Tissue plasminogen activator and plasminogen activator inhibitor in patients with acute ischemic stroke: relation to stroke etiology

Recent studies suggest that high plasma levels of tissue-type plasminogen activator (tPA) and its inhibitor (plasminogen activator inhibitor-1, PAI-1) are markers of an increased risk of atherothrombotic ischemic events such as stroke and myocardial infarction. In this prospective study, we measured tPA antigen, PAI-1 antigen and activity, as well as tPA/PAI-1 complex in patients with acute stroke. Stroke subtypes were classified according to the TOAST criteria. From 132 consecutively screened patients, 89 (100%) were enrolled in this study, including 42 patients (47%) with large artery atherosclerosis (LAA), 32 (36%) with small vessel occlusion (SVO), and 15 (17%) with cardioembolism (CE). Nineteen age-matched neurologic patients without manifestations of cerebrovascular disease served as control subjects (CS). Patients with acute stroke had significantly higher plasma levels of tPA antigen (p < 0.001), PAI-1 antigen (p < 0.05) and PAI activity (p < 0.05) than patients in the control group. t-PA antigen, PAI activity and tPA/PAI-1 complex levels were similar regardless of stroke etiology. Only PAI-1 antigen was lower in patients with cardioembolic stroke than in stroke patients with LAA (p < 0.05). Plasma tPA antigen, PAI-1 antigen, and PAI activity are significantly increased in patients with acute ischemic stroke. Except for PAI-1 antigen, this increase appears not to be related to the underlying stroke etiology.     

Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies

BACKGROUND: While atrial fibrillation (AF) increases the risk of cardioembolic stroke, some ischemic strokes in AF patients are noncardioembolic. OBJECTIVES: To assess ischemic stroke mechanisms in AF and to compare their responses to antithrombotic therapies. METHODS: On-therapy analyses of ischemic strokes occurring in 3,950 participants in the Stroke Prevention in Atrial Fibrillation I-III clinical trials. Strokes were classified by presumed mechanism according to specified neurologic features by neurologists unaware of antithrombotic therapy. RESULTS: Of 217 ischemic strokes, 52% were classified as probably cardioembolic, 24% as noncardioembolic, and 24% as of uncertain cause (i.e., 68% of classifiable infarcts were deemed cardioembolic). Compared to those receiving placebo or no antithrombotic therapy, the proportion of cardioembolic stroke was lower in patients taking adjusted-dose warfarin (p = 0.02), while the proportion of noncardioembolic stroke was lower in those taking aspirin (p = 0.06). Most (56%) ischemic strokes occurring in AF patients taking adjusted-dose warfarin were noncardioembolic vs. 16% of strokes in those taking aspirin. Adjusted-dose warfarin reduced cardioembolic strokes by 83% (p < 0.001) relative to aspirin. Cardioembolic strokes were particularly disabling (p = 0.05). CONCLUSIONS: Most ischemic strokes in AF patients are probably cardioembolic, and these are sharply reduced by adjusted-dose warfarin. Aspirin in AF patients appears to primarily reduce noncardioembolic strokes. AF patients at highest risk for stroke have the highest rates of cardioembolic stroke and have the greatest reduction in stroke by warfarin.     

急性缺血性脑血管病患者肺炎衣原体感染与血清C反应蛋白的关系

目的:探讨肺炎衣原体感染在急性缺血性脑血管病炎症反应中的作用。方法:检测30例急性缺血性脑血管病患者和30例正常对照者血清中肺炎衣原体特异性抗体IgG和IgM,以及血清C反应蛋白水平。结果:缺血性脑血管病患者血清C反应蛋白水平高于对照者(P<0.01)。血清肺炎衣原体IgG抗体阳性脑血管病患者血清C反应蛋白水平(0.57±0.56mg/dl)高于IgG抗体阴性脑血管病患者(0.42±0.21mg/dl)(P>0.05)。血清肺炎衣原体IgM抗体阳性脑血管病患者血清C反应蛋白水平(0.67±0.73mg/dl)高于IgM抗体阴性脑血管病患者(0.47±0.35mg/dl)(P>0.05)。结论:肺炎衣原体急性和慢性感染均参与急性缺血性脑血管病的炎症反应过程,并与其它卒中因素共同引起血清C反应蛋白水平升高。     

