Aortic & peripheral vascular diseaseCohort study
Blood DNA Methylation Patterns Across Carotid, Coronary, and Peripheral Atherosclerosis
- Epigenome-wide association study in 2 prospective cohorts
- Epigenome-wide association studies (EWAS) with 5% false discovery rate correction
- methylation scores trained in one cohort, evaluated in a separate cohort
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 individuals · 2 prospective cohorts
- Outcome
- Differentially methylated CpG sites related to atherosclerosis across vascular beds, and extent reflecting cardiovascular risk factors (CVRFs)
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
| Outcome | HR | P value |
|---|---|---|
| 3-point major adverse cerebrovascular and CV events, epigenetic scores · range across scores; all P < 0.001 | 1.23 to 1.39 | P < 0.001 |
Original publication
Blood DNA Methylation Patterns Across Carotid, Coronary, and Peripheral Atherosclerosis. J Am Coll Cardiol. Published 3 June 2026. doi:10.1016/j.jacc.2026.04.009
Summarised from the published abstract; every number is checked against it