Large Artery Atherosclerosis Subtype Research Articles

Genetic variants in ALDH2 predict risk of ischemic stroke in a Chinese population

Background and purposeGenome-wide association studies discovered a novel correlation between chromosome 12q24 and ischemic stroke in European populations. This study aimed to determine whether two genetic variants (rs10744777 and rs886205) on chromosome 12q24 can modify the risk of ischemic stroke in Chinese population. MethodsWe recruited 1195 patients with ischemic stroke and 642 healthy Chinese individuals. The rs10744777 and rs886205 polymorphisms in aldehyde dehydrogenase2 (ALDH2) was genotyped and compared using multivariate logistic regression. ResultsThe genotype of rs10744777 (CT/TT) was associated with risk of ischemic stroke in males (OR = 1.99, 95% CI = 1.15–3.42, P = 0.013). In contrast, no significant correlation was found in females. Haplotype analysis indicated that haplotype “TA” was associated with increased ischemic stroke risk (OR = 1.85, 95% CI = 1.10–3.12, P = 0.042). Further subtype analysis demonstrated that the rs10744777 (CT/TT) genotype was strongly associated with large artery atherosclerosis subtype in males (OR = 2.27, 95% CI = 1.30–3.95, P = 0.004). After three months follow-up, we found a poorer functional outcome of ischemic stroke associated with the rs886205 GA genotype (OR = 1.76, 95% CI 1.03–3.00, P = 0.057) in males. ConclusionsGenetic polymorphisms in ALDH2 modified ischemic stroke risk and outcome in Chinese males, but not in females.

Effects of Blood Pressure in the Early Phase of Ischemic Stroke and Stroke Subtype on Poststroke Cognitive Impairment.

Blood pressure (BP) control in the early phase of stroke is controversial to reduce the risk of poststroke cognitive impairment (PSCI). This study was to investigate the impact of BP levels in the early phase of ischemic stroke and stroke subtype on PSCI. Seven hundred and ninety-six patients with acute ischemic stroke were included. Cognitive function was assessed after stroke onset using the Montreal Cognitive Assessment. Patients were divided into quintiles according to systolic BP and diastolic BP levels in the early phase. Subtype analyses were according to Trial of ORG 10172 in Acute Stroke Treatment classification (infarct cause) and Oxfordshire Community Stroke Project classification (infarct location). After adjusting for multiple variables, the quintiles with the lowest systolic BP (Q1, 102-127 mm Hg) and with the highest systolic BP (Q5, 171-215 mm Hg) were associated with increased PSCI risk (odds ratio, 1.83; 95% confidence interval, 1.64-2.28; P=0.007 in Q1; odds ratio, 2.32; 95% confidence interval, 1.74-2.90; P<0.001 in Q5) at 3 months as compared with the middle quintile (Q3, 143-158 mm Hg). Similar association was found in diastolic BP quintiles. The analysis of cerebral infarction subtype demonstrated that both large artery atherosclerosis and total anterior circulation infarct were associated with increased risk of PSCI at 3 months after adjusting for multiple variables (large artery atherosclerosis: odds ratio, 1.42; 95% confidence interval, 1.06-1.90; P=0.031; total anterior circulation infarct: odds ratio, 1.68; 95% confidence interval, 1.32-2.15; P=0.001). Lower or higher BP in the early phase of ischemic stroke was correlated with increased PSCI risk at 3 months. Maintaining systolic/diastolic BP in the levels of 143 to 158/93 to 102 mm Hg might be beneficial to reduce the occurrence of PSCI. Moreover, large artery atherosclerosis subtype and total anterior circulation infarct subtype were correlated with increased PSCI risk at 3 months. URL: https://www.chictr.org. Unique identifier: ChiCTR-TRC-14004804.

High serum uric acid levels are a protective factor against unfavourable neurological functional outcome in patients with ischaemic stroke.

