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.     

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.     

The history of sleep apnea is associated with shorter leukocyte telomere length: the Helsinki Birth Cohort Study

ObjectivesSleep apnea poses an elevated risk for chronic age-related diseases. Leukocyte telomere length (LTL), a biomarker and factor associated with accelerated cellular aging processes, may serve as a novel mechanism underlying these disease risks. We investigated if a history of clinician-diagnosed sleep apnea or primary snoring was associated with LTL in later adulthood.MethodsData on sleep apnea, primary snoring and LTL, were available for 1948 participants from the Helsinki Birth Cohort Study. Patients with sleep apnea (n = 44) and primary snoring (n = 29) severe enough to be recorded as an inpatient diagnosis for hospitalization were identified by their case records through the Finnish Hospital Discharge Register. The LTL was measured by using the realtime quantitative polymerase chain reaction (PCR) method at a mean age of 61.5 years (standard deviation [SD], 2.9).ResultsA history of sleep apnea was associated with shorter LTL (P = .010). Adjustment for a number of covariates did not alter the association.ConclusionsAccelerated cellular aging reflected in shorter LTL in patients with a history of sleep apnea may partly explain their higher risk for age-related diseases. Future studies elucidating the impacts of long-term or successful treatment history of sleep apnea on the maintenance of LTL are warranted.     

Increased prevalence of sleep apnea in patients with recurring ischemic stroke compared with first stroke victims

Since sleep apnea (SA) and stroke have many shared risk factors an independent contribution of SA to the overall risk of stroke is not easily proven and has been questioned recently. To contribute to this controversy, we analysed the frequency of SA in groups of patients with first and recurring ischemic stroke. We prospectively studied 102 patients admitted to our stroke unit. The prevalence of vascular risk factors and a history of previous stroke were recorded. All patients received cardio–respiratory polygraphy during the first 72 hours after admission. CT and MRI scans were evaluated for the location of the acute stroke and the presence of older vascular lesions. Thirty–four women and 68 men with a mean age of 64.5 ± 13.7 years were included in the study. Cerebral lesions attributable to a previous stroke were identified in 25 patients, of whom 19 reported to have suffered a stroke before. Patients with stroke recurrence had a higher mean apnea–hypopnea index (AHI) (26.6/h vs. 15.1/h, p<0.05) and more often presented with a sleep apnea syndrome (SA) defined by an AHI ≥ 10/h (80 vs. 52%, p < 0.05) than patients with first ever stroke. Logistic regression analysis including the variables "age", "gender", "cumulative risk factors", "AHI ≥ 10/h", and "diabetes" identified diabetes (Odd’s ratio [OR] = 4.5) and AHI ≥ 10/h (OR = 3.5) as independent risk–factors for stroke recurrence. According to our results SA is an independent risk factor for stroke recurrence. We therefore advocate routine sleep–apnea screening in all patients having suffered an ischemic stroke. The first two authors contributed equally to this work.     

Central sleep apnea is associated with increased risk of ischemic stroke in the elderly

Muñoz R, Durán‐Cantolla J, Martinez‐Vila E, Gállego J, Rubio R, Aizpuru F, De La Torre G, Barbé F. Central sleep apnea and risk of stroke in the elderly.
Acta Neurol Scand: 2012: 126: 183–188.
© 2011 John Wiley & Sons A/S. Objectives – Sleep apnea/hypopnea syndrome is a well‐recognized independent risk factor for stroke in middle‐aged population, but controversy remains in older subjects. We examined the possible association between different respiratory parameters and risk of stroke in a prospective population‐based cohort of 394 stroke‐free elderly subjects. Material and Methods – Fully overnight polysomnography was performed at baseline. Over the 6 year follow‐up period, 20 ischemic strokes occurred. Differences in stroke‐free survival between subjects according to central apnea index (CAI) were assessed. Results – We just observed association with incident ischemic stroke on central sleep apnea (CSA) episodes. Obstructive sleep apnea, time passed under 90% oxygen saturation, or arousal index were not associated. The event‐free survival was lowest in the highest CAI group. This association was independent of any other vascular risk factors. Conclusions – CSA is the specific respiratory event associated with stroke in the elderly. Additionally, CSA could be a marker of silent brain ischemia, as a sign of disturbed regulation of central respiratory mechanisms, tentatively of ischemic origin.     

