Proteomic prediction of incident heart failure and its main subtypes

Author:

Emilsson Valur12ORCID,Jonsson Brynjolfur G.1ORCID,Austin Thomas R.3,Gudmundsdottir Valborg12ORCID,Axelsson Gisli T.1ORCID,Frick Elisabet A.1ORCID,Jonmundsson Thorarinn1ORCID,Steindorsdottir Anna E.1,Loureiro Joseph4ORCID,Brody Jennifer A.5ORCID,Aspelund Thor1ORCID,Launer Lenore J.6ORCID,Thorgeirsson Gudmundur12ORCID,Kortekaas Kirsten A.7ORCID,Lindeman Jan H.8ORCID,Orth Anthony P.9,Lamb John R.10,Psaty Bruce M.11ORCID,Kizer Jorge R.12ORCID,Jennings Lori L.4ORCID,Gudnason Vilmundur12ORCID

Affiliation:

1. Icelandic Heart Association Kopavogur Iceland

2. Faculty of Medicine University of Iceland Reykjavik Iceland

3. Cardiovascular Health Research Unit, Department of Epidemiology University of Washington Seattle WA USA

4. Novartis Institutes for Biomedical Research Cambridge MA USA

5. Cardiovascular Health Research Unit, Department of Medicine University of Washington Seattle WA USA

6. Laboratory of Epidemiology and Population Sciences National Institute on Aging Bethesda MD USA

7. Department of Cardiology Leiden University Medical Center Leiden The Netherlands

8. Department of Surgery Leiden University Medical Center Leiden The Netherlands

9. Novartis Institutes for Biomedical Research San Diego CA USA

10. Monoceros Biosystems San Diego CA USA

11. Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Systems and Population Health University of Washington Seattle WA USA

12. Division of Cardiology, San Francisco Veterans Affairs Health Care System, and Departments of Medicine, Epidemiology and Biostatistics University of California San Francisco CA USA

Abstract

AbstractAimTo examine the ability of serum proteins in predicting future heart failure (HF) events, including HF with reduced or preserved ejection fraction (HFrEF or HFpEF), in relation to event time, and with or without considering established HF‐associated clinical variables.Methods and resultsIn the prospective population‐based Age, Gene/Environment Susceptibility Reykjavik Study (AGES‐RS), 440 individuals developed HF after their first visit with a median follow‐up of 5.45 years. Among them, 167 were diagnosed with HFrEF and 188 with HFpEF. A least absolute shrinkage and selection operator regression model with non‐parametric bootstrap were used to select predictors from an analysis of 4782 serum proteins, and several pre‐established clinical parameters linked to HF. A subset of 8–10 distinct or overlapping serum proteins predicted different future HF outcomes, and C‐statistics were used to assess discrimination, revealing proteins combined with a C‐index of 0.80 for all incident HF, 0.78 and 0.80 for incident HFpEF or HFrEF, respectively. In the AGES‐RS, protein panels alone encompassed the risk contained in the clinical information and improved the performance characteristics of prediction models based on N‐terminal pro‐B‐type natriuretic peptide and clinical risk factors. Finally, the protein predictors performed particularly well close to the time of an HF event, an outcome that was replicated in the Cardiovascular Health Study.ConclusionA small number of circulating proteins accurately predicted future HF in the AGES‐RS cohort of older adults, and they alone encompass the risk information found in a collection of clinical data. Incident HF events were predicted up to 8 years, with predictor performance significantly improving for events occurring less than 1 year ahead, a finding replicated in an external cohort study.

Funder

National Heart, Lung, and Blood Institute

National Institute on Aging

NHLBI Division of Intramural Research

Publisher

Wiley

Subject

Cardiology and Cardiovascular Medicine

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Dissecting the heart failure phenotype through phenomics;European Journal of Heart Failure;2024-03-19

2. Predicting heart failure: The promise of proteomics;European Journal of Heart Failure;2024-01

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