Una Patologia Polidistrettuale:l’Aterotrombosi

Plinio Fabiani

3 ottobre 2009

Ospedale San Giovanni di DioFirenze

What is Atherothrombosis?

• Atherothrombosis is characterized by a sudden (unpredictable) atherosclerotic plaque disruption (rupture or erosion) leading to platelet activation and thrombus formation

• Atherothrombosis is the underlying condition that results in events leading to myocardial infarction, ischemic stroke, and vascular death

Plaque rupture1 Plaque erosion2

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

MI Ischemic stroke/TIACritical leg ischemiaCardiovasculardeath

ACS

Atherosclerosis

Adapted from Stary HC et al. Circulation. 1995; 92: 1355–74, and Fuster V et al. Vasc Med. 1998; 3: 231–9.

Stable angina Intermittent claudication

Atherothrombosis

Major Clinical Manifestations of Atherothrombosis

Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6.

Transient ischemic attack

Angina:• Stable• Unstable

Ischemicstroke

Myocardial infarction

Peripheral arterialdisease:• Intermittent claudication• Rest Pain• Gangrene• Necrosis

Plaquerupture

Platelet activation and aggregation

Non-occlusivethrombus

Acute syndrome:• coronary• cerebrovascular• peripheral

Occlusivethrombus

Healing andresolution

Plaque growth

The Development of Atherothrombosis – a Generalized and Progressive Process

Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6.

Atherothrombosis and Microcirculation

Adapted from: Topol EJ, Yadav JS. Circulation 2000; 101: 570–80, and Falk E et al. Circulation 1995; 92: 657–71.

Plaquerupture

Microvascular obstruction

Embolization

Atherothrombosis* is aLeading Cause of Death Worldwide†1

1. The World Health Report 2002. Geneva: WHO; 2002.

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)

Identifying Those at Risk of Atherothrombosis1,2

1. Yusuf S et al. Circulation 2001; 104: 2746–53. 2. Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6.

Lifestyle• Smoking• Diet• Lack of exercise

Genetic• Genetic traits• Gender• Age

Generaliseddisorders• Obesity• Diabetes

Systemicconditions• History of vascular

events• Hypertension• Hyperlipidemia• Hypercoagulable

states• Homocystinemia

Local factors: • Elevated prothrombotic factors: fibrinogen, CRP, PAI-1• Blood flow patterns, vessel diameter, arterial wall structure

Atherothrombosis manifestations

(myocardial infarction, stroke, vascular death)

Il fumo uccide!

Atherothrombosis is a Systemic Disease: Increased Risk of Stroke in Patients After a

Myocardial Infarction1

1. Lichtman JH et al. Circulation 2002; 105: 1082–7.

0.93

1.43

2.08

2.72

3.58

4.17

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

0 1 2 3 4 5 or more

Six

mon

th s

trok

e ad

mis

sion

rat

e

Number of risk factors

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

1. Vliegenthart R. Stroke 2002; 33: 462–5.

1.0

x 3.3

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

0–100 101–500 > 500

Coronary calcium score

Ris

k in

crea

se

1. O’Leary DH. N Engl J Med 1999; 340: 14–22.

1.0

x 3.61

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

1 2 3 4 5

Quintiles of carotid artery media thickness

Ris

k in

crea

seAtherothrombosis is a Systemic Disease:

Long-term Risk Increase for Myocardial Infarction as a Function of Carotid Intima Media Thickness1

Indice di Winsor (braccio/caviglia)

1. Dormandy JA, Creager MA. Cerebrovasc Dis 1999; 9(suppl 1): 14.

Atherothrombosis is a Systemic Disease: Increase for Myocardial Infarction and Stroke as

a Function of ABI Measurement1

x 2.2

1.0

1.5

2.0

2.5

1.0 0.8 0.6 0.4 0.2

Ankle-brachial index (ABI) index

Ris

k in

crea

se

Causes of Death During Different Time Intervals after First-Ever Stroke1

1. Hankey GJ. Stroke 2000; 31: 2080–6.

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

< 30 days 30d–6m 6m–1yr 1–3yr 3–5yr

Time

Pro

po

rtio

n o

f d

eath

s (%

)

Unknown

Non-vascular

Cardiovascular

Recurrent stroke

Related to first stroke

Manifestations of Atherothrombosis are Commonly Found in More than One Arterial Bed in an Individual Patient*1

1. Coccheri S. Eur Heart J 1998; 19(suppl): P1268.

Coronary disease

Cerebrovascular disease

Peripheral arterial disease

24.7%

3.8% 11.8%

29.9%

3.3%

7.4%

19.2%

*Data from CAPRIE study (n=19,185)

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.