Risk Factors For Brain Infarction Research Articles

In atrial fibrillation epilepsy risk differs between oral anticoagulants: active comparator, nested case-control study.

Atrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC). We performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004. In 2011-17, 227 707 AF patients initiated treatment with a DOAC or PPC, of which 1828 cases developed epilepsy on current treatment with an oral anticoagulant. They were matched to 19 084 controls without epilepsy. Patients with DOAC treatment for AF had an overall higher risk of epilepsy with an odds ratio of 1.39, 95% CI (1.24; 1.55) compared to current PPC treatment. Cases had higher baseline CHA2DS2-VASc scores and more frequently a history of stroke than controls. After excluding patients with ischaemic stroke prior to the diagnosis of epilepsy, the risk of epilepsy was still higher on DOACs than on PPC. In contrast, within a cohort of patients with venous thromboembolism, the risk of epilepsy on treatment with DOACs was less elevated [adjusted odds ratio 1.15, 95% CI (0.98; 1.34)]. In patients with AF initiating oral anticoagulation, treatment with a DOAC was associated with an increased risk of epilepsy compared to the vitamin K antagonist PPC. Covert brain infarction may explain the observed elevated risk of epilepsy.

Habitual snoring as a risk factor for brain infarction.

The association of habitual snoring with cerebral ischaemia was studied, in a case control-study, in 133 patients aged 45-75 years (103 men and 30 women) and 133 controls matched for sex and age. Ischaemic stroke was confirmed by brain computed tomography or magnetic resonance imaging. History of risk factors, especially of snoring and sleeping habits was recorded with structured questionnaire during interview. Prevalence of habitual snoring significantly differs between patients with stroke and controls: 31/133 (23.3%) vs 11/133 (8.3%) (Odds ratio 3.4, 95% confidence interval 1.5 to 7.6, p < 0.001). Even after adjusting for matching variables and confounding risk factors (arterial hypertension, cardiac arrhythmia, and obesity), habitual snoring carries a significant risk factor for stroke (odds ratio: 2.9, 95% confidence interval 1.3 to 6.8 (p = 0.01)). The risk of ischaemic stroke was higher among older male patients with arterial hypertension who always snored. Habitual snoring was not significantly linked with sleep-related stroke nor with the pathophysiology of strokes. Inquiring about habitual snoring should become a routine practice, especially among older male patients with arterial hypertension, and specific preventive measures should be instituted at an earlier stage.

Association between the Glu298Asp polymorphism in the endothelial constitutive nitric oxide synthase gene and brain infarction. The GENIC Investigators.

Nitric oxide (NO) synthesized by endothelial constitutive NO synthase (ecNOS) plays a key role in vascular regulation and atherosclerosis. Little is known concerning the role of the ecNOS gene (NOS3) as a risk factor for brain infarction (BI). Our aim was to investigate the relation between the Glu298Asp polymorphism in exon 7 of NOS3 with BI and its subtypes. Patients (n=460; cases) with BI were consecutively recruited and classified into etiological subtypes. Control subjects (n=460; controls) without a history of stroke were recruited among individuals hospitalized at the same institutions and individually matched on age, sex, and center. Genotypes of the polymorphism were determined by polymerase chain reaction. The distribution of genotypes was significantly different between cases and controls (P=0.008); the GG genotype was more frequent in cases (46.1%) than in controls (35.4%; OR, 1.56; 95% CI, 1.19 to 2.04). Among subtypes, the frequency of the GG genotype was significantly higher in cases than in controls in the lacunar subtype (OR, 2.00; 95% CI, 1.05 to 3. 80); in this group, the relation between BI and LDL level was stronger among carriers of the GG genotype than among noncarriers (P for interaction, 0.05). Homozygosity for the G allele of the Glu298Asp polymorphism in NOS3 was associated with BI, and especially with lacunar stroke. Our findings suggest that genetic susceptibility and LDL cholesterol have a synergistic relation. Although these findings should be replicated in a larger sample of subjects and the functionality of the Glu298Asp polymorphism has not been established, these results may help us to understand the cause of the arteriolopathy underlying lacunae and have future implications in their treatment and prevention.

