Risk Of Ischemic Cerebrovascular Disease Research Articles

APOE and vascular disease: Sequencing and genotyping in general population cohorts

Background and aimsThe apolipoprotein E(APOE) ϵ2/ϵ3/ϵ4 polymorphism plays a central role in lipid metabolism, vascular disease and dementia. The impact of the full range of structural genetic variation in APOE for lipids, lipoproteins and apolipoproteins and for vascular disease in the general population is not known. MethodsWe systematically sequenced APOE in 10,296 individuals from the Copenhagen City Heart Study and genotyped nine rare variants (frequency≥2/10,296) in 95,227 individuals from the Copenhagen General Population Study. The UK Biobank was used for validation of common APOE variants. ResultsRare mutations in APOE, predicted to be deleterious, are present in 1 in 257 individuals in the general population. In the meta-analysis, multifactorially adjusted hazard ratios (95% confidence intervals) for ϵ44 and ϵ22 versus ϵ33 were 1.15 (1.04–1.26) and 1.02 (0.83–1.24) for ischemic cerebrovascular disease (ICVD), 1.11 (1.04–1.19) and 0.94 (0.83–1.08) for ischemic heart disease (IHD) and 1.03 (0.89–1.17) and 1.49 (1.20–1.87) for peripheral arterial disease (PAD). A multifactorially and ϵ2/ϵ3/ϵ4 adjusted weighted allele score on the continuous scale including all common and rare structural variants showed that for individuals with genetically predicted high plasma apoE and remnant cholesterol the risk for PAD was increased. ConclusionsAPOE variants with high apoE, triglycerides, and remnant cholesterol are associated with PAD, whereas common APOE variants with high LDL cholesterol, triglycerides and remnant cholesterol are associated with IHD. APOE variants with low apoE are associated with increased risk of ICVD. These findings highlight that both rare and common structural variations in APOE play a role in vascular disease.

The risk of ischemic cerebrovascular disease associated with benzbromarone use in gout people: A retrospective cohort study in Taiwan.

Epidemiological studies have shown that people having hyperuricemia are at increased risk of ischemic cerebrovascular disease. This research aimed to study the relation of ischemic cerebrovascular disease with benzbromarone use among persons with gout-related disorders. This was a retrospective cohort design utilizing a 2003 to 2015 national health insurance database in Taiwan. Subjects aged 20 to 99 years who already had suffered from gout-related disorders were included as eligible subjects. Eligible persons who had the benzbromarone prescription alone were selected into the benzbromarone group. Sex-matched and age-matched eligible persons who never used any urate-lowering agents were selected into the control group. An index date was set as a date of benzbromarone being prescribed. The end-point was defined as ischemic cerebrovascular disease being newly diagnosed. A hazard ratio was applied to measure the association strength between benzbromarone use and ischemic cerebrovascular disease. Totally, there were 13,398 persons in the benzbromarone group and 13,398 persons in the control group. The incidence rate of ischemic cerebrovascular disease seemed to be modestly higher in the benzbromarone group than the control group, but it did not achieve statistical significance (0.78 vs 0.75 every 100 person-years, incidence rate ratio = 1.05, 95% confidence interval = 0.94-1.16). A crude hazard ratio of ischemic cerebrovascular disease showed 1.05 in the benzbromarone group (95% confidence interval = 0.94-1.17, P = .373) comparing with the control group. No significant association can be detected between benzbromarone use and the probability of ischemic cerebrovascular disease among persons with gout-related disorders. We think that reduction of the serum uric acid by use of benzbromarone could not be related to the probability of ischemic cerebrovascular disease. Further research is suggested to clarify this issue.

Research on risk factors of ischemic cerebrovascular disease in postmenopausal women based on the social-ecological model

