Sex-specific differences in coronary blood flow and flow velocity reserve in symptomatic patients with non-obstructive disease

Aims: Reduced coronary flow velocity reserve (CFVR) is associated with adverse cardiovascular outcomes. Whether CFVR and coronary blood flow (CBF) are similar in men and women with chest pain and non-obstructive CAD remains unknown. We hypothesised sex differences in CFVR and CBF. Methods and results: A total of 1,683 patients with signs/symptoms of ischaemia and angiographically unobstructed coronary arteries (<40% angiographic stenosis) underwent coronary vasomotion evaluation. CFVR was measured as hyperaemic/resting average velocity in the LAD. Mid-LAD diameter was measured with quantitative angiography and CBF calculated at rest (rCBF) and hyperaemia (hCBF). Resting microvascular resistance (rMR) was calculated as mean arterial pressure/rCBF. Of the total number of patients, 1,096 (65%) were women, median age 51 [42, 59] years. Compared to men, women had lower median CFVR (2.7 [2.4, 3.2] vs 3.1 [2.7, 3.6], p<0.001), higher rCBF (49.7 [34.0, 71.1] vs 45.9 [31.8, 68.7] ml/min, p=0.04), lower hCBF (139.5 [93.0, 195.2] vs 147.1 [95.7, 218.6] ml/min, p=0.02), but similar rMR (p=0.82). Female sex was an independent predictor of lower CFVR, higher rCBF, and lower hCBF. Conclusions: Compared to men, women with signs/symptoms of ischaemia and non-obstructive CAD have lower CFVR, higher rCBF, and lower hCBF. Female sex is a predictor of these sex-specific differences. The clinical diagnostic and prognostic implications of sex differences in coronary physiology need further evaluation.