Dr. Guasch-Ferré, a senior research scientist in the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, cautioned in an interview with this news organization.

“Other things are very important, such as not smoking, doing physical activity, etc., but one recommendation could be to try to eat more plant-based food including olive oil and healthy fat,” she added, and to use it for cooking, salad dressing, and baking, and substitute it for saturated fat or animal fat, especially for cooking.

The study suggests that people should “consume a more plant-based diet and prioritize fatty acids such as olive oil because they have a better nutritional composition (high in phenols and antioxidants), instead of using butter or margarines or other animal fats that have been shown to have detrimental effects for health,” she added, which is consistent with recommendations in the Dietary Guidelines for Americans.

“That said,” Dr. Guasch-Ferré summarized, “replication is needed in other cohorts and populations to see if the results are similar.”

In an accompanying editorial, Susanna C. Larsson, PhD, writes that “this was a well-designed study, with long-term follow-up and repeated measurements of dietary intake and other risk factors for diseases.”

“However, the difference in olive oil consumption between those with the highest and those with the lowest/no olive oil consumption was very low (0.5 tablespoon) and a [12%] reduced mortality risk was observed already at a much lower intake (0.5 teaspoon, about 1.5 g/day) of olive oil,” she noted in an email to this news organization.

“It’s a bit hard to believe that such a small amount could have an independent effect on mortality risk,” Dr. Larsson, associate professor of epidemiology at the Karolinska Institutet, Stockholm, cautioned.

Like Dr. Guasch-Ferré, she noted that “just adding one or two teaspoons of olive oil to the diet each day will likely not change the risk of mortality.”

Rather, “people may need to make larger changes in the whole diet, not focus on fat only. An overall healthier diet, rich in nonrefined plant-based foods (vegetables, whole grains, nuts), low/no intake of processed foods, and a switch to healthier fat (eg, olive oil) is needed.”

Importantly, “this study cannot say anything about causality, that is, whether it’s olive oil specifically that reduces mortality risk or if there are many other beneficial factors that act together to reduce mortality rate among those with high olive oil consumption.”

The researchers acknowledge this observational study limitation and that the findings may not be generalizable to other populations.
 

Novel findings regarding Alzheimer’s and respiratory disease

Dr. Larsson highlights two novel findings of this study.

First, it showed a 27% reduction in risk of dementia-related mortality for those in the highest versus lowest category of olive oil consumption. “Considering the lack of preventive strategies for Alzheimer’s disease and the high morbidity and mortality related to this disease, this finding, if confirmed, is of great public health importance,” she said.

Second, the study reported an inverse association of olive oil consumption with risk of respiratory disease mortality. “Because residual confounding from smoking cannot be ruled out,” Dr. Larsson said, “this finding is tentative and requires confirmation in a study that is less susceptible to confounding, such as a randomized trial.”

And although the current study and previous studies have found that consumption of olive oil may have health benefits, she identified several remaining questions.

“Are the associations causal or spurious?” she noted. Is olive oil consumption protective for certain cardiovascular diseases like stroke or atrial fibrillation only, as has been shown in other studies, or also for other major diseases and causes of death, she added. What is the amount of olive oil required for a protective effect?

Further, is the potential effect related to monounsaturated fatty acids (MUFAs) or phenolic compounds; that is, “is the protective effect confined to polyphenol-rich extra-virgin olive oil or are refined olive oil and other vegetable oils as beneficial? More research is needed to address these questions,” she concludes.

“Further studies are needed,” the researchers agree, “to confirm the association of olive oil consumption with reduced mortality, clarify the mechanisms responsible, and quantify the dose/volume boundaries around this effect.”  
 

Virgin olive oil has more polyphenols

Olive oil, a key component of the Mediterranean diet, is high in MUFAs, especially oleic acid, as well as vitamin E and polyphenols, which contribute to its anti-inflammatory and antioxidant properties, the researchers explain.

Virgin olive oil, produced by mechanically pressing ripe olives, contains multiple bioactive and antioxidant components and has an acidity of less than 1.5%. And extra-virgin olive oil is produced the same way but has a higher quality, more intense taste, and lower acidity (less than 1%).

Refined or processed olive oil contains less phytochemicals, as some are lost during processing; it usually contains more than 80% refined oil, plus virgin oil added back to enhance flavor, and may also be labeled “pure” or “light.” However, refined olive oil “still has a good amount of healthy fatty acids but less bioactive compounds,” Dr. Guasch-Ferré noted.

Until now, no large prospective study has examined the link between olive oil intake and all-cause and cause-specific mortality in a U.S. population, where olive oil consumption is limited, compared with Mediterranean countries.

The researchers identified 60,582 women in the Nurses’ Health Study and 31,801 men in the Health Professionals Follow-up Study who were free of CVD or cancer in 1990, the first year that food frequency questionnaires in these studies asked about olive oil.

Participants replied to questionnaires every 4 years that asked about use of olive oil (for salad dressing, baking, frying, sautéing, and spreading on bread), other vegetable oils (for example, corn, safflower, soybean, canola oil), margarine, butter, and dairy fat. The researchers averaged the consumption of these fats during the follow-up years.

From 1990 to 2019, the average consumption of olive oil increased from 1.6 g/day to 4 g/day. Margarine in the 1990s contained saturated fat and trans fats, whereas more recently margarine contains beneficial olive oil or vegetable fat, Dr. Guasch-Ferré noted.

Baseline olive oil consumption in this U.S. population “differed remarkably” from that in the Spanish population in the PREDIMED (Prevención con Dieta Mediterránea) trial, which was, on average, 20-22 g/day of extra-virgin olive oil and 16-18 g/day of refined/mixed olive oil, Larsson pointed out.

Because olive oil consumption was so low in this U.S. study, the researchers did not distinguish between virgin/extra-virgin olive oil and refined/processed olive oil.

The participants were almost all White (99%) and were generally healthier than the average U.S. population; on average, they had a body mass index of 25.3-25.8 kg/m² and ate 4.8-7.2 fruits and vegetables/day.

Those with the highest olive oil consumption were more physically active, had a healthier diet, were more likely to have Southern European or Mediterranean ancestry, and were less likely to smoke.

During 28 years of follow-up, 36,856 participants died. The researchers classified the deaths into five categories: CVD, cancer, neurodegenerative disease (including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis), respiratory disease (such as chronic obstructive pulmonary disease), and all other causes (including suicide, injury, infections, diabetes, and kidney disease).

After adjusting for multiple confounders, compared with participants who rarely or never consumed olive oil, those in the highest quartile for olive oil consumption had a decreased risk of death from all causes (hazard ratio, 0.81; 95% confidence interval, 0.78 - 0.84) and from CVD (HR, 0.81; 95% CI, 0.75-0.87), cancer (HR, 0.83; 95% CI, 0.78-0.89), neurodegenerative disease (HR, 0.71; 95% CI, 0.64-0.78), and respiratory disease (HR, 0.82; 95% CI, 0.72-0.93). 

There was no decrease in mortality in models where the researchers substituted olive oil for vegetable oil, suggesting that vegetable oils may provide similar health benefits as olive oil.

