Mitochondrial DNA haplogroups and short-term neurological outcomes of ischemic stroke.
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ABSTRACT:
SUBMITTER: Cai B
PROVIDER: S-EPMC4438613 | biostudies-literature | 2015 May
REPOSITORIES: biostudies-literature
Publications
Mitochondrial DNA haplogroups and short-term neurological outcomes of ischemic stroke.
Cai Biyang B Zhang Zhizhong Z Liu Keting K Fan Wenping W Zhang Yumeng Y Xie Xia X Dai Minhui M Cao Liping L Bai Wen W Du Juan J Dai Qiliang Q Zhou Shuyu S Zhang Hao H Zhu Wusheng W Ma Minmin M Liu Wenhua W Liu Xinfeng X Xu Gelin G
Scientific reports 20150520
Stroke is one of the leading causes of death and long-term disability worldwide. Mitochondrial DNA (mtDNA) is a potential contributor for the sex differences of ischemic stroke heritability. Although mtDNA haplogroups were associated with stroke onset, their impacts on stroke outcomes remain unclear. This study aimed to evaluate the impacts of mtDNA haplogroups on short-term outcomes of neurological functions in patients with ischemic stroke. A total of 303 patients were included, and their clin ...[more]
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Project description:The Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence trial raised concern that loading doses of clopidogrel may increase hemorrhagic complications. We investigated if similar rates of hemorrhage occur in patients with acute ischemic stroke (AIS) of varying severity.Patients meeting inclusion criteria were divided into 2 groups: the LOAD group and non-LOAD group. The LOAD group was defined as patients who were administered a loading dose of 300 mg or more of clopidogrel with or without aspirin within 24 hours of admission. The non-LOAD group was devised using propensity score (PS): 55 patients who received a loading dose of clopidogrel of 300 mg or more were matched on PS to 55 patients who did not receive loading doses. These patients were taken from a pool of 341 consecutive ischemic patients ineligible for intravenous or intra-arterial fibrinolysis, 162 of whom received a clopidogrel loading dose and the remainder of whom did not. The frequency of hemorrhage was compared between the 2 groups using Student t test and chi-square. Logistic regression was used to assess the relationship between loading dose and serious bleeding events (symptomatic intracerebral hemorrhage [sICH] or transfusion for systemic bleeding).AIS patients (N = 596) were screened during the 31-month period of this retrospective study. Of this sample, 170 patients were excluded: 149 patients were excluded because they were treated with intravenous tissue plasminogen activator (IV t-PA) alone, 11 were excluded because they were treated with IV t-PA combined with intra-arterial therapy (IAT), and 10 were excluded for treatment with IAT alone. An additional 85 patients were excluded because they were not admitted to the stroke service or because they had an in-hospital stroke. Baseline characteristics of the groups were well matched. There were no significant differences in the rates of sICH, transfusion, hemorrhagic transformation, or systemic bleeding. Clopidogrel loading was not associated with increased odds of serious bleeding events in the crude model (odds ratio [OR] .92, 95% confidence interval [CI] .27-3.13) or after adjusting for covariates and confounders of interest (OR 1.06, 95% CI .28-4.04).Contrary to our original hypothesis, patients with AIS receiving clopidogrel loading doses within 24 hours of symptom onset did not appear to experience a higher rate of new serious bleeding events during acute hospitalization when compared with patients who did not receive loading doses. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke trial is expected to provide insight into the safety of clopidogrel loading as an acute intervention after cerebral ischemia.
| S-EPMC4447207 | biostudies-other
Project description:BackgroundGenetic factors have a role in the pathogenesis of ischaemic stroke, but the main genes involved have yet to be defined. Mitochondrial mechanisms have been implicated in the pathophysiology of acute stroke, but the role of mitochondrial DNA (mtDNA) has not been comprehensively studied. We investigated whether there is an association between mtDNA haplotypes and incidence of stroke.MethodsThe major European mtDNA haplogroups were identified in two independent subpopulations (n=950) from a study of occurrence of transient ischaemic attack (TIA) and ischaemic stroke and were compared with those of patients with acute coronary syndromes from the same populations (n=340) and with those of independent population controls (n=2939).FindingsThe presence of mtDNA sub-haplogroup K was significantly less frequent in patients with TIA or stroke than in controls in both subpopulations separately and in a pooled analysis (odds ratio 0.54, 95% CI 0.39-0.75, p<0.00001). This association remained highly significant after adjustment for multiple haplogroup comparisons. The association was significant for patients with TIA and stroke separately and was independent of known risk factors, but was not found for patients with acute coronary events. The mtDNA sub-haplogroup K was present in 8.7% of the total UK population controls and therefore confers a 4.0% (95% CI 2.2-5.7) reduction in population attributable risk of TIA and stroke.InterpretationGenetic variation of mtDNA sub-haplogroup K is an independent determinant of risk of cerebral, but not coronary, ischaemic vascular events. These findings implicate mitochondrial mechanisms in the aetiology of ischaemic stroke and provide a new means for the identification of individuals with a high susceptibility of developing ischaemic stroke.
| S-EPMC2855429 | biostudies-literature