Circulating microRNA‐132 levels improve risk prediction for heart failure hospitalization in patients with chronic heart failure

Abstract

Aims Non‐coding microRNAs (miRNAs) are critically involved in cardiovascular pathophysiology. Since they are measurable in most body fluids, they have been proposed as circulating biomarkers. We examined the prognostic value of a specific candidate miRNA in a large cohort of patients with chronic heart failure (HF) enrolled in a multicentre clinical trial. Methods and results Plasma levels of miR‐132 were measured using miRNA‐specific PCR‐based technologies at randomization in 953 patients with chronic, symptomatic HF from the GISSI‐Heart Failure trial. The association with fatal (all‐cause and cardiovascular death) and non‐fatal events (time to first admission to hospital for cardiovascular reasons or worsening of HF) and the incremental risk prediction were estimated in adjusted models. Higher circulating miR‐132 levels were independently associated with younger age, better renal filtration, ischaemic aetiology of HF, more severe HF symptoms, higher diastolic blood pressure, higher cholesterol, and male sex. After extensive adjustment for demographic, clinical, and echocardiographic risk factors and baseline NT‐proBNP concentrations, miR‐132 remained associated only with HF hospitalizations (hazard ratio 0.79, 95% confidence interval 0.66–0.95, P = 0.01) and improved its risk prediction with the continuous net reclassification index (cNRI 0.205, P = 0.001). Conclusion In well characterized patients with chronic HF, circulating miR‐132 levels rise with the severity of HF. Lower circulating miR‐132 levels improved risk prediction for HF readmission beyond traditional risk factors, but not for mortality. MiR‐132 may be helpful to intensify strategies aimed at reducing re‐hospitalization, which has a substantial health and economic burden in HF.

Biomarkers for heart failure: small molecules with high clinical relevance

“…In chronic HF patients from the GISSI‐HF trial, miR‐132 levels rose with the severity of HF, whereas lower circulating miR‐132 levels improved risk prediction for HF readmission, but not for mortality . Bayes‐Genis et al .…”

ETS2 and microRNA‑155 regulate the pathogenesis of heart failure through targeting and regulating GPR18 expression

“…For example, previous studies have revealed that miRNA (miR)-214 is upregulated in HF and suppresses the transcription factor (TF) X-box binding protein 1 (XBP1)-mediated endothelial cell angiogenesis (6,7). Masson et al (8) reported that increased levels of circulating miR-132 improved the hospitalization of patients with HF, whilst miR-21 was observed to negatively regulate T regulatory cells in coronary heart disease via the transforming growth factor-β1/Smad pathway, including HF (9). Moreover, TFs are considered to serve important roles in the regulation of gene expression (10); Bakker et al (11) demonstrated that T-box TF 3 (TBX3) could reprogram mature cardiac myocytes into pacemaker-like cells, whereas the silenced TF interferon regulatory factor 5 (IRF5) was indicated to reprogram the macrophage phenotype and promote infarct healing (12).…”

Fluid-based assays and precision medicine of cardiovascular diseases: the ‘hope’ for Pandora’s box?

“…For the first time, a large cohort of 953 patients with chronic HF enrolled in the multicentre Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure (GISSI-HF) trial demonstrated that higher circulating miR-132 levels were independently associated with younger age, better renal filtration, ischaemic aetiology of HF, more severe HF symptoms, higher diastolic blood pressure, higher cholesterol and male sex with respect to controls, suggesting a useful risk predictor for hospitalisation. 65 Importantly, in two independent cohorts of 2203 patients with HF, miR-1254 and miR-1306 were associated with increased risk of death and hospitalisation. 66 Beyond the putative role as predictive, diagnostic and prognostic biomarkers, all of these changes in circulating miRNA also suggest innovative therapeutic targets.…”