Abstract
Introduction: Case fatality rates for cardiovascular disease (CVD) are higher for women of all ages as compared with men, yet obstructive coronary artery disease (CAD) is less prevalent in women. Coronary flow reserve (CFR) is an integrated measure of large and small vessel CAD and myocardial ischemia, and identifies patients at risk for CVD death, independently of angiographic disease severity. Methods: Consecutive patients (N=329, 43% women) referred for invasive coronary angiography after stress testing with myocardial perfusion PET and with LV ejection fraction >40% were followed (median 3.0 years) for CVD death, nonfatal MI, or heart failure admission. The extent/severity of angiographic CAD was estimated using the CAD prognostic index (CADPI), and CFR quantified using PET. Results: Although women relative to men had lower pretest clinical scores, rates of prior MI, and burden of angiographic CAD (p<0.001), they demonstrated greater risk of CVD events (adjusted HR 2.05, 95%CI 1.05-4.02, p=0.03), even after adjustment for clinical risk factors, LV ejection fraction and ischemia, angiographic disease and time-dependent early revascularization. Impaired CFR was similarly present among women and men, but in patients with low CFR (<1.6, n=163), women showed higher frequency of nonobstructive CAD, while men showed higher frequency of severely obstructive CAD (p=0.002). After also adjusting for CFR (adjusted HR for unit decrease in CFR, 1.69; 95%CI 1.04-2.76, p=0.03), the effect of sex on outcomes was no longer significant (p=0.10). When stratified by sex and CFR (Figure), only women with impaired CFR demonstrated significantly increased adjusted risk of CVD events (p<0.0001, model p for interaction=0.04). Conclusions: Although women referred for coronary angiography had significantly lower burden of obstructive epicardial CAD relative to men, they were not protected from CVD events. Impaired CFR from diffuse CAD may represent a target for CVD risk reduction.
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