Blood biomarkers of progressive atherosclerosis and restenosis after stenting of symptomatic intracranial artery stenosis.

In-stent restenosis (ISR) represents a major complication after stenting of intracranial artery stenosis (ICAS). Biomarkers derived from routine blood sampling including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) have been associated with progressive atherosclerosis. We investigated the role of CRP, NLR, PLR and MPV on the development of intracranial ISR and recurrent stroke risk. We retrospectively included all patients who had undergone stenting of symptomatic ICAS at our university hospital between 2005 and 2016. ISR (≥ 50% stenosis) was diagnosed by regular Duplex sonography follow-up studies and confirmed by digital subtraction angiography or computed tomography angiography (mean follow-up duration: 5 years). Laboratory parameters were documented before stenting, at the time of restenosis and at last clinical follow-up. Of 115 patients (mean age: 73 ± 13 years; female: 34%), 38 (33%) developed ISR. The assessed laboratory parameters did not differ between patients with ISR and those without (p > 0.1). While ISR was associated with the occurrence of recurrent ischemic stroke (p = 0.003), CRP, NLR, PLR and MPV were not predictive of such events (p > 0.1). Investigated blood biomarkers of progressive atherosclerosis were not predictive for the occurrence of ISR or recurrent ischemic stroke after ICAS stenting during a 5-year follow-up.

Association between fasting blood glucose and intracranial cerebral artery stenosis: a secondary analysis based on a retrospective cross-sectional study in Korean adults.

AIMS: Diabetes mellitus (DM) is one of the main risk factors for intracranial cerebral artery stenosis (ICAS), and fasting blood glucose (FBG) might be an effective predictor of ICAS. However, there are a few studies revealing the relationship between FBG and ICAS. We aim to identify the association between FBG and ICAS in Koreans. METHODS: This was a secondary study based on a cross-sectional study. A total of 1011 Korean individuals who were asymptomatic but with high cerebrovascular risk underwent an examination in a Korean medical centre from March 2008 to December 2014. The main measure was FBG, while the main outcome was ICAS. Multivariate logistic regression analyses of FBG in the presence of ICAS were performed to examine the potential association. The author used the data provided by the paper "Association between Serum Alkaline Phosphatase Level and Cerebral Small Vessel Disease" for secondary analysis. RESULTS: The average age of the participants was 64.2 ± 9.1 years old, and approximately 35% of them were males. There were 24 participants suffering from ICAS in the first FBG tertile (< 5.4 mmol/L), while there were 26 in the second tertile (5.4-7.1 mmol/L) and 50 in the third tertile (≥ 7.1 mmol/L). The non-adjusted relationship between FBG and ICAS was positive. After controlling potential confounders, the association of FPG with ICAS remained positive, as well as in subgroups analysis, such as age, sex, hypertension, diabetes mellitus, hyperlipidaemia and COAD. The association remained unchanged after adjusted sex, age, hypertension, DM, uric acid, hyperlipidaemia, and CAOD (OR = 1.08, 95% CI = 1.02-1.15). The analyses also showed that the positive association was statistically significant (P < 0.05) among individuals without diabetes. CONCLUSIONS: This study showed a positive relationship between FBG and ICAS, which suggests that clinicians may need to be simultaneously concerned about FBG and ICAS.

A cross-sectional, case-control study of intracranial arterial wall thickness and complete blood count measures in sickle cell disease.

In sickle cell disease (SCD), cerebral oxygen delivery is dependent on the cerebral vasculature's ability to increase blood flow and volume through relaxation of the smooth muscle that lines intracranial arteries. We hypothesised that anaemia extent and/or circulating markers of inflammation lead to concentric macrovascular arterial wall thickening, visible on intracranial vessel wall magnetic resonance imaging (VW-MRI). Adult and pediatric SCD (n = 69; age = 19.9 ± 8.6 years) participants and age- and sex-matched control participants (n = 38; age = 22.2 ± 8.9 years) underwent 3-Tesla VW-MRI; two raters measured basilar and bilateral supraclinoid internal carotid artery (ICA) wall thickness independently. Mean wall thickness was compared with demographic, cerebrovascular and haematological variables. Mean vessel wall thickness was elevated (P < 0·001) in SCD (1·07 ± 0·19 mm) compared to controls (0·97 ± 0·07 mm) after controlling for age and sex. Vessel wall thickness was higher in participants on chronic transfusions (P = 0·013). No significant relationship between vessel wall thickness and flow velocity, haematocrit, white blood cell count or platelet count was observed; however, trends (P < 0·10) for wall thickness increasing with decreasing haematocrit and increasing white blood cell count were noted. Findings are discussed in the context of how anaemia and circulating inflammatory markers may impact arterial wall morphology.

