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

Abstract 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.