The role of clonal hematopoiesis of indeterminate potential as a potential driver of cardiovascular diseases and its association with clinical outcome

Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related phenomenon associated with gradual accumulation of somatic mutations and clonal expansion of the peripheral blood cells, mostly leukocytes. This leads to an altered leucocyte function and a pro-inflammatory shift. Inflammation is at the pathogenetic core of many cardiovascular diseases (CVD), including coronary artery disease (CAD) and atrial fibrillation (AF). Therefore, it is no wonder that CHIP is emerging as a previously unrecognized risk factor in the development and progression of CVD, in particular early-onset myocardial infarction (MI). Currently, it is not known whether CHIP-associated CAD has different manifestations and atherosclerotic plague development over time than non-CHIP related CAD. Moreover, although inflammation has been proven as an important factor for AF and dilated cardiomyopathy (DCM) development, CHIP has not been linked to these conditions yet. In the proposed project, we aim to examine the role of CHIP in the development and clinical outcomes of three most common CVD’s: CAD, AF, and DCM, by analyzing deeply phenotyped patient cohorts, as well as using large-scale population data from the UK biobank. In addition to a novel look on the role of CHIP in CVD’s, we will utilize an innovative CHIP detecting approach by analyzing not only the CHIP driver mutations, but also monitoring low-level mitochondrial DNA mutations.