Correlation of intracranial atherosclerosis with carotid stenosis in ischemic stroke patients

Introduction:

Carotid stenosis is a major risk factor for ischemic stroke. However, the effect of carotid stenosis on the site of stroke is still under investigation.

Aims:

This study aimed to elucidate how the presence of carotid stenosis influenced the pattern of stroke and also how it interacted with other risk factors for stroke.

Materials and Methods:

Thirty-eight patients with ischemic stroke were included in this study and were investigated with carotid artery Doppler and magnetic resonance angiography for carotid stenosis and intracranial stenosis in the circle of Willis, respectively. Other known risk factors of stroke were also studied in and compared between the subgroups with and without carotid stenosis.

Results:

In patients without carotid stenosis, anterior cerebral artery was the commonest site of stenosis. In patients with carotid stenosis, middle cerebral artery was the commonest site of stenosis. Overall, middle cerebral artery was the commonest territory of stroke. Patients with hypertension, diabetes and history of smoking had preferential stenosis of the anterior cerebral artery.     

Association between procalcitonin levels and carotid atherosclerosis in acute ischemic stroke patients

Background and purposes: Procalcitonin has been suggested as a new risk factor in atherosclerotic disease. However, whether procalcitonin levels are associated with the risk of carotid atherosclerosis remains unclear. This study aimed to investigate the relationship between procalcitonin levels and carotid atherosclerosis among patients with first-ever acute ischemic stroke.

Methods: Two hundred and thirty consecutive patients were prospectively enrolled in this study. Serum procalcitonin concentrations were measured at admission for all patients. We also performed ultrasound examination to detect the mean carotid intima-media thickness, presence of carotid-wall thickening, plaque and significant stenosis. Multiple regression analysis was used to estimate the association between procalcitonin levels and carotid atherosclerosis.

Results: The median procalcitonin concentration was 0.051 µg/L (interquartile range, 0.036–0.080 µg/L). Of the 230 patients, 102 (44.3%) had carotid-wall thickening, 113 (49.1%) had plaque and 77 (33.5%) had significant stenosis. After adjusting for all potential confounders by multiple logistic regression analysis, patients with procalcitonin levels in the fourth quartile, compared with the first quartile, were more likely to have carotid-wall thickening [odds ratio 2.288, 95% confidence intervals 1.042–5.021, P = 0.039] and significant stenosis [odds ratio 3.871, 95% confidence intervals 1.690–8.867, P = 0.003]. Furthermore, the linear regression analysis revealed a significant positive correlation between procalcitonin levels and the mean carotid intima-media thickness (β = 0.162, P = 0.012).

Conclusions: Higher procalcitonin concentrations at admission might be associated with carotid-wall thickening and significant stenosis in ischemic stroke patients.     

基质金属蛋白酶-9/C1562T基因多态性与缺血性脑卒中的关系

目的探讨基质金属蛋白酶-9(MMP-9)启动子基因C1562T多态性与缺血性脑卒中(IS)的关系。方法采用聚合酶链式反应-限制性片段长度多态性分析(PCR-RFLP)法检测114例IS患者(IS组)及80名正常对照者(NC组)MMP-9/C1562T基因型和等位基因频率,分析其与IS发病的相关性。结果IS组与NC组间MMP-9/C1562T基因型及等位基因频率差异无统计学意义(P>0.05)。结论MMP-9/C1562T多态性可能与IS的发病无关。     

染色体9P21多态性与大动脉粥样硬化型脑梗死的相关性

目的探讨染色体9p21的rs7049105、rs647188、rs1333035位点与湖南长沙汉族人群大动脉粥样硬化型脑梗死(large-artery atherosclerosis stroke,LAS)的相关性,并研究这3个位点在有头颈部动脉粥样硬化证据的人群中与LAS的相关性。方法收集湖南长沙汉族人群中229例LAS患者为病例组,同期门诊及体检中心"健康"人群中233例为对照组1,其中有动脉粥样硬化证据的对照150例(64.38%)纳入对照组2,无动脉粥样硬化证据的对照83例(35.62%)纳入对照组3。利用基质辅助激光解析飞行时间质谱(MALDI-TOF-MS)方法对样本进行基因分型检测。结果 rs647188位点在湖南长沙汉族人群中可能不存在多态性;病例组与对照组1间、病例组与对照组3间rs7049105和rs1333035位点及病例组与对照组2间rs7049105位点的多态性分布比较未发现统计学差异(P0.05)。病例组与对照组2间rs1333035位点的基因型频率分布比较发现有统计学差异(χ~2=6.502,P=0.039)。结论染色体9p21的rs10757274、rs7049105多态性与湖南长沙地区汉族人群LAS可能不相关,在湖南长沙汉族人群中rs647188位点可能不存在多态性,rs1333035位点多态性可能与启动斑块破裂及血栓栓塞相关。     

