Large-Artery Stenosis Predicts Subsequent Vascular Events in Patients with Transient Ischemic Attack

Background and purpose

We investigated subsequent vascular events in patients with transient ischemic attack (TIA) and determined the predictors of such events among vascular risk factors including large-artery disease, TIA-symptom duration, and acute ischemic lesions on diffusion-weighted imaging (DWI).

Methods

We identified 98 consecutive patients with TIA who visited a tertiary university hospital and underwent DWI and brain magnetic resonance angiography within 48 hours of symptom onset. We reviewed the medical records to assess the clinical characteristics of TIA, demographics, and the subsequent vascular events including acute ischemic stroke, TIA, and myocardial infarction.

Results

Large-artery disease was detected in 55 patients (56%). Ten patients (10%) experienced TIA symptoms for longer than 1 hour, and acute infarctions on DWI were identified in 30 patients (31%). During the mean follow-up period of 19 months, seven patients (7%) had an acute ischemic stroke and 20 patients (20%) had TIA. Retinal artery occlusion in two patients, spinal cord infarction in one patient, and peripheral vascular claudication in one patient were also recorded. Cox proportional-hazards multivariate analysis revealed that large-artery disease was an independent predictor of subsequent cerebral ischemia (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.1-7.1; p=0.02) and subsequent vascular events (HR, 2.9; 95% CI, 1.2-6.7; p=0.01).

Conclusions

In patients with TIA, large-artery disease is an independent predictor of subsequent vascular events. Acute infarction on DWI and a symptom duration of more than 1 hour are not significantly correlated with a higher risk of subsequent vascular events. These findings suggest that the underlying vascular status is more important than symptom duration or acute ischemic lesion on DWI.     

The prognostic value of pulsatility index, flow velocity, and their ratio, measured with TCD ultrasound, in patients with a recent TIA or ischemic stroke

Wijnhoud AD, Koudstaal PJ, Dippel DWJ. The prognostic value of pulsatility index, flow velocity, and their ratio, measured with TCD ultrasound, in patients with a recent TIA or ischemic stroke.
Acta Neurol Scand: 2011: 124: 238–244.
© 2011 John Wiley & Sons A/S. Background – Increased flow velocities, and combinations of low mean flow velocity (MFV) and a high pulsatility index (PI) are associated with intracranial arterial disease. We investigated the association of MFV and the ratio of PI and MFV (PI–MFV ratio) in the middle cerebral artery (MCA) with recurrence of vascular events in patients with a transient ischemic attack (TIA) or minor ischemic stroke. Methods – Five hundred and ninety‐eight consecutive patients underwent TCD investigation. Outcome events were fatal or non‐fatal stroke and the composite of stroke, myocardial infarction, or vascular death (major vascular events). Hazard ratios (HR) were estimated with Cox proportional hazards multiple regression method, adjusted for age, gender, and vascular risk factors. Results – TCD registration was successful in 489 patients. Mean follow‐up was 2.1 years. Cumulative incidence was 9% for all stroke and 12% for major vascular events. MFV over 60.5 cm/s increased the risk for both stroke (HR 2.8; 95% CI: 1.3–6.0) and major vascular events (HR 2.6; 95% CI: 1.3–5.0). Each unit increase in PI–MFV ratio was associated with a HR 2.8 (95% CI: 1.7–4.8) for stroke and HR 2.2 (95% CI: 1.3–3.6) for major vascular events. Conclusion – In patients with a TIA or non‐disabling ischemic stroke, MFV and the PI–MFV ratio in the MCA are independent prognostic factors for recurrent vascular events.     

