Hyperhomocysteinaemia in patients with peripheral arterial occlusive disease.

In the Western world, cardiovascular disease is still the most common cause of death. Over the past decade it has become clear that apart from common risk factors, high concentrations of total homocysteine are relavant to the process of atherosclerosis, especially in the development of premature vascular disease. Hyperhomocysteinaemia (HHC) can be found in 25-32% of the patients with premature peripheral arterial occlusive disease (PAD). Retrospective and prospective studies, evaluating the clinical course of patients with PAD, showed significant associations between high concentrations of total homocysteine and the severity of atherosclerosis and with a more rapid disease progression and mortality rates. HHC can be treated with vitamin B6 and folic acid. Although there may be indications that there is a protective effect of treatment, prospective randomized clinical trials are urgently needed to unravel the role of HHC and its treatment in patients with premature PAD.     

北京社区老年人周围动脉闭塞性疾病与基因多态性的关系

目的探讨北京社区老年人群亚甲基四氢叶酸还原酶(methylenetetrahydrofolatereductase,MTHFR)基因多态性与周围动脉闭塞性疾病(peripheralarterialocclusivedisease,PAOD)的关系,为临床治疗及早期康复干预提供理论基础。方法用聚合酶链反应-限制性片段长度多态性(polymerasechainreaction-restrictionfragmentlengthpoly-morphism,PCR-RFLP)技术,检测了83例(男28例,女55例)老年PAOD及100例(男50例,女50例)健康老年对照的MTHFR基因多态性。结果MTHFR基因C677T单核苷酸突变呈多态性,分为3种类型:C/C,C/T,T/T。老年PAOD病例组3种基因型频率为:C/C,13.3%;C/T,51.8%;T/T,34.9%。健康老年对照组分别为:C/C,31%;C/T,50%;T/T,19%。两组MTHFR基因的C677T单核苷酸突变中T突变位点的频率分别为60.8%、44%。病例组与对照组T/T基因型频率和T等位基因频率均呈显著性差异。结论在北京社区老年人群中,MTHFR等位基因C677T突变可能是老年PAOD的危险因素。     

Outpatient rehabilitation in patients with coronary artery and peripheral arterial occlusive disease

Jeger RV, Rickenbacher P, Pfisterer ME, Hoffmann A. Outpatient rehabilitation in patients with coronary artery and peripheral arterial occlusive disease.

Objective

To assess participation rates and outcome in outpatient cardiac rehabilitation (OCR) of patients with peripheral arterial occlusive disease (PAOD).

Design

Prospective cohort study.

Setting

Referral center, ambulatory care.

Participants

All patients undergoing OCR at 2 university hospitals in Switzerland from March 1999 to August 2005.

Intervention

OCR during 3 months.

Main Outcome Measures

Primary endpoints were workload during bicycle stress test and quality of life (QOL), both at the end of OCR. Secondary endpoints were complications during OCR and termination of OCR.

Results

Of 1508 patients, 99 (7%) had PAOD (27 with Fontaine stage I, 69 with stage II, 3 with stage III). Patients with PAOD were older, had more cardiovascular risk factors, and were more likely to have undergone cardiac bypass grafting than those without PAOD. PAOD patients at OCR entry achieved a lower exercise workload than non-PAOD patients (PAOD patients, 105±31W and 69%±17% of target vs non-PAOD patients, 125±38W and 79%±19%; P<.001) but both groups achieved similar gains in exercise capacity at the end of OCR (PAOD patients, 126±44W and 82%±25% vs non-PAOD patients, 153±48W and 98%±24%; P<.001). For both groups, QOL was similar at baseline and follow-up, and improved equally in most dimensions. OCR was discontinued more often in patients with PAOD than in those without (18% vs 10%, P=.018). Cardiac and noncardiac complication rates were similar.

Conclusions

Patients with PAOD undergoing OCR have a similar benefit but higher dropout rates than other patients. Thus, PAOD patients should be encouraged to participate in OCR, possibly by creating specifically tailored concepts.     

Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease

Abstract. Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (≤ 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium-derived proteins, von Willebrand factor (vWF), thrombomodulin (TM), and tissue-type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post-load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post-load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL^-1) levels were above normal. At follow-up, vWF levels had decreased to 170% ( P = 0.01) and TM levels had decreased to 49 ng mL^-1 ( P = 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothelial dysfunction.     

Assessment of peripheral arterial occlusive disease

Many older patients in critical care settings have significant arterial disease, so the assessment of peripheral circulation may be important in their management. A great deal of information can be gained through the physical examination, which can be supplemented by the use of the Doppler velocity detector. This device should be used to obtain quantitative pressure measurements. Special consideration must be given to evaluation early in the postoperative period.     

Evaluating peripheral arterial occlusive disease.

