Association of Ring Finger Protein 213 Gene P.R4810k Polymorphism with Intracranial Major Artery Stenosis/Occlusion.

BACKGROUND: Intracranial major artery stenosis/occlusion (ICASO) is a common cause of ischemic stroke worldwide. A number of studies have assessed the association of the p.R4810K polymorphism in the ring finger protein 213 (RNF213) gene with ICASO, but the results have not been entirely consistent. METHODS: We conducted a case-control study to estimate the association between the p.R4810K polymorphism and the risk of ICASO in a Chinese population. A total of 124 patients and 230 controls were enrolled. Moreover, a meta-analysis was performed to evaluate this association in the East Asian populations. RESULTS: In our case-control study, the frequencies of the G/A genotype of p.R4810K were significantly higher in the ICASO patients than in the control group (4.03% versus .43%, P = .021, respectively). Moreover, in the meta-analysis, we assessed 7 case-control studies that included 1239 patients and 1377 controls. The pooled odds ratios (ORs) indicated significant association between the p.R4810K polymorphism and the ICASO risk in the dominant model (OR = 9.37, 95% confidence interval: 4.61-19.02, P = .000), the heterozygote comparison (OR = 8.97, 95% CI: 4.41-18.25, P = .000), and the allele comparison (OR = 9.50, 95% confidence interval: 4.71-19.19, P = .000) in the East Asian populations. Subgroup analysis based on ethnicity revealed that the risks in the Japanese and the Korean populations were higher than that in the Chinese population. CONCLUSIONS: The p.R4810K polymorphism was associated with an increased risk of ICASO in the East Asian populations. Further studies on the function of the RNF213 protein and the clinical features of this subtype of ICASO are needed.

Distribution of ischemic infarction and stenosis of intra- and extracranial arteries in young Chinese patients with ischemic stroke.

BACKGROUND: The distribution of cerebral ischemic infarction and stenosis in ischemic stroke may vary with age-group, race and gender. This study was conducted to understand the risk factors and characteristics of cerebral infarction and stenosis of vessels in young Chinese patients with ischemic stroke. METHODS: This was a retrospective study, from January 2007 to July 2012, of 123 patients ≤50 years diagnosed with acute ischemic stroke. Patient characteristics were compared according to sex (98 males and 25 females) and age group (51 patients were ≤45 years and 72 patients were 46-50 years). Characteristics of acute ischemic infarction were studied by diffusion weighted imaging. Stenosis of intra- and extracranial arteries was diagnosed by duplex sonography, head magnetic resonance angiography (MRA) or cervical MRA. RESULTS: Common risk factors were hypertension (72.4 %), dyslipidemia (55.3 %), smoking (54.4 %) and diabetes (33.3 %). Lacunar Infarction was most common in our patients (41.5 %). Partial anterior circulation infarction was predominant in females (52.0 vs 32.7 %; P = 0.073) and posterior circulation infarction in males (19.8 vs 4 %; P = 0.073). Multiple brain infarctions were found in 38 patients (30.9 %). Small artery atherosclerosis was found in 54 patients (43.9 %), with higher prevalence in patients of the 46-50 years age-group. Intracranial stenosis was more common than extracranial stenosis, and middle cerebral artery stenosis was most prevalent (27.3 %). Stenosis in the anterior circulation was more frequent than in the posterior circulation (P < 0.001). CONCLUSIONS: In these young patients, hypertension, smoking, dyslipidemia and diabetes were common risk factors. Intracranial stenosis was most common. The middle cerebral artery was highly vulnerable.

Randomized controlled trial of symptomatic middle cerebral artery stenosis: endovascular versus medical therapy in a Chinese population.

BACKGROUND AND PURPOSE: To investigate the efficacy and safety of percutaneous transluminal angioplasty and stenting (PTAS) for symptomatic middle cerebral artery stenosis compared with standard medical treatment in a low-risk Chinese population. METHODS: A prospective, randomized, controlled, single-center clinical trial was conducted comparing PTAS with medical treatment for symptomatic middle cerebral artery stenosis (≥70%). Patients were enrolled according to 1:1 enroll ratio (PTAS: medical). The PTAS group received stenting or balloon angioplasty, whereas the medical treatment group received standard medical treatment (aspirin 100mg plus clopidogrel 75 mg/d), and all the patients were under strict control of the risk factors. The end point events were any kind of ipsilateral stroke or transient ischemic attack, or death from any origin during 1-year follow-up. RESULTS: The enrollment was stopped after 70 patients were enrolled from August 2007 to December 2010, with a 30-day rate of end point events of 8.3% versus 5.9% (P=0.69) for PTAS and medical group, respectively, and 1-year rate of end point events of 19.4% versus 17.6% (P=0.85), respectively. There was no significant difference in baseline characteristics between the 2 groups. The mean follow-up time, which was ongoing, was 9.9±3.9 and 9.7±4.4 months, respectively. Among the risk factors, hypertension was the independent related to the outcome (P=0.015). CONCLUSIONS: This study showed that endovascular treatment is as safe but not better than medical treatment for symptomatic middle cerebral artery stenosis in a low-risk Chinese population. History of hypertension increases the risk of recurrent ischemic events.