ObjectiveWe aimed to evaluate the association between serum uric acid levels at the onset and prognostic outcome in patients with acute ischaemic stroke.MethodsWe retrospectively analysed the outcomes of 1166 patients with ischaemic stroke who were hospitalized in our centre during August 2008 to November 2012. Correlations of serum uric acid levels and prognostic outcomes were analysed.ResultsMen had higher serum uric acid levels and better neurological functional outcomes compared with women. There was a strong negative correlation between serum uric acid levels and unfavourable neurological functional outcomes. Generalized estimated equation analysis showed that a higher serum uric acid level (>237 µmol/L) was a protective factor for neurological functional outcome in male, but not female, patients. Among five trial of ORG 10172 in acute stroke treatment classification subtypes, only patients with the large-artery atherosclerosis subtype had a significant protective effect of serum uric acid levels on neurological outcome.ConclusionsOur study shows that high serum uric acid levels are a significant protective factor in men and in the large-artery atherosclerosis subtype in patients with ischaemic stroke. This is helpful for determining the prognostic value of serum uric acid levels for neurological outcome of acute ischaemic stroke.

Short-term exposure to traffic-related air pollution and ischemic stroke onset in Barcelona, Spain

ObjectiveTo assess the relationship between short-term exposure to outdoor ambient air pollutants (fine particulate matter [PM2.5] and black carbon [BC]), ischemic stroke (IS) and its different subtypes, and the potential modifying effect of neighborhood greenspace and noise. MethodsThis time-stratified case-crossover study was based on IS and transient ischemic attacks (TIA) recorded in a hospital-based prospective stroke register (BASICMAR 2005–2014) in Barcelona (Catalonia, Spain). Daily and hourly pollutant concentrations and meteorological data were obtained from monitoring stations in the city. Time-lags (from previous 72h to acute stroke onset) were analyzed. Greenness and noise were determined from the Normalized Difference Vegetation Index (NDVI) and daily average noise level at the street nearest to residential address, respectively. ResultsThe 2742 cases with known onset date and time, living in the study area, were analyzed. After adjusting for temperature, no statistically significant association between pollutants exposure and overall stroke risk was found. In subtype analysis, an association was detected between BC exposure at 24–47h (odds ratio, 1.251; 95% confidence interval [CI], 1.001–1.552; P = 0.042) and 48–72h (1.211; 95% CI, 0.988–1.484; P = 0.065) time-lag prior to stroke onset and large-artery atherosclerosis subtype. No clear modifying effect of greenness or noise was observed. ConclusionsOverall, no association was found between PM2.5 and BC exposure and acute IS risk. By stroke subtype, large-artery atherosclerotic stroke could be triggered by daily increases in BC, a diesel fuel-related pollutant in the study area.

Association of Polymorphisms of the Matrix Metalloproteinase 9 Gene with Ischaemic Stroke in a Southern Chinese Population

Background/Aims: Matrix metalloproteinase 9 (MMP9), a potent endopeptidase degrading extracellular matrix, plays a pivotal role in the pathogenesis of ischaemic stroke (IS). The present study was undertaken to determine the association of MMP9 gene polymorphisms and the risk of IS in a southern Chinese population. Methods: A cohort of 1274 patients and 1258 age-matched healthy controls were genotyped to detect the four MMP9 polymorphisms (rs17156, rs3787268, rs3918241 and rs3918242) using SNaPshot. Results: Our study demonstrated a significant difference in the genotype and allele frequencies of the MMP9 rs3918242 polymorphism between the IS patients and the controls (P = 0.012 for the genotype and P = 0.0092 for the allele). Stratification by smoking status showed statistically significant differences in the frequency and allele of the rs3918242 polymorphism between IS patients and the controls (P = 0.0052 for the genotype and P = 0.0019 for the allele). Further stratification by IS subtypes revealed that the presence of the T allele of the MMP9 rs3918242 polymorphism confers a higher risk of the large artery atherosclerosis subtype of IS (P = 0.017). Moreover, IS patients with the rs3918242 T allele of MMP9 presented with increased serum MMP9 production, and this increase was more significant in smokers with IS (P = 0.022). Patients carrying the variant T allele of the MMP9 rs3918242 polymorphism exhibited significantly higher infarct volumes than those with the major CC genotype (P = 0.036). Conclusion: Our study provides preliminary evidence that the MMP9 rs3918242 polymorphism is linked to a higher risk of IS, confirming the role of MMP9 in the pathophysiology of IS, with potentially important therapeutic implications.

