High Serum Brain-Derived Neurotrophic Factor Is Associated With Decreased Risks of Poor Prognosis After Ischemic Stroke.

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.

Soluble TREM2 is associated with death and cardiovascular events after acute ischemic stroke: an observational study from CATIS.

BACKGROUND: Soluble triggering receptor expressed on myeloid cells 2 (sTREM2), which reflects microglia activation, has been reported closely associated with neuronal injury and neuroinflammation. We aimed to prospectively investigate the associations between plasma sTREM2 and clinical outcomes in acute ischemic stroke (AIS) patients. METHODS: Study participants were from the China Antihypertensive Trial in Acute Ischemic Stroke, plasma sTREM2 levels in the acute phase of AIS were measured in 3285 participants. The study outcomes were death, cardiovascular events and severe disability at 1 year after AIS. Cox proportional hazards models or logistic regression models were performed to examine the associations of plasma sTREM2 and clinical outcomes. RESULTS: After 1-year follow-up, 288 participants (8.8%) experienced cardiovascular events or died. Multivariable-adjusted hazard ratios or odds ratios (95% confidence intervals) for the highest quartile of sTREM2 were 1.57 (1.11-2.21) for the composite outcome of death and cardiovascular events, 1.68 (1.09-2.60) for death, and 1.53 (1.08-2.18) for death or severe disability compared to the lowest quartile. Moreover, incorporation sTREM2 into traditional risk factors model significantly improved risk prediction of the composite outcome of death and cardiovascular events as evidenced by net reclassification index and integrated discrimination improvement (all p values < 0.05). There were joint effects of sTREM2 and galectin-3 on death and cardiovascular events. Participants with simultaneous elevation of sTREM2 and galectin-3 levels had the highest risk of the composite outcome of death and cardiovascular events. CONCLUSIONS: Elevated sTREM2 levels were independently associated with increased risks of death and cardiovascular events after AIS.

The association between plasma soluble triggering receptor expressed on myeloid cells 2 and cognitive impairment after acute ischemic stroke.

BACKGROUND: Previous researches have suggested that soluble triggering receptor expressed on myeloid cells 2 (sTREM2) plays a pivotal role in central nervous system pathologies and the development of neurodegenerative disorders. This study aimed to prospectively investigate the association between plasma sTREM2 levels and post-stroke cognitive impairment (PSCI). METHODS: A sample of 599 consecutive acute ischemic stroke patients with sTREM2 measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were eventually included in this analysis. Cognitive impairment was defined as a score of <25 for Mini-Mental State Examination, measured at 3-month follow up. Binary logistic regression was used to estimate the odds ratios (ORs) of plasma sTREM2 levels on the risk of PSCI. RESULTS: Of the 599 participants (mean age, 60.0 ± 10.4 years; male, 70.5%), 228 (38.1%) patients were diagnosed as PSCI. The risk of PSCI elevated significantly with higher plasma sTREM2 levels (p for trend <0.01). After adjusting for several confounding factors, the ORs for the highest quartile of sTREM2 compared with the lowest quartile was 2.06 (95% confidence interval, 1.20-3.53) for PSCI. Moreover, the addition of sTREM2 to the conventional model with established risk factors significantly improved risk discrimination (C-statistics increased from 0.668 to 0.691, p = 0.02) and reclassification (net reclassification improvement: 32.2%, p < 0.001; integrated discrimination improvement: 1.3%, p = 0.01) for PSCI. LIMITATIONS: Results might be subject to selective bias and potential confounding. CONCLUSIONS: The present study demonstrated that elevated level of plasma sTREM2 may be associated with PSCI, and sTREM2 has potential value in predicting PSCI.

Soluble ST2 and risk of cognitive impairment after acute ischemic stroke: a prospective observational study.

BACKGROUND: Soluble suppression of tumorigenesis-2 (sST2) was reported to be associated with cognitive performance and risk of incident stroke. However, the impact of sST2 on cognitive function after ischemic stroke is unclear. We aimed to assess the association of sST2 and cognitive impairment at 3 months in acute ischemic stroke patients. METHODS: Baseline plasma sST2 levels were measured in 619 ischemic stroke patients (mean age: 60.0 ± 10.5 years) from 7 participating hospitals of the China Antihypertensive Trial in Acute Ischemic Stroke. Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to assess cognitive status. Cognitive impairment was defined as a MoCA score < 23 or MMSE score < 27. The association between sST2 and cognitive impairment was evaluated by logistic regression analysis. RESULTS: 325 (52.5%) or 323 (52.2%) participants developed cognitive impairment according to MoCA or MMSE. After adjustment for age, sex, education, and other covariates, the odds ratio for the highest vs lowest quartile of sST2 was 2.38 (95% CI, 1.42-4.00) and 1.82 (95% CI 1.09-3.03) risk of cognitive impairment defined by MoCA and MMSE score, respectively. Incorporation sST2 into a model containing conventional risk factors significantly improved reclassification. CONCLUSIONS: Elevated plasma sST2 levels were significantly associated with post-stroke cognitive impairment.