ObjectiveBased on the social-ecological model, this study aimed to comprehensively explore factors affecting the risk of ischemic cerebrovascular disease (ICVD) in postmenopausal women to provide theoretical bases for further prevention and intervention for postmenopausal women.MethodsPostmenopausal women who underwent medical examinations in one health-checkup agency in Tianjin from May 2015 to October 2015 were enrolled in this study. The ICVD 10-year Risk Assesment Form developed by the research team of the National "Tenth Five-Year Plan" research project was used to assess the factors affecting the risk of ICVD. Based on the social-ecological model, multiple types of scales, including physical activities, depression, Type D personality, social supports, and environment score, were used to comprehensively explore the factors associated with ICVD in postmenopausal women.Results300 valid questionnaires were obtained, with an effective rate of 92.0%. The subjects aged 44–74 years, with the average age of 62.06 ± 7.09 years. Among them, 58.67% of the subjects only obtained high-school diploma, 32.67% obtained college or university diploma, 90.33% were retirees, 95.33% were married, 92.33% experienced the natural menopause, 93.33% lived in urban or suburban areas, and 1.00% had a history of breast cancer. Multivariate logistic regression analysis suggested that monthly income (¥), parity, exposure to second-hand or third-hand smoke, easy access to healthy food, physical activities, depression, Type D personality, social support and environmental factors were associated with the risk of ICVD in postmenopausal women (P < 0.05). Among them, easy access to healthy food (OR = 0.242), social support (OR = 0.861) and environmental factors (OR = 0.866) were protective factors from ICVD. OR < 1 indicates that the exposure factor is negatively correlated with the disease, and the exposure factor has a protective effect on preventing the occurrence of the disease. Parity (OR = 3.795), exposure to second-hand or third-hand smoke (OR = 2.886), depression (OR = 1.193), and Type D personality (OR = 1.148) were risk factors of ICVD. OR > 1 means that the exposure factor is positively correlated with the disease, and the exposure factor increases the risk of disease occurrence.ConclusionsFor postmenopausal women, in the future, in addition to prevention and management of the conventional risks, the conditions of their mentality and social support should be paid attention to, at the same time, and if they can, try to choose a good community environment to live in, which could better reduce the incidence and mortality of ICVD in postmenopausal women.

Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta-Analysis.

Migraine, especially migraine with aura (MA), has been linked to increased risk for ischemic cerebrovascular disease. The possible role of elevated serum homocysteine (Hcy, a cause of thrombophilia) in migraine has been demonstrated by several studies. The present study aims to review and meta-analyze data from studies investigating the difference of serum Hcy and Hcy lowering vitamins between migraine patients and healthy controls (HC), as well as between patients with MA and migraine without aura (MO). Literature search involved MEDLINE, Embase, CENTRAL, Google Scholar, and trial registries. The Newcastle-Ottawa Scale was used to evaluate the quality of the retrieved studies. Standardized mean differences (SMDs) and 95% confidence intervals (95%CIs) were calculated. Funnel-plots were utilized for the evaluation of publication bias. Overall, 29 (28 case-control and 1 cross-sectional) studies were retrieved. Meta-analysis was indicative of higher Hcy concentration in migraine patients vs HC overall [adults and children: 16 studies, I2 =81%, SMD=0.41, 95%CI=(0.20, 0.61)]. Hcy was consistently elevated in adults with migraine [adults: 12 studies, I2 =76%, SMD=0.35, 95%CI=(0.15, 0.54); children: 1 study, SMD=0.37, 95%CI=(-0.05, 0.79)]. Subgroup analyses reproduced the results for both adults with MA [7 studies, I2 =83%, SMD=0.37, 95%CI=(0.03, 0.71)] and MO [5 studies, I2 =84%, SMD=0.46, 95%CI=(0.03, 0.89)]. Figures for serum folate were lower in the overall comparison of migraine patients with HC [adults and children: 11 studies, I2 =87%, SMD=-0.36, 95%CI=(-0.68, -0.05); adults: 8 studies, I2 =6%, SMD=-0.11, 95%CI=(-0.22, 0.01); children: 1 study, SMD=-0.71, 95%CI=(-1.14, -0.29); MA adults: 4 studies, I2 =44%, SMD=-0.16, 95%CI=(-0.35, 0.04); MO adults: 4 studies, I2 =47%, SMD=-0.17, 95%CI=(-0.44, 0.10)]. Serum vitamin B12 levels were not different between migraine patients and HC [adults and children: 11 studies, I2 =88%, SMD=-0.24, 95%CI=(-0.57, 0.09); adults: 8 studies, I2 =57%, SMD=-0.10, 95%CI=(-0.28, 0.08); children: 1 study, SMD=0.29, 95%CI=(-0.13, 0.71); MA adults: 4 studies, I2 =63%, SMD=-0.14, 95%CI=(-0.48, 0.20); MO adults: 4 studies, I2 =59%, SMD=-0.15, 95%CI=(-0.45, 0.15)]. Serum Hcy was lower in MO than MA [adults and children: 10 studies, I2 =39%, SMD=0.30, 95%CI=(0.14, 0.46), adults: 6 studies, I2 =29%, SMD=0.21, 95%CI=(0.09, 0.36), children: 1 study, SMD=0.51, 95%CI=(0.22, 0.80)]. Serum folate and vitamin B12 did not differ between MA and MO. Our results suggest that there is a possible link between migraine, mainly MA, and elevated serum Hcy.