Atherosclerotic vascular disease rather than metabolic syndrome predicts ischemic stroke in diabetic patients.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the effect of metabolic syndrome on ischemic stroke in Chinese subjects with type 2 diabetes. METHODS: Anthropometric parameters (waist circumference and body mass index), blood pressure, and plasma biochemical (lipid and glycemic profiles) were collected. Subjects with type 2 diabetes were categorized by the criteria of the updated Adult Treatment Panel III (ATP III) with the modified definitions of obesity in Asians. Transcranial Doppler was performed to define middle cerebral artery stenosis. RESULTS: Of 2,197 patients (age 55.4 +/- 11.3 years; male 40.8%; median follow-up period 8.7 years, interquartile range 7.8-9.5 years) without symptoms of cerebrovascular disease, evidence of middle cerebral artery stenosis was identified in 272 subjects (12.4%). According to NCEP ATP III criteria, 1,324 (60.3%) patients had MetS at baseline. Ischemic stroke occurred in 184 (8.4%, 184/2197) patients during follow-up. Patients with incident stroke had a higher prevalence of MetS compared with those without stroke (p = 0.004), and the number of components of MetS was also significantly increased in patients with stroke (p = 0.001). Cox regression demonstrated that MetS was not associated with incident stroke. CONCLUSIONS: In Chinese type 2 diabetic patients, metabolic syndrome does affect stroke occurrence with a higher stroke incidence among those with metabolic syndrome, but stroke occurrence seems to be better explained by other vascular risk factors than by metabolic syndrome.

Middle cerebral artery stenosis increased the risk of vascular disease mortality among type 2 diabetic patients.

BACKGROUND: In Chinese populations, middle cerebral artery (MCA) stenosis is the most commonly identified intracranial vascular lesion, and has been shown to be associated with an increased risk of secondary stroke mortality, but has yet to be reported for primary events. We assess whether asymptomatic MCA stenosis is associated with mortality in Chinese type 2 diabetic patients. METHODS: The presence of MCA stenosis was determined by transcranial Doppler and mortality data were collated in the Hong Kong Death Registry. Cox proportional hazards regression was used to determine if the MCA stenosis (n = 272, 53.7% 2-vessel disease) in 2,197 diabetics was associated with all-cause or vascular disease mortality, including after adjustment for conventional vascular risk factors. Anthropometric and fasting biochemical parameters were compared between diabetic patients with MCA stenosis and without evidence of stenosis. RESULTS: A total of 191 deaths were identified (30.9% of vascular disease origin) during a follow-up of 18,279 patient years over 8.32 years. After adjustment for age, gender and diabetes duration, the hazard ratios for vascular mortality for 1- and 2-vessel disease were 2.47 (95% CI = 1.13-5.38) and 4.47 (95% CI = 2.24-8.82), p < 0.001 for trend, for increasing vascular mortality with increasing severity of cerebrovascular involvement, but 0.81 (95% CI = 0.45-1.47) and 2.23 (95% CI = 1.45-1.47), p = 0.001 for trend, for all-cause mortality. For vascular mortality, further adjustments for anthropometric and fasting biochemical parameters, or existing disease and treatment history increased the hazard ratios for 1-vessel disease slightly but attenuated the risk for 2-vessel disease evidently, 2.81 (95% CI = 1.10-7.16) and 2.85 (95% = CI 1.11-7.33), p = 0.026. CONCLUSION: The presence of MCA stenoses was an independent predictor of vascular mortality in these diabetics. More aggressive treatment of risk factors in these subjects merits further evaluation.

Polymorphism of apolipoprotein E (APOE) and lipoprotein lipase (LPL) genes and ischaemic stroke in individuals of Yakut ethnicity.