Characterizing lipid profiles associated with asymptomatic intracranial arterial stenosis in rural-dwelling adults: A population-based study.

BACKGROUND: Although individual lipid parameters have been frequently examined in association with asymptomatic intracranial arterial stenosis (aICAS), few population-based studies have investigated the lipid profiles associated with aICAS among Chinese adults. OBJECTIVE: This study aims to characterize the lipid profiles associated with aICAS in rural-dwelling adults in China. METHODS: This population-based study included 2027 persons who were aged ≥40 years and free of stroke. Data were collected via interviews, clinical examinations, and laboratory testing. We diagnosed aICAS by integrating transcranial color Doppler with magnetic resonance angiography. Data were analyzed using binary and multinomial logistic regression models. RESULTS: Of the 2027 participants, 154 were detected with aICAS. The multiadjusted odds ratio (95% confidence interval) of aICAS was 1.41 (0.997-2.00) for high small dense low-density lipoprotein cholesterol, 1.44 (1.02-2.04) for high lipoprotein(a), 1.71 (1.21-2.44) for low apolipoprotein A-1, 1.43 (1.00-2.04) for low high-density lipoprotein cholesterol (HDL-C), 1.61 (1.14-2.27) for high apolipoprotein B/apolipoprotein A-1 ratio, 1.95 (1.38-2.76) for high low-density lipoprotein cholesterol/HDL-C ratio, and 1.51 (1.06-2.14) for high total cholesterol/HDL-C ratio. When severity of aICAS was analyzed, high levels of lipoprotein(a), small dense low-density lipoprotein cholesterol, and lipid ratios were significantly associated with an increased likelihood of moderate-to-severe aICAS (P < .05). An increasing number of abnormal lipid measurements was associated with an increased likelihood of aICAS (P for trend <.001). CONCLUSION: These findings suggest that lipid profiles for aICAS among rural residents in China are characterized by high atherogenic cholesterol, low antiatherogenic cholesterol, and high ratios of atherogenic-to-antiatherogenic cholesterol or lipoproteins.

Role of sLOX-1 in intracranial artery stenosis and in predicting long-term prognosis of acute ischemic stroke.

Objective: The role of sLOX-1 in acute ischemic stroke still remains unclear. This study aims to demonstrate the value of sLOX-1 in evaluating degrees of intracranial artery stenosis and to predict prognosis in stroke. Methods: Two hundred and seventy-two patients were included in this study and basic data were collected within 72 hr on admission. We assessed the association between sLOX-1 levels and stroke conditions in one-year duration. After adjusting for potential confounders, regression analyses were performed. Results: We found that sLOX-1 levels were increased significantly in severe patients compared to the mild stroke group (p = .011). After adjusting confounders, sLOX-1 was associated with a poor functional outcome in patients with an adjusted OR of 2. 946 (95% CI, 1.788-4.856, p < .001). There was also positive correlation between sLOX-1 levels and the degrees of intracranial artery stenosis in the different groups (p = .029). Conclusions: Our study demonstrated that sLOX-1 levels could be used to evaluate the severity of stroke and the degrees of intracranial artery stenosis. Furthermore, sLOX-1 could be exploited to predict the long-term functional outcome of stroke.

The association between serum uric acid and asymptomatic intracranial arterial stenosis in middle-aged Koreans.

