Ulf G. Bronas

Supervised Exercise Versus Primary Stenting for Claudication Resulting From Aortoiliac Peripheral Artery Disease Six-Month Outcomes From the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) Study

Background— Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). Methods and Results— We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8±4.6, 3.7±4.9, and 1.2±2.6 minutes, respectively; P <0.001 for the comparison of SE versus OMC, P =0.02 for ST versus OMC, and P =0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114±274 versus 73±139 versus −6±109 steps per hour), but these differences were not statistically significant. Conclusions— SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study. Clinical Trial Registration— URL: . Unique identifier: [NCT00132743][1]. # Clinical Perspective {#article-title-36} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00132743&atom=%2Fcirculationaha%2F125%2F1%2F130.atomBackground Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise or stent revascularization.Background— Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). Methods and Results— We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8±4.6, 3.7±4.9, and 1.2±2.6 minutes, respectively; P<0.001 for the comparison of SE versus OMC, P=0.02 for ST versus OMC, and P=0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114±274 versus 73±139 versus −6±109 steps per hour), but these differences were not statistically significant. Conclusions— SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study. Clinical Trial Registration— URL: http://clinicaltrials.gov/ct/show/NCT00132743?order=1. Unique identifier: NCT00132743.

Efficacy of arm-ergometry versus treadmill exercise training to improve walking distance in patients with claudication

Abstract The efficacy of treadmill walking training to improve pain-free (PFWD) and maximal (MWD) walking distance in patients with claudication is well documented. The effects of aerobic arm-ergometry to improve PFWD and MWD compared to treadmill walking or usual care are not known. Forty-one participants (29 male, 12 female, mean age 67.7 years, 92.7% smoking history, 36.6% with diabetes) with lifestyle-limiting claudication were randomized to 12 weeks of 3 hours/week of supervised exercise training using either arm-ergometry, treadmill walking, or a combination, versus control. PFWD and MWD were assessed before and after training, and after 12 weeks of follow-up. The 12-week MWD increased significantly in the arm-ergometry (+53%), treadmill (+69%), and combination (+68%) groups (p < 0.002 versus control). The 24-week MWD was maintained in the arm-ergometry (p = 0.009) and treadmill (p = 0.019) groups, whereas the combination group declined (p = 0.751) versus control. The 12-week PFWD increased significantly in the arm-ergometry group (+82%; p = 0.025 versus control). Change in PFWD in treadmill (+54%; p = 0.196 versus control) and combination (+60%; p = 0.107 versus control) groups did not reach statistical significance. PFWD improvement was maintained in the arm-ergometry group after a 12-week follow-up (+123%; p = 0.011 versus control). In conclusion, these pilot data demonstrate for the first time that dynamic arm exercise training can improve walking capability in people with peripheral arterial disease (PAD)-induced claudication compared to participants receiving usual care and that improvement was not different from that seen with treadmill walking exercise training. Dynamic arm exercise may be a therapeutic exercise option for patients with PAD.

Design of the multicenter standardized supervised exercise training intervention for the 'CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study'

Abstract The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

Affecting Cognition and Quality of Life via Aerobic Exercise in Alzheimer’s Disease

Aerobic exercise is a promising behavioral therapy for Alzheimer’s disease (AD), yet few studies have investigated the effect of aerobic exercise on cognition in AD. The purpose of this pilot study was to examine the effect of 6-month aerobic exercise on the change in executive function, global cognition, quality of life (QOL), and depression in community-dwelling older adults with mild to moderate AD. A single group, repeated measures design with outcomes measured at baseline, 3 months, and 6 months was used. Results show that there were no significant changes in any measures except for depression (p = .026). There was a trend toward improvement in executive function and QOL with moderate effect sizes (ESs) and a trend toward deterioration in global cognition with moderate to large ESs. Randomized controlled trials are needed to evaluate the therapeutic effect of aerobic exercise in older adults with AD.

Inflammation and immune system contribution to the etiology of atherosclerosis: Mechanisms and methods of assessment

BackgroundImmune system activation and inflammation are intricately involved in the development and progression of atherosclerosis. PurposeThe purposes of this review are to (a) discuss effects of inflammation and the immune system across the lifespan of atherosclerotic plaque, (b) review current recommended testing techniques for assessing inflammation using blood and within the atherosclerotic plaque, and (c) link basic research in inflammation and immunology with ongoing clinical research with potential to impact prevention and treatment interventions in atherosclerotic disease. ResultsThe atherosclerotic process is typically initiated in the presence of endothelial dysfunction by increased uptake, entrapment, and deposition of lipids, especially low-density lipoprotein (LDL). Once inside the intima, LDL can become oxidized (LDLox), which promotes further endothelial cell activation/injury, stimulates adhesion molecule expression, and releases chemotactic factors that promote leukocyte–endothelial interactions. The process of atherogenesis is highly regulated by the innate and adaptive immune systems and systemic inflammatory response. In addition, proinflammatory mediators play a key role in the lifespan of the atherosclerotic plaque and its vulnerability, favoring eventual plaque fissure when exposed to increasing hemodynamic stress. DiscussionThe complex atherosclerotic process involves the innate and adaptive immune systems and systemic inflammatory activation. Incorporation of advances in understanding inflammation and immune system contributions to the etiology of atherosclerosis into intervention research allows the development of novel approaches to prevention and treatment.

