Abstract
OBJECTIVE: This study aimed to investigate the linear association between lipoprotein(a) [Lp(a)] levels and all-cause and cardiovascular mortality in patients with acute coronary syndrome (ACS). METHODS: This retrospective cohort study included 578 patients with ACS who were hospitalized at Henan Provincial People's Hospital between January 2020 and January 2024. Patients were categorized into two groups: lower Lp(a) group (≤ 300 mg/L) and higher Lp(a) group (> 300 mg/L). Kaplan-Meier survival analysis, Cox regression models, subgroup and sensitivity analyses were used to evaluate the association between Lp(a) and all-cause and cardiovascular mortality. Restricted cubic spline (RCS) analysis was conducted to explore nonlinear associations. RESULTS: During a median follow-up of 27.5 months, a total of 124 all-cause deaths occurred (21.5%), of which 79 cases (13.7%) were classified as cardiovascular deaths. Compared to the lower Lp(a) group, the higher Lp(a) group exhibited a significantly increased risk of all-cause and cardiovascular mortality across all models. In the fully adjusted model (Model 3), the hazard ratio (HR) for all-cause mortality was 1.719 (95% confidence interval [CI]: 1.197-2.470, P = 0.003), while the HR for cardiovascular mortality was 2.505 (95% CI: 1.529-4.102, P < 0.001). In an additional analysis using a 500 mg/L cut-off, patients with Lp(a) > 500 mg/L had a significantly higher risk of cardiovascular mortality (HR = 2.209, P = 0.001), while the association with all-cause mortality (P = 0.284) was not statistically significant in the fully adjusted model. When Lp(a) was analyzed as a continuous variable, each 90 mg/L increase in Lp(a) was associated with a 5% higher risk of all-cause mortality (HR = 1.052, 95% CI: 1.003-1.104, P = 0.038), and each 45 mg/L increase was associated with a 5% higher risk of cardiovascular mortality (HR = 1.054, 95% CI: 1.026-1.084, P < 0.001). For log10-transformed Lp(a), the HR was 1.954 (95% CI: 1.252-3.050, P = 0.003) for all-cause mortality and 3.913 (95% CI: 2.108-7.265, P < 0.001) for cardiovascular mortality. Similarly, for standardized Lp(a) (Z-score), the HR was 1.178 (95% CI: 1.009-1.375, P = 0.038) for all-cause mortality and 1.408 (95% CI: 1.179-1.681, P < 0.001) for cardiovascular mortality. Most subgroup analyses showed that elevated Lp(a) levels were significantly associated with an increased risk of all-cause and cardiovascular mortality (P < 0.05). Sensitivity analyses confirmed the robustness of the findings, with significant associations persisting after excluding patients with early mortality or without stent implantation. Kaplan-Meier analysis showed that both all-cause and cardiovascular survival rates were significantly lower in the high Lp(a) group compared to the low Lp(a) group (P < 0.001 for both). RCS analyses revealed a linear positive association between Lp(a) levels and both all-cause and cardiovascular mortality. CONCLUSIONS: Higher Lp(a) levels were independently and linearly associated with an increased risk of all-cause and cardiovascular mortality in ACS patients.