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      Impact of Kidney Disease on Peripheral Arterial Interventions: A Systematic Review and Meta-Analysis

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          Background: There are limited data on outcomes of patients undergoing peripheral arterial disease (PAD) interventions who have comorbid CKD/ESRD versus those who do not have such comorbid condition. We performed a systematic review and meta-analysis to analyze outcomes in this patient population. Methods: Five databases were searched for studies comparing outcomes of lower extremity PAD interventions for claudication and critical limb ischemia (CLI) in patients with CKD/ESRD versus non-CKD/non-ESRD from January 2000 to June 2019. Results: Our study included 16 observational studies with 44,138 patients. Mean follow-up was 48.9 ± 27.4 months. Major amputation was higher with CKD/ESRD compared with non-CKD/non-ESRD (odds ratio [OR 1.97] [95% confidence interval [CI] 1.39–2.80], p = 0.001). Higher major amputations with CKD/ESRD versus non-CKD/non-ESRD were only observed when indication for procedure was CLI (OR 2.27 [95% CI 1.53–3.36], p < 0.0001) but were similar for claudication (OR 1.15 [95% CI 0.53–2.49], p = 0.72). The risk of early mortality was high with CKD/ESRD patients undergoing PAD interventions compared with non-CKD/non-ESRD (OR 2.55 [95% CI 1.65–3.96], p < 0.0001), which when stratified based on indication, remained higher with CLI (OR 3.14 [95% CI 1.80–5.48], p < 0.0001) but was similar with claudication (OR 1.83 [95% CI 0.90–3.72], p = 0.1). Funnel plot of included studies showed moderate bias. Conclusions: Patients undergoing lower extremity PAD interventions for CLI who also have comorbid CKD/ESRD have an increased risk of experiencing major amputations and early mortality. Randomized trials to understand outcomes of PAD interventions in this at-risk population are essential.

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          Most cited references 37

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          Arterial stiffness and pulse pressure in CKD and ESRD.

          We recognize that increased systolic pressure is the most challenging form of hypertension today and that pulse pressure as an independent cardiovascular risk factor has focused attention on arterial stiffness and wave reflections as the most important factors determining these pressures. In recent years, many studies emphasized the role of arterial rigidity in the development of cardiovascular diseases, and it was shown that stiffening of arteries is associated with increased cardiovascular mortality and morbidity. Moreover,arterial stiffening is linked to decreased glomerular filtration rate, and is predictive of kidney disease progression and the patient’s cardiovascular outcome. Premature vascular aging and arterial stiffening are observed with progression of chronic kidney disease (CKD) and in end-stage renal disease(ESRD). This accelerated aging is associated with outward remodeling of large vessels, characterized by increased arterial radius not totally compensated for by artery wall hypertrophy. Arterial stiffening in CKD and ESRD patients is of multifactorial origin with extensive arterial calcifications representing a major covariate. With aging, the rigidity is more pronounced in the aorta than in peripheral conduit arteries, leading to the disappearance or inversion of the arterial stiffness gradient and less protection of the microcirculation from high-pressure transmission. Various non-pharmacological or pharmacological interventions can modestly slow the progression of arterial stiffness,but arterial stiffness is, in part, pressure dependent and treatments able to stop the process mainly include antihypertensive drugs.
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            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.

            Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). 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. 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. URL: http://clinicaltrials.gov/ct/show/NCT00132743?order=1. Unique identifier: NCT00132743.
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              Is Open Access

              2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary

              Preamble Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines with recommendations to improve cardiovascular health. These guidelines, based on systematic methods to evaluate and classify evidence, provide a cornerstone of quality cardiovascular care. In response to reports from the Institute of Medicine 1,2 and a mandate to evaluate new knowledge and maintain relevance at the point of care, the ACC/AHA Task Force on Clinical Practice Guidelines (Task Force) modified its methodology. 3–5 The relationships among guidelines, data standards, appropriate use criteria, and performance measures are addressed elsewhere. 5 Intended Use Practice guidelines provide recommendations applicable to patients with or at risk of developing cardiovascular disease. The focus is on medical practice in the United States, but guidelines developed in collaboration with other organizations may have a broader target. Although guidelines may be used to inform regulatory or payer decisions, the intent is to improve quality of care and align with patients' interests. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances, and should not replace clinical judgment. Guidelines are reviewed annually by the Task Force and are official policy of the ACC and AHA. Each guideline is considered current until it is updated, revised, or superseded by published addenda, statements of clarification, focused updates, or revised full-text guidelines. To ensure that guidelines remain current, new data are reviewed biannually to determine whether recommendations should be modified. In general, full revisions are posted in 5-year cycles. 3–6 Modernization Processes have evolved to support the evolution of guidelines as “living documents” that can be dynamically updated. This process delineates a recommendation to address a specific clinical question, followed by concise text (ideally 1 drug, strategy, or therapy exists within the same COR and LOE and no comparative data are available, options are listed alphabetically. Relationships With Industry and Other Entities The ACC and AHA sponsor the guidelines without commercial support, and members volunteer their time. The Task Force zealously avoids actual, potential, or perceived conflicts of interest that might arise through relationships with industry or other entities (RWI). All writing committee members and reviewers are required to disclose current industry relationships or personal interests, from 12 months before initiation of the writing effort. Management of RWI involves selecting a balanced writing committee and assuring that the chair and a majority of committee members have no relevant RWI (Appendix 1). Members are restricted with regard to writing or voting on sections to which their RWI apply. For transparency, members' comprehensive disclosure information is available online. Comprehensive disclosure information for the Task Force is also available online. The Task Force strives to avoid bias by selecting experts from a broad array of backgrounds representing different geographic regions, sexes, ethnicities, intellectual perspectives/biases, and scopes of clinical practice, and by inviting organizations and professional societies with related interests and expertise to participate as partners or collaborators. Individualizing Care in Patients With Associated Conditions and Comorbidities Managing patients with multiple conditions can be complex, especially when recommendations applicable to coexisting illnesses are discordant or interacting. 8 The guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances. The recommendations should not replace clinical judgment. Clinical Implementation Management in accordance with guideline recommendations is effective only when followed. Adherence to recommendations can be enhanced by shared decision making between clinicians and patients, with patient engagement in selecting interventions on the basis of individual values, preferences, and associated conditions and comorbidities. Consequently, circumstances may arise in which deviations from these guidelines are appropriate. The reader is encouraged to consult the full-text guideline 9 for additional guidance and details with regard to lower extremity peripheral artery disease (PAD) because the executive summary contains limited information.

                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                July 2020
                22 June 2020
                : 51
                : 7
                : 527-533
                aSection of Cardiovascular Diseases, Yale New Haven Hospital, New Haven, Connecticut, USA
                bSection of Nephrology, Yale New Haven Hospital, New Haven, Connecticut, USA
                Author notes
                *Mahesh Anantha-Narayanan, Section of Cardiovascular Medicine, Yale New Haven Health, 20 York Street, New Haven, CT 06511 (USA), manantha@umn.edu
                508575 Am J Nephrol 2020;51:527–533
                © 2020 S. Karger AG, Basel

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                Page count
                Figures: 2, Pages: 7
                Patient-Oriented, Translational Research: Research Article


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