西洛他唑抗动脉粥样硬化的作用机制

目的观察西洛他唑对兔动脉粥样硬化斑块组织的影响,进一步探讨西洛他唑抗动脉粥样硬化作用及其可能机制。方法将30只新西兰雄性白兔随机分为正常对照组、高脂饮食组和西洛他唑组。酶法检测血脂,免疫沉淀法测定血清C反应蛋白水平,免疫组织化学检测基质金属蛋白酶9和核因子κB的表达,病理形态学分析各组主动脉内膜厚度和斑块面积,逆转录聚合酶链反应检测血管组织单核细胞趋化蛋白1mRNA的表达。结果实验第12周末,西洛他唑组总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平低于高脂饮食组,但高于正常对照组(P均<0.01);西洛他唑组主动脉内膜厚度和斑块面积低于高脂饮食组,但大于正常对照组(P均<0.01);西洛他唑组核因子κB、单核细胞趋化蛋白1和基质金属蛋白酶9的表达弱于高脂饮食组,但强于正常对照组(P均<0.01)。结论西洛他唑有抗动脉粥样硬化作用,其作用机制可能与下调核因子κB、单核细胞趋化蛋白1及基质金属蛋白酶9的表达有关。     

西洛他唑治疗糖尿病肾病的临床观察

应用西洛他唑治疗糖尿病肾功能损害的高粘血症80例.随机分为A组40例为治疗组在胰岛素降糖及血栓通,阿斯匹林等基础上加用西洛他唑50mg每日二次.B组40例为非治疗组,除不加西洛他唑外余同A组.治疗16周.结果A组比B组有显著差异,P＜0.01.结论西洛化唑对糖尿病肾功能损害有一定防治作用,对DN早期,轻型有疗效.     

西洛他唑治疗糖尿病肾病的临床观察

应用西洛他唑治疗糖尿病肾功能损害的高粘血症80例。随机分为A组40例为治疗组在胰岛素降糖及血栓通，阿斯匹林等基础上加用西洛他唑50mg每日二次。B组40例为非治疗组，除不加西洛他唑外余同A组。治疗16周。结果：A组比B组有显著差异，P〈0．01。结论：西洛化唑对糖尿病肾功能损害有一定防治作用，对DN早期，轻型有疗效。     

阿司匹林联合西洛他唑治疗糖尿病合并下肢动脉粥样硬化症的疗效观察

糖尿病合并下肢动脉粥样硬化症是糖尿病患者较常见的慢性并发症,可引起下肢缺血症状,缺血性溃疡,甚至坏疽,导致行走困难,重者截肢［1］。而血糖是影响血小板聚集的独立因素之一,影响抗血小板聚集药物的疗效。本研究对糖尿病合并下肢动脉粥样硬化症患者采取阿司匹林联合西洛他唑治疗,取得了很好的临床效果,现报道如下。     

西洛他唑治疗肢体动脉缺血性疾病的临床疗效观察

我院自1992年11月至1995年2月采用随机双盲法应用抗血小板聚集新药西洛他唑与噻氯匹定对照治疗四肢慢性动脉闭塞缺血性疾病48例，实验结果表明西洛他叹治疗四肢动脉缺血性疾病总有效率为929％，可明显提高息肢血压指数（P＜0．01）和降低血小板聚集率护＜0．01），未发现严重毒副作用；提示西洛他唑是一种安全有效的治疗肢体缺血性疾病的新药。     

西洛他唑治疗老年缺血性心脏病致窦性心动过缓的疗效观察

窦性心动过缓多见于老年患者,或因生理性衰退、心肌纤维化或心肌缺血导致窦房结及其周围组织病变,从而影响窦房结传导功能.目前其临床药物治疗可选择阿托品、麻黄碱、异丙肾上腺素等,药物无效可选择起搏器植入.前者长期应用副反应较多,甚至会引发新的心律失常,后者治疗费用高,且后期并发起搏器综合征.本文拟观察西洛他唑应用于老年缺血性心脏病合并窦性心动过缓患者的疗效,为其治疗提供依据.     

