Effects of Gender on Coronary Microvascular Dysfunction and Cardiac Outcomes
Background—Coronary microvascular dysfunction (CMD) is a prevalent and prognostically important finding in patients with symptoms suggestive of coronary artery disease (CAD). The relative extent to which CMD affects both genders is largely unknown.
Methods and Results—We investigated 405 men and 813 women referred for evaluation of suspected CAD with no previous history of CAD and no visual evidence of CAD on rest/stress positron emission tomography (PET) myocardial perfusion imaging. Coronary flow reserve (CFR) was quantified and CFR<2.0 used to define the presence of CMD. Major adverse cardiac events (MACE), including cardiac death, non-fatal myocardial infarction, late revascularization and hospitalization for heart failure, were assessed in blinded fashion over a median follow-up of 1.3 years (IQR 0.5-2.3 years). CMD 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, CFR was a powerful incremental predictor of MACE (hazard ratio 0.80 [95% CI 0.75-086] per 10% increase in CFR; P<0.0001) and resulted in favorable net reclassification improvement (NRI=0.280 [95% CI 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 (CAC) on gated CT imaging, CMD was common in both genders, despite normal stress perfusion imaging and zero CAC (44% of men versus 48% of women; P(Fisher exact test)=0.56; P(equivalence)=0.041).
Conclusions—CMD is highly prevalent among at risk individuals and is associated with adverse outcomes regardless of gender. The high prevalence of CMD in both genders suggests that it may be a useful target for future therapeutic interventions.
- Received December 30, 2013.
- Revision received March 19, 2014.
- Accepted March 25, 2014.