Obstructive sleep apnea linked to wake-up strokes

Obstructive sleep apnea (OSA) has been considered as one of the risk factors for ischemic stroke, but the impact of OSA on wake-up stroke (WUS) is not well studied. We aimed to determine the relationship between OSA and WUS. We prospectively recruited 71 patients with mild to moderate ischemic stroke during hospitalization. Patients were classified into WUS and non-WUS. A full-night sleep respiratory study was performed between 3 and 14 days after stroke onset. Demographic data, sleep respiratory data, heart rate variability, stroke risk factors, stroke classification and sleep-related scales were recorded. We compared the differences in the variables between the two groups and determined the independent variables associated with WUS. Of the 71 patients, 26 (36.6%) had WUS. The patients with WUS had a significantly higher apnea-hypopnea index (23.1 ± 19.4 vs. 12.5 ± 11.9, p = 0.016), obstructive apnea index (7.8 ± 9.7 vs. 3.0 ± 4.0, p = 0.021) and lower mean blood oxygen saturation (95.1 ± 1.5 vs. 95.8 ± 1.3, p = 0.046) than the non-WUS patients. There were no significant differences in demographic data, stroke risk factors, sleep-related scales or heart rate variability. Logistic regression revealed that severe sleep-disordered breathing (apnea-hypopnea index ≥30) was the only independent variable associated with WUS (OR 6.065, 95% CI 1.451-25.350; p = 0.014). We conclude that in patients with mild to moderate ischemic stroke, OSA is the only risk factor associated with WUS, which cannot be distinguished clinically from non-WUS.     

卒中后睡眠障碍相关危险因素的Meta分析

【摘要】
目的 通过对卒中后睡眠障碍相关文献进行分析,分析卒中后睡眠障碍的常见危险因素。
方法 采用Meta分析方法,对符合条件的11篇有关卒中后睡眠障碍危险因素的文献进行定量分析,对每个危险因素进行异质性检验以及合并优势比（odds ratio,OR）和95％可信区间（confidence interval,CI）的计算。
结果 有5个因素与卒中后睡眠障碍有统计学意义,分别是：习惯性打鼾（OR 14.77,95％CI 5.52～39.53）、高血压（OR 1.3,95％CI 1.03～1.66）、糖尿病（OR 1.41,95％CI 1.08～1.84）、饮酒（OR 1.59,95％CI 1.19～2.12）、皮质型卒中（OR 1.31,95％CI 1.06～1.63）,合并结果稳定性较好。尚不能确定性别（OR 1.12,95％CI 0.96～1.31）、高血脂（OR 0.96,95％CI 0.7～1.33）、吸烟（OR 1.27,95％CI 0.73～2.20）、卒中史（OR 1.05,95％CI 0.74～1.49）与卒中后睡眠障碍有关。
结论 现有的证据表明高血压、糖尿病、饮酒、习惯性打鼾及皮质型卒中是卒中后睡眠障碍的危险因素。     