不同炎症反应在脑梗死与短暂性脑缺血发作患者中表达及意义研究

目的探讨不同炎症因子在脑梗死与短暂性脑缺血发作患者的表达情况。方法选取64例短暂性脑缺血发作患者(TIA组)、58例脑梗死患者(CI组)以及50例健康人员(NC组),分析并统计3组受试对象炎症因子表达情况。结果 CI组MMP-9(83.14±9.27)μg/L、NF-κB(36.88±6.27)%、IL-33(71.63±4.83)ng/m L及hs-CRP(12.57±1.29)mg/L,TIA组分别为(29.17±4.54)μg/L、NF-κB(31.20±5.97)%、IL-33(104.59±8.27)ng/m L及hs-CRP(6.23±1.04)mg/L,两组间比较差异具有统计学意义(P=0.026、P=0.032、P=0.025和P=0.009)。Logistic回归分析显示,TC、MMP-9、IL-33及hs-CRP为CI的独立危险因素。TC、hs-CRP为TIA的独立危险因素。MMP-9+IL-33+hs-CRP预测CI发生的AUC为0.859(95%CI:0.751~0.911),显著高于MMP-9(AUC为0.711,95%CI:0.649~0.824)、IL-33(AUC为0.698,95%CI:0.659~0.855)和hs-CRP(AUC为0.705,95%CI:0.671~0.848)的诊断效能(Z=9.267、11.553和10.234,均P=0.000)。结论脑梗死、短暂性脑缺血发作患者存在炎症因子表达差异,MMP-9、IL-33及hsCRP联合检测对CI具有较高的诊断价值。     

Hemostatic markers in patients at risk of cerebral ischemia

BACKGROUND: Increased levels of markers of hemostasis may assist in the determination of the extent of carotid occlusive disease and the identification of neurologically intact individuals at increased risk of ischemic events. METHODS: We conducted a prospective study of 304 subjects, including 82 with a recent (< or =7 days) transient ischemic attack (TIA), 157 asymptomatic individuals with a cervical bruit, and 65 control subjects. Baseline evaluation included a neurological assessment, ECG, cervical ultrasonography, and cerebral CT and/or MRI. Levels of markers of coagulation and fibrinolytic activity were also determined. Results were analyzed in relation to the degree of carotid disease and the subsequent occurrence of cerebral and cardiac ischemic events. RESULTS: Over a mean follow-up period of 2.8 years (SD, 1.3 years), 114 ischemic events occurred. Survival analyses showed that prothrombin fragment 1.2 (F(1.2)) was a predictor of time to cerebral and cardiac ischemic events in the combined TIA and asymptomatic bruit group (relative risk [RR], 1.46; 95% CI, 1.18 to 1.81) as well as in the asymptomatic bruit group separately (RR, 1.70; 95% CI, 1.14 to 2.53). In the TIA group, both F(1.2) (RR, 2.36; 95% CI, 1.19 to 4.68) and severe (> or =80%) carotid stenosis (RR, 3.53; 95% CI, 1.19 to 10.51) were predictive of time to ischemic stroke, myocardial infarction, or vascular death. CONCLUSIONS: In patients with TIAs and in asymptomatic individuals with cervical bruits, F(1.2) levels were found to be independent predictors of subsequent cerebral and cardiac ischemic events. Our results are consistent with an active role of the coagulation system through upregulation of thrombin in carotid disease progression and in the pathogenesis of ischemic events in patients at risk.     

Absent collateral function of the circle of Willis as risk factor for ischemic stroke

BACKGROUND: Autopsy studies show a higher prevalence of circle of Willis anomalies in brains with signs of ischemic infarction. Our goal was to examine the collateral function of the circle of Willis in ischemic stroke patients and to assess in a case-control study if a collateral deficient circle of Willis is a risk factor for ischemic stroke in patients with severe internal carotid artery (ICA) occlusive disease. METHODS: Our case-control study included 109 patients with an acute ischemic stroke in the anterior circulation and 113 patients with peripheral arterial disease and no known history of cerebral ischemia. The collateral function of the anterior and posterior communicating arteries of the circle of Willis was assessed by means of transcranial color-coded duplex ultrasonography (TCCD) and carotid compression tests. RESULTS: TCCD was successfully performed in 75 case patients (mean age 64 years, range 41-91 years) and in 100 control patients (mean age 61 years, range 35-89 years). In 26 cases and 19 controls, a >/=70% stenosis or occlusion of the ICA was found. A nonfunctional anterior collateral pathway in the circle of Willis was found in 33% of the cases and in 6% of the controls (p < 0.001). The posterior collateral pathway was nonfunctional in 57% of the cases and in 43% of the controls (p = 0.02). In patients with severe ICA occlusive disease, the odds ratios of a nonfunctional anterior and a nonfunctional posterior collateral pathway were 7.33 (95% confidence interval, CI, = 1.19-76.52) and 3.00 (95% CI = 0.77-12.04), respectively. CONCLUSIONS: Patients who suffer ischemic stroke in the anterior circulation have a higher incidence of collateral deficient circles of Willis than those with atherosclerotic vascular disease without ischemic cerebrovascular disease. The presence of a nonfunctional anterior collateral pathway in the circle of Willis in patients with severe ICA occlusive disease is strongly associated with ischemic stroke.     