Radiotherapy can increase the risk of ischemic cerebrovascular disease in head and neck cancer patients: A Korean population-based cohort study

Background and purposeSeveral reports suggested that radiotherapy (RT) was related to an increased risk of cerebrovascular disease (CVD) in head and neck cancer (HNC) patients, but other risk factors of CVD were not properly considered in estimating the risk of RT. The purpose of this study is to analyze the effect of RT on the risk of CVD in HNC patients. Materials and methodsThe Korean Central Cancer Registry data and Korean National Health Insurance Service data were used. A total of 5570 patients with newly diagnosed HNC between the years 2003–2005 was included in our study cohort. We analyzed the effect of treatment modality and other socioeconomic variables on ischemic CVD incidence using the Cox proportional hazard regression model both in the entire cohort (n = 5570) and in the propensity score matching (PSM) cohort (n = 3310). ResultsRT increased the CVD risk by 40.8% (aHR: 1.408, p = 0.006) in the entire cohort and by 44.3% (aHR: 1.443, p = 0.047) in the PSM cohort, respectively. ConclusionThe risk of ischemic CVD increased by RT after adjusting for other socioeconomic and clinical risk factors. Regular follow up and appropriate screening for CVD are required for HNC patients who received RT, and focus should be on advanced-age patients with a low socioeconomic status and known clinical risk factors of CVD.

Clinical analysis of prognosis at 18 months after attack in patients with mild ischemic stroke

Objective To investigate activities of daily living, depression, anxiety, fatigue and cognitive impairments at 18 months after attack in patients with mild ischemic stroke. Methods In this cross-sectional study, 86 patients with acute ischemic stroke were hospitalized in the Neurology Department of Shanghai Ruijin Hospital from January 2013 to April 2013.Among them, 58 cases who were eventually interviewed and selected, were divided into mild stroke group[NIHSS ≤3, n=37]and medium-severe stroke group[NIHSS>3, n=21]according to the admission score of the National Institutes of Health Stroke Scale(NIHSS). Follow-up was done at 1.5 years after stroke to assess NIHSS, modified Rankin scale(mRS), Stroke Impact Scale(SIS), Hamilton depression scale(HAMD), Hamilton Anxiety Scale(HAMA), Modified Fatigue Impact Scale(MFIS)and Montreal Cognitive Assessment(MoCA). Meanwhile, 35 patients with high risk of ischemic cerebrovascular disease were evaluated by HAMD, HAMA, MFIS and MoCA. Results Patients in the mild stroke group showed significantly better prognoses identified by the assessed scores of NIHSS[median(M)=0, interquartile range(IQR)=0, z=-3.879], mRS[M=1, IQR=1, z=-2.381], SIS-total score[697.36 ± 85.66, t=2.351]and SIS-Stroke recovery score(84.15±11.94, t=3.696), as well as the SIS partial items, including strength(79.49±15.88, t=2.099), instrumental activities of daily living[M=97.5, IQR=10, z=-2.858], locomotivity[M=97.2, IQR=0, z=-3.083], hand function[M=100, IQR=20, z=-2.259]and social participation[M=90.6, IQR=28, z=-2.582], at 1.5-year follow-up.These parameters were markedly different from those in the medium-severe group(all P<0.05). Additionally, the high-risk group for cerebrovascular disorder showed no case with depression, anxiety and fatigue, but showed 10 cases(28.6%)with cognitive impairments.Furthermore, the mild stroke group versus the medium-severe stroke group showed a similar incidences of depression(16.2% vs.38.1%, P=0.061), anxiety(10.8% vs.19.0%, P=0.443), fatigue(35.1% vs.38.1%, P=0.822)and cognitive impairments(59.5% vs.66.7%, P=0.587). Conclusions The motor function-evaluated activities of daily living are little affected in mild ischemic stroke at 18months follow-up, but rates of depression, anxiety, fatigue and cognitive decline are not uncommon. Key words: Mild Stroke; Activities of Daily Living; Depression; Anxiety; Fatigue; Cognitive Impairments

Dipeptidyl Peptidase-4 Inhibitors Use and Relative Risk of Ischemic Cerebrovascular Disease in Type 2 Diabetic Patients in a Case-Control Study.