阿托伐他汀在老年缺血性脑卒中患者治疗中氧化应激和脂质过氧化的影响

目的:探讨阿托伐他汀治疗老年缺血性脑卒中(CIS)对患者氧化应激及脂质过氧化的影响.方法:86例老年CIS患者随机分为观察组(n=43)与对照组(n=43),对照组给予常规治疗,观察组在与对照组相同治疗的基础上加用阿托伐他汀治疗,对比两组患者的临床疗效及8-异列腺素F2α(8-isoPGF2α)、氧化低密度脂蛋白(ox-LDL)水平.结果:观察组有效率为98％(42/43),显著高于对照组的74％(32/43)(P＜0.01);两组治疗后血清总胆固醇(TC)、血清甘油三酯(TG)水平均显著低于治疗前(P＜0.05),且治疗后观察组TC、TG水平显著低于对照组(P＜0.05),余观察指标比较差异均无显著意义(P＞0.05);两组患者治疗前8-iso-PGF2α、ox-LDL比较差异均无统计学意义(P＞0.05),治疗后观察组8-iso-PGF2α显著降低,对照组则显著增高(P＜0.01);两组治疗前ox-LDL均显著增高,且治疗后观察组显著低于对照组(P＜0.01).结论:阿托伐他汀对老年CIS患者具有确切疗效,且能够有效缓解或减轻氧化应激与脂质过氧化程度,有利于患者神经功能的恢复.     

Lp-PLA2 as a risk factor of early neurological deterioration in acute ischemic stroke with TOAST type of large arterial atherosclerosis

Introduction: Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a well-known risk factor of atherosclerotic vascular diseases. Nevertheless, its role in the acute phase of ischemic stroke is still unclear. The aim of this study is to identify the relationship between Lp-PLA₂ levels and early neurological deterioration (END) in acute ischemic stroke patients with Trial of Org 10 172 in Acute Stroke Treatment (TOAST) subtype of large arterial atherosclerosis (LAA).

Methods: We enrolled Chinese patients with first ever acute ischemic stroke admitted to Neurology Department of Shenzhen Second People’s Hospital within 48 h from onset of symptoms during January – November 2015. Demographic and laboratory information were collected while END was defined as an increase in the National Institute of Health Stroke Scale score by ≥ 1 point in motor power, or ≥ 2 points in the total score within 10 days after admission.

Results: Overall 181 patients were involved; END was diagnosed in 30 patients within 10 days after admission. The odds ratio for END increased with increasing levels of Lp-PLA₂ (intermediate level, OR = 1.96, 95%CI 1.02–4.27, p = 0.041; high level, OR = 2.99, 95%CI 1.26–5.73, p = 0.023).

Conclution: Intermediate and high level of Lp-PLA₂ was identified as independent predictor of END in multivariate analysis. Lp-PLA₂ could be valued as a risk factor of END in patients with acute ischemic stroke with TOAST subtype of LAA.     

Methylenehydrofolate reductase (C677T) polymorphism and large artery ischemic stroke subtypes

They‐They TP, Nadifi S, Rafai MA, Battas O, Slassi I. Methylenehydrofolate reductase (C677T) polymorphism and large artery ischemic stroke subtypes.
Acta Neurol Scand: 2011: 123: 105–110.
© 2010 John Wiley & Sons A/S. Background – The role for the methylenetetrahydrofolate reductase C677T gene variants in the risk of ischemic stroke is controversial. Method – This first case–control study including 91 cases affected by ischemic stroke and 182 controls matched for age, sex, and same area was conducted in Casablanca, Morocco. Allele and genotype frequency were characterized by using PCR followed by HinfI enzymatic digestion. Results – We found no statistic association of T allele carriers genetic factors with stroke; odds ratio, 1.1; 95% confidence interval (CI), 0.59–2.04, P = 0.303. The results shown significant association of T allele carriers genetic factors with atherothrombotic subtype stroke (n = 42); odds ratio, 2.1; 95% CI: 1.17–3.8; P = 0.012, and adjusted odds ratio of 6.5; 95% CI: 1.86–23.1, P = 0.003, for TT genotype variant compared with CC wild genotype. Conclusion – We suggested that MTHFR C677T variant may be a determinant of atherothrombotic event of ischemic stroke in Morocco.     

