Clonal haematopoiesis of indeterminate potential: associations with heart failure incidence, clinical parameters and biomarkers

Canxia Shi, Joseph Pierre Aboumsallem, Navin Suthahar, Aniek O. de Graaf, Joop H. Jansen, Isabelle A. van Zeventer, Valentina Bracun, Sanne de Wit, Elles M. Screever, Pieter F. van den Berg, Wouter C. Meijers, Ron T. Gansevoort, Stephan J.L. Bakker, Pim van der Harst, Herman H.W. Silljé, Gerwin Huls, Rudolf A. de Boer*

*Corresponding author for this work

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Abstract

Aim: We aimed to analyse the association of clonal haematopoiesis of indeterminate potential (CHIP) with incident heart failure (HF) in a European population cohort. Methods and results: From the prospective Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort, we included all 374 participants with incident HF and selected 1:1 age- and sex-matched control subjects. Peripheral blood samples of 705 individuals were successfully analysed by error-corrected next generation sequencing for acquired mutations at a variant allele frequency ≥2% in 27 CHIP driver genes. The median age of the study population was 65 years (interquartile range 58–70) and 35.6% were female. CHIP mutations positively correlated with age, smoking, hypertension and cardiovascular biomarkers including N-terminal pro-B-type natriuretic peptide and mid-regional pro-A-type natriuretic peptide, but the frequency of CHIP was comparable in individuals with incident HF and in control participants (18.4% vs. 17.3%; p = 0.69). In multivariable Cox regression models, CHIP was not significantly associated with incident HF (hazard ratio [HR] 1.24, 95% confidence interval [CI] 0.93–1.65; p = 0.144). This association, however, was modified by age (p for CHIP–age interaction = 0.002). Among people younger than 65 years, CHIP mutations were more frequently detected in the case cohort compared to the control cohort (14.2% vs. 5.8%; p = 0.009), and were significantly associated with new-onset HF (HR 2.07, 95% CI 1.30–3.29; p = 0.002). Conclusion: Clonal haematopoiesis of indeterminate potential correlates with HF risk factors and biomarkers, and is associated with incident HF in subjects <65 years of age.

Original languageEnglish
Pages (from-to)4-13
Number of pages10
JournalEuropean Journal of Heart Failure
Volume25
Issue number1
Early online date11 Oct 2022
DOIs
Publication statusPublished - Jan 2023

Bibliographical note

Funding Information:
This work was supported by grants from the Dutch Heart Foundation (CVON SHE‐PREDICTS‐HF; grant 2017‐21; CVON RED‐CVD; grant 2017‐11; CVON PREDICT2; grant 2018‐30; CVON DOUBLE DOSE; grant 2020B005), by a grant from the Leducq Foundation Cure PhosphoLambaN induced Cardiomyopathy (Cure‐PLaN), and by a grant from the European Research Council (ERC CoG 818715; SECRETE‐HF). Canxia Shi is supported by a scholarship from the China Scholarship Council (CSC number: 201806170057).

Funding:
This work was supported by grants from the Dutch Heart
Foundation (CVON SHE-PREDICTS-HF; grant 2017-21; CVON
RED-CVD; grant 2017-11; CVON PREDICT2; grant 2018-30;
CVON DOUBLE DOSE; grant 2020B005), by a grant from the
Leducq Foundation Cure PhosphoLambaN induced Cardiomyopathy (Cure-PLaN), and by a grant from the European Research
Council (ERC CoG 818715; SECRETE-HF). Canxia Shi is supported by a scholarship from the China Scholarship Council (CSC
number: 201806170057).
Conflict of interest: The UMCG, which employs Dr. de Boer has
received research grants and/or fees from AstraZeneca, Abbott,
Boehringer Ingelheim, Cardior Pharmaceuticals Gmbh, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche. Dr. de Boer received
speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and
Roche. All other authors have nothing to disclose.

Publisher Copyright:
© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

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