The research was supported by grants from the National Institutes of Health. Dr. Guasch-Ferré was supported by the American Diabetes Association. Coauthor Salas-Salvadó is partially supported by the Catalan Institution for Research and Advanced Studies and received the virgin olive oil that was used in the PREDIMED and PREDIMED-Plus studies from the Patrimonio Communal Olivalero and Hojiblanca (Málaga, Spain). The other study authors and Dr. Larsson have reported no relevant financial relationships.

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

A new document from the American Heart Association summarizes the latest research on cardiovascular risk factor management in type 2 diabetes, including medications, lifestyle, and social determinants of health.

Despite the availability of effective therapies for improving cardiovascular risk, in the United States fewer than one in five people with type 2 diabetes and without known cardiovascular disease meet control targets for a combination of A1c, blood pressure, LDL cholesterol, and nonsmoking status.

Volkan Ünalan/Thinkstock

That proportion drops to less than 1 in 10 if body mass index less than 30 kg/m² is included among the targets, and even less than that among individuals with established atherosclerotic cardiovascular disease, Joshua J. Joseph, MD, and colleagues point out in their paper, published online Jan. 10 in Circulation.

“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance type 2 diabetes treatment and care and reduce cardiovascular disease risk,” wrote Dr. Joseph, assistant professor of medicine in the division of endocrinology, diabetes, and metabolism at The Ohio State University, Columbus, Ohio, and coauthors.

The statement is not a guideline but an expert analysis that may inform future clinical practice guidelines, according to a press release from the AHA.

The new statement reviews evidence through June 2020 for lifestyle management of diabetes and weight, glycemic targets and control, blood pressure management, lipid management, antithrombotic therapy, and screening for cardiovascular and renal complications, including imaging. It also discusses the clinical implications of recent cardiovascular outcomes trials of newer glucose-lowering medications.

However, Dr. Joseph and colleagues point out, clinical care and treatment account for just 10%-20% of modifiable contributors to health outcomes. The other 80%-90% relate to social determinants of health, including health-related behaviors, socioeconomic factors, environmental factors, and racism.

“If we are to continue to advance the management of cardiovascular risk factors, we must also address the [social determinants of health] in the delivery of health care,” they noted.

Overall, they advise a patient-centered approach, meaning “reframing our clinical encounters to think about patients as people who live in families, communities, and societies that must be considered in their cardiovascular risk management.”

“People with [type 2 diabetes] face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients,” Dr. Joseph said in the AHA press release.
 

Lifestyle, medications for lowering A1c, BP, lipids

For lifestyle management, the authors say, “culturally appropriate recommendations through diabetes self-management education and support and medical nutrition therapy are key to meeting individualized goals for behavioral change and diabetes self-management.”

The document summarizes recommendations from other professional societies regarding glycemic targets and glucose lowering medications, i.e., target A1c levels of either < 7% or < 6.5% for the majority, with adjustments based on individual factors, such as life expectancy. It advises on use of metformin as first-line therapy followed by a sodium-glucose cotransporter-2 inhibitor or a glucagon-like peptide-1 agonist for those with established cardiovascular disease or risk factors.

“Cost may be a barrier to taking some [type 2 diabetes] medications as prescribed; however, many of these medications are now more commonly covered by more health insurance plans,” Dr. Joseph said.

“Another barrier is recognition by patients that these newer [type 2 diabetes] medications are also effective in reducing the risk of heart disease, stroke, heart failure, and kidney disease.”

Blood pressure treatment guidelines differ between those of the AHA/American College of Cardiology (ACC) and the American Diabetes Association (ADA), most notably that the AHA/ACC guidelines advise a general target of < 130/80 mm Hg, whereas ADA advises < 140/90 mm Hg or < 130/80 mm Hg for those with high risk if it can be safely achieved.

The decision should be “patient-centered with shared decision-making,” Dr. Joseph and colleagues advised.

For lipid-lowering, the document cites the 2018 ACC/AHA cholesterol guidelines, which include advising statins as first-line therapy for both primary and secondary prevention in diabetes, with highest intensity statins used in those at highest risk. But again, treatment should be individualized, and other agents should be used for patients in whom statins don’t work or aren’t tolerated.

And while use of antiplatelets – that is, aspirin – is well established as secondary prevention in type 2 diabetes, given new data suggesting that the risk for major bleeding could outweigh the benefits for primary prevention, “the relative benefits of antithrombotic approaches need to be weighed carefully against risks using a patient-centered approach,” the authors advised.

Among the many imaging tests available to facilitate cardiovascular risk stratification in type 2 diabetes, coronary artery calcification (CAC) CT screening is one of the few with sufficient data to support routine use in selected patients. The National Lipid Association, for example, recommends escalation to high-intensity statin for CAC > 100.

“One avenue to continue to address and advance diabetes management is through breaking down the four walls of the clinic or hospital through community engagement, clinic-to-community connections, and academic-community-government partnerships that may help address and support modifiable lifestyle behaviors such as physical activity, nutrition, smoking cessation and stress management,” Dr. Joseph concluded.

The AHA receives funding primarily from individuals. Foundations and corporations, including pharmaceutical, device manufacturers, and other companies, also make donations and fund AHA programs and events. The AHA’s strict policies prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers, and health insurance providers and the AHA’s financial information are available on the association’s website. Dr. Joseph has disclosed no relevant financial relationships.

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

A new document from the American Heart Association summarizes the latest research on cardiovascular risk factor management in type 2 diabetes, including medications, lifestyle, and social determinants of health.

Despite the availability of effective therapies for improving cardiovascular risk, in the United States fewer than one in five people with type 2 diabetes and without known cardiovascular disease meet control targets for a combination of A1c, blood pressure, LDL cholesterol, and nonsmoking status.

Volkan Ünalan/Thinkstock

That proportion drops to less than 1 in 10 if body mass index less than 30 kg/m² is included among the targets, and even less than that among individuals with established atherosclerotic cardiovascular disease, Joshua J. Joseph, MD, and colleagues point out in their paper, published online Jan. 10 in Circulation.

“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance type 2 diabetes treatment and care and reduce cardiovascular disease risk,” wrote Dr. Joseph, assistant professor of medicine in the division of endocrinology, diabetes, and metabolism at The Ohio State University, Columbus, Ohio, and coauthors.

The statement is not a guideline but an expert analysis that may inform future clinical practice guidelines, according to a press release from the AHA.

The new statement reviews evidence through June 2020 for lifestyle management of diabetes and weight, glycemic targets and control, blood pressure management, lipid management, antithrombotic therapy, and screening for cardiovascular and renal complications, including imaging. It also discusses the clinical implications of recent cardiovascular outcomes trials of newer glucose-lowering medications.

However, Dr. Joseph and colleagues point out, clinical care and treatment account for just 10%-20% of modifiable contributors to health outcomes. The other 80%-90% relate to social determinants of health, including health-related behaviors, socioeconomic factors, environmental factors, and racism.

“If we are to continue to advance the management of cardiovascular risk factors, we must also address the [social determinants of health] in the delivery of health care,” they noted.

Overall, they advise a patient-centered approach, meaning “reframing our clinical encounters to think about patients as people who live in families, communities, and societies that must be considered in their cardiovascular risk management.”

“People with [type 2 diabetes] face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients,” Dr. Joseph said in the AHA press release.
 

