Abstract
Background: Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) is typically used to interrogate microvascular function; however its variability limits reliability. Alternatively, the index of microcirculatory resistance (IMR) is a direct measure of the microvasculature, but has been less thoroughly studied. We investigated sex differences in CFR and IMR in patients with angina in the absence of obstructive coronary artery disease (CAD). Methods: We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive CAD. We performed CFR, IMR, fractional flow reserve (FFR), and quantitative coronary angiography (QCA) in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn: an inverse correlate to absolute flow) at rest and hyperemia. IMR was measured as distal coronary pressure at hyperemia x hyperemic Tmn. Results: All patients had minimal or no atherosclerosis by QCA (%diameter stenosis: 23.2±12.3%), and epicardial disease was milder in women (FFR: 0.88±0.04 vs. 0.87±0.04, p=0.04). IMR was similar between the sexes (20.7±9.8 vs. 19.1±8.0, p=0.45), but CFR was lower in women (3.8±1.6 vs. 4.8±1.9, p=0.004). This was primarily due to a shorter resting Tmn in women (p=0.005), while hyperemic Tmn was identical (p=0.79) (Figure). The shorter resting Tmn in women, reflecting increased resting coronary flow, accounted for the lower CFR. In multivariate analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn, but not a predictor of IMR or hyperemic Tmn. Conclusions: Despite women and men having similar microvascular function by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The impact of sex differences should be considered in interpretation of physiologic indices using resting coronary flow.
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