BACKGROUND: BDNF (brain-derived neurotrophic factor) has been implicated in cardiovascular homeostasis and ischemic stroke pathogenesis. We aimed to prospectively investigate the associations between serum BDNF levels and the prognosis of ischemic stroke in a multicenter cohort study. METHODS: This prospective study follows the STROBE reporting guideline. Serum BDNF concentrations were measured in 3319 ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke between August 2009 and May 2013 in 26 hospitals across China. The primary outcome was the composite outcome of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke onset. Multivariate logistic regression or Cox proportional hazards regression analysis was used to assess the associations between serum BDNF levels and adverse clinical outcomes. RESULTS: During the 3-month follow-up period, 827 (24.92%) patients experienced a primary outcome, including 734 major disabilities and 93 deaths. After adjusting for age, sex, and other important prognostic factors, elevated serum BDNF levels were associated with decreased risks of primary outcome (odds ratio, 0.73 [95% CI, 0.58–0.93]), major disability (odds ratio, 0.78 [95% CI, 0.62–0.99]), death (hazard ratio, 0.55 [95% CI, 0.32–0.97]), and the composite outcome of death and vascular events (hazard ratio, 0.61 [95% CI, 0.40–0.93]) when 2 extreme tertiles were compared. Multivariable-adjusted spline regression analyses showed a linear association between serum BDNF levels and the primary outcome ( P value for linearity=0.005). The addition of BDNF to conventional risk factors slightly improved reclassification for the primary outcome (net reclassification improvement: 19.33%; P <0.001; integrated discrimination index: 0.24%; P =0.011). CONCLUSIONS: Elevated serum BDNF concentrations were independently associated with decreased risks of adverse outcomes after ischemic stroke, suggesting that serum BDNF may be a potential biomarker for prognosis after ischemic stroke. Further studies are warranted to investigate the potential therapeutic benefit of BDNF for ischemic stroke.
BackgroundPrevious studies suggested that elevated levels of plasma soluble triggering receptor expressed on myeloid cells 2 (sTREM2) was related to increased risk of death, cardiovascular events and cognitive impairment after stroke. We aimed to prospectively investigate the association between plasma sTREM2 levels and post-stroke depression (PSD).MethodsWe measured plasma sTREM2 levels in 590 ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke. The 24-item Hamilton Rating Scale for Depression was used to assess depression at 3 months after ischemic stroke onset, and PSD was defined as a score of ≥8. Logistic regression analysis was performed to evaluate the risk of PSD associated with plasma sTREM2 levels, and net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to assess the predictive value of sTREM2.ResultsOf the 590 participants, 229 (38.8%) patients experienced PSD. The risk of PSD elevated significantly with plasma sTREM2 levels (Pfor trend=0.034). After adjusting for several covariates, the odds ratio for the highest quartile of sTREM2 compared with the lowest quartile was 2.41 (95% CI=1.35-4.31) for PSD. Multiple adjusted spline regression analysis further confirmed the linear dose-response relationship between sTREM2 levels and PSD (Pfor linearity=0.024). The addition of sTREM2 to a conventional model notably improved the risk prediction for PSD (category-free NRI=21.50%, 95% CI=5.92%-37.07%,P=0.011; IDI=1.43%, 95% CI=0.45%-2.42%,P=0.005).ConclusionsThe present study demonstrated that elevated plasma sTREM2 levels were associated with increased risk of PSD, suggesting that sTREM2 may be a promising prognostic biomarker for PSD.RegistrationURL:https://www.clinicaltrials.gov; Unique identifier:NCT01840072.
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