Identification and Management of Cardiometabolic Risk after Spinal Cord Injury: Clinical Practice Guideline for Health Care Providers

Abstract

This text is excerpted from the complete document, which includes the Consortium Member Organizations and Steering Committee Representatives, Acknowledgments, Reviewers, Glossary, and Appendix (Search Strategies).Administrative and financial support provided by Paralyzed Veterans of America.Reprinted with permission from the Paralyzed Veterans of America (PVA) Consortium for Spinal Cord Medicine Clinical Practice Guidelines Consumer Guide: "Cardiometabolic Risk after Spinal Cord Injury: A Clinical Practice Guideline for Health Care Providers." Washington, DC: © 2018 Paralyzed Veterans of America. Copies of the PVA's Guidelines are available at www.pva.org.These guidelines have been prepared based on scientific and professional information available in 2018. Users should periodically review this material to ensure that the advice herein is consistent with current reasonable clinical practice. The websites noted in this document were current at the time of publication; however, because web addresses and the information contained therein change frequently the reader is encouraged to stay apprised of the most current information.Cardiometabolic disease (CMD) can be thought of as a silent killer. The clinical manifestations of this secondary complication of spinal cord injury (SCI) may not be apparent until too late to intervene. Until now, CMD has been less of a focus of the SCI community as a whole, compared to the other major secondary conditions of neurogenic bowel and bladder, autonomic dysfunction, respiratory insufficiency, depression, sexual dysfunction, pressure injuries, and venous thromboembolism, which are overt in their presentation and have been addressed in previous guidelines.The recommendations of this Clinical Practice Guideline (CPG) regarding identifying and managing CMD risks are in line with current recommendations for identifying and managing CMD risks in people without SCI, which have also been recently updated. However, these recommendations also take into consideration the differences between the body composition and physiology of those with SCI and those without SCI, and the risks of certain interventions for persons with SCI, given the presence of other secondary conditions such as neurogenic bowel, and also acknowledge the challenges to implementing the recommendations within the SCI community.We were fortunate in the development and peer review of this CPG to have representation from all the various stakeholders and subspecialties impacted by these recommendations, including a range of experts in nutrition, exercise, cardiology, endocrinology, internal medicine, and rehabilitation. This wide-ranging representation will hopefully translate into uniform, quality practice through the widespread use of this CPG to guide CMD prevention and treatment in all settings, which can only result in the best outcomes and least amount of morbidity and mortality for those who experience SCI.On behalf of the consortium steering committee, I want first to acknowledge the leadership of the guideline panel, namely the Chair, Mark Nash, and Co-Chair Suzanne Groah, in guiding this panel through the ups and downs of a development process which spanned five years. The panel members themselves, who kept to task for so long, and the many reviewers who provided valuable feedback from all areas, are to be commended. Everyone, including the panel Chair and Co-Chair, volunteered their time to help produce this superb document. In addition, I wish to acknowledge the ongoing support of Paralyzed Veterans of America (Paralyzed Veterans), especially President David Zurfluh, Executive Director Carl Blake, and Director of Research and Education Cheryl Vines, as well as the rest of the leadership team, without whose support these guidelines would not exist.Thomas N. Bryce, MDChair, Steering CommitteeConsortium for Spinal Cord MedicineThe following Guideline is the first from the Consortium for Spinal Cord Medicine to address CMD after SCI. In doing so, it reports the emergence of all-cause cardiovascular diseases (CVD) and CVD-related risks as significant health hazards for persons with SCI and establishes a foundational standard for identification and management of cardiometabolic risks. The spinal cord community was first made aware of these risks in the early 1980s. Since then, hundreds of scholarly articles have examined antecedents, causes, personal and population characteristics, co-morbidities and treatments for these hazards. These studies have confirmed that persons with SCI are frequently sedentary, overweight, dyslipidemic and at elevated risk for insulin resistance, thus placing them in jeopardy of developing CMD. None of the health hazards imposed by the five archetypical CMD risk components foretells the long, active, productive, and healthy life we seek for persons with SCI. These conditions may also prohibit persons with SCI from undergoing, or ultimately benefiting from, the restorative therapies in clinical trials, or from using rehabilitation technologies that require a relatively lean and healthy body for their efficient use.Unlike some diseases and disorders addressed by other Consortium Guidelines, CMD typically develops slowly and without overt symptoms. Unless routinely surveilled in the SCI population, CMD may be irreversible once clinically detected. The panel seriously considered the possibility that CMD and its component risks, once identified, will be far more challenging to treat in persons with SCI than their non-disabled counterparts. For these reasons, this guideline will favor scheduled surveillance, early risk assessment, timely symptom recognition, and prudent interventional care. In arriving at these recommendations, the Panel asserts that an enlightened and compassionate health care system, and a caring society, will unquestionably favor early assessment and aggressive preemptive care when not doing so might result in early morbidity and uncertain mortality.The consumers of this guideline – health professionals and stakeholders