Impact of 5A/6A polymorphism of matrix metalloproteinase-3 on recurrent atherosclerotic ischemic stroke in Chinese

Little is known about the impact of the 5A/6A polymorphism of matrix metalloproteinase-3 (MMP-3) on recurrence of atherosclerotic ischemic stroke in Chinese. The aim of this study was to investigate the association of MMP-3 serum level and 5A/6A genetic polymorphism with the recurrence of atherosclerotic ischemic stroke in the Chinese Han population. We analyzed 106 large artery atherosclerosis (LAA) recurrent ischemic stroke patients and 545 LAA first onset ischemic stroke patients from January 2009 to June 2014. Serum MMP-3 concentrations were measured with an enzyme-linked immunosorbent assay. The genotypes of MMP-3 promoter polymorphism (?1171 5A/6A) were determined using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of MMP-3 5A/6A+5A/5A (32.08% vs. 21.47%, p = 0.02) genotype and 5A (16.98% vs. 11.01%, p = 0.01) allele in the recurrent group was significantly higher than those in the first onset group. After adjustment for vascular risk factors, multivariate logistic regression analysis suggested that the MMP-3 5A/6A+5A/5A genotype was an independent risk factor for LAA recurrent ischemic stroke (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.09–2.79, p = 0.021). No significant difference was observed for the MMP-3 serum concentrations between the recurrent group and the first onset group (22.23 ± 8.31 vs. 21.49 ± 7.89 ng/ul, t = 0.88, p = 0.38). The MMP-3 (?1171 5A/6A) polymorphism may contribute to LAA recurrent ischemic stroke susceptibility. Analysis of 5A/6A polymorphism in MMP-3 may identify patients at higher risk for LAA ischemic stroke recurrence, who may be selected for intensive preventive therapy.     

急性缺血性脑卒中患者D-二聚体NT-proBNP及脂蛋白(a)的检测意义

目的检测D-二聚体、NT-proBNP及脂蛋白(a)在急性缺血性脑卒中患者中的临床价值。方法选取240例急性缺血性脑卒中患者为试验组,以60例同期体检者为对照组。采用UniceLDxc800Synchorn全自动生化分析系统,于清晨空腹状态下取肘静脉血,3 000r/min离心10min,取血清,测定D-二聚体和脂蛋白(a)水平,酶联免疫吸附法检测血浆NT-proBNP水平。结果试验组轻度患者D-二聚体、脂蛋白(a)及NT-proBNP水平分别为(0.33±0.04)mg/L、(247.46±51.27)mg/L和(0.42±0.07)mg/L,中度分别为(049±0.06)mg/L、(308.73±59.36)mg/L和(0.96±0.12)mg/L,重度分别为(0.64±0.07)mg/L、(348.49±59.35)mg/L和(1.49±0.64)mg/L,差异均有统计学意义(P0.05)。试验组D-二聚体、脂蛋白(a)及NTproBNP水平分别为(0.58±0.06)mg/L、(327.47±56.76)mg/L和(1.28±0.52)mg/L,对照组分别为(0.19±0.03)mg/L、(185.63±31.28)mg/L和(0.06±0.02)mg/L,差异均有统计学意义(P0.05)。结论检测D-二聚体、脂蛋白(a)及NTproBNP水平有助于急性缺血性脑卒中患者的临床诊断及病情评估。     