Lifestyle, medications for lowering A1c, BP, lipids

For lifestyle management, the authors say, “culturally appropriate recommendations through diabetes self-management education and support and medical nutrition therapy are key to meeting individualized goals for behavioral change and diabetes self-management.”

The document summarizes recommendations from other professional societies regarding glycemic targets and glucose lowering medications, i.e., target A1c levels of either < 7% or < 6.5% for the majority, with adjustments based on individual factors, such as life expectancy. It advises on use of metformin as first-line therapy followed by a sodium-glucose cotransporter-2 inhibitor or a glucagon-like peptide-1 agonist for those with established cardiovascular disease or risk factors.

“Cost may be a barrier to taking some [type 2 diabetes] medications as prescribed; however, many of these medications are now more commonly covered by more health insurance plans,” Dr. Joseph said.

“Another barrier is recognition by patients that these newer [type 2 diabetes] medications are also effective in reducing the risk of heart disease, stroke, heart failure, and kidney disease.”

Blood pressure treatment guidelines differ between those of the AHA/American College of Cardiology (ACC) and the American Diabetes Association (ADA), most notably that the AHA/ACC guidelines advise a general target of < 130/80 mm Hg, whereas ADA advises < 140/90 mm Hg or < 130/80 mm Hg for those with high risk if it can be safely achieved.

The decision should be “patient-centered with shared decision-making,” Dr. Joseph and colleagues advised.

For lipid-lowering, the document cites the 2018 ACC/AHA cholesterol guidelines, which include advising statins as first-line therapy for both primary and secondary prevention in diabetes, with highest intensity statins used in those at highest risk. But again, treatment should be individualized, and other agents should be used for patients in whom statins don’t work or aren’t tolerated.

And while use of antiplatelets – that is, aspirin – is well established as secondary prevention in type 2 diabetes, given new data suggesting that the risk for major bleeding could outweigh the benefits for primary prevention, “the relative benefits of antithrombotic approaches need to be weighed carefully against risks using a patient-centered approach,” the authors advised.

Among the many imaging tests available to facilitate cardiovascular risk stratification in type 2 diabetes, coronary artery calcification (CAC) CT screening is one of the few with sufficient data to support routine use in selected patients. The National Lipid Association, for example, recommends escalation to high-intensity statin for CAC > 100.

“One avenue to continue to address and advance diabetes management is through breaking down the four walls of the clinic or hospital through community engagement, clinic-to-community connections, and academic-community-government partnerships that may help address and support modifiable lifestyle behaviors such as physical activity, nutrition, smoking cessation and stress management,” Dr. Joseph concluded.

The AHA receives funding primarily from individuals. Foundations and corporations, including pharmaceutical, device manufacturers, and other companies, also make donations and fund AHA programs and events. The AHA’s strict policies prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers, and health insurance providers and the AHA’s financial information are available on the association’s website. Dr. Joseph has disclosed no relevant financial relationships.

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

A new document from the American Heart Association summarizes the latest research on cardiovascular risk factor management in type 2 diabetes, including medications, lifestyle, and social determinants of health.

Despite the availability of effective therapies for improving cardiovascular risk, in the United States fewer than one in five people with type 2 diabetes and without known cardiovascular disease meet control targets for a combination of A1c, blood pressure, LDL cholesterol, and nonsmoking status.

Volkan Ünalan/Thinkstock

That proportion drops to less than 1 in 10 if body mass index less than 30 kg/m² is included among the targets, and even less than that among individuals with established atherosclerotic cardiovascular disease, Joshua J. Joseph, MD, and colleagues point out in their paper, published online Jan. 10 in Circulation.

“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance type 2 diabetes treatment and care and reduce cardiovascular disease risk,” wrote Dr. Joseph, assistant professor of medicine in the division of endocrinology, diabetes, and metabolism at The Ohio State University, Columbus, Ohio, and coauthors.

The statement is not a guideline but an expert analysis that may inform future clinical practice guidelines, according to a press release from the AHA.

The new statement reviews evidence through June 2020 for lifestyle management of diabetes and weight, glycemic targets and control, blood pressure management, lipid management, antithrombotic therapy, and screening for cardiovascular and renal complications, including imaging. It also discusses the clinical implications of recent cardiovascular outcomes trials of newer glucose-lowering medications.

However, Dr. Joseph and colleagues point out, clinical care and treatment account for just 10%-20% of modifiable contributors to health outcomes. The other 80%-90% relate to social determinants of health, including health-related behaviors, socioeconomic factors, environmental factors, and racism.

“If we are to continue to advance the management of cardiovascular risk factors, we must also address the [social determinants of health] in the delivery of health care,” they noted.

Overall, they advise a patient-centered approach, meaning “reframing our clinical encounters to think about patients as people who live in families, communities, and societies that must be considered in their cardiovascular risk management.”

“People with [type 2 diabetes] face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients,” Dr. Joseph said in the AHA press release.
 

Lifestyle, medications for lowering A1c, BP, lipids

For lifestyle management, the authors say, “culturally appropriate recommendations through diabetes self-management education and support and medical nutrition therapy are key to meeting individualized goals for behavioral change and diabetes self-management.”

The document summarizes recommendations from other professional societies regarding glycemic targets and glucose lowering medications, i.e., target A1c levels of either < 7% or < 6.5% for the majority, with adjustments based on individual factors, such as life expectancy. It advises on use of metformin as first-line therapy followed by a sodium-glucose cotransporter-2 inhibitor or a glucagon-like peptide-1 agonist for those with established cardiovascular disease or risk factors.

“Cost may be a barrier to taking some [type 2 diabetes] medications as prescribed; however, many of these medications are now more commonly covered by more health insurance plans,” Dr. Joseph said.

“Another barrier is recognition by patients that these newer [type 2 diabetes] medications are also effective in reducing the risk of heart disease, stroke, heart failure, and kidney disease.”

Blood pressure treatment guidelines differ between those of the AHA/American College of Cardiology (ACC) and the American Diabetes Association (ADA), most notably that the AHA/ACC guidelines advise a general target of < 130/80 mm Hg, whereas ADA advises < 140/90 mm Hg or < 130/80 mm Hg for those with high risk if it can be safely achieved.

The decision should be “patient-centered with shared decision-making,” Dr. Joseph and colleagues advised.

For lipid-lowering, the document cites the 2018 ACC/AHA cholesterol guidelines, which include advising statins as first-line therapy for both primary and secondary prevention in diabetes, with highest intensity statins used in those at highest risk. But again, treatment should be individualized, and other agents should be used for patients in whom statins don’t work or aren’t tolerated.

And while use of antiplatelets – that is, aspirin – is well established as secondary prevention in type 2 diabetes, given new data suggesting that the risk for major bleeding could outweigh the benefits for primary prevention, “the relative benefits of antithrombotic approaches need to be weighed carefully against risks using a patient-centered approach,” the authors advised.

Among the many imaging tests available to facilitate cardiovascular risk stratification in type 2 diabetes, coronary artery calcification (CAC) CT screening is one of the few with sufficient data to support routine use in selected patients. The National Lipid Association, for example, recommends escalation to high-intensity statin for CAC > 100.

“One avenue to continue to address and advance diabetes management is through breaking down the four walls of the clinic or hospital through community engagement, clinic-to-community connections, and academic-community-government partnerships that may help address and support modifiable lifestyle behaviors such as physical activity, nutrition, smoking cessation and stress management,” Dr. Joseph concluded.

