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The role of statins in vascular disease.

BACKGROUND: Recent publications have highlighted the benefits of statins in non-cardiac occlusive disease but also the failure of vascular surgeons to recognise and treat the risk factors for atherosclerosis, in particular hypercholesterolaemia. The aim of this review is to clarify the current experimental and clinical evidence for the use of statins in vascular disease. METHODS: Literature compiled from an extensive search of Medline and the Cochrane database has been used for the basis of this review. RESULTS: Experimental and clinical evidence consistently reports that statins improve endothelial dysfunction, are anti-inflammatory, anti-proliferative, anti-thrombogenic and anti-proteolytic. These effects are known to inhibit atherogenesis and improve plaque stability. Independent groups support the use of statins in the prevention of both primary and secondary cardiac events. The National Stroke association recommends their use to reduce strokes following myocardial infarction and the Heart Protection Study reports benefits in patients with non-cardiac occlusive disease. CONCLUSIONS: There is substantial evidence advocating the use of statins in patients with clinically significant vascular disease. In the future this may evolve to include those patients at risk from neointimal hyperplasia, aneurysmal disease and ischaemia reperfusion injury.

Cardiovascular Diseases↗

The influence of preexisting vascular disease on the outcome of renal transplantation in diabetic patients.

We analyzed the impact of prior vascular disease on the outcome of renal transplantation in 99 insulin-dependent diabetic patients. Thirty-three patients (group A) had clinical evidence of vascular disease prior to renal transplantation and 66 patients (group B) had no clinical vascular events in the pretransplant period. The median follow-up in group A patients was 14 months and in group B it was 23 months. The group A patients with preexisting vascular disease had a significant increase in mortality (33%) compared to group B (11%) (A vs. B; p = 0.01). The rate of graft loss was not significantly different between the two groups (45 vs. 42%; p = 0.94). Our data suggest that preexisting clinical vascular disease has a significant negative effect on patient survival in diabetic recipients of cadaver kidney transplants.

Adult↗

[True and presumed contraindications of beta blockers. Peripheral vascular disease, diabetes mellitus, chronic bronchopneumopathy].

Traditional contraindications to beta-blockers are peripheral vascular diseases, diabetes mellitus, chronic obstructive pulmonary disease (COPD) and asthma. Recent data seem to show that rigorous application of these rules are not completely justified and indicate that many patients would be inappropriately excluded from the beneficial effects of this therapy. Appraisal of clear guidelines for a safe use of beta-blockers is thus mandatory for the clinician. A brief review of the effects of beta-adrenergic receptor blockade is offered. The therapy is aimed at blocking beta 1-receptors. On the other hand, the block of beta 2-receptors causes the well known side effects, i.e. vasoconstriction, delayed response to hypoglycemia in diabetic patients, bronchoconstriction. From the first compound, propranolol, with uniform action on beta 1 and beta 2-receptors, further generation of beta-blockers were subsequently developed: beta 1-selective, with intrinsic sympathomimetic activity, and with associated vasodilating "ancillary" property. Some favorable reduction in collateral effects has thus been obtained with new compounds, without reaching complete safety. Examination of exclusion criteria applied in clinical trials offers no useful indications because of their imprecise definition. Examination of the literature and a more accurate understanding of the diseases, traditionally considered contraindications, may help setting up a uniform and clear path: peripheral vascular disease: beta-blockers should be avoided only in those patients with vasospastic disorders, rest pain with severe peripheral vascular disease or nonhealing lesions. In patients with mild to moderate disease, beta-blockers can be prescribed, but careful surveillance for any changes in symptoms related to intermittent claudicatio should be achieved; diabetes mellitus: previous apprehension for the lessening reaction to hypoglycemia in patients treated with insulin has been retracted. Beta-blockers are not contraindicated in these patients. Some caution should be addressed when signs of autonomic disease are present or in patients with difficult glycemic control. Patients on oral long-acting antidiabetic drugs should not be neglected. The risk of prolonged and paucisymptomatic hypoglycemia while taking beta-blocker agents is somewhat more relevant than in patients treated regularly with insulin; COPD and asthma: confusion may arise if rigorous definition of these diseases and their severity is not applied following the guidelines of the American Thoracic Society. Because bronchial hyperreactivity seems the crucial factor in determining collateral effects to beta-blocker agents, agreement can be reached on the following statements. Beta-blockers are contraindicated a) when history of asthma is present, b) when COPD is moderate to severe, i.e. with FEV1 reduction < 50% of the predicted value, c) in patients on chronic bronchodilator treatment, d) in chronic airflow limitation with evidence of > or = 20% reversibility in airway obstruction in response to inhaled salbutamol. When FEV1 is > 50% of the predicted value, beta-blockers can be given, providing adequate control of stability of ventilatory conditions.