西洛他唑联合弥可保治疗DPN疗效观察

对30例DPN患者，随机分为治疗组（15例）和对照组（15例），在治疗糖尿病的同时，治疗组予西洛他唑100mg、口服2次／日，加弥可保500μg、口服3次／日，2月为一疗程，对照组只用弥可保，剂量、方法和疗程与治疗组相同。结果治疗组症状改善率：下肢麻木、疼痛和瘙痒分别为100％、90％和85％，对照组为80％、83．33％和71．42％。两组差异显著（P〈0．01）；肌电图腓胫神经传导速度（运动和感觉）两组有显著性差异（P〈0．01），未见副作用。结论联合治疗DPN有效而安全。     

西洛他唑联合弥可保治疗DPN疗效观察

对30例DPN患者，随机分为治疗组（15例）和对照组（15例），在治疗糖尿病的同时，治疗组予西洛他唑100mg、口服2次／日，加弥可保500μg、口服3次／日，2月为一疗程，对照组只用弥可保，剂量、方法和疗程与治疗组相同。结果治疗组症状改善率：下肢麻木、疼痛和瘙痒分别为100％、90％和85％，对照组为80％、83．33％和71．42％。两组差异显著（P〈0．01）；肌电图腓胫神经传导速度（运动和感觉）两组有显著性差异（P〈0．01），未见副作用。结论联合治疗DPN有效而安全。     

阿司匹林和西洛他唑对冠心病合并糖尿病患者血小板聚集活性的影响

目的:探讨阿司匹林对冠心病合并糖尿病患者血小板聚集活性的影响;西洛他唑对血小板聚集活性作用是否有类似改变。方法:入选的冠心病患者中合并与合并2型糖尿病患者各45例。根据其口服药物又分为阿司匹林组、西洛他唑组和联合用药组,每组各15例。记录患者基本情况并测定血小板聚集活性、血浆血栓素(TX)B2、6-K-前列腺素(PG)F1a和髓过氧化物酶(MPO)水平,并进行统计分析。结果:(1)多元逐步回归分析显示血糖是影响血小板聚集的独立因素(R=0.914,P<0.01);(2)方差分析显示糖尿病患者血小板聚集活性、血浆TXB2、MPO水平较非糖尿病患者明显增高,6-K-PGF1a水平降低(P<0.001);(3)非糖尿病患者阿司匹林组和西洛他唑组血小板聚集活性和TXB2没有明显差异,西洛他唑组血浆6-K-PGF1a水平高于阿司匹林组,而MPO水平低于阿司匹林组(P<0.001);糖尿病患者西洛他唑组血小板聚集活性、TXB2和MPO水平低于阿司匹林组,而6-K-PGF1a水平高于阿司匹林组(P<0.05~0.001)。结论:对冠心病合并糖尿病患者西洛他唑较阿司匹林可以更有效地抑制血小板聚集。     

西洛他唑对老年冠心病不稳定心绞痛患者血小板功能的影响

目的探讨西洛他唑对老年冠心病不稳定心绞痛患者血小板聚集功能及蛋白激酶B(PKB)的活性变化。方法老年冠心病不稳定心绞痛(UAP)患者48例,随机分2组,即西洛他唑(cilostazol,CS)组和阿斯匹林(aspirine,AS)组;26例健康老年人作对照组(NC组)。UAP组在常规抗凝治疗的同时给予抗血小板治疗,即CS组给予CS100mg口服;AS组给予AS300mg口服。于用药前10min及用药后35h、6h、24h测定血小板聚集率、血小板PKB的活性变化。结果所有老年UAP患者血小板最大聚集率均较NC组明显增加(P<001);胞膜PKB表达较对照组明显增高(P<001);而胞浆PKB表达则显著降低(P<001)。口服CS、AS后6h血小板最大聚集率较用药前降低最明显(P<001),但24h时CS对血小板聚集仍有较强的抑制作用,而AS已不明显。口服CS6h后UAP组患者血小板胞膜PKB活性较用药前明显下降(P<001);而胞浆PKB表达则已明显升高。AS组二指标虽有所变化,但用药前后比较无显著差异。结论老年UAP患者体内血小板处于活化状态,CS能有效抑制血小板活化,作用优于AS,为抗血小板治疗提供新的理论基础。     

