Peripheral Arterial Occlusive Disease Group Research Articles

Nordic walking versus walking without poles for rehabilitation with cardiovascular disease: Randomized controlled trial

BackgroundWith Nordic walking, or walking with poles, one can travel a greater distance and at a higher rate than with walking without poles, but whether the activity is beneficial for patients with cardiovascular disease is unknown. ObjectiveThis randomized controlled trial was undertaken to determine whether Nordic walking was more effective than walking without poles on walk distance to support rehabilitation training for patients with acute coronary syndrome (ACS) and peripheral arterial occlusive disease (PAOD). MethodsPatients were recruited in a private specialized rehabilitation centre for cardiovascular diseases. The entire protocol, including patient recruitment, took place over 2 months, from September to October 2013. We divided patients into 2 groups: Nordic Walking Group (NWG, n=21) and Walking Group without poles (WG, n=21). All patients followed the same program over 4 weeks, except for the walk performed with or without poles. The main outcome was walk distance on the 6-min walk test. Secondary outcomes were maximum heart rate during exercise and walk distance and power output on a treadmill stress test. ResultsWe included 42 patients (35 men; mean age 57.2±11 years and BMI 26.5±4.5kg/m2). At the end of the training period, both groups showed improved walk distance on the 6-min walk test and treatment stress test as well as power on the treadmill stress test (P<0.05). The NWG showed significantly greater walk distance than the WG (P<0.05). Both ACS and PAOD groups showed improvement, but improvement was significant for only PAOD patients. ConclusionsAfter a 4-week training period, Nordic walking training appeared more efficient than training without poles for increasing walk distance on the 6-min walk test for patients with ACS and PAOD.

The role of Visfatin in atherosclerotic peripheral arterial obstructive disease

Visfatin is an adipokine molecule acting as an essential coenzyme in multiple cellular redox reactions. The increased serum levels of Visfatin have been correlated with metabolic syndrome and endothelial homeostasis. In this study we investigate the possible relationship of Visfatin serum levels with the severity and location of atherosclerotic peripheral arterial occlusive disease (PAOD).Study protocol included 45 consecutive PAOD and 20 Control patients with age >55years old. Definition of PAOD was based in Rutherord’s classification (RC). End-stage PAOD patients (RC-V & -VI) were excluded from study. Data were collected prospectively and included age, gender, atherosclerotic risk factors and the body mass index (BMI). In PAOD patients recorded the PAOD’s clinical stage and the presence of carotid stenosis >50%. PAOD patients divided in two subgroups, those with mild (RC-I & -II) and moderate disease (RC-III & -IV). In all serum samples Visfatin was measured, blindly, twice by anosoenzymatic technique. Statistical analysis was performed by non-parametric Mann-Whitney U test, Pearson’s chi-square, One Way Anova and Kruskall-Wallis tests, as appropriate.The mean Visfatin value in PAOD and Control groups were 38.5±16.0 and 13.9±3.8ng/ml respectively (p<0.0005). In-PAOD subgroup of patients the visfatin values were not affected by demographics, BMI and atherosclerotic risk factors (p>0.05). Univariate analysis showed that severity of PAOD (mild vs severe), presence of carotid stenosis >50% and multilevel disease significantly affected outcomes (p=0.018, p=0.010 and p=0.006 respectively). In multivariate regression analysis severity of PAOD was the solely factor with strong correlation with high visfatin values (p=0.001).High Visfatin levels seem to be strongly correlated with the presence and severity of PAOD. Further and in depth investigation is needed to define the possible role of Visfatin in atherosclerosis and it’s value as a potential prognostic biomarker of PAOD.

Expression of high-mobility group box protein 1 in diabetic foot atherogenesis.