Lipoprotein(a) in ischemic cerebrovascular disease: a new approach to the assessment of risk for stroke

We estimated the serum levels of lipoprotein(a) [Lp(a)] of 87 patients suffering from ischemic cerebrovascular disease (ICVD) (50 men, 37 women; mean age, 66.7 +/- 10.9 years; median, 66) and of 66 healthy controls (33 men, 33 women; mean age, 62.2 +/- 11.1; median, 63). The Lp(a) serum levels of the ICVD group (mean, 20.5 +/- 23 mg/dl; median, 9.5) were significantly elevated compared with those of controls (mean, 14.2 +/- 23.1 mg/dl; median, 5). In a smaller subgroup, limiting the age range to 30 to 60 years, the difference in the Lp(a) serum levels between the ICVD patients and the controls was even highly significant (p less than 0.001).     

Lipids in ischemic stroke subtypes

In secondary prevention, reduction of the risk of recurrent ischemic stroke might be expected with statins if a correlation can be established between hyperlipidemia and ischemic stroke or some specific ischemic stroke/TIA subtypes. However, such correlation remains controversial, and more particularly with the etiologic stroke/TIA subtypes. Few studies have evaluated the plasma lipid profile in different ischemic stroke subtypes, and notably in lacunar infarctions and cardioembolic strokes. The objectives of this case-control study was to determine (1) which cholesterol fractions is associated with large vessel disease (LVD), small vessel disease (SVD), and cardioembolic disease (CED); (2) whether hypertriglyceridemia is related more to any particular stroke subtype; and (3) whether the lipid profile is different between LVD and SVD which are both responsible for atherothrombotic cerebral ischemia. From a cohort of 485 patients, were selected 240 consecutive cases with ischemic stroke (n = 182) or transient ischemic attack (n = 58) due to a single etiology. The levels of total cholesterol (total-C), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and triglycerides (TG) were measured in 61 patients with LVD, in 65 with SVD, and in 114 with CED, and compared with age- and sex-matched control subjects. Additional analysis was performed to compare the lipid profile between LVD and SVD after adjustment for other risk factors. Compared to controls, the total-C level was significantly higher in patients with SVD (p = 0.005) and LVD (p = 0.018). A significant increase in the LDL-C level (p < 0.004) and a significant decrease in the HDL-C level (p = 0.001) were only observed in the LVD patients. The three stroke subtypes showed higher TG levels than the controls (CED, p = 0.037; SVD, p < 0.001; LVD, p = 0.014). The plasma lipid profile was similar in the SVD and LVD subtypes except for HDL-C, which was significantly lower in LVD than in SVD (p = 0.047). Logistic regression adjusted for confounders showed that decreased HDL-C (p = 0.020), and smoking (p = 0.019) were significant discriminative factors for LVD vs. SVD. In conclusion, this controlled study shows that hypertriglyceridemia is commonly found in patients with ischemic cerebrovascular disease whatever the etiologic subtype, whereas hypercholesterolemia is related more to SVD and LVD. In addition to hypertension and diabetes, hypercholesterolemia may also be involved in the etiology of SVD and differs from LVD by a lower decrease in HDL-C.     

血清脂蛋白（a）与缺血性脑卒中关系的临床研究

目的探讨脂蛋白（a）（Lp（a））是否为缺血性卒中的危险因素,以及Lp（a）水平与缺血性脑卒中类型和预后的关系。方法将缺血性脑卒中患者按急性卒中治疗低分子肝素试验．TOAST）分型标准分为心源性脑栓塞（CE）、大动脉粥样硬化性卒中（LAA）、小动脉卒中（SAA）、其他原因引发的缺血性卒中（SOE）和原因不明的缺血性卒中（SUE）。以同期入院的非脑卒中患者（经头颅CT或磁共振排除）作为对照组。病例组和对照组均于入院次日清晨空腹抽取静脉血,测定Lp（a）及其他各项血脂指标,并于入院及病程两周时分别行NHISS评分评估神经功能缺损程度,分析Lp（a）与卒中类型及NIHSS评分之间的关系。结果缺血性脑卒中组Lp（a）浓度及异常率均高于对照组（P〈0．05）,Lp（a）进入大动脉粥样硬化卒中患病因素的回归方程Lp（a）水平与卒中患者的NIHSS评分无相关性（P〉0．05）。结论高浓度Lp（a）可能参与了缺血性脑卒中的发生,并且可能是大动脉粥样硬化性卒中发生的危险因素,但与神经功能缺失程度和早期功能修复无关。     

