Coronary microvascular disease (CMD) refers to the subset of disorders affecting the structure and function of the coronary microcirculation, is prevalent in patients across a broad spectrum of ...cardiovascular risk factors, and is associated with an increased risk of adverse events. Contemporary evidence supports that most patients with CMD also have macrovessel atherosclerosis, which has important implications for their prognosis and management. In this state-of-the-art review, the authors summarize the pathophysiology of CMD, provide an update of diagnostic testing strategies, and classify CMD into phenotypes according to severity and coexistence with atherosclerosis. They examine emerging data highlighting the significance of CMD in specific populations, including obesity and insulin resistance, myocardial injury and heart failure with preserved ejection fraction, and nonobstructive and obstructive coronary artery disease. Finally, they discuss the role of CMD as a potential target for novel interventions beyond conventional approaches, representing a new frontier in cardiovascular disease reduction.
BACKGROUND—Coronary microvascular dysfunction (CMD) is a prevalent and prognostically important finding in patients with symptoms suggestive of coronary artery disease. The relative extent to which ...CMD affects both sexes is largely unknown.
METHODS AND RESULTS—We investigated 405 men and 813 women who were referred for evaluation of suspected coronary artery disease with no previous history of coronary artery disease and no visual evidence of coronary artery disease on rest/stress positron emission tomography myocardial perfusion imaging. Coronary flow reserve was quantified, and coronary flow reserve <2.0 was used to define the presence of CMD. Major adverse cardiac events, including cardiac death, nonfatal myocardial infarction, late revascularization, and hospitalization for heart failure, were assessed in a blinded fashion over a median follow-up of 1.3 years (interquartile range, 0.5–2.3 years). CMD was highly prevalent both in men and women (51% and 54%, respectively; Fisher exact test =0.39; equivalence P=0.0002). 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 versus 48% of women; Fisher exact test P=0.56; equivalence P=0.041).
CONCLUSIONS—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.
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