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Review
. 2021 Apr 16;135(7):991-1007.
doi: 10.1042/CS20200306.

Clonal haematopoiesis of indeterminate potential: intersections between inflammation, vascular disease and heart failure

Leanne Mooney  1 , Carl S Goodyear  2 , Tamir Chandra  3 , Kristina Kirschner  4 , Mhairi Copland  4 , Mark C Petrie  1 , Ninian N Lang  1
Affiliations
Review

Clonal haematopoiesis of indeterminate potential: intersections between inflammation, vascular disease and heart failure

Leanne Mooney et al. Clin Sci (Lond). .

Abstract

Ageing is a major risk factor for the development of cardiovascular disease (CVD) and cancer. Whilst the cumulative effect of exposure to conventional cardiovascular risk factors is important, recent evidence highlights clonal haematopoiesis of indeterminant potential (CHIP) as a further key risk factor. CHIP reflects the accumulation of somatic, potentially pro-leukaemic gene mutations within haematopoietic stem cells over time. The most common mutations associated with CHIP and CVD occur in genes that also play central roles in the regulation of inflammation. While CHIP carriers have a low risk of haematological malignant transformation (<1% per year), their relative risk of mortality is increased by 40% and this reflects an excess of cardiovascular events. Evidence linking CHIP, inflammation and atherosclerotic disease has recently become better defined. However, there is a paucity of information about the role of CHIP in the development and progression of heart failure, particularly heart failure with preserved ejection fraction (HFpEF). While systemic inflammation plays a role in the pathophysiology of both heart failure with reduced and preserved ejection fraction (EF), it may be of greater relevance in the pathophysiology of HFpEF, which is also strongly associated with ageing. This review describes CHIP and its pathogenetic links with ageing, inflammation and CVD, while providing insight into its putative role in HFpEF.

Keywords: ageing; atherosclerosis; cardiovascular disease; clonal haematopoiesis of indeterminate potential; heart failure.

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Conflict of interest statement

C.G. has received research funding from AstraZeneca, Bristol-Myers Squibb, ISTESSO, Eli-Lilly, MedAnnex, Pfizer and UCB. C.G. is/has been an advisory board member for Bristol-Myers Squibb, MedAnnex, Medincell and Pfizer and has received honoraria from Abbvie and Bristol-Myers Squibb. M.C.P. has received research funding from Novartis, Bristol-Myers Squibb, Cyclacel and Takeda/Incyte, is/has been an advisory board member for Bristol-Myers Squibb, Novartis, Incyte, Daiichi Sankyo, Jazz and Pfizer and has received honoraria from Astellas, Bristol-Myers Squibb, Novartis, Incyte, Pfizer and Gilead. M.C.P. has received research grants or consultancy fees from SQ Innovations, AstraZeneca, Roche, Boehringer Ingelheim, Eli Lilly, Napp Pharmaceuticals, Novartis, and Novo Nordisk and has served on clinical events committees for AbbVie, Alnylam, Astra Zeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Resverlogix, and Novo Nordisk. N.N.L. has received research funding from Roche Diagnostics, Bristol-Myers Squibb, is/has been an advisory board member for Vifor Pharma, Pharmacosmos and has received honoraria from Roche Diagnostics, Takeda, Pfizer and Novartis.

Figures

Figure 1
Figure 1. Development of clonal haematopoiesis, associated risk factors and its role in heart failure (murine and humans)
Abbreviations: HSC, haematopoietic stem cells; EF, ejection fraction; FS, fractional shortening; HFH, heart failure hospitalisation; HFrEF, heart failure with reduced ejection fraction; KO, knockout; LAD, left anterior descending artery; NT-proBNP, B-type natriuretic peptide; TAC, transverse aortic constriction.
Figure 2
Figure 2. Potential mechanistic links between CHIP and HFpEF
Abbreviations: CKD, chronic kidney disease; HFpEF, heart failure with preserved ejection fraction; IL-6, interleukin-6; IL-18, interleukin 18; IL-1β, interleukin-1β.
Figure 3
Figure 3. CHIP and future research
See this image and copyright information in PMC

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