Joint association and interaction of lipoprotein(a) and hyperuricemia with long-term outcomes in chronic total occlusion
- 1Cardiology Department, The First Affiliated Hospital of Anhui Medical University
Abstract
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.
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BibTeX
@article{zhang2026joint,
title = {{Joint association and interaction of lipoprotein(a) and hyperuricemia with long-term outcomes in chronic total occlusion}},
author = {Jian Zhang and BingBing Zhang and Jun Xie},
journal = {Frontiers in Endocrinology},
year = {2026},
month = nov,
doi = {10.3389/fendo.2026.1980408},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1980408/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Joint association and interaction of lipoprotein(a) and hyperuricemia with long-term outcomes in chronic total occlusion
AU - Jian Zhang
AU - BingBing Zhang
AU - Jun Xie
PY - 2026
DA - 2026/11/06
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1980408
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1980408/full
AB - 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.
SN - 1664-2392
ER -