Adrenergic beta-Antagonists↗

Emerging risk factors for atherosclerotic vascular disease: a critical review of the evidence.

CONTEXT: Atherosclerotic vascular disease is an enormous public health problem. A number of emerging risk factors for atherosclerosis have recently been proposed to help identify high-risk individuals. OBJECTIVE: To review the epidemiological, basic science, and clinical trial evidence concerning 4 emerging risk factors: C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine. DATA SOURCES: Using the terms atherosclerosis, cardiovascular disease, risk factors, prevention, screening, C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine, we searched the MEDLINE database from January 1990 to January 2003. Conference proceedings, abstract booklets, bibliographies of pertinent articles and books, and personal files were hand searched to identify additional articles. STUDY SELECTION: Original investigations and reviews of the epidemiology of atherosclerosis and the association of conventional and novel risk factors with vascular risk were selected. On the basis of the search strategy, 373 relevant studies were identified. DATA EXTRACTION: A diverse array of studies were examined, including randomized controlled trials, prospective cohort studies, systematic overviews, case-control, cross-sectional, and mechanistic studies. Data extraction was performed by one of the authors. DATA SYNTHESIS: The available epidemiological and basic science evidence supports, to varying degrees, independent associations between these 4 candidate risk factors and atherosclerotic vascular disease. However, there is relatively little data regarding the additive yield of screening for these factors over that of validated global risk assessment strategies currently in use. Furthermore, controlled intervention studies targeting individuals with these factors for proven risk-reduction therapies, or specifically treating these factors with available therapies, are few. The explanatory power of the major, established cardiovascular risk factors has been systematically underestimated. CONCLUSIONS: Although C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine are associated with vascular disease risk, their optimal use in routine screening and risk stratification remains to be determined.

Arteriosclerosis↗

Association of LMNA 1908C/T polymorphism with cerebral vascular disease and diabetic nephropathy in Japanese men with type 2 diabetes.

OBJECTIVE: The LMNA 1908C/T polymorphism has been reported to be associated with dyslipidaemia, metabolic syndrome, adipose tissue metabolism and obesity phenotypes, suggesting that this polymorphism presents an increased risk of atherosclerosis and vascular diseases. However, there have been no previous reports on the relationship between the LMNA 1908C/T polymorphism and vascular diseases. The aim of this study therefore was to investigate the association between the LMNA 1908C/T polymorphism and the prevalence of vascular disease in Japanese patients with type 2 diabetes. DESIGN: A cross-sectional, hospital-based study of diabetic complications with an LMNA gene background. PATIENTS: One hundred and sixty-six Japanese men with type 2 diabetes. Measurements LMNA 1908C/T polymorphism (by polymerase chain reaction restriction fragment length polymorphism, PCR-RFLP); diabetic retinopathy (by standard fundus photography); diabetic nephropathy (by urinary albumin excretion rate); diabetic neuropathy (by signs, symptoms and/or nerve conduction velocity); coronary heart disease (by symptoms of typical chest pain and/or history of myocardial infarction, and ischaemic electrocardiographic alteration and/or coronary artery bypass graft surgery); cerebral vascular disease (by ultrasonography, computed tomography and/or magnetic resonance imaging). RESULTS: Carriers of the LMNA 1908T allele manifested a significantly higher prevalence of diabetic nephropathy and cerebral vascular disease than carriers of the C allele. Multiple regression analysis showed that the LMNA 1908T allele tended to be associated with cerebral vascular disease, but was independent of age, hypertension, total cholesterol or triglyceride [odds ratio (OR) 7.03, P=0.0611]. Similarly, the LMNA 1908T allele showed a significant association with diabetic nephropathy, not independent of total cholesterol or triglyceride. CONCLUSIONS: The LMNA 1908C/T polymorphism plays an important role in the development of cerebral vascular disease and diabetic nephropathy in Japanese men with type 2 diabetes.

