Evidence map›Paper›PMID 41368835›Full record

ArticleJournal of the American Heart Association2025

Epigenetic Aging Clocks and Incident Cardiovascular Outcomes: Results From the MESA.

Shantanu Srivatsa, Noah Rice, James R Pike, Jennifer A Smith, Jingzhong Ding, Yongmei Liu, Matthew Budoff, Ganga S Bey

Abstract readMulticenter Study
In one paragraph

Article in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Shantanu SrivatsaUNC Chapel Hill School of Medicine Gillings School of Public Health Chapel Hill NC.ORCID 0000-0002-9398-8358
Noah RiceUNC Chapel Hill School of Medicine Gillings School of Public Health Chapel Hill NC.
James R PikeDepartment of Epidemiology, Gillings School of Global Public Health University of North Carolina at Chapel Hill Chapel Hill NC.ORCID 0000-0002-6858-620X
Jennifer A SmithDepartment of Epidemiology, School of Public Health University of Michigan Ann Arbor MI.ORCID 0000-0002-3575-5468
Jingzhong DingDepartment of Medicine Wake Forest Baptist Medical Center Winston-Salem NC.
Yongmei LiuDepartment of Medicine, Division of Cardiology Duke University Medical Center Durham NC.ORCID 0000-0002-6562-1858
Matthew BudoffDepartment of Medicine Lundquist Institute at Harbor-UCLA Torrance CA.ORCID 0000-0002-9616-1946
Ganga S BeyDepartment of Epidemiology, Gillings School of Global Public Health University of North Carolina at Chapel Hill Chapel Hill NC.ORCID 0000-0002-9659-7096

Funding

Task Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2M
Cardiovascular Epidemiology Training GrantT32HL007055 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Wayne D. Rosamond · 1986 to 2026
$10.0M
A Longitudinal Epigenetic Study of AtherosclerosisR01HL135009 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI LIU, YONGMEI · 2017 to 2020
$5.8M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00005 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL E · 2020 to 2025
$5.1M
TO EXERCISE OPTION PERIOD ONE (1) FOR TASK AREA A - MESA CORE OPERATIONS, FIELD CENTER.75N92020D00004 · NHLBI · NORTHWESTERN UNIVERSITY · PI SIEGEL, JONATHAN H · 2020 to 2025
$4.5M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00006 · NHLBI · UNIVERSITY OF MINNESOTA · PI PANKOW, JAMES S · 2020 to 2025
$4.4M
Cell-specific genomic features of Alzheimer's disease progressionRF1AG054474 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI DING, JINGZHONG, LIU, YONGMEI · 2017 to 2019
$4.1M
The Role of Hepatocyte ABCA1 in Lipid Mobilization and TransportR01HL119962 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI PARKS, JOHN S · 2013 to 2022
$3.9M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00003 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI POST, WENDY S · 2020 to 2025
$3.8M
Epigenome-Wide Association Study of DNA Methylation and AtherosclerosisR01HL101250 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI LIU, YONGMEI · 2009 to 2013
$3.6M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00007 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI BERTONI, ALAIN GERALD · 2020 to 2025
$3.5M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00002 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHEA, STEVEN J · 2020 to 2025
$3.4M
NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS R01 HL101250NHLBI NIH HHS R01 HL119962NHLBI NIH HHS R01 HL135009NHLBI NIH HHS T32 HL007055NIA NIH HHS RF1 AG054474NIDDK NIH HHS R01 DK101921NIH HHS 75N98025D00022NIH HHS 75N98025D00024NIH HHS 75N98025D00025NIH HHS 75N98025D00026NIH HHS 75N98025D00027NIH HHS 75N98025D00028
6 · The paper itself

Abstract

backgroundDNA methylation-based aging clocks capture biological aging processes and may improve cardiovascular risk prognostication. However, evidence about epigenetic aging clocks, incident outcomes, and interactions with clinical biomarkers such as coronary artery calcium (CAC) in diverse cohorts are limited.

methodsIn this retrospective cohort study, we assessed 1264 MESA (Multi-Ethnic Study of Atherosclerosis) participants (mean age, 69 years; 49% men) who provided DNA at examination 5 (2010-2012). Epigenetic clock measures included GrimAge and age acceleration (the residual of GrimAge on chronological age). Outcomes included incident myocardial infarction, coronary heart disease, stroke, heart failure (HF) subtypes, and composite cardiovascular disease through 2019. Cox proportional hazards models adjusted for demographics, behaviors, comorbidities, and medications and stratified by CAC presence.

resultsDuring a median 8.3 years of follow-up, 223 cardiovascular disease, 76 myocardial infarction, 148 coronary heart disease, 21 stroke, and 109 HF events (49 HF with reduced ejection fraction, 14 HF with mildly reduced ejection fraction, 46 HF with preserved ejection fraction) occurred. In fully adjusted models, GrimAge was independently associated with higher risk of composite cardiovascular disease (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]), stroke (HR, 1.08 [95% CI, 1.04-1.13]), and HF with mildly reduced ejection fraction (HR, 1.31 [95% CI, 1.13-1.53]). Associations with myocardial infarction attenuated after full adjustment in those without baseline CAC but remained significant among those with baseline CAC >0 (myocardial infarction: HR, 1.09 [95% CI, 1.03-1.16]).

conclusionsAging clocks may capture cardiovascular risk beyond traditional risk factors and work in concert with subclinical disease measures such as CAC. However, given small numbers of stroke/HF subtypes, replication of these results in other populations is needed to assess whether interventions that slow epigenetic aging or target CAC translate into fewer clinical events.

Indexed as

AgingCardiovascular DiseasesDNA MethylationEpigenesis, GeneticAgedAged, 80 and overAge FactorsFemaleHeart Disease Risk FactorsHumansIncidenceMaleMiddle AgedRetrospective StudiesRisk AssessmentRisk Factorscardiovascular diseasecoronary artery calciumepigeneticsprevention

Identifiers

PMID41368835
PMCPMC12826894

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.