Variants in clopidogrel-relevant genes and early neurological deterioration in ischemic stroke patients receiving clopidogrel.

BACKGROUND: Early neurological deterioration (END) is common in acute ischemic stroke (IS). However, the underlying mechanisms for END are unclear. The aim of this study was to evaluate the associations of 16 variants in clopidogrel-relevant genes and interactions among these variants with END in acute IS patients receiving clopidogrel treatment. METHODS: We consecutively enrolled 375 acute IS patients between June 2014 and January 2015. Platelet aggregation was measured on admission and after the 7-10 days of clopidogrel treatment. The 16 variants in clopidogrel-relevant genes were examined using mass spectrometry. The primary outcome was END within the 10 days of admission. Gene-gene interactions were analyzed by generalized multifactor dimensionality reduction (GMDR) methods. RESULTS: Among the 375 patients, 95 (25.3%) patients developed END within the first 10 days of admission. Among the 16 variants, only CYP2C19*2 (rs4244285) AA/AG was associated with END using single-locus analytical approach. GMDR analysis revealed that there was a synergistic effect of gene-gene interactions among CYP2C19*2 rs4244285, P2Y12 rs16863323, and GPIIIa rs2317676 on the risk for END. The high-risk interactions among the three variants were associated with the higher platelet aggregation and independent predictor for END after adjusting for the covariates (hazard ratio: 2.82; 95% confidence interval: 1.36-7.76; P = 0.003). CONCLUSIONS: END is very common in patients with acute IS. The mechanisms leading to END are most likely multifactorial. Interactions among CYP2C19*2 rs4244285, P2Y12 rs16863323, and GPIIIa rs2317676 may confer a higher risk for END. It was very important to modify clopidogrel therapy for the patients carrying the high-risk interactive genotypes. CLINICAL TRIAL REGISTRATION INFORMATION: The study described here is registered at http://www.chictr.org/ (unique Identifier: ChiCTR-OCH-14004724). The date of trial registration was May 30, 2014.

Neutrophil Counts to High-Density Lipoprotein Cholesterol Ratio: a Potential Predictor of Prognosis in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.

Neutrophil counts to high-density lipoprotein cholesterol ratio (NHR) is a relatively new and readily available indicator, and our study aimed to demonstrate its relationship with short-term prognosis after intravenous thrombolysis in acute ischemic stroke (AIS) patients and to make a simple comparison with other prognostic indicators. We compared demographic and laboratory characteristics of AIS patients and healthy controls and grouped AIS patients according to NHR tertiles to contrast 3-month outcomes. Univariate and multivariate regression analyses were carried to further analyze the relationship between NHR and prognosis. Moreover, we compared the accuracy of several factors using receiver-operating characteristic curve. NHR levels of AIS patients were higher than those of healthy controls (p < 0.001). The NHR levels were significantly higher in AIS patients with poor prognosis than those with good prognosis (p = 0.001) and were higher in patients with severe stroke than those with mild stroke (p = 0.011). Multivariate logistic regression analysis indicated that elevated NHR was an independent predictor of poor outcomes (odds ratio = 4.570; 95% CI, 1.841-11.340; p = 0.001). High NHR levels were associated with poor 3-month outcomes after intravenous thrombolysis in AIS patients.

Matrix metalloproteinase-9 gene polymorphisms are associated with ischemic stroke severity and early neurologic deterioration in patients with atrial fibrillation.

OBJECTIVES: The mechanisms of ischemic stroke severity and early neurologic deterioration (END) are not fully understood. The aim of the present study was to investigate the association of six variants in MMP-9 gene with ischemic stroke severity and the risk for END in ischemic stroke (IS) patients with atrial fibrillation (AF). METHODS: This was a multi-center, prospective, observational study of 615 acute IS patients with AF admitted to six participating hospitals between June 2016 and October 2017. Ischemic stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score on admission. END was defined as an increase of four or more points in NIHSS within 10 days of admission. Six variants of MMP-9 gene were examined using mass spectrometry. RESULTS: Among the 615 enrolled patients, 112 (18.2%) patients presented with moderate or severe stroke (NIHSS score ≥16), and 108 (17.6%) patients suffered from END within 10 days of admission. Multiple logistic analysis showed that prestroke antiplatelet therapy, prestroke anticoagulant therapy, rs3918242 CT/TT, and rs3787268 AG/GG were independent predictors for stroke severity. Cox proportional hazard regression revealed that diabetes mellitus, prestroke antiplatelet therapy, prestroke anticoagulant therapy, rs1056628 AC/CC, and rs3918242 CT/TT were independently associated with the risk of END. CONCLUSIONS: The incidence of moderate or severe stroke and END was very common in acute IS patients with AF. MMP-9 polymorphisms were independently associated with severe stroke and higher risk of END, and prestroke antithrombotic treatment was associated with less severe stroke and lower risk of END in patients with AF.