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

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.

[1]  J. Manson,et al.  Healthy Lifestyle and Clonal Hematopoiesis of Indeterminate Potential: Results From the Women's Health Initiative , 2021, Journal of the American Heart Association.

[2]  J. Manson,et al.  Dietary Inflammatory Potential and Risk of Cardiovascular Disease Among Men and Women in the U.S. , 2020, Journal of the American College of Cardiology.

[3]  Stuart M. Gardos,et al.  Cancer therapy shapes the fitness landscape of clonal hematopoiesis , 2020, Nature Genetics.

[4]  J. Manson,et al.  Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women , 2020, Circulation.

[5]  Alexander E. Lopez,et al.  Exome sequencing and characterization of 49,960 individuals in the UK Biobank , 2020, Nature.

[6]  P. Ciais,et al.  Country-Level Relationships of the Human Intake of N and P, Animal and Vegetable Food, and Alcoholic Beverages with Cancer and Life Expectancy , 2020, International journal of environmental research and public health.

[7]  Eun Sug Park,et al.  Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019 , 2020, Lancet.

[8]  Ivana V. Yang,et al.  Inherited Causes of Clonal Hematopoiesis in 97,691 TOPMed Whole Genomes , 2020, Nature.

[9]  A. Khera,et al.  Genome-Wide Polygenic Score, Clinical Risk Factors, and Long-Term Trajectories of Coronary Artery Disease , 2020, Arteriosclerosis, thrombosis, and vascular biology.

[10]  L. Keaver,et al.  Plant- and animal-based diet quality and mortality among US adults: a cohort study , 2020, British Journal of Nutrition.

[11]  Sarah S. Burns,et al.  Putative Mechanisms Underlying Cardiovascular Disease Associated with Clonal Hematopoiesis of Indeterminate Potential , 2020, Stem cell reports.

[12]  A. Zeiher,et al.  Association of Clonal Hematopoiesis of Indeterminate Potential With Inflammatory Gene Expression in Patients With Severe Degenerative Aortic Valve Stenosis or Chronic Postischemic Heart Failure. , 2020, JAMA cardiology.

[13]  P. Libby,et al.  The Clinical Challenge of Clonal Hematopoiesis, a Newly Recognized Cardiovascular Risk Factor. , 2020, JAMA cardiology.

[14]  T. Druley,et al.  The evolutionary dynamics and fitness landscape of clonal hematopoiesis , 2020, Science.

[15]  Francesca N. Delling,et al.  Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association , 2020, Circulation.

[16]  M. Goodell,et al.  Environmental Influences on Clonal Hematopoiesis. , 2019, Experimental hematology.

[17]  S. Gabriel,et al.  Genetic Interleukin 6 Signaling Deficiency Attenuates Cardiovascular Risk in Clonal Hematopoiesis , 2019, Circulation.

[18]  B. Ebert,et al.  Clonal hematopoiesis in human aging and disease , 2019, Science.

[19]  M. Ratajczak,et al.  An Overview of Novel Unconventional Mechanisms of Hematopoietic Development and Regulators of Hematopoiesis – a Roadmap for Future Investigations , 2019, Stem Cell Reviews and Reports.

[20]  S. Kathiresan,et al.  Clonal Hematopoiesis of Indeterminate Potential Reshapes Age-Related CVD: JACC Review Topic of the Week. , 2019, Journal of the American College of Cardiology.

[21]  P. Elliott,et al.  Validation of the Oxford WebQ Online 24-Hour Dietary Questionnaire Using Biomarkers , 2019, American journal of epidemiology.

[22]  Jennifer G. Robinson,et al.  Influence of Cardiovascular Risk Communication Tools and Presentation Formats on Patient Perceptions and Preferences , 2018, JAMA cardiology.

[23]  Binita Shah,et al.  Anti‐Inflammatory Effects of a Vegan Diet Versus the American Heart Association–Recommended Diet in Coronary Artery Disease Trial , 2018, Journal of the American Heart Association.

[24]  P. Donnelly,et al.  The UK Biobank resource with deep phenotyping and genomic data , 2018, Nature.

[25]  S. Faghih,et al.  Substitution of red meat with soybean but not non- soy legumes improves inflammation in patients with type 2 diabetes; a randomized clinical trial , 2018, Journal of Diabetes & Metabolic Disorders.

[26]  L. Ferrucci,et al.  Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty , 2018, Nature Reviews Cardiology.

[27]  S. Kathiresan,et al.  Clonal Hematopoiesis: Somatic Mutations in Blood Cells and Atherosclerosis , 2018, Circulation. Genomic and precision medicine.

[28]  L. Wood,et al.  Effects of fruit and vegetable consumption on inflammatory biomarkers and immune cell populations: a systematic literature review and meta-analysis. , 2018, The American journal of clinical nutrition.

[29]  Vu Dinh,et al.  Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host , 2018, Nature.

