| Title: | Integrative Observational and Genetic Evidence From the UK Biobank Supports Carotid Intima-Media Thickness as a Window Into Cardiac Remodeling. |
| Journal: | Journal of the American Heart Association |
| Published: | 3 Jul 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42396779/ |
| DOI: | https://doi.org/10.1161/jaha.125.049139 |
Publication 20451
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Abstract
BACKGROUND: Carotid intima-media thickness (cIMT) is a noninvasive marker of subclinical atherosclerosis linked to future cardiovascular disease (CVD). However, its relationship with early cardiac remodeling and shared genetic basis with cardiovascular disease remain poorly understood. We investigated the phenotypic and genetic associations between cIMT, aortic and cardiac traits, and cardiovascular disease in the UK Biobank, a large population-based cohort with comprehensive imaging and genetics.</p>
METHODS: We analyzed 46 102 participants with carotid ultrasound and cardiac magnetic resonance imaging, excluding those with prevalent heart failure, atrial fibrillation, or stroke. Multivariable linear and Cox regression models assessed associations between common cIMT, aortic and cardiac traits, and incident cardiovascular disease, with effect estimates expressed per 1 SD increase in cIMT. Genetic correlations and pathway enrichment analyses were performed using genome-wide association studies summary statistics.</p>
RESULTS: Higher cIMT was associated with aortic enlargement, left ventricular hypertrophy, and greater chamber volumes, alongside reduced biatrial ejection fractions (all P<0.001). Higher left cIMT was associated with lower dilated cardiomyopathy (hazard ratio [HR], 0.475 [95% CI, 0.23-0.98], P=0.04) risk. Genetically, cIMT correlated positively with aortic and ventricular traits and negatively with left atrial ejection fraction. Seven shared genes (CDH13, HAND2, ITCH, FBXO32, TBX20, FBN1, and CBFA2AT3) were enriched in pathways related to extracellular matrix organization, vascular development, and cardiac morphogenesis.</p>
CONCLUSION: Increased cIMT is associated with systemic aortic and cardiac remodeling and decreased dilated cardiomyopathy risk. Integrative genetic analyses revealed shared heritable mechanisms, highlighting cIMT as a marker of early cardiovascular structural change, potentially bridging vascular and cardiac disease processes.</p>
15 Keywords
- Aged
- Biological Specimen Banks
- Cardiovascular Diseases
- Carotid Intima-Media Thickness
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Middle Aged
- Phenotype
- Risk Factors
- UK Biobank
- United Kingdom
- Ventricular Remodeling
5 Authors
- Si Hui Chong
- Adama Fatima Saccoh
- Marion van Vugt
- Amand Floriaan Schmidt
- Nikhil Paliwal
1 Application
| Application ID | Title |
|---|---|
| 12113 | Harnessing associations of genetic and phenotypic traits for drug target validation, Ref: 12113. |
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