超声造影定量参数联合同型半胱氨酸及超敏C-反应蛋白对缺血性脑卒中的预测价值

目的探讨超声造影峰值强度(TIC-P)、强度均值(TIC-M)、峰值(FC-P)、锐度(FC-S)、曲线下面积(FC-AUC)联合血清同型半胱氨酸(Hcy)及超敏C-反应蛋白(Hs-CRP)对缺血性脑卒中(ICS)的预测价值。方法选取儋州市人民医院行颈动脉超声检查发现颈动脉粥样硬化患者196例,根据其是否发生ICS,分为ICS组(n=91)和非ICS组(n=105)。记录各组的基线资料,并进行超声造影检查及Hcy及Hs-CRP水平检测。应用ROC曲线分析超声造影定量参数、Hcy及Hs-CRP预测ICS发生的价值。结果 ICS组颈动脉斑块超声造影定量参数TIC-P、TIC-M、FC-P、FC-S和FC-AUC值均明显高于非ICS组(P 0. 05)。ICS组Hcy及Hs-CRP水平均明显高于非ICS组(P 0. 01)。ROC曲线分析显示,三者联合预测ICS的AUC(95%CI)为0. 986 (0. 940～0. 998)明显高于单项超声造影定量参数0. 890 (0. 830～0. 951)、Hcy 0. 827 (0. 770～0. 885)及Hs-CRP 0. 795 (0. 737～0. 856),其预测ICS的敏感度(98. 5%)和特异度(93. 6%)均较高。相关分析显示,ICS患者超声造影定量参数FC-AUC与Hcy、Hs-CRP的相关性较好(r=0. 815、0. 792,P 0. 001)。结论超声造影定量参数联合Hcy及Hs-CRP水平能准确预测ICS的发生。     

ACE I/D polymorphism in Korean patients with ischemic stroke and silent brain infarction

Objectives –  Angiotensin-converting enzyme ( ACE ) polymorphism may play a role in stroke and silent brain infarction (SBI) susceptibility, but the results among the populations studied to date have not been consistent. Thus, we investigated the association between ACE genotypes and ischemic stroke and SBI in Korean patients.
Subjects and methods –  DNA samples from 237 stroke patients, 264 SBI patients and 234 age-matched controls were amplified using polymerase chain reaction to detect the ACE ins/del (I/D) polymorphism. Genotype was determined by the presence of a 490-bp band ( I allele) or a 190-bp band ( D allele) in agarose gel electrophoresis.
Results –  Odds ratios of the I/D and D/D genotypes and the overall (I/D + D/D) for the I/I genotype were significantly different between stroke patients and normal controls. However, there was no significant difference between patients with SBI and controls.
Conclusions –  This study is the first report of a significant association between ACE polymorphism and ischemic stroke in the Asian population. Although no consistent associations have been found between ACE polymorphism and stroke in the populations studied to date, the ACE polymorphism may be a genetic determinant of ischemic stroke, at least in Korean patients.     

术前血清CTRP3,CTRP9水平与缺血性脑卒中患者颈动脉支架成形术后再狭窄的相关性研究

目的 探讨血清补体C1q/肿瘤坏死因子相关蛋白3（Complement-C1q TNF-related protein 3,CTRP3）、补体C1q/肿瘤坏死因子相关蛋白9（Complement-C1q TNF-related protein 9,CTRP9）水平与缺血性脑卒中（Cerebral ischemic stroke,CIS）患者颈动脉支架成形术（Carotid artery stenting,CAS）后支架内再狭窄（In-stent restenosis,ISR）的关系。 方法 选取2018年2月-2021年2月在廊坊市人民医院诊治的234例CIS患者为CIS组,其中CAS后1年内出现ISR的患者作为ISR组（42例）,未出现ISR的患者作为NISR组（192例）;另选择同期体检健康者85例为对照组;检测CIS患者入院后CAS术前、体检健康者体检时血清CTRP3、CTRP9水平;收集CIS患者的临床资料;分析CIS患者血清CTRP3,CTRP9水平与临床指标的相关性、CAS后发生ISR的影响因素,血清CTRP3,CTRP9水平对CIS患者CAS后发生ISR的预测价值。 结果 与对照组比较,CIS组血清CTRP3,CTRP9水平降低（P＜0.05）;与NISR组比较,ISR组血清CTRP3,CTRP9水平降低,术前超敏C反应蛋白（High sensitivity C-reactive protein,hs-CRP）、术前白细胞计数、术前中性粒细胞计数、支架数量、残留狭窄程度比例升高（P＜0.05）;CIS患者血清CTRP3,CTRP9水平与术前hs-CRP水平、术前白细胞计数、术前中性粒细胞计数、支架数量、残留狭窄程度均呈负相关（r<-0.318,P＜0.05）;支架数量多、血清CTRP3低水平、CTRP9低水平为CIS患者CAS后发生ISR的危险因素（P＜0.05）;血清CTRP3,CTRP9、二者联合预测CIS患者CAS后发生ISR的曲线下面积分别为0.811、0.798、0.934,二者联合的预测价值显著高于单一指标（P＜0.05）。 结论 术前血清CTRP3,CTRP9水平异常降低与CIS患者CAS后发生ISR有关,可作为CIS患者CAS后预后评估的生物学指标。     

