Menopause a 'Critical Window' for Lifestyle CVD Prevention

A healthy lifestyle during the menopausal transition is associated with reduced development of atherosclerosis, new research suggests.

Investigators analyzed self-reported data on smoking, diet, and physical activity in more than 1100 women participating in the Study of Women's Health Across the Nation (SWAN), constructing a 10-year average Healthy Lifestyle Score (HLS) during midlife.

They found that 14 years after baseline, markers of subclinical atherosclerosis, including common carotid artery intima-media thickness (CCA-IMT), adventitial diameter (CCA-AD), and carotid plaque were smaller in people with a higher HLS scores.

Of the three components of the HLS, smoking was the one most associated with increased risk for subclinical atherosclerosis.

"We found that women who have a healthy lifestyle (defined by abstinence from smoking, eating a healthy diet, and engaging in regular physical activity) during the midlife (the period that includes the menopausal transition) have lower levels of subclinical atherosclerosis later in their life," coauthors Ana Baylin, MD, DrPH, associate professor of nutritional sciences, epidemiology, and global health, University of Michigan, School of Public Health, Ann Arbor, and Dongqing Wang, PhD candidate, University of Michigan (lead author), told theheart.org | Medscape Cardiology in an e-mail.

"Smoking appears to be more strongly associated with subclinical atherosclerosis than unhealthy diet and lack of physical activity, although the latter two behaviors are also associated with more subclinical atherosclerosis," they said.

The study was published in the December 4 issue the Journal of the American Heart Association.

Modifiable Health Behaviors

"Subclinical atherosclerosis is closely related to cardiovascular disease (CVD) incidence and mortality, and it has been shown previously that the menopausal transition is associated with accelerated progression of subclinical atherosclerosis," Byline and Wang said.

"Few previous studies have examined the prospective association between the long-term lifestyle in midlife women and subclinical atherosclerosis," they noted.

The effect of "modifiable health behaviors," including abstinence from smoking, healthy diet, and physical activity, on subclinical atherosclerosis in women "therefore warrants further investigation."

To look at this question, the researchers used data from SWAN, which they describe as "an ongoing multicenter, multiethnic, prospective cohort study initiated in 1996 to study the natural history of the menopausal transition."

Participants (aged 42 - 52 years) began receiving clinical assessments in 1993 and have been followed with approximately 15 annual visits, the most recent of which took place in 2015/16.

The researchers used the HLS, an instrument previously used in SWAN, to assess the health of participants' lifestyles, using smoking, physical activity, and diet quality quantified by a healthy diet score.

However, they modified the HLS by using the Alternate Healthy Eating Index (AHEI) to quantify diet quality.

The final analytic sample consisted of 1143 women, 98% of whom received a carotid ultrasound scan at visit 12.

Dietary data were collected at baseline, visit 5, and visit 9 using a modified version of the Block Food Frequency Questionnaire (FFQ), which has previously been validated against dietary records and 24-hour recalls.

To determine whether guideline-recommended physical activity (≥150 minutes/week of moderate-intensity physical activity) was being practiced, the researchers used the sports and exercise questions on the Kaiser Physical Activity Survey.

To collect information on smoking status, they used standardized questions from the American Thoracic Association and data collected at baseline, visit 5, and visit 9.

The HLS consisted of the arithmetic sum of the scores for the individual components (i.e., smoking, physical activity, and diet) to create visit-specific HLS for baseline, visit 5, and visit 9.

These visit-specific scores were then averaged across all nonmissing visits to create the average HLS.

The study outcomes of atherosclerosis were the CCA-IMT, CCA-AD, and the extent of carotid plaque, categorized by carotid plaque index.

Baseline covariates included age, race/ethnicity, education level, financial strain, marital status, self-rated depressive symptoms, and menopausal status.

Data on body mass index (BMI), LDL and HDL cholesterol, blood pressure, and fasting glucose were also collected.

Low Rates of Physical Activity

Participants with a high HLS were more likely to have a college degree, self-report "excellent" or "very good" overall health, have a lower BMI at baseline, be premenopausal at baseline, and use hormone therapy during the follow-up period.

