Proteomic biomarkers and pathway analysis for progression to heart failure in three epidemiological representative cohorts

ABSTRACT Aims Biomarkers associated with asymptomatic ventricular dysfunction might improve risk stratification and identify pathways leading to heart failure (HF). We explored the association between proteomic biomarkers and left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and incident HF in three population‐based cohorts. Methods and results A chip was used to measure 92 protein biomarkers in blood samples from >1500 Malmö Preventive Project (MPP) participants, of whom 514 had LVH (34%), 462 had DD (32.4%) and, over a median follow‐up of 13 (11–14) years, 130 developed HF (7.7%). Findings were confirmed in the STANISLAS ( n > 1500, 238 participants with LVH, 76 with DD) and HOMAGE case‐control (562 cases of incident HF, 871 controls) cohorts. In multivariable logistic or Cox regression analyses adjusted for age, sex and cardiovascular risk factors, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) was associated with LVH, DD and incident HF in all cohorts: MPP (LVH odds ratio [OR] [95% confidence interval] 1.48 [1.28–1.71]; DD OR 1.71 [1.53–1.92]; HF HR 1.98 [1.66–2.36]); STANISLAS (LVH OR 1.20 [1.02–1.41]; DD OR 1.46 [1.12–1.90]); HOMAGE (HF HR 1.85 [1.62–2.12]). Galectin‐4, growth differentiation factor 15 and suppression of tumorigenicity‐2 were associated with incident HF in MPP and HOMAGE. A pathway enrichment analysis suggested that inflammation and viral infection were related to incident HF. Conclusion In conclusion, our study reinforces the role of NT‐proBNP as a key biomarker for asymptomatic cardiac dysfunction and incident HF, consistent with its established use in clinical practice. This underscores the value of NT‐proBNP for identifying patients at high risk for HF, and provides insights into pathways leading to HF and potential therapeutic targets.