Euglobulin clot lysis induced by tissue-type plasminogen activator is reduced in subjects with increased levels of lipoprotein (a).

Several reports have evaluated the in vitro effect of lipoprotein(a) [Lp(a)] levels on the fibrinolytic system, suggesting that high Lp(a) levels may inhibit fibrinolysis by competing for plasminogen binding in different systems. We have studied plasminogen activation induced by tissue-type plasminogen activator (t-PA), as well as other fibrinolytic parameters, in 25 subjects with Lp(a) levels greater than 30 mg/dl and the results were compared with those found in 23 subjects with Lp(a) less than 30 mg/dl. Both groups were similar in age, sex distribution, living habits and lipid pattern. Plasminogen activation, when measured by t-PA-induced euglobulin clot lysis, was significantly decreased in the group with elevated Lp(a) levels (lysis time, 16.7 +/- 3.3 min) compared with the group with low Lp(a) levels (11.8 +/- 2.0 min), although 8 of the 25 subjects with high Lp(a) levels showed plasminogen activation within the range of the control group. A positive significant correlation between Lp(a) levels and t-PA-induced euglobulin clot lysis time was found. No statistical differences were demonstrated between groups for the other fibrinolytic parameters studied. Addition of purified Lp(a) to the euglobulin fraction or to plasma resulted in a decrease in euglobulin clot lysis. The present study shows that t-PA induced plasminogen activation is decreased in individuals with high circulating levels of Lp(a) supporting the hypothesis that Lp(a) may interfere with the physiological functions of plasminogen.     

Advantages of lipid-lowering therapy in cerebral ischemia: role of HMG-CoA reductase inhibitors

Dyslipemia as a risk factor for ischemic stroke and indications for statins in the prevention of ischemic stroke are revised. The role of cholesterol levels as a risk factor for ischemic stroke is controversial. This could be due to failures in the design of early epidemiological studies. Recent studies, however, do suggest a clearer risk relationship between cholesterol levels and ischemic stroke. Studies conducted on the prevention of ischemic heart disease (IHD) with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), using pravastatin and simvastatin, unequivocally show reductions in overall mortality, cardiovascular mortality, acute myocardial infarction and other coronary events. These studies show a reduction in the risk of ischemic stroke, and although relative risk reduction is great, absolute risk reduction is low; the reasons for this are analyzed. Apart from lipid mechanisms, statins act on the atheroma plaque; they have antithrombotic and possibly neuroprotecting properties. Statins reduce the number of strokes due to the decrease of atherothrombotic strokes, cardioembolic strokes secondary to IHD, and lacunar strokes related to atherothrombosis and probably to microatheromas. Although there are currently no specific studies available on the secondary prevention of stroke with statins, which are required to clarify certain points, according to European and American guidelines for prevention, statins would be indicated in the secondary prevention of atherothrombotic stroke, and in cardioembolic and lacunar stroke associated with clinical or silent atherosclerosis (IHD, peripheral artery disease). Patients with ischemic stroke of other etiologies, except for stroke in the young or other unusual causes, are patients with a high vascular risk (cardiac and cerebral) owing to the stroke itself, age and other vascular risk factors, and they should also be treated with statins, at least from the point of view of primary prevention of IHD. Natural statins (pravastatin and simvastatin) play an essential part in secondary prevention of ischemic stroke, together with antiaggregants, anticoagulants, angiotensin-converting enzyme inhibitors and the treatment of other vascular risk factors.     

