Castelfranco Veneto 19 Novembre 2004 La prevenzione primaria dell ictus Achille C. Pessina Dipartimento di Medicina Clinica e Sperimentale Università di Padova
American Heart Association-2004 Update
Percentage Breakdown of Deaths From Cardiovascular Diseases United States: 2001 CHD (54%) Other (13%) Congenital CV Defects (0.4%) Rheumatic Heart Disease (0.4%) Disaeses of the arteries (4%) High Blood Pressure (5%) CHF (6%) Stroke (18%) American Heart Association-2004 Update
THE BURDEN OF STROKE 4.4 mil. people die of the consequences of stroke each year; ie 9% of all deaths (Global Bureau od Disease Study, Lancet 1997; 349:1269-76) In western Countries 10-12% of all deaths (Lancet 1992; 339:342-44) Risk doubling every decade over age 50 (Lancet 1997; 349:1498-1504)
Prevalence of Stroke by Age and Gender United States: 1988-94 Percent of Population 14 12 10 8 6 4 2 0 men women 20-24 25-34 35-44 45-54 55-64 65-74 > 75 Decades of age American Heart Association-2003 Update
14-YR ADJUSTED RELATIVE RISK (RR) FOR (RR) STROKE MORTALITY The CArdiovascular STudy in the ELderly (CASTEL) 7 6 5 4 3 2 1 0 * <0.001 vs. 1 st quinile; vs. 1 st quintile. 1 2 3 4 5 Cut-off (yrs) <68 69-71 72-75 75-79 >80 Quintiles of age * Mazza A.et al; Eur J Epid 2001
Ictus... una questione di emergenza 186.000 nuovi casi ogni anno 510 casi ogni giorno 42 casi ogni ora 1 ICTUS OGNI 3 MINUTI L ictus è più frequente dell infarto SPREAD 2001
Mortalità per cause cardiovascolari in Italia nel periodo 1990-2000 1990 1997 2000 IMA M F 23.725 14.701 22.309 14.796 21.130 14.602 Malattie Cerebrovascolari M F 30.698 41.829 30.323 43.421 28.217 40.659 Malattie del S. Cardiocircolatorio M F 108.014 125.907 110.464 131.238 109.518 132.968
Ictus e Attacco Ischemico Transitorio 191.000 ricoveri per acuti/anno (2% del totale) 2 milioni di giornate di degenza/anno (2,9% del totale) 645 milioni di euro/anno Centro di Farmacoeconomia, Università di Milano su dati del Ministero della Salute 2002
STROKE OUTCOME AND RECURRENCE 20% of pts die within 30 days after a stroke 40% of pts die within 1 year (Stroke 2000; 31:2080-86) 30% of sorvivors disabled 10% require institutional care (Stroke 2001; 32:2409-16) 15-30% depression 6-14% further stroke within 1 year 20-37% further stroke within 5 years (Stroke 2001; 32:2409-16)
Asia Pacific Cohort Studies Collaboration Usual SBP and primary stroke Stroke Risk ( 95% CI) (425.251 participants, 4.708 strokes, 3.2M person-years) -10mmHg 70 + yrs - 27% 60-69 yrs - 38% < 60 yrs - 55% 64.00 32.00 16.00 8.00 4.00 2.00 1.00 0.50 0.25 110 120 130 140 150 160 Usual SBP (mmhg) J Hypertens. 2003; 21:707
14-YR ADJUSTED RELATIVE RISK (RR) FOR STROKE MORTALITY The CArdiovascular STudy in the ELderly (CASTEL) RR 4 * <0.001 vs. 1 st quintile; ** <0.01 vs. 1 st quintile 3 2 1 0 ** * Cut-off (mmhg) 1 2 3 4 5 <54 55-64 65-74 75-87 >88 Quintiles of Pulse Pressure Mazza A. et al; Eur J Epid 2001
Primary Prevention of Hypertension (population-based strategy) Systolic BP distribution After Intervention Before Intervention Reduction in BP % Reduction in Mortality (mmhg) Stroke CHD Total 2-6 -4-3 3-8 -5-4 5-14 -9-7 Whelton P. et al. JAMA 2002; 288:1882
Prognostic effect of observation and intervention in a general population (age 65-95 years at screening) Stroke survival 1.00 0.95 0.90 0.85 0.80 Phase A p<0.00 1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Years of follow-up Only screening Active observation Direct intervention Phase B The Castel clinical trial - Casiglia et al, 2002
Relationship between Odds Ratios (calculated for experimental vs reference treatment) for CV events and corresponding differences in SBP Difference (reference minus experimental) in SBP (mmhg) Staessen JA J Hypertens 2003; 21:1055-1076
LIFE: Comparable BP Reduction 180 170 160 150 Atenolol 145.4 mmhg 140 130 Systolic Losartan 144.1 mmhg mmhg 120 110 100 90 80 70 Mean Arterial Diastolic Atenolol 102.4 mmhg Losartan 102.2 mmhg Losartan 81.3 mmhg Atenolol 80.9 mmhg 60 50 40 0 6 12 18 24 30 36 42 48 54 Study Month Dahlöf B et al Lancet 2002;359:995-1003.
