Joint association and interaction of lipoprotein(a) and hyperuricemia with long-term outcomes in chronic total occlusion

Background Long-term outcomes differ substantially among patients with chronic total occlusion (CTO), and risk assessment remains challenging. Lipoprotein(a) [Lp(a)] and hyperuricemia are both associated with cardiovascular risk, but the prognostic significance of their coexistence in this population is uncertain. Methods We retrospectively studied 391 patients with angiographically confirmed CTO. Patients were classified into four groups according to baseline Lp(a) and uric acid (UA) levels: neither elevated, elevated lipoprotein(a) only, hyperuricemia only, and both elevated. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as the first occurrence of all-cause death, non-fatal myocardial infarction, target vessel revascularization, or stroke. Cox regression was used to assess long-term associations, while additive and multiplicative interactions were examined. Incremental prognostic value was evaluated using model discrimination, reclassification, calibration, and bootstrap internal validation. Results During a median follow-up of 73 months, event rates were 12.21%, 29.89%, 28.57%, and 66.27% across the four groups, respectively (P<0.001). Patients with both elevated lipoprotein(a) and hyperuricemia had the highest event risk compared with those with neither factor elevated (adjusted hazard ratio [aHR] 11.46, 95% confidence interval [CI] 6.44–20.41; P<0.001). In a sensitivity analysis restricted to all-cause death, non-fatal myocardial infarction, or stroke, the association remained significant (aHR 4.23, 95% CI 2.13–8.39; P<0.001). A positive additive interaction was observed, whereas the multiplicative interaction was not significant. The apparent C-indices were 0.691 and 0.828 for the Base and Expanded models, respectively; after bootstrap optimism correction, the corresponding C-indices were 0.634 and 0.791. Conclusions Concurrent elevation of Lp(a) and UA was associated with higher long-term cardiovascular risk in patients with CTO and may provide prognostic information beyond either marker considered alone. These findings require external validation before the proposed dual-biomarker classification can be applied clinically.