Dyslipidemia, elevated LDL cholesterol and reduced nocturnal blood pressure dipping denote lacunar strokes occurring during nighttime

Previous studies have shown a peak occurrence of ischemic stroke in the morning but no consistent finding has been attributed to this. Focused on lacunar strokes we performed a prospective study with a detailed diagnostic protocol including parameters of recent infection, indicators of sleep apnea and cerebral vasoreactivity (CVR), aimed at defining differences in risk profiles between diurnal and nocturnal strokes. Consecutively we included 33 nocturnal and 54 diurnal strokes. Baseline characteristics, known risk factors, stroke severity and topology were not different between groups. The mean low-density lipoprotein (LDL) cholesterol level was significantly higher amongst patients with nocturnal strokes (133.3 +/- 35.2 mg/dl vs. 115.5 +/- 39.8 mg/dl; P = 0.04), as well as the proportion of patients with any dyslipidemia (94% vs. 77.8%; P = 0.047). Twenty-four-hour blood pressure recordings showed a reduced nocturnal decrease of blood pressure in subjects with strokes that occurred between 10 pm and 6 am in comparison with those whose strokes occurred between 6 am and 2 pm (5.0 +/- 7.3% vs. 11.0 +/- 6.7%; P = 0.049). No significant differences were found for parameters of recent infection (including seroreactivity against Chlamydia pneumoniae and cytomegalovirus), CVR, indicators of sleep apnea and the degree of white matter disease assessed by magnetic resonance tomography. Dyslipidemia, especially elevated LDL cholesterol is more prevalent in nocturnal lacunar strokes especially when combined with a reduced nocturnal dipping of blood pressure. This risk factor profile can be regarded as an additional target for stroke prevention.     

Elevated Lipoprotein (a) and Risk of Poor Functional Outcome in Chinese Patients with Ischemic Stroke and Type 2 Diabetes

The aim of this study was to evaluate the short-term prognostic value of early measurement of serum lipoprotein (a) [Lp(a)] levels in Chinese patients with type 2 diabetes (T2D) and acute ischemic stroke (AIS). The study population comprised 232 consecutive patients with an AIS diagnosis complicated with T2D. Functional outcome was obtained on month 3 according to the modified Rankin Scale (mRS). Unfavorable functional outcome was defined as a mRS score of 3 to 6 points. The prognostic value of Lp(a) at admission to predict the unfavorable functional outcome 3 months after stroke onset was compared with the National Institutes of Health Stroke Scale score and other known outcome predictors. The Lp(a) levels in those patients were obtained with a median value of 16.8 mg/dl (IQR, 9.5–34.4 mg/dl). At 3-month follow-up, an unfavorable functional outcome was found in 86 patients (37.1%). In multivariate models comparing the second (Q2), third, and fourth quartiles against the first quartile of Lp(a), concentrations of Lp(a) in Q2, Q3, and Q4 were associated with unfavorable outcome, and increased risk of unfavorable outcome by 42, 131, and 211%. Interestingly, an elevated Lp(a, >?30 mg/dl) was also associated with unfavorable outcome, and with adjusted OR of 2.25 (95% CI 1.39–3.68). The AUC was significantly increased by adding Lp(a) to established risk factors (difference, 0.041 [95% CI, 0.034–0.053]; P?=?0.02). The addition of Lp(a) to established risk factors significantly improved net reclassification improvement and integrated discrimination improvement. Higher Lp(a) levels at admission were associated with increased risk of unfavorable functional outcome and might be useful in identifying stroke patients with T2D at risk for unfavorable functional outcome for early prevention strategies.     

Percutaneous closure of the left atrial appendage to prevent ischaemic stroke in patients with atrial fibrillation who require but have contraindications to oral anticoagulation

Atrial fibrillation (AF) is associated with a five-fold increased risk for stroke due to cardioembolic events. Most strokes in patients with AF arise from thrombus formation in the left atrial appendage (LAA). Oral anticoagulation is a standard treatment of AF patients with high risk of stroke. However, the main drawbacks of oral anticoagulation are high risk of major bleeding and imperfect effectiveness dependent on a very narrow therapeutic range. In this article, based on two case reports, we describe a method of percutaneous closure of the LAA. We discuss indications, describe the procedure and mention possible complications. LAA closure seems to be a promising tool to prevent AF-related strokes in a selected group of patients.     