Aged↗

Antioxidants, von Willebrand factor and endothelial cell injury in hypercholesterolaemia and vascular disease.

The relationship between antioxidants and endothelial cell injury was examined in 119 patients with (n = 48) or without (n = 71) vascular disease who were attending a hyperlipidaemia clinic. Serum levels of total antioxidant capacity, glutathione peroxidase (a protein antioxidant), von Willebrand factor (vWf, a specific endothelial cell product and marker of injury) and routine lipids were measured in the patients and from 58 healthy controls. Compared to controls, total antioxidant capacity (P < 0.01) and glutathione peroxidase (P < 0.0001) were lower whilst vWf was higher (P < 0.0001) amongst the patients. Comparing patients with and without vascular disease, glutathione peroxidase was lower (P < 0.03) and vWf was higher (P < 0.05) in the presence of vascular disease but there was no difference in levels of serum lipids or total antioxidant capacity. vWf and glutathione peroxidase were inversely correlated (r = -0.26, P < 0.005). We conclude that patients with hypercholesterolaemia have reduced antioxidant capacity and this is most severe in patients with clinically apparent vascular disease. This, linked to the finding of increased vWf in hypercholesterolaemia with highest levels in those patients with vascular disease, suggests that loss of antioxidant capacity may expose the vascular endothelium to excess oxidative damage. These results suggest a link between hypercholesterolaemia, impaired ability to resist free radical attack, and the development of atherosclerosis.

Antioxidants↗

Plasma histamine concentrations are elevated in patients with diabetes mellitus and peripheral vascular disease.

Previous work has shown that plasma and tissue concentrations of histamine are elevated in rats with experimental diabetes mellitus and that leucocytes and platelets from patients with peripheral vascular disease have a higher histamine content than those from controls. In the present study, we have measured: (a) plasma histamine concentrations; (b) leucocyte and platelet histidine decarboxylase (the enzyme responsible for the biosynthesis of histamine) in patients with diabetes mellitus (Types I and II) and peripheral vascular disease; and (c) platelet and leucocyte histamine content. Plasma histamine concentration was significantly higher in patients with diabetes and peripheral vascular disease respectively than that in age-matched controls. Leucocyte histidine decarboxylase activity in diabetic and peripheral vascular disease patients was similar to that in controls, while platelets had no histidine decarboxylase activity. The leucocyte and platelet content of histamine were greater in patients with peripheral vascular disease than those in controls, but they were not altered in diabetic patients. There was no correlation between plasma histamine concentration, leucocyte and platelet histamine content, and histidine decarboxylase activity. We conclude that plasma histamine is elevated in diabetics and in patients with peripheral vascular disease and that platelet and leucocyte histamine content is increased in the latter. This increase in platelet and leucocyte histamine content is not due to an increase in histidine decarboxylase activity of these cells. The increase in plasma and cellular histamine content may contribute to the pathogenesis of increased endothelial permeability in diabetes and to the pathogenesis of intimal damage in atherosclerosis.

Adult↗

[Epidemiologic study on peripheral vascular diseases in Shanghai].

Epidemiologic investigation and study were made on peripheral vascular diseases in Shanghai area during 1988 and 1989. The total number of examined subjects was 30,712, including peasants and workers from heavy and light industries. The number of the subjects suffered from peripheral vascular diseases was 2,679, with an incidence of 8.72%. Among them, varicosity of the superficial veins in the lower extremities was found in 2,577, and other peripheral vascular diseases were found in 102. Risk factors for varicose veins include hard labour, body mass, standing, pregnancy and sitting. New concepts about the varicose veins were advanced by the authors.

Adolescent↗

Dipyridamole for preventing stroke and other vascular events in patients with vascular disease.

