Peripheral blood endothelial microparticles (CD144+) as a surrogate marker for coronary microcirculatory dysfunction in patients with stable coronary artery disease

Objectives In stable coronary artery disease (CAD), coronary microvascular dysfunction (CMD) is a prevalent cause of myocardial ischemia independent of epicardial stenoses. Although the index of microcirculatory resistance (IMR) is the invasive reference standard for CMD assessment, its routine use is limited by procedural demands and cost. We investigated whether circulating endothelial microparticles (EMPs, CD144+) correlate with IMR and could serve as a non-invasive surrogate for CMD in stable CAD. Methods Fifty patients with stable CAD and 20 controls with normal angiograms underwent invasive physiological assessment, including IMR, fractional flow reserve (FFR), and coronary flow reserve (CFR), using a pressure-temperature sensor-tipped guidewire. Peripheral venous blood was analyzed for CD144+ EMPs by flow cytometry. Associations between EMPs and physiological indices were evaluated, with diagnostic utility assessed via ROC curve analyses. Results Demographic and clinical profiles were similar across groups (all P > 0.05). Circulating EMP counts were markedly higher in CAD patients than controls (145.62 ± 101.35 vs. 119.98 ± 71.93 particles/ μ L, P < 0.001), paralleled by elevated IMR values (22.14 ± 7.42 vs. 16.4 ± 4.41, P = 0.002). Within the CAD cohort, EMP levels correlated positively with IMR ( r = 0.684, P < 0.001), but not in controls ( r = 0.066, P = 0.783). Neither FFR nor CFR was associated with EMPs. Patients with IMR ≥ 23 had significantly higher EMP concentrations than those with IMR < 23 ( P < 0.001). For discriminating CMD (IMR ≥ 23), EMPs yielded an AUC of 0.76 (95% CI: 0.62–0.89); at the optimal threshold of 130 particles/μL, sensitivity was 70.0%, specificity 70.6%, and negative predictive value 85.7%. Conclusions Circulating CD144+ EMPs strongly correlate with invasive IMR in stable CAD. The moderate ROC performance (AUC 0.76) and high NPV suggest that peripheral EMP measurement holds promise as a non-invasive screening tool for CMD. However, these findings are exploratory and require prospective validation in larger, multi-center cohorts before clinical translation.