Differential impact of white matter hyperintensities on long-term outcomes in ischemic stroke patients with large artery atherosclerosis

BackgroundThe presence of white matter hyperintensity (WMH) is related to poor long-term outcomes in stroke patients. However, the long-term outcome is unknown in patients with both large artery atherosclerosis (LAA) and WMH.MethodsWe investigated the impact of WMH on long-term outcome in patients with LAA. Consecutive patients in a prospective stroke registry were included. Patients were followed for a median of 7.7 years (interquartile range, 5.6–9.7). The degree of WMH was assessed by Fazekas grade on fluid-attenuated inversion recovery images. Total WMH burden was calculated by summation of Fazekas scores in periventricular and deep white matter. Severe WMH was defined as total burden score ≥ 3.ResultsAmong 2529 patients, 639 patients (25.3%) were classified with the LAA subtype. After applying exclusion criteria, the data from 538 patients were analyzed. The mean patient age was 65.7 ± 10.3 years. Severe WMHs were found in 243 patients (45.2%). During follow-up, 200 patients (37.2%) died. Cox regression analysis showed that LAA patients with severe WMH had a 1.50-fold (95% CI, 1.12–2.00, p = 0.007) higher death rate compared to those without. In the older age group (≥65 years), Cox regression revealed that patients with severe WMH had a 1.75-fold (95% CI, 1.15–2.65, p = 0.008) higher 5-year death rate, whereas the younger age group did not have this association.ConclusionThe degree of WMH might be a surrogate marker for long-term outcome in patients with LAA. Atherosclerotic burdens in both small and large arteries might impact long-term prognosis in ischemic stroke patients.

Joint Effects of PON1 Polymorphisms and Vegetable Intake on Ischemic Stroke: A Family-Based Case Control Study.

Paraoxonase 1 gene (PON1) polymorphisms and dietary vegetable and fruit intake are both established determinants of ischemic stroke (IS). However, little is known about whether these factors jointly influence the risk of IS. We analyzed the main effects of PON1, as well as the interactions between PON1 and dietary vegetable or fruit intake with the risk of total IS and its subtypes in a family-based case-control study conducted among 2158 Chinese participants (1007 IS cases and 1151 IS-free controls) from 918 families. Conditional logistic regression models, with each family as a stratum, were used to examine the association between rs662 and IS. Gene-diet interactions were tested by including a cross-product term of dietary vegetable or fruit intake by rs662_G allele count in the models. Each copy of the PON1 rs662_G allele was associated with 28% higher risk of total IS (p = 0.008) and 32% higher risk of large artery atherosclerosis subtype (LAA) (p = 0.01). We observed an interaction between rs662 and vegetable intake for both total IS (p = 0.006) and LAA (p = 0.02) after adjustment for covariates. Individuals who carry the rs662_A allele may benefit to a greater extent from intake of vegetables and thus be more effectively protected from ischemic stroke, whereas carriers of the G allele may still remain at greater risk for ischemic stroke due to their genetic backgrounds even when they consume a high level of vegetables. More studies are needed to replicate our findings among other populations.

Genetic predisposition to ischaemic stroke by RAGE and HMGB1 gene variants in Chinese Han population.

Emerging evidence suggests that the multiligand receptor for advanced glycation end products (RAGE) and its ligand high mobility group box 1 protein (HMGB1) contribute to the pathophysiology of ischaemic stroke (IS). The present study aimed to investigate the association of RAGE and HMGB1 variants with the risk of IS. A total of 1,034 patients and 1,015 age- and sex-matched healthy controls were genotyped to detect five genetic variants of the RAGE gene and four genetic variants of the HMGB1 gene using the Multiplex SNaPshot assay. We found that the rs2070600 variant of RAGE was associated with an increased risk of IS (OR = 1.19, 95% CI: 1.02-1.38, P = 0.043), whereas the rs2249825 variant of HMGB1 was associated with a decreased risk of IS (OR = 0.83, 95% CI: 0.71-0.98, P = 0.041). Further stratification by IS subtypes revealed that the presence of the TT genotype of the RAGE rs2070600 variant confers a higher risk of the large artery atherosclerosis subtype of IS (P = 0.036). Moreover, patients with the variant T allele of the RAGE rs2070600 variant presented with reduced serum soluble RAGE production. Patients carrying the variant G allele of the HMGB1 rs2249825 variant exhibited significantly lower infarct volumes than those with the major CC genotype. These clues may help in the development of optimal personalized therapeutic approaches for IS patients.

