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

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.

Automated summary

Ageing is a significant risk factor for the development of cardiovascular disease and cancer. Clonal haematopoiesis of indeterminant potential (CHIP) is identified as an additional key risk factor, involving accumulation of potentially pro-leukaemic gene mutations within haematopoietic stem cells. CHIP carriers have a low risk of haematological malignant transformation, but exhibit a 40% increased relative risk of mortality due to excess cardiovascular events. The role of inflammation in linking CHIP, atherosclerotic disease, and heart failure, particularly heart failure with preserved ejection fraction (HFpEF), is increasingly recognized.