Profile of cardiovascular risk factors and mortality in patients with symptomatic peripheral arterial disease

Introduction: The present study examines cardiovascular risk factor profiles and 24-month mortality in patients with symptomatic peripheral arterial disease. Design Study: Prospective observational study including 75 consecutive patients with PAD (67 ± 9.7 years of age; 52 men and 23 women) hospitalized for planned peripheral vascular reconstruction. Doppler echocardiograms were performed before surgery in 54 cases. Univariate analyses were performed using Student's t-test or Fisher's exact test. Survival analysis at 24-month follow-up was performed using the Cox regression model and Kaplan-Meier method including age and chronic use of aspirin as covariates. Survival curves were compared using the log-rank test. Results: Hypertension and smoking were the most frequent risk factors (52 cases and 51 cases, respectively), followed by diabetes (32 cases). Undertreated dyslipidemia was found in 26 cases. Fasting glycine levels (131 ± 69.1 mg/dl) were elevated in 29 cases. Myocardial hypertrophy was found in 18 out of 54 patients. Thirty-four patients had been treated with aspirin. Overall mortality over 24 months was 24% and was associated with age (HR: 0.064; CI95: 0.014-0.115; p=0.013) and lack of use of aspirin, as no deaths occurred among those using this drug (p<0.001). No association was found between cardiovascular death (11 cases) and the other risk factors. Conclusion: There is a high prevalence of uncontrolled (treated or untreated) cardiovascular risk factors in patients undergoing planned peripheral vascular reconstruction, and chronic use of aspirin is associated with reduced all-cause mortality in these patients.

Walking performance, oxygen uptake kinetics and resting muscle pyruvate dehydrogenase complex activity in peripheral arterial disease

In the present study, we tested the hypothesis that walking intolerance in intermittent claudication (IC) is related to both slowed whole body oxygen uptake (Vo(2)) kinetics and altered activity of the active fraction of the pyruvate dehydrogenase complex (PDCa) in skeletal muscle. Ten patients with IC and peripheral arterial disease [ankle/brachial index (ABI) = 0.73 +/- 0.13] and eight healthy controls (ABI = 1. 17 +/- 0.13) completed three maximal walking tests. From these tests, averaged estimates of walking time, peak Vo(2) and the time constant of Vo(2) (tau) during submaximal walking were obtained. A muscle sample was taken from the gastrocnemius medialis muscle at rest and analysed for PDCa and several other biochemical variables. Walking time and peak Vo(2) were approx. 50 % lower in patients with IC than controls, and tau was 2-fold higher (P < 0.05). r was significantly correlated with walking time (r = -0.72) and peak Vo(2) (r = -0.66) in patients with IC, but not in controls. PDCa was not significantly lower in patients with IC than controls; however, PDCa tended to be correlated with tau (r = -0.56, P = 0.09) in patients with IC, but not in controls (r = -0.14). A similar correlation was observed between resting ABI and tau (r = -0.63, P = 0.05) in patients with IC. These data suggest that the impaired Vo(2) kinetics contributes to walking intolerance in IC and that, within a group of patients with IC, differences in Vo(2) kinetics might be partly linked to differences in muscle carbohydrate oxidation.

Optimising exercise training in peripheral arterial disease

Peripheral arterial disease (PAD) is an obstructive condition where the flow of blood through peripheral arteries is impeded. During periods of increased oxygen demand (e.g. during exercise), peripheral limb ischaemia occurs, resulting in the sensation of muscle pain termed 'claudication'. As a result of claudication, subjects' ability to exercise is greatly reduced affecting their quality of life. Although many treatment options for patients with PAD exist, exercise training is an effective and low-cost means of improving functional ability and quality of life. Currently, there are limited specific recommendations to assist the exercise prescription and programming of these individuals. This review summarises data from 28 exercise training studies conducted in patients with PAD and formulates recommendations based on their results. Exercise training for patients with PAD should involve three training sessions per week comprising 45 minutes of intermittent treadmill walking in a supervised environment for a time period of 20 weeks or more. Encouragement and direction is given to further research aimed at investigating the effectiveness of training programmes in these patients.

