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Effect of apheresis of low-density lipoprotein on peripheral vascular disease in hypercholesterolemic patients with coronary artery disease.

BACKGROUND: Apheresis of low-density lipoprotein (LDL) is an effective lipid-lowering treatment in hypercholesterolemic patients who have coronary artery disease and are refractory to drugs. More aggressive lipid-lowering therapy may further slow the progression of atherosclerosis. OBJECTIVE: To compare the effect of LDL apheresis and simvastatin therapy with the effect of simvastatin therapy alone on the progression of peripheral vascular disease. DESIGN: Open, randomized, single-center study. SETTING: University hospital. PATIENTS: 42 men with primary hypercholesterolemia (total cholesterol level > 8.0 mmol/L) and extensive coronary atherosclerosis. INTERVENTION: Biweekly apheresis of LDL plus simvastatin, 40 mg/d (n = 21), or simvastatin, 40 mg/d (n = 21), for 2 years. MEASUREMENTS: Lipid and lipoprotein levels, changes in hemodynamically significant stenoses in the aortotibial tract (measured by ankle:arm systolic blood pressure ratio combined with Doppler spectrum analysis of the femoral artery), and changes in the mean intima-media thickness of three carotid artery segments. RESULTS: Mean baseline LDL cholesterol levels decreased from 7.8 to 3.0 mmol/L in the apheresis and simvastatin group and from 7.9 to 4.1 mmol/L in the simvastatin-only group; mean lipoprotein(a) levels decreased from 57.0 to 44.5 mg/dL (change, -19%) in the former group and increased from 38.4 to 44.5 mg/dL (change, 15%) in the latter group. In the apheresis group, the number of patients with hemodynamically significant stenoses in the aortotibial tract decreased from 9 to 7; in the simvastatin-only group, the number increased from 6 to 13 (P = 0.002). Mean intima-media thickness decreased by a mean +/- SD of 0.05 +/- 0.34 mm in the apheresis group and increased by 0.06 +/- 0.38 mm in the simvastatin-only group (P < 0.001). According to multiple regression analysis, changes in apolipoprotein B, total cholesterol, and lipoprotein(a) levels accounted for changes in the aortotibial tract (R2 = 0.36); changes in lipoprotein(a) and apolipoprotein A1 levels accounted for changes in the intima-media thickness of the carotid artery (R2 = 0.49). CONCLUSIONS: Aggressive lipid lowering with simvastatin and LDL apheresis decreased the intima-media thickness of the carotid artery and prevented an increase in the number of hemodynamically significant stenoses in the lower limbs. Therapy with simvastatin alone did not prevent progression of carotid or aortotibial vascular disease.

Adult↗

Tissue concentrations of ofloxacin in necrotic lesions in patients with peripheral vascular disease and in diabetics.

In a pilot study six patients (three diabetics with gangrenous lesions of the lower limbs, mean age 74 years, three patients with peripheral vascular disease stage IV according to Fontaine, mean age 70 years) were treated with 200 mg ofloxacin orally b.i.d. The tissue concentrations of ofloxacin in the necrotic material (1.6 to 6.4 mg/kg) were in the same range as the plasma levels (2.3 to 5.9 mg/l) or even higher. In conclusion, besides local therapy, ofloxacin seems to be effective in the systemic treatment of infected necrotic and gangrenous lesions.

Aged↗

Characterisation of post exercise pressure response curves in the pedal arteries of patients with peripheral vascular disease.

The response of the systolic pressure in the pedal arteries to the stress of exercise is one of several ways of assessing the severity of peripheral vascular disease. We have examined 2607 such pressure response curves in an attempt to produce a simple method of response classification. Regression analysis of the curves has shown that errors are least when the regression used is the same order as the number of data points. We conclude that post exercise response curves can be adequately classified from three data points, one obtained within two minutes of the cessation of exercise, a second obtained between 4 and 6 minutes from the end of exercise and a third taken 10 minutes after exercise. The use of a response curve indexed to systemic systolic pressure was not found to produce a better correlation between full and three point curves, though the absolute classification differed slightly from that obtained from the non-indexed curve. Neither classification system proved significantly superior in relating to the degree of arterial disease.

