Role of inflammation in the development of cardiac autonomic disfunction in patients with systemic lupus erythematosus

Objective. To evaluate role of inflammation in pathogenesis of cardiac autonomic dysfunction assessed by heart rate variability (HRV) analyses, in patients (pts) with systemic lupus erythematosus (SLE). Material and methods. 75 female pts with SLE aged before 55 years were included. Control group consisted of 32 healthy women of comparable age. Clinical symptoms, activity degree and main cardiovascular risk factors were assessed. Common carotid duplex scanning with measurement of intima-media thickness, echocardiography, 24 h ECG ambulatory recording with determination of time domain parameters, evaluation of serum inflammation markers level (CRP, IL-6, TNFa) were performed. Results. HRV time domain parameters adjusted by McanNN - SDNNn%, SDNNin%, rMSSDn%, pNN50% in women with SLE were lower than in healthy control. HRV parameters inversely correlated with inflammation markers in SLE (p<0,05). SLE pts were divided into 4 groups: 1 (n=12) - pts with low HRV parameters and high level of IL-6; 2 (n=13) - low HRV and normal IL-6; 3 (n=6) - normal HRV and high IL-6; 4 (n=44) - normal HRV and IL-6. SLEDA1 2K, left atrium size, levels of markers of inflammation in group 1 were higher, then in group 4 (p<0,05). Hypertension, dyslipidemia, smoking and subclinical atherosclerosis of carotid arteries were more frequent in group 2 compared to group 4 (p<0,05). Conclusion. These results suggest important role of autoimmune inflammation in pathogenesis of cardiac autonomic dysfunction in SLE pts with high disease activity and traditional cardiovascular risk factor, atherosclerotic changes - in low SLE activity. HRV, traditional cardiovascular risk factors and inflammatory markers combined measurement can help to identify subjects at risk of cardiovascular mortality among SLE pts.

heart rate variability, inflammation, systemic lupus erythematosus, atherosclerosis

