Lipid Changes Around the Final Menstrual Period Predict Carotid Subclinical Disease in Postmenopausal Women

Abstract

Background and purpose: Atherogenic changes in lipids occur among women around the time of the natural menopause, that is, within 1 year of the final menstrual period (FMP). We investigated whether lipid changes around the FMP are related to carotid intima-media thickness, interadventitial diameter, and plaque in postmenopausal women.

Methods: A total of 863 natural postmenopausal women with no history of heart attack or stroke underwent carotid ultrasound scans at follow-up year 12 or 13 of the Study of Women's Health Across the Nation. Estimates of their annual change in lipids were segmented into the year before and after the FMP, before the year before FMP, and 1 year after FMP. Multivariate analyses were adjusted for sociodemographic characteristics, time from FMP to scan, baseline body mass index and systolic blood pressure, and use of medications for hypertension and diabetes mellitus at the scan.

Results: Smaller increases in high-density lipoprotein cholesterol and apolipoprotein A1 within 1 year of the FMP were related to greater interadventitial diameter, β (SE)=-0.036 (0.015), P=0.02, and β (SE)=-0.035 (0.013), P=0.006, respectively. Greater increases in low-density lipoprotein cholesterol within 1 year of FMP were related to greater likelihood of plaque scores ≥2, odds ratio, 1.071; 95% confidence interval, 1.018-1.127; P=0.009. Magnitude of associations was reduced but remained significant with further adjustment for premenopausal lipid levels. The difference in probability of elevated plaque scores was 50% between those in the highest and lowest low-density lipoprotein cholesterol change tertiles.

Conclusions: Changes in lipids as women approach the FMP provide useful clinical information for understanding postmenopausal carotid indices.

Keywords: atherosclerosis; body mass index; cholesterol; lipids; menopause; race.

Figure 1

(Panel A) Predicted means of interadventitial diameter (IAD) by tertiles of HDL-C annual change within one year of FMP. Models were adjusted for site, ethnicity, age, time since FMP until carotid scan, education, baseline SBP and BMI, medications for hypertension and diabetes at time of scan; trend p-value=.02. HDL-C change tertiles (mg/dL/year): T1: <0.085; T2: 0.085 to <0.830, T3: ≥0.830. (Panel B). Predicted probabilities of plaque index ≥2 by tertiles of LDL-C annual change within one year of FMP. Models were adjusted for site, ethnicity, age, time since FMP until carotid scan, education, baseline SBP and BMI, medications for hypertension and diabetes at time of scan, trend p-value = .05. LDL-C change tertiles (mg/dL/year): T1: −3.67≤LDL-C change<5.44, T2: 5.44≤LDL-C change<7.32, T3: LDL-C≥7.32.

Figure 2

Predicted means of carotid IMT by tertiles of LDL-C annual change within one year of FMP and premenopausal obesity status. Models were adjusted for site, ethnicity, age, time since FMP, education, baseline SBP and BMI, use of medications for hypertension and diabetes at time of scan, and baseline LDL-C; interaction p value=0.03; T3 comparing BMI groups, p-value=0.05 (adjusted for multiple comparisons). LDL-C change tertiles (mg/dL/year): T1: −3.67 ≤LDL-C change<5.44, T2: 5.44≤LDL-C change<7.32, T3: LDL-C≥7.32.