High-density lipoprotein cholesterol and arterial calcification in midlife women: the contribution of estradiol and C-reactive protein

OBJECTIVE: Studies suggest a reversal in the protective association of high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease in women traversing menopause. Decreasing estrogen levels during the transition, as well as inflammation, may explain this reversal. We tested whether either estradiol or C-reactive protein (CRP) concentrations modified the association of HDL-C with aortic (AC) or coronary artery calcification (CAC). METHODS: A total of 478 participants between ages 46 to 59 from the Study of Women's Health Across the Nation Heart baseline visit were included. AC and CAC presence were defined as Agatston score of 100 or higher and 10 or higher, respectively. Logistic regression was used for analysis. RESULTS: A total of 112 (23.53%) participants had AC 100 or higher and 104 (21.76%) had CAC 10 or higher. In unadjusted models, a 1-mg/dL higher in HDL-C was associated with 3% lower odds of AC (95% CI: 0.95-0.99) and 4% lower odds of CAC (95% CI: 0.95-0.98). In adjusted models, a significant interaction between HDL-C and estradiol with respect to AC but not CAC was detected, such that higher HDL-C level was protective at the highest estradiol quartile (odds ratio: 0.91, 95% CI: 0.84-0.99 per 1 mg/dL higher HDL-C, P = 0.03) but tended to associate with greater risk at the lowest quartile (odds ratio: 1.04, 95% CI: 0.98-1.10 per 1 mg/dL higher HDL-C, P = 0.16). CRP did not modify any association. CONCLUSIONS: The protective cardiovascular association of higher HDL-C levels on AC was modified by estradiol but not CRP concentrations. The pathways through which estradiol might influence this association should be further investigated.