The association of vertebrobasilar calcification with etiological subtypes, stroke recurrence and outcome in acute brainstem ischemic stroke

Arterial calcification (AC), a frequent finding on imaging studies, has been reported as a risk factor for ischemic stroke. However few studies have explored the association of AC with etiological subtypes and prognostic implications. The purpose of this study was to investigate the association of AC with demograhics, risk factors and etiological subtypes and to determine whether it predicts stroke recurrence and functional outcome in patients with acute brainstem ischemic stroke. We analyzed our database consisting of patients who were diagnosed as acute brainstem ischemic stroke admitted within 24hours of onset. Etiological classification of stroke was made based on The Trial of ORG in Acute Stroke Treatment (TOAST) Classification. AC in vertebral and basilar arteries were assessed from baseline brain CT. AC degree was categorized according to calcification along the circumference in the densest calcified segment of each vessel (0 point if no calcification in any of the CT slices, 1 point if calcification <50% of circumference and 2 points if calcification ≥50% of circumference). Three AC categories were defined according to the total AC score as follows: no AC (0 point), mild AC (1–2 points), severe AC (≥3 points). Recurrent stroke within the first 3 months of follow up and modified Rankin Score (mRS) at 3-month were reviewed. 42% of 188 patients had AC in at least of the vertebrobasilar arteries. Severe AC was related to age and the presence of diabetes mellitus and coronary artery disease. The prevalence of AC was significantly higher in large artery atherosclerosis subtype. The presence of AC was marginally associated with recurrent stroke but did not find to be related with functional outcome. Further studies with larger sample size are warranted to explore this topic.

Distribution of atherosclerotic stenosis determining early neurologic deterioration in acute ischemic stroke.

Background and purposeEarly neurologic deterioration (END) during the acute stage of stroke is clinically important because of its association with poor outcomes. The purpose of this study was (1) to investigate variables associated with END, (2) to determine the distribution of atherosclerotic stenosis associated with END, and (3) to clarify the relationship between END and clinical outcomes.Methods516 patients with acute ischemic stroke were included. The median follow-up period was 31.7 months. END was defined as a ≥2 point increase in the National Institutes of Health Stroke Scale (NIHSS), ≥1 point increase in level of consciousness or motor item of the NIHSS, or the development of any new neurological deficits during the first 72 hours of hospitalization. A signal loss on 1.5-T magnetic resonance angiography exceeding 50% was considered to be significant for the categorization of stenosis pattern.ResultsThe prevalence of END was 19.0%. END was associated with intracranial atherosclerotic stenosis (IAS) together with large artery atherosclerosis (LAA) subtype. In particular, stenosis of basilar artery or posterior cerebral artery was independently associated with END. Lesion growth or hypoperfusion was more accountable for END in patients with IAS, whereas intracerebral hemorrhage or edema/herniation was more frequently observed in END patients without IAS. Patients with END had a higher rate of mortality, but a similar rate of further vascular events compared to patients without END.ConclusionPre-stroke IAS and LAA subtype could determine the development of END during the acute stage of ischemic stroke.

LDL Subclasses in Ischemic Stroke: A Risk Factor?

