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Original Investigation
June 9, 2021

Association of Diet Quality With Prevalence of Clonal Hematopoiesis and Adverse Cardiovascular Events

Author Affiliations
  • 1Cardiovascular Research Center, Massachusetts General Hospital, Boston
  • 2Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, Massachusetts
  • 3Department of Medicine, Harvard Medical School, Boston, Massachusetts
  • 4Cardiovascular Research Center, Massachusetts General Hospital, Boston
  • 5Yale School of Medicine, New Haven, Connecticut
  • 6Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
  • 7Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts
  • 8Epigenomics Program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts
  • 9Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 10Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
JAMA Cardiol. Published online June 9, 2021. doi:10.1001/jamacardio.2021.1678
Key Points

Question  Is an unhealthy diet associated with clonal hematopoiesis of indeterminate potential, and are they together associated with an increased risk of adverse cardiovascular events?

Findings  In this cohort study of 44 111 adult participants in the UK Biobank, an unhealthy diet was independently associated with a 25% increased likelihood of the presence of clonal hematopoiesis of indeterminate potential and increases in adverse cardiovascular events and death.

Meaning  The results of this study suggest that unhealthy eating habits may be associated with the development of clonal hematopoiesis of indeterminate potential as well as substantially increased risk of adverse cardiovascular events and death.

Abstract

Importance  Clonal hematopoiesis of indeterminate potential (CHIP), the expansion of somatic leukemogenic variations in hematopoietic stem cells, has been associated with atherosclerotic cardiovascular disease. Because the inherited risk of developing CHIP is low, lifestyle elements such as dietary factors may be associated with the development and outcomes of CHIP.

Objective  To examine whether there is an association between diet quality and the prevalence of CHIP.

Design, Setting, and Participants  This retrospective cohort study used data from participants in the UK Biobank, an ongoing population-based study in the United Kingdom that examines whole-exome sequencing data and survey-based information on health-associated behaviors. Individuals from the UK Biobank were recruited between 2006 and 2010 and followed up prospectively with linkage to health data records through May 2020. The present study included 44 111 participants in the UK Biobank who were age 40 to 70 years, had data available from whole-exome sequencing of blood DNA, and were free of coronary artery disease (CAD) or hematologic cancer at baseline.

Exposures  Diet quality was categorized as unhealthy if the intake of healthy elements (fruits and vegetables) was lower than the median of all survey responses, and the intake of unhealthy elements (red meat, processed food, and added salt) was higher than the median. Diets were classified as healthy if the intake of healthy elements was higher than the median, and the intake of unhealthy elements was lower than the median. The presence of CHIP was detected by data from whole-exome sequencing of blood DNA.

Main Outcomes and Measures  The primary outcome was CHIP prevalence. Multivariable logistic regression analysis was used to examine the association between diet quality and the presence of CHIP. Multivariable Cox proportional hazards models were used to assess the association of incident events (acute coronary syndromes, coronary revascularization, or death) in each diet quality category stratified by the presence of CHIP.

Results  Among 44 111 participants (mean [SD] age at time of blood sample collection, 56.3 [8.0] years; 24 507 women [55.6%]), 2271 individuals (5.1%) had an unhealthy diet, 38 552 individuals (87.4%) had an intermediate diet, and 3288 individuals (7.5%) had a healthy diet. A total of 2507 individuals (5.7%) had CHIP, and the prevalence of CHIP decreased as diet quality improved from unhealthy (162 of 2271 participants [7.1%]) to intermediate (2177 of 38 552 participants [5.7%]) to healthy (168 of 3288 participants [5.1%]; P = .003 for trend). Compared with individuals without CHIP who had an intermediate diet, the rates of incident cardiovascular events progressively decreased among those with CHIP who had an unhealthy diet (hazard ratio [HR], 1.52; 95% CI, 1.04-2.22) and those with CHIP who had a healthy diet (HR, 0.99; 95% CI, 0.62-1.58) over a median of 10.0 years (interquartile range, 9.6-10.4 years) of follow-up.

Conclusions and Relevance  This cohort study suggests that an unhealthy diet quality may be associated with a higher prevalence of CHIP and higher rates of adverse cardiovascular events and death independent of CHIP status.

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