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Physical Activity-Related Metabolites Are Associated with Mortality: Findings from the Atherosclerosis Risk in Communities (ARIC) Study.

ABSTRACT: Habitual physical activity can diminish the risk of premature death. Identifying a pattern of metabolites related to physical activity may advance our understanding of disease etiology. We quantified 245 serum metabolites in 3802 participants from the Atherosclerosis Risk in Communities (ARIC) study using chromatography-mass spectrometry. We regressed self-reported moderate-to-vigorous intensity leisure-time physical activity (LTPA) against each metabolite, adjusting for traditional risk factors. A standardized metabolite risk score (MRS) was constructed to examine its association with all-cause mortality using the Cox proportional hazard model. We identified 10 metabolites associated with LTPA (p < 2.04 × 10^-4) and established that an increase of one unit of the metabolic equivalent of task-hours per week (MET·hr·wk^-1) in LTPA was associated with a 0.012 SD increase in MRS. During a median of 27.5 years of follow-up, we observed 1928 deaths. One SD increase of MRS was associated with a 10% lower risk of death (HR = 0.90, 95% CI: 0.85-0.95). The highest vs. the lowest MRS quintile rank was associated with a 22% reduced risk of death (HR = 0.78, 95% CI: 0.62-0.94). The effects were consistent across race and sex groups. In summary, we identified a set of metabolites associated with LTPA and an MRS associated with a lower risk of death. Our study provides novel insights into the potential mechanisms underlying the health impacts of physical activity.

SUBMITTER: Xu J

PROVIDER: S-EPMC7835806 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Physical Activity-Related Metabolites Are Associated with Mortality: Findings from the Atherosclerosis Risk in Communities (ARIC) Study.

Xu Jun J Liu Guning G Hegde Sheila M SM Palta Priya P Boerwinkle Eric E Gabriel Kelley P KP Yu Bing B

Metabolites 20210119 1

Habitual physical activity can diminish the risk of premature death. Identifying a pattern of metabolites related to physical activity may advance our understanding of disease etiology. We quantified 245 serum metabolites in 3802 participants from the Atherosclerosis Risk in Communities (ARIC) study using chromatography-mass spectrometry. We regressed self-reported moderate-to-vigorous intensity leisure-time physical activity (LTPA) against each metabolite, adjusting for traditional risk factors ...[more]

PMID: 33477977

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Project description:Rationale & objectivePhysical activity is associated with lower risk for cardiovascular disease, diabetes, and hypertension, which have shared risk factor profiles with chronic kidney disease (CKD). However, there are conflicting findings regarding the relationship between physical activity and CKD. The objective was to evaluate the association between physical activity and CKD development over long-term follow-up using the Atherosclerosis Risk in Communities (ARIC) Study.Study designProspective cohort study.Setting & participants14,537 participants aged 45 to 64 years.PredictorsBaseline physical activity status was assessed using the modified Baecke Physical Activity Questionnaire at visit 1 (1987-1989) and categorized according to the 2018 Physical Activity Guidelines for Americans to group participants as inactive, insufficiently active, active, and highly active.OutcomesIncident CKD defined as estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2 at follow-up and≥25% decline in eGFR relative to baseline, CKD-related hospitalization or death, or initiation of kidney replacement therapy.Analytical approachCox proportional hazards regression.ResultsAt baseline, 37.8%, 24.2%, 22.7%, and 15.3% of participants were classified as inactive, insufficiently active, active, and highly active, respectively. During a median follow-up of 24 years, 33.2% of participants developed CKD. After adjusting for age, sex, race-center, education, smoking status, diet quality, diabetes, coronary heart disease, hypertension, antihypertensive medication, body mass index, and baseline eGFR, higher categories of physical activity were associated with lower risk for CKD compared with the inactive group (HRs for insufficiently active, 0.95 [95% CI, 0.88-1.02]; active, 0.93 [95% CI, 0.86-1.01]; highly active, 0.89 [95% CI, 0.81-0.97]; P for trend = 0.007).LimitationsObservational design and self-reported physical activity that was based on leisure time activity only. Due to low numbers, participants who were not Black or White were excluded.ConclusionsHighly active participants had lower risk for developing CKD compared with inactive participants.

