Cardiac, oxidative stress, and fibrosis-related biomarkers and new-onset heart failure: Systematic review and meta-analysis

Background: Circulating biomarkers reflecting pathophysiological pathways, including myocardial stress, injury, oxidative stress, and fibrosis, may facilitate early identification of individuals at increased risk of heart failure (HF) in the general population. However, the strength and consistency of associations between these biomarkers and incident HF have not been comprehensively evaluated. Methods: A comprehensive search of relevant databases (inception-September 2024) identified population-based studies reporting biomarkers associated with incident HF in individuals without a prior HF history. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random effects meta-analysis. Results: Across 47 included studies, nine biomarkers were significantly associated with new-onset HF in multivariate-adjusted analyses: N-terminal pro b-type natriuretic peptide (NT-proBNP) (HR 2.03, 95% CI: 1.82-2.25, P < 0.01), high-sensitivity cardiac troponin I (hs-cTnI) (HR 1.58, 95% CI: 1.42-1.76, P < 0.01), high-sensitivity cardiac troponin T (hs-cTnT) (HR 1.74, 95% CI: 1.36-2.22, P < 0.01), midregional pro-atrial natriuretic peptide (MR-proANP) (HR 1.54, 95% CI: 1.39-1.71, P < 0.01), b-type natriuretic peptide (BNP) (HR 1.57, 95% CI: 1.44-1.71, P < 0.01), growth differentiation factor 15 (GDF-15) (HR 1.51, 95% CI: 1.36-1.68, P < 0.01), midregional proadrenomedullin (MR-proADM) (HR 1.38, 95% CI: 1.10-1.74, P < 0.01), fibroblast growth factor 23 (FGF-23) (HR 1.17, 95% CI: 1.10-1.25, P < 0.01), and galectin-3 (Gal-3) (HR 1.23, 95% CI: 1.12-1.35, P < 0.01). HF phenotypes and sex differences were also evaluated. Conclusions: Higher levels of NT-proBNP, hs-cTnI, hs-cTnT, MR-proANP, BNP, GDF-15, MR-proADM, FGF-23, and Gal-3 were associated with a larger risk of incident HF, supporting their utility as biomarkers for predicting HF development.