CVD risk

Arm Fat Raises CVD Risk in People With Type 2 Diabetes

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In people with type 2 diabetes (T2D), higher levels of arm and trunk fat are associated with an increased risk for cardiovascular disease (CVD) and mortality, while higher levels of leg fat are associated with a reduced risk for these conditions.

METHODOLOGY:

  • People with T2D have a twofold to fourfold higher risk for CVD and mortality, and evidence shows obesity management helps delay complications and premature death, but an elevated body mass index (BMI) may be insufficient to measure obesity.
  • In the “obesity paradox,” people with elevated BMI may have a lower CVD risk than people of normal weight.
  • Researchers prospectively investigated how regional body fat accumulation was associated with CVD risk in 21,472 people with T2D (mean age, 58.9 years; 60.7% men; BMI about 29-33) from the UK Biobank (2006-2010), followed up for a median of 7.7 years.
  • The regional body fat distribution in arms, trunk, and legs was assessed using bioelectrical impedance analysis.
  • The primary outcomes were the incidence of CVD, all-cause mortality, and CVD mortality.

TAKEAWAY:

  • Participants in the highest quartile of arm fat percentage (multivariate-adjusted hazard ratio [HR], 1.63; 95% CI, 1.29-2.05) and trunk fat percentage (HR, 1.27; 95% CI, 1.06-1.52) were at a higher risk for CVD than those in the lowest quartile.
  • However, participants in the highest quartile of leg fat percentage had a lower risk for CVD than those in the lowest quartile (HR, 0.72; 95% CI, 0.58-0.90).
  • A nonlinear relationship was observed between higher leg fat percentage and lower CVD risk and between higher trunk fat percentage and higher CVD risk, whereas a linear relationship was noted between higher arm fat percentage and higher CVD risk.
  • The patterns of association were similar for both all-cause mortality and CVD mortality. Overall patterns were similar for men and women.

IN PRACTICE:

“Our findings add to the understanding of body fat distribution in patients with T2D, which highlights the importance of considering both the amount and the location of body fat when assessing CVD and mortality risk among patients with T2D,” wrote the authors.

Menopausal hormone therapy safe for most women at low CVD risk

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Menopausal hormone therapy for bothersome vasomotor or other symptoms is safe and appropriate for most women at low atherosclerotic CVD risk, whereas a nuanced approach is needed for intermediate-risk women, researchers reported.

“Many cardiologists are reluctant to prescribe hormone therapy (HT) to patients with symptoms of menopause because of concerns with CVD risk,” Leslie Cho, MD, director of the Cleveland Clinic’s Women’s Cardiovascular Center, told Healio. “There is confusion around the evidence-based guidelines that support hormone use. We thought this was a perfect time to address this issue, as there has been this enormous resurgence of interest in menopausal hormone treatment and major consumer wellness organizations have entered the fray.”

Graphical depiction of data presented in article

At one time, menopausal HT was almost universally recommended, Cho and colleagues wrote in a review published in Circulation. With the publication of the Heart and Estrogen/progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI) trial, both of which reported excess CV risk with HT, use of HT declined substantially, Cho said.

However, during the past 20 years, the relationship of CVD risk with timing of menopause, initiation of HT and route of HT delivery has been better understood. Four major North American medical societies — the American College of Obstetricians and Gynecologists, American Association of Clinical Endocrinology, the Endocrine Society, and the North American Menopause Society — now recommend HT in appropriate patients for the management of menopausal symptoms.

“No one recommends hormones for CVD prevention,” Cho said in an interview. “HT does not impact weight or lower heart disease risk. HT is recommended for bothersome menopausal symptoms.”

Ideal candidates for HT

The review, led by the American College of Cardiology Cardiovascular Disease in Women Committee, along with leading gynecologists, women’s health internists and endocrinologists, states that ideal candidates for menopausal HT are women who are younger than 60 years or within 10 years of menopause onset, who have a 10-year estimated ASCVD risk of less than 5% and do not have an increased risk for breast cancer or history of venous thromboembolism.

A more nuanced approach for HT is recommended for women at intermediate CVD risk, defined as women who have diabetes, who smoke, have hypertension, obesity, metabolic syndrome or an autoimmune disease, among other risk factors.

“The presence of CVD risk factors alone does not preclude the use of HT, but a patient’s worsening cardiovascular risk profile around the menopause transition emphasizes the need to optimize primary prevention efforts, including lifestyle and pharmacological management,” the researchers wrote.

“There are many HT formulations, including systemic hormones, transdermal estrogen and progesterone, vaginal estrogen,” Cho said. “The lowest risk is vaginal estrogen because it is not systemically absorbed. Transdermal HT seems to be associated with less of an increase in cholesterol and BP and less risk for development of clots.”

Guidance does not recommend the use of bioidentical hormones, which are not FDA-regulated, Cho said.

