TY - JOUR
T1 - Protein Biomarkers of New-Onset Heart Failure
T2 - Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study
AU - Girerd, Nicolas
AU - Levy, Daniel
AU - Duarte, Kevin
AU - Ferreira, Joao Pedro
AU - Ballantyne, Christie
AU - Collier, Timothy
AU - Pizard, Anne
AU - Björkman, Jens
AU - Butler, Javed
AU - Clark, Andrew
AU - Cleland, John G.
AU - Delles, Christian
AU - Diez, Javier
AU - González, Arantxa
AU - Hazebroek, Mark
AU - Ho, Jennifer
AU - Huby, Anne Cécile
AU - Hwang, Shih Jen
AU - Latini, Roberto
AU - Mariottoni, Beatrice
AU - Mebazaa, Alexandre
AU - Pellicori, Pierpaolo
AU - Sattar, Naveed
AU - Sever, Peter
AU - Staessen, Jan A.
AU - Verdonschot, Job
AU - Heymans, Stephane
AU - Rossignol, Patrick
AU - Zannad, Faiez
N1 - Funding Information:
Drs Ferreira, Girerd, Rossignol, and Zannad are supported by the French National Research Agency Fighting Heart Failure (ANR-15-RHU-0004), by the French PIA project Lorraine Université d’Excellence GEENAGE (ANR-15-IDEX-04-LUE) programs, and the Contrat de Plan Etat Région Lorraine and FEDER IT2MP. Dr Girerd reports honoraria from Novartis, AstraZeneka, Boehringer, and Vifor. Dr Rossignol received personal fees (consulting) from Idorsia and G3P, honoraria from AstraZeneca, Bayer, CVRx, Fresenius, Grunenthal, Novartis, NovoNordisk, Servier, StealthPeptides, Ablative Solutions, Corvidia, Relypsa, and Vifor Fresenius Medical Care Renal Pharma, outside the submitted work, and is the cofounder of CardioRenal. Dr Zannad reports steering committee personal fees from Applied Therapeutics, Bayer, Boehringer, Boston Scientific, Novartis, Janssen, and CVRx, advisory board personal fees from AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, and Merck, stock options at G3Pharmaceutical, and being the founder of CardioRenal and CVCT. Dr Mebazaa received honoraria for lectures from Roche and Abbott, consultation fees from Sanofi and Servier, and research grants from Adrenomed and Sphyngotec. Dr Ballantyne is the coinventor on a provisional patent (patent 61721475) entitled Biomarkers to Improve Prediction of Heart Failure Risk filed by Roche and Baylor College of Medicine on their behalf. Dr Ballantyne has received grant support from Abbott Diagnostics and Roche Diagnostics and is a consultant for Roche Diagnostics and Abbott Diagnostics. The other authors report no conflicts.
Funding Information:
The research leading to these results has received funding from the European Union Commission’s Seventh Framework Programme under grant agreement 305507 (HOMAGE [Heart Omics in Ageing consortium]). The authors acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with the support of the Dutch Heart Foundation CVON2016-Early HFPEF, and CVON 2017, ShePREDICTS.
Publisher Copyright:
© 2023 The Authors.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - 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.
AB - 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.
KW - biomarkers
KW - cardiovascular diseases
KW - heart failure
KW - protein interaction maps
KW - proteomics
U2 - 10.1161/CIRCHEARTFAILURE.122.009694
DO - 10.1161/CIRCHEARTFAILURE.122.009694
M3 - Article
C2 - 37192292
SN - 1941-3289
VL - 16
SP - 426
EP - 441
JO - Circulation-Heart Failure
JF - Circulation-Heart Failure
IS - 5
M1 - e009694
ER -