Arteries↗

Effect of buflomedil chlorhydrate on local oxygen delivery in peripheral vascular disease.

Modifications in transcutaneous oxygen pressure (TcPO2), induced by the administration of 3 mg/kg/day buflomedil chlorhydrate for seven days were evaluated in 12 subjects suffering from peripheral vascular disease (PVD). After the treatment a significant increase in TcPO2 basal values was observed in Stage III and Stage IV PVD patients (+32.2%) while a significant reduction of 12% in the half-recovery time to basal values after an induced ischemia was recorded in Stage II PVD patients by the seventh day. Buflomedil did not, however, cause any significant variations in the ankle/arm pressure ratio or in the plethysmographic peak flow.

Aged↗

Ketanserin in the treatment of diabetic foot ulcer with severe peripheral vascular disease.

The aim of this study was to evaluate if ketanserin, a selective serotoninantagonist, could improve wound healing in diabetic patients with foot ulcers and severe peripheral vascular disease. In a double blind study 40 diabetic patients with foot ulcer and a systolic toe pressure below 45 mmHg were randomly allocated to either ketanserin (20-40 mg three times a day) or placebo for a period of 3 months. The treatment was carried out on an out-patient basis by a combined medical/orthopedic foot care team at the Department of Internal Medicine, University Hospital, Lund, Sweden. Both groups were comparable regarding age, sex, duration and treatment of diabetes, cardiovascular disease and type of lesion. Wound healing (defined as intact skin for at least 3 months) or wound size reduction of 50% or more were sen in 11 out of 19 (58%) in the ketanserin group and in 7 out of 19 (37%) in the placebo group. Gangrene developed in 6 patients with placebo and 2 with ketanserin. Two patients died during the study and their ulcers were not evaluated. The systolic toe pressure was measured at admission, at end of run in, after 1 month and 3 months with strain gauge technique. Only one out of nine patients (11%) with a toe pressure below 30 mmHg in the placebo group healed or improved their ulcers compared to nine out of 16 (56%) in the ketanserin group. The healing rate in the ketanserin group was higher than expected considering the lower systolic toe pressure in this group compared to placebo at randomization (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Lower extremity amputees with peripheral vascular disease: graded exercise testing and results of prosthetic training.

Thirty-nine subjects, mean age 72 (range 52 to 89), with a leg amputation because of peripheral vascular disease performed graded exercise testing at the start of their prosthetic training program. Their walking performance at the end of the program was assessed and compared with the test findings. They had a history and rest electrocardiogram (ECG) examination which revealed cardiac problems in 75% of the patients. The exercise test was performed on a specially designed arm ergometer permitting coordinated exercise of arm and trunk muscles. Cardiac condition was judged by the achieved peak heart rate (mean 125 +/- 3.8 beats per minute) and observed ECG abnormalities. In only three patients exercise-induced ECG abnormalities were found at peak workload. The mean peak workload was 52 +/- 1.9W. It was concluded from these results that the average physical and cardiac condition is poor in vascular leg amputees. In 34 patients (87%) the prosthetic training was successful. Fourteen patients needed a walking frame and twenty could walk without a walking frame. The probability of achieving walking without a walking frame was 70% in patients with peak workload above 45W and 30% in those with peak workload lower than 45W.

Aged↗

Ischemia-modified albumin concentrations in patients with peripheral vascular disease and exercise-induced skeletal muscle ischemia.

