Proteomic Biomarkers and Pathway Analysis for Progression to Heart Failure in Three Epidemiological Representative Cohorts
Year: 2024
Type: article
Study design: Observational Study
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.
DOI: 10.1002/ejhf.3502
Authors: Anna Dieden, Nicolas Girerd, Filip Ottosson, John Molvin, Manan Pareek, Olle Melander, Erasmus Bachus, Lennart Råstam, Ulf Lindblad, Bledar Daka, Margrét Leósdóttir, Peter M. Nilsson, Michael H. Olsen, Andrew L. Clark, John G.F. Cleland, Christian Delles, Arantxa González, Zohra Lamiral, Kevin Duarte, Patrick Rossignol, Faiez Zannad, Petri Gudmundsson, Amra Jujić, Martin Magnusson
Institutions: Malmö University, Lund University, Inserm, Centre Hospitalier Régional et Universitaire de Nancy, French Clinical Research Infrastructure Network, Université de Lorraine, Statens Serum Institut, Skåne University Hospital, University of Copenhagen, Copenhagen University Hospital, Rigshospitalet, University of Gothenburg, University of Southern Denmark, Holbæk Sygehus, Castle Hill Hospital, Hull York Medical School, British Heart Foundation, University of Glasgow, Instituto de Salud Carlos III, Centro de Investigación en Red en Enfermedades Cardiovasculares, Navarre Institute of Health Research, Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Universidad de Navarra, Princess Grace Hospital Centre, North-West University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,250
Funders: Merck KGaA, Aase og Ejnar Danielsens Fond, Lunds Universitet, Hjärt-Lungfonden, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Ernhold Lundströms stiftelse, Hulda och E Conrad Mossfelts Stiftelse för Vetenskaplig Forskning Inom Hjärt- och Kärlsjukdomarnas Område, Region Skåne, Skånes universitetssjukhus, Medicinska Fakulteten, Lunds Universitet, Danish Cardiovascular Academy
Awards: G3607181024, G5943844871, G706423436
OpenAlex ID: W4403825916