Abstract

Introduction: Substantial hormonal and adverse lipid changes have been reported within one-year interval of the final menstrual period (FMP) suggesting this interval as a critical time period in midlife women. Significant structural vascular remodeling has been documented during the late peri-menopausal stage, a stage characterized by amenorrhea for at least 3 months. Whether vascular functional changes also accompany the menopause transition and occur within one-year interval of the FMP is not clear. Central arterial stiffness as measured by aortic pulse wave velocity (aPWV), is a marker of vascular functional changes and a significant predictor of CVD events. Our aim was to test whether the change in aPWV differs by time elapsed since the FMP in midlife women. We hypothesized that aPWV would significantly increase within one-year of the FMP independent of aging and traditional CVD risk factors. Methods: We evaluated participants with no self-reported CVD from the Study of Women’s Health Across the Nation (SWAN) Heart Ancillary study, a study of subclinical measures of atherosclerosis in midlife women at the Pittsburgh and Chicago sites. Women had up to two aPWV scans over a median of 2.2 years of follow-up and known FMP dates. Yearly % changes in aPWV were estimated in three time segments relative to the FMP (segment 1: more than 1 year before FMP, segment 2: within 1 year before and after FMP, and segment 3: more than 1 year after FMP) and compared using piecewise linear mixed-effects model with random intercepts. Final model was adjusted for time-varying age, race, study site, baseline systolic blood pressure, waist circumference, insulin resistance, physical activity, and history of hormone therapy use. Results: The study included 304 women (At baseline: age mean(SD): 51.1(2.8) y; 62% White, 38% Black; 10% premenopausal, 52% early perimenopausal, 12% late perimenopausal, and 26% postmenopausal). In final model, estimates of the annual % change (95% CI) in aPWV were: -0.6% (-2.1%, 0.8%) for more than one year before the FMP, 3.8% (0.3%, 7.4%) within one year-interval of the FMP, and -2.1% (-4.0%, -0.1%) for more than one year after the FMP. The estimated annual % change in aPWV within the one year-interval of the FMP was significantly greater than the estimated changes in the other two segments in final model, p<0.05 for both comparisons. Conclusions: The one year-interval around the FMP is a critical period in women’s life when vascular functional alterations occur in central arteries independent of aging. These results are consistent with previous findings showing significant vascular structural changes and lipid levels worsening around the time of the FMP. Future research should examine the impact of the reported vascular functional changes on CVD risk after menopause.

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