Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Disease

The purpose of this review article is to summarize the preclinical and clinical evidence supporting the notion of clonal hematopoiesis of indeterminate potential (CHIP), highlight current knowledge gap, and provide future directions. Epidemiological studies show that advanced age is a major risk factor for the development of cardiovascular disease (CVD) and cancer, the two leading causes of morbidity and mortality worldwide. While the negative effect of aging on CVD is a reflection of cumulative exposure to various established traditional CVD risk factors, genetic sequencing of whole blood–derived DNA recently revealed that clonal mutations in myeloid stem cells are associated with higher risks of cardiovascular events and hematopoietic malignancies. The clinical repercussions of this biological state, termed CHIP, are increasingly appreciated. Historically, CHIP has been associated with an increased risk of hematological malignancies. However, new research is showing that CHIP is also associated with an increased risk of several cardiac-related conditions, including atherosclerosis, myocardial infarction, aortic valve stenosis, and congestive heart failure. CHIP is increasingly being appreciated worldwide as a CVD risk factor, and further studies are needed to better understand the complex relationship between these two disorders.