There is evidence that most forms of ischaemic stroke (IS) result from synergistic effects of the modifiable predisposing factors and multiple genes. In the present work, we report results of case-control study of IS association with apolipoprotein E gene (APOE) (promoter and coding polymorphisms) and lipoprotein lipase gene (LPL) (presence/absence of a HindIII cutting site). We studied 107 unrelated patients of Yakut ethnicity (69 men and 38 women, mean age 58.4+/-11.5 years) with first-ever IS in carotid/middle cerebral artery regions. The control group included 101 subjects of the same ethnicity (61 men and 40 women, mean age 57.6+/-11.6 years) free of clinically detectable cerebrovascular disease, and without any history of stroke. A positive association of IS with APOE -427T allele (p=0.0012, OR=3.99) and -427T/T genotype (p=0.0005, OR=4.96) and a negative association with -427C allele (p=0.0012, OR=0.25), -427T/C genotype (p=0.0003, OR=0.18), epsilon2 allele (p=0.018, OR=0.35), epsilon2/3 genotype (p=0.017, OR=0.28) and -491A/-427C/epsilon2 haplotype (p=0.0026, OR=0.18) were observed. For atherothrombotic subgroup the same allele and genotype associations were found plus association with APOE -491A allele (p=0.026, OR=3.98). No reliable IS associations were found with LPL T+495G (HindIII) polymorphism. An association of APOE promoter polymorphisms (A-491T, T-427C) with an IS is shown in our study for the first time. Our study provides evidence for the role of APOE gene as a prognostic genetic marker for IS, especially for its atherothrombotic subtype.

Effects of the ultrasound contrast-enhancing agent Levovist on the detection of intracranial arteries and stenoses in chinese by transcranial Doppler ultrasound.

Proper assessment of intracranial arteries by transcranial Doppler sonography (TCD) in patients with intracranial stenoses is occasionally made difficult by an insufficient temporal bone window, an unfavourable insonation angle, or low flow velocity or volume. This condition is frequently found in Chinese. In these cases, echocontrast could be helpful. We investigated 48 temporal windows of 24 acute Chinese stroke patients with insufficient native transtemporal insonation conditions before and after the application of the echo enhancer Levovist (galactose/palmitic acid) by an injection pump. We classified the signal quality from four segments of the main intracranial arteries: anterior cerebral artery (A1), main stem of the middle cerebral artery (MCA, M1), intracranial segment of the carotid artery (C1), and posterior cerebral artery (P1). The signal quality was classified as follows: 0 = no signal, 1 = poor, envelope curve does not follow spectrum, 2 = adequate, envelope curve follows spectrum. As compared to the pre-contrast scans, echocontrast allowed for more segments to be evaluated by pulsed Doppler sonography. Before Levovist, only 12% of the segments could be detected, after Levovist 63%. For all arteries, signal quality was better after Levovist, p between 0.0180 and 0.0003. In 3 patients, MCA stenoses with peak systolic Doppler flow velocities above 160 cm/s were found only after Levovist. In patients with poor pre-contrast detection, echocontrast-enhanced TCD allows for more arterial segments to be insonated and for the detection of stenoses unnoted during the non-enhanced investigation.

Vascular risk factors for atherosclerotic lesions of the middle cerebral artery detected by magnetic resonance angiography (MRA).

OBJECTIVES: To examine the relationship between atherosclerotic lesions of the middle cerebral artery (MCA) detected on MRA and vascular risk factors. MATERIAL AND METHODS: We retrospectively assessed 279 patients (mean age, 69.0+/-11.3 years) who visited the Department of Neurology of Masuda Red Cross Hospital and underwent three-dimensional, time-of-flight MRA of the head between January 1996 and October 1998. Cases of cerebral embolism and internal carotid artery occlusion were excluded. Diagnoses were cerebral infarction (n = 152) and others (n = 127). We evaluated stenotic or occlusive lesions of the MCA (M1 portion), using MRA. Age, sex, history of hypertension, HbA1c, total cholesterol, fasting triglyceride, high density lipoprotein, lipoprotein(a), blood pressure, hematocrit, smoking and left ventricular hypertrophy (LVH) on ECG were included in the analysis. RESULTS: 36 patients (12.9%) had stenotic or occlusive lesions of the MCA on MRA. Univariate analysis showed that age, hypertension and HbA1c were significantly correlated with MCA lesions. Multiple logistic regression analysis showed that HbA C and hypertension were significant and independent predictors for MCA lesions. CONCLUSION: Hypertension and high serum HbAlc levels may contribute to the development of atherosclerotic lesions of the MCA in Japanese people.