The clinical history and physical examination remain the most important factors in determining the presence, anatomic location, and physiologic extent of arterial occlusive disease and the need for operation. The physician should refrain from ordering arteriography to confirm the diagnosis of arterial disease unless operation is warranted. If peripheral arterial occlusive disease is diagnosed clinically, its anatomic and physiologic extent can be determined qualitatively and quantitatively by Doppler ultrasonic studies. These studies are also useful in following the natural history of or the influence of therapy on the course of arterial occlusive disease. Ultrasonic studies coupled with careful clinical assessment and with arteriographic evaluation prior to planned operation provide an optimal armamentarium for the diagnosis and management of peripheral arterial occlusive disease.     

Anticoagulation and antiaggregation in patients with peripheral arterial occlusive diseases

Peripheral vascular occlusive disease (PAOD) is frequently seen in patients suffering from coronary heart or cerebrovascular disease and is, considered as a prognostic predictor for the morbidity and mortality of this patient group. Thus, secondary antithrombotic and antiplatelet prophylaxis in these patients is not limited to achievement of long-term patency of the revascularized or recanalized arterial segment, but plays as well a pivotal role for the prevention of myocardial infarction and stroke. Generally, claudicants as well as patients undergoing percutaneous transluminal angioplasty (PTA), supragenicular femoro-popliteal artificial bypass surgery, aortofemoral, iliaco-femoral unilateral bypass, or aortobifemoral Y-graft implantation with unimpaired arterial outflow are treated life-long with low dose acetylsalicylic acid (ASA) 75-250 mg. On the other hand, those undergoing axillo-femoral, femoro-femoral crossover, aorto-profundal or femoro-popliteal infragenicular and femoro-distal venous bypass surgery should be treated with vitamin K antagonists. The role of Clopidogrel in secondary prevention after peripheral revascularization and recanalization still needs to be defined.     

Bioabsorbable stenting for peripheral arterial occlusive disease

Bioabsorbable stents offer an unproven but theoretically appealing means to address the deficiencies of current stent designs. Ideally, these stents would provide early postprocedural scaffolding support yet undergo a predictable process of reabsorption, thus removing the persistent stimulus for neointimal hyperplasia. Prototypes include polymeric formulations and magnesium-based absorbable metal stents. Current and future human trials will ascertain if bioabsorbable stents truly deliver a physiologic advantage in the treatment of peripheral occlusive disease.     

Human leucocyte-endothelial interactions in peripheral arterial occlusive disease

Abstract. This ex vivo study determined the expression of leucocyte adhesion receptors for endothelial adhesion molecules in 10 patients with peripheral arterial occlusive disease (PAOD) and in 10 healthy controls before and after treadmill exercise. Granulocytes from venous blood samples were separated on a Ficoll-Hypaque gradient and the phenotypical expression of CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1) and CD11c/CD18 (p150,95) was observed by double indirect immunofluorescence using specific monoclonal antibodies. The total and differential white blood cell counts were monitored before and after exercise. In the PAOD patients a significant reduction in the number of granulocytes expressing CD11b/CD18 (Mac-1) and CD11c/CD18 (p150,95) associated with a significant neutropenia was observed after exercise, suggesting that leucocyte-endothelial interactions occur during ischaemia.     

Risk factor assessment for patients with peripheral arterial disease

Peripheral arterial disease is a chronic condition that affects a significant proportion of the adult population. Treatment is often prolonged and may be painful, with a slow rate of healing. However, current evidence to support risk-factor assessment highlights the role of the nurse in encouraging lifestyle modification, leading to an improvement in the patient's quality of life.     

周围动脉闭塞性疾病患者认知功能的调查

目的:探讨周围动脉闭塞性疾病与认知功能的关系.方法:对北京万寿路地区1 730例60岁以上老年人进行电话访问、神经系统查体认知功能问卷及多普勒检查,对其中患有周围动脉闭塞性疾病人群的认知功能与非患病人群进行比较.结果:周围动脉闭塞人群的简易智能状态检查(MMSE)得分低于正常人群,其中计算力、延迟记忆及画钟测试两组得分差异有显著性.影响MMSE得分的因素包括年龄、文化程度、糖尿病、脑卒中史、肱踝动脉压力指数阳性、血浆纤维蛋白原水平.结论:周围动脉闭塞性疾病影响认知功能,可作为认知功能下降的预示指标.     

Prostanoids in therapy of peripheral arterial occlusive disease.

Therapy of chronical arterial occlusive disease primarily includes evaluation and treatment of risk factors as prophylaxis for preventing progression of arteriosclerosis. When patients suffer from claudication walking exercise is the therapy of choice. Only in cases with severe claudication (walking distance under 100 m) and rest pain or ischemic ulcers reopening procedures are necessary. Bypass surgery is supported by the different transluminal angioplasty techniques, which are suited even for the older and multimorbide patients. A pharmacological treatment of peripheral arterial occlusive disease should be introduced only for preventing progression of the disease or reocclusions following surgery or angioplasty or in those cases in whom reopening techniques are not possible or not successful. Here prostaglandin E1 has been proven to be effective in many clinical trials. The combination of surgery, angioplasty and pharmacological treatment allows to avoid major amputations in most patients with critical limb ischemia.     

