Carotid intima-media thickness stratifies early and supernormal vascular aging phenotypes in UK biobank: Implications for cardiovascular risk prediction

Background Chronological age is central to cardiovascular risk assessment but may inadequately capture biological vascular aging. Carotid intima-media thickness (cIMT), a non-invasive marker of subclinical atherosclerosis, may provide additional insight into individualized cardiovascular risk. Methods In this prospective cohort study, We analyzed 31,311 UK Biobank participants with cIMT measurements. Vascular age and Δ-age were derived using multivariable models incorporating cIMT and conventional risk factors, and extreme Δ-age deciles were used to define early vascular aging (EVA) and supernormal vascular aging (SUPERNOVA). Associations with major adverse cardiovascular events (MACE) were assessed using Cox models, and incremental predictive value was evaluated using discrimination and reclassification metrics. Results During a median follow-up of 4.18 years, 682 MACE cases were recorded. After multivariable adjustment, EVA was associated with a twofold increase in MACE risk (HR 2.00, 95% CI 1.45–2.75), whereas SUPERNOVA demonstrated a significant protective effect (HR 0.70, 95% CI 0.54–0.91). Stratified analyses revealed that these associations were most pronounced in the high-risk group (Framingham Risk Score > 20%), where EVA further increased MACE risk (HR 2.69, 95% CI 1.72–4.20) and SUPERNOVA remained protective (HR 0.64, 95% CI 0.47–0.85). Incorporating these vascular aging phenotypes into traditional risk models significantly improved predictive performance, yielding a Net Reclassification Improvement (NRI) of 13.1% (95% CI 8.7–16.8). Conclusion cIMT-derived vascular age effectively stratifies extreme vascular aging phenotypes and is associated with future cardiovascular events. Incorporation of vascular age into conventional risk models provides incremental prognostic value beyond traditional risk scores.