Participants with a high average HLS were less likely to be Hispanic or black. They were also less likely to experience difficulty paying for basics, be separated/widowed/divorced, experience depressive symptoms, and have high blood pressure, impaired fasting glucose, or dyslipidemia.

Between baseline and visit 9, the HLS scores remained "relatively" stable over time and the AHEI scores remained "moderately" stable.

However, more than half (64%) the participants reported a change in their activity status (in terms of fully, partially, or not meeting recommended amounts of physical activity).

At all three visits, 62.2% of participants remained never-smokers, but only 17.8% remained consistently in the top tertile of AHEI scores, and only 7.2% self-reported physical activity status that consistently met the recommendation.

Only 1.7% remained in the top category components at all three visits.

Over 10 years of follow-up, the average HLS was found to be inversely and statistically significantly associated with CCA-IMT and CCA-AD — an association that persisted, even after "extensive" adjustment for confounders (P = .0031) and physiological risk factors (P < .001 for both CCA-IMT and CCA-AD).

In the fully adjusted models, compared with participants in the lowest level of average HLS, those in the highest level had a 0.024 mm smaller CCA-IMT — a difference equaling 17% of the standard deviation (SD) of CCA-IMT in the analytical sample.

Individuals in the lowest level of average HLS also had a 0.16 mm smaller CCA-AD, compared with those in the highest level — a difference equaling 24% of the SD of CCA-AD.

An association was found between average HLS and carotid plaque after adjustment for major confounders (P = .024); however, it did not retain statistical significance after further adjustment for physiological risk (P = .25).

Smoking Conferred Highest Risk

To estimate the independent associations of each component of the HLS, the researchers adjusted for the other two components in the same model and found that abstinence from smoking was strongly and inversely associated with all three measures of subclinical carotid atherosclerosis (P-trends < .01).

Compared with the participants who smoked at some point during the follow-up period, those who remained never-smokers had a 0.047 mm smaller CCA-IMT, a 0.24 mm smaller CCA-AD, and 49% lower odds of having a higher carotid plaque index.

In contrast, there was an inverse association between average AHEI score and CCA-AD after adjustment for major confounders and physiological risk factors, except BMI (P-trend = .016).

Results from sensitivity analyses were found to be consistent with primary analyses.

Baylin and Wang speculated why abstinence from smoking was more protective against subclinical atherosclerotic than healthy diet and physical activity.

"Cigarette smoking is a major behavioral risk factor associated with atherosclerosis through mechanisms including thrombosis, dyslipidemia, insulin resistance, vascular inflammation, abnormal vascular growth and angiogenesis, and loss of endothelial and hemostatic and regenerative functions," they said.

They noted that multiple studies have "shown that prolonged smoking confers a higher CVD risk in women than it does in men."

They also suggested that because smoking is "measured more accurately than diet and exercise, the associations for diet and exercise are somewhat attenuated."

Critical Window

Commenting on the study for theheart.org | Medscape Cardiology, Nieca Goldberg, MD, medical director, Joan H. Tisch Center for Women's Health, NYU Langone Medical Center, New York City, said that the study "is the first to show the correlation between subclinical or asymptomatic plaque and lifestyle changes."

She noted that, "in this study and in real-life practice, exercise is underutilized."

The take-home messages for clinicians include "the importance of lifestyle counseling for smoking cessation, diet modification, and physical activity in menopausal women" and that "participating in a healthy lifestyle reduced risk for cardiovascular disease," she said.

Baylin and Wang called midlife in women "a critical window of opportunity for prevention," adding that "lifestyle education programs targeting overall lifestyle might be able to slow the menopause-related progression of atherosclerosis."

The Study of Women's Health Across the Nation (SWAN) has grant support from the NIH through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women's Health (ORWH). Baylin, Wang, and coauthors report no conflicts of interest. Goldberg reports no conflicts of interest.

J Am Heart Assoc. 2018;7:e010405. Abstract

For more theheart.org | Medscape Cardiology news, join us on Facebook and Twitter.