‘Be thoughtful’ about menopausal HT

For the WHI, researchers randomly assigned women aged 50 to 79 years without CVD continuous combined oral conjugated equine estrogen (CEE) with medroxyprogesterone acetate or placebo; women without a uterus were randomly assigned to CEE alone or placebo. The initial findings suggested that compared with placebo, risks for CHD, stroke and VTE, including pulmonary embolism, were increased with HT. Subsequent analyses of the WHI, which were age-stratified with longer cumulative follow-up (median duration, 13 years) supported a more nuanced approach to HT, Cho said.

“The WHI initially showed that HT increases risk. That trial included women of all ages, women older than 60 years, those more than 10 years after menopause,” Cho said. “That scared everyone. But what we have learned since then — almost 20 years later — is that starting HT for younger women, and being mindful of HT type and for the shortest duration possible for symptom relief is actually quite safe. The nuanced approach is an important message to convey.”

Cho said for women aged 50 years and older with one or more risk factor for CVD, shared decision-making is key.

“We want to be thoughtful about which hormones are prescribed, and risk for women who have a history of stroke or blood clots, who should never receive HT,” Cho said. “The biggest takeaway is it is important that cardiologists know that HT for low-risk women is very safe. For intermediate-risk women — women with one or more risk factors — think about transdermal formulations. Those at high risk are not candidates for HT. The other important thing is we have to respect patient wishes and what is important for them. Using a nuanced approach and adopting shared decision-making is really important,” Cho told Healio.

For more information:

Leslie Cho, MD, can be reached at chol@ccf.org.

Perspective

Howard Weintraub, MD)

Howard Weintraub, MD

This review is encouraging. There was a time in the 1990s when the beneficial role of estrogens in vascular health seemed clear and convincing. Then, data from HERS and the WHI suggested menopausal HT could be deleterious. Estrogens were vilified in any other form other than transvaginal or for women who began menopause early, age 45 years or younger. Patients experiencing bothersome symptoms would see a clinician only to be told, “Sorry, I don’t have anything to make you feel better.”

We now know that the role of estrogen is more nuanced. Data from WHI show that, if you wait until 10 years or more after menopause, HT can be deleterious, for reasons that are still not completely understood today. It is now clear that there is a benefit to sustaining the estrogen effect; however, there appears to be potential for deleterious activity in some people prescribed menopausal HT, so discrimination between low-, intermediate- and high-risk people is important. The 2018 ACC guidelines for the treatment of CVD notes that menopause is a CVD risk enhancer. Data now suggest estrogen deprivation may explain why.

I do not typically treat vasomotor symptoms, but such symptoms weigh in my decision making. Typically, HT decisions are made in conjunction with an OB/GYN. Menopausal symptoms can be perplexing and disruptive; quality of life suffers for the patient and their family. Professional societies including the North American Menopause Society, Endocrine Society and the American Association of Clinical Endocrinology have all endorsed HT for menopause symptoms when appropriate. What this review offers is a finessing of the way these medications should be delivered, noting clinicians should be selective in who is prescribed HT.

Howard Weintraub, MD

Clinical Director, Center for the Prevention of Cardiovascular Disease
Clinical Professor, Department of Medicine, Leon H. Charney Division of Cardiology
NYU Langone Health

Exercising in the morning could reduce CVD risk

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The timing of physical activity could affect the risk for CVD, according to study findings published in the European Journal of Preventive Cardiology.

Using data collected from February 2013 to December 2015 in the UK Biobank, the researchers identified several “chrono-activity” (daily physical activity timing) subgroups of 86,657 participants (mean age, 62 years; 58% women).

Female running
The timing of physical activity could affect the risk for CVD.
Source: Adobe Stock

“Physical activity remains one of the most distinct cornerstones in CVD prevention. The present study adds to the previous evidence that timing of physical activity is an additional independent contributing factor to CVD risk, and therefore adds a novel dimension to CVD risk prevention,”Gali Albalak, PT,PhD candidate at the Leiden University Medical Center in the Netherlands, and colleagues wrote.

Participants wore an accelerometer for 7 days to measure objective physical activity.

At 6 years, compared with participants who had a midday pattern of physical activity, those who had an early morning pattern of physical activity had lower risk for incident CAD (HR = 0.84; 95% CI, 0.77-0.92) and stroke (HR = 0.83; 95% CI, 0.7-0.98), according to the researchers.

The effect was more pronounced in women than in men (P for interaction = .001), Albalak and colleagues wrote.

The results did not vary by total physical activity level or by sleep chronotype, according to the researchers.

“These present results might suggest that time-dependent physical activity interventions might be an added beneficial behavioral factor to reach maximum health benefits and to lower the risk of CVD,” Albalak and colleagues wrote.

Influence of insulin resistance illustrates heightened CVD risk in ‘pre-prediabetes’

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 Insulin resistance is a more important cardiometabolic risk factor than glucose tolerance, increasing cardiovascular risk even before hyperglycemia increases risk for diabetes, according to a speaker at the third annual Heart in Diabetes conference.