Seven low-density lipoprotein (LDL) subclasses are identified, and smaller LDL particles are associated with an increased risk for cardiovascular events. However, there is limited data about the relationship between the acute ischemic stroke (AIS) subtypes and LDL subclasses. The aim of our study is to investigate the relationship between AIS subtypes and LDL subclasses. This study consisted of 110 AIS patients and 60 healthy controls. Stroke patients were classified according to the TOAST classification system as cardioembolic infarct (CI), large artery atherosclerosis (LAA), and lacunar infarct (LI). LDL subclasses were distributed as seven bands (LDL-1 and-2 defined as large, and LDL-3 to-7 defined as small-LDL particle), using the LipoPrintª System. Control group and AIS subtypes were compared in terms of LDL subclasses; p<0.05 was considered statistically significant. AIS patients had higher LDL-2, LDL-3 and LDL-4 subclasses compared to the control groups, while LDL-1 was similar in two groups. In addition, LDL-2 and LDL-3 subclasses were significantly higher in each AIS subtype when compared to the control group. LDL-4 subclasses were significantly higher in LAA and LI subtypes than in the control group, but there was no relationship for CI subtypes. Smaller subclasses LDL-5 to LDL-7 were undetectable in both AIS patients and controls. Using regression analysis; age, LDL-2, LDL-3 and LDL-4 were found to be independent predictors of AIS development. Our study showed that examination of LDL subclasses may be important in management of AIS patients. LDL-2, LDL-3, and LDL-4 are independent predictors of AIS development. These findings should be supported by further large studies.

The role of high-sensitivity C-reactive protein levels in functional outcomes in patients with large-artery atherosclerosis and small-artery occlusion

Background: High-sensitivity C-reactive protein (hs-CRP) is an inflammatory marker that is associated with the outcomes of ischemic stroke. However, the role of hs-CRP levels in the functional outcomes after large-artery atherosclerosis (LAA) and small-artery occlusion (SAO) is poorly understood. Methods: We recruited 1299 patients diagnosed as having LAA and 453 patients diagnosed as having SAO from 1 January 2009 to 31 December 2013, from the Department of Neurology, Tianjin Huanhu Hospital. The hs-CRP values were classified into two groups based on the significant threshold of hs-CRP level in the receiver operating characteristic (ROC) curve (≥3.215 mg/L in LAA and ≥1.72 mg/L in SAO). We examined the relationship between hs-CRP levels on admission and the modified Rankin scale scores using univariate and multivariate analyses. Results: Patients with LAA had a higher hs-CRP mean value than patients with SAO (7.69 vs. 4.12 mg/L). The ROC curve showed a significant hs-CRP threshold value at 3.215 mg/L in patients with LAA and at 1.72 mg/L in patients with SAO. Logistic regression analyses showed that patients with LAA with hs-CRP levels ≥3.215 mg/L had a significant risk of poor outcome compared with those with hs-CRP levels <3.215 mg/L (odds ratio [OR], 1.545; 95% confidence interval [CI], 1.155–2.067; p = 0.003). Meanwhile, patients with SAO with hs-CRP levels ≥1.72 mg/L had a significant risk of poor outcome compared with those with hs-CRP levels <1.72 mg/L (OR, 1.97; 95% CI, 1.02–3.801; p = 0.043). Moreover, combining hs-CRP with National Institutes of Health Stroke Scale could predict outcome with satisfying clinical accuracy both in LAA and SAO subtype. Conclusions: Patients with LAA with hs-CRP levels <3.215 mg/L and patients with SAO with hs-CRP levels <1.72 mg/L on admission had favorable functional outcomes at 3 months after stroke onset.

Validation of the Essen Stroke Risk Score in different subtypes of ischemic stroke

Objective: Predictive scores are important tools for stratifying patients based on their risk of future vascular events and for selecting preventive therapies. The aim of this study is to validate the Essen Stroke Risk Score (ESRS) for stratifying stroke recurrence in different subtypes of non-atrial fibrillation ischemic stroke in a large Chinese cohort.Methods: Data were derived from the Blood pressure and clinical Outcome in Stroke Survivors registry, which includes a cohort of 2204 stroke patients. All patients were further classified according to the TOAST (Trial of Org 10 172 in Acute Stroke Treatment) criteria. We stratified one-year cumulative rates for stroke and composite vascular events using the ESRS. The predictive power of the ESRS was assessed using the area under the receiver–operator curves (AUC).Results: Among 1699 patients included in the study, the AUC of ESRS was 0.58 (95% CI: 0.52–0.64) for recurrent stroke, whereas 0.59 (95% CI: 0.53–0.64) for composite vascular events at 1 year. In patients with large-artery atherosclerosis (LAA) subtype of stroke, the AUC of ESRS was both 0.61 (95% CI: 0.54–0.68) for recurrent stroke and composite vascular events. However, no significant AUC was observed in patients with small-artery occlusion subtype of stroke.Conclusions: In patients with LAA subtype of non-atrial fibrillation stroke, the ESRS has moderate accuracy in stratifying the risk of both recurrent strokes and major vascular events within the first year. However, the ESRS couldn’t accurately stratify the risk of recurrent strokes in patients with small-artery atherosclerosis subtype of non-atrial fibrillation stroke.

