Background: Coronary flow reserve (CFR) is a measure of coronary microvascular dysfunction (CMD) in patients with non-obstructive CAD, and reduced CFR is associated with adverse cardiovascular outcomes. Similar hyperemic coronary blood flow between men and women, but lower CFR in women, has been previously reported. We hypothesized that resting baseline coronary blood flow (CBF) is an independent predictor of CMD and that higher resting baseline CBF in women accounts for lower CFR.
Methods: One thousand six hundred and eighty eight patients with chest pain referred for coronary vasomotion evaluation and found to have angiographically normal coronary arteries or mild CAD (<40%) were included. CFR was calculated as the ratio of peak flow velocity (measured using a Doppler wire) in response to intracoronary adenosine (36-72 μg) over baseline velocity in the left anterior descending artery (LAD). CMD was defined as CFR <2.5. Mid-LAD diameter was measured with quantitative angiography and baseline CBF calculated.
Results: 35% of patients were men and median age was 51 (42, 59) years. Median baseline CBF was significantly higher in both women (37%) and men (20%) with CMD compared to their counterparts with normal microvascular function [54.3 (36.3, 81.4) vs. 48.1 (32.5, 67.8) ml/min, p=0.01 for women, and 61.3 (38.4, 85.9) vs. 44.4 (31.2, 64.7) ml/min, p=0.003 for men]. As compared to men, women had significantly lower CFR [2.7 (2.4, 3.2) vs. 3.1 (2.7, 3.6), p<0.0001], higher baseline CBF [49.7 (34.0, 71.1) vs. 45.9 (31.8, 68.7) ml/min, p=0.04], and smaller baseline mid-LAD coronary artery cross-sectional area (CAA) [3.80 (2.69, 5.31) vs. 4.26 (3.11, 6.15) mm2, p<0.0001]. There was a modest inverse linear relationship (r= -0.21, p<0.0001) between baseline CBF and CFR. After adjusting for age, gender, hypertension, diabetes, hyperlipidemia, body mass index (BMI), smoking, baseline heart rate (HR), mean arterial pressure, CAA and baseline CBF, the independent predictors of CMD were age (p<0.0001), female gender (p=0.006), diabetes (p=0.013), BMI (p<0.0001), HR (p<0.0001), CAA (p<0.0001) and CBF (p<0.0001).
Conclusions: Women have lower CFR, higher resting CBF and lower CAA as compared to men. Both female gender and resting CBF are independent predictors of CMD.