The role of high mobility group box 1 (HMGB1) has been demonstrated in stroke and coronary artery disease but not in peripheral arterial occlusive disease (PAOD). The pathogenesis of HMGB1 in acute and chronic vascular injury is also not well understood. We hypothesized that HMGB1 induces inflammatory markers in diabetic PAOD patients. We studied 36 diabetic patients, including 29 patients with PAOD, who had undergone amputation for diabetic foot and 7 nondiabetic patients who had undergone amputation after traumatic injury. Expression of HMGB1 and inflammatory markers were quantified using immunohistochemical staining. Mitochondrial DNA copy number was quantified using real-time polymerase chain reaction. Compared with that in the traumatic amputation group, HMGB1 expression in vessels was significantly higher in the diabetes and diabetic PAOD groups. In all subjects, arterial stenosis grade was positively correlated with the expression levels of HMGB1, 8-hydroxyguanosine, malondialdehyde, vascular cell adhesion molecule 1, and inflammatory markers CD3, and CD68 in both the intima and the media of vessels. Furthermore, HMGB1 expression level was positively correlated with 8-hydroxyguanosine, vascular cell adhesion molecule 1, nuclear factor-kB, CD3, and CD68 expression. Within the PAOD subgroup, subjects with HMGB1 expression had higher expression of the autophagy marker LC3A/B and higher mitochondrial DNA copy number. HMGB1 may be an inflammatory mediator with roles in oxidative damage and proinflammatory and inflammatory processes in diabetic atherogenesis. Moreover, it may have dual effects by compensating for increased mitochondrial DNA copy number and increased autophagy marker expression.

Evaluation of Serum Adipokines in Peripheral Arterial Occlusive Disease

Aim. Out study aimed to assess the serum levels of adipokines in patients with peripheral arterial occlusive disease (PAOD) caused by atherosclerosis. Methods. Serum samples were obtained from 221 patients. One hundred and forty patients, (26 females and 114 males) met the inclusion criteria and were assigned into the case group. Eighty one patients (17 females and 64 males), were included in the control group. Circulating plasma levels of adiponectin, leptin, resistin, and TNF-α were measured using the enzyme-linked immunosorbent assay (ELISA) method. Results. Significant lower levels of adiponectin were present (P = 0.0061) in PAOD patients (2380.23 ± 1634.42 pg/mL) compared to the control group (3065.06 ± 1901.2 pg/mL). The mean value of leptin (2844.42 ± 3301.08 pg/mL) and resistin (2047.81±3301.08 pg/mL) patients included in the PAOD group was higher, as compared to the control group. Statistically significant difference was found between the two groups for leptin (P = 0.0332) and for resistin (P = 0.0352). No statistically significant difference for TNF-α was found between the two groups (P > 0.05). Conclusion. The markers of inflammation secreted by the adipose tissue (adiponectin, leptin, resistin) showed significant differences in patients from the case group (with PAOD) compared to the control group.

The Role of Oxidative Stress and Antioxidant Defenses in Buerger Disease and Atherosclerotic Peripheral Arterial Occlusive Disease

The aim of this study was to determine the status and the role of oxidative stress and antioxidant defenses in patients with Buerger disease and atherosclerotic peripheral arterial occlusive disease (PAOD). Seventy-three subjects resembling each other in general characteristics were involved in the study: 21 with lower extremity PAOD (mean age 53.05 +/- 10.8 years, 17 men and four women), 22 with Buerger disease (mean age 38.59 +/- 6.4 years, 19 men and three women), and 30 healthy volunteers (mean age 38.59 +/- 6.4 years, 22 men and eight women). We measured the levels of plasma malondialdehyde (MDA), paraoxonase (PON1), protein carbonyls, arylesterase, nitric oxide (NO), serum oxidized low-density lipoprotein (ox-LDL) and MDA, glutathione (GSH), glutathione reductase (GSH-red), glutathione peroxidase (GSH-px), superoxide dismutase (SOD), and catalase (CAT) in erythrocytes. Plasma protein carbonyls, serum ox-LDL, and plasma and erythrocyte MDA were significantly high in the Buerger disease group compared to the PAOD and control groups (p < 0.001). Plasma PON1 levels and GSH and GSH-px levels in erythrocytes in the Buerger disease group were significantly low compared to the PAOD and control groups (p < 0.001). GSH-red, SOD, and CAT levels in erythrocytes in the Buerger disease group were significantly lowcompared to the PAOD group (p < 0.01, p < 0.001, and p < 0.001, respectively). NO levels were significantly lower in the PAOD group compared to the control group (p < 0.05). The balance between oxidative stress and antioxidant capacity is more seriously impaired in Buerger disease than PAOD.