The AHA receives funding primarily from individuals. Foundations and corporations, including pharmaceutical, device manufacturers, and other companies, also make donations and fund AHA programs and events. The AHA’s strict policies prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers, and health insurance providers and the AHA’s financial information are available on the association’s website. Dr. Joseph has disclosed no relevant financial relationships.

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

Patients with complex coronary artery disease (CAD) – either three-vessel disease and/or left main disease – who also had heavy coronary artery calcification (CAC) had greater all-cause mortality 10 years after revascularization, compared with those without such lesions.

However, perhaps unexpectedly, patients with heavily calcified lesions (HCLs) had similar 10-year survival whether they had undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).

These findings from a post hoc analysis of the SYNTAX Extended Survival (SYNTAXES) study led by Hideyuki Kawashima, MD, PhD, National University of Ireland, Galway, and the University of Amsterdam, were published online Dec. 29, 2021, in JACC: Cardiovascular Interventions.

“There was an apparent lack of benefit at very long-term with CABG versus PCI in the presence of HCL,” Dr. Kawashima and corresponding author Patrick W. Serruys, MD, PhD, National University of Ireland and Imperial College London, summarized in a joint email to this news organization.

“Since HCLs – the final status of atherosclerosis and inflammation – reflect the aging process, complexity, and extensiveness of CAD, and comorbidity, it is possible that the currently available revascularization methods do not provide benefit in the prevention of long-term [10-year] mortality,” they suggested.  

In an accompanying editorial, Usman Baber, MD, commented that this study provides a “novel insight.”

Specifically, while patients without HCLs had significantly lower 10-year mortality with CABG versus PCI (18.8% vs. 26.0%; P = .003), an opposite trend was observed among those with HCLs (39.0% vs. 34.0%; P = .26; P int = .005).

The patients with HCLs had higher SYNTAX scores (30.8 vs. 22.4; P < .001) and more complex CAD, so their lack of 10-year mortality benefit with CABG “is somewhat unexpected and warrants further scrutiny,” added Dr. Baber, from the University of Oklahoma Health Sciences Center in Oklahoma City.

Dr. Serruys and Dr. Kawashima agreed that “this study highlights the need for further research on this topic focusing on this specific population with HCLs,” which were 30% of the patients with complex lesions who participated in SYNTAXES.
 

Consider factors beyond coronary anatomy

The current findings reinforce “the importance of considering not just coronary anatomy, but patient age and other comorbid factors when evaluating mode of revascularization,” said Dr. Baber.

“Coronary calcification is a strong factor in deciding between CABG versus PCI, as multiple studies have shown that CAC increases risk after PCI, even with contemporary safe stent platforms,” he explained in an email.

The current study suggests the adverse prognosis associated with CAC also persists for patients treated with CABG.

Dr. Baber said that, “for patients in whom PCI may not be feasible due to extensive and bulky coronary calcification, it is important to emphasize that the benefits of CABG (versus PCI) may not be as significant or durable.”

“The lack of benefit with CABG,” he added, “is likely due to comorbid factors that tend to increase in prevalence with vascular calcification (older age, peripheral arterial disease, renal impairment, etc).”

This study reinforces “the importance of not just considering coronary complexity, but also additional noncoronary factors that influence long-term prognosis in patients with advanced multivessel CAD,” Dr. Baber stressed.

More aggressive lipid-lowering or antithrombotic therapy may improve the prognosis for such patients, he suggested.

“In general,” Dr. Serruys and Dr. Kawashima similarly noted, “for short-/mid-term outcomes, CABG is preferred to PCI in patients with HCLs because of a higher rate of complete revascularization and less need for repeat revascularization.”

“Our findings at 10 years are in line with the general findings preferring CABG in mid and long term, whereas the benefit of very long-term follow-up might be more complex to capture and comprehend,” they concluded. “Whether HCLs require special consideration when deciding the mode of revascularization beyond their contribution to the SYNTAX score deserves further evaluation.

“Newer PCI technology or CABG methods may become a game-changer in the future,” they speculated.
 

Worse clinical outcomes

Heavy coronary calcification is associated with worse clinical outcomes after PCI or CABG, but to date, no trial has compared 10-year outcomes after PCI or CABG in patients with complex CAD with versus without HCLs.

To look at this, Dr. Kawashima and colleagues performed a subanalysis of patients in the SYNTAXES study. The original SYNTAX trial had randomized 1,800 patients with complex CAD who were eligible for either PCI or CABG 1:1 to these two treatments, with a 5-year follow-up, and SYNTAXES extended the follow-up to 10 years.  

Of the 1,800 patients, 532 (29.6%) had at least one HCL and the rest (70.4%) did not.

The median follow-up in SYNTAXES was 11.2 years overall and 11.9 years in survivors.

At baseline, compared with other patients, those with HCLs were older and had a lower body mass index and higher rates of insulin-treated diabetes, hypertension, previous cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, chronic kidney disease, and heart failure.

After adjusting for multiple variables, having a HCL was an independent predictor of greater risk of 10-year mortality (hazard ratio, 1.36; 95% confidence interval, 1.09-1.69; P = .006).

In patients without HCLs, mortality was significantly higher after PCI than CABG (HR, 1.44; 95% CI, 1.14-1.83; P = .003), whereas in those with HCLs, there was no significant difference (HR, 0.85; 95% CI, 0.64-1.13; P = .264).

The location of the HCL did not have any impact on 10-year mortality regardless of the assigned treatment.

Among patients with at least one HCL who underwent CABG, those with at least two HCLs had greater 10-year all-cause mortality than those with one HCL; this difference was not seen among patients with at least one HCL who underwent PCI.

The researchers acknowledge study limitations include that it was a post hoc analysis, so it should be considered hypothesis generating.

In addition, SYNTAX was conducted between 2005 and 2007, when PCI mainly used first-generation paclitaxel drug-eluting stents, so the findings may not be generalizable to current practice.

SYNTAXES was supported by the German Foundation of Heart Research. SYNTAX, during 0- to 5-year follow-up, was funded by Boston Scientific. Dr. Serruys reported receiving personal fees from SMT, Philips/Volcano, Xeltis, Novartis, and Meril Life. Dr. Kawashima reported no relevant financial relationships. Dr. Baber reported receiving honoraria and speaker fees from AstraZeneca, Biotronik, and Amgen.

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

Patients with complex coronary artery disease (CAD) – either three-vessel disease and/or left main disease – who also had heavy coronary artery calcification (CAC) had greater all-cause mortality 10 years after revascularization, compared with those without such lesions.

However, perhaps unexpectedly, patients with heavily calcified lesions (HCLs) had similar 10-year survival whether they had undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).

These findings from a post hoc analysis of the SYNTAX Extended Survival (SYNTAXES) study led by Hideyuki Kawashima, MD, PhD, National University of Ireland, Galway, and the University of Amsterdam, were published online Dec. 29, 2021, in JACC: Cardiovascular Interventions.

“There was an apparent lack of benefit at very long-term with CABG versus PCI in the presence of HCL,” Dr. Kawashima and corresponding author Patrick W. Serruys, MD, PhD, National University of Ireland and Imperial College London, summarized in a joint email to this news organization.

