Estradiol may influence association between HDL cholesterol, aortic calcification – Healio

January 11, 2021

2 min read


Disclosures: El Khoudary reports she received grant funding from the National Institute on Aging supporting the SWAN HDL ancillary.

High HDL cholesterol levels alone may not be cardioprotective for midlife women; estradiol may influence the risk for cardiovascular disease, according to data from the SWAN Heart study.

“Levels of endogenous estradiol may play an important role in cardioprotective associations of HDL cholesterol,” Samar R. El Khoudary, PhD, MPH, FAHA, associate professor of epidemiology in the Graduate School of Public Health at the University of Pittsburgh, told Healio. “In midlife women, the protective association of high levels of HDL cholesterol with lower risk of aortic calcification is only evident at higher levels of endogenous estradiol.”

El Khoudary is an associate professor of epidemiology in the Graduate School of Public Health at the University of Pittsburgh.

El Khoudary and colleagues’ findings were published in Menopause.

Researchers analyzed data from 478 midlife women (mean age, 50.9 years; 37% Black) who participated in the Study of Women’s Health Across the Nation (SWAN) Heart study, which focused on the progression of subclinical measures of CVD during midlife. Data for the study were obtained from the SWAN Heart baseline visit. Aortic and coronary artery calcification (CAC) scores were measured via CT scan. Waist circumference, systolic blood pressure, HDL cholesterol, triglycerides, glucose, C-reactive protein and estradiol were measured at baseline.

Of the study population, 23.53% had an aortic calcification score of 100 or higher and 21.76% had a CAC score of 10 or higher. There were 55 women who had high aortic calcification and CAC scores. In unadjusted models, each 1 mg/dL increase in HDL cholesterol was associated 3% lower odds for aortic calcification and a 4% decrease in odds for CAC.

Adjusted models showed no significant association between HDL cholesterol and either aortic calcification or CAC without the interaction between cholesterol and estradiol. After adjusting for confounders, there was a significant interaction between HDL cholesterol and estradiol with respect to aortic calcification. A higher HDL cholesterol level was associated with a lower risk for aortic calcification with high estradiol, and there was a greater risk for aortic calcification with high HDL cholesterol and low estradiol after adjusting for C-reactive protein. The interaction between HDL cholesterol and estradiol was not significant for CAC in any models.

“When evaluating women’s risk for CVD at midlife, other factors, such as maintaining healthy weight and diet, being physically active and having low LDL cholesterol, controlled blood pressure and sugar, would collectively provide better picture of women’s risk than a high level of HDL cholesterol,” El Khoudary said. “Current clinical guidelines recommend risk estimation for individuals aged 40 to 75 years using the Pooled Cohort Equation, which predicts lower 10-year risk of atherosclerotic CVD with increasing HDL cholesterol. Our results indicate that this equation may underestimate that risk for women who have transitioned through menopause, even if this reversal is only temporary.”

El Khoudary said future research should examine whether estrogen therapy during menopause modifies the protective association of HDL cholesterol with aortic calcification.

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Samar R. El Khoudary, PhD, MPH, FAHA, can be reached at