Microvascular Resistance Reserve Predicts CAD Outcomes: HR 0.75 per Unit Increase

BACKGROUND: Microvascular resistance reserve (MRR) is a novel index for evaluating coronary microvascular function independently of epicardial disease. Its prognostic significance in coronary artery disease (CAD) remains uncertain. OBJECTIVES: The aim of this study was to assess the association between MRR and adverse cardiovascular outcomes across various CAD presentations. METHODS: A systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MEDLINE and Embase were searched from January 2019 to January 2025 for prospective studies reporting HRs for major adverse cardiovascular events in relation to MRR. Risk for bias was assessed using the Quality in Prognosis Studies tool. Pooled HRs were calculated using a random-effects model; heterogeneity was evaluated using the I statistic. RESULTS: Five studies (n = 3,186) were included. Higher MRR was significantly associated with lower risk for adverse events (HR per unit increase: 0.75; 95% CI: 0.64-0.88; I = 80.9%). When dichotomized, low MRR conferred a more than 2-fold increased risk for major adverse cardiovascular events (HR: 2.39; 95% CI: 1.66-3.43). Subgroup analysis showed a stronger prognostic effect for ST-segment elevation myocardial infarction (HR: 0.46) vs stable CAD (HR: 0.86; P for interaction < 0.0001). Threshold analysis identified MRR ≥ 3 as optimal for sensitivity (58.9%) and rule-out performance, while lower thresholds improved specificity. CONCLUSIONS: MRR is a robust, independent predictor of cardiovascular outcomes of both acute and chronic CAD. Its prognostic impact is particularly pronounced for acute coronary syndrome. A threshold of 3 provides the best prognostic balance, supporting its integration into invasive physiological assessment for risk stratification.