Background and Objectives: Limited research focuses on the risk of ischemic cerebrovascular disease associated with use of dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) in patients with type 2 diabetes mellitus in Taiwan. This study aimed to investigate the association between DPP-4 inhibitors use and the first episode of ischemic cerebrovascular disease.Methods: We designed a case-control study using the database of the Taiwan National Health Insurance Program. There were 1999 type 2 diabetic subjects aged 20–84 years with the first episode of ischemic cerebrovascular disease from 2000 to 2013 as the cases, and 7996 sex- and age-matched, randomly selected type 2 diabetic subjects aged 20–84 years without any type of cerebrovascular diseases as the matched controls. We estimated the odds ratio (OR) and 95% confidence interval (CI) of ischemic cerebrovascular disease associated with cumulative duration of DPP-4 inhibitors use by the multivariable logistic regression model.Results: After adjustment for confounding variables, the adjusted OR of ischemic cerebrovascular disease was 0.96 (95% CI 0.95, 0.97) in subjects with ever use of DPP-4 inhibitors as increase in use duration for every 1 month, compared with never use. The sub-analysis disclosed that the adjusted ORs of ischemic cerebrovascular disease were 1.57 (95% CI 1.36, 1.80) for subjects with cumulative duration of DPP-4 inhibitors use <1 year, and 0.70 (95% CI 0.57, 0.87) for subjects with cumulative duration of DPP-4 inhibitors use ≥1 year, compared with never use.Conclusion: Our findings suggest that DPP-4 inhibitors use correlates with relative risk reduction of the first episode of ischemic cerebrovascular disease in type 2 diabetic patients in a duration-dependent response. The beneficial effect will be marked when DPP-4 inhibitors use is ≥1 year.

The association between tinnitus and the risk of ischemic cerebrovascular disease in young and middle-aged patients: A secondary case-control analysis of a nationwide, population-based health claims database.

BackgroundTinnitus and ischemic cerebrovascular disease (ICVD) may share common pathophysiologic mechanisms. Nevertheless, no studies have investigated whether tinnitus is associated with a higher risk of ICVD. The aim of this study was to evaluate the risk of ICVD among young and middle-aged patients with tinnitus.MethodsUsing the Taiwan’s National Health Insurance Research Database, we identified 3,474 patients 20–45 years old with incident ICVD diagnosed between January 1, 2000 and December 31, 2010 and 17,370 controls, frequency matched on age interval, sex, and year of the index date. Risk of ICVD associated with tinnitus was assessed using multiple logistic regression analyses.ResultsTinnitus was significantly associated with a higher risk of incident ICVD among young and middle-aged patients (adjusted odds ratio [OR] 1.66, 95% confidence interval [CI] 1.34–2.04), adjusting for sex, age, and comorbidities. In addition, sex-stratified analysis showed that the associations were significant in both male (adjusted OR 1.55, 95% CI 1.16–2.07) and female patients (adjusted OR 1.77, 95% CI 1.30–2.41). Furthermore, tinnitus was significantly associated with a higher risk of ICVD in the 20.0–29.9 years (adjusted OR 4.11, 95% CI 1.98–8.52) and 30.0–39.9 years (adjusted OR 2.19, 95% CI 1.57–3.05) age groups, but not in the 40.0–45.0 years age group.ConclusionsTinnitus could be a novel risk factor or clinical indicator for young ischemic stroke, and further investigations are warranted.

Tamoxifen Use Correlates with Increased Risk of the First Episode of Ischemic Cerebrovascular Disease in Older Women with Breast Cancer: A Case-Control Study in Taiwan.

