Aortic & peripheral vascular disease

Blood DNA Methylation Patterns Across Carotid, Coronary, and Peripheral Atherosclerosis: A Comparative Analysis in 2 Prospective Cohorts

J Am Coll CardiolPublished Epigenome-wide association study in 2 prospective cohorts

Authors' conclusion

Results suggest that in blood, the epigenetic signature of atherosclerosis largely reflects cumulative exposure, particularly smoking and cardiometabolic dysregulation, rather than strongly distinguishing vasculature-specific biological processes.

Study context

Population
Individuals from 2 prospective cohort studies; carotid, coronary and peripheral atherosclerosis
Participants
3,688 individuals2 prospective cohorts
Outcome
Differentially methylated CpG sites related to atherosclerosis across vascular beds, and extent reflecting cardiovascular risk factors (CVRFs)
Methodological detailsEpigenome-wide association studies (EWAS) with 5% false discovery rate correction, methylation scores trained in one cohort, evaluated in a separate cohort
  • EWAS with 5% false discovery rate correction
  • Methylation scores trained in one cohort, evaluated in a separate cohort

Main finding

As reported in the abstract

CpG sites associated with atherosclerosis
CpG sites associated with carotid atherosclerosis
1,687
CpG sites associated with coronary atherosclerosis
3,131
CpG sites associated with peripheral atherosclerosis
5,852
CpG sites associated in 2 or more settings
2,155
Atherosclerosis-associated CpG sites intersecting with CVRF-associated sites
>90%
Overlap with smoking-associated sites
up to 90%
Overlap with inflammation-associated sites
60%
Overlap with metabolic trait-associated sites
44%
Reduction in median absolute estimate after adjustment for smoking pack-years alone
19.6% to 29.0%
Reduction in median absolute estimate after joint adjustment for all CVRF markers
25.5% to 32.8%

Observational data: associations, not effects.

Further findings

OutcomeHRP value
3-point major adverse cerebrovascular and CV events, epigenetic scoresRange across scores; all P < 0.0011.23 to 1.39P < 0.001

Original publication

Blood DNA Methylation Patterns Across Carotid, Coronary, and Peripheral Atherosclerosis: A Comparative Analysis in 2 Prospective Cohorts. J Am Coll Cardiol. Published 3 June 2026. doi:10.1016/j.jacc.2026.04.009

Composed by AI from the published abstract and checked against it. How Briefs are made →

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