Apolipoproteins as predictors of ischaemic stroke in patients with a previous transient ischaemic attack

BACKGROUND: Weak associations between total and LDL cholesterol and ischaemic stroke compared with coronary heart disease (CHD) are at odds with the similar effectiveness of statin drugs in preventing ischaemic stroke and CHD, suggesting that other lipid sub-fractions that are affected by statins might be better predictors of ischaemic stroke. Apolipoprotein B levels are reduced by statins and are a stronger predictor of CHD than total and LDL cholesterol in patients both on and off statins. However, there are very few published data on apolipoproteins and stroke risk and no studies in patients with previous transient ischaemic attack (TIA). METHODS: We performed a prospective cohort study of the associations of baseline total cholesterol, LDL, HDL, apolipoproteins A1 and B (apo A1; apo B) and risk of ischaemic stroke in 261 patients with previous TIA. Cox proportional hazards models were used to determine crude and multivariate-adjusted hazard ratios (HR) above versus below median values at 10-years follow-up. RESULTS: The apo B/apo A1 ratio was the strongest independent predictor of ischaemic stroke (HR=2.94, 95% CI 1.43-5.88, p=0.003) followed by apo B (HR=2.26, 95% CI 1.16-4.38, p=0.02). The associations between total cholesterol, LDL, HDL, LDL/HDL ratio and apo A1 and ischaemic stroke risk did not reach statistical significance. CONCLUSIONS: Apo B and the apo B/apo A1 ratio are predictive of ischaemic stroke in patients with previous TIA. Further studies are required to determine whether the prognostic value of apolipoprotein levels is maintained in patients on statins.     

Comparison of the impact of atrial fibrillation on the risk of early death after stroke in women versus men

BACKGROUND: Atrial fibrillation (AF) is considered a predictive factor of poor clinical outcome in patients with an ischemic stroke (IS). This study addressed whether the impact of AF on the in-hospital mortality after first ever IS is different according to the patient's gender. METHODS: We prospectively studied 1678 patients with first ever IS consecutively admitted to two University Hospitals. We recorded demographic data, vascular risk factors, and the stroke severity (NIHSS) at admission analyzing their impact on the in-hospital mortality and on the combined mortality-dependency at discharge using a Cox proportional hazards model. Two variable interactions between those factors independently related to in-hospital mortality and combined mortality-dependency at discharge were tested. RESULTS: Overall in-hospital mortality was 11.3%. Cox proportional hazards model showed that NIHSS at admission (HR: 1.178 [95% CI 1.149-1.207]), age (HR: 1.044 [95% CI 1.026-1.061]), AF (HR: 1.416 [95% CI 1.048-1.913]), male gender (HR: 1.853 [95% CI 1.323-2.192) and ischemic heart disease (HR: 1.527 [95% CI 1.063-2.192]) were independent predictors of in-hospital mortality. A significant interaction between gender and AF was found (p = 0.017). Data were stratified by gender, showing that AF was an independent predictor of poor outcome just for woman (HR: 2.183 [95% CI 1.403-3.396]; p < 0.001). The independent predictors of combined mortality-disability at discharge were NIHSS at admission (HR: 1.052 [95% CI 1.041-1.063]), age (HR: 1.011 [95% CI 1.004-1.018]), AF (HR: 1.197 [95% CI 1.031-1.390]), ischemic heart disease (HR: 1.222 [95% CI 1.004-1.488]), and smoking (HR: 1.262 [95% CI 1.033-1.541]). CONCLUSIONS: The impact of AF is different in the two genders and appears as a specific ischemic stroke predictor of in-hospital mortality just for women.     