BACKGROUND: Patients with limited cerebral ischaemia of arterial origin are at risk of serious vascular events (4% to 11% annually). Aspirin reduces that risk by 13%. In one trial, adding dipyridamole to aspirin was associated with a 22% risk-reduction compared with aspirin alone. However, a systematic review of all trials of antiplatelet agents by the Antithrombotic Trialists' Collaboration showed that, in high-risk patients, there was virtually no difference between the aspirin-dipyridamole combination and aspirin alone. OBJECTIVES: To assess the efficacy and safety of dipyridamole versus control in the secondary prevention of vascular events in patients with vascular disease. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (searched November 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to November 2005) and EMBASE (1980 to November 2005). SELECTION CRITERIA: Randomised long-term secondary prevention trials with concealed treatment allocation, treatment for more than one month, starting within six months after presentation of an arterial vascular disease were selected. Treatment consisted of dipyridamole with or without other antiplatelet drugs compared with no drug or an antiplatelet drug other than dipyridamole. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion, assessed trial quality and extracted data. Data were analysed according to the intention-to-treat principle. MAIN RESULTS: Twenty-seven trials were included, with 20242 patients, among whom 1399 vascular deaths and 3090 fatal and non-fatal vascular events occurred during follow up. Compared with control, dipyridamole had no clear effect on vascular death (relative risk (RR) 1.02, 95% confidence internal (CI) 0.90 to 1.17). This result was not influenced by the dose of dipyridamole or type of presenting vascular disease. In the presence of aspirin, dipyridamole appeared to reduce the risk of vascular events compared with control (RR 0.90, 95% CI 0.82 to 0.97), due to a single large trial in patients presenting with cerebral ischaemia. AUTHORS' CONCLUSIONS: For patients who presented with arterial vascular disease, there was no evidence that dipyridamole, in the presence or absence of another antiplatelet drug reduced the risk of vascular death, though it may reduce the risk of further vascular events. However, this benefit was found in only one single large trial and only in patients presenting after cerebral ischaemia. There was no evidence that dipyridamole alone was more efficacious than aspirin. Further trials comparing the effects of the combination of dipyridamole with aspirin versus aspirin alone are justified.

Anticoagulants↗

Endothelial cell expression of adhesion molecules is induced by fetal plasma from pregnancies with umbilical placental vascular disease.

OBJECTIVE: To test the hypothesis that local production with spill into the fetal circulation of factor(s) injurious to endothelium is responsible for the vascular pathology present when the umbilical artery Doppler study is abnormal. Expression of adhesion molecules is a feature of endothelial cell activation. DESIGN: Case-control study. SETTING: University teaching hospital. SAMPLES: Fetal plasma was collected from 27 normal pregnancies, 39 pregnancies with umbilical placental vascular disease defined by abnormal umbilical artery Doppler and 11 pregnancies with pre-eclampsia and normal umbilical artery Doppler. METHODS: Isolated and cultured human umbilical vein endothelial cells from normal pregnancies were incubated with fetal plasma from three study groups. mRNA expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) were assessed by reverse transcription-polymerase chain reaction. To confirm the occurrence of this in vivo, we measured the levels of soluble fractions of sICAM-1, sVCAM-1 and sPECAM-1 in the fetal circulation in the fetal plasma used for endothelial cell incubation. RESULTS: The mRNA expression of ICAM-1 [median 1.1 (interquartile range 0.5-1.9) vs 0.7 (0.3-1.2), P < 0.05] and PECAM-1 [2.1 (1.2-3.0) vs 1.5 (0.7-2.1), P < 0.05] was significantly higher following incubation with fetal plasma from umbilical placental vascular disease compared with the normal group. There was no difference in the expression of VCAM-1 [1.2 (0.9-1.8) vs 1.1 (0.8-1.6), ns]. The group with maternal pre-eclampsia and normal umbilical artery Doppler did not differ from the normal group. In the umbilical placental vascular disease group, the results were similar in the presence or absence of pre-eclampsia. For soluble fractions of the adhesion molecules released into the fetal circulation, we found the levels (ng/mL) of sICAM- I [median 248.5 (interquartile range 197.3-315.7) vs 174.2 (144.5-212.9), P < 0.05] and sPECAM-1 [9.3 (6.2-11.1) vs 6.1 (5.4-7.7), P < 0.05] in fetal plasma to be significantly increased in the presence of umbilical placental vascular disease compared with the normal. CONCLUSIONS: Vascular disease in the fetal umbilical placental circulation is associated with an elevation in mRNA expression by endothelial cells of ICAM-1 and PECAM-1. Our study provides evidence for endothelial cell activation and dysfunction in umbilical placental vascular disease. We speculate that the plasma factor(s) affecting the vessels of the umbilical villous tree is locally released by the trophoblast. The occurrence of the maternal syndrome of pre-eclampsia appears to be independent of this.

