Abstract
BACKGROUND: The mechanism of the fractional flow reserve (FFR) difference according to sex has not been clearly understood. OBJECTIVES: This study sought to evaluate sex differences in coronary stenosis, plaque characteristics, and left ventricular (LV) mass and their implications for physiological significance. METHODS: This was a post hoc analysis of a pooled population of multicenter, international prospective cohorts. Patients (166 women and 489 men) underwent coronary computed tomography angiography (CCTA) within 90 days before invasive FFR measurements were included. The minimal lumen area, percent of plaque burden, whole vessel plaque volume by composition, high-risk plaque characteristics, and LV mass were analyzed from CCTA images. RESULTS: Among 1,188 vessels analyzed, the FFR value was higher in women than that in men (0.85 ± 0.13 vs 0.82 ± 0.14; P = 0.001) despite a similar percentage of diameter stenosis between the sexes (45.9% ± 18.9% vs 46.1% ± 17.7%; P = 0.920). The composition of fibrofatty plaque + necrotic core (13.1% ± 16.9% vs 21.2% ± 19.9%; P < 0.001) and frequencies of low attenuation plaque (12.7% vs 24.5%; P < 0.001) and positive remodeling (33.8% vs 45.5%; P = 0.001) were lower in women than in men. Vessel, plaque, and lumen volumes were significantly smaller in women than that in men (all P < 0.001); however, no sex difference was observed in any of these parameters after adjustment for LV mass (all P > 0.10). Sex was not an independent predictor of the FFR value after adjustment for stenosis severity, plaque characteristics, and LV mass. CONCLUSIONS: Higher FFR values for the same stenosis severity in women can be explained by fewer high-risk plaque characteristics and smaller myocardial mass in women than that in men. (CCTA-FFR Registry for Risk Prediction; NCT04037163).