Clonal Hematopoiesis: Somatic Mutations in Blood Cells and Atherosclerosis

Abstract

The most important prognostic factor for atherosclerotic cardiovascular disease is age, independent of all other recognized risk factors. Recently, exome sequence analyses showed that somatic mutations in blood cells, a process termed clonal hematopoiesis, are common and increase in prevalence with age, with at least 1 in 10 adults older than 70 years affected. Carriers of clonal hematopoiesis have been shown to be not only at heightened risk for hematologic malignancy but also at increased risk for atherosclerotic cardiovascular disease. Here, we review the prior literature of clonal selection and expansion of hematopoietic stem cells and the evidence supporting its causal association with atherosclerotic cardiovascular disease.

Keywords: blood cell; clonal evolution; coronary artery disease; genetics; hematologic neoplasms; hematopoiesis; human.

Figure 1. Sequential model of clonal hematopoiesis

A sequential model of progression from normal hematopoiesis to clonal hematopoiesis.

Figure 2. Prevalence of clonal hematopoiesis of indeterminate potential by age

Clonal hematopoiesis of indeterminate potential prevalence by age detected by exome sequencing of blood-derived DNA in three studies of individuals without hematologic malignancy.^{, ,} Shaded areas represent 95% confidence intervals. Adapted from Jan M et al.

Figure 3. Inflammatory mediators of clonal hematopoiesis influencing atherosclerosis

Summary of inflammatory factors observed to be upregulated in Jaiswal et al and Fuster et al and proposed influences on atherosclerosis plaque formation and destabilization.