BACKGROUND AND AIMS: Intracranial arterial stenosis (ICAS) is one of the most common causes of stroke, especially in Asians. Hyperuricemia has been associated with an increased risk of comorbidities such as metabolic syndrome or cardiovascular diseases. However, there are few studies focusing on the association between serum uric acid (SUA) levels and asymptomatic ICAS. The aim of this study was to explore the association between SUA and the prevalence of ICAS in middle-aged Korean health screening examinees. METHODS AND RESULTS: A cross-sectional study was performed on 9417 males and 7755 females who underwent a comprehensive health examination including transcranial Doppler (TCD) ultrasonography. The association of SUA and ICAS was analyzed using multivariate logistic regression. The prevalence of ICAS among the total examinee population was 3.55%. In females, the multivariate-adjusted odds ratio for ICAS was 1.52 (confidence interval 1.13-2.04) in the 3rd quartile of SUA and 1.45 (1.05-2.00) in the highest quartile, compared to the reference (P for trend 0.008). This trend was evident in all clinically relevant subgroups evaluated, including women with low inflammation status. SUA was not significantly associated with the prevalence of ICAS among males. In a sensitivity analysis, the multivariate-adjusted odds ratio of middle cerebral artery stenosis in females was 1.60 (1.09-2.37) in the highest quartile compared to the reference (P for trend 0.023). CONCLUSIONS: Higher SUA level was associated with increased risk of ICAS among middle-aged females but not males. A further cohort study is warranted to elucidate the effect of SUA on asymptomatic ICAS.

Dyslipidemia in Children With Arterial Ischemic Stroke: Prevalence and Risk Factors.

BACKGROUND: Risk factors for pediatric stroke are poorly understood and require study to improve prevention. Total cholesterol and triglyceride values peak to near-adult levels before puberty, a period of increased stroke incidence. The role of lipids in childhood arterial ischemic stroke has been minimally investigated. METHODS: We performed a cross-sectional analysis of lipid and Lp(a) concentrations in children with arterial ischemic stroke in the International Pediatric Stroke Study to compare the prevalence of dyslipidemia and high- or low-ranking lipid values in our dataset with reported population values. We analyzed sex, body mass index, race, ethnicity, family history, and stroke risk factors for associations with dyslipidemia, high non-high-density lipoprotein cholesterol, and hypertriglyceridemia. RESULTS: Compared with the National Health and Nutrition Examination Survey, a higher proportion of children ≥5 years with arterial ischemic stroke had dyslipidemia (38.4% versus 21%), high total cholesterol (10.6% versus 7.4%), high non-high-density lipoprotein cholesterol (23.1% versus 8.4%), and low high-density lipoprotein cholesterol (39.8% versus 13.4%). The lipid values that corresponded to one standard deviation above the mean (84th percentile) in multiple published national studies generally corresponded to a lower ranking percentile in children aged five years or older with arterial ischemic stroke. Dyslipidemia was more likely associated with an underweight, overweight, or obese body mass index compared with a healthy weight. Ethnic background and an acute systemic illness were also associated with abnormal lipids. CONCLUSIONS: Dyslipidemia and hypertriglyceridemia may be more prevalent in children with arterial ischemic stroke compared with stroke-free children.

Association between serum cystatin C levels and the severity or potential risk factors of acute ischemic stroke.

OBJECTIVE: We sought to investigate whether serum cystatin C levels are correlated with either stroke severity or with potential risk factors of acute ischemic stroke. METHODS: 171 patients with acute ischemic stroke and 99 control subjects with minor, unrelated diseases with stroke were included in this retrospective study. Serum cystatin C levels were determined in all subjects. Serum concentrations of several vascular risk factors in stoke patients were determined by biochemical assays. The severity of strokes was scored via the National Institutes of Health Stroke Scale (NIHSS). RESULTS: Serum cystatin C levels were significantly increased in patients with acute ischemic stroke compared with control subjects (1.26 ± 0.34 mg/L vs. 0.78 ± 0.24 mg/L, p < 0.001).When analyzed in quartiles of serum cystatin C levels, concentrations were low (<0.75 mM) for 5 stroke patients (2.92%), intermediate (0.75-1 mM) for 42 patients (24.56%), high (1-1.25 mM) for 45 patients (26.32%), and very high (>1.25 mM) for 79 patients (46.20%). However, serum cystatin C levels were not correlated with NIHSS scores, serum total cholesterol, high-density lipoprotein, low-density lipoprotein, apolipoprotein a, or apolipoprotein b levels. Further, serum cystatin C concentrations in stroke patients were not correlated with the presence of intracranial arterial stenosis, hypertension, or diabetes. CONCLUSION: Our study suggests that there is a close relationship between cystatin C and acute ischemic stroke, independently of conventional risk factors. But the levels of cystatin C are not correlated with the stroke severity.

