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Emerging Science for the Clinician
March 13, 2019

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

Author Affiliations
  • 1Ted Rogers Program in Cardiotoxicity Prevention, Toronto General Hospital, Toronto, Ontario, Canada
  • 2Instituto Nacional de Cancerología, Mexico City, Mexico
  • 3Department of Pathology, Stanford University School of Medicine, Stanford, California
  • 4Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
  • 5Division of Cardiovascular Medicine, Cardio-oncology Program, Vanderbilt University Medical Center, Nashville, Tennessee
  • 6Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
  • 7Princess Margaret Cancer Center, Toronto, Ontario, Canada
  • 8MedStar Heart and Vascular Institute, Georgetown University, Washington, DC
JAMA Cardiol. 2019;4(4):380-387. doi:10.1001/jamacardio.2019.0302

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.

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