The elevated lipoprotein-associated phospholipase A2 activity is associated with the occurrence and recurrence of acute cerebral infarction.

There is a strong association between lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and atherosclerosis-related diseases. The aim of this study was to investigate the role of Lp-PLA2 in the ischemic stroke and further offer clinical evidence that measuring Lp-PLA2 helps predict the risk of stroke occurrence and recurrence. A total of 328 hospitalized patients were recruited, including 179 cases of acute cerebral infarction (ACI) and 149 non-ACI controls. The serum level of Lp-PLA2 in ACI was significantly higher than non-ACI. The serum level of Lp-PLA2 in the recurrence of ACI was significantly higher than the nonrecurrence. The serum levels of Lp-PLA2 in large-artery atherosclerosis subtype were the highest among the subtypes of the Trial of Org 10172 in Acute Stroke Treatment and non-ACI controls. The level of Lp-PLA2 in large-artery atherosclerosis and the cardioembolism group was statistically significantly higher than that of the control cases. There was no statistically significant difference between the small-vessel occlusion group and the control cases. The present study confirmed that the elevated Lp-PLA2 level can be a risk factor for ischemic stroke in the Chinese population. The serum level of Lp-PLA2 may be a predictive factor for the recurrence of ACI.

Analysis of risk factors of cerebral infarction in young adults and its correlation with TOAST types

Objective To explore the risk factors of youth cerebral infarction and its correlation with clinical TOAST types. Methods 82 young patients with acute cerebral infarction(aged from 18 to 45 years old) were selected.The risk factors for youth cerebral infarction patients, and the proportion of TOAST subtype and related risk factors were analyzed. Results Risk factors for youth cerebral infarction were as follows: hyperlipidemia (χ2=48.703, P<0.05), hypertension (χ2=40.829, P<0.05), carotid sclerosis (χ2=46.217, P<0.05), hyperhomocysteinemia (χ2=40.255, P<0.05), smoking history (χ2=7.853, P<0.05), diabetes (χ2=18.256, P<0.05) and family history (χ2=5.944, P<0.05), heart disease (χ2=5.754, P<0.05). The proportion of their TOAST subtypes were as following: small artery occlusion lacunar(SAD)(39.0%), large artery atherosclerosis(LAA)(24.4%), stroke of other undetemined etiology(SUE)(17.0%), and acute stroke of other detemined etiology(SOE)(12.2%), cardioembolism(CE) type(7.3%). Major risk factors for LAA subtype included hyperlipidemia, hypertension and carotid atherosclerosis; Major risk factor for SUE subtype was hyperhomocysteinemia; Major risk factors for SOE included hypertension, diabetes.Major risk factor for CE subtype was heart disease. Conclusion The highest proportion of TOAST types in youth cerebral infarction group is small artery occlusion lacunar.Major risk factors for this group of youth cerebral infarction are as follows: hypertension, carotid atherosclerosis, heart disease, diabetes, hyperhomocysteinemia, obesity, smoking and family history, and these risk factors should be actively intervened. Key words: Cerebral infarction; Youth; TOAST types; Risk factors

Endothelial function and arterial stiffness indexes in subjects with acute ischemic stroke: Relationship with TOAST subtype