Intracranial arterial stenosis in Ecuadorian Natives/Mestizos. A population-based study in older adults (The Atahualpa Project).

BACKGROUND: Intracranial arterial stenosis (IAS) is more prevalent among Asians, Blacks and Caribbean Hispanics than in Whites. However, there is no information on the importance of this common cause of stroke among Mestizo/Native populations of Latin America. We aimed to assess prevalence and correlates of IAS in an indigenous Ecuadorian population of older adults. METHODS: Atahualpa residents aged ≥60 years were identified during door-to-door surveys and invited to undergo brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of intracranial vessels for identification of stroke lesions and arterial stenosis. Prevalence of IAS was assessed in patients with strokes as well as in stroke-free individuals. A logistic regression model was constructed with stroke as the outcome, IAS as the exposure, and confounders (demographics and cardiovascular risk factors) as independent variables. RESULTS: Out of 267 participants (mean age 71 ± 8 years, 57% women), 15 (5.6%) had intracranial arterial stenosis, including 10 out of 52 (19.2%) persons with stroke and five out of 215 (2.3%) without. The multivariate logistic regression model showed significant association of IAS with stroke after adjusting for demographics and cardiovascular risk factors (OR: 7.9, 95% C.I.: 2.2-27.8, p=0.001). Mechanisms underlying stroke in patients with IAS included perforator occlusion, artery-to-artery embolism and hypoperfusion. CONCLUSIONS: Prevalence of IAS in Ecuadorian Natives/Mestizos is similar to that in Asians. Individuals aged ≥60 years with IAS are almost eight times more likely to have a stroke after adjusting for confounding variables.

Association of Lp-PLA2 Mass and Aysmptomatic Intracranial and Extracranial Arterial Stenosis in Hypertension Patients.

BACKGROUND AND PURPOSE: Intracranial arterial stenosis (ICAS) is a common cause of ischemic stroke in Asians, whereas whites tend to have more extracranial lesions. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been associated with ischemic stroke by a large amount of work. However, there are few studies focusing on the relationship of Lp-PLA2 and asymptomatic ICAS or extracranial arterial stenosis (ECAS). Wehereby sought to explore the relationship of Lp-PLA2 and ICAS, ECAS and concurrent stenosis in stroke-free hypertensive patients in Chinese population. METHODS: All the subjects were evaluated for the presence and severity of ICAS and ECAS through computerized tomographic angiography (CTA) covered the whole brain down to the level of aortic arch. Lp-PLA2 mass was measured by enzyme linked immunoassay. The association of Lp-PLA2 and vascular stenosis was analyzed through multivariate logistic regression. RESULTS: Among 414 participants, 163 (39.4%) had no ICAS or ECAS, 63 (15.2%) had ECAS only, 111 (26.8%) had ICAS only and 77 (18.6%) had concurrent extraintracranial stenosis. Lp-PLA2 mass was significantly associated with isolated ICAS (OR: 2.3; 95% CI: 1.14-4.64), and concurrent stenosis (OR: 3.93; 95% CI: 1.62-9.51), but was not related to isolated ECAS (OR: 1.54; 95% CI: 0.68-3.48). Lp-PLA2 mass was also associated with moderate to severe ICAS no matter how was the ECAS. Moreover, patients with higher Lp-PLA2 mass showed more sever ICAS and had more intracranial arterial lesions. CONCLUSION: This study revealed the association of Lp-PLA2 mass with ICAS in stroke-free hypertensive patients in Chinese population. The further long-term cohort study was warranted to elucidate the concrete effect of Lp-PLA2 on the asymptomatic ICAS.