Background and Objectives: There are inconsistent results about the association between ischemic cerebrovascular disease and tamoxifen use in women with breast cancer. The study aimed to evaluate the association between the risk of ischemic cerebrovascular disease and tamoxifen use in older women with breast cancer in Taiwan.Methods: We designed a retrospective, nationwide, case-control study using the database of the Taiwan National Health Insurance Program. A total of 800 female subjects with breast cancer aged ≥65 years with the first episode of ischemic cerebrovascular disease from 2000 to 2011 were identified as the cases. Additionally, 2,876 female subjects with breast cancer aged ≥65 years without any type of cerebrovascular diseases were selected as the control subjects. The cases and the control subjects were matched with age and comorbidities. Ever use of tamoxifen was defined as a subject who had at least a prescription for tamoxifen before the index date. Never use of tamoxifen was defined as a subject who never had a prescription for tamoxifen before the index date. We used the multivariable logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) for ischemic cerebrovascular disease associated with tamoxifen use.Results: After adjusting for confounding variables, the adjusted OR of ischemic cerebrovascular disease was 2.5 for subjects with ever use of tamoxifen (95% CI 2.10, 2.97), compared with never use of tamoxifen. In addition, the adjusted OR of ischemic cerebrovascular disease was 1.15 (95% CI 1.10, 1.21) in subjects with ever use of tamoxifen as increase in use duration per 1 year. The adjusted OR of ischemic cerebrovascular disease was 2.54 (95% CI 2.03, 3.17) in subjects with ever use of tamoxifen as increase in dosage per 1 mg.Conclusions: Tamoxifen use is significantly associated with 2.5-fold increased odds of ischemic cerebrovascular disease among older women with breast cancer in Taiwan. There are duration-dependent and dose-dependent effects of tamoxifen use on the risk of ischemic cerebrovascular disease.

Ankle-brachial index and brachial-ankle pulse wave velocity are risk factors for ischemic stroke in patients with Type 2 diabetes.

The incidence of ischemic stroke in patients with diabetes is increasing. While brachial-ankle pulse wave velocity (BaPWV) and ankle-brachial index (ABI) are known to be associated with ischemic cardiovascular and cerebrovascular diseases, whether these measures predict the risk of ischemic cerebrovascular disease in diabetic patients remains unclear. 117 patients with type 2 diabetes were enrolled in this study. According to the results of head magnetic resonance imaging, the patients were divided into a diabetes-only group (n = 55) and a diabetes and ischemic stroke group (n = 62). We then performed ABI and BaPWV examinations for all patients. Compared with the diabetes-only group, we found decreased ABI and increased BaPWV in the diabetes and ischemic stroke group. Multivariate logistic regression analyses revealed that BaPWV and ABI were risk factors for ischemic stroke in patients with type 2 diabetes. Our findings indicate that decreased ABI and increased BaPWV are objective indicators of increased risk of ischemic stroke in patients with type 2 diabetes.

NADPH oxidase p22phox C242T polymorphism and ischemic cerebrovascular disease: an updated meta-analysis.

BackgroundA growing number of studies on the associations between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox C242T polymorphism and risk of ischemic cerebrovascular disease have recently been published, but the results remain inconsistent.Material/MethodsWe performed an updated meta-analysis to evaluate this association. Eight case-control studies were included, involving 2045 cases and 2102 controls. Heterogeneity was assessed by the Q test and the I2 statistic. Begg and Egger’s tests were conducted to evaluate publication bias. Odds ratio (OR) was tested to identify the associations.ResultsSignificant associations between p22phox gene C242T polymorphism and ischemic cerebrovascular disease (ICVD) risk were observed in the allelic genetic model (OR=1.33, 95% confidence interval [CI] 1.00–1.77, p=0.048). No statistical significant association was found in the dominant model (OR=0.74, 95% CI 0.54–1.02, p=0.064) and recessive model (OR=1.40, 95% CI 0.89–2.19, p=0.146). Subgroup analysis showed an association in European populations for recessive model (OR=2.13, 95% CI 1.06–4.26, p=0.034) and no significant evidence of association in Asian populations was found (dominant model: OR=0.64, 95% CI 0.41–1.00, p=0.05; recessive model: OR=0.98, 95% CI 0.53–1.81, p=0.948; allelic model: OR=1.51, 95% CI 0.98–2.32, p=0.061).Conclusionsp22phox gene C242T polymorphism was associated with ICVD risk in the allelic genetic model, as well as in European populations for recessive model. No evidence showed association between p22phox gene C242T polymorphism and ICVD risk in the dominant model and recessive model. Furthermore, no association existed in Asian populations for any of the 3 genetic models and European populations in the dominant model and allelic model.