Adult↗

Collagen vascular diseases: cutaneous manifestations in ophthalmology.

PURPOSE: To describe the effects of collagen vascular diseases on the eyelids and periorbital tissues. METHODS: Retrospective review of dermatologic pathology slides at Massachusetts General Hospital and eye pathology slides at Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. RESULTS: A spectrum of dermatologic manifestations of collagen vascular diseases was observed, affecting the eyelids and periorbital region. CONCLUSIONS: Collagen vascular diseases may present complicated diagnostic and clinical challenges for the practicing ophthalmologist. Familiarity with the cutaneous periocular manifestations of these diseases may facilitate early recognition, diagnosis, and ophthalmologic intervention where necessary.

Collagen Diseases↗

Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine metabolism and late-onset vascular disease.

BACKGROUND: Increased homocysteine levels are a risk factor for atherosclerosis and its sequelae. A common genetic mutation in methylenetetrahydrofolate reductase (MTHFR), an enzyme required for efficient homocysteine metabolism, creates a thermolabile enzyme with reduced activity. We determined the prevalence of this mutation in many subjects with and without vascular disease and related it to homocysteine and folate levels. METHODS AND RESULTS: DNA from 247 older subjects with vascular disease and 594 healthy subjects without vascular disease (in three different control groups) was screened for the MTHFR 677 C-to-T mutation. Within each group, 9% to 17% of the subjects were homozygous for this mutation, and the mutant allele frequency was 31% to 39%. The genotype distributions, homozygote frequencies, and allele frequencies did not differ significantly between the study groups. In the vascular disease subjects, despite significantly lower folate levels in MTHFR homozygotes, there was no significant difference in homocysteine levels among the MTHFR genotype groups. The negative slope of the regression line relating homocysteine and folate was significantly steeper for those with a homozygous MTHFR mutation compared with those without this mutation. CONCLUSIONS: Although the thermolabile MTHFR mutation is very common, it does not appear to be a significant genetic risk factor for typical late-onset vascular disease. Because MTHFR homozygotes have increased homocysteine with low folate levels, this mutation may contribute to early-onset or familial vascular disease. The genotype dependence of the folate-homocysteine correlation further suggests that homozygotes for this mutation may have both an exaggerated hyperhomocysteinemic response to folic acid depletion and a better response to folic acid therapy.

Adult↗

Plasma total cysteine as a risk factor for vascular disease: The European Concerted Action Project.

BACKGROUND: Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease. Although cysteine is structurally similar and metabolically linked to tHcy, its relation to the risk of cardiovascular disease has received little attention. We studied the relation between plasma total cysteine (tCys) levels and the risk of vascular disease in the coronary, cerebral, and peripheral vessels. METHODS AND RESULTS: This case-control study included 750 patients with vascular disease and 800 age- and sex-matched control subjects recruited from 19 centers in 9 European countries. Conventional risk factors for cardiovascular disease were recorded. In addition, plasma levels of tCys, tHcy, folate, B(6), B(12), and creatinine were measured. Overall, a U-shaped relationship was observed between tCys and risk of vascular disease. With the middle range of 250 to 275 micromol/L tCys used as the reference category, the adjusted risk of vascular disease at low (</=225 micromol/L) tCys levels was 2.1 (95% CI 1.2 to 3.6), and the risk at high (>300 micromol/L) tCys levels was 1.6 (95% CI 1.1 to 2.3). Different shapes of the dose-response relationship were seen for the 3 vascular disease categories. The relation with peripheral vascular and cerebrovascular disease was U-shaped, whereas a weak positive relation was observed with coronary heart disease. CONCLUSIONS: Our data show a significant U-shaped relationship between tCys and cardiovascular disease after adjustment for tHcy, creatinine, and other cardiovascular disease risk factors.

Adult↗

[Vascular diseases in 534 Swiss diabetics within the scope of a multinational study].

