Circulating CD31+/Annexin V+ microparticles correlate with cardiovascular outcomes

Abstract

CD31⁺/Annexin V⁺ microparticles (MPs) are increased in patients with cardiovascular risk factors and impaired coronary endothelial function. We evaluated whether MPs are an independent marker for cardiovascular events in patients with stable coronary artery disease (CAD). The number of CD31⁺/Annexin V⁺ MP was determined by flow cytometry in 200 patients (age 66.1 ± 10.4 years) and correlated with cardiovascular outcomes. The median follow-up time for major adverse cardiovascular and cerebral event (MACCE)-free survival was 6.1 (6.0/6.4) years. Four patients were lost to follow-up. A first MACCE occurred in 72 patients (37%). Microparticle levels were significantly higher in patients with MACCE compared with patients without event (P = 0.004). The prevalence of diabetes (P = 0.02) and male gender (P = 0.05) was significantly related to the MP level. In multivariate analysis (cardiovascular risk factors, number of diseased vessels, use of angiotensin-converting enzyme-inhibitors and statins), high MP levels were associated with a higher risk for cardiovascular death [Hazard ratio (HR) 4.0, 95% confidence interval (CI) 1.1–14.6; P = 0.04], the need for revascularization (HR 2.4, 95% CI 1.3–4.4; P = 0.005), and the occurrence of a first MACCE (HR 2.3, 95% CI 1.4–3.8; P = 0.001). Inclusion of the MP level into a classical risk factor model substantially increased c-statistics from 0.637 (95% CI: 0.557–0.717) to 0.702 (95% CI: 0.625–0.780) (P = 0.03). The level of circulating CD31⁺/Annexin V⁺ MPs is an independent predictor of cardiovascular events in stable CAD patients and may be useful for risk stratification.