Association of lipoprotein(a) and composite inflammatory indices with functional outcomes in acute ischemic stroke: a prospective cohort study

BACKGROUND: Dysregulated lipid metabolism and systemic inflammatory cascades significantly disrupt the neurofunctional trajectory of acute ischemic stroke (AIS). However, the precise pathomechanisms underlying the interactive pathogenic effects of lipoprotein(a) [Lp(a)] and whole-blood composite inflammatory markers in prognostic interventions remain elusive. This study aims to investigate whether Lp(a) and multiple traditional blood inflammation markers jointly influence the early and 90-day functional outcomes in elderly AIS patients. METHODS: This prospective cohort study enrolled patients aged ≥ 60 years diagnosed with AIS. Baseline Lp(a) levels and seven systemic inflammatory indices, including the C-reactive protein-to-albumin ratio (CAR), were measured upon admission. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) score ≥ 3 at 90 days post-onset. The associations were evaluated using multivariable logistic regression, weighted quantile sum (WQS) regression, and exploratory mediation analyses. RESULTS: Among 732 included patients, 108 (14.8%) experienced a poor functional outcome at 90 days. In fully adjusted models, each 1-standard deviation (SD) increase in Lp(a) was independently associated with a more than twofold higher odds of a 90-day poor outcome (odds ratio [OR], 2.12; 95% CI, 1.70-2.66). Patients in the highest Lp(a) tertile faced significantly increased risk compared with those in the lowest tertile (OR, 2.74; 95% CI, 1.52-5.07). Among the evaluated inflammatory indices, CAR showed the most robust independent association with 90-day poor outcomes (OR per 1-SD increase, 1.59; 95% CI, 1.28-2.13). Notably, patients presenting with both high Lp(a) and high CAR exhibited the greatest risk for an adverse 90-day prognosis (OR, 4.60; 95% CI, 2.29-9.81). Compared with individual inflammatory markers, Lp(a) demonstrated modest prognostic discriminatory ability (AUC, 0.696). Exploratory mediation analysis suggested that CAR mediated only a limited proportion of the association between Lp(a) and 90-day poor outcome, with an indirect effect estimate of 0.008 (95% CI, 0.002-0.026; P = 0.011). CONCLUSIONS: Elevated baseline Lp(a) and CAR were independently associated with poor early and 90-day functional outcomes in this cohort of older patients with AIS. Concurrent elevation of Lp(a) and CAR was associated with the highest odds of adverse outcome.