Impaired vasoreactivity despite an increase in plasma nitrite in patients with abdominal aortic aneurysms

Objective: This investigation was designed to determine whether differences in vasoreactivity occur in patients with abdominal aortic aneurysms (AAAs) as compared with patients with peripheral arterial occlusive disease (PAOD) or individuals (controls) without known vascular disease. Methods: Brachial artery vasoreactivity was assessed in a blinded fashion, after endothelium-dependent (ED) and endothelium-independent (EI) flow-mediated vasodilation, in age-matched, male patients with AAAs (n = 11) or PAOD (n = 9) or in controls (n = 10). There were no significant differences in prestudy systolic or diastolic blood pressure, body mass index, or antilipidemic medications among the groups studied. Exclusion criteria included diabetes and tobacco use within 3 months. Quantitative ultrasound scan measurements of brachial artery diameters were performed at rest and after either forearm ischemia (ED) or administration of 0.4 mg sublingual nitroglycerin (EI). Plasma nitric oxide (NOX = NO2 + NO3) was measured with the Saville assay. Asymmetric dimethylarginine, an endogenous inhibitor of NOX synthase, was measured with liquid chromatography. Results: Initial brachial artery diameters were not significantly different among the groups studied (4.85 ± 0.18 mm for AAA group, 4.82 ± 0.17 mm for PAOD group, 4.68 ± 0.20 mm for controls). ED and EI vasodilation was significantly less (P =.02 and.03, respectively) in the AAA group (−1.71 ± 1.52 and 8.33 ± 1.13, respectively) when compared with the controls (2.96 ± 1.04 and 13.88 ± 2.16, respectively). However, plasma NOX was significantly increased (P =.01) in the AAA group (7.86 ± 0.85 μmol/L) as compared with both controls (5.13 ± 0.63 μmol/L) and PAOD (4.85 ± 0.46 μmol/L). Asymmetric dimethylarginine levels were decreased in the AAA group (0.34 ± 0.05 μmol/L) as compared with the PAOD group (0.46 ± 0.09 μmol/L). No correlation existed between aneurysm size and ED or EI vasodilation or plasma NOX. Conclusion: This study is the first to document a divergence between ED and EI vasoreactivity and systemic NO metabolites in patients with AAAs. It is speculated that a dysfunctional vessel wall response, rather than a lack of NO, may be important in the pathogenesis of AAAs. (J Vasc Surg 2002;35:363-7.)

Diameter Comparison of Saphenous Vein Bypasses for Popliteal Aneurysm Versus Peripheral Arterial Occlusive Disease in Matched Subjects

Previous research has suggested that arterial aneurysm might result from a systemic tendency to dilatation. This systemic effect would involve both arterial and venous dilatation. The authors investigated whether venous grafts implanted to bypass popliteal artery aneurysms (PAA) had larger diameters than those implanted to treat peripheral arterial occlusive disease (PAOD). They compared representative diameters of 20 vein grafts implanted for PAA with matched bypass grafts implanted for PAOD. Graft diameters were obtained by means of CVI-Q M-mode ultrasound imaging. Each PAA patient/graft was matched to an equivalent PAOD patient/graft based on the patient's gender and age and the vein graft type and distal anastomosis. Secondarily, graft proximal anastomosis was matched in 60% (12/20) of the cases. Age was matched if the difference was < or = 4 years. Average age at the time of surgery was 68 +/-12 years for PAA and 68 +/-13 for PAOD groups. There were 11 reversed greater saphenous vein (GSV), 2 nonreversed GSV, and 7 in situ GSV in each group. Distal anastomoses were at the popliteal (15), peroneal (3), posterior (1), and anterior tibial (1) arteries in each group. Matching was not possible for lesser saphenous and cephalic vein grafts or bypasses to the tibial-peroneal trunk. Graft diameters were significantly larger for the PAA group, 6.24 +/-0.66 mm (standard deviation), than for the PAOD group, 5.73 +/-0.69 mm (p < 0.02, Mann-Whitney U test). Of 10 bypasses with diameter >6.5 mm, 8 were implanted for PAA. If these 10 largest bypasses were eliminated from the calculations, the mean graft diameters were 5.82 +/-0.51 mm and 5.57 +/-0.52 mm for the PAA and PAOD groups, respectively (p = 0.28). Bypass grafts implanted in PAA patients had significantly greater diameters than grafts implanted in PAOD patients. This finding, however, was due to a subgroup of grafts with diameters >6.5 mm. Perhaps systemic abnormalities associated with PAA should be first studied in patients with large vein grafts or large original veins.