4.接着分子,組織因子

The role of cell adhesion molecules and tissue factor as risk factor for brain infarction has been emphasized. By primate models of middle cerebral artery occlusion and reperfusion (MCA : O/R), we have tested the potential role of these molecules in the microvasculature in ischemic brain tissue. Significant increase of cell adhesion molecules (P-selectin, E-selectin, ICAM-1, and GP IIb/IIIa) of immunoreactive expression was recognized in the affected site of MCA : O/R. Infusion of monoclonal antibody of β 2 integrin subunit (CD 11 b), IB 4 produced significant increase in reflow. Preischemia infusion of the anti-tissue factor monoclonal anti-body, TF 9-6 B 4 resulted in significant reduction of intramicrovascular fibrin in MCA : O/R. These results in-dicate that cell adhesion molecules and tissue factor-mediated events may play an important role in the proc-esses of brain ischemia, coagulation system activation and inflammation, which are interrelated each other.

Lifestyle-associated risk factors for acute brain infarction among persons of working age.

This study was designed to identify whether cigarette smoking, alcohol drinking, obesity, and use of oral contraceptives are independent risk factors for brain infarction among persons of working age. Health habits and previous diseases of 506 patients (366 men and 140 women aged 16 to 60 years) with acute first-ever symptomatic brain infarction were compared with those of 345 hospitalized control patients (219 men and 126 women) who did not differ from case subjects in respect to day of onset of symptoms or acuteness of disease onset. With the use of stepwise logistic regression, the variables for which the simultaneous risks of acute brain infarction were tested by sex were age, amount of alcohol consumed within 24 hours and 1 week before the illness, heavy drinking, smoking status, current smoking, cardiac disease, hypertension, diabetes, hyperlipemia, migraine, body mass index, and, in women, current use of oral contraceptives. Intake of > 40 g ethanol within the 24 hours preceding the onset of illness increased the risk for acute brain infarction both among men (P < .001) and women (P < .01) independently from other risk factors. Other significant independent risk factors for brain infarction among men were hypertension (P < .001), cardiac disease (P < .01), current smoking (P < .01), diabetes (P < .05), and history of migraine (P < .05) and among women, current use of oral contraceptives (P < .01) and current smoking (P < .05). Recent heavy drinking of alcohol, hypertension, cardiac disease, current smoking, diabetes, and history of migraine among men, and recent heavy drinking of alcohol, current use of oral contraceptives, and current smoking among women, seem to be independent risk factors for acute brain infarction.

Development of ischemic stroke in normotensive and hypertensive diabetic patients with or without antihypertensive treatment: An 8-year followup study

Although the impact of hypertension as a risk factor for brain infarction in diabetes mellitus is evident, the beneficial effect of antihypertensive therapy has not been demonstrated. Therefore, we designed a prospective cohort study to elucidate the effects of antihypertensive therapy on the development of ischemic stroke in diabetic out-patients. Two hundred forty patients, 219 non-insulin-dependent diabetes mellitus (NIDDM) and 21 insulin-dependent diabetes mellitus (IDDM), without history of cerebrovascular accident were followed for 8 years, from January 1981 until December 1988, in our diabetic clinic. Forty-eight of 88 hypertensive patients had received antihypertensive drugs. Among 40 untreated hypertensive and 152 initially normotensive diabetics, 14 hypertensives and 11 normotensives required antihypertensive therapy during followup period. Twenty-three patients were dropped out because of the unidentified reasons. Cerebrovascular accident occurred in 24 patients (10%): 18 brain infarctions, 4 transient ischemic attack (TIA), 1 subarachnoidal hemorrhage, and 1 brain hemorrhage. The percent incidence of ischemic strokes in the hypertension-treated patients was 8.9% which was similar to the 8.1% of the normotensives. In contrast, ischemic strokes developed in 29% of the untreated hypertensives, being significantly more frequent than in the former two groups. Multivariate analysis showed that serum total cholesterol and male gender were independent significant precursors of brain infarction in diabetic patients. In conclusion, antihypertensive treatment decreased the incidence of ischemic stroke in diabetics. Serum total cholesterol turned to independent risk factors for ischemic stroke in diabetic patients.