Prevalence of risk factors and of coronary artery disease, ischemic stroke, carotid arterial disease and lower extremity peripheral arterial disease in 96 patients undergoing elective surgery for an abdominal aortic aneurysm

Ninety-six patients (77 men and 19 women), with a mean (± SD) age of 77±9 years, underwent elective surgery between 2006 and 2007 for an abdominal aortic aneurysm (AAA) greater than 5.5 cm in diameter. Of the 96 patients with an AAA, 31 (32%) were smokers, 85 (89%) had hypertension, 78 (81%) were treated with statins for hypercholesterolemia and 24 (25%) had diabetes mellitus. As well, 71 (74%) had coronary artery disease, 17 (18%) had a previous ischemic stroke, 19 (20%) had carotid arterial disease and 37 (39%) had peripheral arterial disease of the lower extremities.     

Management of atherothrombotic risk factors in high-risk Canadian outpatients

BACKGROUND:

The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international, prospective cohort of 68,236 patients with established coronary artery, cerebrovascular or peripheral arterial disease, or three or more atherothrombotic risk factors. Baseline data from the 1976 Canadian patients in the REACH Registry provide opportunities to assess atherothrombotic risk and treatment in a real-world Canadian setting.

OBJECTIVES:

To present baseline characteristics of Canadian REACH Registry patients, and to compare cardiovascular risk and treatment among Canadian, United States (USA) and global patients.

METHODS:

Patients 45 years of age or older with established atherosclerotic vascular disease or three or more cardiovascular risk factors were enrolled during 2004. Baseline data were used in analyses of risk factor prevalence and control and medication use. Comparisons between the Canadian and USA populations, Canadian and global populations, and the Canadian regions were conducted.

RESULTS:

Of the 1976 Canadian REACH patients, 82.5% had documented vascular disease, 12.6% of whom had manifestations in more than one vascular bed (polyvascular disease). A high prevalence of hypercholesterolemia (84.4%), hypertension (76.6%) and diabetes mellitus (43.7%) were noted, and 75.1% of patients were overweight or obese. Of the 1976 Canadian REACH patients, 75.1% were at target cholesterol levels, 67.4% were at target fasting blood glucose levels and 60.6% were at target blood pressure levels. Significant differences existed in the prevalence of risk factors and their management among Canadian, USA and global REACH populations, as well as within Canada.

CONCLUSIONS:

Canada compared favourably with USA and global REACH populations in the use of proven risk-reducing medications.     

Atherosclerosis in sickle cell disease - a review

Acute, vaso-occlusive crises are the most common and earliest clinical manifestations of sickle cell disease. Recent thoughts about development of atherosclerosis as a result of this disease are presented. Current insights into the pathogenesis of atherosclerosis in sickle cell disease are reviewed, in particular the role of endothelial dysfunction, homocysteine and platelets. Common and uncommon sites of atherosclerosis are described. Radiological assessment and potential therapeutic agents to slow the progression of atherosclerosis are discussed. Finally, treatment of atherosclerosis in certain sites is evaluated and reviewed.     

Chronic HCV infection is a risk factor of ischemic stroke

Objectives

Cerebrovascular diseases are leading cause of death worldwide. Plaque rupture and embolization account for one-third of ischemic stroke. The causes are not fully known, but inflammation plays a pathogenic role. Recently, HCV infection has been identify as risk of atherosclerosis. HCV replicates within carotid plaques and brain endothelia cells; moreover, HCV patients showed higher levels of inflammation. Thus, we hypothesized that subjects carrying HCV are at higher risk of stroke. Accordingly, we evaluated prevalence and role of HCV infection in patients with stroke.

Methods

A priori sample size was calculated. Overall, 820 consecutive patients were enrolled, 123 with stroke and, as control, 697 age- and gender-matched (295 with COPD; 402 with diseases other than HCV-associated). Patients were evaluated for HCV and conventional risk of stroke.