Cerebral arteriostenosis associated with elevated serum-immunoglobulin E level in young adults without risk factors for ischemic stroke: a possible manifestation of cerebral vasculitis?

We report a series of young adults with symptomatic cerebral arteriostenosis characterized by elevated serum immunoglobulin (Ig) E levels. All patients had no definite risk factors for cerebral vascular diseases. The clinical data of 26 young adults (age 18-50 years) with ischemic stroke, characterized only by increased serum IgE levels and without risk factors for cerebral vascular disease, were retrospectively reviewed. Arteriostenosis was surveyed and followed-up by digital subtraction angiography (DSA), and the stenosis rate was estimated using the warfarin-aspirin symptomatic intracranial disease technique. All patients were treated with corticosteroids according to the common strategy for vasculitis. There was no recurrent stroke during follow-up. The mean degree of stenosis before and after treatment was 69.3±29.8% and 47.9±45.1%, respectively. The difference of stenosis rates between initial and follow-up DSA evaluation was significant using a paired samples test (21.31±26.88, 95% confidence interval [CI] 13.58-29.03, t=5.55, p<0.001). Kaplan-Meier survival analysis revealed that the 13-month cumulative improved lesion rate was 40.3±8.7%. This remained the same at 18 months. The mean time to lesion improvement was 12.58 ± 0.96 months (95% CI 10.70-14.46) and median time was 13±3.88 months (95% CI 5.39-20.61). To our knowledge, cerebral arteriostenosis with only elevated IgE serum levels has not been reported. Our data showed that corticosteroid treatment can achieve clinical and artery improvement. This suggests that the cerebral arteriostenosis seen in our study might be caused by some specific type of vessel inflammation.

Higher numbers of circulating endothelial progenitor cells in stroke patients with intracranial arterial stenosis.

BACKGROUND: Bone marrow-derived endothelial stem cells participate in vascular repairs. Numbers of circulating endothelial progenitor cells (cEPCs) are associated with atherosclerosis. Fibrinogen plays a key role in atherosclerosis. Objective was to assess if cEPC counts were associated with atherosclerotic intracranial artery stenosis (IAS). METHODS: Three hundred subjects (108 patients with stroke and IAS (IAS), 120 control patients with stroke without IAS (CP), and 72 healthy controls (HC)) were retrospectively analyzed. cEPCs were identified and counted by flow cytometry using CD34, CD133 and KDR. Plasma fibrinogen was measured by immunoturbidimetry. cEPC counts were compared between the three groups. RESULTS: cEPC numbers were significantly higher in IAS (0.059 ± 0.031%) than in CP (0.026 ± 0.012%) (P < 0.001) and HC (0.021 ± 0.011%) (P < 0.001), but without difference between CP and HC (P = 0.401). Multiple logistic regression analysis showed that cEPC levels (OR 3.31, 95%CI 1.26-8.87, P = 0.025; IAS vs. CP) were independent markers of IAS after adjustment for hypertension, diabetes and smoking. No significant correlation between cEPC counts and plasma fibrinogen levels was observed (P > 0.05). CONCLUSION: cEPC numbers were associated with degrees of IAS. This measurement may be useful for non-invasive evaluation of atherosclerotic IAS.

Release of serum S-100ß protein and neuron-specific enolase after off-pump coronary artery bypass grafting with and without intracranial and cervical artery stenosis.

PURPOSE: The aim of this study was to quantify the amount of brain damage suffered by patients who underwent off-pump coronary artery bypass grafting (OPCAB) in which S-100ß protein and neuron-specific enolase were used. METHODS: Thirty-four patients undergoing scheduled OPCAB were enrolled in the study. The patients were divided into two groups according to the results of their magnetic resonance angiography (MRA) and cervical ultrasonography: 13 patients had cervical or intracranial arterial stenosis (Group A), and 21 patients did not (Group B). Blood samples were collected from the arterial catheters immediately before surgery, upon arrival to the intensive care unit, and 6 and 24 hours after surgery. RESULTS: In blood samples collected from patients upon arrival to the intensive care unit, the maximum concentration of serum s-100ß protein in Group A was significantly higher than that of Group B (p = 0.029). Though patients in Group A tended to have higher maximum neuron-specific enolase (NSE) concentrations, there were no significant differences in NSE concentrations at any point between the two groups. CONCLUSIONS: Our findings show a correlation between the stenosis detected by MRA or cervical ultrasonography and brain damage after OPCAB.