Precipitants of brain infarction. Roles of preceding infection/inflammation and recent psychological stress.

Antecedent febrile infection and psychological stress are described as predisposing risk factors for brain infarction. We examined the temporal relationship between preceding infection/inflammation and stroke onset as well as the role of recent psychological stress as a potential precipitant for brain infarction. In this case-control study, a standardized evaluation including a signs/symptoms-based questionnaire was used to characterize the prevalence and timing of recent prior (< 1 month) infectious and inflammatory syndromes in 37 adults with acute brain infarction, 47 community control subjects, and 34 hospitalized nonstroke neurological patient controls. Recent psychological stress was measured with scales of stressful life events and negative affect. The prevalence of infection/inflammation was significantly higher in the stroke group only within the preceding 1 week compared with either community control subjects (13/37 versus 6/47, P < .02) or hospitalized neurological patient controls (3/34, P < .02). Upper respiratory tract infections constituted the most common type of infection. A substantial proportion of stroke patients with preceding (< 1 week) infection/inflammation (5/13) had no accompanying fever or chills. There were no significant differences between the stroke and control groups in the levels of stressful life events within the prior 1 month or in negative-affect scale scores within the prior 1 week. Our data suggest that both febrile and nonfebrile infectious/inflammatory syndromes may be a common predisposing risk factor for brain infarction and that the period of increased risk is confined within a brief temporal window of less than 1 week. Results of this study argue against a role for recent psychological stress as a precipitant for cerebral infarction.

Impairments of the protein C system and fibrinolysis in infection-associated stroke.

Infection/inflammation appears to be an important predisposing risk factor for brain infarction, but little is known regarding underlying molecular mechanisms. We examined the hypothesis that patients with brain infarction preceded by infection/inflammation within 1 week could be identified by a distinctive procoagulant laboratory profile characterized by abnormalities in the protein C system and endogenous fibrinolysis. We performed a case-control study examining the relationship between preceding systemic infectious/inflammatory syndromes and selected immunohematologic variables in 36 patients with acute brain infarction and 81 control subjects (community control subjects [n = 47] and hospitalized nonstroke neurological patient controls [n = 34]). The stroke group had a lower mean level of the circulating antithrombotic enzyme activated protein C (APC) (4.33 +/- 0.34% [log-transformed percentage of control value, mean +/- SD]) than community control subjects (4.51 +/- 0.27%, P < .02) or hospitalized neurological patient controls (4.57 +/- 0.31%, P < .005). The lowest circulating APC levels were found in the stroke group with antecedent infection/inflammation within 1 week preceding index brain infarction (4.23 +/- 0.4%, n = 12). Within the stroke group, circulating APC levels were inversely related to IgG isotype anticardiolipin antibody titers (r = -.55, P < .001). Only the stroke group with infection/inflammation within 1 week had elevated plasma C4b binding protein compared with control subjects (141 +/- 61% versus 112 +/- 44%, P < .05). Stroke patients with antecedent infection/inflammation had a distinctively lower ratio of active tissue plasminogen activator to plasminogen activator inhibitor (0.11 +/- 0.04, n = 9) than other stroke patients (0.19 +/- 0.06, n = 9, P < .01) and control subjects (0.22 +/- 0.16, n = 17, P < .02). Impairments in the protein C pathway and endogenous fibrinolysis may contribute to the increased risk for brain infarction after recent (< or = 1 week) infection/inflammation. A decrease in the circulating anticoagulant APC may be related to elevated antiphospholipid antibody titers.