Metabolism of intravenously administered prostaglandin E1 in patients with peripheral arterial occlusive disease]

Using high performance liquid chromatography and radioimmunoassay we have investigated the stability of prostaglandin (PG) E1 and its metabolite 13,14-dihydro-PGE1 in human plasma as well as the initial metabolism of PGE1 infused intravenously (80 micrograms/patient/hour) in patients with peripheral arterial occlusive disease. 13,14-dihydro-PGE1 degraded like PGE1 in human plasma at 37 degrees C with a half-life of several hours. During infusion of PGE1 higher plasma concentrations of the major metabolite 15-keto-13,14-dihydro-PGE1 and lower plasma levels of PGE1 and 13,14-dihydro-PGE1 were observed. The metabolite 13,14-dihydro-PGE1 is of interest, since in contrast to 15-keto-13,14-dihydro-PGE1 it is biologically active. The biosynthesis of 13,14-dihydro-PGE1 could contribute to the therapeutic efficacy of PGE1 administered intravenously in patients with peripheral arterial occlusive disease.     

Angioplasty increases target site concentrations of ciprofloxacin in patients with peripheral arterial occlusive disease.

OBJECTIVE: Patients with peripheral arterial occlusive disease are prone to soft tissue infections and frequently require antibiotics. To date, however, it is not known whether improvement of arterial blood flow by angioplasty of stenosis increases antibiotic concentrations in ischemic lesions. PATIENTS AND METHODS: All patients were scheduled to undergo elective percutaneous transluminal angioplasty (n = 10). Following a single, 400-mg dose of ciprofloxacin, drug concentrations in plasma, ischemic and healthy soft tissue; arterial peak systolic velocity; and ankle-brachial pressure index were assessed before and after angioplasty. Unbound ciprofloxacin concentrations were measured at the site of infection with use of in vivo microdialysis. RESULTS: Angioplasty increased peak systolic velocity and ankle-brachial pressure index compared with baseline (P <.002). Before angioplasty area under concentration-time curve (AUC(0-300)) values for ciprofloxacin were lower in ischemic tissue than in healthy tissue, with median values of 7.1 mg.h/L (range, 3.5-13.0) and 11.3 mg.h/L (range, 3.4-19.0), respectively (P =.03). After angioplasty AUC(0-300) values were identical in ischemic and healthy adipose tissue; median AUC(0-300) values were 8.0 mg.h/L (range, 4.0-20.7) and 8.5 mg.h/L (range, 4.4-22.9), respectively (P =.7). A combined in vivo pharmacokinetic/in vitro pharmacodynamic simulation based on tissue concentration data indicates that this difference in pharmacokinetics is also reflected in antimicrobial effect. CONCLUSION: Antibiotic concentrations are reduced significantly in ischemic lesions compared to those of healthy adipose tissue in patients with peripheral arterial occlusive disease. From the present data it might be speculated that improvement of arterial blood flow at the affected extremity is associated with increased cure rates of soft tissue infections in these patients.     

再谈严格掌握下肢动脉硬化闭塞性疾病手术和血管腔内治疗的指征

周围动脉闭塞性疾病（peripheral arterial occlusire disease,PAOD）通常指周围动脉硬化性闭塞症,是由于动脉粥样硬化导致动脉狭窄、闭塞引起的缺血性疾病,常见于下肢。随着生活水平的不断提高,动脉硬化性闭塞症的发病率逐年上升。同时随着血管外科的兴起,治疗动脉硬化下肢缺血的下肢血管旁路转流术和扩张支架术在国内广泛开展,手术量增长迅猛。但在不断提高手术水平的同时,也应严格掌握手术和介入治疗的指征,临床医生尤其是血管外科专业人员对此应有清醒的认识。     

Rehabilitation in patients with peripheral arterial disease

Rehabilitation is a recommended first-line therapy for patients with peripheral arterial disease (PAD) and consists of supervised exercise training and therapeutic education. Proved benefits are significant: improve pain-free walking distance, functional status and quality of life; reduce cardiovascular risk factors and mortality. At least three sessions weekly are recommended during 3 months. Exercise conditioning (global training and lower limb resistance training) is tailored by the preliminary evaluation of walking ability (free walking test, treadmill tests, 6-min walk test) and of the cardiac tolerance (maximal effort tests). Then the exercise workload is progressively improved. The four main goals of therapeutic education are: smoking cessation, prolonged physical activity, Mediterranean diet and observing pharmacological therapies. The limited compliance of the patients with PAD is often an obstacle for educational needs. The chronic patients with important functional limitations and unchecked risk factors will be preferentially enrolled in such programs. When a revascularization is discussed, rehabilitation can serve as trial treatment. Despite its efficacy, rehabilitation is still underutilized in clinical practice and should be promoted.