In Switzerland 278 diabetic men and 256 women in the age group 35 to 54 were examined for the presence of angiopathic lesions, according to a standardized protocol of a multinational study comprising 6,695 diabetics from 14 countries. The diabetics were distributed according to sex, age, and duration of the disease into groups of equal size. Macro-angiopathy, as the sum of coronary heart disease, stroke, and vascular disease of the legs was found in 28% of men and in 29% of women in the Swiss group. The prevalence of myocardial infarction alone was 6.8% in men and 5.5% in women. These rates did not differ from those found in the other national groups. Micro-angiopathy was found in the form of retinopathy in 35% and as nephropathy in 32% of the Swiss diabetics. These rates were not different from those of all groups. Severe retinopathy was found more frequently in Swiss diabetics than in the whole study. Micro-angiopathy was strongly related to duration, hypertension, and type of treatment in all centres. Japanese diabetics showed a higher frequency of micro-angiopathy, although macrovascular disease was found at a low rate. Systolic blood pressure (BP) in the Swiss diabetics did not differ from the results of the whole group. In 14% of the Swiss diabetic men and in 18% of the women, systolic BP was over 160 mmHg. These rates were remarkably higher than in an age- and sex-matched sample of a randomly selected sample of a Swiss population (3.2% in men, 2.4% in women). Cholesterol was high in the Swiss diabetic groups, whereas body mass index was in the intermediate range. Of the Swiss diabetic men 38% smoked regularly. The frequency of coronary heart disease in Swiss men and women was similar. This is different from the lower rate usually found in non-diabetic women. Age, and not duration of the disease was the most important factor relating to macro-angiopathy. The different rates of macro- and microvascular complications in various populations, selected according to the same protocol, suggests that the risk factors for macrovascular disease differ from those of microvascular complications. Race, nutrition, treatment, exercise, and hypertension may further influence the prevalence of angiopathy in diabetics of same sex, age, and duration of the disease.

Adult↗

Cochrane review: dipyridamole for preventing major vascular events in patients with vascular disease.

BACKGROUND: Patients enrolled in clinical trials after nondisabling cerebral ischemia have an annual risk of vascular events (death from all vascular causes, nonfatal stroke, or nonfatal myocardial infarction) of 4% to 11%. Aspirin reduces the incidence by 13%. Many trials in patients presenting with vascular disease investigated the efficacy of (addition of) dipyridamole in secondary prevention. We systematically compared the efficacy and safety of dipyridamole versus control in the presence and absence of other antiplatelet drugs in clinical trials on the secondary prevention of vascular events in patients with vascular disease. SUMMARY OF REVIEW: Randomized trials with concealed treatment allocation in patients with a nonembolic arterial vascular disease were selected. Therapy consisted of dipyridamole in the presence or absence of other antiplatelet drugs compared with no drug or an antiplatelet drug(s) other than dipyridamole. Twenty-six trials were included, with a total of 19 842 patients. Dipyridamole was not more efficacious in the prevention of vascular death (relative risk [RR], 1.02; 95% CI, 0.90 to 1.17). It appeared more efficacious in the prevention of vascular events (RR, 0.90; 95% CI, 0.83 to 0.98), but this result only reached statistical significance because of 1 large trial in patients presenting with cerebral ischemia. Combination treatment of dipyridamole and aspirin compared with aspirin had an RR of 1.03 (95% CI, 0.87 to 1.22) for vascular death and an RR of 0.90 (95% CI, 0.80 to 1.00) for vascular events. CONCLUSIONS: For patients who presented with arterial vascular disease, there was no evidence that dipyridamole, in the presence or absence of another antiplatelet drug (chiefly aspirin), reduced the risk of vascular death, although it may reduce the risk of further vascular events. However, this benefit was found only in a single large trial and only in patients presenting after cerebral ischemia. There was no evidence that dipyridamole alone was more efficacious than aspirin. Further trials comparing the effects of the combination of dipyridamole plus aspirin with aspirin alone are justified.

Death, Sudden, Cardiac↗

Free-tissue transfer in patients with peripheral vascular disease: a 10-year experience.