Management and outcome of patients with transient ischemic attack admitted to a stroke unit

BACKGROUND: The way in which patients with transient ischemic attack (TIA) are investigated and treated varies substantially worldwide. There are no data on the management and outcome of TIA patients admitted to a stroke unit. We assessed to what extent rapid management of TIA patients admitted to a stroke unit led to specific treatments which can prevent stroke and evaluated the early risk and predictors of stroke in these patients. METHODS: From January 2003 to November 2005, 203 consecutive patients with a recent (<48 h) TIA were admitted to our stroke unit. All patients had a diffusion-weighted imaging (DWI) on admission, a standardized etiological workup, and were followed up to 3 months. RESULTS: The median (interquartile range) time from TIA onset to admission to the stroke unit was 12 h (5-25). DWI revealed acute lesions in 64 patients (32%). Of the 203 patients, 147 (72%) were treated by antiplatelet therapy and 56 (28%) with high doses of heparin, soon after their admission. In addition, 7 patients (3%) had a carotid revascularization. The risk of stroke was 2.5% (95% CI, 0.3-4.7) at 1 week, and 3.5% (1.0-6.1) at 3 months. In multivariate analysis, a score > or =5 at the previously validated ABCD score (HR = 5.0; 1.0-25.8; p = 0.06) and the presence of DWI abnormalities (HR = 10.3; 1.2-86.7; p = 0.03) were independent predictors of stroke at 3 months. CONCLUSION: Early management of TIA in a stroke unit leads to specific treatments in a significant proportion of cases. The presence of acute lesions on DWI and the ABCD score predict the 3-month risk of stroke after TIA.     

Upregulation of CD40 ligand and enhanced monocyte-platelet aggregate formation are associated with worse clinical outcome after ischaemic stroke

The white blood cell count and mean platelet volume determined shortly after the symptom onset are known as independent predictors for clinical outcome after stroke. In the present study we sought to evaluate the prognostic value of platelet-derived inflammatory biomarkers measured prospectively after an ischaemic event. Using five-colour flow cytometry, the platelet surface expression of CD40L, CD62P and subpopulations of leukocyte-platelet aggregates were assessed in 93 stroke patients on the first (V(0)), 10th (V(1)) and 90th (V(2)) day after stroke, and once in 65 disease controls. The clinical outcome was evaluated using the Scandinavian Stroke Scale (SSS) and modified Rankin Scale (mRS) at the same time points as blood sampling and 24 months after the event. Patients with either CD40L surface expression or the percentage of monocyte-platelet aggregates (M-plt) in the third tertile (T3) at V0 had a significantly lower score on the SSS at V(1). Patients with the percentage M-plt at V(0) higher than the median value of M-plt in controls were at increased risk of SSS < 40 at V(1) (odds ratio: 2.6; 95% confidence interval [CI]: 1.4 - 8.7; p=0.006). Patients with the percentage of M-plt in T3 at V(0) showed progressive decline in survival (hazard ratio [HR]: 1.6; 95% CI: 1.1-1.9; p=0.02) and a significantly higher number of recurrent vascular events (HR: 2.64; 95% CI: 1.3-3.2; p=0.02) when compared to the first tertile. In conclusion, increased levels of M-plt could be a predictive marker for both early outcome and long-term prognosis while increased CD40L was correlated with worse clinical outcome.     

Do antiphospholipid antibodies increase the long‐term risk of thrombotic complications in young patients with a recent TIA or ischemic stroke?

BACKGROUND: The purpose of our study was to determine the relative risk of thrombotic events in young patients with a recent TIA or ischemic stroke and positive antiphospholipid antibodies (aPL). METHODS: We included 128 consecutive patients aged 18-45 years with a recent TIA or ischemic stroke. All patients underwent computed tomography scanning and were screened for cardiovascular risk factors, cardiac disorders and large vessel disease. Lupus anticoagulant (LA) was screened for by an APTT-based assay and a diluted PT-assay. Anticardiolipin antibodies (aCL) were tested by enzyme-linked immunosorbent assay, using cardiolipin and anti-human IgG and IgM. Thrombotic events could be TIA, stroke, myocardial infarction, deep venous thrombosis or pulmonary embolism. Product limit estimates of the time free of TIA or stroke and of the time free of any thrombotic event were made. The relative risk was estimated by means of a Cox proportional hazards regression model. RESULTS: Of the 128 patients, 22 (17.2%) had aPL. The mean follow-up was 3 years and 3 months (range 41 days to 6 yrs). The incidence of any thrombotic event per 100 patient years of follow-up was 9.0, and the incidence of recurrent stroke or TIA was 7.9. The relative risk of any thrombotic event in patients with aPL was 0.9 (95% CI: 0.3-2.4) and for recurrent ischemic stroke or TIA 0.7 (95% CI: 0.3-2.2). CONCLUSION: In young patients with a recent TIA or ischemic stroke, aPL do not seem to be a strong risk factor for recurrent stroke or TIA, nor for other thrombotic complications.