Risk factors for cryptogenic ischaemic stroke

This case-control study was designed to identify risk factors for cryptogenic brain infarction. We assessed the frequency of prothrombotic states, homocysteine, lipoprotein (a) [Lp(a)] and other lipids and the apolipoprotein E phenotype together with conventional risk factors in 46 patients (19 women and 27 men) with cryptogenic brain infarction aged from 15 to 60 years and in 104 community-based controls. Multivariate odds ratios (ORs) for risk factors and 95% CIs were calculated by logistic regression. Hypertension (OR 4.5; 95% CI, 1.5-13.2; P = 0.006), current smoking (OR 2.9; 95% CI, 1.2-6.8; P = 0.012), low HDL cholesterol (HDL-C) (OR 5.4; 95% CI, 1.1-25.5; P = 0.035) and high clotting factor VIII activity (OR 3.6; 95% CI, 1.1-12.2; P = 0.041) were variables associated with cryptogenic brain infarction. These risk factors were not equally frequent in women and men. Low HDL-C and high factor VIII activity in the women, and hypertension, current smoking and a low level of plasma folate in the men were risk factors for cryptogenic stroke. Several of the observed risk factors for cryptogenic brain infarction were lifestyle-associated, which emphasizes the role of health education in addition to pharmacological treatment in the prevention of stroke.     

Central sleep apnea is uncommon after stroke

Objective/backgroundStroke is often considered a risk factor for central sleep apnea (CSA). The goal of this study was to determine the prevalence and clinical correlates of CSA in patients with ischemic stroke.Patients/methodsIn this analysis, 1346 participants in the Brain Attack Surveillance in Corpus Christi (BASIC) project underwent a home sleep apnea test shortly after ischemic stroke. Respiratory events during sleep were classified as central apneas, obstructive apneas, or hypopneas. Central apnea index (CAI) was defined as number of central apneas divided by recording time. CSA was defined as CAI ≥5/hour with at least 50% of all scored respiratory events classified as central apneas. Demographics and co-morbidities were ascertained from the medical record.ResultsMedian CAI was 0/hour. Nineteen participants (1.4%) met criteria for CSA. Participants with CSA were more likely to be male, and had lower prevalence of obesity than participants without CSA. There was no association between CSA and other co-morbidities.ConclusionsCSA was uncommon in this large cohort of patients with recent ischemic stroke.     

Wake-up stroke is not associated with obstructive sleep apnea

Objective/BackgroundObstructive sleep apnea is a risk factor for stroke. This study sought to assess the relationship between obstructive sleep apnea (OSA) and wake-up strokes (WUS), that is, stroke symptoms that are first noted upon awakening from sleep.Patients/methodsIn this analysis, 837 Brain Attack Surveillance in Corpus Christi (BASIC) project participants completed an interview to ascertain stroke onset during sleep (WUS) versus wakefulness (non-wake-up stroke, non-WUS). A subset of 316 participants underwent a home sleep apnea test (HSAT) shortly after ischemic stroke to assess for OSA. Regression models were used to test the association between OSA and WUS, stratified by sex.ResultsOf 837 participants who completed the interview, 251 (30%) reported WUS. Among participants who underwent an HSAT, there was no significant difference in OSA severity [respiratory event index (REI)] among participants with WUS [median REI 17, interquartile range (IQR) 10, 29] versus non-WUS (median REI 18, IQR 9, 30; p = 0.73). OSA severity was not associated with increased odds of WUS among men [unadjusted odds ratio (OR) 1.011, 95% confidence interval (95% CI) 0.995, 1.027] or women (unadjusted OR 0.987, 95% CI 0.959, 1.015). These results remained unchanged after adjustment for age, congestive heart failure, body mass index, and pre-stroke depression in men (adjusted OR 1.011, 95% CI 0.994, 1.028) and women (adjusted OR 0.988, 95% CI 0.959, 1.018).ConclusionsAlthough OSA is a risk factor for stroke, the onset of stroke during sleep is not associated with OSA in this large, population-based stroke cohort.     