Advances in free-tissue transfer have allowed for lower limb salvage in patients with significant peripheral vascular disease and limb-threatening soft-tissue wounds. The authors retrospectively reviewed their 10-year experience with free flaps for limb salvage in patients with peripheral vascular disease to assess postoperative complication rates and long-term functional outcome. They identified all patients undergoing free-tissue transfer with significant peripheral vascular disease and otherwise unreconstructible soft-tissue defects. Charts were reviewed for perioperative and long-term outcome. Parameters studied included perioperative morbidity and mortality, flap success, bypass graft patency, ambulatory results, and long-term limb and patient survival. Survival data were analyzed using life-table analysis, Kaplan-Meier survival analysis, and Cox testing. A total of 79 flaps were examined in 75 patients with peripheral vascular disease from July of 1990 to November of 1999. All patients would have required a major amputation had free-tissue transfer not been performed. Mean age was 60 years, average hospital stay was 32 days, and perioperative mortality was 5 percent. Within the first 30 days after operation, there were four cases of primary flap loss, and another two were lost as the result of bypass graft failure (8 percent); five of these cases resulted in amputation. There were no primary flap failures after 30 days. Follow-up ranged to 91 months (mean, 24 months). During this time, another 14 limbs were lost, most commonly because of progressive gangrene and/or infection in sites remote from the still-viable free flap. Using Kaplan-Meier survival analysis, 5-year flap survival was 77 percent, limb salvage 63 percent, and patient survival 67 percent. Sixty-six percent of patients were able to ambulate independently with the use of their reconstructed limb at least 1 year after hospital discharge, although some of these later went on to amputation. Free-tissue transfer for lower extremity reconstruction can be performed with acceptable morbidity and mortality in patients with peripheral vascular disease. Flap loss is low, and limb salvage, ambulation, and long-term survival rates in these patients are excellent.

Follow-Up Studies↗

Peripheral vasodilators and the management of peripheral vascular disease and Raynaud's syndrome in general practice.

There is no convincing evidence that peripheral vasodilators produce any significant improvement in exercise tolerance in patients with peripheral vascular disease, and these drugs may do more harm than good. In the treatment of severe Raynaud's syndrome, however, thymoxamine, prazosin or nifedipine is recommended. A descriptive study was carried out, firstly, to determine why these drugs are prescribed in general practice, and secondly, to describe the drug choices in the treatment of both Raynaud's syndrome and peripheral vascular disease in a representative sample of 22 practices in Northern Ireland. Of those patients prescribed peripheral vasodilators 69.6% were diagnosed as peripheral vascular disease, claudication or atherosclerosis. Over three-quarters of peripheral vasodilators prescribed were repeat prescriptions. Of those with Raynaud's syndrome only half were treated appropriately, and certainty of diagnosis did not guarantee appropriate treatment. Peripheral vasodilators accounted for the majority (51.5%) of items prescribed for peripheral vascular disease. A minority of patients with peripheral vascular disease (20.3%) were prescribed aspirin, and a smaller minority (4.4%) had undergone amputation. Peripheral vasodilators were prescribed unnecessarily and inappropriately. Measures to promote evidence-based treatment of both Raynaud's syndrome and peripheral vascular disease in general practice need to be taken.

Journal Article↗

Dose-response relationship between peripheral vascular disease and ingested inorganic arsenic among residents in blackfoot disease endemic villages in Taiwan.

The purpose of this study was to examine the correlation between previous arsenic exposure and peripheral vascular disease after stopping consumption of high-arsenic artesian well water for more than two decades in blackfoot disease endemic villages in Taiwan. A total of 582 adults (263 men and 319 women, aged 52.6 +/- 10.6 years) living in these villages underwent Doppler ultrasound measurement of systolic pressures on bilateral ankle (posterior tibial and dorsal pedal) and brachial arteries and estimation for long-term arsenic exposure. The diagnosis of peripheral vascular disease was based on an ankle-brachial index (the ratio between ankle and brachial systolic pressures) <0.90 on either side. Three indices of arsenic exposure were estimated: (1) duration of living in blackfoot disease endemic villages; (2) duration of artesian well water consumption; and (3) cumulative arsenic exposure in mg/l-years based on the detailed history of residential addresses and artesian well water consumption and the arsenic concentration in artesian well water. Multiple logistic regression analysis was used to assess the association between peripheral vascular disease and arsenic exposure. A dose-response relation was observed between the prevalence of peripheral vascular disease and the long-term arsenic exposure. The odds ratios (95% confidence intervals) after adjustment for age, sex, body mass index, cigarette smoking, serum cholesterol and triglyceride levels, diabetes mellitus and hypertension were 2.77 (0.84-9.14), and 4.28 (1.26-14.54) for those who had cumulative arsenic exposure of 0.1-19.9 and > or = 20.0 mg/l-years, respectively, compared with those who were not exposed. This study suggests a close relation between long-term arsenic exposure and peripheral vascular disease in blackfoot disease endemic villages in Taiwan after stopping consumption of artesian well water.

Adult↗