The Clinical Challenge of Clonal Hematopoiesis, a Newly Recognized Cardiovascular Risk Factor

Importance: Despite current standards of cardiovascular care, a considerable residual burden of risk remains in both primary and secondary prevention. Clonal hematopoiesis of indeterminate potential (CHIP) has recently emerged as a common, potent, age-associated, independent risk factor for myocardial infarction, stroke, heart failure events, and survival following percutaneous aortic valve intervention. The presence of CHIP results from the acquisition of somatic mutations in a small number of leukemia driver genes found in bone marrow stem cells, leading to the expansion of leukocytes clones in peripheral blood. The association between CHIP and cardiovascular disease likely involves activation of the inflammasome pathway. More common DNA sequencing identifies individuals with CHIP who then seek advice regarding management of their cardiovascular risk. Observations: Using clinical vignettes based on real encounters, we highlight some of the diverse presentations of CHIP, ranging from incidental identification to that detected during cancer care, that have brought patients to the attention of cardiovascular practitioners. We illustrate how we have applied a consensus-based approach to the evaluation and management of cardiovascular risk in specific patients with CHIP. Since we currently lack evidence to guide the management of these individuals, we must rely on expert opinion while awaiting data to furnish a firmer foundation for our recommendations. Conclusions and Relevance: These vignettes illustrate that the management of CHIP should involve an individualized plan based on features such as comorbidities, life expectancy, and other traditional cardiovascular risk factors. Because individuals with CHIP will increasingly seek advice from cardiovascular specialists regarding management, these examples provide a template for approaches based on a multidisciplinary perspective. The current need for reliance on expert opinion illustrates a great need for further investigation into the management of this newly recognized contributor to residual cardiovascular risk, both in patients who are apparently well and those with established cardiovascular or malignant disease..