Perimenopausal lipid changes predict subclinical carotid plaque

December 15, 2016

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Women with steeper increases in cholesterol in the perimenopausal period have a higher probability of carotid plaque in the postmenopausal years, new research suggests.

"The prognostic value of increases in low-density lipoprotein cholesterol (LDL) around the final menstrual period were independent of premenopausal levels of cardiovascular risk factors, which were also related to later carotid plaque," lead author Dr. Karen A. Matthews of the University of Pittsburgh, Pennsylvania, told Reuters Health by email.

"The findings suggest that it is important to monitor lipid changes frequently during the perimenopause, even among women who have 'normal' cholesterol levels," she said.

As reported in Stroke, online December 1, Dr. Matthews and her colleagues analyzed data from 863 natural postmenopausal women with no history of heart attack or stroke who underwent carotid ultrasound scans at follow-up year 12 or 13 of the multiethnic, community-based, longitudinal SWAN study of midlife aging and menopause.

The mean age at the carotid assessment was 60, and eight years had elapsed since the final menstrual period (FMP). At enrollment, the women had at least one ovary, were not pregnant or lactating, were not using oral contraceptives or hormone therapy, and had at least one menstrual cycle in the previous 3 months. The plaque index was categorized as 0 or 1 vs 2 or higher.

The authors created piecewise linear mixed effects models with three time segments: >12 months before the FMP, within 12 months before or after the FMP, and >12 months after the FMP. They adjusted multivariate analyses for sociodemographic characteristics, time from FMP to scan, baseline systolic blood pressure and body mass index, and medications for hypertension and diabetes mellitus at the scan.

Compared to women in the lowest tertile of perimenopausal LDL change (

In addition, smaller increases in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (ApoA 1) within a year of the FMP were associated with larger interadventitial diameter.

The magnitude of associations decreased but stayed significant after further adjustment for premenopausal lipid levels.

Dr. Elizabeth Ratchford, director of the Johns Hopkins Center for Vascular Medicine in Baltimore, Maryland, said in an email, "I'm pleased to see a study on this important area of women's health research published in such a high-profile journal. This study provides further evidence of the impact of the perimenopausal period on subsequent cardiovascular risk."

"I agree with the authors that increased surveillance is warranted in the perimenopausal period, and perhaps more aggressive treatment is warranted if rapid changes in the lipid profile are seen," added Dr. Ratchford, who was not involved in the study. "I look forward to further research looking at whether aggressive treatment (e.g., with a statin, in addition to lifestyle interventions) could attenuate the observed risk."

Dr. Fadi Nahab, medical director of the Stroke Program at Emory University in Atlanta, Georgia, who also was not involved in the study, called it important.

"The results may encourage providers caring for women during this period to monitor lipid levels at least once a year," he said in an email.

But, Dr. Nahab noted, "It remains unclear what amount of LDL-C annual change should prompt the addition of or dosage change in lipid-lowering medications such as statins."

According to the authors, strengths of the study include the large number of ethnically diverse patients, the availability of covariates, and the central reading of carotid scans using similar criteria used by other epidemiological studies. Limitations include carotid ultrasound performed only once during the postmenopausal period and the lack of annual lipid measures after year 7.

Going forward, Dr. Matthews said, "We hope to ask whether the menopause-induced changes in cardiovascular risk factors are related to later clinical heart disease events as we continue to follow the women in the parent study."

The National Institutes of Health (NIH), Department of Health and Human Services through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women's Health, supported the Study of Women's Health Across the Nation (SWAN).


Stroke 2016.

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