“Since HCLs – the final status of atherosclerosis and inflammation – reflect the aging process, complexity, and extensiveness of CAD, and comorbidity, it is possible that the currently available revascularization methods do not provide benefit in the prevention of long-term [10-year] mortality,” they suggested.  

In an accompanying editorial, Usman Baber, MD, commented that this study provides a “novel insight.”

Specifically, while patients without HCLs had significantly lower 10-year mortality with CABG versus PCI (18.8% vs. 26.0%; P = .003), an opposite trend was observed among those with HCLs (39.0% vs. 34.0%; P = .26; P int = .005).

The patients with HCLs had higher SYNTAX scores (30.8 vs. 22.4; P < .001) and more complex CAD, so their lack of 10-year mortality benefit with CABG “is somewhat unexpected and warrants further scrutiny,” added Dr. Baber, from the University of Oklahoma Health Sciences Center in Oklahoma City.

Dr. Serruys and Dr. Kawashima agreed that “this study highlights the need for further research on this topic focusing on this specific population with HCLs,” which were 30% of the patients with complex lesions who participated in SYNTAXES.
 

Consider factors beyond coronary anatomy

The current findings reinforce “the importance of considering not just coronary anatomy, but patient age and other comorbid factors when evaluating mode of revascularization,” said Dr. Baber.

“Coronary calcification is a strong factor in deciding between CABG versus PCI, as multiple studies have shown that CAC increases risk after PCI, even with contemporary safe stent platforms,” he explained in an email.

The current study suggests the adverse prognosis associated with CAC also persists for patients treated with CABG.

Dr. Baber said that, “for patients in whom PCI may not be feasible due to extensive and bulky coronary calcification, it is important to emphasize that the benefits of CABG (versus PCI) may not be as significant or durable.”

“The lack of benefit with CABG,” he added, “is likely due to comorbid factors that tend to increase in prevalence with vascular calcification (older age, peripheral arterial disease, renal impairment, etc).”

This study reinforces “the importance of not just considering coronary complexity, but also additional noncoronary factors that influence long-term prognosis in patients with advanced multivessel CAD,” Dr. Baber stressed.

More aggressive lipid-lowering or antithrombotic therapy may improve the prognosis for such patients, he suggested.

“In general,” Dr. Serruys and Dr. Kawashima similarly noted, “for short-/mid-term outcomes, CABG is preferred to PCI in patients with HCLs because of a higher rate of complete revascularization and less need for repeat revascularization.”

“Our findings at 10 years are in line with the general findings preferring CABG in mid and long term, whereas the benefit of very long-term follow-up might be more complex to capture and comprehend,” they concluded. “Whether HCLs require special consideration when deciding the mode of revascularization beyond their contribution to the SYNTAX score deserves further evaluation.

“Newer PCI technology or CABG methods may become a game-changer in the future,” they speculated.
 

Worse clinical outcomes

Heavy coronary calcification is associated with worse clinical outcomes after PCI or CABG, but to date, no trial has compared 10-year outcomes after PCI or CABG in patients with complex CAD with versus without HCLs.

To look at this, Dr. Kawashima and colleagues performed a subanalysis of patients in the SYNTAXES study. The original SYNTAX trial had randomized 1,800 patients with complex CAD who were eligible for either PCI or CABG 1:1 to these two treatments, with a 5-year follow-up, and SYNTAXES extended the follow-up to 10 years.  

Of the 1,800 patients, 532 (29.6%) had at least one HCL and the rest (70.4%) did not.

The median follow-up in SYNTAXES was 11.2 years overall and 11.9 years in survivors.

At baseline, compared with other patients, those with HCLs were older and had a lower body mass index and higher rates of insulin-treated diabetes, hypertension, previous cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, chronic kidney disease, and heart failure.

After adjusting for multiple variables, having a HCL was an independent predictor of greater risk of 10-year mortality (hazard ratio, 1.36; 95% confidence interval, 1.09-1.69; P = .006).

In patients without HCLs, mortality was significantly higher after PCI than CABG (HR, 1.44; 95% CI, 1.14-1.83; P = .003), whereas in those with HCLs, there was no significant difference (HR, 0.85; 95% CI, 0.64-1.13; P = .264).

The location of the HCL did not have any impact on 10-year mortality regardless of the assigned treatment.

Among patients with at least one HCL who underwent CABG, those with at least two HCLs had greater 10-year all-cause mortality than those with one HCL; this difference was not seen among patients with at least one HCL who underwent PCI.

The researchers acknowledge study limitations include that it was a post hoc analysis, so it should be considered hypothesis generating.

In addition, SYNTAX was conducted between 2005 and 2007, when PCI mainly used first-generation paclitaxel drug-eluting stents, so the findings may not be generalizable to current practice.

SYNTAXES was supported by the German Foundation of Heart Research. SYNTAX, during 0- to 5-year follow-up, was funded by Boston Scientific. Dr. Serruys reported receiving personal fees from SMT, Philips/Volcano, Xeltis, Novartis, and Meril Life. Dr. Kawashima reported no relevant financial relationships. Dr. Baber reported receiving honoraria and speaker fees from AstraZeneca, Biotronik, and Amgen.

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

Patients with complex coronary artery disease (CAD) – either three-vessel disease and/or left main disease – who also had heavy coronary artery calcification (CAC) had greater all-cause mortality 10 years after revascularization, compared with those without such lesions.

However, perhaps unexpectedly, patients with heavily calcified lesions (HCLs) had similar 10-year survival whether they had undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).

These findings from a post hoc analysis of the SYNTAX Extended Survival (SYNTAXES) study led by Hideyuki Kawashima, MD, PhD, National University of Ireland, Galway, and the University of Amsterdam, were published online Dec. 29, 2021, in JACC: Cardiovascular Interventions.

“There was an apparent lack of benefit at very long-term with CABG versus PCI in the presence of HCL,” Dr. Kawashima and corresponding author Patrick W. Serruys, MD, PhD, National University of Ireland and Imperial College London, summarized in a joint email to this news organization.

“Since HCLs – the final status of atherosclerosis and inflammation – reflect the aging process, complexity, and extensiveness of CAD, and comorbidity, it is possible that the currently available revascularization methods do not provide benefit in the prevention of long-term [10-year] mortality,” they suggested.  

In an accompanying editorial, Usman Baber, MD, commented that this study provides a “novel insight.”

Specifically, while patients without HCLs had significantly lower 10-year mortality with CABG versus PCI (18.8% vs. 26.0%; P = .003), an opposite trend was observed among those with HCLs (39.0% vs. 34.0%; P = .26; P int = .005).

The patients with HCLs had higher SYNTAX scores (30.8 vs. 22.4; P < .001) and more complex CAD, so their lack of 10-year mortality benefit with CABG “is somewhat unexpected and warrants further scrutiny,” added Dr. Baber, from the University of Oklahoma Health Sciences Center in Oklahoma City.

Dr. Serruys and Dr. Kawashima agreed that “this study highlights the need for further research on this topic focusing on this specific population with HCLs,” which were 30% of the patients with complex lesions who participated in SYNTAXES.
 