Clinical analysis of the cerebral DSA in 99 patients with ischemic cerebrovascular disease

Objective To explore the distribution of vascular lesions in the cerebral digital subtraction angi-ography（ DSA） and associated diseases in patients with ischemic cerebrovascular disease（ ICVD） ,and complications, as well as the value of DSA in ICVD.Methods The DSA data of 99 ICVD cases were analyzed retrospectively, patients treated by ischemia type were divided into the cerebral infarction（CI） and transient ischemic attack（TIA） group.All patients were examined by 3D-TOF and neck vascular ultrasound screening,the final diagnosis by DSA. While observing the perioperative complications and associated diseases.Results 99 patients with ICVD,88 cases of the presence of vascular lesions diagnosed by DSA.In 99 cases,there were 252 lesions,accounting for the top three for the internal carotid artery（ICA）,vertebral artery（VA） and the middle cerebral artery（MCA）.While there were 121 bifurcation lesions,accounting for the top three for ICA,VA,and the external carotid artery（ECA）.TIA in patients with concomitant diseases accounted for the top three for hypertension（HTN）,type 2 diabetes mellitus（T2DM） and hyperlipidemia and renal insufficiency;Patients with CI associated diseases accounted for the top three for HTN, T2DM and hyperlipidemia.There were 10 cases of patients with DSA complications,most of the vasovagal reflex in five cases;serious for TIA and CI in 1 case （ not cause any neurological deficits at discharge ） .Conclusion Carotid vascular disease plays an important role in the occurrence of ICVD, especially in the blood vessels of bifurcation lesion.Within ICVD risk factors in HTN in the majority, followed by T2DM, hyperlipidemia.DSA surgery rarely serious complications,blood vessels can provide more comprehensive information,and provide the basis for further development of ICVD prevention and treatment programs,this checking method is safe and reliable. Key words: Angiography; Digital Subtraction Brain Ischemia Brain Infarction Ischemic Attack; Transient

Association Between VKORC1 Gene Polymorphisms and Ischemic Cerebrovascular Disease in Chinese Han Population

The vitamin K epoxide reductase subunit 1 gene (VKORC1) plays a key role in vitamin K recycling, and there is a close association between VKORC1 gene single-nucleotide polymorphisms (SNPs) and the required dose of warfarin, an anticoagulant. However, the association between VKORC1 SNPs and ischemic cerebrovascular disease (ICVD) has not been defined. This case-control study involved 370 patients with ICVD and 408 healthy individuals (controls) from Chinese Han population. Two VKORC1 gene SNPs (1639A/G and 1173T/C) were genotyped by PCR-RFLP method. The G allele frequencies of the 1639A/G locus and C allele frequencies of the 1173T/C locus were higher in the ICVD group than in the control group (p = 0.014 and p = 0.008, respectively). Haplotype analysis showed that 1639G-1173C was associated with an increased risk of ICVD (odds ratio (OR) = 1.163, 95% confidence interval (CI) = 1.137~2.288), while 1639A-1173T was associated with decreased risk of ICVD (OR = 0.620, 95% CI = 0.437~0.880). Our findings suggested that individuals carrying the 1639G or 1173C allele might be at increased risk for ICVD. Furthermore, the 1639G-1173C haplotype was a risk factor for ICVD, and 1639A-1173T was a protective factor in Chinese Han population.

Two polymorphisms in the Fractalkine receptor CX3CR1 gene influence the development of atherosclerosis: a meta-analysis.

Background. The associations between the Fractalkine receptor (CX3CR1) gene T280M (rs3732378) and V249I (rs3732379) polymorphisms and atherosclerosis (AS) risk are conflicting. The aim of this meta-analysis was undertaken to assess their associations. Methods. PubMed, Embase, Web of Science, Medline, Cochrane database, and CNKI were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0. Results. Twenty-five articles involving 49 studies were included in the final meta-analysis. The analysis showed that the 280M allele carriers of the CX3CR1 T280M polymorphism decreased the risk of AS and coronary artery disease (CAD) in the heterozygous state but increased the risk of ischemic cerebrovascular disease (ICVD) in the homozygote state. The 249I allele carriers of the CX3CR1 V249I polymorphism decreased the risk of AS and CAD in the heterozygous state. The V249I-T280M combined genotype VITM and IITM also decreased the risk of AS. Conclusions. The present meta-analysis suggests that the CX3CR1 T280M and V249I polymorphisms are associated with the susceptibility to AS. However, the results should be interpreted with caution because of the high heterogeneity in the meta-analysis.

