| Title: | Accelerated biological aging, genetic susceptibility, and the risk of peripheral arterial disease: Evidence from the UK Biobank cohort study |
| Journal: | International Journal of Cardiology Cardiovascular Risk and Prevention |
| Published: | 25 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42404028/ |
| DOI: | https://doi.org/10.1016/j.ijcrp.2026.200664 |
Publication 20528
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Background: Peripheral artery disease (PAD) is a condition in which atherosclerosis causes narrowing or blockage of the peripheral arteries, leading to insufficient blood supply to the limbs. Although accelerated biological aging has been recognized as a driving factor in the development and progression of many age-related diseases, its exact role in the risk of developing PAD remains unclear. This study investigated the relationship of biological aging and genetic susceptibility with the risk of incident PAD.</p>
Methods: This prospective study included 403,780 UK Biobank participants free of PAD at baseline. Biological age was estimated from routine clinical biomarkers using the Klemera-Doubal method (KDM-BA) and PhenoAge algorithms. BAA was defined as the residual from regression of biological age on chronological age. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) for incident PAD after adjustment for demographic, socioeconomic, lifestyle, and clinical covariates. A polygenic risk score (PRS) was constructed to evaluate genetic predisposition to PAD. We also examined the interaction between genetic susceptibility and accelerated biological aging in relation to PAD risk.</p>
Results: Our findings indicated that accelerated biological aging was significantly associated with an increased risk of PAD, whether assessed by the KDM residual (HR 1.21, 95% CI 1.18-1.24) or the PhenoAge residual (HR 1.34, 95% CI 1.31-1.37). Furthermore, joint association analysis showed that participants with both accelerated biological aging and high genetic risk had the greatest risk of PAD (KDMAge: HR 2.07, 95% CI 1.83-2.34; PhenoAge: HR 6.14, 95% CI 5.30-7.12). A significant additive interaction was also observed between high genetic risk and accelerated biological aging as measured by PhenoAge.</p>
Conclusion: Accelerated biological ageing were independently and jointly associated with incident PAD. This finding support the potential value of integrating biological ageing metrics into PAD risk assessment.</p>
4 Authors
- Wenkai Zhang
- Peng Qiu
- Chenshu Li
- Ruihua Wang
1 Application
| Application ID | Title |
|---|---|
| 88192 | Investigating associations between blood pressure and peripheral vascular diseases. |
Enabling scientific discoveries that improve human health