Association of Diet Quality With Prevalence of Clonal Hematopoiesis and Adverse Cardiovascular Events
TL;DR: In this article, the authors examined whether there is an association between diet quality and the prevalence of clonal hematopoiesis of indeterminate potential (CHIP), the expansion of somatic leukemogenic variations in hepatopoietic stem cells, has been associated with atherosclerotic cardiovascular disease.
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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TL;DR: A review of the cellular and molecular mechanisms underlying ageing in the regenerative regions of different tissues as well as potential rejuvenation strategies is presented in this paper , focusing primarily on brain, muscle and blood tissues.
Abstract: Most adult organs contain regenerative stem cells, often organized in specific niches. Stem cell function is critical for tissue homeostasis and repair upon injury, and it is dependent on interactions with the niche. During ageing, stem cells decline in their regenerative potential and ability to give rise to differentiated cells in the tissue, which is associated with a deterioration of tissue integrity and health. Ageing-associated changes in regenerative tissue regions include defects in maintenance of stem cell quiescence, differentiation ability and bias, clonal expansion and infiltration of immune cells in the niche. In this Review, we discuss cellular and molecular mechanisms underlying ageing in the regenerative regions of different tissues as well as potential rejuvenation strategies. We focus primarily on brain, muscle and blood tissues, but also provide examples from other tissues, such as skin and intestine. We describe the complex interactions between different cell types, non-cell-autonomous mechanisms between ageing niches and stem cells, and the influence of systemic factors. We also compare different interventions for the rejuvenation of old regenerative regions. Future outlooks in the field of stem cell ageing are discussed, including strategies to counter ageing and age-dependent disease. Stem cell function declines during ageing, resulting in the loss of tissue integrity and health deterioration. Ageing is associated with defects in the maintenance of stem cell quiescence and cell differentiation ability, clonal expansion and infiltration of immune cells in the niche. This Review discusses the mechanisms underlying ageing in stem cells and their niches, and potential rejuvenation strategies.
48 citations
TL;DR: In this paper , the authors investigated the joint effects of habitual physical activity (PA) and long-term fine particulate matter (PM2.5) exposure on COPD incidence in a prospective population-based cohort.
Abstract: The combined health impact of physical activity (PA) and air pollution on chronic obstructive pulmonary disease (COPD) remains unclear. We investigated the joint effects of habitual PA and long-term fine particulate matter (PM2.5) exposure on COPD incidence in a prospective population-based cohort.A prospective cohort study was conducted using data from the UK Biobank. Incidence of COPD was ascertained through linkage to the UK National Health Services register. Annual mean PM2.5 concentration was obtained using land use regression model. PA was measured by questionnaire and wrist-worn accelerometer. Cox proportional hazard models were applied to examine the associations between PM2.5, PA, and COPD. Additive and multiplicative interactions were examined.A total of 266,280 participants free of COPD at baseline were included in data analysis with an average follow-up of 10.64 years, contributing to around 2.8 million person-years. Compared with participants with low level of PA, those with higher PA levels had lower risks of COPD incidence [hazard ratio (HR): 0.769, 95% CI: 0.720, 0.820 for moderate level; HR: 0.726, 95% CI: 0.679, 0.776 for high level]. By contrast, PM2.5 was associated with increased risk of COPD (HR per interquartile range increment: 1.065, 95% CI: 1.032, 1.099). Limited evidence of interaction between habitual PA and PM2.5 exposure was found. Similar results were found for accelerometer-measured PA.Our study suggests that habitual PA could reduce risk of COPD incidence, and such protective effects were not affected by ambient PM2.5 pollution exposure.
20 citations
TL;DR: The Mediterranean diet has emerged as a comprehensive lifestyle, including specific foods and meal composition and a set of behavioural and social features, that has been shown to promote health and reduce the prevalence of chronic diseases.
Abstract: The Mediterranean diet has emerged as a comprehensive lifestyle, including specific foods and meal composition and a set of behavioural and social features. Adherence to the Mediterranean diet has been shown to promote health and reduce the prevalence of chronic diseases. The actual implementation of the Mediterranean diet is affected by several sociocultural factors as well as geographical components. Indeed, the geographical location, such as a specific country or different areas in a country and specific latitude and climate, appears to be an important factor that may strongly affect the implementation of the Mediterranean diet or some of its principles as well as the adherence to it. Another dynamic component affecting personal nutritional choices, also regarding adherence to the Mediterranean diet and its principles, is the individual life-long trajectory of food preference and nutrition habits and awareness. In this review, we discuss the current evidence on the impact of geographical location on adherence to the Mediterranean diet.
14 citations
TL;DR: In this article , the association of healthy sleep pattern with the risk of cardiovascular disease and all-cause mortality among people with diabetes has been assessed by using Royston-Parmar proportion-hazard models.
