Effects of Gender on Coronary Microvascular Dysfunction and Cardiac Outcomes

Study Questions:

Does the association between coronary microvascular dysfunction and coronary artery disease (CAD) differ by gender?


Men and women were referred for evaluation of suspected CAD by positron emission tomography (PET) myocardial perfusion. Patients with known CAD and those with visual evidence of CAD on rest/stress PET imaging were excluded. Coronary flow reserve was quantified and coronary flow reserve <2.0 was used to define the presence of coronary microvascular dysfunction. Major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, late revascularization, and hospitalization for heart failure, were assessed in blinded fashion over a median follow-up of 1.3 years (interquartile range, 0.5-2.3 years).


A total of 405 men and 813 women were included in the present study. Women were slightly older, and more likely to be Hispanic and nonwhite than men. Compared to men, women were also more frequently obese and hypertensive. However, women were less likely to use tobacco. Chest pain and dyspnea were also more frequent in women than men. The pretest clinical risk based on the gender-neutral modified Duke clinical risk score was higher among women than men (35% vs. 29%, respectively, p = 0.007). Left ventricular ejection fractions were slightly higher among women, although they were normal in both genders. Coronary microvascular dysfunction was highly prevalent both in men and women (51% and 54%, respectively; P [Fisher exact test] = 0.39; P [equivalence] = 0.0002). Regardless of gender, coronary flow reserve was a powerful incremental predictor of MACE (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 female/97 male) without evidence of coronary artery calcification on gated CT imaging, coronary microvascular dysfunction was common in both genders, despite normal stress perfusion imaging and zero coronary artery calcification (44% of men vs. 48% of women; P [Fisher exact test] = 0.56; P [equivalence] = 0.041).


The investigators concluded that coronary microvascular dysfunction is highly prevalent among at-risk individuals and is associated with adverse outcomes regardless of gender. The high prevalence of coronary microvascular dysfunction in both genders suggests that it may be a useful target for future therapeutic interventions.


These data suggest that PET imaging is a useful tool to identify both men and women at increased risk for cardiac events despite having normal rest/stress images. Understanding what is effective medical management, and does such management translate into reduced events, is an important clinical question to address.

Clinical Topics: Heart Failure and Cardiomyopathies, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure

Keywords: Coronary Artery Disease, Myocardial Infarction, Tobacco, Chest Pain, Heart Failure, Stroke Volume, Dyspnea, Hispanic Americans, Hospitalization

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