睡眠质量对青年缺血性卒中短期预后的影响

目的 研究睡眠质量对青年缺血性卒中短期预后的影响。 方法 连续性、前瞻性地收集年龄在18～45岁的首发卒中患者223例作为观察对象。建立完善基线资 料、青年缺血性卒中预后可能相关因素的数据库,采用匹兹堡睡眠质量指数（Pittsburgh Sleep Quality Index,PSQI）问卷评分评估睡眠质量,美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale,NIHSS）评分、改良Rankin量表（modified Rankin Scale,mRS）评分评估其入院后病情及发 病后3个月的预后情况,采用单因素及多元Logistic回归分析法对影响青年缺血性卒中预后的相关因素 进行分析,并分析研究睡眠质量对青年缺血性卒中短期预后的影响。 结果 共获取观察组有效病例223例,其中男性170例（76.2%）,女性53例（23.8%）。单因素分析结 果显示与青年缺血性卒中短期预后的相关因素有：NIHSS评分、睡眠质量、高同型半胱氨酸血症。将上 述有意义的变量纳入Logistic回归模型,显示睡眠质量差与青年缺血性卒中3个月mRS评分有关,比值 比（odds ratio,OR）1.829;95%可信区间（confidence interval,CI）1.014～3.301。 结论 睡眠质量差能影响青年缺血性卒中短期预后。     

Common genetic variants of homocysteine metabolism in ischemic stroke: a case–control study

Hyperhomocysteinemia is a risk factor for ischemic stroke. We investigated five functional polymorphisms involved in homocysteine metabolism in each 159 stroke patients and controls. The folate-sensitive polymorphism methylenetetrahydrofolate reductase (MTHFR) c. 677 C > T (A222V) referred a non-significant risk of ischemic stroke (odds ratio: 1.20) in all patients, and homozygosity for MTHFR c. 677 C > T was associated with an earlier onset of stroke selectively in patients younger than 60 years (38 +/- 3 years vs. 45 +/- 1 years; P = 0.043). This study suggests that the investigated polymorphisms are no major risk factors for stroke, although MTHFR c. 677 C > T could be a minor factor of vulnerability especially in young patients (TT genotype), which might be helpful for the clinical work-up of stroke cases and for preventive dietary strategies.     

Predictors of primary medical care consultation for sleep disorders

ObjectivesTo describe the prevalence and risk factors for primary care consultations for insomnia and/or snoring/sleep apnea.MethodsRetrospective cross-sectional, population-based postal survey of 10,000 people randomly selected from the New South Wales electoral roll; 3300 responded (35.6%). Direct contact with a random subset from the non-responders (n = 100) was also undertaken with a response rate of 49%.ResultsThe population weighted prevalence for having insomnia was 33.0%, with 11.1% visiting a doctor. The weighted prevalence for reporting a visit to the doctor for snoring/sleep apnea was 6.2%, while 2.9% reported having visited a doctor for both disorders. The percentages of males and females consulting their doctor for either sleep disorder were similar. Independent risk factors for insomnia visits were: being older, daytime sleepiness, short sleep durations, and reduced enthusiasm. Self-medication for insomnia symptoms was common. Independent risk factors for snoring/sleep apnea visits were: being older, daytime sleepiness, short sleep durations, and reduced enthusiasm.ConclusionsThe risk factors for seeking medical help for self-suspected insomnia or snoring/sleep apnea were similar. The reported excess proportion of men being diagnosed in sleep apnea clinics appears to be related to a differential referral by clinicians. We recommend that clinicians discuss both insomnia and snoring/sleep apnea because these disorders are commonly found in patients presented with either condition.     

Early clinical differentiation of cerebral infarction from severe atherosclerotic stenosis and cardioembolism.

