LAUSR

C ardiovascular disease (CVD) is the leading cause of death among women in the United States, and lipid and lipoprotein levels are powerful risk predictors. The role of high-density lipoprotein cholesterol (HDL-c), however, has been enigmatic. Epidemiological studies have shown that HDL-c is inversely associated with CVD risk in the overall population, but may have differential roles in premenopausal and postmenopausal women. With dramatic declines in estrogen levels at menopause, the risk of CVD in women increases markedly, and the association of HDL-c with risk of CVD in midlife and older women has been controversial. The Multi-Ethnic Study of Atherosclerosis study and the Study of Women’s Health Across the Nation (SWAN) Heart study suggested that higher HDL-c was associated with greater carotid intima-media thickness and higher levels of aortic calcification among postmenopausal women. It is unknown whether an apparent reversal in the protective association of HDL-c with CVD as women traverse menopause is related to changes in estrogen levels. In this issue of Menopause, Swabe et al explore the associations of HDL-c with arterial calcification in midlife women in the SWAN Heart Study, and specifically assess whether estradiol and C-reactive protein levels modify the association. The authors found significant interaction between HDL-c and estradiol in relation to aortic calcification. Higher HDL-c was associated with lower risk of aortic calcification among women in the highest estradiol quartile, while higher HDL-c tended to be associated with higher risk of aortic