Prognostic value of serum microRNA-675 expression levels in patients with chronic heart failure

Background MicroRNAs (miR), which can be measured from serum samples, have emerged as novel biomarkers in several scientific fields, including cardiovascular disease. Although it has been shown that miR-675 plays an important role in inhibiting cardiac hypertrophy, the prognostic value of miR-675 in patients with heart failure (HF) remains unknown. Purpose The aim of this study was to examine the association between serum miR-675 expression levels and mortality in patients with HF. Methods We prospectively examined 336 consecutive patients with chronic HF from a multicentre registry (29 Japanese sites) from January 2020 to March 2021, and assessed the expression levels of serum miR-675 by quantitative polymerase chain reaction. The patients were divided into low and high miR-675 groups based on the median value of 3.64. For subgroup analysis, the patients were further classified into HF with reduced ejection fraction (HFrEF) (left ventricular ejection fraction [LVEF] ≤ 40%) and non-HFrEF (LVEF > 40%) groups. The primary outcome was all-cause death. Results Of studied patients (149 male, mean age 70 ± 14 years, mean LVEF 48 [interquartile range (IQR) 35–63] %), 124 (37%) were classified as HFrEF. Patients with lower miR-675 levels had lower haemoglobin, estimated glomerular filtration rate, serum albumin, higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels compared to those with higher miR-675 levels. Over a median follow-up period of 3.8 (IQR 3.3–4.1) years, the primary outcome occurred in 53 patients. In overall population, patients with lower miR-675 levels showed a significantly higher incidence of the primary outcome compared to those with higher miR-675 levels (Figure 1A). Subgroup analysis revealed that patients with lower miR-675 levels showed a significantly higher incidence of the primary outcome compared to those with higher miR-675 in HFrEF group (P = 0.021, Figure 1B), whereas there were no significant differences in non-HFrEF group (P = 0.70, Figure 1C) with significant interaction (P = 0.007). Moreover, patients with lower miR-675 and higher NT-proBNP showed the highest incidence of the primary outcome in overall population and subgroups (Figure 2). In a multivariable Cox regression analysis, lower miR-675 levels were independently associated with the primary outcome (HR 1.83, 95% CI 1.03–3.26) even after adjusting for significant covariates including the Meta-Analysis Global Group in Chronic Heart Failure risk score, serum sodium, and LV mass index. Conclusions In patients with HF, particularly those with HFrEF, lower miR-675 levels were independently associated with a higher risk of all-cause death. Furthermore, the combination of lower miR-675 and higher NT-proBNP can identify the patients at the high-risk profile, suggesting that miR-675 would be useful for risk stratification in patients with HF.