Does phenotypic age acceleration increase the risk of carotid atherosclerosis in the general population?
Phenotypic age acceleration is independently associated with an increased risk of carotid atherosclerotic plaque and stenosis, suggesting its utility as a complementary risk indicator for subclinical atherosclerosis.
Cardiovascular disease onset and mortality vary substantially among individuals of the same chronological age, reflecting differences in the pace of biological aging. This multi-stage study aimed to investigate the association between phenotypic age acceleration (PhenoAgeAccel) and subclinical carotid atherosclerosis. We conducted a case-control study (2,088 matched pairs) and a prospective validation cohort (n = 3,833) to assess the association between PhenoAgeAccel and carotid atherosclerotic plaque (CAP) presence in a Chinese general population. We then extended the analysis to occlusion and stenosis of the carotid artery (OSCA) in an external UK Biobank cohort (n = 362,893). PhenoAgeAccel was calculated using chronological age and nine clinical parameters, and PhenoAgeAccel ≤ 0 and > 0 were defined as biologically younger and older, respectively. Multivariable logistic regression and Cox proportional hazards regression models were employed for analyses. In the case-control study, each 1-SD increase in PhenoAgeAccel was associated with a 17% higher risk of CAP presence (OR: 1.17, 95% CI: 1.07–1.26) after adjusting for multiple covariates. A similar association was observed for incident CAP, with each 1-SD increase in PhenoAgeAccel associated with an 17% increase in hazard (HR: 1.17, 95% CI: 1.08–1.27). The transportability analysis in the UK Biobank revealed a 26% increased risk of OSCA per-SD increase in PhenoAgeAccel (HR:1.26, 95% CI: 1.20–1.33). The area under receiver operating characteristic curve (AUC) for a model containing PhenoAgeAccel (AUC = 0.700) was significantly (P = 0.026) larger than the standard model (AUC = 0.689). The restricted cubic splines further confirmed a dose-response association between PhenoAgeAccel and risk of CAP or OSCA (P for overall < 0.001). Subgroup analyses showed significant interactions with diabetes and BMI, with stronger associations in non-diabetic and normal-weight individuals (P < 0.001). PhenoAgeAccel was independently associated with an increased risk of CAP presence and incident OSCA, suggesting its potential as a complementary indicator for identifying individuals at higher risk of carotid atherosclerosis.
Zeng et al. (Mon,) studied this question.