Accuracy of ICD-9 codes in identifying ischemic stroke in the General Hospital of Lugo di Romagna (Italy)

We assessed the sensitivity and the positive predictive value (PPV) of the ICD-9 codes in identifying ischemic strokes. The study involved the cross-sectional comparison between patients with an ischemic stroke diagnosis made by neurologists and patients with the 434 or 436 discharge codes. Sensitivity of the codes (all diagnostic levels and first level respectively) was 82% and 76%; PPV: 71% and 76%. The annual crude incidence of ischemic stroke was 2.62 per 1000 based on verified strokes and 3.03 per 1000 based on 434 or 436 coded medical records (at all diagnostic levels). Thirty-day case fatality ratio was 22.3% in verified strokes and 36.8% among patients diagnosed with codes 434 or 436 but without stroke (all levels). Our results disclosed inaccuracy in use of the ICD-9 codes in the diagnosis of ischemic stroke in the general hospital of Lugo di Romagna, Ravenna Province, Italy. The misdiagnosis of patients could be influenced by the degree of severity of clinical features. Epidemiological data and cost-analysis forecasts based only on the ICD-9 system must be considered with caution. Received: 10 July 2002 / Accepted in revised form: 28 February 2003 Correspondence to: R. Rinaldi     

Ultrasound, atherosclerosis and stroke at a young age: a cross-sectional long-term follow-up in western Norway

Background and purpose:  Previous studies have shown significantly higher mortality and vascular morbidity amongst patients with ischaemic stroke onset at a young age compared with controls after a mean observation time of more than 11 years.
Methods:  In the present cross-sectional study, we measured the carotid intima-media thickness (IMT) in 140 (75%) of 187 survivors of ischaemic stroke after a mean observation time of 11.9 years. Their mean age when included was 41.1 years. IMT was measured by B-mode ultrasonography.
Results:  Total maximum IMT <1.0 mm was found in 34 (24%) patients, [1.0–1.2 mm) in 29 (21%) patients, [1.2–1.5 mm) in 29 (21%) patients and ≥1.5 mm in 48 (34%) patients. Increasing total maximum IMT was related to increasing age, male gender, recurrent ischaemic stroke, coronary atherosclerosis, peripheral atherosclerosis, smoking, hypertension and diabetes mellitus.
Discussion:  IMT changes confirm increased vascular morbidity in patients who suffered ischaemic stroke at a young age.     

2型糖尿病患者基质金属蛋白酶-12基因多态性与缺血性卒中的相关性研究

目的探讨2型糖尿病患者基质金属蛋白酶12(MMP-12)基因多态性与缺血性卒中的相关性。方法选择2013年1月至2015年12月在本科治疗的217例2型糖尿病合并缺血性卒中患者作为病例组,按照TOAST分型结果将病例组患者分为大动脉粥样硬化性卒中(LAA)组88例和非大动脉粥样硬化性卒中(n-LAA)组129例,选择同期在我院体检的无缺血性卒中的2型糖尿病患者100例作为对照组,采用聚合酶链反应-限制性内切酶分析(PCR-RFLP)法比较MMP-12(-82 A/G)和MMP-12(-1082 A/G)基因型多态性在各组间的差异。结果病例组和n-LAA组MMP-12(82 A/G)基因型和等位基因与对照组比较,差异均无统计学意义(P0.05)。LAA组(G/G+A/G)基因型频率显著高于对照组(22.73%vs 11.00%,P=0.031);G等位基因频率也高于对照组(18.18%vs 10.05%,P=0.033)。n-LAA组MMP-12(-1082 A/G)基因型和等位基因与对照组比较,差异均无统计学意义(P0.05)。病例组和LAA组(G/G+A/G)基因型频率均显著高于对照组(33.64%vs 22.00%,P=0.036;37.50%vs 22.00%,P=0.020);两组G等位基因频率也均高于对照组(25.58%vs 17.00%,P=0.017;30.68%vs 17.00%,P=0.002)。多因素Logistic回归分析结果显示MMP-12-82A/G等位基因G和MMP-12-1082A/G等位基因G均是2型糖尿病患者发生LAA的危险因素(OR=1.107,95%CI 1.010-1.371,P=0.031;OR=1.285,95%CI 1.142-1.817,P=0.010)。结论对于2型糖尿病患者,MMP-12基因-82位点G等位基因和-1082位点G基因多态性与大动脉粥样硬化性卒中密切相关。     

