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Upalni biljezi u akutnom koronarnom sindromu

Upalni biljezi u akutnom koronarnom sindromu. M. Bergovec, Z. Trstenjak, V. Raos, S. Pavlović, M. Raguž, J. Šikić Vagić, Ž. Romić, D. Kranjčec. ,,,,,,,,,,,. UPALA? IMUNOLOŠKI SUSTAV?.

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Upalni biljezi u akutnom koronarnom sindromu

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  1. Upalni biljezi u akutnom koronarnom sindromu M. Bergovec, Z. Trstenjak, V. Raos, S. Pavlović, M. Raguž, J. Šikić Vagić, Ž. Romić, D. Kranjčec

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  3. UPALA? • IMUNOLOŠKI SUSTAV?

  4. 1.VEĆA UČESTALOST KORONARNE BOLESTI KOD OSOBA SA KRONIČNIM UPALNIM ZBIVANJIMA U ORGANIZMU (H.Pylori,C.Pneumoniae,CMV,EBV infekcija) • Whinchup PH, et al. Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men. Heart 1996,75:568-72 • Mendall MA. Chlamydia pneumoniae: risk factors for seropositivity and association with coronary heart disease. J Infect 1995;30:121-8 • Choussat J et al. Effect of prior exposure to C. Pneumoniae, H. Pylori or citomegalovirus on the degree of inflammation and one-year prognosis of patients with unstable angina or non-Q-wave acute myocardialinfarction. Am J Cardiol 2000;86:379-84

  5. 2. NIŽA STOPA KORONARNE BOLESTI U OSOBA SA NIŽIM RAZINAMA UPALNIH MEDIJATORA (umjerena fizička aktivnost) • Willich SN, et al. Physical activity and risk of peripheral arterial disease in the general population: Edinburgh artery study. J Epidemiol Community health 1993;47:475-80 • Stratton JR, et al. Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults. Circulation 1991;83:1692-7

  6. 3.VIŠE VRIJEDNOSTI UPALNIH MARKERA KOD OSOBA SA KORONARNOM BOLEŠĆU U ODNOSU NA KONTROLNU SKUPINU • de Maat MP, et al. Association of plasma fibrinogen levels with coronary artery disease,smoking and inflammatory markers. Atherosclerosis 1996;121:185-91 • Ridker PM et al. Inflammation,aspirin and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973-9 • Haverkate F et al. Production of C-reactive protein and risk of coronary events in stable and unstableangina. European Concerted Action on thrombosis and Disabilities Angina Pectoris Study Group. Lancet 1997;349:462-6

  7. »UPALNI BILJEZI U AKUTNOM KORONARNOM SINDROMU» ZNANSTVENO-ISTRAŽIVAČKI PROJEKT MINISTARSTVA ZNANOSTI I TEHNOLOGIJE RH br. 019800 VODITELJ PROJEKTA:prof.dr.sc. M. Bergovec SURADNICI:- dr.M.Bergovec -dr.D.Kranjčec -vms.V.Markač -mr.sc.J.Mirat -prim.dr.S.Pavlović -mr.sc.M.Raguž -prim.dr.V.Raos -prof.dr.sc.Ž.Romić -ms M.Slanc -mr.sc.J.Šikić Vagić -dr.Z.Trstenjak

  8. AKUTNI KORONARNI SINDROM • 400 pacijenata sa AKS: • NESTABILNA ANGINA PEKTORIS • NSTEMI • STEMI

  9. RUTINSKE LABORATORIJSKE PRETRAGE: • E,Hb,Htc,L,SE,Trc • kolesterol,trigliceridi,HDL,LDL • urea,kreatinin,acidum uricum,AST,ALT • Na,K,Cl • CK,CK-MB,Troponin I

  10. ANAMNESTIČKI PODACI: • hipertenzija • hiperlipidemija • pušenje • diabetes mellitus • BMI • prijašnja koronarna bolest

  11. UPALNI MARKERI: • interleukin-6 • s-amiloid a • high sensitive-C-reaktivni protein • neopterin • fibrinogen

  12. IL-6 • limfociti, fibroblasti, endotelne stanice • rast i sazrijevanje B-limfocita; poliklonska produkcija imunoglobulina • jedini stimulira sintezu svih proteina akutne faze: CRP, S-AA, fibrinogena, α1-kimotripsina i haptoglobina • Woods A et al. Genetics of inflammation and risk of coronary heart disease:the central role of interleukin-6.Eur Heart J 2000;21:1574-83 • Castell JV et al. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes. FEBS Lett 1989;24:237-9

