Tratamentul medicamentos al aterosclerozei Dan Gaita Institutul de

”Tratamentul medicamentos al aterosclerozei" Dan Gaita Institutul de Boli Cardiovasculare Fundatia Cardio. Prevent Timisoara

Conflict de interese Am sustinut conferinte si am organizat evenimente educationale pentru: Amgen, Astra. Zeneca, Berlin Chemie, Boehringer Ingelheim, Galenica, GSK, MSD, Mylan, Novartis, Pfizer, Sanofi, Servier

Adevar sau ! E R A provocare? C O R P V O

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Europe - SDR, diseases of circulatory system all ages per 100, 000 European Union 221. 7

WHO Targets and WHF Goal

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”Tratamentul medicamentos al consecintelor aterosclerozei" Dan Gaita Institutul de Boli Cardiovasculare Fundatia Cardio. Prevent Timisoara

ASCVD Prevention Pyramid and Components of Cardiac Rehabilitation/Secondary Prevention Programs

CHD deaths prevented or postponed by treatments and risk factor changes in the United States population, 1980– 2000.

Therapeutic control of blood pressure*, LDL-C** and diabetes*** EUROASPIRE III EUROASPIRE IV p=0. 01 p=0. 69 P<0. 0001 *In patients on BP lowering drugs; **In patients on lipid-lowering drugs; *** In patients with known diabetes

”Preventia aterosclerozei" Dan Gaita Institutul de Boli Cardiovasculare Fundatia Cardio. Prevent Timisoara

Total CV Risk INTERHEART Odds Ratio (99% CI) 2. 9 2. 4 1. 9 3. 3 13. 0 42. 3 68. 5 182. 9 333. 7 n s g o i A 1 e n t i s o k e n p o b rte o. B/A e Sm Dia p Ap Hy Yusuf S. Lancet 2004; 364: 937 t ct 4 h a 3 f g + + i 3 c 2 1+ 1+2+ verwe hoso O yc Ps AAllll

ROMANIA at the glance! r o l i l o B ? l u tii r e a t t s a i n in a M l S la ru e te d nis a i e l M a C a l DETERMINANT Prevalence of SMOKING RANK* among European countries (for male/female) Level of comparison 22 M/9 F Eu (42) Daily VEGETABLE consumption 15 M/16 F Eu (42) Daily FRUIT consumption 23 M/36 F Eu (42) 22 EU (27) 6 EU (27) 35 Eu (42) Prevalence of raised blood pressure 31 M/26 F Eu (42) Prevalence of raised cholesterol (≥ 6. 2 mmol/L) cholesterol 13 M/14 F Eu (42) 4 Eu (42) 22 Eu (42) Prevalence of adults who do no moderate intensity physical activity in a week activity Prevalence of adults who participate in physical activity at least 5 times/week Alcohol consumption Prevalence of obesity among adult Prevalence of diabetes * ascending order of indicator’s value

U N “POPULATIONAL” I ! U L U • Comunitati locale T A • “Civilizatie” M U • Exemplu personal F

“RISC INALT” H A T • Program national • Cabinete de Preventie in judete • Control periodic obligator m t ir A o lg

? “PREVENTIE SECUNDARA” M I t s o • Programe nationale/ patologii p s i • Modernizare -Tehnicizare t a r • Registre – date reale! g a it n a t S

British Heart Foundation S n a t a e V C

Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, αtocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Curr Pharm Des. 2013; 19(33): 5909 -28

Antiatherosclerotic    Cyclic AMP    Prostacyclin    Prostaglandin E 2    Artificial high-density lipoprotein (HDL)   Antioxidants    Calcium antagonists    Trapidil and its derivatives    Lipoxygenase inhibitors    Lipostabil    Mushroom extracts   Proatherogenic    Beta-blockers    Thromboxane А 2    Phenothiazine Anti-atero -sclerotice?

Polymeal ? 7 main elements: n wine n fish n dark chocolate n fruits n vegetables n almonds n garlic decrease of global risk with 76% Dutch Polymeal 1) Eat fish four times a week; 2) Drink 4 -5 oz. of wine a day; 3) Eat 100 g (3 -4 oz. ) of dark chocolate a day; 4) Eat 400 g (14 oz. ) of fruits & vegetables a day; 5) Eat 2. 7 g (a pinch) of garlic a day; 6) Eat 68 g (2 -3 oz. ) of almonds a day.

