Table 1_Interactive effects of systemic inflammation and nutritional status on 1-year functional outcomes in acute ischaemic stroke: a multidimensional biomarker cohort study.docx

To circumvent mathematical coupling bias, nine composite indices were rigorously deconstructed into four independent pathophysiological axes. The primary endpoint was a poor functional outcome (modified Rankin Scale score >2) at 1 year after stroke onset. Representative biomarkers were selected using bootstrap-based stability inference.

Restricted cubic splines (RCS) and modified Poisson regression with robust standard errors were used to assess non-linear trajectories and synergistic interactions, respectively. A final joint predictive model was constructed following dimensionality reduction via the bootstrap-LASSO algorithm, and the E-value was introduced to quantify the robustness of the findings against unmeasured confounding.</p>Results<p>We included 495 patients, among whom 111 (22.4%) experienced a poor functional outcome.

Following rigorous validation procedures, the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), albumin (ALB), and prognostic nutritional index (PNI) were identified as the optimal representative indices for their respective axes. RCS analysis revealed significant non-linear dynamics: the risk trajectory for high-sensitivity C-reactive protein (hsCRP) exhibited a plateau effect, whereas CAR demonstrated an inverted U-shaped pattern.

Cross-classification analysis demonstrated that the co-occurrence of elevated NLR and diminished ALB significantly increased the risk of adverse outcomes (adjusted RR 2.45, 95% CI 1.33–4.49), with an absolute risk of 36.9% in the joint exposure group (absolute risk difference [RD] 25.4% versus the reference cohort). Although neither multiplicative nor additive interaction tests achieved statistical significance (multiplicative interaction p = 0.856; RERI 0.432, 95% CI spanning zero), this association suggests a potential trend towards compounded high-risk exposure.

The bootstrap-LASSO joint predictive model demonstrated excellent calibration (slope 0.805) and clinical net benefit. E-value analysis (2.16) and probabilistic simulations corroborated that these findings were highly robust against unmeasured confounders, such as baseline neurological deficits (e.g., missing National Institutes of Health Stroke Scale scores).</p>Conclusion<p>The concurrence of systemic inflammatory activation and relatively diminished albumin concentrations constitutes a clinical phenotype robustly associated with long-term adverse outcomes in AIS.

By uncoupling collinear biomarkers, this study unmasks complex, non-linear prognostic trajectories that are typically obscured under conventional single-marker or linear assumptions. Furthermore, the compounded high-risk profile of elevated inflammation and diminished albumin provides preliminary epidemiological rationale to inform future investigations into acute-phase anti-inflammatory therapies combined with metabolic homeostasis support.</p>