Prognostic potential of circulatory miR-19a-3p, miR-19b-3p, and miR-329-3p for future hypertension diagnosis

MicroRNAs have been suggested as essential hypertension biomarkers, but evidence remains inconclusive due to limited high-throughput studies in population cohorts. We analyzed data from the Young Finns Study (YFS) from 2011 and 2018-2020 to assess cross-sectional and prospective associations between circulatory microRNAs, blood pressure (BP), and hypertension. Hypertension risk prediction potential was assessed using nested logistic and Weibull survival models; model performance was evaluated with likelihood ratio (LR) test and c-statistic. All models were adjusted with relevant risk factors. In 2011, whole blood microRNAs were profiled for 871 individuals (83 with hypertension); in 2018-2020, 760 were re-examined, with 67 newly diagnosed. Cross-sectionally, 16 miRNAs correlated with BP (Spearman, PFDR  < 0.05); miR-122-5p (fold change = 1.33) and miR-144-5p (fold change = -1.10) differentiated hypertensive individuals ( U test, PFDR  < 0.05). Associations persisted in adjusted regression models and some replicated in LURIC ( n  = 999) and YFS serum data ( n  = 126). Prospectively, miR-19a-3p [odds ratio (OR) = 1.51, 95% confidence interval (95% CI): 1.14-2.18], miR-19b-3p (OR = 1.50, 95% CI:1.11-2.04), and miR-329-3p (OR = 0.58, 95% CI: 0.39-0.74) levels prognosed hypertension incident. miR-329-3p improved model fit (LR test, P  = 2.85×10 -4 ) and discrimination (c-statistic = 0.849, Δ = 0.026). miR-19b-3p predicted time to onset (hazard ratio = 2.13, 95% CI: 1.38-4.45), improving model fit (LR test, P  = 0.0012) and time-dependent discrimination at 7 and 8-year horizons. Our findings highlight both novel and previously reported miRNAs associating with BP and hypertension and suggest that miR-329-3p, miR-19a-3p, and miR-19b-3p as promising candidates for further investigation in hypertension risk prediction.