Dataset Information

Prospective Study of Epigenetic Age Acceleration and Incidence of Cardiovascular Disease Outcomes in the ARIC Study (Atherosclerosis Risk in Communities).

ABSTRACT: BACKGROUND:DNA methylation-based patterns of biological aging, known as epigenetic age acceleration, are predictive of all-cause mortality, but little is known about their association with cardiovascular disease (CVD). METHODS:We estimated 2 versions of epigenetic age acceleration (Horvath and Hannum) using whole-blood samples from 2543 blacks. Linear and Cox proportional hazards regression, respectively, were used to assess the association of age acceleration with carotid intima-media thickness (cross-sectionally) and incident cardiovascular events, including CVD mortality, myocardial infarction, fatal coronary heart disease, peripheral arterial disease, and heart failure, during a median 21-year follow-up. All models were adjusted for chronological age and traditional CVD risk factors. RESULTS:In comparison to chronological age, the 2 measures of epigenetic age acceleration were weaker, but independent, potential risk markers for subclinical atherosclerosis and most incident cardiovascular outcomes, including fatal coronary heart disease, peripheral arterial disease, and heart failure. For example, each 5-year increment of epigenetic age acceleration was associated with an average of 0.01 mm greater carotid intima-media thickness (each P≤0.01), and the hazard ratios (95% confidence intervals) of fatal coronary heart disease per 5-year increment in Horvath and Hannum age acceleration were 1.17 (1.02-1.33) and 1.22 (1.04-1.44), respectively. CONCLUSIONS:In this sample of blacks, increased epigenetic age acceleration in whole blood was a potential risk marker for incident fatal coronary heart disease, peripheral arterial disease, and heart failure independently of chronological age and traditional CVD risk factors. DNA methylation-based measures of biological aging may help to identify new pathophysiological mechanisms contributing to the development of CVD.

SUBMITTER: Roetker NS

PROVIDER: S-EPMC5863591 | biostudies-other | 2018 Mar

REPOSITORIES: biostudies-other

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Prospective Study of Epigenetic Age Acceleration and Incidence of Cardiovascular Disease Outcomes in the ARIC Study (Atherosclerosis Risk in Communities).

Roetker Nicholas S NS Pankow James S JS Bressler Jan J Morrison Alanna C AC Boerwinkle Eric E

Circulation. Genomic and precision medicine 20180301 3

<h4>Background</h4>DNA methylation-based patterns of biological aging, known as epigenetic age acceleration, are predictive of all-cause mortality, but little is known about their association with cardiovascular disease (CVD).<h4>Methods</h4>We estimated 2 versions of epigenetic age acceleration (Horvath and Hannum) using whole-blood samples from 2543 blacks. Linear and Cox proportional hazards regression, respectively, were used to assess the association of age acceleration with carotid intima- ...[more]

PMID: 29555670

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Project description:Estimated glomerular filtration rate (eGFR) and albuminuria are central for diagnosis, staging, and risk evaluation in chronic kidney disease (CKD). Universal thresholds regardless of age, sex, and race are recommended, but relatively little is known about how these demographic factors alter the relationship of eGFR and albuminuria to cardiovascular outcomes.Observational cohort study.11,060 whites and blacks aged 52-75 years in the Atherosclerosis Risk in Communities (ARIC) Study with median follow-up of 11.2 years.eGFR by the CKD-EPI (CKD Epidemiology Collaboration) creatinine equation (reference, 95 mL/min/1.73 m(2)) and urinary albumin-creatinine ratio (ACR; reference, 5 mg/g).Cardiovascular events (coronary disease, stroke, and heart failure) and all-cause mortality.Adjusted HRs associated with eGFR and ACR in subgroups according to age, sex, and race.Cardiovascular risk significantly increased at eGFR <70 mL/min/1.73 m(2) in all subgroups according to age (<65 vs ?65 years), sex, and race (P for interaction >0.2 for these subgroups; eg, at eGFR of 30 mL/min/1.73 m(2), the adjusted HR was 2.19 [95% CI, 1.10-4.35] at age 52-64 years vs 2.23 [95% CI, 1.33-3.72] at age 65-75 years). Results were similar for mortality. Log(ACR) was associated linearly with cardiovascular risk without threshold effects in all subgroups, with some quantitative interactions. HRs according to ACR tended to be lower in men versus women (eg, at ACR of 40 mg/g, 1.18 [95% CI, 0.98-1.41] vs 1.77 [95% CI, 1.45-2.15]) and in the older versus younger population (1.24 [95% CI, 1.04-1.49] vs 1.73 [95% CI, 1.42-2.12]; P for interaction <0.01 for sex and age). Less evident interactions were observed for mortality.Single measurement of eGFR with creatinine and ACR and relatively narrow age range.The associations of eGFR and ACR with cardiovascular events were largely similar, with some quantitative interactions, in age, sex, and racial subgroups, generally supporting universal thresholds of GFR and ACR for CKD definition/staging.

Dataset Information

Prospective Study of Epigenetic Age Acceleration and Incidence of Cardiovascular Disease Outcomes in the ARIC Study (Atherosclerosis Risk in Communities).

Publications

Prospective Study of Epigenetic Age Acceleration and Incidence of Cardiovascular Disease Outcomes in the ARIC Study (Atherosclerosis Risk in Communities).

Similar Datasets

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