Clonal haematopoiesis in cardiovascular disease: prognostic role and novel therapeutic target

Abstract

Clonal haematopoiesis is the clonal expansion of blood stem cells with acquired mutations. Clonal haematopoiesis of indeterminate potential (CHIP), traditionally defined as clonal haematopoiesis driven by a pre-leukaemic mutation in at least 2% of sequenced alleles, affects 10–20% of individuals aged >70 years. Although CHIP is considered a precursor condition for haematological malignancies, population-based data suggest that the majority of CHIP-associated mortality is attributable to non-malignant conditions, such as cardiovascular disease. Observational human studies have shown that CHIP is a strong and independent predictor of the onset and progression of atherosclerotic cardiovascular disease, heart failure and arrhythmia. In addition, findings from animal experiments suggest that CHIP is causally involved in these diseases and might be a risk factor that can be targeted with therapeutics. As our understanding of the cardiovascular implications of CHIP and other types of clonal haematopoiesis rapidly expands, it has become increasingly clear that clonal haematopoiesis subtypes have substantial heterogeneity with respect to magnitude of effect and underlying mechanisms for different cardiovascular diseases. In this Review, we discuss clonal haematopoiesis as a prognostic factor for numerous cardiovascular diseases, highlight its potential as a therapeutic target and propose a potential role for CHIP in cardiovascular precision medicine.