Fig. 1.

Study design for miRNA identification associated with albuminuria and cardiovascular events. The study design involved a discovery phase including hypertensives (HTN) (n = 48) with urinary albumin excretion (UAE) or normoalbuminuric (Non-UAE) by small RNA sequencing (Small RNA-Seq). In a second validation stage with a large hypertensive cohort (n = 69), including UAE or Non-UAE, and healthy controls (CNT, n = 29), 5 microRNA (miRNAs) were validated by real-time quantitative polymerase chain reaction (RT-qPCR). Finally, in a testing population cohort (Hortega's cohort), at baseline (n = 1025), the associations with 3 miRNAs (miR-374a-5p, miR-1260b and miR-126–3p) and albuminuria were tested. Then, at the 14-year follow-up (n = 926), the predictive power of miRNA levels with cardiovascular disease (CVD) events and combined coronary artery disease (CAD) + stroke incidence was investigated.