Abstract
OBJECTIVE: To investigate whether the "obesity paradox" in acute ischemic stroke (AIS) is a masking effect of metabolic lipid reserves. We evaluated the independent and opposing associations of body weight status and admission triglycerides (TG) with 90-day functional outcomes to distinguish the structural burden of obesity from metabolic health. METHODS: This dual-center retrospective cohort study included 571 consecutive AIS patients recruited between 2019 and 2024. Patients were categorized into normal-weight (NW, n = 245; BMI 18.5-23.9 kg/m(2)) and overweight-or-obesity (OW, n = 326; BMI ≥ 24.0 kg/m(2)) groups. The primary endpoint was an excellent functional outcome [modified Rankin Scale (mRS) 0-1] at 90 days. Multivariable logistic regression and inverse probability weighting (IPW) were employed to isolate the independent effects of weight status and TG levels. RESULTS: At 90 days, the proportion of patients achieving an excellent outcome was significantly higher in the NW group than in the OW group (60.4% vs. 50.6%; p = 0.020). In univariable analysis, patients who achieved an excellent outcome (mRS 0-1) had significantly higher admission TG levels than those who did not [median 1.33 (IQR 0.97-1.92) vs. 1.13 (IQR 0.90-1.48) mmol/L; p < 0.001]. After adjusting for comprehensive confounders including age, NIHSS, and other lipid profiles, overweight-or-obesity was independently associated with lower odds of an excellent outcome (adjusted OR = 0.611, 95% CI: 0.394-0.945; p = 0.027). Conversely, higher admission TG levels were significantly associated with better recovery (adjusted OR = 1.405 per 1 mmol/L increase, 95% CI: 1.057-1.867; p = 0.019). These opposing associations remained robust in IPW sensitivity analyses. CONCLUSION: The "obesity paradox" in AIS appears to be a masking effect driven by TG reserves. Once disentangled from metabolic benefits, overweight and obesity emerge as independent risk factors for poorer recovery. These findings support a phase-specific metabolic management strategy: mitigating the physical and systemic burdens of obesity while ensuring sufficient TG levels within the physiological range to support neural repair during the acute window.