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

• Published in: European journal of heart failure 2023-01, Vol.25 (1), p.4-13
• Main Authors: Shi, Canxia, Aboumsallem, Joseph Pierre, Suthahar, Navin, Graaf, Aniek O., Jansen, Joop H., Zeventer, Isabelle A., Bracun, Valentina, Wit, Sanne, Screever, Elles M., Berg, Pieter F., Meijers, Wouter C., Gansevoort, Ron T., Bakker, Stephan J.L., der Harst, Pim, Silljé, Herman H.W., Huls, Gerwin, Boer, Rudolf A.
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers; CHIP; Clonal haematopoiesis; Clonal Hematopoiesis; Female; Heart failure; Heart Failure - epidemiology; Heart Failure - genetics; Humans; Incidence; Male; Middle Aged; Pathophysiology; Prospective Studies; Risk Factors
• ISSN: 1388-9842; 1879-0844
• DOI: 10.1002/ejhf.2715

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