Abstract 16180: Prognostic Implications Of Circulating miRs As Biomarkers In Cardiovascular Primary Prevention - Results From The Population-based DETECT-study

Abstract

Introduction: MicroRNA (miRs) are small non-coding RNAs that intracellularly control gene expression by binding target mRNAs. Circulating levels of miRs have been recently proposed as biomarkers for cardiovascular disease. In order to identify a potential significance of miRs as biomarker for cardiovascular risk stratification in primary care, we measured concentrations of circulating miRs representing different pathobiological pathways - heart-muscle-enriched miR-499, platelet-enriched miR-223, aging-related miR 34a, and miR 378 involved in metabolism and in cardiac remodeling by PCR in EDTA-plasma in a representative case-control-study of 192 subjects free of cardiovascular disease within the 55518 subjects of the population-based DETECT study and determined their prognostic significance for MACE events within the five-year-follow-up-period.

Results: All tested miRs are associated with different established cardiovascular risk factors, in particular miR 223 levels show significant inverse associations with age (r=-0.343), Framingham-risk-score (r=-0.233), impaired renal function (r=-0.299), elevated homocystein (r=-0.202) and NT-pro-BNP levels (r=-0.175) and a direct correlation with smoking status (r=0.209) and HDL-cholesterol (r=0.174). Furthermore, elevated concentrations of circulating miRs implied prognostic information: increased levels of circulating miR 34a and miR 378 demonstrated a significant relationship with incident MACE (HR=4.68 for miR 34a and HR=4.17 for miR 378) during 5-year follow-up. A single measurement of circulating miR 34a- and miR 378- concentrations contributes significantly to cardiovascular risk prediction (C statistics: miR 34a C=0.671, miR 378 C=0.670) and was superior to the established biomarker NT-pro-BNP (C=0.607) for prediction of incident MACE. The combination of NT-pro-BNP with elevated miR 34a and with elevated miR 378 concentrations further significantly improved C-statistics for cardiovascular risk prediction.

Conclusions: In a representative primary prevention cohort, circulating miR-concentrations correlate with cardiovascular risk profile and are associated with incident major cardiovascular events within five years of follow-up.