3-D magnetic resonance angiography versus conventional angiography in peripheral arterial disease: Pilot study

Angiography is usually performed as the preoperative road map for those requiring revascularization for lower extremity peripheral arterial disease (PAD). The alternative investigations are ultrasound, 3-D magnetic resonance angiography (3-D MRA) and computed tomography angiography. This pilot study aimed to assess whether 3-D MRA could replace the gold standard angiography in preoperative planning. Eight patients considered for aortoiliac or infrainguinal arterial bypass surgery were recruited. All underwent both imaging modalities within 7 days. A vascular surgeon and a radiologist each reported on the images from both the 3-D MRA and the angiography, with blinding to patient details and each others reports. Comparisons were made between the reports for the angiographic and the 3-D MRA images, and between the reports of the vascular surgeon and the radiologist. Compared to the gold standard angiogram, 3-D MRA had a sensitivity of 77% and specificity of 94% in detecting occlusion, and a sensitivity of 72% and specificity of 90% in differentiating high grade (> 50%) versus low grade (< 50%) stenoses. There was an overall concordance of 78% between the two investigations with a range of 62% in the peroneal artery to 94% in the aorta. 3-D MRA showed flow in 23% of cases where conventional angiography showed no flow. In the present pilot study, 3-D MRA had reasonable concordance with the gold standard angiography, depending on the level of the lesion. At times it showed vessel flow where occlusion was shown on conventional angiogram. 3-D MRA in peripheral vascular disease is challenging the gold standard, but is inconsistent at present.

Short-term effects of cycle and treadmill training on exercise tolerance in peripheral arterial disease

Background. To explore the efficacy of cycle training in the treatment of intermittent claudication, the present study compared performance and physiologic effects of cycle training with more conventional treadmill walking training in a group of patients with claudication. Method: Forty-two individuals with peripheral arterial disease and intermittent claudication (24 men, 18 women) were stratified by gender and the presence or absence of type 2 diabetes mellitus and then randomized to a treadmill (n = 13), cycle (n = 15), or control group (n = 14). Treadmill and cycle groups trained three times a week for 6 weeks, whereas the control group did not train during this period. Maximal and pain-free exercise times were measured on graded treadmill and cycle tests before and after training. Results. Treadmill training significantly improved maximal and pain-free treadmill walking times but did not improve cycle performance. Cycle training significantly improved maximal cycle time but did not improve treadmill performance. However, there was evidence of a stronger cross-transfer effect between the training modes for patients who reported a common limiting symptom during cycling and walking at baseline. There was also considerable variation in the training response to cycling, and a subgroup of responsive patients in the cycle group improved their walking performance by more than the average response observed in the treadmill group. Conclusion: These findings suggest that cycle exercise is not effective in improving walking performance in all claudication patients but might be an effective alternative to walking in those who exhibit similar limiting symptoms during both types of exercise.

Effect of training on the response of plasma vascular endothelial growth factor to exercise in patients with peripheral arterial disease

Expansion of the capillary network, or angiogenesis, occurs following endurance training. This process, which is reliant on the presence of VEGF (vascular endothelial growth factor), is an adaptation to a chronic mismatch between oxygen demand and supply. Patients with IC (intermittent claudication) experience pain during exercise associated with an inadequate oxygen delivery to the muscles. Therefore the aims of the present study were to examine the plasma VEGF response to acute exercise, and to establish whether exercise training alters this response in patients with IC. In Part A, blood was collected from patients with IC (n = 18) before and after (+ 20 and + 60 min post-exercise) a maximal walking test to determine the plasma VEGF response to acute exercise. VEGF was present in the plasma of patients (45.11 +/- 29.96 pg/ml) and was unchanged in response to acute exercise. Part B was a training study to determine whether exercise training altered the VEGF response to acute exercise. Patients were randomly assigned to a treatment group (TMT; n = 7) that completed 6 weeks of high-intensity treadmill training, or to a control group (CON; n = 6). All patients completed a maximal walking test before and after the intervention, with blood samples drawn as for Part A. Training had no effect on plasma VEGF at rest or in response to acute exercise, despite a significant increase in maximal walking time in the TMT group (915 + 533 to 1206 + 500 s; P = 0.009) following the intervention. The absence of a change in plasma VEGF may reflect altered VEGF binding at the endothelium, although this cannot be confirmed by the present data.

The Effects of Cilostazol on Exercise-induced Ischaemia-reperfusion Injury in Patients with Peripheral Arterial Disease

Objectives: Cilostazol improves walking distance in peripheral arterial disease (PAD) patients. The study objectives were to assess the effects of cilostazol on walking distance, followed by the additional assessment of cilostazol on exercise-induced ischaemiaereperfusion injury in such patients.

Methods: PAD patients were prospectively recruited to a double-blinded, placebo-controlled trial. Patients were randomised to receive either cilostazol 100 mg or placebo twice a day. The primary end-point was an improvement in walking distance. Secondary end-points included the assessment of oxygen-derived free-radical generation, antioxidant consumption and other markers of the in?ammatory cascade. Initial and absolute claudication distances (ICDs and ACDs, respectively) were measured on a treadmill. In?ammatory response was assessed before and 30 min post-exercise by measuring lipid hydroperoxide, ascorbate, atocopherol, b-carotene, P-selectin, intracellular and vascular cell-adhesion molecules (I-CAM and V-CAM), thromboxane B2 (TXB2), interleukin-6, interleukin-10, high-sensitive C-reactive protein (hsCRP), albuminecreatinine ratio (ACR) and urinary levels of p75TNF receptor. All tests were performed at baseline and 6 and 24 weeks.

