Effect of Exercise On Cardiac Autonomic Function In Female Rheumatoid Arthritis Patients
Introduction: Cardiovascular morbidity and mortality is increased in rheumatoid arthritis(RA) patients(1,2). Autonomic dysfunction has been mentioned as part of the explanation(3). A literature search conducted(1963-2010) found only 27 publications, using 8 different testing protocols to determine the extent of autonomic nerve involvement in RA patients. Autonomic tests included were: sweat response(4,5), cardiovascular reflex tests(6-17), divergent autonomic reactions to specific tasks(18), pre-ejection period and respiratory sinus arrhythmia(19), sympathetic skin response and RR interval variation(20,21), pupillography(22,23), heart rate variability (HRV)(3,16,17,24-28) and Heart Rate Turbulence(29). Autonomic dysfunction was reported by some but not all authors. Review results were inconclusive as study results could not be compared due to numerous disparate tests used and heterogeneous study methodology. Problems identified were incomplete information on exclusion criteria, non-stabilisation of environment, males and females in the same small study groups and use of inappropriate statistical methods(3-29) I therefore firstly executed a study that confirmed cardiac autonomic dysfunction comparing females suffering from RA (n=45) to a healthy female group (n=39). This was subsequently followed by the undermentioned study. Methods:The aim of this study was to evaluate the effect of exercise on cardiac autonomic function as measured by short-term heart rate variability (HRV) in females suffering from RA. Females with confirmed Rheumatoid Arthritis (RA) were randomly assigned to an exercise group (RAE) and a sedentary group (RAC). RAE was required to train under supervision two to three times per week, for three months. Three techniques (time domain-, frequency domain-, and Poincaré plot analyses) were used to measure HRV at baseline and study completion. Results: At baseline RAC (n=18) had significantly better HRV compared to RAE (n=19). At study completion the variables showing significant changes (p=0.01 to 0.05) favoured RAE in all instances. Wilcoxon signed rank tests were performed to assess changes within groups from start to end. RAE showed significant improvement for most of the standing variables, including measurements of combined autonomic influence e.g. RRSTD (p=0.002) and variables indicating only vagal influence e.g. pNN50 (p=0.014). RAC mostly deteriorated with emphasis on variables measuring vagal influence [RMSSD, pNN50, SD1 and HF(ms2)]. Posture change showed a mixture of outcome for both groups. Discussion: Exercise intervention has an effect on cardiac autonomic function in RA patients. Especially the standing variables indicating improved vagal influence are affected positively. Exercise can thus be used as an instrument to improve cardiac health in a patient group known for increased cardiac morbidity.References1. Meune C, Touze E, Trinquart L, Allanore Y. Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford) 2009 Oct;48(10):1309-1313.2. Maradit-Kremers H, Crowson CS, Nicola PJ, Ballman KV, Roger VL, Jacobsen SJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2005 Feb;52(2):402-411. 3. Evrengul H, Dursunoglu D, Cobankara V, Polat B, Seleci D, Kabukcu S, et al. Heart rate variability in patients with rheumatoid arthritis. Rheumatol.Int. 2004 Jul;24(4):198-202. 4. Bennett PH, Scott JT. Autonomic neuropathy in Rheumatoid Arthritis. Ann.Rheum.Dis. 1965 Mar;24:161-168.5. Kalliomaki JL, Saarimaa HA, Toivanen P. Axon reflex sweating in rheumatoid arthritis. Ann.Rheum.Dis. 1963 Jan;22:46-49.6. Edmonds ME, Jones TC, Saunders WA, Sturrock RD. Autonomic neuropathy in rheumatoid arthritis. Br.Med.J. 1979 Jul 21;2(6183):173-175.7. Leden I, Eriksson A, Lilja B, Sturfelt G, Sundkvist G. Autonomic nerve function in rheumatoid arthritis of varying severity. Scand.J.Rheumatol. 1983;12(2):166-170.8. Piha SJ, Voipio-Pulkki LM. Elevated resting heart rate in rheumatoid arthritis: possible role of physical deconditioning. Br.J.Rheumatol. 1993 Mar;32(3):212-215.9. Toussirot E, Serratrice G, Valentin P. Autonomic nervous system involvement in rheumatoid arthritis. 50 cases. J.Rheumatol. 1993 Sep;20(9):1508-1514.10. Bekkelund SI, Jorde R, Husby G, Mellgren SI. Autonomic nervous system function in rheumatoid arthritis. A controlled study. J.Rheumatol. 