Effect of yoga therapy on disease activity, cardiac autonomic functions and inflammatory markers in patients of Rheumatoid arthritis - A randomized control trial

1.Background :

Rheumatoidarthritis (RA) is a chronic debilitating condition that affects 0.5 to 1percent of the Indian population (1). RA is characterized by chronic jointinflammation, bony erosions, deformities, joint destruction, physicaldisability and is associated with significant morbidity, premature mortalityand decline in the functional status of the patient (2). Major biological advances have been made in recent years, andaggressive pharmacologic treatment has resulted in patient improvements.However, not all patients respond effectively to treatment, and the use of somebiological agents has been associated with medical risks and socioeconomiccosts. Even when joint inflammation is medically controlled, some patientsexperience RA-related disability, suggesting the utility of complementaryrehabilitation efforts, such as yoga.

A. Rationale :

RA isassociated with altered body composition leading to reduction in fat-free mass,higher body fat content is present even in the underweight and normal weight RApatients.There is a higher incidence of centripetal obesity  in RA patients, without any obvious change intotal body weight (3) In alteredbody composition, BMI may not be a valid predictor of Body fat .

Obesity isa chronic inflammatory condition and it independently associates withclassical cardiovascular disease (CVD) risk factors in RA; RA patients are morelikely to have such CVD risk factors.For a given Body Fat content, patientswith RA have a significantly lower BMI, by almost 2 kg/m2 comparedwith the general population.If BMI cut-offs of 23 % and 28 % are taken foroverweight and obesity similar to Asian-Indian population in whom bodycomposition is also altered, prevalence of higher overweight (∼45%) and obesity (∼37%) occurs among RA patients(4).

Previousstudies have reported adipokines like Leptin, adiponectin, visfatin andresistin, secreted from adipose tissue(5), are involved in the increasedproduction of proinflammatory agents like TNF-α,  IL-1, IL-6 and CRP, which play important rolein the pathogenesis of RA.Central adiposity is associated with insulinresistance and endothelial dysfunction in other metabolic conditions like DM .Inspite of close associations of obesityboth with CVD risk and inflammation, as well as the body composition changesobserved in RA patients, there is paucity of data on the study of obesity andbody composition in RA patients.

Incidenceof CV mortality has been reported higher in RA than in general population. Previous studies report that conventional CVD risk factors do notfully explain excess CV morbidity and mortality in RA patients.In previousstudies, cardiovascular autonomic dysfunction has been reported around 61–75%in RA patients(6). Oneprevious study done in AIIMS reported overactivity of sympathetic nervoussystem and underactivity of parasympathetic nervous system in RA patients (7). The main pattern of dysfunction is impairment of cardiovascularreflexes and altered HRV, indicative of reduced cardiac parasympathetic (strongevidence) activity and elevated cardiac sympathetic activity (limited evidence). The literature up to date is underpowered to determine the causalrelationships between inflammation, ANS dysfunction, & adiposity inRA.Other reports suggest that local inflammatory mediators like IL-1 andTNF-alpha upregulate expression of adhesion molecules in endothelial cellsleading to endothelial dysfunction and leading to increase in CVatherosclerosis & CVD events(8).

Yoga is amind body technique involving breath control, physical exercise and meditation.Beneficial in healthy subjects as well as in various diseases including autoimmune disorders, rheumatoid arthritis and osteoarthritis. An RCT from the USA compared a 6-week Iyengar yoga intervention twiceweekly with usual care. It  included 30 youngwomen with RA. The RCT found no group differences in bodily pain on the SF-36but Significant effects were reported for disability,pain(9). Another RCToriginating from India included 80 patients with RA , yoga intervention givenfor 7 weeks compared with usual care, yoga significantly reduced pain on the(SDPIS) Simple Descriptive Pain Intensity Scale (10). Similarlyfew other small sized studies have reported that yoga therapy is beneficial onthe hand grip strength, Quality of Life, pain scores, immune parameters likeIL-6, depression and anxiety of rheumatoid arthritis patients (11,12,13). The evidence drawn from previous studiesof yoga therpay on RA is still limited due to low methodological quality andoutcome measures.

B.        Novelty :

There ispaucity of data on the assessment and to find association, if any, between diseaseactivity,  bodycomposition, cardiac autonomic functions, inflammatory, and oxidativemarkers  in thepatients of RA. Also, to the best of ourknowledge, there is no previous study in which, effect of 12 weeks of yogatherapy has been studied in the RA patients. Therefore, present study has beenconceived.