1. <div><p>Рациональная фармакотерапия ревматических заболеваний: Руководство для практикующих врачей. Под ред. Насоновой В.А., Насонова Е.Л. М.; Литтерра, 2003, 507 с.</p><p>Насонов Е.Л. Антифосфолипидный синдром. М., Литтерра. 2004, 440 с.</p><p>Manzi S., Meilahn Е. N., Rairie J.E. et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am. J. Epidemiol., 1997, 145,408-415.</p><p>Westerwel! P.E., Remco K.M., Luyten A.C. et al. Premature atherosclerotic cardiovascular disease in systemic lupus erythematosus. Arthr. Rheum., 2007, 56, 1384 - 1396.</p><p>Ross R. Atherosclerosis — an inflammatory disease. N. Engl. J. Med. 1999, 340, 115- 126.</p><p>Hansson G.K. Inflammation, atherosclerosis and coronary artery disease. N. Eng. J. Med., 2005. 352, 1685-1695.</p><p>Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation, 1996, 93,1043-1065.</p><p>Соколов С.Ф., Малкина T.A. Клиническое значение оценки вариабельности ритма сердца. Сердце, 2002, 2, 72- 75.</p><p>SajadiehA., Nielsen О., Rusmussen V. et al. Increased heart rate and reduced heart rate variability are associated with subclinical inflammation in middle-age and elderly subjects with no apparent heart diseases. Eur. Heart J. 2004, 25, 363 -370.</p><p>von Kanel R., Nelesen R.A., Mills P.J. et al. Relationship between heart rate variability, interleukin-6, and soluble tissue factor in healthy subjects. Brain Beliav. Immun., 2008, 22. 461 - 468.</p><p>Janszky /., Ericson М., Lekander M. et al. Inflammatory markers and heart rate variability in women with coronary heart diseases. J. Intern. Med., 2004, 5. 421 - 428.</p><p>Shebab A.M., MacFadyen R.J., McLaren M. et at. Sudden unexpected death in heari failure may be preceded by short term, intraindividual increases in inflammation and in autonomic dysfunction: a pilot study. Heart, 2004, 90, 1263 — 1268.</p><p>Shinohara Т., Tacahashi N., Yufu K. et al. Role of interleukine-6 levels in cardiovascular autonomic dysfunction in type 2 diabetic patients. Eur. J. Nucl. Med. Mot Imaging. 2008; Epub ahead of print.</p><p>Amnson D., Mittleman M.A., BurgerA.J. Interleukin-6 levels are inversely correlated with heart rate variability in patients with decompensated heart failure. J. Cardiovasc. Electrophysiol., 2001, 12, 294 - 300.</p><p>Hochberg M.C. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthr. Rheum. 1997,40, 1725.</p><p>Gladman D.D., Ibanez D., Urowitz M.B. Systemic lupus erythematosus disease activity index 2000. J. Rheumatol. 2002, 29, 288-291.</p><p>Gladman D.D., Urowitz M.B., Goldsmith C.ll. et al. The reliability of the Systemic Lupus International Collaborating Clinics. American College of Rheumatology Damage Index in patients with systemic lupus erythematosus. Arthr. Rheum. 1997, 40, 809-813.</p><p>Перова H.B., Косматова О. В. Простой метод оценки снижения суммарного коронарного риска при лечении гипертонии и гиперлипидемии. Кардиология, 2002, 3, 23-25.</p><p>Sidhu P.S., Desai S. R. A simple and reproducible methodfor assessing intimal-medial thickness of the common carotid artery. Br. J. Radiol. 1997, 70, 85 — 89.</p><p>Wranicz J.K., Cygankiewich /., Zielinska M. et al. Non-invasive evaluation in patients with systemic lupus erythematosus. J. Med., 2001, 32, 195 - 206.</p><p>Lagana B., Schillaci O., Tubani L. et at. Lupus carditis: evaluation with technetium-99m MIBI myocardial SPECT and heart rate variability. Angiology, 1999, 50 (2): 143 - 148.</p><p>Lagana B., Gentile R., Vella C. eta I. Heart and autonomic nervous system in connective tissue disorders. Recent. Prog. Med. 1997, 88(12), 579 - 584.</p><p>Laversuch C.J., Seo //., Modarres H. et al. Reduction in heari rate variability in patients with systemic lupus erythematosus. J. Rheumatol. 1997, 24, 1540 - 1544.</p><p>Lagana B., Tubani L., Maffeo N. et al. Heart rate variability and cardiac autonomic function in patients with systemic lupus erythematosus. Lupus, 1996, 5 (I), 44 - 48.</p><p>Stein K.S., McFarlane 1.С., Goldberg N. et al. Heart rate variability in patients with systemic lupus erythematosus. Lupus, 1996, 5(1), 49-55.</p><p>Stojanovich L., Milovanovich B., de Luka S.R. Cardiovascular autonomic dysfunction in systemic lupus, rheumatoid arthritis, primary Sjogren syndrome and other autoimmune diseases. Lupus, 2007, 16 (3), 181-185.</p><p>Rho Y.H., Chung C. P., Oeser A. et al. Novel cardiovascular risk factors in premature coronary&gt; atherosclerosis associated with systemic lupus erythematosus. J. Rheumatol. 2008, 15 Epub ahead of print.</p><p>de Carvalho J.F., Hanaoka B. Szyper-Kravitz М., Shoenfeld Y. C-reactive protein and its implications in systemic lupus erythematosus. Acta Reumatol. Port, 2007, 32, 317 - 322.</p><p>Lee S.S., Singh S., Link K. et al. High-sensitivity C-reactive protein as an associate of clinical subsets and organ damage in systemic lupus eiythematosus. semin. arthr. rheum., 2008, Epub ahead of print.</p><p>Suh С.И., Kim H.A. Cytokines and their receptors as biomarkers of systemic lupus erythematosus. Expert Rev. Mol. Diagn., 2008, 8,189— 198.</p><p>Chun H.Y., Chung J.W., Yun J.M. et al. Cytokine 1L-6 and IL-10 as biomarkers in systemic lupus erythematosus. J. Clin. Immunol., 2007, 27, 461 — 465.</p><p>Woods A., Brull D.J., Humphries S.E. et al. Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6. Eur. Heart J. 2000, 21, 1574 - 1583.</p><p>MarslandA.L., Gianaros P.J., PratherA.A. Stimulated production of proinflammatory cytokines covaries inversely with heart rate variability. Psychosom. Med. 2007; 8: 709 - 716.</p><p>Sloan R.P., McCreath H., Tracey K.J. RR interval variability is inversely related to inflammatory markers: the CARD 1 A study. Mol. Med., 2007, 13, 178 -184.</p><p>Новикова Д.С., Попкова Т.В., Панафидина Т.А. и соавт. Клиническое значение оценки вариабельности ритма сердца у больных системной красной волчанкой. Тер.архив; 2008 (в печати).</p><p>Karp /., Abrahamowicz М., Fortin P.R. et al. Recent corticosteroid use and recent disease activity: independent determinants of coronary heart disease risk factors in systemic lupus erythematosus? Arthr. Rheum., 2008, 59, 169- 175.</p><p>Roman M.J., Shanker B.A., Davis A. etal. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N. Eng. J. Med., 2003, 349, 2399-2406.</p><p>Ahmad Y, Shelmerdine J., Bodill H. etal. Subclinical atherosclerosis in systemic lupus erythematosus (SLE): the relative contribution of classic risk factors and the lupus phenotype. Rheumatology, 2007, 46, 983 — 988. Ferreira G.A., Sato E.I., Andrade L.C. et al. The immunosuppressive therapy is associated with better endothelial function in SLE patients. Ann. Rheum. Dis., 2007, 66 (suppl 11), 462. Lesiak A., Sysa-Jedrzejowska A., Narbutt J. et al. Proinflammatory cytokines in inactive systemic lupus erythematosus. Przegl. Lek., 2005, 62, 838 - 842.</p></div><br />