Consider factors beyond coronary anatomy

The current findings reinforce “the importance of considering not just coronary anatomy, but patient age and other comorbid factors when evaluating mode of revascularization,” said Dr. Baber.

“Coronary calcification is a strong factor in deciding between CABG versus PCI, as multiple studies have shown that CAC increases risk after PCI, even with contemporary safe stent platforms,” he explained in an email.

The current study suggests the adverse prognosis associated with CAC also persists for patients treated with CABG.

Dr. Baber said that, “for patients in whom PCI may not be feasible due to extensive and bulky coronary calcification, it is important to emphasize that the benefits of CABG (versus PCI) may not be as significant or durable.”

“The lack of benefit with CABG,” he added, “is likely due to comorbid factors that tend to increase in prevalence with vascular calcification (older age, peripheral arterial disease, renal impairment, etc).”

This study reinforces “the importance of not just considering coronary complexity, but also additional noncoronary factors that influence long-term prognosis in patients with advanced multivessel CAD,” Dr. Baber stressed.

More aggressive lipid-lowering or antithrombotic therapy may improve the prognosis for such patients, he suggested.

“In general,” Dr. Serruys and Dr. Kawashima similarly noted, “for short-/mid-term outcomes, CABG is preferred to PCI in patients with HCLs because of a higher rate of complete revascularization and less need for repeat revascularization.”

“Our findings at 10 years are in line with the general findings preferring CABG in mid and long term, whereas the benefit of very long-term follow-up might be more complex to capture and comprehend,” they concluded. “Whether HCLs require special consideration when deciding the mode of revascularization beyond their contribution to the SYNTAX score deserves further evaluation.

“Newer PCI technology or CABG methods may become a game-changer in the future,” they speculated.
 

Worse clinical outcomes

Heavy coronary calcification is associated with worse clinical outcomes after PCI or CABG, but to date, no trial has compared 10-year outcomes after PCI or CABG in patients with complex CAD with versus without HCLs.

To look at this, Dr. Kawashima and colleagues performed a subanalysis of patients in the SYNTAXES study. The original SYNTAX trial had randomized 1,800 patients with complex CAD who were eligible for either PCI or CABG 1:1 to these two treatments, with a 5-year follow-up, and SYNTAXES extended the follow-up to 10 years.  

Of the 1,800 patients, 532 (29.6%) had at least one HCL and the rest (70.4%) did not.

The median follow-up in SYNTAXES was 11.2 years overall and 11.9 years in survivors.

At baseline, compared with other patients, those with HCLs were older and had a lower body mass index and higher rates of insulin-treated diabetes, hypertension, previous cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, chronic kidney disease, and heart failure.

After adjusting for multiple variables, having a HCL was an independent predictor of greater risk of 10-year mortality (hazard ratio, 1.36; 95% confidence interval, 1.09-1.69; P = .006).

In patients without HCLs, mortality was significantly higher after PCI than CABG (HR, 1.44; 95% CI, 1.14-1.83; P = .003), whereas in those with HCLs, there was no significant difference (HR, 0.85; 95% CI, 0.64-1.13; P = .264).

The location of the HCL did not have any impact on 10-year mortality regardless of the assigned treatment.

Among patients with at least one HCL who underwent CABG, those with at least two HCLs had greater 10-year all-cause mortality than those with one HCL; this difference was not seen among patients with at least one HCL who underwent PCI.

The researchers acknowledge study limitations include that it was a post hoc analysis, so it should be considered hypothesis generating.

In addition, SYNTAX was conducted between 2005 and 2007, when PCI mainly used first-generation paclitaxel drug-eluting stents, so the findings may not be generalizable to current practice.

SYNTAXES was supported by the German Foundation of Heart Research. SYNTAX, during 0- to 5-year follow-up, was funded by Boston Scientific. Dr. Serruys reported receiving personal fees from SMT, Philips/Volcano, Xeltis, Novartis, and Meril Life. Dr. Kawashima reported no relevant financial relationships. Dr. Baber reported receiving honoraria and speaker fees from AstraZeneca, Biotronik, and Amgen.

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

The new 2021 coronary revascularization guidelines are spurring controversy, as surgical associations raise concerns about the interpretation of the evidence behind key recommendations and the makeup of the writing committee.

The guideline was published in December by the American College of Cardiology, American Heart Association, and Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI), and replaces the 2011 coronary artery bypass surgery (CABG) and the 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.

The American Association for Thoracic Surgery (AATS) and Society of Thoracic Surgeons (STS) were part of the development of the document but have withdrawn their support, citing three areas of concern in a recent editorial in Annals of Thoracic Surgery.

“I do have to emphasize this is not just the AATS and STS – the European societies, Latin American societies, Asian societies, and even cardiologists are all coming out against these guidelines,” Joseph F. Sabik III, MD, University Hospitals Cleveland Medical Center, lead author of the editorial, said in an interview. “So, I think that tells us that something didn’t go right here.”

The main objection is the downgrading of CABG surgery from a class 1 to weak 2b recommendation to improve survival in patients with three-vessel coronary artery disease (CAD) and normal left ventricular function.

The ISCHEMIA trial was used to support this two-level downgrade and a class 1 to 2a downgrade for CABG in three-vessel CAD with mild to moderate left ventricular dysfunction. But the trial wasn’t powered for survival, only 20% of patients underwent CABG as the initial invasive strategy, and patients were followed for less than 5 years, the editorialists observed.

At the same time, there’s plenty of observational and randomized studies such as SYNTAX, EXCEL, and FAME 3 showing a clear survival benefit of CABG over PCI, Dr. Sabik said. “The criticism is that these are old studies and aren’t applicable today, but we don’t understand downgrading without any evidence suggesting it [CABG] isn’t effective anymore.”
 

CABG and PCI treated as equal

AATS and STS also object to the new guidelines treating PCI and CABG as equivalent revascularization strategies in decreasing ischemic events. Both were given a 2b recommendation for survival with triple-vessel disease, but randomized trials have demonstrated not only lower mortality with surgery but fewer reinterventions and myocardial infarctions.

“None of that gets acknowledged in the guidelines; they are treated equally,” Dr. Sabik said. “So if you’re going to say that CABG isn’t any better than medical therapy, in our mind, you have to say that PCI is worse than medical therapy. And we don’t believe that, I want you to know. We just think that the logic doesn’t make any sense. The committee used what it wanted to but didn’t use many things that committees have used in the past to give CABG a level 1 recommendation.”

The downgrade is also at odds with the 2018 European Society of Cardiology (ESC)/ European Association for Cardio-Thoracic Surgery (EACTS) guidelines, which give CABG a class 1 recommendation in three-vessel CAD as well as one- or two-vessel CAD with proximal left atrial descending artery stenosis.

In a Dec. 14 letter to the ACC/AHA Joint Committee, the Latin American Association of Cardiac and Endovascular Surgery (LACES) also called out the guideline committee for the 2b class of recommendation (COR) for PCI and CABG, saying it contradicts the text, which “clearly considers” the need to give a weaker endorsement for PCI than for CABG in patients with multivessel CAD.

“Considering that this section has the most significant impact due to the prevalence of stable ischemic heart disease in patients with multivessel CAD, such a contradiction may affect the lives and survival of millions of patients worldwide and have a major socioeconomic impact,” the letter states.