C.        Expected outcome &application :

Theexpected outcome of the proposed study is the effect of 12 weeks of yogatherapy on disease activity, body composition, cardiac autonomic functions,inflammatory and oxidative markers in patients with  rheumatoid arthritis

Applicability

The outcomeof the study will be highly useful for the treatment / management of  rheumatoid arthritis patients along with thestandard medical treatment

3.         Research question(s) :

What is the effect of yoga on diseaseactivity, body composition, cardiac autonomic functions and inflammatory and oxidative markers in patients with  rheumatoid arthritis ?

4.        Research hypothesis (es), if any :

Twelve weeks of yoga practice will reducethe disease activity, inflammation & oxidative stress andimprove the body composition, cardiac autonomicfunctions in patients with  rheumatoidarthritis.

5.         Aim and objectives:

Primary objective(s) :

1.     Toassess the effect of 12 weeks of yoga therapy on disease activity, bodycomposition, cardiac autonomic functions, inflammatory and oxidative markers inpatients with  rheumatoid arthritis.

2.     Toassess body composition, cardiac autonomic functions, inflammatory, oxidativemarkers and disease activity in patients with rheumatoid arthritis.

3.     Toidentify the association of body composition, cardiac  autonomic functions, inflammatory, oxidativemarkers and disease activity among rheumatoid arthritis patients.

Secondary objective(s)

To assess the effect of yogaon quality of life by HealthAssessment Questionnaire among  the patientswith rheumatoid arthritis.

Relevant referencesfor the project (in Vancouver style, cited sequentially in the text ofproject) :

• 1.    Sokka T, Abelson B, Pincus T. Mortalityin rheumatoid arthritis: 2008 update. Clin Exp Rheumatol  2008; 26(5): 35–61.
• 2.    Mutru O, Laakso M, Isomaki H, Koota K.Ten year mortality and causes of death in patients with rheumatoid arthritis. BrMed J  1985; 290(6484): 1797-9.
• 3.    Roubenoff R, Roubenoff RA, Ward LM, Holland SM,Hellman DB. Rheumatoid cachexia: depletion of lean body mass in rheumatoidarthritis: possible association with tumor necrosis factor. J Rheumatol 1992; 19: 1505–10.
• 4.    KremersHM, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Prognostic importance of lowbody mass index in relation to cardiovascular mortality in rheumatoidarthritis. Arthritis Rheum 2004; 50: 3450–7.
• 5.    Hauner H. Secretory factors from human adiposetissue and their functional role. ProcNutrSoc2005; 64: 163–9.
• 6.    Stojanovich L, Milovanovich B , DeLuka SR,Popovich-Kuzmanovich D, Bisenich V, Djukanovich B et al. Cardiovascularautonomic dysfunction in systemic lupus, rheumatoid arthritis, primary Sjogrensyndrome and other autoimmune diseases. Lupus2007; 16: 181-5.
• 7.    Yadav RK, Gupta R, Deepak KK. A pilot study on shortterm heart rate variability & its correlation with disease activity inIndian patients with rheumatoid arthritis. Indian J Med Res 2012; 136: 593–8.
• 8.    Manzi S, Wasko MC. Inflammation-mediated rheumaticdiseases and atherosclerosis. AnnRheum Dis 2000; 59: 321–5.
• 9.     Evans S, Moieni M, Lung K et al. Impact of Iyengar yoga on quality oflife in young women with rheumatoid arthritis. Clin J Pain  2013; 29(11): 988-97.
• 10.  Singh VK, Bhandari RB, Rana BB. Effect of yogic package on rheumatoidarthritis. Indian J Physiol Pharmacol 2011; 55: 329-35.
• 11. Williams K, Steinberg L, Petronis J. TherapeuticApplication of Iyengar Yoga for Healing Chronic Low Back Pain. Int J Yoga 2003; 13: 55-67.
• 12. Balaji PA, Varne SR, Ali SS. Physiological effectsof yogic practices and    transcendentalmeditation in health and disease. N AmJ Med Sci  2012; 4: 442-8.
• 13.  Badsha H, Chhabra V, Leibman C et al. Thebenefits of yoga for rheumatoid arthritis: results of a preliminary, structured8-week program. Rheumatol Int  2009; 29:1417-21.