Prognostic Value of Microrna-126-3p for Cardiovascular Events in a General Population

Abstract

Objective: Endothelial dysfunction is a forerunner of atherosclerosis, leading to cardiovascular disease, and albuminuria is a marker of endothelial dysfunction. Measurement of circulating levels of microRNAs is emerging as potential biomarkers for cardiovascular disease. We aimed to estimate the predictive value of a plasma microRNAs signature associated with albuminuria in the incidence of cardiovascular events. Design and method: The first study phase was to identify the plasma miRNAs associated with albuminuria in patients with HTN and controls. In a second step, a predictive model of miRNAs to assess the risk to develop CV events was analyzed in a retrospective study of the general population (HORTEGA Follow-up Study), on those who did not have previous CVD and had complete basal information on relevant covariates. Plasma miRNAs quantified in hypertensive patients by next generation sequencing were validated in a cohort of patients and controls by real-time quantitative PCR. The microRNAs associated with albuminuria were tested and their prognostic value for cardiovascular event incidence were analyzed on a retrospective, population-based study using Cox proportional hazard models. Results: A plasma microRNA profile was identified in the discovery cohort (n = 48) associated with albuminuria and three microRNAs (miR-126-3p, miR-1260b and miR-374a-5p) were confirmed in the validation cohort (n = 98). The microRNA signature discriminates urinary albumin excretion at baseline (n = 1025), and predicts the incidence of cardiovascular events and coronary heart disease and stroke in a general population retrospective study within a 14-year follow-up (n = 926). Thus, high miR-126-3p levels were associated with a shorter time free of both cardiovascular events (HR = 1.48, (1.36–1.62), p < 0.0001), as well as coronary artery disease and stroke combined (HR = 2.49, (2.19–2.83), p < 0.0001) (Figure). Conclusions: An increased plasma microRNAs profile was identified in hypertensive patients with albuminuria. Increased miR-126-3p emerges as a prognostic marker for cardiovascular events in a long-term general population. Further studies will assess the potential role of miR-126-3p as a guide for the status of endothelial dysfunction.