51 Impact of sex on the assessment of the microvascular resistance reserve Univariate regression analysis indicated that age and minimal lumen diameter were significantly associated with MRR in women. In men, also BMI, the presence of hypertension or diabetes, and the percent diameter stenosis were found to be associated with MRR. Multivariate analysis including these confounders showed that only age and the minimal lumen diameter were significantly correlated with the MRR in both women and men. There was no statistical difference between the two prediction models stratified by sex (p = 0.675). MRR threshold analysis Time dependent ROC-analysis were performed to assess the discriminative characteristics of MRR for the occurrence of MACE during 5-year follow-up period (Figure 2). The AUC showed a limited discriminative value of MRR for the occurrence of MACE and was similar between women and men (AUC 0.64 vs 0.59, p = 0.06 for the difference). The optimal cut-off value for the occurrence of MACE in women was 2.8 and in men 3.2. Prognostic value of MRR in women and comparison with men The median follow-up period was 3.7 years (Q1,Q3; 2.0,5.1) for women, and 2.9 years (Q1,Q3; 1.9, 5.1) for men. A total of 9.2% women experienced at least one MACE, versus 11.7% of men. Univariate Cox regression analysis indicated that in women, age, diabetes mellitus, hypertension, a family predisposition for cardiovascular disease, previous myocardial infarction were significant confounders for MACE. After correction for these confounders, the MRR as a continuous variable was significantly associated with MACE at 5-year follow-up (HR 0.67, 0.47–0.96, p = 0.027). The same analysis showed that in men the MRR as a continuous variable was also independently and significantly associated with MACE at 5-year follow-up (HR 0.84, 0.74–0.95, p = 0.007). Using a cut-off value of 3.0 and after the correction of significant confounders, abnormal MRR was unequivocally associated with an increased risk for MACE at 5-year follow-up in women (HR 1.9, 95% CI 1.1–3.4, p = 0.023). A sensitivity analysis with the optimal cut-off value for women did not alter the conclusions significantly (data not shown). Similarly, for men an abnormal MRR based on a cut-off value of 3.0 showed an increased risk for MACE at 5-year follow-up (HR 2.3, 95% CI 1.3–3.7, p = 0.002) and applying the optimal cut-value for men did not alter the conclusions. Figure 3 shows the cumulative incidence of MACE according to normal and abnormal MRR, based on the cut-off value of 3.0 and according to sex. There was no significant difference in the risk of MACE between sexes (p = 0.430). 3
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