Recent Alcohol Consumption, Cigarette Smoking, and Cerebral Infarction in Young Adults

The role of recent heavy drinking of alcohol as a risk factor for ischemic brain infarction is unclear. We investigated this problem in young adults, in whom even a thorough workup often fails to reveal any predisposing factor. This was a hospital-based case-control study comprising 75 consecutive subjects aged 16 to 40 years with first-ever ischemic brain infarction and 133 control subjects from the same hospital who were group-matched with the case patients for age, sex, day of the onset of symptoms, and acuteness of disease onset. Multiple logistic regression analysis showed that alcohol intake exceeding 40 g of ethanol within the 24 hours preceding disease onset was a significant independent risk factor for brain infarction among both men (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.8 to 20.3) and women (OR, 7.8; 95% CI, 1.0 to 60.8). Cigarette smoking was not found to be an independent risk factor in the model, whereas among men arterial hypertension was (OR, 6.2; 95% CI, 1.5 to 24.7). We conclude that very recent alcohol drinking, particularly drinking for intoxication, may trigger the onset of brain infarction in young adults and that there might be a variety of mechanisms behind this effect.

Snoring and the risk of ischemic brain infarction.

To determine if a history of snoring is a risk factor for brain infarction, I conducted a case-control study of risk factors for ischemic stroke using 177 consecutive male patients aged 16-60 (mean 49) years with acute brain infarction. For each patient I chose an age-matched (+/- 6 years) male control. Arterial hypertension, coronary heart disease, snoring (habitually or often), and heavy drinking (greater than 300 g/wk) were risk factors in the stepwise multiple logistic regression analysis. The odds ratio of snoring for brain infarction was 2.13. By McNemar's test this association increased strongly if a history of sleep apnea, excessive daytime sleepiness, and obesity were all present with snoring (odds ratio 8.00). My study indicates that snoring may be a risk factor for ischemic stroke, possibly because of the higher prevalence of an obstructive sleep apnea syndrome among snorers than nonsnorers.

Progression and regression of carotid atherosclerosis in clinical trials.

Progression and regression of carotid atherosclerosis in clinical trials 1524-4636 Copyright © 1991 American Heart Association. All rights reserved. Print ISSN: 1079-5642. Online ISSN: 7272 Greenville Avenue, Dallas, TX 72514 Arteriosclerosis, Thrombosis, and Vascular Biology is published by the American Heart Association. 1991, 11:443-451 Arterioscler Thromb Vasc Biol http://atvb.ahajournals.org/content/11/2/443.citation located on the World Wide Web at: The online version of this article, along with updated information and services, is

Snoring as a risk factor for sleep-related brain infarction.

We studied 177 consecutive male patients aged 16-60 years with brain infarction verified by neuroradiology and analyzed the time of onset of stroke symptoms related to sleep and the role of possible or known risk factors for brain infarction. Brain infarction occurred relatively more often during the first 30 minutes after awakening than at any other time. In multiple stepwise logistic regression analyses, snoring was the only independent risk factor differentiating stroke occurring during sleep and stroke occurring either during sleep or during the first 30 minutes after awakening from stroke occurring at other times of the day. The risk ratios were 2.65 (95% confidence interval 1.32-5.29, p less than 0.005) and 3.16 (95% confidence interval 1.61-6.22, p less than 0.001), respectively. Other factors tested were age, arterial hypertension, diabetes mellitus, smoking, alcohol consumption, and body mass index. Arterial hypertension seemed to have an additive effect on the independent risk caused by snoring.

FEBRILE INFECTION IS A RISK FACTOR FOR ISCHEMIC STROKE.

To ascertain whether febrile infection is a risk factor for brain infarction, investigators conducted a case- control study of 54 young and middle-aged