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


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


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.

 

Early Menarche, Menopause Tied to Higher CVD Risk


Several reproductive factors contributed to a higher risk of cardiovascular disease among women, including early periods and early menopause, researchers found.

A history of hysterectomy was also linked with increased risk of cardiovascular disease (CVD) and coronary heart disease, reported Sanne AE Peters, PhD, and Mark Woodward, PhD, both of the University of Oxford in England.

However, history of oophorectomy, as well as age at first birth, had either no associations or only minor inverse associations with increased risk for cardiovascular disease, the authors wrote in Heart.

They pointed to “increasing evidence” that in addition to traditional risk factors such as elevated blood pressure, smoking, and obesity, certain reproductive factorsmay be linked with later cardiovascular disease, though the evidence is “mixed and inconsistent.”

This cross-sectional analysis of UK Biobank data comprised 267,440 women and 215,088 men ages 40 to 69 without a history of cardiovascular disease. The authors found that during 7 years of follow-up, there were 9,054 cases of cardiovascular disease, 5,782 cases of coronary heart disease, and 3,489 cases of stroke. Women comprised about a third of cardiovascular disease cases, a little under 30% of coronary heart disease cases, and about 40% of stroke cases.

Examining demographic data for women, the mean age was 56, about half were from a higher socioeconomic bracket in the U.K., and 60% said they never smoked.

Results were mixed for certain reproductive factors and increased risk for cardiovascular disease. The mean age for menarche was 13 years, and women who had their first periods prior to age 12 had a higher risk of cardiovascular disease (adjusted HR 1.10, 95% CI 1.01-1.30) than women who had menarche at a later age. Similar increased risks were seen for coronary heart disease (adjusted HR 1.05, 95% CI 0.93-1.18) and stroke (adjusted HR 1.17, 95% CI 1.03-1.32).

 Sixty-one percent of women in the study were postmenopausal, with a mean age at natural menopause of 50 years. But early menopause was also linked with increased risk of cardiovascular disease (adjusted HR 1.33, 95% CI 1.19-1.49), coronary heart disease (adjusted HR 1.29, 95% CI 1.10-1.51), and stroke (adjusted HR 1.42, 95% CI 1.21-1.66).

Likewise, history of hysterectomy was linked with an increased risk of cardiovascular disease (adjusted HR 1.12, 95% CI 1.03-1.22) and coronary heart disease (adjusted HR 1.20, 95% CI 1.07-1.34).

Eighty-five percent of women had been pregnant, and 44% of women had two children, while 42% of men had fathered two children. Compared with women and men without children, there was a significantly higher risk of coronary heart disease in women (adjusted HR 1.21, 95% CI 1.05-1.40). But because these risks were similar among men (adjusted HR 1.13, 95% CI 1.04-1.23), the authors concluded that “this is unlikely to be due to a biological cause.”

The authors suggested that, “More frequent cardiovascular screening would seem to be sensible among women who are early in their reproductive cycle, or who have a history of adverse reproductive events or a hysterectomy, as this might help to delay or prevent their onset of CVD.”

Early Menarche, Menopause Tied to Higher CVD Risk


More frequent heart screening for women may be useful

Several reproductive factors contributed to a higher risk of cardiovascular disease among women, including early periods and early menopause, researchers found.

A history of hysterectomy was also linked with increased risk of cardiovascular disease (CVD) and coronary heart disease, reported Sanne AE Peters, PhD, and Mark Woodward, PhD, both of the University of Oxford in England.

However, history of oophorectomy, as well as age at first birth, had either no associations or only minor inverse associations with increased risk for cardiovascular disease, the authors wrote in Heart.

They pointed to “increasing evidence” that in addition to traditional risk factors such as elevated blood pressure, smoking, and obesity, certain reproductive factorsmay be linked with later cardiovascular disease, though the evidence is “mixed and inconsistent.”