Background and aimsOnly one study has examined endothelial function in subjects with acute ischemic stroke and no study has yet assessed arterial stiffness and reactive hyperemia peripheral arterial tonometry (RH-PAT) in ischemic stroke and its clinical subtypes. Our study aimed to evaluate arterial stiffness and endothelial dysfunction indexes in patients with acute ischemic stroke and the relationship between endothelial dysfunction indexes and arterial stiffness markers and stroke subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) Classification. MethodsWe enrolled 98 patients with a diagnosis of acute ischemic stroke and 105 hospitalized patients without a diagnosis of acute ischemic stroke. Arterial stiffness analysis was conducted by applanation tonometry to record radial artery pressure waveform continuously; augmentation index (Aix) and pulse wave velocity (PWV) were calculated. The reactive hyperemia index (RHI) was assessed by peripheral arterial tonometry. ResultsIn comparison to controls, ischemic stroke subjects had higher mean levels of PWV, Aix, and significantly lower mean RHI values. Compared to subjects with lacunar and cardioembolic stroke, those with Large Artery AtheroSclerosis (LAAS) subtype of stroke had higher median levels of PWV and significantly lower median levels of RHI. On multinomial logistic regression analysis of predictive variables of stroke subtype (lacunar vs. LAAS and lacunar vs. cardioembolic), we observed a negative association between RHI value and LAAS subtype and a negative association of PWV with cardioembolic subtype. ConclusionsOur findings underline the relationship between endothelial and arterial stiffness index correlations in patients with acute ischemic stroke, also suggesting the use of a combination of PAT and arterial stiffness indexes to better categorize patients with ischemic stroke.

Platelet-to-White Blood Cell Ratio: A Prognostic Predictor for 90-Day Outcomes in Ischemic Stroke Patients with Intravenous Thrombolysis

This study is aimed to investigate the relationship between platelet-to-white blood cell ratio (PWR) and 90-day outcomes in acute stroke patients with intravenous thrombolysis (IVT). A retrospective analysis was performed on 168 patients receiving IVT for acute ischemic stroke. Complete blood count evaluation was conducted at admission before IVT. A modified Rankin Scale (mRS) score of 3-6 at 90 days was considered an unfavorable outcome. A total of 168 patients were included from 2013 to 2015. The mean age of the sample was 64.6 (±12.3) years, and 23.2% were women. The median baseline National Institutes of Health Stroke Scale score was 7.5 (interquartile range [IQR] 8.0) and the 90-day mRS score was 2 (IQR 2). In our multivariate logistic regression model, a PWR greater than 23.52 (odds ratio .454, 95% confidence interval: .212-.973, P < .050) was a predictor of 90-day outcomes. In addition, there was a significant difference in the PWR values of patients between favorable outcome and unfavorable outcome in the large-artery atherosclerosis subtype (28.241 ± 11.581 and 21.899 ± 9.107, respectively; P = .005). The PWR at admission predicts 90-day outcomes in ischemic stroke patients with IVT. With the easy and routine use of hemogram analysis, the PWR should be investigated in further prospective randomized controlled trials of acute stroke.

Smoking-Thrombolysis Relationship Depends on Ischemic Stroke Subtype.

The relationship between smoking and the outcome in patients received thrombolysis is undetermined. The outcome could be influenced by different stroke subtypes. This study aimed to explore whether smoking had any impact on the outcome in patients with stroke of different subtypes who received intravenous thrombolysis. All patients who received intravenous thrombolysis within 4.5 hours after symptom onset from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) database were eligible to be entered into this analysis. Smokers were considered if they smoked at least 1 cigarette/d for >6 months before stroke. Ischemic stroke subtype was classified by using the Trial of Org 10172 in Acute Stroke Treatment criteria. Outcome measurements included post-intravenous thrombolysis symptomatic intracranial hemorrhage within 7 days, mortality, and functional independence at 90 days. The relationship between smoking and thrombolysis was analyzed by using univariate and multivariate logistic regression models. Of 1118 patients enrolled, we identified 454 smokers and 664 nonsmokers. After stratifying for ischemic stroke subtypes, multivariate analysis revealed a significant relationship between smoking and functional independence in patients with noncardioembolism stroke subtypes (large artery atherosclerosis: odds ratio [OR], 1.452; 95% confidence interval [CI], 1.053-2.264; small artery occlusion: OR, 4.275; 95% CI, 1.098-16.649; other: OR, 3.120; 95% CI, 1.162-8.373). Furthermore, smoking was specially related to lower rates of symptomatic intracranial hemorrhage (OR, 0.316; 95% CI, 0.120-0.832) and mortality (OR, 0.272; 95% CI, 0.128-0.577) in patients with large artery atherosclerosis subtype. In patients treated with intravenous thrombolysis, smoking could be related to a better chance of functional independence if their subtype of stroke was noncardioembolic, and a lower risk of symptomatic intracranial hemorrhage and mortality in those with large artery atherosclerosis.

