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ACUTE CORONARY SYNDROME
ACUTE CORONARY SYNDROMES PATHOPHYSIOLOGY ,[object Object],[object Object],[object Object],[object Object],[object Object]
FRISC - II PROTOCOL ,[object Object],[object Object],[object Object],[object Object]
FRISC - II  ELIGIBILITY ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
THE TIMI RISK SCORE FOR UA/NSTEMI ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Antman et al JAMA 2000, 784 835
RITA-3 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
TROPONIN T LEVELS  IN ACS & CARDIAC DEATH 1506 Patients FRISC – Circ. 1996, 93 : 1651
TACTICS – TIMI 18 New Eng. J. Med, 2001, 344 : 1879 21 % risk reduction  (p=0.048) 36 % risk reduction  (p=0.018)
TACTCS - TIMI 18 ,[object Object],[object Object],[object Object],[object Object]
RITA - 3  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Lancet 2002,360,743
RITA - 3  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Lancet 2002,360,743
ACS – Report Incidence & D/MI  CONS. V/s INV. ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Risk Ratio (95 % CI)
ASSESSMENT OF THE CLINICAL UTILITY OF NOVEL MARKERS OF CARDIOVASCULAR RISK ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
100 80 60 40 20 0 (n=895) (n=915) (n=856) (n=873) (n=799) (n=814) Intervention  Conservative Intervention  Conservative Intervention  Conservative Proportion of patients (%) Baseline  4 months 1 year Prevalence of angina over time treatment Lancet 2002,360,743 Grade 1 Grade 2 Grade 3/4
Nitricoxide (NO)   Thrombomodulin TM   Protects  Endothelium     Endothelium  Damages Endothelium   Depletion of NO and TM   Reactive Oxygen Species   Oxidation   Homocysteine   Mechanism of Homocysteine Induced Vascular Damage
RITA - 3  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Lancet 2002,360,743
RITA - 3  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Lancet 2002,360,743
ACS – Report Incidence & D/MI  CONS. V/s INV. ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Risk Ratio (95 % CI)
ASSESSMENT OF THE CLINICAL UTILITY OF NOVEL MARKERS OF CARDIOVASCULAR RISK ADDITIVE TO   TOTAL AND ASSAY  PROSPECTIVE   HIGH-DENSITY CONDITIONS  STUDIES   LIPOPROTEIN MARKER  STANDARDIZED ? CONSISTENT ?   CHOLESTEROL ? Lipoprotein (a)   No  Yes/no    Yes /no Total homocysteine Yes Yes/no   Yes /no Tissue-type plasminogen activator     Yes/no Yes   Yes/no And plasminogen activator inhibitor Fibrinogen   Yes/no Yes Yes High-sensitiviety-C-reactive protein   Yes Yes Yes From Ridker PM: Evaluating novel cardiovascular risk factors : Can we better predict heart attacks  ?Ann Intern Med 130:933-937,1999
100 80 60 40 20 0 (n=895) (n=915) (n=856) (n=873) (n=799) (n=814) Intervention  Conservative Intervention  Conservative Intervention  Conservative Proportion of patients (%) Baseline  4 months 1 year Prevalence of angina over time treatment Lancet 2002,360,743 Grade 1 Grade 2 Grade 3/4
Conventional Fisk Factors for CAD ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
ACUTE CORONARY SYNDROMES PATHOPHYSIOLOGY ,[object Object],[object Object],[object Object],[object Object],[object Object]
Factors influencing homocysteine metabolism ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Conventional Fisk Factors for CAD ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
New and Emerging Risk Factors for CAD ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Association between angiotensin-converting enzyme (ACE) genotypes and incidence of myocardial infarction in men with primary hypercholesteolemia 100 90 80 70 60 50 40 30 20 10 0   40   45 50 55 60 65 Incidence of Myocardial Infarction (%) Age (years) DI + II DD
CAD – INFECTION  Circ. 2002, 105, 1555 Patients randomized (n=152)  Patients commencing treatment (n = 148) Placebo (n=74) Clarithromycin (n=74) Urgent revascularization (n=2) Pancreatitis (n = 1) Renal failure (n=1)
Kaplan-Meier plot of cumulative survival during follow-up Circ. 2002, 105, 1555
LEVELS OF HOMOCYSTEINE  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Hyperhomocysteinemia and risk of atherosclerotic vascular disease  Meta analysis of 27 studies *  P < 0.05 v/s normal (Boushey et al) * * *
Homocysteine levels in  CAD patients and controls A  Higher plasma homocysteine levels in Indian patients with CAD B  Increased risk in CAD in Indian Asians  due to hyperhomocysteinemia 1.5 1.4 1.3 1.2 1.1 1.0 11-12  12-1  113-1  14-15  >=15 Odds ratio for CHD Homocysteine conc. (micrommol/L) *p<0.05 n=775 * 1.07 1.15 1.24 1.33 1.43
ONGOING STUDIES ON HOMOCYSTEINEMIA  ,[object Object],[object Object],[object Object],[object Object],[object Object]
HOMOCYSTEINE LEVELS  IN DIFFERENT DIETS ,[object Object],[object Object],[object Object],[object Object]
Joint effects of antimicrobial antibodies, smoking  and CRP on the risk of coronary events
HOMOCYSTEINE METABOLISM
RELATION OF tHcy LEVELS WITH MORTALITY RATES  ,[object Object],[object Object],[object Object],[object Object]
EMERGING / NOVEL  RISK FACTORS FOR CAD SERUM FIBRINOGEN  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
NOVEL RISK FACTORS FOR CAD ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Antman RM et al JAMA 2000, 284, 835 % Population  4.3  17.3  32.0  29.3  13.0  3.4 6-7 SABATINE AND ANTMAN  TIMI RISK SCORE FOR UA/NSTEMI

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ACUTE CORONARY SYNDROME PATHOPHYSIOLOGY AND RISK FACTORS

  • 2.