Rapidly progressive stroke in a young adult with very low high-density lipoprotein cholesterol.

Ischemic strokes can affect young adults (15-45 years old). Most such strokes are caused by cardioembolic events, small vessel disease, or illicit drug use, and less frequently by large vessel atherosclerosis. Large vessel cerebral atherosclerosis is usually associated with high levels of low-density lipoprotein (LDL) cholesterol, but a low level of high-density lipoprotein (HDL) is also a risk factor for ischemic strokes. The magnitude of increased risk is unclear, particularly with extremely low HDL levels found only in various genetic and inherited disorders. Advanced atherosclerosis developed in the patient in this study, with HDL of 3 mg/dL, leading to rapidly progressive stroke with a fatal outcome. The disease primarily affected the posterior circulation. The course of this case illustrates that very low HDL may be associated with advanced cerebrovascular atherosclerosis and fatal stroke, and as such should be considered in young individuals with stroke.     

A prospective study of atrial fibrillation and stroke

In a prospective study of 72 patients with stroke and atrial fibrillation, we classified strokes as cardioembolic or noncardioembolic based on arterial assessment using Doppler sonography and angiography. We analyzed and cross-tabulated 18 clinical characteristics and found four to be significantly associated with a cardioembolic mechanism: stroke with onset during activity and peak deficit at onset (p less than 0.008), previous infarct in a different vascular territory (p less than 0.01), previous transient ischemic attack in a different vascular territory (p less than 0.01), and transient ischemic attack lasting greater than 1 hour (p less than 0.02). Starting with these four characteristics, we used a step-down procedure to select variables for a logistic regression model. Only previous infarct in a different vascular territory (odds ratio = 7.38) and transient ischemic attack lasting greater than 1 hour (odds ratio = 7.89) were selected by the model. Using M-mode and two-dimensional echocardiography, we compared left atrial size in 46 patients with that in 78 controls who had atrial fibrillation without stroke. Left atrial size in patients and controls with mitral valvulopathy was significantly larger than that in patients and controls without mitral valve disease. There was, however, no difference in left atrial size between patients with nonvalvular atrial fibrillation and cardioembolic stroke and controls or patients with nonvalvular atrial fibrillation and noncardioembolic stroke. We concluded that some clinical characteristics are closely related to cardioembolic stroke and that left atrial enlargement reflects underlying cardiopathy rather than atrial emboli-forming capability.     

Trends in risk factors, patterns and causes in hospitalized strokes over 25 years: The Lausanne Stroke Registry

BACKGROUND AND OBJECTIVE: The Lausanne Stroke Registry includes, from 1979, all patients admitted to the department of Neurology of the Lausanne University Hospital with the diagnosis of first clinical stroke. Using the Lausanne Stroke Registry, we aimed to determine trends in risk factors, causes, localization and inhospital mortality over 25 years in hospitalized stroke patients. METHODS: We assessed temporal trends in stroke patients characteristics through the following consecutive periods: 1979-1987, 1988-1995 and 1996-2003. Age-adjusted cardiovascular risk factors, etiologies, stroke localizations and mortality were compared between the three periods. RESULTS: Overall, 5,759 patients were included. Age was significantly different among the analyzed periods (p < 0.001), showing an increment in older patients throughout time. After adjustment for age, hypercholesterolemia increased (p < 0.001), as opposed to cigarette smoking (p < 0.001), hypertension (p < 0.001) and diabetes and hyperglycemia (p < 0.001). In patients with ischemic strokes, there were significant changes in the distribution of causes with an increase in cardioembolic strokes (p < 0.001), and in the localization of strokes with an increase in entire middle cerebral artery (MCA) and posterior circulation strokes together with a decrease in superficial middle cerebral artery stroke (p < 0.001). In patients with hemorrhagic strokes, the thalamic localizations increased, whereas the proportion of striatocapsular hemorrhage decreased (p = 0.022). Except in the older patient group, the mortality rate decreased. CONCLUSIONS: This study shows major trends in the characteristics of stroke patients admitted to a department of neurology over a 25-year time span, which may result from referral biases, development of acute stroke management and possibly from the evolution of cerebrovascular risk factors.     