Results: One hundred and six PAD patients (of whom 73 were males) were recruited and successfully randomised from December 2004 to January 2006. Patients who received cilostazol demonstrated a more signi?cant improvement in the mean percentage change from baseline in ACD (77.2% vs. 26.6% at 6 weeks, pZ0.026 and 161.7% vs. 79.0% at 24 weeks, pZ0.048) as compared to the placebo. Cilostazol reduced lipid hydroperoxide levels compared to a placebo-related increase before and after exercise (6 weeks: pre-exercise: 11.8% vs.

Optimization and validation of a new 3D-US imaging robot to detect, localize and quantify lower limb arterial stenoses

L’athérosclérose est une maladie qui cause, par l’accumulation de plaques lipidiques, le durcissement de la paroi des artères et le rétrécissement de la lumière. Ces lésions sont généralement localisées sur les segments artériels coronariens, carotidiens, aortiques, rénaux, digestifs et périphériques. En ce qui concerne l’atteinte périphérique, celle des membres inférieurs est particulièrement fréquente. En effet, la sévérité de ces lésions artérielles est souvent évaluée par le degré d’une sténose (réduction >50 % du diamètre de la lumière) en angiographie, imagerie par résonnance magnétique (IRM), tomodensitométrie ou échographie. Cependant, pour planifier une intervention chirurgicale, une représentation géométrique artérielle 3D est notamment préférable. Les méthodes d’imagerie par coupe (IRM et tomodensitométrie) sont très performantes pour générer une imagerie tridimensionnelle de bonne qualité mais leurs utilisations sont dispendieuses et invasives pour les patients. L’échographie 3D peut constituer une avenue très prometteuse en imagerie pour la localisation et la quantification des sténoses. Cette modalité d’imagerie offre des avantages distincts tels la commodité, des coûts peu élevés pour un diagnostic non invasif (sans irradiation ni agent de contraste néphrotoxique) et aussi l’option d’analyse en Doppler pour quantifier le flux sanguin. Étant donné que les robots médicaux ont déjà été utilisés avec succès en chirurgie et en orthopédie, notre équipe a conçu un nouveau système robotique d’échographie 3D pour détecter et quantifier les sténoses des membres inférieurs. Avec cette nouvelle technologie, un radiologue fait l’apprentissage manuel au robot d’un balayage échographique du vaisseau concerné. Par la suite, le robot répète à très haute précision la trajectoire apprise, contrôle simultanément le processus d’acquisition d’images échographiques à un pas d’échantillonnage constant et conserve de façon sécuritaire la force appliquée par la sonde sur la peau du patient. Par conséquent, la reconstruction d’une géométrie artérielle 3D des membres inférieurs à partir de ce système pourrait permettre une localisation et une quantification des sténoses à très grande fiabilité. L’objectif de ce projet de recherche consistait donc à valider et optimiser ce système robotisé d’imagerie échographique 3D. La fiabilité d’une géométrie reconstruite en 3D à partir d’un système référentiel robotique dépend beaucoup de la précision du positionnement et de la procédure de calibration. De ce fait, la précision pour le positionnement du bras robotique fut évaluée à travers son espace de travail avec un fantôme spécialement conçu pour simuler la configuration des artères des membres inférieurs (article 1 - chapitre 3). De plus, un fantôme de fils croisés en forme de Z a été conçu pour assurer une calibration précise du système robotique (article 2 - chapitre 4). Ces méthodes optimales ont été utilisées pour valider le système pour l’application clinique et trouver la transformation qui convertit les coordonnées de l’image échographique 2D dans le référentiel cartésien du bras robotisé. À partir de ces résultats, tout objet balayé par le système robotique peut être caractérisé pour une reconstruction 3D adéquate. Des fantômes vasculaires compatibles avec plusieurs modalités d’imagerie ont été utilisés pour simuler différentes représentations artérielles des membres inférieurs (article 2 - chapitre 4, article 3 - chapitre 5). La validation des géométries reconstruites a été effectuée à l`aide d`analyses comparatives. La précision pour localiser et quantifier les sténoses avec ce système robotisé d’imagerie échographique 3D a aussi été déterminée. Ces évaluations ont été réalisées in vivo pour percevoir le potentiel de l’utilisation d’un tel système en clinique (article 3- chapitre 5).