47 Impact of sex on the assessment of the microvascular resistance reserve for the impact of epicardial coronary artery disease severity (expressed by FFR), and the impact of pharmacological vasodilatation on perfusion pressure (expressed by the ratio of resting to hyperemic aortic pressure). Treatment and clinical follow-up PCI was performed according to clinical practice guidelines at the time of the procedure. However, final decisions regarding revascularization were at the discretion of the operator. Clinical follow-up was obtained at outpatient clinic visits or by telephone contact to ascertain the occurrence of major adverse cardiac events (MACE). MACE was defined as the composite of all-cause death, acute myocardial infarction of the target vessel, and clinically driven (urgent) revascularization by means of coronary artery bypass or percutaneous coronary intervention (PCI).7 All patient-reported events were verified by evaluating hospital records or contacting the treating cardiologist or general practitioner. Statistical analysis Data were analyzed on a per-patient basis. Normality and homogeneity of the variances were tested using Shapiro-Wilk and Levene tests. Continuous variables are presented as mean ± SD or median (first, third quartile [Q1, Q3]) and were compared with the student t-test or Mann-Whitney U test. Categorical variables are presented as counts and percentages and were compared using Fisher exact test. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy of the MRR in women. For this analysis, the presence of reversible perfusion abnormalities during non-invasive stress testing prior to coronary angiography was used as the standard of reference. Additionally, time-dependent ROC analysis was performed to derive the optimal MRR cut-off value for MACE in women and men. The optimal cut-off value was determined using the Liu method.8 We subsequently evaluated the association of MRR as a continuous variable with MACE at 5-year follow-up. Survival analyses were performed based on time-to-first-event analyses. The hazard ratio for MACE per unit increase of MRR and CFR was calculated with the use of a Cox proportional hazards model. All models were adjusted for the effect of relevant clinical and angiographic characteristics (P < 0.1 for inclusion). All clinical and angiographic characteristics (Table 1) were considered as covariates. A p-value <0.05 was considered statistically significant. Stata version 14.0 (StataCorp, College Station, Texas) software package was used for calculations. 3
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