This cross-sectional analysis of UK Biobank data comprised 267,440 women and 215,088 men ages 40 to 69 without a history of cardiovascular disease. The authors found that during 7 years of follow-up, there were 9,054 cases of cardiovascular disease, 5,782 cases of coronary heart disease, and 3,489 cases of stroke. Women comprised about a third of cardiovascular disease cases, a little under 30% of coronary heart disease cases, and about 40% of stroke cases.

Examining demographic data for women, the mean age was 56, about half were from a higher socioeconomic bracket in the U.K., and 60% said they never smoked.

Results were mixed for certain reproductive factors and increased risk for cardiovascular disease. The mean age for menarche was 13 years, and women who had their first periods prior to age 12 had a higher risk of cardiovascular disease (adjusted HR 1.10, 95% CI 1.01-1.30) than women who had menarche at a later age. Similar increased risks were seen for coronary heart disease (adjusted HR 1.05, 95% CI 0.93-1.18) and stroke (adjusted HR 1.17, 95% CI 1.03-1.32).

Sixty-one percent of women in the study were postmenopausal, with a mean age at natural menopause of 50 years. But early menopause was also linked with increased risk of cardiovascular disease (adjusted HR 1.33, 95% CI 1.19-1.49), coronary heart disease (adjusted HR 1.29, 95% CI 1.10-1.51), and stroke (adjusted HR 1.42, 95% CI 1.21-1.66).

Likewise, history of hysterectomy was linked with an increased risk of cardiovascular disease (adjusted HR 1.12, 95% CI 1.03-1.22) and coronary heart disease (adjusted HR 1.20, 95% CI 1.07-1.34).

Eighty-five percent of women had been pregnant, and 44% of women had two children, while 42% of men had fathered two children. Compared with women and men without children, there was a significantly higher risk of coronary heart disease in women (adjusted HR 1.21, 95% CI 1.05-1.40). But because these risks were similar among men (adjusted HR 1.13, 95% CI 1.04-1.23), the authors concluded that “this is unlikely to be due to a biological cause.”

The authors suggested that, “More frequent cardiovascular screening would seem to be sensible among women who are early in their reproductive cycle, or who have a history of adverse reproductive events or a hysterectomy, as this might help to delay or prevent their onset of CVD.”

Sudden Deafness May Flag CVD Risk


Interrupted vascular supply to the cochlea suggested as contributor

Sudden sensorineural hearing loss may be a risk factor for future cerebrovascular events, Korean researchers suggested.

Patients who experienced this dysfunction of the inner ear were more likely to develop cardiocerebrovascular disease over an 11-year follow-up period (13.5 versus 7.5 cases per 1,000 person-years, adjusted HR 2.18, 95% CI 1.20 to 3.96), particularly strokes (12.0 versus 6.2 cases per 1,000 person-years, adjusted HR 2.02, 95% CI 1.16 to 3.51).

However, this group was not at greater risk for acute MI, Dong-Kyu Kim, MD, PhD, of Korea’s Chuncheon Sacred Heart Hospital, and colleagues reported in a study in JAMA Otolaryngology–Head & Neck Surgery.

“This finding suggests that sudden sensorineural hearing loss may be a risk factor for the development of cardiocerebrovascular disease; therefore, clinicians should consider patients with sudden sensorineural hearing loss to be at an increased risk of developing cardiocerebrovascular disease, and take specific precautions to reduce their risk of stroke,” they concluded.

“Although the exact mechanism of sudden sensorineural hearing loss development remains unclear, interruption of the vascular supply to the cochlea is thought to be a contributing factor,” they said. In addition, this kind of hearing loss shares several risk factors with cardiocerebrovascular disease, including smoking, alcohol consumption, and thromboembolic events.

For this retrospective study, Kim’s group utilized National Sample Cohort from the Korea National Health Insurance Service with data spanning 2002 through 2013. Hearing loss patients (n=154) were matched 1:4 to controls by propensity score.

The study population was half women, and half were between the ages of 45 and 64 years.

Although nationally representative, the database provided no information on other baseline health data, such as BMI, smoking, or alcohol consumption by the patients, leaving room for possible confounding. Nor was mortality data available.

