Connections Between Clonal Hematopoiesis, Cardiovascular Disease, and Cancer A Review

Oscar Calvillo-Arguelles, Siddhartha Jaiswal, Liran I. Shlush, Javid J. Moslehi, Aaron Schimmer, Ana Barac, Paaladinesh Thavendiranathan*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

55 Citations (Scopus)

Abstract

IMPORTANCE Clonal hematopoiesis (CH) has been recently described as a novel driver for cancer and cardiovascular disease (CVD). Clonal hematopoiesis is a common, age-associated disorder marked by expansion of hematopoietic clones carrying recurrent somatic mutations. Current literature suggests that patients with CH have a higher risk of subsequent hematological malignant conditions and mortality attributable to excess CVD. This review discusses the association of cancer with CVD with CH as a potential unifying factor.

OBSERVATIONS The prevalence of CH varies based on the sequencing depth, diagnostic criteria, and patient age and ranges from less than 1% in those younger than 40 years to more than 15% to 20% in those 90 years and older. Clonal hematopoiesis is associated with a 0.5% to 1.0% absolute annual risk of hematological malignant condition and a 2-fold to 4-fold higher risk of coronary artery disease, stroke, and CVD deaths, independent of traditional cardiovascular risk factors. In fact, CH appears to have a relative risk similar to that of traditional cardiovascular risk factors for CVD. Experimental studies suggest that the link between CVD and CH is causal, with inflammation as 1 potential mechanism. There may be also a link between CH and CVD in survivors of cancer; however, data to support this association are currently limited.

CONCLUSIONS AND RELEVANCE Clonal hematopoiesis represents a premalignant state, with carriers having an increased risk of hematological malignant conditions. Although most carriers will not develop a malignant condition, CH confers an increased risk of CVD, possibly via inflammation. Clonal hematopoiesis may also contribute to CVD in survivors of cancer, although this hypothesis requires validation. Clinically, as advanced sequencing techniques become available, CH may pave the way for precision medicine in the field of cardio-oncology.

Original languageEnglish
Pages (from-to)380-387
Number of pages8
JournalJAMA Cardiology
Volume4
Issue number4
DOIs
Publication statusPublished - Apr 2019

Funding

Dr Moslehi’s salary was supported by National Institutes of Health grant R56 HL141466. Author Contributions: Dr Thavendiranathan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Calvillo-Argüelles, Jaiswal, Shlush, Schimmer, Thavendiranathan. Acquisition, analysis, or interpretation of data: Moslehi, Barac, Thavendiranathan. Drafting of the manuscript: Calvillo-Argüelles, Jaiswal, Schimmer, Thavendiranathan. Critical revision of the manuscript for important intellectual content: Calvillo-Argüelles, Shlush, Moslehi, Barac, Thavendiranathan. Administrative, technical, or material support: Thavendiranathan. Supervision: Shlush, Schimmer, Thavendiranathan.

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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