Toll-like receptor 4 gene Asp299Gly polymorphism in ischemic cerebrovascular disease: a meta-analysis

Epidemiological studies have evaluated the association between Toll-like receptor 4 (TLR4) gene Asp299Gly (rs4986790) polymorphism and the risk of ischemic cerebrovascular disease, but the results are inconsistent. In an effort to clarify earlier inconclusive results, a meta-analysis was performed. We searched the PubMed, Web of Science, Embase, Cochrane database, Clinicaltrials.gov, Current Controlled Trials, CNKI, CBMdisc, Chinese Clinical Trial Registry and Google Scholar until up to 20 July 2013. Additionally, hand searching of the references of identified articles was performed. Original observational studies investigating the association between TLR4 gene Asp299Gly polymorphism and ischemic cerebrovascular disease risk were included. All statistical analyses were performed using Stata 11.0. The search strategy identified 1038 potentially relevant articles, seven of which were included in the final meta-analysis, covering a total of 1767 cases and 2785 controls. Overall, no significant association was found between TLR4 gene Asp299Gly polymorphism and ischemic cerebrovascular disease risk (for G allele versus A allele: OR = 0.95, 95% CI = 0.75–1.21, p = 0.69; for G/G+A/G versus A/A: OR = 0.96, 95% CI = 0.75–1.22, p = 0.73). In addition, the similar results were obtained in the sensitivity analysis based on studies with the high quality. In summary, the present meta-analysis indicates that TLR4 gene Asp299Gly polymorphism is not associated with increased ischemic cerebrovascular disease risk.

Ischemic stroke susceptibility gene in a Northern Han Chinese population.

Interleukin-18 gene promoter polymorphisms are potential risk factors for ischemic cerebrovascular disease, and the –607C allele may increase ischemic stroke risk in the Han Chinese population. In the present study, we recruited 291 patients with ischemic cerebrovascular disease from the Affiliated Hospital of Qingdao University Medical College, China, and 226 healthy controls. Both patients and controls were from the Han population in northern China. Immunoresonance scattering assays detected increased serum amyloid A protein, C-reactive protein, and interleukin-18 levels in ischemic cerebrovascular disease patients compared with healthy controls. Analysis of the –607C/A (rs1946518) polymorphism in the interleukin-18 gene promoter showed ischemic cerebrovascular disease patients exhibited increased frequencies of the CC genotype and C alleles than healthy controls. Genotype and allele frequencies of the interleukin-18 –137G/C (rs187238) polymorphism and the –13T/C (rs11024595) polymorphism in the 5’-flanking region of serum amyloid A, showed no significant difference between the two groups. Multivariate logistic regression analysis on the interleukin-18 promoter A/C genetic locus, for correction of age, gender, history of smoking, hypertension, diabetes mellitus, hypercholesteremia, and an ischemic stroke family history, showed ischemic cerebrovascular disease risk in individuals without the A allele (C homozygotes) was 2.2-fold greater than in A allele carriers. Overall, our findings suggest that the –13T/C (rs11024595) polymorphism in the 5’-flanking region of serum amyloid A has no correlation with ischemic cerebrovascular disease, but the C allele of the –607C/A (rs1946518) polymorphism in the interleukin-18 promoter is a high-risk factor for ischemic cerebrovascular disease in the Han population of northern China. In addition, the A allele is likely a protective gene for ischemic cerebrovascular disease.

