53 Impact of sex on the assessment of the microvascular resistance reserve portends important prognostic value in both men and women. As such, this study underlines the potential of the MRR as an index of the vasodilator capacity of the coronary microcirculation, despite its theoretical limitations in women. Coronary hemodynamics and sex differences: implications for the MRR Sex differences in the assessment of the coronary hemodynamics in patients with anginal symptoms are increasingly recognized. Women presenting with anginal symptoms present at older age, have smaller vessel size and a generally lower vasodilator capacity expressed by lower CFR values, all of which impact the physiological assessment of the coronary circulation.9 Consequently, for comparable angiographic stenosis severity, women have higher FFR values compared to men.10 Hence, using the MRR, basically correcting the CFR for FFR, could theoretically impact the identification of coronary microvascular dysfunction in women compared to men. In addition, we found that age and minimal lumen diameter significantly impact the MRR value in both women and men. Despite these considerations, we document that the diagnostic characteristics of MRR are similar between women and men. MRR, although generally lower in women, showed a similar agreement with CFR in both sexes (r = 0.80 for women, r = 0.81 for men) and comparable with the previously reported agreement in the overall CCS population.4 The time dependent ROC-analysis showed a similar, but limited discriminative function for MACE at 5-year follow-up. The optimal cut-off value for MACE at 5-year follow-up was 2.8 in women and 3.2 in men. These findings are in line with previously reported cutoff value analysis in the general population (3.0), and with a recent publication by de Vos et al. whom reported that an MRR above 2.7 rules out microvascular dysfunction defined by concordant normal CFR and IMR in an ANOCA population dominated by women.11 Additional prospective studies are warranted to confirm these findings. Prognostic value of MRR in female patients While the exact threshold defining abnormal vasodilatory capacity remains debated, the clinical and prognostic value of a reduced vasodilatory capacity is undisputed. The traditional indices of an abnormal vasodilatory capacity, CFR and indices of minimal microvascular resistance, have shown to portend prognostic value. However, both indices are susceptible of their own limitations. The MRR, theoretically addressing these limitations, was found to be a robust and prognostically valuable index in the general CCS population.4 The current study addresses the theoretical concerns of the MRR in women and affirms its applicability in both women and men. The MRR as a continuous variable was independently and significantly associated with an increased risk of MACE in female patients (HR 0.67, 0.47–0.96, p = 0.027). An abnormal MRR in women based on the general cut-off value of 3.0 had a similar increased risk of MACE as it did in men (HR 1.9 vs 2.3, p = 0.430). Using the optimal cut-off value of 2.8 for women and 3.2 for men did not alter the conclusions. As such, based on the prognostic value, it can be assumed that the MRR is equally applicable in both women and men. 3
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