Testosterone therapy does not increase CVD risk, suggests expert


Testosterone replacement therapy (TRT) in hypogonadal men was associated with a lower cardiovascular (CV) risk, according to a presentation at the recent Urological Association of Asia Annual Congress (UAA 2016) held in Singapore, allaying concerns about the safety of TRT amidst controversial findings from previous studies.

TRT has been associated with an increased risk of cardiovascular disease (CVD) in several clinical trials, but Dr. Gerald Brock, a professor from the Division of Urology, St. Joseph’s Health Centre in London, Ontario, Canada, noted that these studies were either conducted without randomization or placebo, or that CVD was not an endpoint in the design of the studies. [JAMA 2013;310:1829-1836;PLoS One 2014;9:e85805]

On the other hand, many other studies have showed that TRT was associated with either no increased risk or a reduced incidence of CV events. [Am J Cardiol 2016;117:794-799; Int J Clin Pract2016;70:244-253; Eur Heart J 2015;36:2706-2715]

“Evidence from epidemiological and observational studies shows that low testosterone is associated with a higher CV risk in men,” said Brock.

Low testosterone levels were associated with increased CV mortality, he added, as revealed by the EPIC-Norfolk* prospective population study which followed 2,314 men from 1993-2003 in Norfolk, UK. [Circulation 2007;116:2694-2701]

“Androgen deprivation therapy [ADT] in patients with prostate cancer has negative effects on all major CV risk factors.”

Previous studies have shown that men with obesity (body mass index [BMI] ≥30 kg/m2), a known risk factor for CVD, had lower testosterone levels than those with a lower BMI across all age groups, and that 52.4 percent of 2,162 obese men had low testosterone levels. [J Clin Endocrin Metab2008;93:2737-2745; Int J Clin Pract 2006;60:762-769]

On the contrary, testosterone therapy with testosterone undecanoate (TU) improved body composition in terms of reduced fat mass and increased fat-free mass in hypogonadal men (p<0.001 for both), as well as reduced waist circumference by 13 cm after 36 months of TU treatment (p<0.0001) compared with placebo. [Int J Impot Res 2008;20:378-387; Aging Male 2012;15:96-102]

According to Brock, men who underwent long-term ADT had a higher prevalence of metabolic syndrome including diabetes, and a higher CV mortality. [J Androl 2008;29:534-539; J Urol2009;181:1998-2006]

Conversely, TU significantly reduced fasting glucose levels (p=0.001 in insulin-resistant group) and decreased HbA1c levels compared with baseline levels in hypogonadal men (p<0.0001). [J Sex Med2010;7:2253-2260; Endocr Rev 2012;33:MON-49]

TU also significantly improved lipid profile of 334 hypogonadal men in terms of decreased low-density lipoprotein (LDL) and triglycerides, and increased high-density lipoprotein (HDL) over a period of 15 years. [Endocr Rev 2012;33:SAT-117]

Supplementation of transdermal testosterone to a diet and exercise regime improved blood glucose control and HDL levels (p<0.001 for both) compared with a diet and exercise only intervention for 52 weeks in 32 hypogonadal men with type 2 diabetes.  [J Androl 2009;30:726-733]

TU administration significantly decreased inflammatory markers associated with CVD risk, such as C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-α; p<0.001 and p=0.03, respectively) compared with placebo in a double-blind randomized controlled trial involving 184 hypogonadal men with metabolic syndrome. [Clin Endocrinol (Oxf) 2010;73:602-612]

Lipids and inflammation constitute some of the risk factors for atherosclerosis, and hence development of CVD, said Brock.

Other CV risk factors such as blood pressure and carotid intima media thickness (CIMT) were also decreased in hypogonadal men receiving TU compared with baseline levels. [Endocr Rev2012;33:SAT-117; J Sex Med 2010;7:2253-2260]

“Normalization of testosterone improves all major CV risk factors, including body fat, insulin resistance, dyslipidemia, coagulation, inflammation, and blood pressure,” Brock concluded.