Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition?

Abstract

Objectives: This prospective study examined whether changes in traditional and novel coronary heart disease (CHD) risk factors are greater within a year of the final menstrual period (FMP), relative to changes that occur before or after that interval, in a multiethnic cohort.

Background: Understanding the influence of menopause on CHD risk remains elusive and has been evaluated primarily in Caucasian samples.

Methods: SWAN (Study of Women's Health Across the Nation) is a prospective study of the menopausal transition in 3,302 minority (African American, Hispanic, Japanese, or Chinese) and Caucasian women. After 10 annual examinations, 1,054 women had achieved an FMP not due to surgery and without hormone therapy use before FMP. Measured CHD risk factors included lipids and lipoproteins, glucose, insulin, blood pressure, fibrinogen, and C-reactive protein. We assessed which of 2 models provided a better fit with the observed risk factor changes over time in relation to the FMP: a linear model, consistent with chronological aging, or a piecewise linear model, consistent with ovarian aging.

Results: Only total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B demonstrated substantial increases within the 1-year interval before and after the FMP, consistent with menopause-induced changes. This pattern was similar across ethnic groups. The other risk factors were consistent with a linear model, indicative of chronological aging.

Conclusions: Women experience a unique increase in lipids at the time of the FMP. Monitoring lipids in perimenopausal women should enhance primary prevention of CHD.

Figure 1. FSH annual and estimated means

Pattern of FSH across the SWAN follow-up period showing the annual covariate adjusted mean values compared to estimated values by the better fitting piece-wise linear model (menopause-related) and the linear model (aging-related); relative AIC fit for piece-wise linear vs linear models (95% CI) is 0.6640 (0.6096, 0.7184).

Figure 2. Lipids annual and estimated means

Pattern of LDL-C, Apo-B, HDL-C, and ApoA1 across the SWAN follow-up period showing the annual covariate adjusted mean values compared to estimated values by the better fitting piece-wise linear model (menopause-related); relative AIC fit for piece-wise linear vs linear models (95% CI), 1.0430 (1.0130, 1.0730), 1.0340 (1.0092, 1.0588), 1.0486 (1.0203, 1.0769), and1.0255 (1.0036, 1.0474), respectively.

Figure 3. Systolic Blood Pressure and Plasminogen Activator Inhibitor Type 1 Lipid Annual Means according to Baseline Weight

Pattern of total cholesterol, LDL-C and Apo-B across SWAN follow-up period showing the annual covariate adjusted mean values in women categorized by baseline weight tertiles. Slopes around the FMP interval were identical in the three groups for total cholesterol, LDL-C, and ApoB, Ps >0.28, respectively, whereas slopes more than 1 year after the FMP differed, Ps < 0.01, respectively.