Ralph A. DeFronzo

“I’m not really a believer that hyperglycemia is a major risk factor in developing cardiovascular disease, and the problem starts long before you develop diabetes,” Ralph A. DeFronzo, MD, director of the diabetes research unit at the University of Texas Health Science Center at San Antonio, said during the presentation. “You’re going to see a new word that’s going to be introduced and that’s ‘pre-prediabetes,’ because the disease actually starts long before you become prediabetic, and the implication for this, of course, is that glucose is really not the big bad actor in the development of cardiovascular disease.”

Glucose level effect on CV risk

DeFronzo and colleagues conducted a meta-analysis in which they examined findings from 19 studies to determine whether prevalence and risk for CV complications, such as acute myocardial infraction, as well as mortality differed significantly between different ranges of glucose tolerance. Each study excluded participants with diabetes or prediabetes or previous MI at baseline.

The researchers found that among 41,509 patients who developed acute MI during the studies, 51.5% had normal glucose tolerance whereas 28.8% had developed prediabetes and 19.7% had developed diabetes. DeFronzo noted that a coin flip essentially determined whether participants with diabetes or prediabetes or those with normal glucose tolerance would experience an MI.

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Insulin resistance is a more important cardiometabolic risk factor than glucose tolerance, increasing cardiovascular risk even before hyperglycemia increases risk for diabetes.

Adobe Stock

The meta-analysis further revealed that participants with prediabetes had a 43% higher major adverse cardiovascular event incidence ratio than those with normal glucose tolerance whereas those with diabetes had a 50% increase in the ratio. In addition, compared with those with normal glucose tolerance, those with prediabetes had a 44% higher incidence rate ratio for annual mortality, and the measure was 71% higher for those with diabetes.

However, the differences between the groups with prediabetes and diabetes for both MACE and mortality did not reach significance, suggesting that the progression from HbA1c levels associated with prediabetes to those with diabetes does not alter CV risk to a significant degree, according to DeFronzo.

Insulin resistance predicts CVD

DeFronzo said that the underlying elements of metabolic syndrome, or what he calls “insulin resistance syndrome,” is where the real problem resides. These include obesity, hypertension, dyslipidemia, inflammation and hyperinsulinemia, which DeFronzo said have all showed similar insulin resistance rates compared with diabetes in insulin clamp studies.

“That’s why if you have diabetes and you gain weight, that’s a major problem; because now you’re superimposing the insulin resistance of obesity on the insulin resistance of diabetes,” DeFronzo said during the presentation. “These are all very different diseases, but they all have the same biochemical defect. … The insulin resistance is there long before you develop diabetes.”

Even when looking at glucose measures, DeFronzo warned against lumping measures of impaired fasting glucose and impaired glucose tolerance together when assessing risk. Although there is an association between heightened CVD risk and IGT as measured by 2-hour oral glucose tolerance tests, the same does not hold for IFG.

“You cannot have the same pathophysiology with people with IGT,” DeFronzo said during the presentation. “When we talk about IGT, you really have to distinguish between IGT and IFG.”

DeFronzo and colleagues performed an additional meta-analysis of 17 studies that assessed how well CVD could be predicted by insulin resistance. One study revealed that those with higher measures of insulin resistance according to HOMA-IR were at greater risk for CVD over 8 years of follow-up, and another found that the relative risk for coronary heart disease reached 73% for those with normal glucose tolerance and metabolic syndrome vs. those without metabolic syndrome.

To combat insulin resistance and its apparent ability to raise CVD risk, DeFronzo outlined details from the Insulin Resistance after Stroke study in which researchers recruited 3,876 participants without diabetes but with insulin resistance who had experienced a stroke. Participants were randomly assigned to either pioglitazone or placebo during 5 years of follow-up. Pioglitazone reduced the incidence of recurrent stroke or MI by 24% (HR = 0.76; 95% CI, 0.62-0.93) and also had positive effects on obesity, hypertension and dyslipidemia, according to DeFronzo.

“I would argue that the best drug that we have for the treatment of cardiovascular disease is pioglitazone,” DeFronzo said. “The problem is there’s a perception with pioglitazone and that’s the problem. It’s not that the drug doesn’t work.”

DeFronzo further described the molecular mechanisms that lead to the blocking of nitric oxide and activation of atherogenesis as well as genetically inherited insulin resistance, which means that developing CVD can be just a matter of time for some patients.

“The whole story of hyperglycemia in diabetes has really very little to do with cardiovascular disease. The problem starts long before you are hyperglycemic,” DeFronzo said. “From the diabetic standpoint, we’ve got to control the glucose. We don’t want people going blind or on dialysis. However, that has very, very little to do with protection against cardiovascular disease. From the standpoint of cardiovascular disease, what we really need to do is to correct the underlying components of the insulin resistance syndrome.” – by Phil Neuffer

Reference:

DeFronzo RA, et al. Prediabetes: The Prelude to Macrovascular Complications. Presented at: Heart in Diabetes CME Conference; July 12-14, 2019; Philadelphia.

Hanley AJG, et al. Diabetes Care. 2002;doi:10.2337/diacare.25.7.1177.

Insomaa B, et al. Diabetes Care. 2001;doi: 10.2337/diacare.24.4.683.

Kernan WN, et al. N Engl J Med. 2016;doi: 10.1056/NEJMoa1506930.

