Analysis of the effects of statin therapy on clonal dynamics in clonal haematopoiesis of indeterminate potential: insights from the English Longitudinal Study of Ageing.

Clonal haematopoiesis of indeterminate potential (CHIP) is the acquisition of somatic mutations in leukaemia-associated genes in haematopoietic progenitors with age. It increases the risk of haematological malignancy (HM), cardiovascular disease (CVD) and mortality mediated by CHIP-associated inflammation, with larger clones posing higher risks. Statins have been found to reduce the risk of progression from myelodysplastic syndrome to acute myeloid leukaemia and have also shown efficacy in vitro against TET2 deficient AML cell lines. However, their effect on CHIP has not been described. This study characterises the English Longitudinal Study of Ageing as a novel longitudinal CHIP cohort, through genetic analysis of 13270 longitudinal peripheral blood samples from participants aged over 50. Using logistic and robust regression analysis, we show that statin therapy is associated with reduced TET2 CHIP clonal expansion in a gene specific manner. We also find that statin primary prevention is associated with significantly lower incidence of myocardial infarction and stroke in individuals with CHIP compared to controls. These findings provide evidence that a commonly prescribed mediation with a well characterised safety profile may modify the natural history of TET2 CHIP, thereby mitigating its associated health risks.