with SCI– will note that its evidence and opinions may sometimes point to persons with SCI being at no greater risk for a diagnosis of CMD or its component risks than their non-disabled cohorts. It should be emphasized, however, that all-cause CVD and related conditions are among the most prevalent, life threatening, function compromising and costly of known medical hazards. In making recommendations, the Panel has also taken into consideration that our health care system is even less prepared to effectively treat CMD in those with SCI than to prevent it. Given these circumstances, we believe it is practical to embrace primary prevention as a best-practice, strategic approach. In some instances, the Panel found no evidence or clinical intuition to sidestep the adoption of several recommendations that currently exist for CMD diagnosis and management in the general population. These strategic guidelines provide an extensively vetted, evidence-based standard in cases where no such guideposts have been fashioned or applied for the benefit of the SCI population. When adopting standards used for the general population, we have also identified areas in need of investigation so that the foundational evidence for CMD identification and management can become even more representative of, and relevant for, the SCI population.In publishing the Guideline, we extend our sincerest thanks for the dedicated work and meaningful contributions of Panel Members, Drs. Trevor Dyson-Hudson, David Gater, Jesse Lieberman, Jonathan Myers, Sunil Sabharwal and Allen Taylor. We further note with appreciation the contributions of Ms. Cheryl Vines, Dr. Thomas Bryce, the Paralyzed Veterans CPG Steering Committee, and the Consortium Partners who collectively recognized the importance of this topic and unfailingly supported the Panel's activities to their completion.Mark S. Nash, PhD, FACSM, Panel ChairLeonard M. Miller School of Medicine,The University of MiamiMiami, FLSuzanne L. Groah, MD, MPH, Panel Co-ChairMedstar National Rehabilitation HospitalGeorgetown University Medical CenterWashington, DCThe overall objective of this guideline is to improve the care of patients with spinal cord injury by guiding clinicians and policymakers with its recommendations. The following recommendations use available evidence and – where evidence is limited – Panel experience and consensus. The Panel based its evidence ratings primarily on research in which the focus of the study was SCI. This information was supplemented using evidence from trials, guidelines, and expert opinions contained in the scientific literature of non-SCI populations.For individual patients, decisions are best made by considering these recommendations combined with clinical judgment, the latter based on specific knowledge about each patient's risk factors for cardiometabolic disease, the potential for adverse effects, and the availability of various options within one's center. The bracketed rating refers to the level of scientific evidence, the strength of the evidence, and the level of panel agreement with the recommendations.1Recommendations:Recommendations:Recommendations:Recommendations:Recommendations:Recommendations:Recommendation:Recommendations:Recommendations:Recommendations:Recommendations:Recommendations:The Consortium of Spinal Cord Medicine is a collaboration of professional and consumer organizations with a common interest in healthcare for individuals living with spinal cord injury. The Consortium's mission is to direct the development and dissemination of evidence-based clinical practice guidelines (CPGs) and companion consumer guides. This mission is solely directed to improving the health care and quality of life for persons with SCI.The Consortium is funded and administered by Paralyzed Veterans of America (Paralyzed Veterans). The Steering Committee, administratively supported by Paralyzed Veterans's Research and Education Department, is made up of one representative from each consortium-member organization.The development of these guidelines involved the following major steps: creating a list of formal, key questions to be addressed, systematic searches of published literature related to these questions, critical appraisal of the quality of the retrieved studies, abstraction of relevant study results, creation of evidence-based recommendations, development of rationale that explain the recommendations, and review and agreement by panel members. The SCI Consortium's CPG development process also involved extensive field review and a legal review.Paralyzed Veterans contracted the literature searches and evidence reviews to an independent firm and provided administrative support for the process. Panel members received no compensation for their participation and declared all potential financial or other conflicts of interest.A medical librarian searched Ovid MEDLINE® (1980 through September, Week 2 2015), the Cochrane Central Register of Controlled Trials® (1980 through September 22, 2015), Cochrane Health Technology Assessments (searched September 22, 2015), and the Cochrane Database of Systematic Reviews® (2005 through September 2015) using search terms related to chronic spinal cord injury. We also searched Ovid MEDLINE for names of authors known to have published in this area (on September 22, 2015). See the Appendix for complete search strategies. We attempted to identify additional studies through hand searches of reference lists of included studies and reviews. All citations were imported into an electronic database (Endnote® X7, Thomson Reuters).Selection of included studies was based on the inclusion criteria created in consultation with Paralyzed Veterans. Two reviewers independently assessed titles and abstracts of citations identified through literature searches for inclusion, using the criteria below. Full-text articles of potentially relevant citations were retrieved and were assessed for inclusion by both reviewers. Disagreements were resolved by consensus. Results published only in abstract form were not included because inadequate details were available for quality assessment (risk of bias). Abstracts that had additional information