Acs ppt

ACUTE CORONARY SYNDROMES PATHOPHYSIOLOGY PLAQUE RUPTURE & SUPERIMPOSED NONOCCLUSIVE THROMBUS DYNAMIC OBSTRUCTION PROGRESSIVE MECHANICAL OBSTRUCTION INFLAMMATION AND/OR INFECTION SECONDARY UNSTABLE ANGINA INCREASED O 2 DEMAND

FRISC - II PROTOCOL 2457 PATIENTS JUNE 17, 1996 TO MAY 6, 1998 (2 YEARS) 58 SCANDINAVIAN CENTERS 1.76 PATIENTS PER MONTH PER CENTER

FRISC - II ELIGIBILITY ST DEPRESSION MORE THAN 0.1 MV T WAVE INVERSION MORE THAN 0.1 MV RAISED BIOCHEMICAL MARKERS CPK - MB MORE THAN 6  G/L, TROPORIN T MORE THAN 0.1  G/L MB ISOENZYME ABOVE LIMIT FOR DIAGNOSIS OF MI MAJORITY ABOVE 65 YEARS AND WITH MULTIPLE RISK FACTORS HIGHLY SELECTIVE GROUP OF ACS (IN BLOCKS & CAPS - DIFFERENT COLUR)

THE TIMI RISK SCORE FOR UA/NSTEMI Characteristics Points Historical Age  65 years 1  3 Risk factors for CAD 1 Known CAD (stenosis  50%) 1 Aspirin use in past 7 days 1 Presentation Recent (  24 h) severe angina 1 ST-segment deviation  0.5 mm 1  Cardiac markers 1 Risk Score = Total Points 0-7 Antman et al JAMA 2000, 784 835

RITA-3 1810 PATIENTS WITH ACS 915 CONSERVATIVE STRATEGY 895 INTERVENTION STRATEGY INTERVENTION : ASPIRIN, ENOX, GP II B / III A, TICLO / CLOPIDOGREL CONSERVATIVE ASPIRIN, ENOX ? GPIIB/IIIA ? TICLO / CLOPIDOGREL LANCET 2002, 360, 743

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 2220 PATIENTS WITH ACS INVASIVE 1114 CONSERVATIVE 1106 CHARACTERISED ACCORDING TO TIMI RISK SCORE

RITA - 3 Intervention Conservative (n =895) (n=915) Deaths 4 months 26 23 1 year 41 36 All follow-up 60 72 Myocardial infarctions (MIS) 4 months 30 34 1 year 34 44 All follow – up 45 56 Lancet 2002,360,743

RITA - 3 Intervention Conservative (n =895) (n=915) Refractory angina 4 months 39 85 1 year 58 106 Primary endpoints Death, MI, or 86 (9.6%) 133 (14.5 %) Refractory angina 4 months Death or MI 68(7.6%) 76 (8.3 %) 1 year Lancet 2002,360,743

ACS – Report Incidence & D/MI CONS. V/s INV. Number of deaths or MIS within 1 year Intervention Conservative RITA 68/895(7.6%) 68/895(7.6%) VINO 4/64(6.36%) 15/(22.4%) TACTICS-TIMI 18 81/1114(7.3%) 105/1106(9.5%) TRUCS 6/76(7.6%) 12/72(16.7%) FRISC II 127/1219(10.4%) 68/895(7.6%) MATE 11/111(9.9%) 6/90(6.7%) VANQWISH 111/462(24.0%) 85/458(18.6%) TIMI IIIB 52/484(10.8%) 62/509(12.2%) 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

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 Intervention Conservative (n =895) (n=915) Deaths 4 months 26 23 1 year 41 36 All follow-up 60 72 Myocardial infarctions (MIs) 4 months 30 34 1 year 34 44 All follow – up 45 56 Lancet 2002,360,743

Conventional Fisk Factors for CAD 1. DysIipidaemia : elevated LDL-C and low HDL-C 2. Smoking 3. Diabetes 4. Hypertension 5. Obesity 6. Sedentary lifestyle 7. Positive family history of premature vascular disease 8. Advancing age 9. Male gender and postmenopausal state in women

Factors influencing homocysteine metabolism Inherited Enzyme deficiencies in the metabolic pathway (cysthionine B synthase, 5, 10 – methylene tetrahydrofolate reductase, methionine synthase) Age and sex Advancing age, male sex, menopause Nutritional Folic acid, vitamins B 6 and B 12 deficiencies Disease Status Renal failure, malignancies, psoriasis, Rheumatoid arthritis, systemic lupus eythematosus, hypothyroidism Diabetes mellitus Medications Metformin, methotrexate, Anticonvulsants, Niacin and theophylline, decreased levels of betaine.

New and Emerging Risk Factors for CAD 1. Inflammation and infectious agents 2. Hyperhomocysteinemia 3. Elevated lipoprotein (a) Lpa 4. Insulin resistance 5. Hypertriglyceridemia and increased IDE 6 Hyperfibrinogenemia 7. Small dense LDL phenotype Psychosocial factors 9. Non-lipid related gene polymorphisms 10. Miscellaneous : oxidation susceptibility and antioxidant intake WBC count and Hemostatic / Fibrinolytic abnormalities, iron overload

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 Normal Male 8.0 - 14.0  mol/L Female 6.0 - 12.0  mol/L Homocysteinemia Moderate 16-30  mol/L  Intermediate 31-100  mol/L Severe > 100  mol/L

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 VISP NORVIT WENBIT SEARCH PACIFIC

HOMOCYSTEINE LEVELS IN DIFFERENT DIETS Vegetarian Vegan Omnivore Hcy level 13.2mmol/L 15.8mmol/L 10.2mmol/L Vitamin B 12 214.8pmol/L 140pmol/L 344.7pmol/L Deficiency of vitamin B 12 26 % 78 % 0 %

Joint effects of antimicrobial antibodies, smoking and CRP on the risk of coronary events

RELATION OF tHcy LEVELS WITH MORTALITY RATES Homocysteine (micromol/L) Mortality (%) < 9 3.8 9-14.9 8.6 >15 24.7

EMERGING / NOVEL RISK FACTORS FOR CAD SERUM FIBRINOGEN MAJOR DETERMINANT OF PLASMA VISCOSITY PLAYS ROLE IN THROMBOSIS 1.8 FOLD INCREASE IN INCIDENCE FOR CAD GENETIC POLYMORPHISM – GENE IDENTIFIED FREQUENT BLOOD DONATIONS OFFER PROTECTION AGAINST CAD ?  VISCOSITY

NOVEL RISK FACTORS FOR CAD ANXIETY DEPRESSION HOSTILITY RAGE SOCIAL ISOLATION DEPRESSION

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

Acs ppt

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Acs ppt