Estradiol may influence association between HDL cholesterol, aortic calcification
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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 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.
For more information:
Samar R. El Khoudary, PhD, MPH, FAHA, can be reached at elkhoudarys@edc.pitt.edu.
Perspective
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Cholesterol associated with HDL cholesterol is often termed “good” cholesterol because of a generally negative, ie, protective, association with adverse atherosclerotic cardiovascular disease outcomes. While therapeutic interventions to lower “bad” LDL cholesterol consistently decrease adverse atherosclerotic CVD risk, agents that result in higher HDL cholesterol levels have not conferred a similar benefit. The complexity of HDL cholesterol associations is underscored by some observations that higher HDL cholesterol in perimenopausal women may confer increased risk for subclinical adverse atherosclerotic CVD, as cited in the current study by Swabe and colleagues, who suggest that such relationship may be mediated through inflammatory factors or estradiol, both of which can influence HDL cholesterol as well as atherosclerosis.
Atheromatous calcification can readily be detected in association with the aortic valve or (as more commonly employed in clinical practice) the coronary arteries by noncontrast CT using minimal radiation. Calcium scores are widely used as a surrogate for an individual’s cumulative exposure to the atherosclerotic process, and the coronary artery calcium score can powerfully restratify individuals’ adverse atherosclerotic CVD risk level beyond that of conventional risk calculators based on demographic factors and cholesterol levels.
In a cohort of perimenopausal women, Swabe and colleagues found that increasing HDL cholesterol was associated with lower coronary artery calcium as well as aortic valve calcium scores in an unadjusted model, consistent with the protective effect of HDL that is generally recognized. However, when stratifying the associations by estradiol level, they noted that HDL cholesterol had a positive association with aortic valve calcium among those subjects with lower estradiol values.
It is important to recognize that HDL cholesterol is an imperfect surrogate for HDL function or cholesterol efflux, as illustrated in certain forms of CETP deficiency in which higher HDL cholesterol and increased adverse atherosclerotic cardiovascular disease risk are seen simultaneously. Future study is warranted to uncover the mechanistic underpinnings of the complexity between HDL, sex hormones and atherosclerosis.
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