Results

Prevalence of HCV was higher in patients with stroke than that observed in control (26.8% vs. 6.6%, p = 0.0001). An analysis of stroke patients showed that those HCV positive were younger (p = 0.017) had lower serum levels of cholesterol (p = 0.001), triglycerides (p = 0.045), and higher serum levels of inflammation markers (ESR, p = 0.001; CRP, p = 0.0001; fibrinogen, p = 0.012). A multivariate analysis showed that HCV infection was an independent risk factor of stroke (O.R. 2.04, 95% C.I. 1.69–2.46; p = 0.0001). A secondary analysis showed that HCV patients had higher (p = 0.031) prevalence of past ischemic heart disease.

Conclusions

HCV infected patients are at higher and earlier risk of stroke. Inflammation is a key mediator. Clinicians in clinical practice and researchers in future trials should take into account these new findings.     

Office Management of Peripheral Arterial Disease

Patients with peripheral arterial disease are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease. Smoking should be stopped, and hypertension, diabetes mellitus, and dyslipidemia should be treated. Statins reduce the incidence of intermittent claudication and increase exercise duration until the onset of intermittent claudication in patients with peripheral arterial disease and hypercholesterolemia. Antiplatelet drugs, such as aspirin or clopidogrel, angiotensin-converting enzyme inhibitors, and statins, should be given to all patients with peripheral arterial disease. Beta-blockers should be given if coronary artery disease is present. Exercise rehabilitation programs and cilostazol improve exercise time until the onset of intermittent claudication. Indications for lower-extremity angioplasty, preferably with stenting, or bypass surgery are incapacitating claudication interfering with work or lifestyle in patients; limb salvage in patients with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, infection, or gangrene; and vasculogenic impotence.     

老年周围动脉闭塞性疾病患者血栓前状态的初步研究

目的　探讨老年周围动脉闭塞性疾病 (PAOD)患者是否存在血栓前状态 (PTS)及其临床意义。方法　检测 33例确诊为老年 PAOD患者的血浆血小板α颗粒膜蛋白 - 1 4 0 (GMP- 1 4 0 )、血管性假血友病因子 (v WF)、纤维蛋白原 (FIB)、纤溶酶原 (PLG)和 D-二聚体 (DD)以及凝血酶 -抗凝血酶 复合物 (TAT)水平 ,并分别与 40例健康老人及 30例具有心血管危险因素的非 PAOD患者进行比较。结果　老年 PAOD组的 GMP- 1 4 0(1 4 .0 6± 2 .1 8μg/ L )、DD(2 .92± 1 .3μg/ L)、v WF(1 0 4 .42 %± 31 .4%)及 FIB(60 6.8± 1 1 7.8mg/ dl)水平显著高于健康对照组 (依次为 8.2 3± 1 .86μg/ L、0 .35± 0 .1 8μg/ L、53.67%± 1 1 .33%及 2 4 2 .3± 41 .7mg/ dl) (P<0 .0 0 0 1 )和心血管危险因素组 (依次为 1 1 .97± 1 .96μg/ L、1 .0 6± 0 .53μg/L、75.8%± 4.59%及 41 3.4± 67.78mg/ dl) (P<0 .0 0 1 ) ,而 PLG活性、TAT水平各组间无显著差异。结论　老年 PAOD患者存在血栓前状态 ,且与内皮功能失调密切相关 ;积极使用抗血小板制剂和抗凝剂 ,改善血管内皮功能是 PAOD治疗的核心之一。     

Polymorphism in the methylenetetrahydrofolate reductase (C677T) gene and homocysteine levels: a comparison in Brazilian patients with coronary arterial disease, ischemic stroke and peripheral arterial obstructive disease

This study aimed to compare plasma levels of total homocysteine (tHcy) in different arterial events as well as to investigate an association between homocysteine levels and C677T polymorphism in Brazilian patients. A total of 145 subjects were enrolled in this study including 43 patients with coronary arterial disease (CAD), 21 with ischemic stroke (IS), 44 with peripheral arterial obstructive disease (PAOD) and 37 control subjects. A preliminary analysis showed significant difference for tHcy plasma levels between patients with CAD (P = 0.003) or PAOD (P = 0.03) compared to controls. However, after adjustment for sex, age, total cholesterol, LDL, diabetes, tabagism or C677T polymorphism, no significant differences were detected in tHcy levels among patients groups and controls. No significant correlation was demonstrated for C677T polymorphism and homocysteine levels. These results indicate that increased Hcy levels may not be considered an independent risk factor for atherothrombotic diseases in Brazilian patients.     