11 citations
TL;DR: The cellular effectors and molecular signals across multi-organ systems, which regulate the inflammatory and reparative responses after myocardial infarction are discussed.
Abstract: Despite recent scientific and technological advances, myocardial infarction (MI) still represents a major global health problem, leading to high morbidity and mortality worldwide. During the post-MI wound healing process, dysregulated immune inflammatory pathways and failure to resolve inflammation are associated with maladaptive left ventricular remodeling, progressive heart failure, and eventually poor outcomes. Given the roles of immune cells in the host response against tissue injury, understanding the involved cellular subsets, sources, and functions is essential for discovering novel therapeutic strategies that preserve the protective immune system and promote optimal healing. This review discusses the cellular effectors and molecular signals across multi-organ systems, which regulate the inflammatory and reparative responses after MI. Additionally, we summarize the recent clinical and preclinical data that propel conceptual revolutions in cardiovascular immunotherapy.
10 citations
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TL;DR: New insights into inflammation in atherosclerosis not only increase the understanding of this disease, but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance.
Abstract: Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an ongoing inflammatory response. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and, ultimately, the thrombotic complications of atherosclerosis. These new findings provide important links between risk factors and the mechanisms of atherogenesis. Clinical studies have shown that this emerging biology of inflammation in atherosclerosis applies directly to human patients. Elevation in markers of inflammation predicts outcomes of patients with acute coronary syndromes, independently of myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker C-reactive protein, prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors. Moreover, certain treatments that reduce coronary risk also limit inflammation. In the case of lipid lowering with statins, this anti-inflammatory effect does not appear to correlate with reduction in low-density lipoprotein levels. These new insights into inflammation in atherosclerosis not only increase our understanding of this disease, but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance.
7,116 citations
TL;DR: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates, and there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries.
5,802 citations
TL;DR: This year's edition of the Statistical Update includes data on the monitoring and benefits of cardiovascular health in the population, metrics to assess and monitor healthy diets, an enhanced focus on social determinants of health, a focus on the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors, implementation strategies, and implications of the American Heart Association’s 2020 Impact Goals.
Abstract: Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports on the most up-to-date statistics related to heart disease, stroke, and cardiovas...
5,078 citations
TL;DR: Deep phenotype and genome-wide genetic data from 500,000 individuals from the UK Biobank is described, describing population structure and relatedness in the cohort, and imputation to increase the number of testable variants to 96 million.
Abstract: The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
4,489 citations
Broad Institute1, Harvard University2, Hannover Medical School3, Minerva Foundation Institute for Medical Research4, University of Helsinki5, University of Southern California6, National Institutes of Health7, National Institute for Health and Welfare8, University of Mississippi Medical Center9, University of Mississippi10, Massachusetts Institute of Technology11, University of Michigan12, University of Oxford13, Danube University Krems14, King Abdulaziz University15, Albert Einstein College of Medicine16
TL;DR: Age-related clonal hematopoiesis is a common condition that is associated with increases in the risk of hematologic cancer and in all-cause mortality, with the latter possibly due to an increased risk of cardiovascular disease.
Abstract: Background The incidence of hematologic cancers increases with age. These cancers are associated with recurrent somatic mutations in specific genes. We hypothesized that such mutations would be detectable in the blood of some persons who are not known to have hematologic disorders. Methods We analyzed whole-exome sequencing data from DNA in the peripheral-blood cells of 17,182 persons who were unselected for hematologic phenotypes. We looked for somatic mutations by identifying previously characterized single-nucleotide variants and small insertions or deletions in 160 genes that are recurrently mutated in hematologic cancers. The presence of mutations was analyzed for an association with hematologic phenotypes, survival, and cardiovascular events. Results Detectable somatic mutations were rare in persons younger than 40 years of age but rose appreciably in frequency with age. Among persons 70 to 79 years of age, 80 to 89 years of age, and 90 to 108 years of age, these clonal mutations were observed in 9.5% (219 of 2300 persons), 11.7% (37 of 317), and 18.4% (19 of 103), respectively. The majority of the variants occurred in three genes: DNMT3A, TET2, and ASXL1. The presence of a somatic mutation was associated with an increase in the risk of hematologic cancer (hazard ratio, 11.1; 95% confidence interval [CI], 3.9 to 32.6), an increase in all-cause mortality (hazard ratio, 1.4; 95% CI, 1.1 to 1.8), and increases in the risks of incident coronary heart disease (hazard ratio, 2.0; 95% CI, 1.2 to 3.4) and ischemic stroke (hazard ratio, 2.6; 95% CI, 1.4 to 4.8). Conclusions Age-related clonal hematopoiesis is a common condition that is associated with increases in the risk of hematologic cancer and in all-cause mortality, with the latter possibly due to an increased risk of cardiovascular disease. (Funded by the National Institutes of Health and others.)
3,183 citations