CVD risk evaluation in prediabetes not improved by incorporating HbA1c

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Using HbA1c may not alter the effectiveness of screening for cardiovascular disease risk among adults with prediabetes, although CVD risk is greater among this group vs. those with lower HbA1c levels, according to findings published in Diabetes Care.

“People with prediabetes are on average much heavier, have higher blood pressure and more abnormal lipids than those without — these factors lead such people to be at greater risk for cardiovascular disease much more so than their slightly raised sugar levels. However, prediabetes is a strong risk factor for incident diabetes,” Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow in the U.K., told Healio. “This is why when we adjust analysis for usual risk CVD factors, risk for cardiovascular disease in those with prediabetes is only minimally increased. In other words, this confirms that the independent effect of a slightly raised glucose into the prediabetes range on CVD is very modest indeed.”

Sattar and colleagues evaluated HbA1c levels and CVD events from the QRISK3 risk score, American College of Cardiology/American Heart Association (ACC/AHA) guideline and European Systematic Coronary Risk Evaluation, such as coronary heart disease, stroke and transient ischemic attack, across 8.9 years of median follow-up in a cohort of 357,833 adults with data in the UK Biobank. The researchers found that an HbA1c of between 6% and 6.4% was identified for 11,665 participants, who were categorized as having prediabetes (mean age, 59.7 years; 54.7% women), and an HbA1c of 6.5% or more was identified for 2,573 participants, who were categorized as having undiagnosed diabetes (mean age, 57.9 years; 41.1% women). The remaining 343,595 participants had an HbA1c of less than 6% (mean age, 56 years; 55.9% women).

The researchers wrote that 3.6% of adults experienced CVD events from the QRISK3 risk score assessment, 1.9% experienced CVD events from the ACC/AHA guideline and 0.5% experienced CVD events from the European Systematic Coronary Risk Evaluation.

Blood tests general 2019

Using HbA1c may not alter the effectiveness of screening for cardiovascular disease risk among adults with prediabetes, although CVD risk is greater among this group vs. those with lower HbA1c levels.

Source: Adobe Stock

CVD risk was 1.83 times greater for adults with prediabetes vs. those without prediabetes (HR = 1.83; 95% CI, 1.69-1.97) 2.26 times greater for those with undiagnosed diabetes vs. without diabetes (HR = 2.26; 95% CI, 1.96-2.6). However, the researchers noted that these calculations were made before adjustments; when adjustments were added CVD risk was 1.11 times greater for individuals with prediabetes (HR = 1.11; 95% CI, 1.03-1.2) and 1.2 times greater for individuals with undiagnosed diabetes (HR = 1.2; 95% CI, 1.04-1.38).

“The added predictive gain from inclusion of HbA1c in risk prediction was modest,” the researchers wrote.

“If someone is picked up in practice with prediabetes, they should have their other CVD risk factors measured as, on average, they will be around 10 kg heavier than average, have 6 mm Hg higher systolic blood pressure and have more abnormal lipids. All these abnormalities should be used as further incentives to people to make lifestyle changes to lessen their risks not only of diabetes but also of associated cardiovascular disease,” Sattar said. “In some, preventive medications might be needed, but in most cases, these should be reserved [for] after people are given a real chance to make lifestyle changes. How we help people with lifestyle changes is improving, but we can do even better with good training.”

Poorer sleep health associated with elevated CVD risk

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Poor sleep health was associated with increased risk for experiencing CVD, according to data published in Scientific Reports.

Researchers reported that for each component (regularity, satisfaction, alertness, efficiency, duration and sleep actigraphy) of a composite sleep health measure, participants experienced an incrementally larger risk for CVD compared with those with healthy sleep.

Heart clock

“Insufficient or poor sleep is a significant risk factor for heart disease. Studies have mostly used single sleep measures (often focusing only on sleep duration, quality or insomnia). However, a composite of multidimensional sleep health may be more predictive of heart disease than single sleep measures,” Soomi Lee, PhD, assistant professor in the College of Behavioral and Community Sciences at the University of South Florida School of Aging Studies, and colleagues wrote. “Our approach lends itself to characterizing a ‘sleep health’ message that will be more effective in motivating the public to engage in multiple sleep health behaviors that may have synergistic effects on decreasing the risk of heart disease.”

For this study, researchers utilized the data of 6,820 individuals (mean age, 53 years) from the Midlife in the U.S. study (MIDUS) to evaluate whether composite measures of sleep health were associated with CVD. Researchers assessed two sleep health composites: the first, based on self-report only, assessed regularity, satisfaction, alertness, efficiency and duration of sleep; the second was based on each of the previous self-reported variables plus sleep actigraphy.

The outcome of CVD was also self-reported (MI, angina, valvular disease, atrial septal defect, ventricular septal defect, CAD, CHD, ischemia, arrhythmia, heart murmur, HF and/or other). Hypertension was excluded as a sleep health-related CVD.