  • 3.
  • 4.
  • 5.
  • 6.
  • 7. TROPONIN T LEVELS IN ACS & CARDIAC DEATH 1506 Patients FRISC – Circ. 1996, 93 : 1651
  • 8. TACTICS – TIMI 18 New Eng. J. Med, 2001, 344 : 1879 21 % risk reduction (p=0.048) 36 % risk reduction (p=0.018)
  • 9.
  • 10.
  • 11.
  • 12.
  • 13.
  • 14. 100 80 60 40 20 0 (n=895) (n=915) (n=856) (n=873) (n=799) (n=814) Intervention Conservative Intervention Conservative Intervention Conservative Proportion of patients (%) Baseline 4 months 1 year Prevalence of angina over time treatment Lancet 2002,360,743 Grade 1 Grade 2 Grade 3/4
  • 15. Nitricoxide (NO) Thrombomodulin TM Protects Endothelium Endothelium Damages Endothelium Depletion of NO and TM Reactive Oxygen Species Oxidation Homocysteine Mechanism of Homocysteine Induced Vascular Damage
  • 16.
  • 17.
  • 18.
  • 19. ASSESSMENT OF THE CLINICAL UTILITY OF NOVEL MARKERS OF CARDIOVASCULAR RISK ADDITIVE TO TOTAL AND ASSAY PROSPECTIVE HIGH-DENSITY CONDITIONS STUDIES LIPOPROTEIN MARKER STANDARDIZED ? CONSISTENT ? CHOLESTEROL ? Lipoprotein (a) No Yes/no Yes /no Total homocysteine Yes Yes/no Yes /no Tissue-type plasminogen activator Yes/no Yes Yes/no And plasminogen activator inhibitor Fibrinogen Yes/no Yes Yes High-sensitiviety-C-reactive protein Yes Yes Yes From Ridker PM: Evaluating novel cardiovascular risk factors : Can we better predict heart attacks ?Ann Intern Med 130:933-937,1999
  • 20. 100 80 60 40 20 0 (n=895) (n=915) (n=856) (n=873) (n=799) (n=814) Intervention Conservative Intervention Conservative Intervention Conservative Proportion of patients (%) Baseline 4 months 1 year Prevalence of angina over time treatment Lancet 2002,360,743 Grade 1 Grade 2 Grade 3/4
  • 21.
  • 22.
  • 23.
  • 24.
  • 25.
  • 26. Association between angiotensin-converting enzyme (ACE) genotypes and incidence of myocardial infarction in men with primary hypercholesteolemia 100 90 80 70 60 50 40 30 20 10 0 40 45 50 55 60 65 Incidence of Myocardial Infarction (%) Age (years) DI + II DD
  • 27. CAD – INFECTION Circ. 2002, 105, 1555 Patients randomized (n=152) Patients commencing treatment (n = 148) Placebo (n=74) Clarithromycin (n=74) Urgent revascularization (n=2) Pancreatitis (n = 1) Renal failure (n=1)
  • 28. Kaplan-Meier plot of cumulative survival during follow-up Circ. 2002, 105, 1555
  • 29.
  • 30. Hyperhomocysteinemia and risk of atherosclerotic vascular disease Meta analysis of 27 studies * P < 0.05 v/s normal (Boushey et al) * * *
  • 31. Homocysteine levels in CAD patients and controls A Higher plasma homocysteine levels in Indian patients with CAD B Increased risk in CAD in Indian Asians due to hyperhomocysteinemia 1.5 1.4 1.3 1.2 1.1 1.0 11-12 12-1 113-1 14-15 >=15 Odds ratio for CHD Homocysteine conc. (micrommol/L) *p<0.05 n=775 * 1.07 1.15 1.24 1.33 1.43
  • 32.
  • 33.
  • 34. Joint effects of antimicrobial antibodies, smoking and CRP on the risk of coronary events
  • 36.
  • 37.
  • 38.
  • 39. Antman RM et al JAMA 2000, 284, 835 % Population 4.3 17.3 32.0 29.3 13.0 3.4 6-7 SABATINE AND ANTMAN TIMI RISK SCORE FOR UA/NSTEMI