Cold-driven biphasic vascular healing in elderly patients: 4D optical coherence tomography stratification of major adverse cardiovascular event risk based on age-environment interactions.

Background: Biological aging and prolonged cold exposure each impair vascular healing after implantation of a drug-eluting stent. However, their combined effect-particularly in older adults living in cold climates-remains poorly understood. Objective: To evaluate the joint impact of aging and cold exposure on vascular healing and their association with major adverse cardiovascular events (MACEs) after sirolimus-eluting stent implantation. Methods: In this retrospective cohort study, 119 patients were stratified into three age groups (≤55, 56-65, and >65 years). Vascular healing was assessed using serial optical coherence tomography (OCT) at 6 and 12 months, with a focus on strut coverage, neointimal hyperplasia (NIH), and spatial heterogeneity. Cold exposure was quantified with the validated Cold Exposure Diary Questionnaire and corroborated by regional meteorological data. The primary end point was the incidence of MACEs at 12 months. Results: OCT showed delayed endothelialization at 6 months in patients above 65 years compared to younger cohorts (uncovered struts, 11.7% vs. 6.1%; P < 0.001), along with accelerated late-phase NIH progression (3.33 vs. 1.67 μm/month; P < 0.001). Prolonged cold exposure (>12 h/day) was independently associated with greater neointimal heterogeneity (P = 0.003) and a higher risk of MACEs (hazard ratio, 3.42; 95% CI, 1.65-7.11). A 4D Risk Score, combining OCT-derived healing metrics and cold-exposure data, predicted MACEs; however, external validation is required. Conclusions: In older patients, the interaction between aging and prolonged cold exposure results in biphasic vascular healing, characterized by early delayed endothelialization followed by excessive neointimal proliferation. The proposed 4-D Risk Score may facilitate individualized risk stratification after percutaneous coronary intervention and warrants prospective validation.