available in slide sets from conference presentations, or those that provided supplemental data from published studies, were considered for inclusion.In consultation with Paralyzed Veterans, 14 key questions were formulated relating to the prevalence of CMD and risk factors for disease, screening for CMD, CMD diagnosis methods, and the comparative effectiveness of treatment for CMD in the SCI population. Key questions 13 and 14 regarding CMD guidelines were not part of the systematic review, but they provide information on relevant guideline recommendations. Key questions and inclusion criteria are below.Patients with nonacute, traumatic, or atraumatic irreversible spinal cord injury or dysfunction resulting in paralysis (excluding patients with spinal stroke)Information was abstracted on population characteristics, interventions, subject enrollment, prevalence, results for efficacy, effectiveness, and harms outcomes for trials, observational studies, and systematic reviews. When reported, intent-to-treat results were recorded. Data abstraction was performed by one reviewer and independently checked by a second reviewer. Differences were resolved by consensus.We assessed the internal validity (risk of bias) of trials, observational studies, and systematic reviews based on predefined criteria. These criteria are based on the U.S. Preventive Services Task Force and the National Health Service Centre for Reviews and Dissemination (United Kingdom) criteria7–8 and the GRADE guidelines.9 We rated the internal validity of each trial based on the methods used for randomization, allocation concealment, blinding, the similarity of compared groups at baseline, loss to follow-up, and the use of intent-to-treat analysis. Trials that had a fatal flaw were rated at a high risk of bias, trials that met all criteria were rated at a low risk of bias, and the remainder were rated at a moderate risk of bias. As the moderate risk of bias category is broad, studies with this rating vary in their strengths and weaknesses. The results of some studies rated moderate risk of bias are likely to be valid, while others are only possibly valid. A fatal flaw is reflected by failure to meet combinations of items on the risk-of-bias checklist. An example would be a study with high attrition (e.g., 60%) combined with the inadequate handling of missing data, or one where details on randomization and/or allocation concealment were lacking, and there were baseline differences in important prognostic characteristics. Observational studies were rated on non-biased selection, loss to follow-up, pre- specification of outcomes, well-described and adequate ascertainment techniques, statistical analysis of potential confounders, and adequate duration of follow-up. Systematic reviews were rated on the clarity of review questions, the specification of inclusion and exclusion criteria, use of multiple databases and search for grey literature, sufficient detail of included studies, adequate assessment of the risk of bias of included studies, and adequate summarization of primary studies.Two reviewers independently assessed the quality of each study and differences were resolved by consensus.We graded quality of evidence (QoE) based on the GRADE approach.10–14 Developed to grade the overall quality of a body of evidence, this approach incorporates four key domains: risk of bias (includes study design and aggregate risk of bias), consistency, directness, and precision of the evidence. It also considers other optional domains that may be relevant for some scenarios, such as a dose- response association, plausible confounding that would decrease the observed effect, the strength of association (magnitude of effect), and publication bias.Table 1 describes the grades of evidence that can be assigned. Grades reflect the quality of the body of evidence to answer key questions. Grades do not refer to the general efficacy or effectiveness of treatments, for example. Two reviewers independently assessed each domain for each outcome and differences were resolved by consensus.The quality of the body of evidence was evaluated for each outcome by key question.We constructed evidence tables showing the study characteristics, quality ratings, and results for all included studies. We reviewed studies using a hierarchy of evidence approach, where the best evidence is the focus of our synthesis for each question, population, intervention, and outcome addressed.The following section addresses hazards for CMD and its risk components in persons with SCI.CMD is a coalescing of interrelated cardiovascular, renal,metabolic,pro-thrombotic,andinflammatory health hazards,1 and is recognized as a disease entity by the American Society of Endocrinology, the AHA, the International Diabetes Federation (IDF), the American Diabetes Association (ADA), and the World Health Organization (WHO).2 The AHA and the National Institutes of Health (NIH) National Heart Lung Blood Institute (NHLBI) define CMD as the co-occurrence of any three of the medical hazards described in Table 2.Abdominal (central) obesity, hypertension, hyperglycemia, hypertriglyceridemia, and low high-density lipoproteinemia.3 While still lacking a fully harmonized diagnosis,2 CMD is recognized to increase the probability of developing atherosclerotic disease, heart failure, and diabetes.4–5 Prevalence in the U.S. is estimated at 34% of the non-disabled adult population6 and is increasing with population aging. The CMD diagnosis confers a health risk equivalent to either the diagnosis of diabetes mellitus or extant coronary disease.CMD is ultimately caused or worsened by a mismatch between energy consumption that is excessive in intake of kilocalories and saturated fats, and insufficient daily energy expenditure.7 These risks are typically expressed through lifestyle factors reflecting poor compliance with optimal nutrition and an active lifestyle. The primary metabolic abnormality of CMD is insulin resistance, while the unified cause ensues excessive body mass, whose clinical feature is excessive visceral and ectopic fat. Inflammatory stress and endocrinopathies are not included among the AHA guideline risks, although both are recognized as either cause or consequence of the disorder. 