BACKGROUND: Ischemia-modified albumin (IMA) is a new marker of myocardial ischemia, there is concern that IMA concentrations may be affected by ischemia occurring in tissues other than the myocardium. METHODS: We assessed 23 consecutive patients (15 males; mean age, 67 years) with typical leg claudication and documented peripheral vascular disease (PVD). All patients underwent both treadmill-exercise stress testing to induce leg ischemia and dobutamine stress echocardiography 1 week apart for the assessment of myocardial ischemia. Blood samples for IMA measurements were obtained at baseline, immediately after peak exercise/stress, and 1 h after exercise/stress. Statistical analysis was performed with the ANOVA repeated-measures test. RESULTS: Compared with baseline, mean (SD) IMA was significantly lower after the induction of skeletal muscle ischemia and returned to baseline values at 1 h: baseline, 74.6 (15.6) kilounits/L; peak stress, 69.5 (14.0) kilounits/L (P <0.0001 vs baseline); 1 h after stress, 75.9 (15.7) kilounits/L (P <0.0001 vs peak stress; P = 0.3 vs baseline). Baseline, peak stress, and 1-h poststress IMA concentrations were inversely correlated with the ankle-brachial index after exercise (r = -0.4; P <0.05). None of the patients showed regional wall motion abnormalities during dobutamine stress echocardiography, and IMA concentrations remained unchanged from baseline. There were no differences in baseline [74.6 (15.6) vs 72.7 (11.5) kilounits/L; P = 0.6], peak stress, or poststress IMA concentrations when exercise testing and dobutamine stress echocardiography values were compared. CONCLUSIONS: The relationship between disease severity (of a noncardiac origin) and baseline IMA values is an important and novel finding. IMA is significantly lower immediately after exercise-induced leg ischemia in patients with PVD and is related to disease severity. IMA concentrations can therefore be affected by the development of skeletal muscle ischemia, and this may have implications regarding the ability of IMA to detect myocardial ischemia in PVD patients.

Aged↗

Lowering of plasma viscosity by the oral administration of the glycosaminoglycan sulodexide in patients with peripheral vascular disease.

The aim of the double-blind, crossover, placebo-controlled study was to evaluate whether oral administration of sulodexide, a medium molecular weight glycosaminoglycan, had an effect on whole blood, plasma and serum viscosity, and/or plasma fibrinogen concentrations. The drug was administered orally at a dose of 500 lipoproteinlipase releasing units twice daily for 1 month to two groups of 20 patients with peripheral vascular disease; one group was administered a placebo--drug sequence and the other a drug--placebo sequence. Orally administered sulodexide had a marked effect on plasma viscosity and on plasma fibrinogen concentrations, whereas there were no effects on whole blood viscosity. No significant side-effects were observed. The fact that sulodexide was highly effective, even after oral administration, suggests it may be useful for the treatment of patients with atheromatous vascular diseases of the lower limbs requiring chronic therapy.

Administration, Oral↗

MR angiography with gadofosveset trisodium for peripheral vascular disease: phase II trial.

PURPOSE: To evaluate the dose response and safety of gadofosveset trisodium-enhanced magnetic resonance (MR) angiography compared with nonenhanced two-dimensional time-of-flight MR angiography and with x-ray angiography as the standard. MATERIALS AND METHODS: In this randomized, 20-center, double-blind study, 238 men and women who had peripheral vascular disease or were suspected of having it received intravenous injection of placebo or gadofosveset (0.005, 0.01, 0.03, 0.05, or 0.07 mmol per kilogram of body weight). MR angiographic images were evaluated by three blinded readers, and x-ray angiographic images were evaluated by two readers. Hypothesis testing for the presence of a dose response was based on a linear test for trend for increase in area under the receiver operating characteristic curve as a function of dose for each reader of MR angiographic images independently. RESULTS: Gadofosveset administration resulted in a dose-dependent increase in diagnostic accuracy for detection of aortoiliac occlusive disease as reflected in the area under the receiver operating characteristic curve for each reader (P <.001). The plateau in effectiveness improvement began at the 0.03 mmol/kg dose. At doses of 0.03 mmol/kg and higher, gadofosveset-enhanced MR angiography provided an approximate 20% increase in accuracy over nonenhanced MR angiography for diagnosis of clinically significant aortoiliac occlusive disease. Gadofosveset exhibited a good safety profile in all dose groups. Three serious adverse events were possibly or probably related to gadofosveset administration. There were no dose-related trends in severe or serious adverse events in patients receiving gadofosveset. CONCLUSION: A dose of 0.03 mmol/kg of gadofosveset was safe and effective for evaluation of aortoiliac occlusive disease with MR angiography.

Adult↗

Magnetic resonance morphological, chemical shift and flow imaging in peripheral vascular disease.