Serum nitrate concentrations in patients with peripheral arterial occlusive disease.

Nitric oxide (NO), an endogenous product of L-arginine oxidation, seems to account for the vasodilatatory effect of the endothelium-derived relaxing factor. It was the aim of the present study to measure serum nitrate concentrations, the degradation product of nitric oxide in patients with peripheral arterial occlusive disease (PAOD). 20 patients with PAOD in Fontaine stage IIb, 10 patients in stage III and IV respectively were included in the study. Serum samples for determination of nitrate were taken at admission after fasting overnight. Nitrate concentrations were determined using a recently developed high performance liquid chromatography which allows direct measurement of nitrate. The control group comprised 14 age and risk factor matched volunteers. We found significantly increased nitrate concentrations in patients with PAOD compared to the control group [stage IIb: 6.65 +/- 1.58 mumol/l; stage III: 6.94 +/- 1.85 mumol/l, stage IV: 7.05 +/- 1.16 mumol/l; control: 4.41 +/- 1.24 mumol/l], however no significance was calculated within the different PAOD groups. There was no association of either diabetes mellitus, hypertension and smoking behaviour with increased nitrate levels. These data might indicate that NO might be involved in adaptive vasodilatation already in the early phase of the disease. The source of nitrate in PAOD patients, however, remains unclear.

The relationship between free-living daily physical activity and the severity of peripheral arterial occlusive disease.

The purposes of this study were to assess the magnitude of the reduction in free-living daily physical activity of claudicants compared with age-matched controls, and to examine the relationship between the severity of peripheral arterial occlusive disease (PAOD) and free-living daily physical activity. Eighty-five PAOD patients with intermittent claudication and 59 non-PAOD subjects with a resting ankle/brachial index (ABI) of 0.63 +/- 0.20 and 1.21 +/- 0.08, respectively, were monitored for 2 consecutive weekdays with an accelerometer and pedometer worn on each hip. The times to onset and to maximal claudication pain were also measured in the claudicants during a graded treadmill test to assess the functional limitations imposed by PAOD. The PAOD group had a 42% lower energy expenditure as measured from the accelerometer (357 +/- 238 kcal/day versus 616 +/- 363 kcal/day; p < 0.001) and a 45% lower pedometer reading (4737 +/- 2712 steps/day versus 8672 +/- 4235 steps/day; p < 0.001) than the non-PAOD group. Furthermore, the relationship between free-living daily physical activity and ABI in PAOD patients was significant for both the accelerometer (r = 0.41; p < 0.001) and the pedometer (r = 0.41; p < 0.001). The rate of decline in free-living daily activity was 42 kcal/day and 612 steps/day per 0.10 drop in ABI. The correlation between free-living daily physical activity and time to maximal claudication pain (6:25 +/- 3:30 min:s) in the PAOD group was significant for both the accelerometer (r = 0.30; p = 0.05) and the pedometer (r = 0.36; p = 0.03). However, the time to onset of claudication pain (3:02 +/- 2:22 min:s) in the PAOD group was not related to either the accelerometer (r = -0.02; p = 0.86) or the pedometer (r = 0.18; p = 0.28) activity values. In conclusion, free-living daily physical activity was 42% to 45% lower in PAOD patients with intermittent claudication than in apparently healthy subjects of similar age. Moreover, claudicants were progressively more sedentary with an increase in PAOD severity.

Defective Interaction between von Willebrand Factor and Platelet Glycoprotein I b – A Familial Study of Peripheral Arterial Occlusive Disease

Hemostatic variables and platelet function were assessed as a part of a genetic study in 15 patients with symptomatic peripheral arterial occlusive disease (PAOD) and 15 healthy siblings from ten families. D-dimer, a degradation product of cross-linked fibrin, was increased in the PAOD group (mean +/- SD) (448 +/- 177 vs. 333 +/- 121 ng/ml, p < 0.05). Ristocetin-induced maximal platelet aggregation (RIPA) was reduced in the PAOD group in response to both a higher (0.75 mg/ml) (67 +/- 28 vs. 87 +/- 14%, p = 0.02) and a lower (0.55 or 0.60 mg/ml) (33 +/- 21 vs. 59 +/- 32%, p = 0.02) concentration of ristocetin. Accordingly, the rate of primary aggregation was smaller, and a larger threshold concentration of ristocetin was needed to cause aggregation. However, ristocetin cofactor activity, von Willebrand factor (vWF) antigen and its multimer distribution, plasma glycocalicin, platelet glycoprotein Ib content and the binding of vWF to frozen and thawed washed platelets were equal in both groups. Thus, the observed reduced RIPA in patients with PAOD is less likely to reflect a down-regulation or blunted binding affinity in the platelet surface glycoprotein Ib.