Polymeal efficiency Ingredients Wine(150 ml/day) % CV risk reduction 32% Risk factors reduced CVD Source Di Castelnuovo et al Fish (114 g 4 x/week) Dark Chocolate (100 g/day) 14% 21% CVD Whelton et al ¯ SBP – 5. 1 mm. Hg Taubert et al ¯ DBP - 1. 8 mm. Hg Fruits & vegetables (400 g/day) 21% ¯ SBP - 4 mm. Hg ¯ DBP -1. 5 mm. Hg John et al Garlic (2. 7 g/day) 25% ¯TC – 17. 1 mg/d. L Ackermann et al ¯ TC - 10 mg/d. L Jenkins et al Almonds (68 g/day) 12. 5%

Continuum Cardiovascular BCV Diabet zaharat Boala cronica de rinichi Factori de risc Subiecti sanatosi Populatia generala Risc crescut Preventie secundara

”PRECOCITATEA interventiei asupra aterosclerozei" Dan Gaita Institutul de Boli Cardiovasculare Fundatia Cardio. Prevent Timisoara

Total CV Risk INTERHEART Odds Ratio (99% CI) 2. 9 2. 4 1. 9 3. 3 13. 0 42. 3 68. 5 182. 9 333. 7 n s g o i A 1 e n t i s o k e n p o b rte o. B/A e Sm Dia p Ap Hy Yusuf S. Lancet 2004; 364: 937 t ct 4 h a 3 f g + + i 3 c 2 1+ 1+2+ verwe hoso O yc Ps AAllll

Hypoglycemia as Pro-atherosclerotic factor

Hypoglycemia followed by Hyperglycemia! … Ceriello A et al. Diabetes 2012; 61: 2993 -7

Early vs late glycemic intervention

Defining metabolic memory Antonio Ceriello, Michael A. Ihnat and Jessica E. Thorpe The "Metabolic Memory": Is More Than Just Tight Glucose Control Necessary to Prevent Diabetic Complications? J Clin. Endocrinol. Metab. 2009 94: 410 -415 • “Epidemiological and prospective data support a long-term influence of early metabolic control on clinical outcomes” • “. . . early glycaemic environment is remembered in the target organs (i. e. , eye, kidney, heart, extremities)” • “The concept of a metabolic memory is of diabetic vascular stresses persisting after glucose normalization”

The Metabolic Memory • UKPDS Holman R et al. N Engl J Med. 2008 ; 359: 1577 -89 • VADT Del Prato S, Diabetologia 2009; 52: 1219– 1226

The take-home message is that “good glucose control should be started as early as possible to delay or prevent serious diabetes-related complications, ” said Alan D. Cherrington, Ph. D, president, American Diabetes Association. ADA S. Diego 2005

Total CV Risk INTERHEART Odds Ratio (99% CI) 2. 9 2. 4 1. 9 3. 3 13. 0 42. 3 68. 5 182. 9 333. 7 n s g o i A 1 e n t i s o k e n p o b rte o. B/A e Sm Dia p Ap Hy Yusuf S. Lancet 2004; 364: 937 t ct 4 h a 3 f g + + i 3 c 2 1+ 1+2+ verwe hoso O yc Ps AAllll

Lowering LDL-C Levels With Statins in Patients With or Without Prior CV Events Has Been Shown to Improve CV Outcomes!!! 30 4 S Secondary prevention trials 1 Active treatment/Statin Placebo CHD Events (%) 25 4 S 20 15 10 TNT (80 mg atorvastatin) LIPID CARE HPS TNT (10 mg atorvastatin) 5 0 50 ASCOT 70 90 LIPID CARE HPS WOSCOPS 130 WOSCOPS AFCAPS ASCOT AFCAPS 110 Primary prevention trials 2 Active treatment/Statin Placebo 150 170 190 210 (mg/d. L) LDL Cholesterol 1. La. Rosa JC, et al. N Engl J Med. 2005; 352: 1425 -1435. 2. O’Keefe J, et al. J Am Coll Cardiol. 2004; 43: 2142 -2146.

REVERSAL: modificarea volumului placii de aterom coronare apare la reducerea LDL-C cu ~50% Modificarea volumului placii de aterom, mm 3 20 15 10 5 0 Reducerea LDL–C cu 50% -5 -10 -15 -80 -70 -60 -50% -40 -30 -20 -10 Reducerea LDL colesterol (%) Nissen S et al. JAMA 2004; 291: 1071 -80. 0 10 20

Program de Monitorizare Globală pentru Prevenţia şi Controlul Bolilor Cronice Netransmisibile : 25 X 25 OBIECTIV : REDUCEREA CU 25% A RATEI MORTALITĂȚII CAUZATE DE BOLILE CRONICE NETRANSMISIBILE (IN PRNCIPAL BOLILE CARDIOVASCULARE, CANCER, DIABET SI BOLILE CRONICE RESPIRATORII) REDUCEREA CU 10% A CONSUMULUI DE ALCOOL DIABET/OBEZITATE REDUCEREA CU 10% A SEDENTARISMULUI REDUCEREA CU 30% A CONSUMULUI DE SARE/SODIU REDUCEREA CU 30% A CONSUMULUI DE TUTUN REDUCEREA CU 25% A HIPERTENSIUNII ARTERIALE CREȘTEREA CU 0% A RATEI DE MASURI DEDICATE FIECARUI FACTOR DE RISC IN PARTE MINIM 50 % DINTRE PACIENȚII LA RISC SA PRIMEASCA TRATAMENT ADECVAT ȘI CONSILIERE ÎN VEDEREA PREVENIRII APARITIEI BOLILOR MINIM 80% DINTRE PACIENȚI SA AIBA ACCES LA TEHNICI DE DIAGNOSTIC SI LA TRATAMENT MODERN NECESAR TRATĂRII BOLILOR 2025