We have used magnetic resonance imaging to study the aorto-iliac region in 13 patients with peripheral disease. Five healthy volunteers were studied for comparison. Magnetic resonance spin-echo imaging, chemical shift imaging to determine lipid content of atheroma, phase-shift velocity mapping and quantitative flow studies were obtained and the findings compared with radiological angiograms. The velocity profiles study showed an increased velocity at the site of a stenosis in eight patients who had iliac artery disease. Quantitative flow measurements made in both iliac arteries and the aorta in five patients and five volunteers showed a flow ratio in both iliac arteries less than 0.85 in patients with a stenosis of one iliac artery and a ratio greater than 0.85 in the volunteers. In one patient studied before and after angioplasty, flow improved post-angioplasty. The flow curve showed a characteristic distortion in diseased vessels compared with healthy vessels. In the chemical shift images of aortic atheroma five were classified as fibrous and three were lipid rich. This preliminary study showed the potential of magnetic resonance to assess non-invasively the morphology, composition and the haemodynamic significance of atheroma. This could be important in the study of the progression of peripheral vascular disease and its response to pharmacological and surgical intervention and in the planning treatment of lesions.

Adult↗

Effects of lifestyle modification and lipid intake variations on patients with peripheral vascular disease.

The aim of the present study was to evaluate the effects of diets enriched in monounsaturated fatty acids (MUFA) (olive oil) or MUFA plus n-3 polyunsaturated fatty acids (PUFA) (olive oil plus fish oil), associated with an intervention program that focused on lifestyle habits, physical performance, plasma lipids, and lipoprotein composition in patients with peripheral vascular disease (PVD). A 15-month longitudinal nutritional and lifestyle intervention study was carried out with 24 free-living male patients aged 58.0 +/- 2.2 years diagnosed with PVD (Fontaine grade II). The patients were clinically evaluated and counseled to change their dietary and lifestyle habits for six months, after this period they consumed an olive oil-based diet for three months: after a three-month wash-out period, their diet was supplemented with a combination of fish oil and olive oil for the final three months. Lifestyle interventions resulted in a significant decrease in cigarette smoking and an increase in physical activity. Claudicometry was lower at the end of the study than at the beginning. Intake of the fish oil supplement led to significant changes in lipid lipoprotein composition, decreasing low-density lipoprotein (LDL) cholesterol. The lifestyle intervention program, together with a high intake of olive plus fish oil, seems to produce important beneficial effects in nutritional management, physical performance, and clinical parameters of PVD patients.

Biomarkers↗

The iron (Fe) and atherosclerosis study (FeAST): a pilot study of reduction of body iron stores in atherosclerotic peripheral vascular disease.

BACKGROUND: Levels of body iron stores, represented by the serum ferritin concentration, rise with age after adolescence in men and menopause in women. This rise has been implicated mechanistically and epidemiologically in the pathogenesis of atherosclerosis through iron-induced oxygen free radical-mediated lipid oxidation. However, the precise contribution of iron stores to atherosclerosis and its complications are unknown because prospective randomized trials designed to test effects of reduction of iron stores on clinical outcomes in this disease have not been performed. METHODS AND RESULTS: In preparation for a prospective randomized trial, a randomized pilot study was conducted to evaluate the feasibility, safety, and methodologic accuracy of calibrated reduction in iron stores by phlebotomy in a cohort of patients with advanced peripheral vascular disease. Phlebotomy resulted in a significant reduction in serum ferritin concentration to near targeted levels. Thus the formula for calculating the volume of blood to be removed to achieve a predetermined decrement in serum ferritin concentration was accurate and phlebotomy was not associated with any adverse laboratory or clinical effects. CONCLUSIONS: Reduction of body iron stores to a predetermined level is feasible and can be achieved in a timely manner with excellent patient compliance. Prospective randomized trials of calibrated reduction of body iron stores may be undertaken to define their pathophysiologic significance in atherosclerosis and other diseases in which excessive iron-induced oxidative stress has been implicated.

Aged↗

Peripheral vascular disease: blinded study of dedicated calf MR angiography versus standard bolus-chase MR angiography and film hard-copy angiography.