Sleep health and CVD risk

After full adjustment, researchers reported a significant association between self-reported sleep health and risk for heart disease, with each unit increase in measures of poor sleep health associated with a 54% greater risk for CVD (adjusted RR = 1.54; P < .001). For each unit increase in measures of poor sleep health from the second composite including actigraphy, researchers observed a 141% greater risk for CVD (aRR = 2.41; P < .001).

Lee and colleagues proceeded to conduct a sensitivity check using unweighted sleep health composites and reported generally consistent yet weaker findings, with a 14% greater risk for CVD with each additional dimension of poor sleep (aRR = 1.14; P < .001). The association between poor sleep health and CVD failed to meet statistical significance in the sensitivity check using the unweighted self-reported second composite plus actigraphy (aRR = 1.22; P = .073).

Subgroup analyses by sex and race

Lee and colleagues noted that women reported more sleep health problems based on the first composite but not the second composite that included actigraphy. Although men were more likely to report CVD compared with women, sex did not moderate the association between sleep health and risk for CVD.

Although Black individuals experienced the highest number of unhealthy sleep variables and the highest prevalence of CVD, researchers reported that sleep health and CVD risk were more strongly related in white participants compared with all other races in the self-reported second composite plus actigraphy (P = .001).

Moreover, the slope for the association between more sleep health problems and increased risk for CVD was similar between both Black and white participants (P = .151), but other races and ethnicities did not follow the same pattern.

“The current study shows the importance of considering ‘co-existing sleep health problems’ within an individual to assess the risk of heart disease,” the researchers wrote. “Findings revealed having more sleep health problems may increase the risk of heart disease in middle adulthood. Results were consistent between two independent samples using different sleep health composites (using self-report only and both actigraphy and self-report). Despite known differences in the prevalence of sleep and heart disease by sex and race, the association between sleep health and the risk of heart disease did not generally differ by sex and race in our study. The findings highlight the importance and utility of assessing multidimensional sleep health in predicting the risk of heart disease and potentially other health outcomes.”

Eating one egg per day does not increase CVD risk

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Moderate egg consumption, defined as up to one egg per day, was not linked to CVD risk, according to a study published in The BMJ.

The study also found that moderate egg consumption may be associated with lower CVD risk in Asian patients.

“Our main finding that no evidence supports a higher risk of CVD associated with moderate egg consumption (up to 1 egg per day) can be easily translated into practice,” Jean-Philippe Drouin-Chartier, RD, PhD, assistant professor in the faculty of pharmacy and researcher at NUTRISS Center of INAF at Université Laval in Quebec City and visiting scientist in the department of nutrition at Harvard T.H. Chan School of Public Health, told Healio. “Still, while moderate egg consumption can be part of a healthy eating pattern, they are not essential. There is a range of other foods that can be included in a healthy breakfast, such as whole grain toasts, plain yogurt and fruits.”

Prospective cohort study

Researchers analyzed data from 83,349 women from the Nurses’ Health Study, 90,214 women from the Nurses’ Health Study II and 42,055 men from the Health Professionals’ Follow-Up Study who were free from CVD, cancer and diabetes at baseline.

Patients from all three cohorts completed questionnaires to collect information on disease risk factors, disease diagnosis, lifestyle characteristics, drug use and food frequency, which asked patients how often they consumed whole eggs in the past year.

The primary endpoint was incident CVD, defined as fatal CHD, nonfatal MI, and fatal and nonfatal stroke.

During 5,540,314 person-years of follow-up, 14,806 patients developed incident CVD. Patients with a higher egg intake were less likely to be treated with statins, had a higher BMI and had higher intakes of unprocessed red meat, calories, bacon and other unprocessed meats, whole milk, potatoes, refined grains, coffee and sugar-sweetened beverages. In 1998-1999, 1.24% of patients ate at least one egg per day, and of these patients, 0.2% consumed at least two eggs per day.

After adjusting for lifestyle and dietary characteristics linked to egg intake, consuming at least one egg per day was not associated with incident CVD risk compared with consuming less than one egg per month in a pooled multivariable analysis (HR = 0.93; 95% CI, 0.82-1.05).

An increase in egg consumption of one per day was also not linked to CVD risk in an updated meta-analysis of prospective cohort studies (RR = 0.98; 95% CI, 0.93-1.03; I2 = 62.3%). Results were similar for stroke (RR = 0.99; 95% CI, 0.91-1.07; I2 = 71.5%) and CHD (RR = 0.96; 95% CI, 0.91-1.03; I2 = 38.2%).

When stratified by geographical location, there was no association between egg consumption and CVD risk in European cohorts (RR = 1.05; 95% CI, 0.92-1.19; I2 = 64.7%) and U.S. cohorts (RR = 1.01; 95% CI, 0.96-1.06; I2 = 30.8%), although there was an inverse association for Asian cohorts (RR = 0.92; 95% CI, 0.85-0.99; I2 = 44.8%).

“Recent studies reignited the debate on this controversial topic, but our study provides compelling evidence supporting the lack of an appreciable association between moderate egg consumption and cardiovascular disease,” Drouin-Chartier said in an interview.

