Background: Aggressive lipid-lowering therapy is recommended for patients with ischemic stroke; however, lipid paradox has been reported in several clinical studies. The mechanism of lipid paradox remains uncertain, and nutrition maybe one explanation. In this prospective cohort study, we explored the associations between baseline remnant cholesterol (RC) concentrations and clinical outcomes in patients with ischemic stroke, stratified by nutritional status. Materials and Methods: A total of 5257 patients with ischemic stroke were recruited for analysis. The Controlling Nutritional Status (CONUT) score was utilized to investigate the risk of malnutrition. Individuals were classified into 4 groups based on their CONUT score. Poor outcomes and all-cause mortality were compared among patients with varied nutritional status and RC levels. Results: Patients with moderate-severe malnutrition had the highest incidences of in-hospital complications, including pulmonary infection, renal dysfunction, and hemorrhagic transformation, and the highest rates of poor outcomes (61.3%, P?0.001) and all-cause mortality (32.8%, P?0.001) during the 3-month follow-up period. Baseline higher RC level was an independent protective factor of adverse clinical outcomes for patients with any degree of malnutrition, which was not observed in patients without malnutrition. In addition, compared with the moderate-severe malnourished with RC ?0.471 mmol/L, the adjusted ORs for poor outcomes and all-cause mortality were 0.805 (0.450?1.438) and 0.898 (0.502-1.607) for participants with 0.471-0.632 mmol/L, 0.259 (0.095-0.704) and 0.222 (0.061-0.810) for 0.633-0.868 mmol/L, and 0.160 (0.037?0.689) and 0.202 (0.042-0.967) for ? 0.869 mmol/L, prospectively. Conclusion: Lipid paradox was only observed in the malnourished patients with ischemic stroke. Strict lipid reduction therapy is still recommended for patients with ischemic stroke and good nutritional status. However, when treating patients at any risk of malnutrition, the improvement of nutritional status may be more crucial than aggressive lipid control.

The authors have declared no competing interest.

This study was supported by the National Natural Science Foundation of China grants/awards (82173646 and 81973157), and Fundamental Medical Project of Minhang Hospital of Fudan University Project Foundation (Grant Nos 2023MHBJ02).

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