D-dimers increase in acute ischemic stroke patients with the large artery occlusion, but do not depend on the time of artery recanalization.

D-dimers are one of the basic laboratory markers of fibrinolytic system activity. The aim of this prospective study was to detect changes in D-dimer levels in acute stroke patients as a function of the time of artery recanalization and the therapy used. During a 12-month period, 80 acute ischemic stroke patients admitted to the hospital within a 6-h time window were consecutively enrolled in the study. The clinical neurologic examination, brain computed tomography, neurosonologic examination, and biochemical and hematological blood tests (including D-dimers and fibrinogen) were performed on all patients on admission. The control examinations of D-dimer and fibrinogen blood levels were performed 3 (optional), 6, and 24 h after stroke onset. The Mann-Whitney test, Kruskal-Wallis test, ANOVA test, multiple comparison test, and Pearson test were used for statistical evaluation. Application of intravenous thrombolysis significantly increased the D-dimer levels and decreased the fibrinogen level 6 h after stroke onset in comparison with patients treated with antiplatelets or anticoagulants (P < 0.01), with normalization of blood levels over a 24 h period. The use of sonothrombotripsy showed a tendency to increase the D-dimer levels (P = 0.09) with a significant decrease of the fibrinogen level 6 h after stroke onset (P < 0.05). A significant increase in the D-dimer levels was detected in patients with strokes of cardioembolic and atherothrombotic etiologies, and patients with occlusion of cervical or large intracranial arteries (P < 0.05). There was no correlation between the changes in D-dimer or fibrinogen levels and age, gender, time to artery recanalization, risk factors, and the seriousness of neurologic deficits on admission (P > 0.05). D-dimer levels significantly increased during the first 6 h after stroke onset in patients with large artery occlusion and patients treated using intravenous thrombolysis. However, this increase was independent on the time of artery recanalization thus cannot be used as its marker.

Epidemiology of intracranial stenosis.

Intracranial stenosis is a common etiology for ischemic stroke. Due to limitations of imaging studies, there are limited data on the prevalence of symptomatic and asymptomatic intracranial stenosis. Intracranial stenosis is more prevalent in Asian, Hispanic, and African-American populations. The reported proportion of patients with symptomatic intracranial stenosis among those hospitalized for ischemic cerebral events varies from 1% in non-Hispanic whites to as high as 50% in Asian populations. In population-based studies, the estimated prevalence of symptomatic intracranial disease varies from 1 in 100,000 for whites to 15 in 100,000 in African Americans. A Chinese population-based study reported intracranial stenosis in 7% of the population aged more than 40 years. Autopsy studies have noted intracranial atherosclerotic disease in about 23% of population in the 6th decade and 80% of population in the 9th decade of life. Angiotensin-converting enzyme polymorphisms, plasma endostatin/vascular endothelial growth factor ratio, glutathione S-transferase omega-1 gene polymorphism, and plasma homocysteine levels are non-modifiable risk factors noted to be associated with intracranial stenosis. Hypertension and serum lipid profile are major modifiable risk factors, whereas sickle cell disease is an uncommon risk factor that can be managed to reduce risk. Associations of intracranial atherosclerosis with diabetes mellitus, metabolic syndrome, Alzheimer's disease, aortic plaques, radiotherapy, and meningitis are less well documented.

Anti-endothelial serum antibodies in a patient with Susac's syndrome.