‘Convincingly null’

In a related editorial, Andrew O. Odegaard, PhD, assistant professor of epidemiology at University of California, Irvine School of Medicine, wrote: “The results of this study are convincingly null save for a couple of subgroup findings. Yet, we should not put all our eggs in this observational basket for formal guidance on eating eggs. Given the unique challenges in nutrition research, it is necessary to triangulate evidence from different study designs and populations to provide the most robust basis to answer questions about diet and disease.” – by Darlene Dobkowski

Social isolation, loneliness drive CVD risk among older women

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Social isolation and loneliness are independently associated with an 11% to 16% higher risk for CVD among older women, according to research published in JAMA Network Open.

Natalie M. Golaszewski

“Social isolation and loneliness, while related to one another, are distinct social factors and our study showed that both factors are associated with increased risk for cardiovascular disease among older women,” Natalie M. Golaszewski, PhD, a postdoctoral fellow with the Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, told Healio. “The overall CVD risk was highest for women who had high social isolation and high loneliness.”

sad woman at window

In a prospective study, Golaszewski and colleagues analyzed data from 57,825 older women participating in the Women’s Health Initiative II study with no history of CVD at baseline (mean age, 79 years; 89.1% white). Participants completed questionnaires assessing social isolation and loneliness. The main outcome was major CVD, defined as CHD, stroke and CV death.

During 186,762 person-years, researchers observed 1,599 major CVD events.

Compared with women reporting low social isolation scores, women with high social isolation scores were 18% more likely to experience a major CVD event (HR = 1.18; 95% CI, 1.13-1.23). Similarly, women with a high loneliness score were 14% more likely to experience a major CVD event vs. those with low loneliness scores (HR = 1.14; 95% CI, 1.1-1.18). The risk was slightly attenuated but persisted after adjusting for health behaviors and health status, with an HR of 1.08 for women with a high vs. low social isolation score (95% CI, 1.03-1.12) and an HR of 1.05 for women with a high vs. low loneliness score (95% CI, 1.01-1.09).

Women with both high social isolation and high loneliness scores had a 13% to 27% higher risk for incident CVD compared with women with low social isolation and low loneliness scores. Social support was not a significant effect modifier of the associations.

“Both social isolation and loneliness are social factors that are important in the lives of patients and should be incorporated in clinical conversations and systematically measured in doctors’ offices,” Golaszewski told Healio. “It is important to further understand the acute and long-term effects of social isolation and loneliness on cardiovascular health and overall well-being.”

John Bellettiere

Causal information is also needed to confirm conclusions from the study that reducing social isolation and loneliness can reduce CVD, according to John Bellettiere, PhD, assistant professor of epidemiology at the Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego.

“This could take the form of randomized clinical trials or causal evaluations of existing programs designed to reduce social isolation and loneliness such as programs in the U.K.,” Bellettiere told Healio.

Longer Breastfeeding Key to Moms’ Slim Waists, Lower CVD Risk

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Breastfeeding for 6 months or more was associated with a slimmer waist in mothers years later, compared with shorter or no breastfeeding, new data show.

“Waist circumference…as a measure of central adiposity has been shown to be a superior proxy for assessing long-term risk of coronary artery disease mortality, hypertension, diabetes, dyslipidemia, and the metabolic syndrome, independent of BMI,” Gabrielle G. Snyder, MPH, University of Pittsburgh, Pennsylvania, and colleagues note.

Thus, “breastfeeding duration may be important to consider when studying long-term maternal cardiovascular and metabolic health,” they conclude in their article published online December 11 in the Journal of Women’s Health.

“We consistently detected that a threshold effect may exist,” they report, “for breastfeeding greater than 6 months.” The benefit remained after accounting for demographic, lifestyle, and socioeconomic factors.

Snyder and colleagues analyzed data from 676 women in the Pregnancy Outcomes and Community Health (POUCH) cohort who participated in the POUCHmoms study, 7 to 15 years after delivery. They matched moms with a similar likelihood to breastfeed, and then compared the moms who breastfed for > 6 months versus not at all or less than 6 months.

“This study extends conventional observational study methods,” they write, “to incorporate propensity score approaches that make it possible to…account for systematic differences in women who did and did not breastfeed.”

Central Adiposity

“Metabolically active visceral adipose tissue, a measure of abdominal obesity primarily distributed about the intra-abdominal organs, may increase substantially with a single pregnancy, independent of total body fat,” Snyder and colleagues write.

The World Health Organization recommends exclusive breastfeeding for 6 months for optimal infant health. In addition, breastfeeding consumes nearly 500 calories a day for moms.

Prior studies have reported that women who breastfed their babies had less central obesity years later than women who did not do this, but the studies did not account for different baseline characteristics of the women.

Therefore, Snyder and colleagues compared central obesity after about a decade in women in the POUCHmoms study who were seen in clinics in Michigan communities. Of the women in the cohort, 63% of the mothers were white, 31% were black, and 6% were Asian or Native American.

Prior to pregnancy, about half of the women (49%) had a body mass index (BMI) below 25 kg/m2 (normal weight) and the rest were overweight (21%) or obese (30%).