Transcutaneous Oxygen Tension and Doppler Ankle Pressure During Upper and Lower Body Exercise in Patients with Peripheral Arterial Occlusive Disease

The effects of upper and lower body exercise on blood supply to the lower extremities were investigated in patients with peripheral arterial occlusive disease (PAOD) by measurements of transcutaneous oxygen tension (tcPO2) and Doppler ankle pressure (DAP). Twenty patients with PAOD (PAOD group) and 10 subjects without PAOD (control group) performed treadmill test (TT), recumbent cycle ergometry (CE), and rowing ergometry (RE) with a fixed seat. The tcPO2 was registered on the calf and DAP was measured at the end of each step of CE and RE. The walking distance in TT of the control group was not limited (> 1000 m), whereas that of the PAOD group was 161 m in median. In the control group there was no significant difference of performance between CE (125 +/- 33 W) and RE (111 +/- 24 W), whereas in the PAOD group, performance was lower in CE (72 +/- 31 W) than in RE (102 +/- 28 W) (P < 0.01). DAP of controls increased during both CE (136 to 165 mmHg) and RE (170 to 213 mmHg), whereas the DAP of the PAOD group decreased during CE (from 85 to 44 mmHg) and remained relatively constant during RE (113 to 101 mmHg). In controls, tcPO2 did not distinctly change during TT (70 to 66 mmHg) and increased during CE (58 to 73 mmHg) and RE (69 to 82 mmHg), whereas in the PAOD group, tcPO2 decreased during TT (66 to 33 mmHg) and CE (50 to 22 mmHg) and remained almost unchanged in RE (64 to 60 mmHg). A hyperbolic relationship was found between tcPO2 and DAP. In conclusion, during upper body exercise, blood supply to the lower extremities in patients with PAOD was not affected, whereas lower body exercise led to exhaustion of the functional reserve of blood supply. Because of a hyperbolic relationship between tcPO2 and DAP, tcPO2 remained relatively constant if blood supply was sufficient, but in disturbed blood supply a small change of DAP was accompanied by a great change of tcPO2. Therefore, in critical ischemia the change of tcPO2 was more sensitive than that of DAP.

Flow cytometric assessment of platelet function in patients with peripheral arterial occlusive disease

This study compared new and traditional measures of platelet function in 16 patients with severe peripheral arterial occlusive disease and 15 age-matched controls. Circulating platelets were characterized by the use of fluorescence flow cytometry to assess platelet aggregate formation and expression of the secretion-dependent alpha granule membrane protein GMP-140, by measurement of plasma beta-thromboglobulin (beta-TG), and by performance of platelet-rich plasma aggregation studies. In addition, blood samples were treated with graded concentrations of adenosine diphosphate (ADP; 0 to 10 mumols/L) to characterize by fluorescence flow cytometry the secretory and aggregatory responses to mild stimulation. No differences were detected between the two groups with regard to platelet function in unstimulated circulating blood by use of these techniques. Values (mean +/- SEM) observed were: GMP-140-positive platelets, 11% +/- 3% versus 13% +/- 2%; platelet aggregates in circulating whole blood, 4% +/- 1% versus 9% +/- 3%; plasma beta-TG, 92 +/- 12 versus 94 +/- 22 ng/ml; and ED50 (concentration of ADP required to produce half maximal aggregation), 3.8 +/- 1.1 versus 3.1 +/- 0.5 mumol/L in the patients with peripheral arterial occlusive disease and controls, respectively. Treatment with ADP caused a dose-related increase in GMP-140 expression in both groups, without significant differences in this parameter between the groups at any given concentration. However, stimulation with ADP concentrations greater than 1 mumol/L resulted in more frequent aggregate formation in the control than in the peripheral arterial occlusive disease group (25% +/- 4% versus 11% +/- 2%, respectively at 5.0 mumols/L, p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)