“Therefore, LACES respectfully but vehemently believes the Task Force should seriously reconsider the wording and recommendations in this specific large group of patients.”
 

Class I for radial conduit

AATS and STS also express concern about the new class 1 recommendation for the radial artery as a conduit in CABG. They note this is higher than bilateral internal mammary artery grafting and based on a meta-analysis of six relatively small studies with very strict inclusion criteria favorable for radial artery usage and patency.

“There’s a lot of studies that showed if you use the radial artery incorrectly, you have worse outcomes, and that’s what scares us a bit,” Dr. Sabik said. “If they’re giving it a class 1 recommendation, does that mean that becomes standard of care and could that cause patient harm? We think that level 1 is too high and that a [class] 2a with qualifications would be appropriate.”
 

Unequal footing

In a Dec. 23 letter, EACTS said it is “extremely concerned” about downgrading the COR for CABG without new randomized controlled trials to support the decision or to reject previously held evidence.

“The downgrading of CABG, and placing PCI at the same COR, does not meet our interpretation of the evidence, and may lead to avoidable loss of life,” EACTS officials said. “These guidelines also have implications on patient care: A COR IIb entails that CABG may not be reimbursable in some countries.”

EACTS called on AHA, ACC, and SCAI to review the evidence and called out the makeup of the guideline writing committee. “It is astonishing that no surgical association was involved, coauthored, or endorsed these guidelines.”

The AATS and STS each had a single representative on the guidelines’ writing committee but note that the six remaining surgeons were chosen by the ACC and AHA. Surgeons were also in the minority and only a majority was needed to approve the guidelines, highlighting the need to revisit the guideline development process to ensure equal representation by multidisciplinary experts across specialties.

“I hope the cardiology and surgical societies can come together and figure out how we do this better in the future, and we take a look again at these guidelines and come up with what we think is appropriate, especially since this is not just AATS and STS,” Dr. Sabik said.

In an emailed statement, the ACC/AHA said the AATS and STS representatives “actively participated throughout the writing process the past 3 years” and that the AATS and STS were involved in the “extensive peer review process” for the document with a reviewer from each organization. Nevertheless, AATS and STS both elected not to endorse the guidelines when at the organizational approval stage.

“Consequently, the AATS representative chose to stay with the committee and be recognized as having been appointed on behalf of the ACC and the AHA,” according to the statement. “The STS representative chose to withdraw from the committee and is not listed as a writing committee member on the final guideline. The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed by the ACC, AHA, SCAI, and the full writing committee.”

Despite pleas from the surgical groups to reconsider the evidence, “there is no further review process for the revascularization guideline,” the ACC/AHA spokesperson noted.

Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair, did not respond to numerous requests for comment.

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

The new 2021 coronary revascularization guidelines are spurring controversy, as surgical associations raise concerns about the interpretation of the evidence behind key recommendations and the makeup of the writing committee.

The guideline was published in December by the American College of Cardiology, American Heart Association, and Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI), and replaces the 2011 coronary artery bypass surgery (CABG) and the 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.

The American Association for Thoracic Surgery (AATS) and Society of Thoracic Surgeons (STS) were part of the development of the document but have withdrawn their support, citing three areas of concern in a recent editorial in Annals of Thoracic Surgery.

“I do have to emphasize this is not just the AATS and STS – the European societies, Latin American societies, Asian societies, and even cardiologists are all coming out against these guidelines,” Joseph F. Sabik III, MD, University Hospitals Cleveland Medical Center, lead author of the editorial, said in an interview. “So, I think that tells us that something didn’t go right here.”

The main objection is the downgrading of CABG surgery from a class 1 to weak 2b recommendation to improve survival in patients with three-vessel coronary artery disease (CAD) and normal left ventricular function.

The ISCHEMIA trial was used to support this two-level downgrade and a class 1 to 2a downgrade for CABG in three-vessel CAD with mild to moderate left ventricular dysfunction. But the trial wasn’t powered for survival, only 20% of patients underwent CABG as the initial invasive strategy, and patients were followed for less than 5 years, the editorialists observed.

At the same time, there’s plenty of observational and randomized studies such as SYNTAX, EXCEL, and FAME 3 showing a clear survival benefit of CABG over PCI, Dr. Sabik said. “The criticism is that these are old studies and aren’t applicable today, but we don’t understand downgrading without any evidence suggesting it [CABG] isn’t effective anymore.”
 

CABG and PCI treated as equal

AATS and STS also object to the new guidelines treating PCI and CABG as equivalent revascularization strategies in decreasing ischemic events. Both were given a 2b recommendation for survival with triple-vessel disease, but randomized trials have demonstrated not only lower mortality with surgery but fewer reinterventions and myocardial infarctions.

“None of that gets acknowledged in the guidelines; they are treated equally,” Dr. Sabik said. “So if you’re going to say that CABG isn’t any better than medical therapy, in our mind, you have to say that PCI is worse than medical therapy. And we don’t believe that, I want you to know. We just think that the logic doesn’t make any sense. The committee used what it wanted to but didn’t use many things that committees have used in the past to give CABG a level 1 recommendation.”

The downgrade is also at odds with the 2018 European Society of Cardiology (ESC)/ European Association for Cardio-Thoracic Surgery (EACTS) guidelines, which give CABG a class 1 recommendation in three-vessel CAD as well as one- or two-vessel CAD with proximal left atrial descending artery stenosis.

In a Dec. 14 letter to the ACC/AHA Joint Committee, the Latin American Association of Cardiac and Endovascular Surgery (LACES) also called out the guideline committee for the 2b class of recommendation (COR) for PCI and CABG, saying it contradicts the text, which “clearly considers” the need to give a weaker endorsement for PCI than for CABG in patients with multivessel CAD.

“Considering that this section has the most significant impact due to the prevalence of stable ischemic heart disease in patients with multivessel CAD, such a contradiction may affect the lives and survival of millions of patients worldwide and have a major socioeconomic impact,” the letter states.

“Therefore, LACES respectfully but vehemently believes the Task Force should seriously reconsider the wording and recommendations in this specific large group of patients.”
 

Class I for radial conduit

AATS and STS also express concern about the new class 1 recommendation for the radial artery as a conduit in CABG. They note this is higher than bilateral internal mammary artery grafting and based on a meta-analysis of six relatively small studies with very strict inclusion criteria favorable for radial artery usage and patency.

“There’s a lot of studies that showed if you use the radial artery incorrectly, you have worse outcomes, and that’s what scares us a bit,” Dr. Sabik said. “If they’re giving it a class 1 recommendation, does that mean that becomes standard of care and could that cause patient harm? We think that level 1 is too high and that a [class] 2a with qualifications would be appropriate.”
 

Unequal footing

In a Dec. 23 letter, EACTS said it is “extremely concerned” about downgrading the COR for CABG without new randomized controlled trials to support the decision or to reject previously held evidence.

“The downgrading of CABG, and placing PCI at the same COR, does not meet our interpretation of the evidence, and may lead to avoidable loss of life,” EACTS officials said. “These guidelines also have implications on patient care: A COR IIb entails that CABG may not be reimbursable in some countries.”

EACTS called on AHA, ACC, and SCAI to review the evidence and called out the makeup of the guideline writing committee. “It is astonishing that no surgical association was involved, coauthored, or endorsed these guidelines.”