[30]  M. Touvier,et al.  Red and processed meat intake and cancer risk: Results from the prospective NutriNet‐Santé cohort study , 2018, International journal of cancer.

[31]  R. Wells,et al.  An inflammatory environment containing TNFα favors Tet2-mutant clonal hematopoiesis. , 2017, Experimental hematology.

[32]  M. Ladanyi,et al.  Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes. , 2017, Cell stem cell.

[33]  O. Abdel-Wahab,et al.  Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression , 2017, Cell.

[34]  Kari Stefansson,et al.  Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. , 2017, Blood.

[35]  E. Rimm,et al.  Association of Changes in Diet Quality with Total and Cause‐Specific Mortality , 2017, The New England journal of medicine.

[36]  S. Gabriel,et al.  Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease , 2017, The New England journal of medicine.

[37]  V. Beneš,et al.  Vitamin A-Retinoic Acid Signaling Regulates Hematopoietic Stem Cell Dormancy , 2017, Cell.

[38]  W. Liao,et al.  Influence of diet on the gut microbiome and implications for human health , 2017, Journal of Translational Medicine.

[39]  Matthew A. Cooper,et al.  Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice , 2017, Science.

[40]  S. Armstrong,et al.  Myeloid progenitor cluster formation drives emergency and leukemic myelopoiesis , 2017, Nature.

[41]  E. Boerwinkle,et al.  Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. , 2016, The New England journal of medicine.

[42]  W. Goessling,et al.  Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production , 2016, Cell reports.

[43]  T. Druley,et al.  Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults , 2016, Nature Communications.

[44]  E. Pietras,et al.  Chronic interleukin-1 drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal , 2016, Nature Cell Biology.

[45]  A. Blaes,et al.  Shared Risk Factors in Cardiovascular Disease and Cancer , 2016, Circulation.

[46]  M. Nahrendorf,et al.  Lifestyle effects on hematopoiesis and atherosclerosis. , 2015, Circulation research.

[47]  M. McCarthy,et al.  Age-related clonal hematopoiesis associated with adverse outcomes. , 2014, The New England journal of medicine.

[48]  S. Gabriel,et al.  Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. , 2014, The New England journal of medicine.

[49]  Joshua F. McMichael,et al.  Age-related cancer mutations associated with clonal hematopoietic expansion , 2014, Nature Medicine.

[50]  D. Reid,et al.  Patterns of dietary intake and serum carotenoid and tocopherol status are associated with biomarkers of chronic low-grade systemic inflammation and cardiovascular risk , 2014, British Journal of Nutrition.

[51]  A. Subar,et al.  Higher diet quality is associated with decreased risk of all-cause, cardiovascular disease, and cancer mortality among older adults. , 2014, The Journal of nutrition.

[52]  R. B. Ruiz,et al.  Diet and cancer: risk factors and epidemiological evidence. , 2014 .

[53]  David A Sinclair,et al.  The intersection between aging and cardiovascular disease. , 2012, Circulation research.

[54]  Jennifer G. Robinson,et al.  The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis , 2012, The Lancet.

[55]  Elizabeth A Spencer,et al.  Development and evaluation of the Oxford WebQ, a low-cost, web-based method for assessment of previous 24 h dietary intakes in large-scale prospective studies , 2011, Public Health Nutrition.

[56]  A. Folsom,et al.  Community prevalence of ideal cardiovascular health, by the American Heart Association definition, and relationship with cardiovascular disease incidence. , 2011, Journal of the American College of Cardiology.

[57]  T. Jørgensen,et al.  The Dietary Quality Score: validation and association with cardiovascular risk factors: the Inter99 study , 2007, European Journal of Clinical Nutrition.

[58]  Antonio Ceriello,et al.  The effects of diet on inflammation: emphasis on the metabolic syndrome. , 2006, Journal of the American College of Cardiology.

[59]  Peter Libby,et al.  Inflammation and cardiovascular disease mechanisms. , 2006, The American journal of clinical nutrition.

[60]  W. Willett,et al.  Diet quality is associated with the risk of estrogen receptor-negative breast cancer in postmenopausal women. , 2006, The Journal of nutrition.

[61]  D. English,et al.  Red meat, chicken, and fish consumption and risk of colorectal cancer. , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[62]  Walter C Willett,et al.  Optimal diets for prevention of coronary heart disease. , 2002, JAMA.

[63]  E. Riboli,et al.  Meat consumption and colorectal cancer risk: Dose‐response meta‐analysis of epidemiological studies , 2002, International journal of cancer.

[64]  P. Libby,et al.  Inflammation and Atherosclerosis , 2002, Circulation.

[65]  C. la Vecchia,et al.  Red meat intake and cancer risk: A study in Italy , 2000, International journal of cancer.

[66]  B. Hedblad,et al.  A high quality diet is associated with reduced systemic inflammation in middle-aged individuals. , 2015, Atherosclerosis.