  13. S-AA • protein akutne faze, prekursor tkivnog AA • apolipoprotein-veže se na HDL čestice-modulacija metabolizma lipoproteina (brže uklanjanje HDL lipoproteina iz cirkulacije) • Liuzzo G et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina.N Engl J Med 1997;336:973-9 • Malle E et al. Serum amyloid A (SAA):an acute phase protein and apolipoprotein. Atherosclerosis 1993;102:131-46

  14. hs-CRP • najduže poznat i najviše puta istraživan upalni protein • bazalne razine značajno više kod nestabilne angine ili AIM • prediktivni faktor za pojavu AKS?! • Liuzzo G et ak. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina.N Engl J Med 1997;336:973-9 • Morrow DA et al. C-reactive protein is a potent predictor of mortality independently of and in combination with Troponin T in acute coronary syndromes:a TIMI 11 A substudy. J Am Coll Cardiol 1998;31:1460-65 • Nomoto K et al.Involvement of inflammation in acute coronary syndromes assessed by levels of hs-C-reactive protein,matrix metalloproteinase-9 and soluble vascular-cell adhesion molecule-1. J Cardiol 2003 Nov;42(5):201-6

  15. neopterin • derivat pteridina • sekrecija iz makrofaga nakon stimulacije sa IFN-γ • značajno povišene razine kod nestabilne AP ili AIM u usporedbi sa stabilnom AP • Gupta S et al. Serum neopterin in acute coronary syndromes. Lancet 1997;349:1252-3 • Kaski JC. Increased neopterin in patients with chronic and acute coronary syndromes. J Am Coll Cardiol 1998;31:523-6 • Schumacher M et al. Increased neopterin in patients with chronic and acute coronary syndromes. J Am Coll Cardiol 1997;30:703-7

  16. fibrinogen • reaktant akutne upalne faze • vezanje na II b/III a→agregacija trombocita • stvaranje fibrina •  viskoznost plazme • Hennekens CH et al. A prospective study of fibrinogen and risk of myocardial infarction in the Physicians' Health Study. J Am Coll Cardiol 1999;33:1347-1352 • Stec JJ et al. Association of fibrinogen with cardiovascular risk factors and cardiovascular disease in the Framingham Offspring Population. Circulation 2000;102:1634-1638

  17. METABOLIČKI SINDROM X (WHO definicija): • DIABETES MELLITUS ILI INTOLERANCIJA GLUKOZE + 2 ili više od slijedećih parametara: • sistolički tlak 140 mmHg i/ili dijastolički tlak 90 mmHg i/ili primjena antihipertenzivne terapije • centralni tip pretilosti WHR0,9 (M) WHR0,85 (F) • mikroalbuminurija (20 g/min) • dislipidemija: trigliceridi  150 mg/dl i/ili HDL 35 mg/dl(M) HDL 39 mg/dl(F)

  18. PARAMETRI ISPITIVANJA: • KLINIČKA SLIKA • RTG SRCA I PLUĆA • EJEKCIJSKA FRAKCIJA (UZV METODOM PO SIMPSONU ILI INVAZIVNOM METODOM) • HOLTER EKG • ERGOMETRIJA

  19. UKLJUČENI BOLESNICI: Do 14. svibnja 2004. u studiju je uključeno ukupno 149 bolesnika (97 M i 52 Ž): ►IAP→52 (36 M i 13 Ž) ►NSTEMI→45 (27 M i 18 Ž) ►STEMI→52 (32 M i 20 Ž) ►45 pacijenata(30 %) ima DM ili intol. glukoze ►27 pacijenata(18 %) zadovoljava WHO kriterije za dijagnozu metaboličkog sindroma X Statistička multivarijantna analiza –SPSS program for Windows 6.0.

  20. RADNA HIPOTEZA: • serumske razine upalnih markera biti će statistički značajno više u prvim danima nakon pojave AKS u odnosu na vrijednosti tijekom kasnijeg praćenja • pozitivna korelacija sa stupnjem dekompenzacije i postotkom smrtnosti,težinom sistoličke disfunkcije i patološkim EKG promjenama

  21. CILJ STUDIJE: • dokazati važnost uloge upale u nastanku aks • doprinijeti eventualnom razvoju novih preventivnih i terapijskih mjera za aks u budućnosti

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