Overall, 38% of the mothers did not breastfeed their babies, while the others did so for > 0 to 3 months (22%), > 3 to 6 months (13%), or > 6 months (27%).  In unadjusted analyses, women who breastfed for > 6 months were older and more likely to be white and have a higher education level, and less likely to be obese before pregnancy.

At a mean follow-up of 11 years, the mothers had a mean waist circumference of 94 cm if they had breastfed their child for up to 6 months, and 86 cm if they had breastfed longer.

Two types of propensity analyses showed that the mothers who reported breastfeeding their infants for more than 6 months had a mean waist circumferencethat was 3.6 cm smaller and 3.1 cm smaller than other mothers.

“We emphasize [waist circumference] as the outcome of interest,” the researchers write, “given that central adiposity is a better predictor of long-term cardiometabolic and cardiovascular disease risk than BMI alone.”

They acknowledge that study limitations include potential pre-pregnancy differences in diet and exercise, for example, that were not accounted for.

Snyder and colleagues call for more research to investigate the effect of breastfeeding in multiple pregnancies on lifetime risk of cardiovascular disease.

“Our results warrant further analyses of cumulative lifetime duration of breastfeeding,” they write, “to understand the magnitude of the relationship with maternal central adiposity over time.”

Mediterranean Diet Linked to Drop in CVD Risk

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Adherence to the Mediterranean diet (MED) is associated with a 25% reduction in the risk for cardiovascular disease (CVD), compared with those who do not follow this diet, new research suggests.

Investigators used data from the Women’s Health Study, which followed close to 26,000 women between their late forties and early sixties over a 12-year period, assessing 40 biomarkers known to be associated with CVD risk.

Higher baseline MED intake was associated with a 28% relative risk reduction in CVD events, attributed mostly to a reduction in biomarkers of inflammation, glucose metabolism and insulin resistance, and adiposity, the researchers say.

“The cardiovascular benefit seen with a Mediterranean dietary pattern in this large US population of women was similar in magnitude to benefit from statins or other commonly used preventive medications,” senior author Samia Mora, MD, MHS, Center for Lipid Metabolomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, told theheart.org | Medscape Cardiology.

“Even modest changes in CVD risk factors with a heart-healthy diet contribute to the benefit of the Mediterranean diet on CVD risk and may have important downstream consequences for primary prevention,” she said.

The study was published online December 7 in JAMA Network Open .

Precise Mechanisms Unknown

“The Mediterranean diet has been associated with lower risk of CVD events, but the precise mechanisms through which Mediterranean diet intake may reduce long-term risk of CVD are not well understood,” Mora said.

“We aimed to investigate the biological mechanisms that may mediate this cardiovascular benefit,” she noted.

Previous observational studies have reported that a 20-percentile higher MED intake was associated with a 9% lower CVD event risk reduction, but the follow-up period was short (only 4 years), leaving uncertainty about whether MED intake protects against CVD events in American populations over the long term.

To elucidate the question, the researchers analyzed blood samples of 25,994 participants in the Women’s Health Study (mean [SD] age, 54.7 [7.1] years).

At baseline, participants completed a 131-item questionnaire on their dietary patterns and provided demographic information about history of hypertension, use of postmenopausal hormone therapy, smoking, physical activity, alcohol consumption, and family history of myocardial infarction (MI).

Body mass index (BMI) and blood pressure were also reported at baseline.

A MED score was calculated on the basis of nine components of MED intake, including vegetables, fruits, nuts, whole grains, legumes, fish, and the ratio of monounsaturated fatty acids to saturated fatty acids.

The primary end point was incident CVD, defined as a first event of MI, stroke, coronary arterial revascularization, or cardiovascular death. Coronary and stroke events were also examined separately.

Because baseline measures of MED intake “attenuate with time,” the primary analyses were conducted with a maximum follow-up of 12 years from baseline, whereas secondary analyses were performed in the sample with a median (IQR) follow-up of 21.4 (19.2 – 22.1) years.

The researchers measured total cholesterol, high-density cholesterol (HDL), low-density cholesterol (LDL), high-sensitivity C-reactive protein (hsCRP), triglycerides, apolipoprotein (apo)B100, and apoA1, soluble intracellular adhesion molecule 1 (ICAM-1), fibrinogen, creatinine, and homocysteine.

Nuclear magnetic resonance (MR) spectroscopy was used to measure lipoprotein subfraction particles for LDL, HDL, and very low-density lipoproteins (VLDL), branched-chain amino acids, glycoprotein acetylation (a measure of inflammation).

Lipoprotein insulin resistance index and insulin resistance diabetes risk factor index are insulin resistance scores, including subfractions of triglyceride-rich lipoproteins also derived from nuclear MR spectroscopy.

Quarter Reduction

Of the 25,994 female participants, 39.0%, 36.2%, and 24.8% had low (≤3), middle (4 or 5), and high (6 – 9) MED scores, respectively, and of the total sample, 3.96% experienced a first CVD event.

