Insights Into Coronary Plaque Microstructure Differences Between Women and Men

Abstract

The difference between men and women is getting harder and harder to invent.-Marty Rubin C ardiovascular disease remains the leading cause of death in men and women in the United States. Over the past 2 decades, both clinicians and researchers have paid increased attention to the problem of cardiovascular disease in women, with some improvements in the recognition of the problem and in outcomes. Historically, women with acute coronary syndrome (ACS) have had worse outcomes. However, with the improvement in the availability of revascularization and application of guideline-directed therapies for both sexes, the gap in outcomes between men and women has been closing. 1 See Article by Kataoka et alDuring the same period of time, we have learned more about the sex differences in cardiovascular risk factor profiles, coronary anatomy, and physiology. Women presenting with symptomatic coronary artery disease (CAD) tend to have larger burden of cardiovascular risk factors, especially of current smoking and metabolic syndrome, and a higher Framingham Risk Score. 2Coronary atherosclerosis in women is characterized not only by smaller plaque burden but also by smaller size of coronary arteries.1-6 Therefore, due to smaller luminal size women may develop symptoms even with smaller plaque burden or thrombus load. The observational studies that examined coronary plaque morphology differences in men and women have been far from conclusive, some suggesting lower prevalence of plaque ruptures and thin-cap fibroatheroma (TCFA), higher prevalence of plaque erosions in women and others showing no significant differences. 4,[7][8][9][10] Interestingly, the sex differences in plaque size and morphology were more pronounced in younger patients and attenuated in patients >65 years of age.2,10 In addition to coronary plaque morphology, there were also differences in coronary flow characteristics, with women having higher fractional flow reserve values for any given stenosis and higher degree of mismatch between fractional flow reserve measurements and luminal size.1 Studies demonstrated higher prevalence of coronary microvascular dysfunction with coronary flow reserve <2.5, especially in perimenopausal women.1 In patients with early atherosclerosis without obstructive CAD, men had more structural and functional abnormalities in epicardial coronary arteries, whereas women had greater microvascular dysfunction independent of epicardial endothelial function.11 In contrast, a more recent study using quantitative flow measured by positron emission tomography in a large population with no evidence of ischemia failed to show differences in coronary flow reserve between men and women.12 Finally, nonatherosclerotic causes of symptoms such as coronary vasospasm, coronary dissection, and stress-induced cardiomyopathy were more often observed in women.1 In summary, although there has been increasing understanding of differences and similarities in CAD characteristics between men and women, more information is needed to tailor therapies and improve ...

Regulatory Role of Sex Hormones in Cardiovascular Calcification

“…Interestingly, sex differences in the atherosclerotic phenotype observed in Apoe −/− mice have been well-defined, whereby females tend to have larger plaques and increased calcification in those plaques [ 136 ]. Conversely, in human patients, females typically have smaller plaques and less calcification within the plaques [ 137 ]. Whilst investigations are frequently limited by the focus on a single sex, those rodent studies that have employed males and females to interrogate cardiovascular calcification pathways ( Table 1 ), have produced divergent findings; highlighting the constraints of these animal models, and the importance of investigating both sexes in pre-clinical studies.…”

Sex-Related Differences in the Association of BMI and Pericardial Fat Volume With Coronary Atherosclerotic Markers in Young

“…19 Thus, females may develop symptoms even with smaller plaque burden or thrombus load. 20,21 It has been reported that increasing cardiac fat deposition, measured by volumetric analysis rather than linear thickness assessment, is significantly associated with the presence of high-risk plaque features in a systematic review and meta-analysis of 9 studies. This association may be mediated via cellular cross-talk which may lead to the development of plaque characteristics considered to be "high risk" given their association with major adverse coronary events.…”