PURPOSE: To compare the accuracy of contrast material-enhanced three-dimensional (3D) dedicated calf magnetic resonance (MR) angiography with that of bolus-chase MR angiography, with conventional angiography as the reference standard, in patients with symptomatic peripheral vascular disease (PVD). MATERIALS AND METHODS: Thirty men with symptomatic PVD were examined. MR angiography was performed at 1.5 T before conventional angiography. MR angiographic examination included 3D contrast-enhanced dedicated calf MR angiography and three-station bolus-chase MR angiography. Two radiologists blinded to conventional angiographic results evaluated the MR angiograms independently. Two angiographers evaluated the conventional angiograms in consensus. Calf artery segments were graded as having 50% or less stenosis, greater than 50% stenosis, or occlusion or as being nondiagnostic. Statistical analyses were performed with paired permutation testing. RESULTS: Analyses of 472 calf segments and 420 pelvic and thigh segments were performed. Of the 472 calf segments, three and 75 segments (reader 1) and seven and 91 segments (reader 2) were graded as nondiagnostic at dedicated calf MR angiography and bolus-chase MR angiography, respectively. Differences in diagnostic grade between the two examinations were significant (P <.001), accounting for within-subject correlations, with a mean estimated difference of -17.1% (95% confidence interval [CI]: -25.8%, -8.4%). In the calf arteries, the dedicated and bolus-chase MR angiographic sequences had diagnostic accuracies, respectively, of 81.5% (reader 1) and 79.1% (reader 2) and of 67.8% (reader 1) and 63.4% (reader 2). The dedicated calf sequence was significantly more accurate than the bolus-chase sequence (P =.001). The point estimate of the difference was 14.7%, with estimated correct diagnosis rates of 80.3% and 65.6% for the dedicated calf and bolus-chase examinations, respectively (95% CI for difference: 4.0%, 25.4%). The diagnostic accuracy of bolus-chase MR angiography at the pelvis-thigh level was slightly higher when it was performed first: 81.9% (reader 1) and 83.8% (reader 2) versus 74.3% (reader 1) and 80.0% (reader 2) when it was performed last. The difference was not significant (P =.21). CONCLUSION: Use of dedicated calf MR angiography led to significantly increased diagnostic accuracy in the calf arteries compared with standard bolus-chase MR angiography. Use of the dual-bolus technique did not jeopardize the diagnostic accuracy in the pelvic and thigh arteries.

Aged↗

Endovascular brachytherapy for peripheral vascular disease.

The most common cause of morbidity and mortality in the United States is vascular disease, which afflicts a wide spectrum of organs such as the heart (cardiovascular system), brain (cerebrovascular system), kidney (renal system), liver (hepatic system), and extremities (peripheral vascular system). The most common pathology of vascular diseases is occlusion. Percutaneous Transluminal Angioplasty (PTA) is currently the most common nonsurgical treatment for obstructive arteries. Unfortunately, the long-term effectiveness of PTA is limited by a high restenosis rate. Efforts to reduce post-PTA restenosis, including laser, mechanical atherectomy, intravascular stenting, and pharmacologic agents, have not been successful. With recent advances in the pathogenesis of restenosis, we have learned that the major problem is the intimal hyperplastic reaction in response to vessel injury. Encouraging animal data in the use of various radiotherapeutic approaches to prevent restenosis has led to a large number of multi-national, multicenter, randomized trials on coronary vascular systems. Because early results have been in favor of radiation therapy, and because the basic process of restenosis is similar for coronary and noncoronary vascular systems, many investigators extend the application of radiotherapy to the prevention of restenosis in peripheral vascular systems. However, the clinical scenarios are much different for peripheral vascular systems than for the coronary vascular system. This article discusses the current views of the pathophysiology of restenosis, major clinical trials, and perspectives on future studies. Experimental studies on animal models have documented the profound effects of endovascular brachytherapy in reducing restenosis caused by angioplasty and stenting. Early results of clinical trials are encouraging and confirm these positive results. Long-term follow-up data are needed to show that radiation does prevent, not merely delay, restenosis; Several areas of opportunity exist for both basic science research and clinical studies to enhance our knowledge of the pathophysiology. This would optimize the treatment strategy, maximizing the benefits and minimizing late complications.

Angioplasty, Balloon↗