Participants with higher MED intake had a higher intake of vegetables, fruits, nuts, whole grains, legumes, and fish, and a greater ratio of monounsaturated to saturated fat. They also had a lower intake of processed and red meat.

Participants with low MED intake experienced the most incident CVD events (4.2%), followed by those with middle and high MED intake scores (both 3.8%).

The middle and upper groups experienced the greatest CVD risk reductions, with respective hazard ratios (HRs0 of 0.77 (95% CI, 0.67 – 0.90) and 0.72 (95% CI, 0.61 – 0.86, P for trend <.001), compared with the lowest group.

A total of 1030 individuals experienced a first CVD event during a maximum follow-up of 12 years (mean [SD], 11.6 [1.5] years), including 681 coronary events and 339 strokes.

The middle and upper groups both showed CVD risk reduction (HR, 0.77; 95% CI, 0.67 – 0.90 and 0.72, 0.61 – 0.86, respectively, P for trend < .001), compared with the reference group of participants with low MED intake.

The researchers also observed CVD relative risk reductions of 23% and 28% for middle and higher groups, respectively, compared with the lower MED intake group, after adjusting for age, randomized treatment, and energy intake.

“American women consuming a Mediterranean-type diet had a quarter reduction in CVD events over long-term (12 year) follow-up,” Mora summarized.

Inflammatory Mediators Most Important

Beyond actual CVD events, MED intake was generally associated with more favorable profiles of CVD risk factors and biomarkers.

However, there were several exceptions. For example, total cholesterol was actually significantly more elevated in the higher than in the lower MED intake group (median, 209.0 [184.0 – 236.0] and 207.0 [183.0 – 234.0], respectively; P = .03).

In contrast, systolic blood pressure, LDL-C, apoB100, LDL particle concentration, creatinine, and HbA1c were similar across the groups (P > .05).

However, when separate Cox models were additionally adjusted with each of the individual biomarkers one at a time, there was some attenuation of HRs (comparing higher vs lower MED intake) before and after adjustment for most variables, except for LDL-C, total cholesterol, Lp(a), citrate, and creatinine.

Biomarkers of inflammation turned out to be the largest mediators of the CVD risk, accounting for 29.2%of the MED-CVD association, followed closely by glucose metabolism and insulin resistance (27.9%), and body mass index (27.3%).

Blood pressure, traditional lipids, HDL measures or VLDL measures (26.6%, 26.0%, 24,0%, and 20.8%, respectively) were next, with lesser contributions from low-density lipoproteins (13.0%), branched-chain amino acids (13.6%), apolipoproteins (6.5%), or other small-molecule metabolites (5.8%).

The fully adjusted CVD HRs for the middle- and upper-intake groups, compared with the low-intake group, were 0.88 (0.76 – 1.02) and 0.89 (0.74 – 1.06), respectively (P for trend = .15).

The total mediation effect was 27.3%, with a “generally similar pattern of risk reduction” was observed for CHD and stroke risk.

When the researchers repeated these analyses using the total follow-up of 21.4 median years, they observed “materially similar results.”

“For the MED-CVD risk reduction, biomarkers of inflammation, glucose-metabolism/insulin resistance, and adiposity contributed most to explaining the association, with additional contributions from pathways related to blood pressure and lipids — in particular, HDL or triglyceride-rich lipoprotein metabolism and, to a lesser extent, LDL cholesterol, branched chain amino acids, and small molecule metabolites,” Mora said.

“Palatable and Achievable”

Commenting on the study for theheart.org | Medscape Cardiology, Erin D. Michos, MD, MHS, associate professor of medicine and epidemiology and associate director of preventive cardiology, Ciccarone Center for the Prevention of Heart Disease, Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, who was not involved with the study, said that, although it is observational, “it helps to fill in a few gaps.”

She noted that the study focused on “a broad pattern of eating more adherent to Mediterranean style and did not focus on any single component of the score,” suggesting that overall dietary patterns, “rather than any single component, matter.”

She said her patients frequently ask about “reducing inflammation,” and that “a Mediterranean-style diet pattern may be one means to do so.”

Diet is frequently tied to “sociocultural norms,” and behaviors can be “difficult to change,” so the Mediterranean diet might be a good choice to recommend because “it is very palatable and achievable, not too restrictive or extreme,” she suggested.

“Dietary recommendations likely need to be tailored to the individuals, based on personal preferences and cardiometabolic considerations,” and “there is no one diet that fits all,” Michos advised.

Also commenting on the study for theheart.org | Medscape Cardiology, Thomas Keyserling, MD, MPH, professor of medicine, Division of General Medicine and Clinical Epidemiology, University of North Carolina at Chapel Hill School of Medicine, who was not involved with the study, called it “consistent with prior studies; that is, a Mediterranean dietary pattern is associated with a substantial reduction in risk for CVD events.”

The study “adds to the literature on the mechanisms of risk reduction, including the Mediterranean diet’s impact on inflammation and glucose metabolism,” he said, adding that more research into this association is needed.

Mora suggested that there “may be additional pathways, such as improvements in vascular function or antiarrhythmic effects, which could be improved with the Mediterranean diet, that we did not measure in our study.