Microvesicle protein levels are associated with increased risk for future vascular events and mortality in patients with clinically manifest vascular disease

Background and objectives: Microvesicles (MVs) are small membrane vesicles that are involved in atherotrombotic processes. In the present study, we evaluated the risk of MV protein levels on the occurrence of new vascular events in patients with clinically manifest vascular disease.

Methods: In this cohort study 1060 patients were prospectively followed for the occurrence of a new vascular event or death (median follow up 6.4 years, interquartile range 5.2-7.3 years). MVs were isolated from plasma and MV protein levels of Cystatin C, Serpin G1, Serpin F2 and CD14 were measured. Multivariable Cox proportional hazards models were used to estimate the risk for new vascular events, vascular mortality and all-cause mortality. During follow up 136 vascular events occurred, 65 vascular mortality and 114 all-cause mortality.

Results: An increase in 1 standard deviation (SD) of Cystatin C MV level was related to an increased risk for myocardial infarction (HR 1.49; 95%CI 1.20-1.86), vascular mortality (HR 1.48; 95%CI 1.17-1.86), vascular events (HR 1.27; 1.07-1.52) and all-cause mortality (HR 1.41; 95%CI 1.18-1.69). Serpin F2 MV levels were related to an increased risk for myocardial infarction (HR 1.22; 95%CI 1.00-1.51), vascular mortality (HR 1.25; 95%CI 1.00-1.56), and all-cause mortality (HR 1.22; 95% CI 1.03-1.45). CD14 MV levels were related to an increased risk for myocardial infarction (HR 1.55; 95%CI 1.27-1.91), vascular mortality (HR 1.37; 95%CI 1.10-1.70), vascular events (HR 1.32; 95%CI 1.12-1.55), all-cause mortality (HR 1.36; 95%CI 1.15-1.62) and occurrence of ischemic stroke (HR 1.32; 95%CI 1.00-1.74).

Conclusions: Cystatin C, Serpin F2 and CD14 MV levels are related to an elevated risk for future vascular events and mortality in patients with clinically manifest vascular disease.