Interactions among Candidate Genes Selected by Meta-Analyses Resulting in Higher Risk of Ischemic Stroke in a Chinese Population.

Ischemic stroke (IS) is a multifactorial disorder caused by both genetic and environmental factors. The combined effects of multiple susceptibility genes might result in a higher risk for IS than a single gene. Therefore, we investigated whether interactions among multiple susceptibility genes were associated with an increased risk of IS by evaluating gene polymorphisms identified in previous meta-analyses, including methylenetetrahydrofolate reductase (MTHFR) C677T, beta fibrinogen (FGB, β-FG) A455G and T148C, apolipoprotein E (APOE) ε2–4, angiotensin-converting enzyme (ACE) insertion/deletion (I/D), and endothelial nitric oxide synthase (eNOS) G894T. In order to examine these interactions, 712 patients with IS and 774 controls in a Chinese Han population were genotyped using the SNaPshot method, and multifactor dimensionality reduction analysis was used to detect potential interactions among the candidate genes. The results of this study found that ACE I/D and β-FG T148C were significant synergistic contributors to IS. In particular, the ACE DD + β-FG 148CC, ACE DD + β-FG 148CT, and ACE ID + β-FG 148CC genotype combinations resulted in higher risk of IS. After adjusting for potential confounding IS risk factors (age, gender, family history of IS, hypertension history and history of diabetes mellitus) using a logistic analysis, a significant correlation between the genotype combinations and IS patients persisted (overall stroke: adjusted odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.22–2.02, P < 0.001, large artery atherosclerosis subtype: adjusted OR = 1.50, 95% CI: 1.08–2.07, P = 0.016, small-artery occlusion subtype: adjusted OR = 2.04, 95% CI: 1.43–2.91, P < 0.001). The results of this study indicate that the ACE I/D and β-FG T148C combination may result in significantly higher risk of IS in this Chinese population.

Thrombus Features in Hyperacute Ischemic Stroke: A Perspective on Using Length and Density Evaluation

More insights in the etiopathogenesis of thrombi could be helpful in the treatment of patients with acute ischemic stroke (AIS). One of the most confident and early imaging findings of stroke includes arterial hyperdensity. The purpose of this study was to determine whether thrombi's density and length would be useful for predicting their origin. We evaluated 68 consecutive patients with AIS to correlate the presence of thrombi and their imaging features with the stroke subtype. After excluding patients with small-artery occlusion mechanism and undetermined and other causes, the stroke etiologic subtypes were large-artery atherosclerosis (LAA) in 59.0% of the patients, cardioembolism in 31.0%, and cervical artery dissection (CAD) in 10.0%. CAD more often caused thrombi with the longest length and highest attenuation, while thrombi that originated from the LAA had the smallest length and lowest attenuation. The mean Hounsfield unit (HU) values of all thrombi (with and without hyperdensity) on noncontrast computed tomography were 62.4 (50.0-70.0) in CAD, 53.8 (42.0-65.0) in cardioembolism, and 48.6 (27.0-65.0) in LAA. The length measurements were 28.5 mm (12.0-52.0) in CAD, 13.7 mm (5.0-31.0) in cardioembolism, and 10.8 mm (3.0-25.0) in the LAA subtype. The minimum cutoff value of 60 HU and a length greater than 20 mm were able to discriminate the CAD thrombi with an accuracy of 86.8% and 92.6%, respectively. Our study findings show how important thrombus analysis is in patients with AIS. Thrombus analysis can allow early suspicion of CAD before dedicated imaging of the cervical arteries is performed.