Association between NADPH Oxidase p22phox C242T Polymorphism and Ischemic Cerebrovascular Disease: A Meta-Analysis

BackgroundEpidemiological studies have evaluated the association between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox C242T polymorphism and risk of ischemic cerebrovascular disease (ICVD), but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies.Methodology/Principal FindingsSystematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.7) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 6 studies including 1,948 cases and 2,357 controls were combined showing no statistical evidence of association between NADPH oxidase p22phox C242T polymorphism and overall ICVD (allelic model: OR = 1.08, 95%CI = 0.93–1.26; additive model: OR = 1.33, 95%CI = 0.81–2.17; dominant model: OR = 1.00, 95%CI = 0.86–1.15; recessive model: OR = 1.06, 95%CI = 0.77–1.45). Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR = 1.12, 95%CI = 0.88–1.41; additive model: OR = 1.36, 95%CI = 0.60–3.09; dominant model: OR = 1.25, 95%CI = 0.74–2.11; recessive model: OR = 2.17, 95%CI = 1.11–4.23). No statistical evidence of significant association was observed for small-vessel occlusive stroke, as well as Asian subgroup and Caucasian subgroup. Statistical powers on the combined sample size (total and subgroup) were all lower than 80%.Conclusions/SignificanceThis meta-analysis indicates that NADPH oxidase p22phox C242T polymorphism is more associated with large-artery atherosclerotic stroke than small-vessel occlusive stroke. However, this conclusion should be interpreted with caution due to the small sample size. Larger sample-size studies with homogeneous ICVD patients and well-matched controls are required.

Genetic relationship between serum pregnancy-associated plasma protein-A gene polymorphism and ischemic cerebrovascular disease in a Northern Han Chinese population.

The present study recruited 193 patients with ischemic cerebrovascular disease from Inpatient and Outpatient Departments at the Affiliated Hospital of Qingdao University Medical College, China from August 2008 to May 2010, as well as 120 healthy volunteers from the Medical Examination Center at the Affiliated Hospital of Qingdao University Medical College, China, who served as controls for this study. Patients and control subjects were from the Han population in northern China. Enzyme- linked immunosorbent assay analysis revealed increased levels of serum pregnancy-associated plasma protein-A (PAPP-A) in ischemic cerebrovascular disease patients compared with healthy controls. In addition, the patients exhibited greater frequency of genotype CC and C alleles in a missense A/C (Tyr/Ser) polymorphism (dbSNP: rs7020782) of exon 14 in the PAPP-A gene. Multiple-factor logistic regression analysis on correction of age, gender, history of smoking, hypertension, diabetes mellitus, hypercholesteremia, and ischemic stroke family history showed that the risk for ischemic cerebrovascular disease in the population without the A allele at the A/C genetic locus in exon 14 of the PAPP-A was 2-folds greater than the population expressing the A allele. These experimental findings suggested that ischemic cerebrovascular disease correlated with the C allele in exon 14 of PAPP-A. In addition, the A allele is likely a protective gene; individuals carrying the A allele were less prone to ischemic cerebrovascular disease compared with individuals without the A allele.

Heterozygosity for R1141X in ABCC6 and Risk of Ischemic Vascular Disease

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease caused by loss-of-function mutations in ABCC6 and characterized by elastic calcification leading to dermal, ocular, and ischemic vascular disease. We tested the hypothesis that heterozygosity for R1141X, the most frequent PXE-causing mutation in Caucasians, associated with risk of ischemic vascular disease, as previous studies suggested 4- to 11-fold risk of ischemic heart disease (IHD) in heterozygotes. We studied 10,276 persons from the general population, including 1985 with IHD and 989 with ischemic cerebrovascular disease (ICVD). We examined 45,603 individuals from a cross-sectional general population study, of whom 3738 had IHD and 2335 had ICVD. Finally, we compared 4851 patients with IHD and 625 patients with ICVD with, respectively, 4851 and 625 matched control subjects. We genotyped participants in all studies for ABCC6 R1141X. The frequency of R1141X was 0.6% in all populations studied. ABCC6 R1141X genotype was not associated with an increased risk of IHD, myocardial infarction, ICVD, or ischemic stroke. Furthermore, R1141X genotype did not interact with age on risk of the largest end point, IHD. Finally, R1141X genotype did not associate with variation in plasma levels of high-sensitivity C-reactive protein, fibrinogen, blood pressure, or lipid and lipoproteins in the general population. In 4 studies including 66 831 participants and 13 642 cases with ischemic vascular events, heterozygosity for ABCC6 R1141X did not associate with risk of IHD, myocardial infarction, ICVD, or ischemic stroke.

Prevalence, Awareness, and Control of Hypertension among Diabetic Koreans

Prevalence, Awareness, and Control of Hypertension among Diabetic Koreans