Background
A team from INSERM in Nancy have carried out a study to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts: HOMAGE cohort (Heart Omics and Ageing), the ARIC study (Atherosclerosis Risk in Communities, and FHS (Framingham Heart Study). The incidence of HF is increasing in conjunction with increasing life expectancy and the associated increases in the exposure to several risk factors, including hypertension, diabetes, and obesity. While therapy for HF has advanced in recent years, new personalized strategies are needed to enable HF prevention at a population level. In this study, three Olink® Target 96 panels were used to measure plasma proteomics in the three independent cohorts to identify new biomarkers and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone.
Outcome
A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Multiple proteins associated with incident HF were identified in the three cohorts: 62 in ARIC, 16 in FHS and 116 in Homage. While the proteins identified as significantly associated with HF varied across cohorts, they were all related to inflammatory (e.g., TNF and interleukins) and remodeling (e.g., extracellular matrix and apoptosis) pathways when analyzed in a complex network analysis.
Several proteins were associated with incident HF in all 3 cohorts: BNP,NT-proBNP, 4E-BP1, HGF, Gal-9, TGF-alpha, THBS2 & U-PAR. When these proteins were assessed in a multi-marker approach, they significantly and substantially improved the prediction of incident HF on top of standard clinical HF risk factors in all 3 cohorts (C-index increases all >10%). Further pathway analysis then identified 9 key mechanistic clusters related to these proteins, mostly related to inflammatory pathways, which further emphasizes the pivotal role of inflammation in the pathogenesis of HF.
