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Plasma Endostatin Levels at Acute Phase of Ischemic Stroke Are Associated with Post-Stroke Cognitive Impairment

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The effect of plasma endostatin on cognitive impairment after ischemic stroke remains unclear. We conducted this study to explore the association between plasma endostatin in the acute phase of ischemic stroke and post-stroke cognitive impairment (PSCI). Baseline plasma endostatin levels were measured, and cognitive function status was assessed by Montreal cognitive assessment at 3 months among 613 ischemic stroke patients. PSCI was defined as Montreal cognitive assessment score less than 26. The association of endostatin with PSCI was analyzed by logistic regression model. The receiver operating characteristic curve was applied to explore the optimal cutoff value of plasma endostatin levels in predicting PSCI. In a multivariable-adjusted model, the odds ratio for the highest vs lowest quartile of endostatin was 2.01 (95% CI, 1.15–3.53) for PSCI. Restricted cubic spline regression model showed a linear dose-response association between endostatin and PSCI (p for linearity = 0.01). The optimal cut point of endostatin was 84.22 ng/mL; higher endostatin levels (≥ 84.22 ng/mL) were associated with increased risk of 2.17-fold for PSCI (adjusted odds ratio, 2.17; 95% CI, 1.44–3.26; p = 0.0002). Furthermore, adding endostatin to a model containing conventional factors led to significant reclassification for PSCI (net reclassification improvement, 0.20; p = 0.025; integrated discrimination improvement, 0.016; p = 0.002). Our findings showed that elevated plasma endostatin levels were associated with cognitive impairment at 3 months after acute ischemic stroke, independently of established conventional risk factors, suggesting that endostatin may be an important biomarker of cognitive impairment after ischemic stroke.

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We thank the study participants and their relatives and the clinical staff at all participating hospitals for their support and contribution to this project.


This study was supported by the National Natural Science Foundation of China (grant: 81773522); Undergraduate Training Program for Innovation and Entrepreneurship, Soochow University (grant: 201910285131Y); and a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions, China; Tulane University and Collins C. Diboll Private Foundation, both in New Orleans, LA.

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Correspondence to Tan Xu or Chongke Zhong.

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This study was approved by the ethical committee at Soochow University in China and Tulane University in the USA, as well as ethical committees at the participating hospitals. All participants provided written informed consent. The CATIS trial was registered at clinicaltrials.gov (NCT01840072).

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The authors declare that they have no conflict of interest.

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Qian, S., Li, R., Zhang, C. et al. Plasma Endostatin Levels at Acute Phase of Ischemic Stroke Are Associated with Post-Stroke Cognitive Impairment. Neurotox Res (2020). https://doi.org/10.1007/s12640-020-00173-5

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  • Cognitive impairment
  • Ischemic stroke
  • Endostatin
  • Montreal cognitive assessment