Enhanced in vivo platelet activation in subtypes of ischemic stroke

It remains uncertain whether platelet activation in ischemic stroke is contributory or secondary to brain ischemia. The efficacy of aspirin (ASA) in stroke prevention suggests that platelet activation contributes to the occurrence of stroke. On the other hand, platelet activation may be simply a generalized consequence of cerebral ischemic damage. To examine this issue, plasma levels of the platelet specific proteins beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were measured in fifty-eight patients with various defined types of acute ischemic strokes. beta-TG was a broader indicator of platelet activation than PF4. Compared with an age-matched control group, thromboembolic and cardioembolic stroke patients had significantly elevated beta-TG levels (p less than 0.001). Also, beta-TG levels in these stroke categories were significantly higher in samples drawn within the first week after the event than in those drawn later (p less than 0.001). In contrast, beta-TG levels in lacunar stroke patients and in most TIA patients were normal. beta-TG levels did not correlate with the volume of cerebral infarction as measured by planimetry from CT scans. Moreover, beta-TG levels in patients on chronic ASA therapy at the time of stroke did not differ from those in patients of the same diagnostic categories not taking aspirin. These data indicate that platelet activation may be important in some, but not all, subtypes of ischemic stroke and that platelet activation can occur in stroke even though the platelet cyclooxygenase pathway is suppressed.     

Preferential Effect of Premorbid Statins on Atherothrombotic Strokes through Collateral Circulation Enhancement

Background/Aims: Endovascular recanalization therapies are an increasingly used strategy for acute cerebral ischemia with heterogeneous clinical outcomes. We aimed to determine the impact of previous medication on ischemic stroke following intra-arterial revascularization therapy. Methods: Consecutive patients receiving intra-arterial reperfusion therapy after an acute intracranial occlusion were analyzed. Premorbid use of antiplatelets, statins, oral antidiabetic drugs, antihypertensive drugs and oral anticoagulants were recorded. Collateral pial circulation (CPC) was scored on initial angiogram. Results: 118 patients were included (mean age 70.4 ± 11 years, 45% female). 66 patients (56%) were cardioembolic, 30 (25%) atherothrombotic, and 22 (19%) other/unknown etiologies. No significant impact of medication was detected in all the series or cardioembolic strokes. However, relevant differences were found among atherothrombotic strokes. The previous use of antiplatelets was associated with smaller infarct volume (64 vs. 170 ml; p = 0.043) whereas premorbid statin predicted reduced infarct volume (64 vs. 215 ml; p = 0.019), clinical improvement (79 vs. 29%; p = 0.016) and good CPC (100 vs. 20%; p = 0.04). Statins were the only medication independently predicting reduced infarct volume and clinical improvement and this effect depended on CPC. Conclusion: Previous use of statins may preferentially benefit patients with atherothrombotic strokes by favoring the development of CPC.     

Effect of ximelagatran and warfarin on stroke subtypes in atrial fibrillation

BACKGROUND AND PURPOSE: The most common stroke subtype among atrial fibrillation (AF) patients not receiving anticoagulants is cardioembolic. In the SPORTIF III and V trials, the oral direct thrombin inhibitor ximelagatran was as effective as warfarin in reducing the risk of stroke in patients with nonvalvular AF. We assessed any differential effect of warfarin versus ximelagatran on the risk and outcome of cardioembolic and noncardioembolic stroke. METHODS: 7329 patients with AF and > or = 1 risk factors for stroke were randomized to treatment with warfarin (target international normalized ratio 2.0--3.0) or fixed-dose ximelagatran. Strokes were classified into specific subtypes. Therapeutic effect of warfarin and ximelagatran, adverse events, and stroke outcomes were assessed according to stroke subtype. RESULTS: The annual stroke rate was low for both cardioembolic (ximelagatran, 0.39%; warfarin, 0.47%) and noncardioembolic stroke (ximelagatran, 0.57%; warfarin, 0.37%). In ischemic strokes, 33.9% (ximelagatran) and 34.3% (warfarin) had strokes of presumed cardioembolic origin. When fatal stroke, disabling stroke, myocardial infarction, and death from any cause were combined as poor outcome, patients with cardioembolic strokes had the highest rate of poor outcome (40%) but this was non- significant. CONCLUSIONS: In SPORTIF III and V the efficacy of warfarin and ximelagatran were similar for prevention of cardioembolic and noncardioembolic strokes. Overall outcome tended to be worse following cardioembolic stroke. Ximelagatran has been withdrawn from the market due to hepatic side effects, but similar compounds are presently being studied.     

