Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study

Author:

Girerd Nicolas1ORCID,Levy Daniel23ORCID,Duarte Kevin1ORCID,Ferreira Joao Pedro1ORCID,Ballantyne Christie4ORCID,Collier Timothy5ORCID,Pizard Anne16ORCID,Björkman Jens7ORCID,Butler Javed8ORCID,Clark Andrew9ORCID,Cleland John G.1011,Delles Christian12ORCID,Diez Javier1314ORCID,González Arantxa141516ORCID,Hazebroek Mark17ORCID,Ho Jennifer23ORCID,Huby Anne-Cécile1,Hwang Shih-Jen23ORCID,Latini Roberto18,Mariottoni Beatrice19,Mebazaa Alexandre20,Pellicori Pierpaolo10ORCID,Sattar Naveed21ORCID,Sever Peter22,Staessen Jan A.23ORCID,Verdonschot Job23ORCID,Heymans Stephane242526ORCID,Rossignol Patrick1ORCID,Zannad Faiez1ORCID

Affiliation:

1. Université de Lorraine, Inserm, Centre d’Investigations Cliniques- Plurithématique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.G., K.D., J.P.F., A.P., A.-C.H., P.R., F.Z.).

2. National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA (D.L., J.H., S.-J.H).

3. Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (D.L., J.H., S.-J.H.).

4. Baylor College of Medicine, Houston, TX (C.B.).

5. London School of Hygiene and Tropical Medicine, United Kingdom (T.C.).

6. Inserm 1024, Institut de Biologie de l’École Normale Supérieure (IBENS), PSL University of Paris, France (A.P.).

7. TATAA Biocenter AB, Gothenburg, Sweden (J.B.).

8. Department of Medicine, University of Mississippi School of Medicine, Jackson (J.B.).

9. Hull York Medical School, Castle Hill Hospital, Cottingham, United Kingdom (A.C.).

10. Robertson Centre for Biostatistics and Clinical Trials, Institute of Health and Wellbeing, University of Glasgow, United Kingdom (J.G.C., P.P.).

11. National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, United Kingdom (J.G.C.).

12. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (C.D.C.).

13. Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (J.D.C., A.G.C.).

14. CIBERCV, Carlos III Institute of Health, Madrid, Spain (J.D.C., A.G.C.).

15. Instituto de Investigación Sanitaria de Navarra (IdiSNA), Spain (J.D.C., A.G.C.).

16. Departments of Nephrology, and Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (A.G.C.).

17. Department of Cardiology, Maastricht University Medical Centre, Center for Heart Failure Research, Cardiovascular Research Institute Maastricht (CARIM), University Hospital Maastricht, the Netherlands (M.H.C.).

18. IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy (R.L.).

19. Department of Cardiology, Cortona Hospital, Arezzo, Italy (B.M.).

20. UMRS 942; University Paris Diderot; APHP, University Hospitals Saint Louis Lariboisière, France (A.M.).

21. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (N.S.).

22. International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, United Kingdom (P.S.).

23. Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium (J.A.S.).

24. Department of Cardiovascular Research, University of Leuven, UZ Herestraat, Belgium (S.H.).

25. Netherlands Heart Institute (ICIN), Utrecht, the Netherlands (S.H.).

26. Department of Clinical Genetics, Maastricht University Medical Center, the Netherlands (S.H.).

Abstract

Background: We sought to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts (HOMAGE cohort [Heart Omics and Ageing], ARIC study [Atherosclerosis Risk in Communities], and FHS [Framingham Heart Study]) and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone. Methods: A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Plasma concentrations of 276 proteins were measured at baseline in ARIC (250 cases/250 controls), FHS (191/191), and HOMAGE cohort (562/871). Results: In single protein analysis, after adjusting for matching variables and clinical risk factors (and correcting for multiple testing), 62 proteins were associated with incident HF in ARIC, 16 in FHS, and 116 in HOMAGE cohort. Proteins associated with incident HF in all cohorts were BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), eukaryotic translation initiation factor 4E-BP1 (4E-binding protein 1), hepatocyte growth factor (HGF), Gal-9 (galectin-9), TGF-alpha (transforming growth factor alpha), THBS2 (thrombospondin-2), and U-PAR (urokinase plasminogen activator surface receptor). The increment in C -index for incident HF based on a multiprotein biomarker approach, in addition to clinical risk factors and NT-proBNP, was 11.1% (7.5%–14.7%) in ARIC, 5.9% (2.6%–9.2%) in FHS, and 7.5% (5.4%–9.5%) in HOMAGE cohort, all P <0.001), each of which was a larger increase than that for NT-proBNP on top of clinical risk factors. Complex network analysis revealed a number of overrepresented pathways related to inflammation (eg, tumor necrosis factor and interleukin) and remodeling (eg, extracellular matrix and apoptosis). Conclusions: A multiprotein biomarker approach improves prediction of incident HF when added to natriuretic peptides and clinical risk factors.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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