BACKGROUND AND PURPOSE: Hyperacute cerebral infarction trials require early differentiation of infarction subtype. Our aim was to determine clinical factors predictive of infarction subtype from data collected in the early hours of admission. METHODS: Using the 1,273 patients enrolled in the Stroke Data Bank, stroke risk factors and demographic, clinical, and radiological features were compared between the 246 cardioembolic and 113 large-vessel atherosclerotic cerebral infarcts. RESULTS: Stroke Data Bank definitions ensured more transient ischemic attacks in atherosclerotic infarcts and more cardiac disease in cardioembolic infarcts, but the diagnosis was distinguished further using a logistic regression model. Fractional arm weakness (shoulder different from hand) (odds ratio 3.1, 95% confidence interval [CI] 1.6-5.8), hypertension (odds ratio 2.8, CI 1.4-5.3), diabetes (odds ratio 2.5, CI 1.2-5.1) and male gender (odds ratio = 2.2, CI 1.2-4.1) occurred more frequently in patients with atherosclerotic than cardioembolic infarcts. Reduced consciousness (odds ratio = 3.2, CI 1.4-7.3) was more frequent in cardioembolism. For a male patient with hypertension, diabetes, and fractional arm weakness, the estimated odds of an atherosclerotic infarction were 47-fold that of a cardioembolic infarction. Patients with atherosclerotic infarcts were more likely to have a fractional arm weakness regardless of infarct size, whereas, for those with cardioembolic infarctions, fractional weakness was more frequent in infarcts less than 20 cc in volume. CONCLUSIONS: Clinical features that are observed at stroke onset can help distinguish cerebral infarction subtypes and may allow for early stratification in therapeutic trials.     

Prevalence of ischemic heart disease among patients with sleep apnea syndrome

Abstract We investigated the prevalence of ischemic heart disease (IHD) in sleep apnea syndrome (SAS) and the presence of coronary risk factors involved in the onset of IHD in 386 subjects with suspected SAS due to heavy snoring. The prevalence of IHD among patients with untreated SAS was found to be 23.8%, and the percentage of patients having SAS complicated with IHD was high among those with moderate or severe SAS. Sleep apnea syndrome patients with IHD also showed high prevalences of hypertension and hyperlipidemia. It appears that sleep apnea aggravates the factors that cause coronary vascular disorders, and is involved in the onset of IHD.     

Clinical study of lacunar infarcts in non-hypertensive patients

Lacunar infarcts in non-hypertensive patients have been scantly assessed. The objective of this study was to determine clinical features of lacunar infarct in patients without hypertension (n = 91) in comparison with characteristics of lacunar infarcts occurring in patients with hypertension (n = 283) collected from a prospective hospital-based stroke registry in which 2000 patients with acute stroke are included. Predictors of lacunar infarct in patients without hypertension were assessed by multiple logistic regression analysis. The group of non-hypertensive patients with lacunar infarction showed a significantly higher frequency of male gender, age 85 years or older, history of atrial fibrillation, chronic obstructive pulmonary disease and diabetes mellitus, and a significantly lower frequency of female gender and absence of limitation at hospital discharge than hypertensive patients with lacunar infarct. Differences between hypertensive and non-hypertensive patients in relation to frequency of the different lacunar syndromes were not observed. After multivariate analysis, age 85 years or older (odds ratio 3.13), diabetes (odds ratio 2.57), and male gender (odds ratio 1.99) seemed to be independent factors associated with lacunar infarct in patients without hypertension. Lacunar infarct in non-hypertensive patients showed some differential clinical features compared to the remaining lacunar infarctions because it occurred more frequently in male patients aged 85 years or older. In this group, diabetes was the most important modificable risk factor. These results suggest an ealier effect of arteriopathy caused by hypertension favoring lacunar brain ischemia, whereas in non-hypertensive patients, arteropathy responsible for small vessel disease would take a more prolonged time in causing lacunar infarction.     

Respiratory infectious complications after acute ischemic stroke]

