BIOMARKERS ROLE IN THE DEVELOPMENT OF SINUS NODE DYSFUNCTION

Aim. In patients with different types of sinus node dysfunction (SND), to study inflammation marker levels and assess their value as predictors of SND development. Material and methods. The study included 83 individuals: 63 patients with SND (the main group) and 20 controls. The main group was divided into three subgroups: Subgroup 1, with vegetative SND (VSND); Subgroup 2, with Type I and II sick sinus syndrome (SSS); and Subgroup 3, with tachy-brady syndrome, or Type III SSS. In all participants, the measurement of serum levels of inflammation markers, cardiac electrophysiological testing, and long-term electrocardiography monitoring were performed. The inflammation markers of interest included tumour necrosis factor alpha (THF-α), interleukin (IL) 6, IL-4, C-reactive protein (CRP), and fibrinogen. Results. Compared to controls, SND patients were characterised by increased levels of TNF-α and IL-6. TNF-α concentration was linked to SND type, with the highest levels observed in patients with tachy-brady syndrome. Elevated levels of inflammation markers independently predicted SND development. In particular, VSND risk was 2,5 times higher in patients with IL-6 concentration >3 pg/ml. SSS risk doubled when the levels of IL-6 increased from 2,5 pg/ml to 4 pg/ml. TNF-α levels >16 pg/ml were associated with a 1,5-fold increase in the risk of Type I-II SSS transformation into tachy-brady syndrome. Conclusion. Increased expression of inflammation cytokines in SND patients could be directly linked to pathogenetic mechanisms of this arrhythmic syndrome.

Sinus node dysfunction, C-reactive protein, fibrinogen, tumour necrosis factor alpha, interleukin-4, interleukin-6

1. Shul, man V.A., Nikulina S.Ju., Matjushin G.V Idiopathic (primary) diseases of spending system of heart. Kardiologija 2000; № 1: 89–92. Russian (Шульман В.А., Никулина С.Ю., Матюшин Г.В. и др. Идиопатические (первичные) заболевания проводящей системы сердца. Кардиология 2000; № 1:89–92).

2. Strain J. Results of endomyocardinal byopsy in patients with spontaneous ventricular tachycardia but without apparent structural heart disease. Circulation 2001; Vol.104:2886– 2891.

3. Vasilec L. M., Tarasova O.A. СRP and the FNO-Alpha at fibrillation of auricles. Aktual’nye voprosy klinicheskoj mediciny. Perm, 2005;146–150. Russian (Василец Л.М., Тарасова О.А. СРП и ФНО-альфа при фибрилляции предсердий. Актуальные вопросы клинической медицины. Пермь, 2005;146–150).

4. Kobalava Zh. D., Kotovskaja Ju. V., Dogotar’i O. A. i dr. Characteristic of a subclinical inflammation at patients with not complicated arterial hypertension. Arterial hypertensia 2006; № 3 (Vol.2):216–221 Russian (Кобалава Ж.Д., Котовская Ю.В., Доготарьи О.А. и др. Характеристика субклинического воспаления у больных с неосложненной артериальной гипертонией. Артериальная гипертензия 2006; № 3 (2 том):216–221).

5. Tarasova O. A. A role of markers of an inflammation at fibrillation of auricles. “Vrachaspirant”. Voronezh, 2007; 1 (16):49–53. Russian (Тарасова О. А. Роль маркеров воспаления при фибрилляции предсердий. «Врач-аспирант». Воронеж, 2007; 1 (16):49–53).

6. Nasonov E. L., Panjukova E. V., Aleksandrov E.N C-reacrive protein – an inflammation marker at an atherosclerosis (the new data). Cardiology 2002; № 37:53–62. Russian (Насонов Е. Л., Панюкова Е. В., Александров Е. Н. С-реактивный белок – маркер воспаления при атеросклерозе (новые данные). Кардиология 2002; № 37:53–62).

7. Rosen B.D., Cushman M, Nasir K, et al. Relationship between C-reactive protein levels and regional left ventricular function in asymptomatic individuals: the Multi-Ethnic Study of Atherosclerosis. J Am Coll Cardiol 2007; 49:594–600.

8. Lee KWJ, Hill JS, Walley KR et al. Relative value ofmultiple plasma biomarkers as risk factors for coronary arterydisease and death in an angiography cohort. CMAJ 2006; 174:461–466.

9. Rauchaus M., Clark A. L., Doehner W. et al. The relationship between cholesterol and survival in patients with chronic heart failure. J Am Coll Cardiol 2003;42:1933– 1944.

10. Adamjan K. G., Azarapetjan L. G., Grigorjan S. V. Role of a latent inflammation in patogenese fibrillations of auricles. Vestnik aritmologii, 2008; 54:34–41. Russian (Адамян К. Г., Азарапетян Л. Г., Григорян С.В. Роль латентного воспаления в патогенезе фибрилляции предсердий. Вестник аритмологии 2008; 54:34–41).

11. Albert CM, Ma J, Rifai N et al. Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death. Circulation 2002; 105:2595–9.

12. Chung MK, Martin DO, Sprecher D, et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation 2001; 104:2886–91.

13. Acevedo M, Corbalan R, Braun S et al. C- reacrive protein and atrial fibrillation: evidence for the presence of inflammation in the perpetuation of the arrhythmia. Int. J Cardiolog. 2006; 14,108 (3):326–331.

14. Aviles R.J., Martin D.O., Apperson-Hansen C. et al. Inflammation as a rick factor for atrial fibrillation. Circulation 2003; 108 (24):3006–3010.