Does claudication affect the development of coronary collaterals?

Atherothrombosis is a generalized disease process that affects large- and medium-diameter arteries throughout the arterial tree. In this study, we aimed to evaluate the correlation between collaterals in different vascular beds. Patients who had undergone digital subtraction angiography for symptomatic lower extremity peripheral arterial disease and coronary angiography after an acute anterior myocardial infarction (MI) were compared with a control group composed of those patients who were hospitalized for acute anterior MI and underwent coronary angiography but had no claudication and had an ankle-brachial index of greater than 0.9 in both legs. In claudicants, stenosis in the left anterior descending artery (LAD) (90.3 ± 17.5 vs 78.6 ± 13.8, P = 0.005) was greater compared with the patients without claudication. The collaterals to the LAD (88% vs 37.5%, P = 0.001) and the collateral grades (1.7 ± 0.7 vs 0.7 ± 0.9, P = 0.001) were higher in the patients with claudication compared with those without claudication. A previous history of angina (52.2% vs 16.3%, P = 0.001), claudication (39.1% vs 4.6%, P = 0.001), and peripheral collaterals (45.7% vs 6.9%, P = 0.001) were higher in the patients with coronary collaterals than in those without. The factors affecting the development of coronary collaterals were claudication [relative risk (RR): 8.8; 95% confidence interval (CI): 2.1–39.8], peripheral collaterals (RR: 1.1; 95% CI: 1.1–1.3), and LAD stenosis (RR: 1.2; 95% CI: 0.03–29.1). Our results suggest that the presence of collateralization or angiogenesis in one vascular bed highly predicts collateralization in another arterial bed.     

Perspectives on optimizing trial design and endpoints in peripheral arterial disease: a case for imaging-based surrogates as endpoints of functional efficacy

Surrogate endpoints are important for validation of mechanism, early proof of concept, and the rational design of clinical trials for regulatory approval of drugs. The recent failure of several drugs in peripheral arterial disease (PAD) and in atherosclerosis highlights the importance of understanding drug effect and is a clarion call for better endpoints. This review focuses on aspects relating to the current state of surrogate endpoints in PAD and reviews emerging endpoints using imaging approaches that may have the potential of improving study design in PAD.     

Prevalence and clinical profile and management of peripheral arterial disease in elderly patients with diabetes

Introduction

Peripheral arterial disease (PAD) increases with age and diabetes. The aim of this study was to assess the prevalence of PAD in an elderly population with diabetes.

Methods

This multicenter and cross-sectional study included patients > 70 years, with an established diagnosis of diabetes. PAD was defined as those patients with a history of revascularization or amputation due to ischemia, or a pathological ankle-brachial index (ABI). Adequate blood pressure (BP), LDL cholesterol and HbA1c control were considered as < 130/80 mm Hg, < 100 mg⁄dL and < 7.0%, respectively.

Results

A total of 1462 patients were included. The most frequent cardiovascular risk factor and cardiovascular disease were hypertension (80.37%) and PAD (60.60% overall; 83.2% of those assisted by vascular surgeons vs 31.9% of those attended by other medical specialists; p < 0.001), respectively. However, when ABI was measured, 70.99% of the study population had PAD (80.2% of those assisted by vascular surgeons vs 59.6% of those attended by other medical specialists; p < 0.001). The predictors for a pathological ABI included male gender, smoking, dyslipidemia, family history of premature cardiovascular disease, sedentary lifestyle, diabetic-related complications, heart and cerebrovascular diseases. Although risk factors control was very poor, it was even lower in patients with PAD.

Conclusions

The prevalence of PAD is high in diabetic elderly patients. The concomitance with other risk factors and cardiovascular diseases was very high. The ABI allowed increasing the diagnosis of PAD.