Exercise and physical activity in systemic lupus erythematosus: A systematic review with meta-analyses
Introduction
Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease which, despite advances in therapy, continues to associate with premature mortality, largely attributable to cardiovascular (CV) causes [1], [2]. The excess CV morbidity in SLE is multifactorial, contributed to by disease and treatment-specific features, in addition to both traditional and non-traditional CV risk factors. Notwithstanding innumerable advances in SLE therapy over the past six decades, including corticosteroids, immunosuppressives, immunomodulators, improved antibiotics and angiotensin converting enzyme inhibitors, CV outcomes remain unchanged [3], [4].
Myocardial infarction, the leading cause of death in people with SLE, occurs on an average at 49 years of age, 20 years earlier than the general population [5]. Patients with SLE also have significantly increased subclinical atherosclerosis, measured as carotid artery plaque or coronary artery calcification [6], [7]. Of further concern is the fact that medications, proven in primary and secondary prevention in the general population, such as HMG-CoA reductase inhibitors, are yet to be shown to be beneficial in SLE [8].
Individuals with SLE have many actual and perceived barriers to exercise [9]. Physical impediments include arthritis, arthralgias and avascular necrosis, serositis, pulmonary involvement and anaemia. Fatigue, depression and co-morbid fibromyalgia are contributing factors. Furthermore, individuals with SLE appear to have lower cardiovascular capacity [10], [11] and diminished muscular strength [11] compared to controls. These barriers mean that patients are often reluctant to exercise and it is likely that their sedentary lifestyle is infrequently addressed by clinicians despite the numerous health benefits associated with physical activity [12].
Physical inactivity is an independent risk factor for cardiovascular events [13] and is highly prevalent in SLE [9], [14]. Exercise and physical activity decrease cardiovascular morbidity and mortality in the general population [12], [15]. Data from the Framingham Heart Study indicate that high levels of physical activity (in those over the age of 50) associate with an increased life expectancy of 3.7 years in men and 3.5 years in women [16]. In women with SLE, decreased physical activity has been shown to associate with pro-inflammatory high-density lipoprotein (HDL) and with increased carotid plaque [17].
Exercise is an important component of the management of a number of rheumatic conditions, and associated co-morbidities (RA [18], AS [19] and OA [20]). However, exercise has not traditionally been part of the care plans for individuals with SLE. Despite minimal SLE-specific evidence, in 2008 EULAR made recommendations for the management of SLE [21]. Physical activity, weight control and smoking cessation were identified as positive lifestyle modification strategies, particularly for individuals with increased CVD risk. In the years since, researchers have investigated the impact of therapeutic exercise on various outcomes in SLE. To date, only fatigue has been the subject of a systematic review; del Pino-Sedeño et al. [22] and Yuen and Cunningham [23] concluded that aerobic exercise appears effective in reducing fatigue in individuals with SLE. Other narrative reviews have suggested that habitual exercise has a role in preventing cardiovascular risks [24], [25], [26], in addition to reducing physical and psychological symptoms of SLE [24], enhancing physical fitness [25], [26] and improving health-related quality of life [25], [26]. There is a need for a systematic synthesis of studies to date to evaluate current evidence regarding the role of exercise in managing SLE.
This systematic review with meta-analyses aimed to establish the effect of exercise and physical activity on disease activity in adults with SLE, including any deleterious effects. Additionally, this study evaluated the effects of exercise interventions on (1) cardiovascular function and risk factors, (2) physical fitness and function, (3) health-related measures and (4) habitual physical activity levels, in adults with SLE. A final objective was to explore the effects of different types of exercise programmes.
Section snippets
Materials and methods
A protocol outlining the planned search strategy and methods of analysis for this review was registered online with a registry of systematic reviews (available at http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42016036407). The reporting was guided by the ‘Preferred Reporting Items for Systematic Reviews and Meta-analyses’ (PRISMA) recommendations [27].
Study selection
A total of 10 studies, reported across 11 articles published between 1989 and 2016, were included in this review. The search strategy is summarised in Figure 1. The electronic database search returned 3143 records and an additional 151 reports were identified from the conferences abstracts search. Of the 3068 records screened for eligibility, 31 titles were considered for full-text review. Studies were excluded for not meeting study design criteria (n = 1), not investigating a discrete SLE
Discussion
This systematic review investigated the effects of exercise and physical activity interventions on adults with SLE. No studies reported any deleterious effect on disease activity measured on the SLE disease activity index (SLEDAI); five studies [11], [31], [36], [41], [43] reported disease activity to be unchanged following exercise, with four of these demonstrating a non-significant trend towards improvement following exercise intervention. Only one study measured the influence of exercise on
Conclusions
This systematic review reports an emerging evidence-base broadly favouring therapeutic exercise interventions among individuals with SLE. Within this cohort, exercise was reported to be safe and well tolerated, while adverse effects were rare. Furthermore, meta-analysis suggests that exercise does not deleteriously effect disease activity. SLE associates with enhanced CV risk; although exercise programmes significantly improved aerobic capacity and cardiovascular function, cardiovascular risk
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