Circulating microRNAs as diagnostic biomarkers for cardiovascular

37 One of the major challenges in cardiovascular disease is the identification of reliable clinical 38 biomarkers which can be measured routinely in plasma. MicroRNAs were recently 39 discovered to circulate in the bloodstream in a remarkably stable form. Because of their 40 stability and often tissueand disease-specific expression, and the possibility to measure 41 them with high sensitivity and specificity, miRNAs are emerging as new diagnostic 42 biomarkers. In this review we will provide an overview of the potential of circulating miRNAs 43 as biomarkers for a wide range of cardiovascular diseases such as coronary artery disease, 44 myocardial infarction, hypertension, heart failure, viral myocarditis and type 2 diabetes 45 mellitus. Furthermore we will discuss the challenges with regard to further validation in large 46 patient cohorts and we will discuss how measurement of multiple miRNAs simultaneously 47 might improve accuracy of the diagnostic test. 48 49