Genetic Research and Women’s Heart Disease: a Primer

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.

Genetic variants associated with earlier age at menopause increase the risk of cardiovascular events in women

“…16 It should be noted that few studies consider that sex can modify the effect of genetic variants on cardiovascular diseases. 17…”

Article Commentary: Considering Sex as a Biological Variable in Biomedical Research

“…[20][21][22][23] Cholesterol plaque in women might not build up into major artery blockages, but instead would spread evenly throughout artery walls. 24 Consequently, artery blockages can be more difficult to detect on coronary angiography in women, who may also present with subtle symptoms of ischemia but are still at high risk for myocardial infarction. 25,26 And, women experience higher rates of adverse drug reactions than men.…”

Menopause and cardiometabolic diseases: What we (don't) know and why it matters

“…[2,3] However, the underlying biological pathways remain insufficiently studied, and disentangling the effect of age and menopause on cardiometabolic status worsening has been challenging. [4,5] Considering that the midlife period could be a critical window of opportunity to optimize cardiometabolic health and initiate early prevention strategies, we conducted a narrative review in which we discuss the current understanding of the impact of menopause (timing, type and menopause stages) and associated modifying and/or mediating factors such as hormone therapy, genes, lifestyle and environment on CMD risk (e.g., risk factors such as blood pressure, lipid and glucose metabolism, obesity and T2D and CVD) in aging women.…”