Effects of Sex on Coronary Microvascular Dysfunction and Cardiac Outcomes

Study Questions:

Does coronary microvascular dysfunction (CMD) affect men and women differently?


A total of 405 men and 813 women who were referred for evaluation of suspected coronary artery disease (CAD) and had no prior history of CAD and no visual evidence of CAD on rest/stress positron emission tomography myocardial perfusion imaging were included. Coronary flow reserve was quantified and coronary flow reserve <2.0 was used to define the presence of CMD. The primary outcome of interest was major adverse cardiac events (including cardiac death, nonfatal myocardial infarction, late revascularization, and hospitalization for heart failure), which were assessed in a blinded fashion over a median follow-up of 1.3 years.


Among the 1,218 patients with normal stress perfusion imaging, women were slightly older and more likely to be Hispanic and nonwhite than men. Compared with men, women were also more frequently obese and hypertensive. Women were less likely to use tobacco. Chest pain and dyspnea were more frequent in women than in men. The pretest clinical risk based on the sex-neutral modified Duke clinical risk score was higher among women than men (35% vs. 29%, respectively; p = 0.007). CMD was highly prevalent both in men and women (51% and 54%, respectively). Regardless of sex, coronary flow reserve was a powerful incremental predictor of major adverse cardiac events (hazard ratio, 0.80; 95% confidence interval, 0.75-086 per 10% increase in coronary flow reserve; p < 0.0001) and resulted in favorable net reclassification improvement (0.280; 95% confidence interval, 0.049-0.512), after adjustment for clinical risk and ventricular function. In a subgroup (n = 404; 307 women/97 men) without evidence of coronary artery calcification on gated computed tomography imaging, CMD was common in both sexes, despite normal stress perfusion imaging and no coronary artery calcification (44% of men vs. 48% of women).


The investigators concluded that CMD is highly prevalent among at-risk individuals, and is associated with adverse outcomes regardless of sex. The high prevalence of CMD in both sexes suggests that it may be a useful target for future therapeutic interventions.


This study suggests clinical utility in measurement of CMD for both men and women. Given that CMD was associated with traditional cardiovascular disease risk factors, examining whether optimization of such risk factors is associated with improvement in CMD may be an important area to explore.

< Back to Listings