BACKGROUND: Susac's syndrome (SS) is a rare arteriopathy affecting the microvasculature of the brain, retina, and inner ear, resulting in encephalopathy, branch retinal artery occlusion and hearing loss. Anecdotal reports exist on SS being associated with a humoral immune response against endothelial cells. However, no original data has ever been published. OBJECTIVE: To analyze serum and CSF from a patient with SS for the presence of CNS auto-antibodies and, if present, to further characterize such antibodies immunologically. METHODS: Serum and CSF samples were examined by indirect immunofluorescence on adult mouse cerebrum, cerebellum, brain stem, and inner ear tissue sections, and IgG subclasses were determined. RESULTS: Anti-endothelial antibodies were found at a titre of 1:960 in serum but not CSF. Antibodies belonged to the complement activating IgG1 subclass. Glucocorticoid treatment resulted in a decrease of titres (1:480), though the antibodies remained clearly detectable. CONCLUSION: Our finding of anti-endothelial cell antibodies in a patient with SS is important in the light of previous pathological data suggesting that SS is associated with endothelial damage. Larger serological studies are now warranted to assess systematically the frequency and relevance of auto-antibodies in SS.

Monocyte count is an underlying marker of lacunar subtype of hypertensive small vessel disease.

BACKGROUND: In the hypertensive small vessel disease (HSVD), it remains unclear why some patients develop lacunar infarcts (LIs) whilst others develop deep intracerebral hemorrhages (dICHs). Inflammation might be related to LI, and leukocyte and monocyte counts are regarded as an inflammatory marker of ischemic stroke. OBJECTIVE: We investigated the relationship between leukocyte and monocyte counts determined in the first 24 h after stroke onset in HSVD patients. METHODS: We prospectively studied 236 patients with first acute stroke because of HSVD (129 LI and 107 dICH). We analyzed demographic data, vascular risk factors, and white blood cell count subtypes obtained in the first 24 h after stroke. RESULTS: The multivariate analysis showed that LI subtype of HSVD was correlated with hyperlipidemia (P < 0.0001), a higher monocyte count (P = 0.002), and showed a trend with current smoking (P = 0.051), whereas dICH subtype was correlated with low serum total cholesterol (P = 0.003), low serum triglycerides (P < 0.0001), and high neutrophil count (P = 0.050). CONCLUSIONS: In patients who developed HSVD-related stroke, high monocyte count, current smoking, and hyperlipidemia are prothrombotic factors related to LI, whereas low cholesterol and triglyceride values are related to dICH. Monocyte count might be an inflammatory risk marker for the occlusion of small vessels in hypertensive patients.

C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease.

BACKGROUND AND PURPOSE: The role of inflammation in intracranial large-artery occlusive disease is unclear. We sought to investigate the relationship between high-sensitivity C-reactive protein (CRP) levels and the risk of further ischemic events in first-ever transient ischemic attack (TIA) or stroke patients with intracranial large-artery occlusive disease. METHODS: Of a total of 127 consecutive first-ever TIA or ischemic stroke patients with intracranial stenoses detected by transcranial Doppler ultrasonography, 71 fulfilled all inclusion criteria, which included angiographic confirmation. Serum high-sensitivity CRP level was determined a minimum of 3 months after the qualifying event. Patients were followed up during 1 year after blood sampling. RESULTS: Thirteen patients (18.3%) with intracranial large-artery occlusive disease experienced an end point event: 9 cerebral ischemic events, 7 of which were attributable to intracranial large-artery occlusive disease, and 4 myocardial infarctions. Patients in the highest quintile of high-sensitivity CRP level had a significantly higher adjusted odds ratio for new events compared with those in the first quintile (odds ratio, 8.66; 95% CI, 1.39 to 53.84; P=0.01). A high-sensitivity CRP level above the receiver operating characteristic curve cutoff value of 1.41 mg/dL emerged as an independent predictor of new end point events (hazard ratio, 7.14; 95% CI, 1.77 to 28.73; P=0.005) and of further intracranial large-artery occlusive disease-related ischemic events (hazard ratio, 30.67; 95% CI, 3.6 to 255.5; P=0.0015), after adjustment for age, sex, and risk factors. Kaplan-Meier curves showed that a significantly lower proportion of patients with a high-sensitivity CRP >1.41 mg/dL remained free of a new ischemic event (P<0.0001). CONCLUSIONS: High-sensitivity CRP serum level predicts further intracranial large-artery occlusive disease-related and any major ischemic events in patients with first-ever TIA or stroke with intracranial large-artery occlusive disease. These findings are consistent with the hypothesis that inflammation may be involved in the progression and complication of intracranial large-artery occlusive disease.