急性脑梗死患者外周血Th17、Treg、Th17/Treg及炎症因子的动态变化过程研究

目的探讨急性脑梗死(AIS)患者外周血Th17、Treg、Th17/Treg及相关炎症因子的表达及其动态演变过程。方法选取32例AIS患者为实验组及32名健康人为对照组。分别检测AIS患者第1 d、4 d、7 d,外周血中Th17及Treg占CD4+T细胞比例及Th17/Treg比值,并检测白介素6(IL-6)、中性粒细胞与淋巴细胞比值(NLR)、C反应蛋白(CRP)和红细胞沉降率(ESR),分析其在AIS后的变化规律。结果AIS组于起病后第1 d、4 d,外周血Th17、Treg比例分别与对照组相比,差异有统计学意义(均P<0.05);AIS患者第7 d Th17、Treg比例逐渐恢复,与对照组比较差异无统计学意义(均P>0.05);AIS患者Th17/Treg比值在第1 d、4 d、7 d逐渐减小,但始终明显高于对照组(均P<0.05)。在AIS后的第1 d、4 d、7 d,IL-6、NLR及CRP分别均明显高于对照组(均P<0.05);AIS患者ESR第1 d与对照组比较无统计学意义(P>0.05),第4 d、7 d明显高于对照组(均P<0.05)。AIS患者外周血Th17比例及Th17/Treg、NLR、CRP、ESR分别与IL-6呈正相关(ρ=0.298,P=0.007;ρ=0.351,P=0.001;ρ=0.377,P=0.001;ρ=0.582,P=0.000;ρ=0.388,P=0.000);Treg比例与IL-6呈负相关(ρ=-0.242,P=0.029)。结论AIS患者早期存在Th17/Treg失衡,且合并有全身炎症反应。     

Angiotensin converting enzyme (I/D) gene polymorphism contributes to ischemic stroke risk in Caucasian individuals: a meta-analysis based on 22 case-control studies

Background: Stroke is a multifactorial disease in which genetic factors play an important role. Previous studies associated angiotensin converting enzyme (ACE) (insertion/deletion, I/D) gene polymorphism with ischemic stroke risk in Caucasian individuals reported conflicting results. The purpose of this study was to evaluate the association between ACE (I/D) gene polymorphism and ischemic stroke risk by a meta-analysis. Methods: The related studies were searched in MEDLINE, EMBASE and HuGEnet databases. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for ischemic stroke risk associated with this polymorphism were estimated using fixed-effect or random-effects model. Twenty-two studies (5528/5081 cases/controls) were eligible in our meta-analysis. Results: Overall, statistical associations of the ACE (I/D) polymorphism with ischemic stroke risk were found in dominant model (DD + ID versus II) : OR = 1.21, 95% CI = (1.06,1.38), P = 0.006, recessive model (DD versus ID + II): OR = 1.28, 95% CI = (1.05,1.55), P = 0.01, and homozygote comparison (DD versus II): OR = 1.37, 95% CI = (1.14,1.65), P = 0.001 for Caucasians. When stratifying according to stroke subtypes, there were similarly significant differences for small vessel disease in dominant model (DD + ID versus II) : OR = 1.44, 95% CI = (1.01,2.05), P = 0.04, recessive model (DD versus ID + II): OR = 1.30,95% CI = (1.09,1.55), P = 0.004, and homozygote comparison (DD versus II): OR = 1.44, 95% CI = (1.15,1.80), P = 0.001. Conclusion: This analysis suggests that the ACE (I/D) polymorphism may be a risk factor for ischemic stroke, genotype DD of ACE could increase the risk of ischemic stroke in Caucasians. Subgroup analyses indicate that stroke subtypes may be a genetic risk factor of ischemic stroke, and there might be a greater genetic liability with small vessel disease.