Abstract
Purpose of ReviewThis review provides a brief synopsis of sexual dimorphism in atherosclerosis with an emphasis on genetic studies aimed to better understand the atherosclerotic process and clinical outcomes in women. Such studies are warranted because development of atherosclerosis, impact of several traditional risk factors, and burden of coronary heart disease (CHD) differ between women and men.Recent FindingsWhile most candidate gene studies pool women and men and adjust for sex, some sex-specific studies provide evidence of association between candidate genes and prevalent and incident CHD in women. So far, most genome-wide association studies (GWAS) also failed to consider sex-specific associations. The few GWAS focused on women tended to have small sample sizes and insufficient power to reject the null hypothesis of no association even if associations exist.SummaryFew studies consider that sex can modify the effect of gene variants on CHD. Sufficiently large-scale genetic studies in women of different race/ethnic groups, taking into account possible gene-gene and gene-environment interactions as well as hormone-mediated epigenetic mechanisms, are needed. Using the same disease definition for women and men might not be appropriate. Accurate phenotyping and inclusion of relevant outcomes in women, together with targeting the entire spectrum of atherosclerosis, could help address the contribution of genes to sexual dimorphism in atherosclerosis. Discovered genetic loci should be taken forward for replication and functional studies to elucidate the plausible underlying biological mechanisms. A better understanding of the etiology of atherosclerosis in women would facilitate future prevention efforts and interventions.
Highlights
Cardiovascular disease (CVD) remains the leading cause of mortality among women and men [1, 2]
In spite of statistics that show coronary heart disease (CHD) develops on average 7– 10 years later in women compared with men, adverse trends in many risk factors among women are of growing concern [3, 8]
We provide a review of sex differences in atherosclerosis, the contribution of genetic research to explaining sex differences in atherosclerosis, possible sex hormone-mediated epigenetic mechanisms, and use of subclinical measures of atherosclerosis for genetic studies
Summary
Cardiovascular disease (CVD) remains the leading cause of mortality among women and men [1, 2]. Overall CVD mortality rates have declined, the annual mortality rate for women remains higher than men [3]. Despite the excess CHD incidence and prevalence in men compared to women, CHD remains the leading contributor to CVD morbidity and mortality among both women and men [1, 2]. In spite of statistics that show CHD develops on average 7– 10 years later in women compared with men, adverse trends in many risk factors among women are of growing concern [3, 8]. While the decrease in CHD mortality among women is well documented, the decline still lags behind that of men, with an alarming tendency towards an increase
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