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Ospedale San Giovanni di Dio Firenze 3 ottobre 2009 Una Patologia Polidistrettuale: l’Aterotrombosi Plinio Fabiani What is Atherothrombosis? • Atherothrombosis is characterized by a sudden (unpredictable) atherosclerotic plaque disruption (rupture or erosion) leading to platelet activation and thrombus formation Plaque rupture1 Plaque erosion2 • Atherothrombosis is the underlying condition that results in events leading to myocardial infarction, ischemic stroke, and vascular death 1. Falk E et al. Circulation 1995; 92: 657–71. 2. Arbustini E et al. Heart 1999; 82: 269–72. La due fasi dell’atero-trombosi Infarto Miocardico Acuto Atherothrombosis: A Generalized and Progressive Process Unstable angina ACS MI Ischemic stroke/TIA Critical leg ischemia Cardiovasculardeath Atherosclerosis Atherothrombosis Stable angina Intermittent claudication Adapted from Stary HC et al. Circulation. 1995; 92: 1355–74, and Fuster V et al. Vasc Med. 1998; 3: 231–9. Major Clinical Manifestations of Atherothrombosis Ischemic stroke Myocardial infarction Transient ischemic attack Angina: • Stable • Unstable Peripheral arterial disease: • • • • Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6. Intermittent claudication Rest Pain Gangrene Necrosis The Development of Atherothrombosis – a Generalized and Progressive Process Acute syndrome: • coronary • cerebrovascular • peripheral Occlusive thrombus Plaque rupture Platelet activation and aggregation Non-occlusive thrombus Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6. Healing and resolution Plaque growth Atherothrombosis and Microcirculation Plaque rupture Embolization Microvascular obstruction Adapted from: Topol EJ, Yadav JS. Circulation 2000; 101: 570–80, and Falk E et al. Circulation 1995; 92: 657–71. Atherothrombosis* is a Leading Cause of Death Worldwide†1 Mortality (%) *Cardiovascular disease, ischemic heart disease and cerebrovascular disease †Worldwide defined as Member States by WHO Region (African, Americas, Eastern Mediterranean, European, South-East Asia and Western Pacific) 1. The World Health Report 2002. Geneva: WHO; 2002. Identifying Those at Risk of Atherothrombosis1,2 Local factors: • Elevated prothrombotic factors: fibrinogen, CRP, PAI-1 • Blood flow patterns, vessel diameter, arterial wall structure Generalised disorders • Obesity • Diabetes Atherothrombosis manifestations (myocardial infarction, stroke, vascular death) Genetic • Genetic traits • Gender • Age Lifestyle • Smoking • Diet • Lack of exercise 1. Yusuf S et al. Circulation 2001; 104: 2746–53. 2. Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6. Systemic conditions • History of vascular events • Hypertension • Hyperlipidemia • Hypercoagulable states • Homocystinemia Il fumo uccide! Six month stroke admission rate Atherothrombosis is a Systemic Disease: Increased Risk of Stroke in Patients After a Myocardial Infarction1 4.5 4.0 4.17 3.58 3.5 3.0 2.5 2.0 1.5 1.0 2.72 2.08 1.43 0.93 0.5 0.0 0 1 2 3 Number of risk factors 1. Lichtman JH et al. Circulation 2002; 105: 1082–7. 4 5 or more Calcificazioni coronariche L’aterosclerosi coronarica è il più comune fattore predisponenete per l’aterostrombosi Atherothrombosis is a Systemic Disease: Long-Term Risk Increase for Stroke As a Function of Coronary Calcification1 x 3.3 3.5 Risk increase 3.0 2.5 2.0 1.5 1.0 1.0 0.5 0.0 0–100 101–500 Coronary calcium score 1. Vliegenthart R. Stroke 2002; 33: 462–5. > 500 Atherothrombosis is a Systemic Disease: Long-term Risk Increase for Myocardial Infarction as a Function of Carotid Intima Media Thickness1 4.0 x 3.61 Risk increase 3.5 3.0 2.5 2.0 1.5 1.0 1.0 0.5 0.0 1 2 3 4 Quintiles of carotid artery media thickness 1. O’Leary DH. N Engl J Med 1999; 340: 14–22. 5 Indice di Winsor (braccio/caviglia) Atherothrombosis is a Systemic Disease: Increase for Myocardial Infarction and Stroke as a Function of ABI Measurement1 2.5 Risk increase x 2.2 2.0 1.5 1.0 1.0 0.8 0.6 Ankle-brachial index (ABI) index 1. Dormandy JA, Creager MA. Cerebrovasc Dis 1999; 9(suppl 1): 14. 0.4 0.2 Causes of Death During Different Time Intervals after First-Ever Stroke1 100% Proportion of deaths (%) 90% 80% 70% Unknown 60% Non-vascular 50% Cardiovascular 40% 30% Recurrent stroke 20% Related to first stroke 10% 0% < 30 days 30d–6m 6m–1yr Time 1. Hankey GJ. Stroke 2000; 31: 2080–6. 1–3yr 3–5yr Manifestations of Atherothrombosis are Commonly Found in More than One Arterial Bed in an Individual Patient*1 Cerebrovascular disease Coronary disease 7.4% 24.7% 29.9% 3.3% 11.8% 3.8% 19.2% Peripheral arterial disease *Data from CAPRIE study (n=19,185) 1. Coccheri S. Eur Heart J 1998; 19(suppl): P1268. Conclusioni • L’Aterotrombosi è caratterizzata da un’improvvisa rottura di placca che determina attivazione piastrinica e formazione del trombo1 • L’aterotrombosi rappresenta il legame patologico comune a tutte le maggiori manifestazioni cliniche delle malattie vascolari: infarto del miocardio, ictus ischemico ed ateriopatia obliterante periferica2 • Pazienti con manifestazioni cliniche di aterotrombosi in un letto vascolare non sono solo a rischio di un evento ricorrente nella stessa distribuzione arteriosa, ma corrono il rischio di eventi ischemici anche in altri letti vascolari3 • L’Aterotrombosi è la maggiore causa di mortalità nel mondo intero4 1. Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6. 2. Nenci GG. Eur Heart J 1999; 1(suppl A): A27–A30. 3. Lichtman JH et al. Circulation 2002; 105: 1082–7. 4. The World Health Report 2002. Geneva: WHO; 2002.