Upalni biljezi u akutnom koronarnom sindromu

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Upalni biljezi u akutnom koronarnom sindromu

• M. Bergovec, Z. Trstenjak, V. Raos, S. Pavlovic,
  M. Raguž, J. Šikic Vagic, Ž. Romic, D. Kranjcec

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• UPALA?
• IMUNOLOŠKI SUSTAV?

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1. VECA UCESTALOST KORONARNE BOLESTI KOD
OSOBA SA KRONICNIM 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 1996,75568-72
• Mendall MA. Chlamydia pneumoniae risk factors
  for seropositivity and association with coronary
  heart disease. J Infect 199530121-8
• 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
  myocardial infarction. Am J Cardiol 200086379-84

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2. NIŽA STOPA KORONARNE BOLESTI U OSOBA SA
NIŽIM RAZINAMA UPALNIH MEDIJATORA (umjerena
fizicka aktivnost)

• Willich SN, et al. Physical activity and risk of
  peripheral arterial disease in the general
  population Edinburgh artery study. J Epidemiol
  Community health 199347475-80
• Stratton JR, et al. Effects of physical
  conditioning on fibrinolytic variables and
  fibrinogen in young and old healthy adults.
  Circulation 1991831692-7

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3.VIŠE VRIJEDNOSTI UPALNIH MARKERA KOD OSOBA SA
KORONARNOM BOLEŠCU U ODNOSU NA KONTROLNU SKUPINU

• de Maat MP, et al. Association of plasma
  fibrinogen levels with coronary artery
  disease,smoking and inflammatory markers.
  Atherosclerosis 1996121185-91
• Ridker PM et al. Inflammation,aspirin and the
  risk of cardiovascular disease in apparently
  healthy men. N Engl J Med 1997336973-9
• Haverkate F et al. Production of C-reactive
  protein and risk of coronary events in stable and
  unstable angina. European Concerted Action on
  thrombosis and Disabilities Angina Pectoris Study
  Group. Lancet 1997349462-6

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UPALNI BILJEZI U AKUTNOM KORONARNOM SINDROMU

• ZNANSTVENO-ISTRAŽIVACKI PROJEKT
• MINISTARSTVA ZNANOSTI I TEHNOLOGIJE RH
• br. 019800
• VODITELJ PROJEKTAprof.dr.sc. M. Bergovec
• SURADNICI- dr.M.Bergovec
• -dr.D.Kranjcec
• -vms.V.Markac
• -mr.sc.J.Mirat
• -prim.dr.S.Pavlovic
• -mr.sc.M.Raguž
• -prim.dr.V.Raos
• -prof.dr.sc.Ž.Romic
• -ms M.Slanc
• -mr.sc.J.Šikic Vagic
• -dr.Z.Trstenjak

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AKUTNI KORONARNI SINDROM

• 400 pacijenata sa AKS
• NESTABILNA ANGINA PEKTORIS
• NSTEMI
• STEMI

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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

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ANAMNESTICKI PODACI

• hipertenzija
• hiperlipidemija
• pušenje
• diabetes mellitus
• BMI
• prijašnja koronarna bolest

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UPALNI MARKERI

• interleukin-6
• s-amiloid a
• high sensitive-C-reaktivni protein
• neopterin
• fibrinogen

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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,
• a1-kimotripsina i haptoglobina
• Woods A et al. Genetics of inflammation and risk
  of coronary heart diseasethe central role of
  interleukin-6.Eur Heart J 2000211574-83
• Castell JV et al. Interleukin-6 is the major
  regulator of acute phase protein synthesis in
  adult human hepatocytes. FEBS Lett 198924237-9

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S-AA

• protein akutne faze, prekursor tkivnog AA
• apolipoprotein-veže se na HDL cestice-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
  1997336973-9
• Malle E et al. Serum amyloid A (SAA)an acute
  phase protein and apolipoprotein. Atherosclerosis
  1993102131-46

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hs-CRP

• najduže poznat i najviše puta istraživan upalni
  protein
• bazalne razine znacajno 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
  1997336973-9
• Morrow DA et al. C-reactive protein is a potent
  predictor of mortality independently of and in
  combination with Troponin T in acute coronary
  syndromesa TIMI 11 A substudy. J Am Coll Cardiol
  1998311460-65
• 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 Nov42(5)201-6

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neopterin

• derivat pteridina
• sekrecija iz makrofaga nakon stimulacije sa IFN-?
• znacajno povišene razine kod nestabilne AP ili
  AIM u usporedbi sa stabilnom AP
• Gupta S et al. Serum neopterin in acute coronary
  syndromes. Lancet 19973491252-3
• Kaski JC. Increased neopterin in patients with
  chronic and acute coronary syndromes. J Am Coll
  Cardiol 199831523-6
• Schumacher M et al. Increased neopterin in
  patients with chronic and acute coronary
  syndromes. J Am Coll Cardiol 199730703-7

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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
  1999331347-1352
• Stec JJ et al. Association of fibrinogen with
  cardiovascular risk factors and cardiovascular
  disease in the Framingham Offspring Population.
  Circulation 20001021634-1638

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METABOLICKI SINDROM X (WHO definicija)

• DIABETES MELLITUS ILI INTOLERANCIJA GLUKOZE 2
  ili više od slijedecih parametara
• sistolicki tlak ?140 mmHg i/ili dijastolicki 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)

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PARAMETRI ISPITIVANJA

• KLINICKA SLIKA
• RTG SRCA I PLUCA
• EJEKCIJSKA FRAKCIJA (UZV METODOM PO SIMPSONU ILI
  INVAZIVNOM METODOM)
• HOLTER EKG
• ERGOMETRIJA

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UKLJUCENI BOLESNICI

• Do 14. svibnja 2004. u studiju je ukljuceno
  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 metabolickog sindroma X
• Statisticka multivarijantna analiza SPSS
  program for Windows 6.0.

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RADNA HIPOTEZA

• serumske razine upalnih markera biti ce
  statisticki znacajno više u prvim danima nakon
  pojave AKS u odnosu na vrijednosti tijekom
  kasnijeg pracenja
• pozitivna korelacija sa stupnjem dekompenzacije i
  postotkom smrtnosti,težinom sistolicke
  disfunkcije i patološkim EKG promjenama

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CILJ STUDIJE

• dokazati važnost uloge upale u nastanku aks
• doprinijeti eventualnom razvoju novih
  preventivnih i terapijskih mjera za aks u
  buducnosti