Clonal Hematopoiesis: Crossroads of Aging, Cardiovascular Disease, and Cancer: JACC Review Topic of the Week

Abstract

A novel, common, and potent cardiovascular risk factor has recently emerged: clonal hematopoiesis of indeterminate potential (CHIP). CHIP arises from somatic mutations in hematopoietic stem cells that yield clonal progeny of mutant leukocytes in blood. Individuals with CHIP have a doubled risk of coronary heart disease and ischemic stroke, and worsened heart failure outcomes independent of traditional cardiovascular risk factors. The recognition of CHIP as a nontraditional risk factor challenges specialists in hematology/oncology and cardiovascular medicine alike. Should we screen for CHIP? If so, in whom? How should we assess cardiovascular risk in people with CHIP? How should we manage the excess cardiovascular risk in the absence of an evidence base? This review explains CHIP, explores the clinical quandaries, strives to provide reasonable recommendations for the multidisciplinary management of cardiovascular risk in individuals with CHIP, and highlights current knowledge gaps.

Keywords: cancer; cardio-oncology; cardiovascular risk; leukemia; leukocyte.

Figure 1:. Pathways to the Diagnosis of CHIP.

The detection of CHIP can arise through several portals: ranging from an incidental finding in apparently well individuals, to patients with known malignancy. This diversity of presentations highlights the need for multidisciplinary approaches to the counseling and management of individuals found to bear CHIP mutations by physicians of different specialties.

Figure 2:. Proposed Clinical Algorithm for Primary Prevention of Cardiovascular Disease in Patients with Clonal Hematopoiesis.

We propose the following pathway for management of individuals with CHIP. We lack an evidence base for such recommendations, as recognition of the relationship between CHIP and cardiovascular disease has only recently become apparent. Yet, clinicians must be able to offer assistance and counseling to CHIP carriers while building a body of evidence.

Central Illustration:. Clonal hematopoiesis: a potent newly recognized risk factor for atherothrombosis and adverse heart failure outcomes.

A mutation in a hematopoietic stem cell in the bone marrow confers a proliferative advantage that yields a clone of mutant leukocytes (top panel) that appear in peripheral blood (middle panel). The presence of these clones in blood associates with a heightened risk of atherothrombotic events and with worsened outcomes in patients predisposed to ischemic cardiomyopathy (lower panel, left). Individuals with CHIP transition to acute leukemia only at an annual rate of 0.5-1% (lower panel, left) Thus, for an individual, CHIP may entail a greater risk of cardiovascular events than for cancer.