LIFE: Fatal and non-fatal stroke Proportion of patients with first event (%) 8 7 6 5 4 3 2 1 0 0 Atenolol Losartan Adjusted Risk Reduction 24.9%, p=0.001 Unadjusted Risk Reduction 25.8%, p=0.0006 6 12 18 24 30 36 42 48 54 60 66 Study Month Dahlöf B et al Lancet 2002;359:995-1003.
Relative risks with 95% CI for CV events and total mortality in SCOPE and LIFE study Relative risk Lithell H et al. J Hypertens 2003; 21:875-886
Favourable Non-Haemodynamic Actions of AIIRB Endothelial dysfunction Vascular remodelling Cardiovascular matrix synthesis Arterial stiffness Arterial wave reflection Central aortic pressure LV systolic stress Williams B et al Am J Cardiol 2001;87: 10C-17C
Kaplan Meier curves for stroke (VALUE study) Modified from Julius S. et al. Lancet 2004;363:2022-2031
VALUE: Blood Pressure Reduction in the two treatment groups (Difference between groups <0.000 at every time point. Overall SBP difference=2.23 mmhg, DBP difference=1.59 mmhg) Modified from Julius S. et al. Lancet 2004;363:2022-2031
VALUE: Outcome e differenze nella PAS a scadenze specifiche: Ictus Intervallo di Tempo (mesi) D PAS (mmhg) ICTUS Odds Ratios e 95% IC Studio complessivo 2.2 0 3 3 6 3.8 2.3 6 12 2.0 12 24 1.8 24 36 1.6 36 48 1.4 Fine dello studio 1.7 0.25 0.5 1.0 2.0 4.0 A Favore di valsartan A Favore di amlodipina Julius S et al. Lancet. Giugno 2004;363.
VALUE: Outcome e differenze nella PAS a scadenze specifiche: Infarto del Miocardio Intervallo di Tempo (mesi) Studio Complessivo 0 3 3 6 6 12 12 24 24 36 36 48 Fine dello Studio D PAS (mmhg) 2.2 3.8 2.3 2.0 1.8 1.6 1.4 1.7 Infarto del Miocardio Odds Ratios e 95% IC 0.25 0.5 A Favore di valsartan 1.0 2.0 4.0 A Favore di amlodipina Julius S et al. Lancet. Giugno 2004;363.
Comparison of more intensive BP lowering strategy vs. less intensive strategy (1) Favours more intensive Favours less intensive Lancet 2000; 356:1955-1961
4S(Simvastatina) Lancet,1994 CARE(Pravastatina) NEJM,1996 LIPID(Pravastatina) NEJM, 1998 MIRACL(Atorvastatina) JAMA, 2001 HIPS (Simavastatina) Lancet, 2002 Greace (Atorvastatina) Curr Res Med Open, 2002 PROSPER (Pravastatina) Lancet, 2002 WOSCOPS (Pravastatina) NEJM, 1995 ALLHAT-LLT (Pravastatina) JAMA, 2002 ASCOT-LLA(Atorvastatina) Lancet, 2003
80 70 Trattamento Intensivo Terapia Convenzionale p= 0,006 p<0,001 p= 0,19 p= 0,001 p= 0,21 60 Pazienti (%) 50 40 30 20 10 0 Emoglobina Glicata <6,5% Colesterolo <175 mg/dl Trigliceridi <150 mg/dl PAS <130 mmhg PAD <80 mmhg
60 50 Terapia Convenzionale Trattamento Intensivo 40 30 20 10 0 p= 0,007
A Strategy to Reduce Cardiovascular Disease by More Than 80% NJ WALD,professor MR LAW, professor Dept. of Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Barts and the London Queen Mary s School of Medicine and Dentistry University of London. BMJ 2003; 326:1419