Association Between Clonal Hematopoiesis and Cardiometabolic Disease: A Systematic Review and Meta-Analysis.

BACKGROUND

Clonal hematopoiesis (CH) is the age-related expansion of hematopoietic stem cells. CH encompasses mosaic chromosomal alterations or somatic mutations in leukemia-driver genes (CH of indeterminate potential). Although CH has been associated with overall mortality, driven largely by cardiovascular disease, its links to individual cardiometabolic endpoints remain unclear.

OBJECTIVES

The aims of this study were to systematically quantify the associations of CH with incident myocardial infarction, stroke, cardiovascular mortality, and type 2 diabetes and to assess whether these associations differ according to CH driver gene.

METHODS

MEDLINE, Embase, Cochrane, and CENTRAL were searched from inception through June 2025 for observational studies reporting age-adjusted associations between CH and cardiometabolic outcomes in adults. Animal and phenome-wide association studies were excluded. Using random-effects models, HRs were generated for primary outcomes. The risk for bias was assessed using the Newcastle-Ottawa Scale.

RESULTS

Eighteen studies encompassing more than 650,000 individuals were included, with 1 study of participants with hematological malignancy. CH was associated with increased incidence of myocardial infarction (HR: 1.14; 95% CI: 1.00-1.29), stroke (HR: 1.12; 95% CI: 1.03-1.23), cardiovascular mortality (HR: 1.20; 95% CI: 1.07-1.36), and type 2 diabetes (HR: 1.20; 95% CI: 1.02-1.41). In driver gene analyses, TET2 mutations were associated with a higher hazard of stroke (HR: 1.41; 95% CI: 1.03-1.93) and ASXL1 mutations with cardiovascular mortality (HR: 2.22; 95% CI: 1.37-3.60).

CONCLUSIONS

CH is associated with cardiometabolic outcomes and may exhibit heterogeneity across mutations and clinical phenotypes, supporting its role as a somatic genomic marker of cardiometabolic risk. However, cautious interpretation and further study are required, as CH definitions were heterogeneous. (Association of Clonal Hematopoiesis with Type 2 Diabetes and Cardiovascular Disease: A Systematic Review and Meta Analysis; CRD420251156288).