High-sensitivity C-reactive protein is associated with clonal hematopoiesis of indeterminate potential

Lambert Busque, Maxine Sun, Manuel Buscarlet, Sami Ayachi, Yassamin Feroz Zada, Sylvie Provost, Vincent Bourgoin, Luigina Mollica, Marlies Meisel, Reinhard Hinterleitner, Bana Jabri, Marie Pierre Dubé, Jean Claude Tardif

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50 Scopus citations


Clonal hematopoiesis of indeterminate potential (CHIP) is predictive of hematological cancers and cardiovascular diseases, but the etiology of CHIP initiation and clonal expansion is unknown. Several lines of evidence suggest that proinflammatory cytokines may favor mutated hematopoietic stem cell expansion. To investigate the potential link between inflammation and CHIP, we performed targeted deep sequencing of 11 genes previously implicated in CHIP in 1887 subjects aged >70 years from the Montreal Heart Institute Biobank, of which 1359 had prior coronary artery disease (CAD), and 528 controls did not. We assessed association of CHIP with log transformed high-sensitivity C-reactive protein (hs-CRP), a validated biomarker of inflammation. CHIP was identified in 427 of the 1887 subjects (22.6%). CHIP mutations were more frequently identified in DNMT3A (11.6%) and TET2 (6.1%), with a higher proportion of TET2 mutations occurring in controls than in patients with CAD (9.0% vs 4.9%, P < .001). CHIP carriers had 21% higher hs-CRP levels compared with their noncarrier counterparts (eβ 5 1.21, 95% confidence interval [CI]: 1.08 to 1.36; P 5 .001). A similar effect was observed in the subgroup of patients with known CAD (eβ 5 1.22, 95% CI: 1.06 to 1.41; P 5 .005). These findings confirm the association between inflammation and CHIP. This association may open investigational avenues aimed at documenting mechanisms linking inflammation to clonal progression and ultimately supports prevention interventions to attenuate CHIP's impact on cardiovascular disease and cancer.

Original languageEnglish
Pages (from-to)2430-2438
Number of pages9
JournalBlood advances
Issue number11
StatePublished - 9 Jun 2020
Externally publishedYes


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