Serum GFAP levels in optic neuropathies

ObjectiveExperimental studies have indicated that adipocytokines are associated with vascular diseases with regard to the pathology of atherosclerotic plaque. We hypothesized that the strength of the associations between adipocytokines and stroke would differ between ischemic stroke subtypes.MethodsA total of 96 acute ischemic stroke patients (within 5 days from onset) and 48 non-stroke subjects were analyzed in this study. Stroke patients were comprised of 26 strokes due to large artery atherosclerosis (LAA) and 72 non-LAA strokes. Venous blood from all participants was drawn after an overnight fast, and serum levels of leptin, adiponectin and resistin were measured by multiple sandwich immunoassay techniques.ResultsCompared with non-LAA strokes, patients with LAA strokes had lower levels of serum adiponectin (6.4 ± 3.1 vs. 8.5 ± 3.9 μg/mL; P = 0.04), and a higher level of leptin-to-adiponectin ratio (L:A ratio; 1.6 ± 1.4 vs. 0.9 ± 0.9; P < 0.01). Multinomial logistic regression analyses showed that, although none of the adipocytokines was associated with non-LAA strokes, lower adiponectin (adjusted OR, 0.79 per 1-μg/mL increase; 95% CI, 0.64–0.98), higher leptin (aOR, 1.12 per 1-ng/mL increase; 95% CI, 1.004–1.25) and higher L:A ratio (aOR, 2.93 per 1-quartile increase; 95% CI, 1.39–6.15) showed significant associations with increased odds of having LAA stroke, compared to non-stroke subjects.ConclusionFrom our study, we documented that leptin and adiponectin had differential association patterns with ischemic stroke according to the stroke subtype. Careful consideration of the heterogeneity of stroke subtypes would be warranted in studying the utility of biomarkers including adipocytokines.     

Increased levels of elastin-derived peptides in cerebrospinal fluid of patients with lacunar stroke

OBJECTIVE: To investigate whether elastin-derived peptides (EDP) are detectable in the cerebrospinal fluid (CSF) of healthy controls and of patients with acute brain ischemia and if so to assess possible trends in EDP levels in different groups of ischemic stroke patients (small-vessel disease vs. other ischemic strokes; first-ever vs. recurrent stroke). PATIENTS AND METHODS: Levels of EDP were determined by ELISA in blood sera and CSF of 80 patients with acute ischemic stroke (mean age 61.5+/-10.8; age range 47-70; 22 women) and in 15 healthy age- and sex-matched controls (mean age 57.3+/-13.4; age range 50-65). The patients were divided into a group with first ever lacunar stroke (27); first ever non-lacunar ischemic stroke (27) and recurrent stroke (26). EDP were measured early (mean 7 days, range 1-15) after stroke onset. RESULTS: Serum EDP levels were mildly higher in recurrent strokes as compared to first ever lacunar lesion and controls. However, in the CSF the concentrations of EDP in stroke patients were strongly elevated (from 2 up to 30 times depending on subgroup) as compared with healthy subjects. The highest level of EDP in CSF and in the serum was found in recurrent strokes. Subgroup analysis revealed a trend for significantly higher EDP concentrations in CSF in lacunar and recurrent stroke as compared with non-lacunar. CONCLUSIONS: This study is the first application of elastin peptide measurement to human CSF and stroke patients. The increased levels of EDP were detected in CSF of patients with lacunar and recurrent strokes.