1996 Oct;23(10):1710-1714.11. Maule S, Quadri R, Mirante D, Pellerito RA, Marucco E, Marinone C, et al. Autonomic nervous dysfunction in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA): possible pathogenic role of autoantibodies to autonomic nervous structures. Clin.Exp.Immunol. 1997 Dec;110(3):423-427.12. Louthrenoo W, Ruttanaumpawan P, Aramrattana A, Sukitawut W. Cardiovascular autonomic nervous system dysfunction in patients with rheumatoid arthritis and systemic lupus erythematosus. QJM 1999 Feb;92(2):97-102.13. Sandhu V, Allen SC. The effects of age, seropositivity and disease duration on autonomic cardiovascular reflexes in patients with rheumatoid arthritis. Int.J.Clin.Pract. 2004 Aug;58(8):740-745.14. Stojanovich L, Milovanovich B, de Luka SR, Popovich-Kuzmanovich D, Bisenich V, Djukanovich B, et al. Cardiovascular autonomic dysfunction in systemic lupus, rheumatoid arthritis, primary Sjogren syndrome and other autoimmune diseases. Lupus 2007;16(3):181-185.15. Bidikar MP, Ichaporia RB. Autonomic (sympathetic) nervous system involvement in rheumatoid arthiritis patients. Indian J.Physiol.Pharmacol. 2010 Jan-Mar;54(1):73-79.16. Milovanovic B, Stojanovic L, Milicevik N, Vasic K, Bjelakovic B, Krotin M. Cardiac autonomic dysfunction in patients with systemic lupus, rheumatoid arthritis and sudden death risk. Srp.Arh.Celok.Lek. 2010 Jan-Feb;138(1-2):26-32.17. Aydemir M, Yazisiz V, Basarici I, Avci AB, Erbasan F, Belgi A, et al. Cardiac autonomic profile in rheumatoid arthritis and systemic lupus erythematosus. Lupus 2010 Mar;19(3):255-261.18. Geenen R, Godaert GL, Jacobs JW, Peters ML, Bijlsma JW. Diminished autonomic nervous system responsiveness in rheumatoid arthritis of recent onset. J.Rheumatol. 1996 Feb;23(2):258-264.19. Dekkers JC, Geenen R, Godaert GL, Bijlsma JW, van Doornen LJ. Elevated sympathetic nervous system activity in patients with recently diagnosed rheumatoid arthritis with active disease. Clin.Exp.Rheumatol. 2004 Jan-Feb;22(1):63-70.20. Tan J, Akin S, Beyazova M, Sepici V, Tan E. Sympathetic skin response and R-R interval variation in rheumatoid arthritis. Two simple tests for the assessment of autonomic function. Am.J.Phys.Med.Rehabil. 1993 Aug;72(4):196-203.21. Gozke E, Erdogan N, Akyuz G, Turan B, Akyuz E, Us O. Sympathetic skin response and R-R interval variation in cases with rheumatoid arthritis. Electromyogr.Clin.Neurophysiol. 2003 Mar;43(2):81-84.22. Barendregt PJ, van der Heijde GL, Breedveld FC, Markusse HM. Parasympathetic dysfunction in rheumatoid arthritis patients with ocular dryness. Ann.Rheum.Dis. 1996 Sep;55(9):612-615.23. Schwemmer S, Beer P, Scholmerich J, Fleck M, Straub RH. Cardiovascular and pupillary autonomic nervous dysfunction in patients with rheumatoid arthritis - a cross-sectional and longitudinal study. Clin.Exp.Rheumatol. 2006 Nov-Dec;24(6):683-689.24. Anichkov DA, Shostak NA, Ivanov DS. Heart rate variability is related to disease activity and smoking in rheumatoid arthritis patients. Int.J.Clin.Pract. 2007 May;61(5):777-783.25. Goldstein RS, Bruchfeld A, Yang L, Qureshi AR, Gallowitsch-Puerta M, Patel NB, et al. Cholinergic anti-inflammatory pathway activity and High Mobility Group Box-1 (HMGB1) serum levels in patients with rheumatoid arthritis. Mol.Med. 2007 Mar-Apr;13(3-4):210-215.26. Bruchfeld A, Goldstein RS, Chavan S, Patel NB, Rosas-Ballina M, Kohn N, et al. Whole blood cytokine attenuation by cholinergic agonists ex vivo and relationship to vagus nerve activity in rheumatoid arthritis. J.Intern.Med. 2010 Jul;268(1):94-101.27. Vlcek M, Rovensky J, Blazicek P, Radikova Z, Penesova A, Kerlik J, et al. Sympathetic nervous system response to orthostatic stress in female patients with rheumatoid arthritis. Ann.N.Y.Acad.Sci. 2008 Dec;1148:556-561.28. Holman AJ, Ng E. Heart rate variability predicts anti-tumor necrosis factor therapy response for inflammatory arthritis. Auton.Neurosci. 2008 Dec 5;143(1-2):58-67.29. Avsar A, Onrat E, Evcik D, Celik A, Kilit C, Kara Gunay N, et al. Cardiac autonomic function in patients with rheumatoid arthritis: heart rate turbulence analysis. Anadolu Kardiyol Derg. 2011 Feb;11(1):11-15.
Janse van Rensburg, Dina C.; Ker, James A.; Grant, Catharina C.; and Fletcher, Lizelle
"Effect of Exercise On Cardiac Autonomic Function In Female Rheumatoid Arthritis Patients,"
International Journal of Exercise Science: Conference Proceedings: Vol. 5
, Article 21.
Available at: https://digitalcommons.wku.edu/ijesab/vol5/iss2/21