8–9The prevalence of CMD reported in adults with SCI ranges from 31–72%, contingent on the number of possible risk factors included in the definition.10–11 Depending on the study, this prevalence at least equals, and often exceeds, the CMD prevalence for the general population, which the Panel feels informs the SCI community about the risk that it poses.The guideline component risks for CMD include obesity, insulin resistance, dyslipidemia, and hypertension. The following section addresses the hazards imposed by these individual risk components on the SCI population."Obesity is a chronic, relapsing, neurochemical disease produced by the interaction of environment and host."13 Emerging data suggests adipose tissue (especially visceral adiposity) and its associated connective tissue are the primary sources of systemic proinflammatory cytokines, vasoactive hormones and non-esterified in the development of dyslipidemia, insulin resistance, hypertension, and by the scientific community as body in or in the of was to by the at the of the to more at risk for cardiovascular the five AHA component risks, after SCI has been most challenging to and to non-SCI in persons with SCI to in reflecting and body associated with and autonomic of the spinal The standard for of in persons with SCI, such that the prevalence of CMD the prevalence of CMD in persons with SCI reported in the studies have reported a of in persons with SCI to which is well the standard for of in the non-SCI population. study CMD prevalence with and found that doing so the range from to between persons with SCI and those for of and should be to and risk is However, the use of this has not been in SCI and is likely inadequate as a to and of prevalence of diabetes in people with SCI with the of the population being Prevalence studies for diabetes in people with SCI in the S. have on U.S. so may not be to other U.S. studies a prevalence of diabetes in people with SCI to than those in other to that the prevalence of diabetes among U.S. with SCI is not from without However, moderate quality evidence from other that persons with SCI have a prevalence of diabetes than risk factors for diabetes and in the general population, such as increasing or or and of likely to the SCI population as evidence specific to SCI is limited and of low prevalence of among persons with SCI is high when based on guidelines as well as to non-disabled on reflecting cardiovascular risk among persons with SCI, compared to non-disabled have included the of including of to and and and All these support the Panel's recommendations. The most consistent from studies of persons with SCI is when compared to non-disabled However, many of these studies regarding which are and their potential association with the level and of the injury and other population characteristics. This has to in results between studies of persons with SCI non-disabled For in a study U.S. Veterans and with SCI, Veterans, and no differences were observed in the prevalence of and in a the prevalence of was in persons with SCI than non-disabled have reported and but and a of to among SCI individuals compared with groups of non-SCI the overall prevalence of in the general population also to be and some research has the prevalence of is in persons with SCI (e.g., of have some form of is a of consistent data regarding the of level of injury as well as other clinical and factors on the prevalence of in persons with SCI.The reported prevalence of in people with SCI from to and other of the population being may the reported prevalence, as may differences in methods to the presence of hypertension. on the prevalence of in SCI in the have been in U.S. may not be to other to the spinal cord the of of the SCI, including level and of may the prevalence of hypertension. Prevalence of is reported to be in people with compared with especially those with low and The of were in injuries, compared to without SCI in a study of U.S. while had of as Veterans with SCI had of compared with those with SCI after for available SCI characteristics, and following section addresses the hazards associated with SCI that are population but not included among the AHA risk component hazards of is a in and cardiovascular and metabolic health for persons of all and health The unified American of Medicine and and provide guidelines for health and in the general population, which to the best of their are also for individuals with These guidelines are in agreement with both the Guidelines for and and also the Guidelines for with SCI that were for SCI are also to the for for with Spinal Cord recommendations of the American lifestyle either imposed on or by persons with SCI has identified as a population health a identified cause for a a study reported that 1 in persons with SCI to a level of to many activities of daily it was reported that of patients with SCI no and the for meaningful health benefit This that of the estimated individuals currently living with SCI in the are and in a considered inadequate to While those with of and have far greater for and more extensive they are not more than persons with is not included among the five component risks of CMD, it is with and considered a major cause of obesity, insulin resistance, hypertension, and however, point to after SCI as a major to a CMD the SCI population was identified at the of the making as a cause for a common after SCI is a low of which is known in persons without to be both and with low of to participation are common after SCI and may include to participation or to exercise, of limited professional and financial an SCI, body composition is by a significant loss of an increase in visceral and an decrease in system As a persons with SCI have energy to energy and when compared to individuals without is common among persons with chronic SCI and is more than in persons without SCI. the increase in often the first after has as a to excessive some persons with SCI increase energy with are limited by their level of and as well as other to on the evidence, and that from for excessive to be a more practical for management a