BACKGROUND AND PURPOSE: Respiratory infection is a frequent complication in acute ischemic stroke, but it seems to have been made light of in stroke care. The purpose of this study is to examine the clinical characteristics of respiratory infectious complications in patients with acute ischemic stroke. METHOD: Two-hundred and fifty-eight consecutive patients (158 men, 100 women, 70.6 +/- 12.9 years old) with acute ischemic stroke were admitted to our hospitals between May and October in 1999. Age, gender, history of stroke, the severity of stroke on admission, stroke subtype (lacunar brain infarction, atherothrombotic brain infarction, cardioembolic brain infarction, and others), aspiration, naso-gastric tube feeding, vascular risk factors, the length of hospital stay and outcome of patients were noted. We compared them between patients with and without respiratory infections. RESULTS: Forty-five (17.4%) patients were developed respiratory infections. Cardioembolic stroke patients were more frequently developed respiratory infections (67%) compared with other stroke subtypes. The independent risk factors for respiratory infectious complications by multiple logistic regression model were the aspiration (OR, 5.513; 95% CI, 1.793-16.946) and the severity of stroke on admission (OR, 1.090; 95% CI, 1.034-1.150). Mortality of patients with respiratory infectious complications was as high as 24%, and all survivors discharged to another hospital. After adjustment for age and the severity of stroke, respiratory infection was one of the independent risk factors of poor stroke outcome (OR, 5.838; 95% CI, 1.792-19.018). CONCLUSION: Aspiration and the severity of stroke independently predict development of respiratory infectious complication in acute ischemic stroke. Respiratory infections may make worse their stroke outcome. A measure to infectious complications and aspiration needs to be taken for the patients suffering from severe ischemic stroke.     

Is there a link between the severity of sleep‐disordered breathing and atherosclerotic disease of the carotid arteries?

Epidemiological studies have shown a strong association between sleep-disordered breathing (SDB) and cerebrovascular diseases. A total of 114 male patients, aged 40-65 years, referred to sleep laboratory for the evaluation of snoring and disturbed sleep were studied. Subjects were divided into three groups: habitual snoring, mild-moderate and severe obstructive sleep apnea syndrome (OSAS), respectively, determined by using three respiratory disturbance index (RDI) cut points (/=30). Measurement of intima-media thickness (IMT) and the presence of plaque were determined by ultrasonographic evaluation. Major vascular risk factors such as hypertension, diabetes, smoking, hyperlipidemia, and obesity were determined. The OSA groups had significantly higher IMT values compared with the habitual snoring group. Three groups were significantly different with regard to the presence of plaque. Age and body mass index were found to be significantly associated with IMT while age and RDI were found to be most probably predictive for plaque. There were no significant differences amongst the three groups with respect to age, prevalence of hypertension and diabetes, smoking, total cholesterol and total triglyceride levels. These findings suggested that SDB is a predisposing factor for the atherosclerotic process and precipitate plaque particularly when associated with higher RDI.     

非心源性缺血性卒中近期再发危险因素分析

目的 探讨首发非心源性缺血性卒中且二级预防药物依从性好的患者近期再发的相关危险因素。      

Prospective study of Chlamydia pneumoniae IgG and IgA seropositivity and risk of incident ischemic stroke

BACKGROUND AND PURPOSE: Chlamydia pneumoniae infection or exposure to C. pneumoniae was implicated as a risk factor for ischemic stroke. Our aim was to evaluate prospectively the association between the presence of antibodies to C. pneumoniae (IgG and IgA) and the risk of incident ischemic stroke among patients with pre-existing vascular disease. METHODS: Sera were collected from 3,090 coronary heart disease patients enrolled in a secondary prevention trial. We measured baseline antibodies (IgG and IgA) in the sera of patients who developed subsequent ischemic strokes (cases, n = 134) during follow-up (mean 8.2 years), and in 134 age- and gender-matched pairs without subsequent stroke or myocardial infarction. RESULTS: The crude relative odds (95%CI) of incident ischemic strokes in seropositive patients at baseline (>1.1 relative value units) were 1.29 (95%CI, 0.69-2.47) for IgG and 1.31 (95% CI, 0.69-2.55) for IgA by matched-pair analyses, and 1.42 (95%CI, 0.69-2.98) for IgG and 1.57 (95%CI, 0.76-3.35) for IgA after adjustments for conventional risk factors and the inflammatory marker, soluble intercellular adhesion molecule-1. We explored the possibility that the risk of ischemic stroke may increase in parallel to increasing antibody titers, but did not demonstrate any significant association. CONCLUSIONS: Serological evidence for prior infection with C. pneumoniae did not emerge as an independent risk factor for incident ischemic stroke among patients at high risk due to pre-existing vascular disease.