The AATS and STS each had a single representative on the guidelines’ writing committee but note that the six remaining surgeons were chosen by the ACC and AHA. Surgeons were also in the minority and only a majority was needed to approve the guidelines, highlighting the need to revisit the guideline development process to ensure equal representation by multidisciplinary experts across specialties.

“I hope the cardiology and surgical societies can come together and figure out how we do this better in the future, and we take a look again at these guidelines and come up with what we think is appropriate, especially since this is not just AATS and STS,” Dr. Sabik said.

In an emailed statement, the ACC/AHA said the AATS and STS representatives “actively participated throughout the writing process the past 3 years” and that the AATS and STS were involved in the “extensive peer review process” for the document with a reviewer from each organization. Nevertheless, AATS and STS both elected not to endorse the guidelines when at the organizational approval stage.

“Consequently, the AATS representative chose to stay with the committee and be recognized as having been appointed on behalf of the ACC and the AHA,” according to the statement. “The STS representative chose to withdraw from the committee and is not listed as a writing committee member on the final guideline. The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed by the ACC, AHA, SCAI, and the full writing committee.”

Despite pleas from the surgical groups to reconsider the evidence, “there is no further review process for the revascularization guideline,” the ACC/AHA spokesperson noted.

Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair, did not respond to numerous requests for comment.

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

The new 2021 coronary revascularization guidelines are spurring controversy, as surgical associations raise concerns about the interpretation of the evidence behind key recommendations and the makeup of the writing committee.

The guideline was published in December by the American College of Cardiology, American Heart Association, and Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI), and replaces the 2011 coronary artery bypass surgery (CABG) and the 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.

The American Association for Thoracic Surgery (AATS) and Society of Thoracic Surgeons (STS) were part of the development of the document but have withdrawn their support, citing three areas of concern in a recent editorial in Annals of Thoracic Surgery.

“I do have to emphasize this is not just the AATS and STS – the European societies, Latin American societies, Asian societies, and even cardiologists are all coming out against these guidelines,” Joseph F. Sabik III, MD, University Hospitals Cleveland Medical Center, lead author of the editorial, said in an interview. “So, I think that tells us that something didn’t go right here.”

The main objection is the downgrading of CABG surgery from a class 1 to weak 2b recommendation to improve survival in patients with three-vessel coronary artery disease (CAD) and normal left ventricular function.

The ISCHEMIA trial was used to support this two-level downgrade and a class 1 to 2a downgrade for CABG in three-vessel CAD with mild to moderate left ventricular dysfunction. But the trial wasn’t powered for survival, only 20% of patients underwent CABG as the initial invasive strategy, and patients were followed for less than 5 years, the editorialists observed.

At the same time, there’s plenty of observational and randomized studies such as SYNTAX, EXCEL, and FAME 3 showing a clear survival benefit of CABG over PCI, Dr. Sabik said. “The criticism is that these are old studies and aren’t applicable today, but we don’t understand downgrading without any evidence suggesting it [CABG] isn’t effective anymore.”
 

CABG and PCI treated as equal

AATS and STS also object to the new guidelines treating PCI and CABG as equivalent revascularization strategies in decreasing ischemic events. Both were given a 2b recommendation for survival with triple-vessel disease, but randomized trials have demonstrated not only lower mortality with surgery but fewer reinterventions and myocardial infarctions.

“None of that gets acknowledged in the guidelines; they are treated equally,” Dr. Sabik said. “So if you’re going to say that CABG isn’t any better than medical therapy, in our mind, you have to say that PCI is worse than medical therapy. And we don’t believe that, I want you to know. We just think that the logic doesn’t make any sense. The committee used what it wanted to but didn’t use many things that committees have used in the past to give CABG a level 1 recommendation.”

The downgrade is also at odds with the 2018 European Society of Cardiology (ESC)/ European Association for Cardio-Thoracic Surgery (EACTS) guidelines, which give CABG a class 1 recommendation in three-vessel CAD as well as one- or two-vessel CAD with proximal left atrial descending artery stenosis.

In a Dec. 14 letter to the ACC/AHA Joint Committee, the Latin American Association of Cardiac and Endovascular Surgery (LACES) also called out the guideline committee for the 2b class of recommendation (COR) for PCI and CABG, saying it contradicts the text, which “clearly considers” the need to give a weaker endorsement for PCI than for CABG in patients with multivessel CAD.

“Considering that this section has the most significant impact due to the prevalence of stable ischemic heart disease in patients with multivessel CAD, such a contradiction may affect the lives and survival of millions of patients worldwide and have a major socioeconomic impact,” the letter states.

“Therefore, LACES respectfully but vehemently believes the Task Force should seriously reconsider the wording and recommendations in this specific large group of patients.”
 

Class I for radial conduit

AATS and STS also express concern about the new class 1 recommendation for the radial artery as a conduit in CABG. They note this is higher than bilateral internal mammary artery grafting and based on a meta-analysis of six relatively small studies with very strict inclusion criteria favorable for radial artery usage and patency.

“There’s a lot of studies that showed if you use the radial artery incorrectly, you have worse outcomes, and that’s what scares us a bit,” Dr. Sabik said. “If they’re giving it a class 1 recommendation, does that mean that becomes standard of care and could that cause patient harm? We think that level 1 is too high and that a [class] 2a with qualifications would be appropriate.”
 

Unequal footing

In a Dec. 23 letter, EACTS said it is “extremely concerned” about downgrading the COR for CABG without new randomized controlled trials to support the decision or to reject previously held evidence.

“The downgrading of CABG, and placing PCI at the same COR, does not meet our interpretation of the evidence, and may lead to avoidable loss of life,” EACTS officials said. “These guidelines also have implications on patient care: A COR IIb entails that CABG may not be reimbursable in some countries.”

EACTS called on AHA, ACC, and SCAI to review the evidence and called out the makeup of the guideline writing committee. “It is astonishing that no surgical association was involved, coauthored, or endorsed these guidelines.”

The AATS and STS each had a single representative on the guidelines’ writing committee but note that the six remaining surgeons were chosen by the ACC and AHA. Surgeons were also in the minority and only a majority was needed to approve the guidelines, highlighting the need to revisit the guideline development process to ensure equal representation by multidisciplinary experts across specialties.

“I hope the cardiology and surgical societies can come together and figure out how we do this better in the future, and we take a look again at these guidelines and come up with what we think is appropriate, especially since this is not just AATS and STS,” Dr. Sabik said.

In an emailed statement, the ACC/AHA said the AATS and STS representatives “actively participated throughout the writing process the past 3 years” and that the AATS and STS were involved in the “extensive peer review process” for the document with a reviewer from each organization. Nevertheless, AATS and STS both elected not to endorse the guidelines when at the organizational approval stage.

“Consequently, the AATS representative chose to stay with the committee and be recognized as having been appointed on behalf of the ACC and the AHA,” according to the statement. “The STS representative chose to withdraw from the committee and is not listed as a writing committee member on the final guideline. The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed by the ACC, AHA, SCAI, and the full writing committee.”

Despite pleas from the surgical groups to reconsider the evidence, “there is no further review process for the revascularization guideline,” the ACC/AHA spokesperson noted.

Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair, did not respond to numerous requests for comment.

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

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

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

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

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

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

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