Project description:The Atherosclerosis Risk in Communities (ARIC) Study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a prospective epidemiologic study conducted in four U.S. communities. The four communities are Forsyth County, NC; Jackson, MS; the northwest suburbs of Minneapolis, MN; and Washington County, MD. ARIC is designed to investigate the etiology and natural history of atherosclerosis, the etiology of clinical atherosclerotic diseases, and variation in cardiovascular risk factors, medical care and disease by race, gender, location, and date. ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community. A total of 15,792 participants received an extensive examination, including medical, social, and demographic data. These participants were reexamined every three years with the first screen (baseline) occurring in 1987-89, the second in 1990-92, the third in 1993-95, and the fourth and last exam was in 1996-98. Follow-up occurs yearly by telephone to maintain contact with participants and to assess health status of the cohort. In the Community Surveillance Component, currently ongoing, these four communities are investigated to determine the community-wide occurrence of hospitalized myocardial infarction and coronary heart disease deaths in men and women aged 35-84 years. Hospitalized stroke is investigated in cohort participants only. Starting in 2006, the study conducts community surveillance of inpatient (ages 55 years and older) and outpatient heart failure (ages 65 years and older) for heart failure events beginning in 2005. ARIC is currently funded through January 31, 2012. This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to atherosclerosis and cardiovascular disease through large-scale genome-wide association studies of well-characterized cohorts of adults in four defined populations. Genotyping was performed at the Broad Institute of MIT and Harvard, a GENEVA genotyping center. Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

Project description:BACKGROUND:Previous studies suggest that heart failure (HF) is an independent risk factor for cognitive decline. A better understanding of the relationship between HF, cognitive status, and cognitive decline in a community-based sample may help clinicians understand disease risk. OBJECTIVE:To examine whether persons with HF have a higher prevalence of cognitive impairment and whether persons developing HF have more rapid cognitive decline. DESIGN:This observational cohort study of American adults in the Atherosclerosis Risk in Communities (ARIC) study has two components: cross-sectional analysis examining the association between prevalent HF and cognition using multinomial logistic regression, and change over time analysis detailing the association between incident HF and change in cognition over 15 years. PARTICIPANTS:Among visit 5 (2011-2013) participants (median age 75 years), 6495 had neurocognitive information available for cross-sectional analysis. Change over time analysis examined the 5414 participants who had cognitive scores and no prevalent HF at visit 4 (1996-1998). MEASUREMENTS:The primary outcome was cognitive status, classified as normal, mild cognitive impairment [MCI], and dementia on the basis of standardized cognitive tests (delayed word recall, word fluency, and digit symbol substitution). Cognitive change was examined over a 15-year period. Control variables included socio-demographic, vascular, and smoking/drinking measures. RESULTS:At visit 5, participants with HF had a higher prevalence of dementia (adjusted relative risk ratio [RRR] = 1.60 [95% CI 1.13, 2.25]) and MCI (RRR = 1.36 [1.12, 1.64]) than those without HF. A decline in cognition between visits 4 and 5 was - 0.07 standard deviation units [- 0.13, - 0.01] greater among persons who developed HF compared to those who did not. Results did not differ by ejection fraction. CONCLUSION:HF is associated with neurocognitive dysfunction and decline independent of other co-morbid conditions. Further study is needed to determine the underlying pathophysiology.

Dataset Information

Physical Activity-Related Metabolites Are Associated with Mortality: Findings from the Atherosclerosis Risk in Communities (ARIC) Study.

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Physical Activity-Related Metabolites Are Associated with Mortality: Findings from the Atherosclerosis Risk in Communities (ARIC) Study.

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