The PADQOL: development and validation of a PAD-specific quality of life questionnaire.

Understanding the impact of peripheral artery disease (PAD) requires broad evaluation of how functional limitations of PAD affect patients’ perceptions of health-related quality of life (HRQL). The objective of this study was to describe the development, testing, and psychometric properties of the PAD Quality of Life Questionnaire (PADQOL). The PADQOL was developed in three steps: (1) interviews of symptomatic PAD patients provided content of the initial questionnaire; (2) co-administration with the SF-36 (a 36-item short-form health survey), Walking Impairment Questionnaire, and Profile of Mood States examined construct validity; and (3) a three-phased factor analysis identified factors and shortened the questionnaire. Data analyses from 297 symptomatic PAD patients resulted in a 38-item questionnaire of five factors: Social relationships and interactions, Self-concept and feelings, Symptoms and limitations in physical functioning, Fear and uncertainty, and Positive adaptation (α = 0.92–0.73) and items related to sexual function, intimate relationships and employment. Between-instrument correlations established construct validity. In conclusion, PADQOL is a validated measure to assess the disease-specific physical, psychosocial and emotional effects of PAD for research and practice.

Reactive oxygen and nitrogen species: Impact on endothelial dysfunction

BackgroundReactive oxygen and nitrogen species, known as free radicals, play a key role in the etiology and progression of atherosclerotic cardiovascular disease by creating vascular oxidative stress. PurposeThis review will discuss current biological research about the enzymatic and nonenzymatic sources of oxidative stress, free radical chemistry, and how it pertains to endothelial dysfunction—a hallmark of cardiovascular disease. MethodsAn integrative review of the literature was conducted. FindingsFree radicals lower the bioavailability of the potent vasodilator nitric oxide and therefore, through numerous chemical reactions, negatively affect vascular biology and endothelial function. Endothelial dysfunction is considered to be integral in the initiation of atherosclerosis. ConclusionsThe success and failures of current therapies to reduce oxidative stress are discussed in terms of implications for nursing research on exogenous antioxidants, pharmacotherapy, and lifestyle change.

Maintaining physical fitness and function in Alzheimer's disease: a pilot study.

Background: Little is known about how aerobic exercise affects physical functioning in persons with Alzheimer’s disease (AD). Methods: This pilot study used a 1-group repeated measures design to examine the feasibility and impact of a 6-month individualized moderate intensity cycling intervention on cardiorespiratory fitness and lower extremity function in 8 participants aged 81.4 ± 3.58. Cardiorespiratory fitness was measured using the shuttle walk and modified YMCA cycle ergometer tests, and lower extremity function was measured using the Short Physical Performance Battery (SPPB) at baseline, 3 months and 6 months. Results: The YMCA test showed a significant reduction in heart rate at stage 2 (103.4 vs 90.9 vs 91.6; P = .01), while no significant changes were observed in the shuttle walk and SPPB tests. Conclusions: Persons with AD are able to improve cardiorespiratory conditioning from aerobic exercise. Randomized, controlled trials are needed to confirm these findings. Implications for future research are detailed.

Dyslipidemia and risk of coronary heart disease: role of lifestyle approaches for its management.

Multiple risk factors have a causative relationship to the etiology of coronary heart disease (CHD). However, it is clear that dyslipidemia plays a central role. The chain of evidence is strongest for elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). An inverse association has also been demonstrated between levels of high-density lipoprotein cholesterol (HDL-C) and its principal apolipoprotein, A-1, and risk of CHD. Elevated levels of fasting triglyceride (TG) also are a predictor of CHD, but the independent contribution of TG is difficult to prove because of its usual association with reduced levels of HDL-C; elevated levels of small, dense, highly-atherogenic LDL particles; and the metabolic syndrome. Elevated fasting levels of non—HDL-C (TC — LDL-C) and apolipoprotein B also are strongly predictive of the risk of CHD. Therapeutic lifestyle changes are important adjuncts to pharmacologic management of dyslipidemia. The purpose of this article is to review these contributions with an emphasis on dietary habits (particularly lipid intake), weight management, and aerobic exercise.

The Role of Endothelial Dysfunction on Development and Progression of Atherosclerosis and Methods to Assess Vascular Function and Structure

The endothelium was originally thought to be just a semipermeable barrier between the vessel wall and the bloodstream, but today we now realize that it is actually a highly active autocrine, paracrine, and endocrine organ. Researchers have also begun to realize that the endothelium plays a key role in the development of atherosclerosis as well as other diseases. This increased recognition has resulted in considerable effort by both researchers and clinicians to develop accurate and reliable methods to measure and track changes in both vascular structure and function. In addition, research interest has focused on various cardiovascular risk factors (eg, age, gender, obesity, physical inactivity) and the effect they have on vascular structure and function. In this review, the authors discuss different research and clinical methods to assess vascular structure and function as well as the effect of various cardiovascular risk factors on the endothelium and the vascular system. They also discuss the ability to modify vascular structure and function through various lifestyle modifications such as weight loss and exercise.