Atherosclerosis and ischemic stroke

Atherosclerosis and ischemic stroke
Maurizio Paciaroni
Stroke Unit – Division of Cardiovascular Medicine
University of Perugia
Perugia Stroke Registry
• Tot. 2194 pazienti
-
547
490
421
350
202
184
Cardioembolia
Aterosclerosi
Malattia dei piccoli vasi
Causa indeterminata
Più possibili cause
Altre cause
25.0%
22,3%
19,2%
15.9%
9,2%
8,4%
Paciaroni 2014, unpublished data
Sottotipi di ictus ischemico e recidive
30 giorni
1 anno
5 anni
Aterotrombotico (%)
18.5
21.4
24.4
Cardioembolico (%)
5.3
13.7
31.7
Lacunare (%)
Criptogenico (%)
1.4
3.3
7.1
13.2
24.8
33.2
p
0.0006
ns
ns
Petty et al, Stroke 2000
Sopravvivenza dopo primo episodio di ictus in
base al sottotipo
Lac=339
At=435
Card=224
p=<0.0001
Giorni di follow up
De Jong et al J Clin Epidemiol 2003
Atherosclerosis
Elkind, Stroke 2010
Progression of an atherosclerotic lesion
Moore and Tabas, Cell 2011
Atherosclerosis: mechanisms of stroke
There are three main hypothesised mechanisms of
stroke related to atherosclerosis:
• Artery-to-artery embolism
• Plaque extension
• Hypoperfusion
• Small penetrating artery ostia (also known as
branch atheromatous disease)
• Combinations of these ischaemic mechanisms
Atherosclerosis: mechanisms of stroke
Border-zone infarct
Stroke: atherosclerotic plaque localization
• Extracranial arteries
– Internal carotid artery
– Vertebral artery
– Aortic arch
• Intracranial arteries
Extracranial atherosclerosis: Internal Carotid Artery
Extracranial carotid stenosis: general population
- Asimptomatic carotid stenosis (≥50%)
- Males aged up 80 y
- Females aged up 80 y
- Annual risk of stroke
- Symptomatic carotid stenosis (≥50%)
- 5 year cumulative risk ipsilateral stroke
7.5%
5.0%
2%
21.2%
•
247 paz. con stenosi carotide interna 70-99%
•
•
63/247 (25,5%) dopo 2 anni: occlusione della carotide
20/63 (31.7%) avevano presentato stroke ipsilaterale
•
•
184/247 rimaste pervie
49/184 (26,6%) dopo 5,5 anni aveva presentato stroke
ipsilaterale
Stroke 2000; 31: 2037-2042
• 53/177 (29,9%) deceduti entro 30 giorni
• 80/177 (45,2%) deceduti dopo 1,2 anni
• 132/177 (74.6%) deceduti o disabili
• 10/177 (6.0%) recidiva ipsilaterale
Severe (tight) carotid stenosis
Benefit Of Carotid Endarterectomy In Patients
With Symptomatic Severe Stenosis
Barnett et al, NEJM 1991
Moderate carotid stenosis
Benefit Of Carotid Endarterectomy In Patients
With Symptomatic Severe Stenosis
Barnett et al, NEJM 1991
CEA vs. Stenting
Endovascular treatment was associated with lower risks of
myocardial infarction (OR 0.44, 95% CI 0.23 to 0.87, P = 0.02
Ederle et al. Lancet 2010
Endarterectomy for symptomatic carotid stenosis in
relation to clinical subgroups and timing of surgery
Operative stroke and death after emergency carotid
endarterectomy for unstable neurological deficit (crescendo TIA
and stroke in evolution) vs nonemergency surgery.
Rerkasem et al, Stroke 2009
Early risk of stroke after a TIA in patients
with internal carotid artery disease
Eliasziw et al, CMJ 2004
Extracranial atherosclerosis: Vertebral Artery
- 9% of posterior strokes
- Absence of RCT
- CAVATAS randomized 16 patients with vertebral stenosis
Extracranial atherosclerosis: Aortic arch
Prevalenza dell’ateromasia dell’arco aortico.
1. Studio autoptico 2. studio su popolazione con TEE
Ateromasia dell’arco aortico
Rischio di stroke e patologia embolica periferica
Profilassi secondaria in paziente con stroke
criptogenetico e ateromasia dell’arco aortico.
No studi randomizzati:
• 2 studi retrospettivi: warfarin superiore all’aspirina;
Dressler et al, JACC 1998; Ferrari et al, JACC 1999
• 1 studio retrospettivo (519 paz., placche >4mm):
statine
antiacoagulanti orali
aspirina
OR 0.39 95% CI 0.24-0.62
OR 1.18 95% CI 0.91-1.54
OR 0.77 95% CI 0.51-1.15
Tunick et al, Am J Cardiol 2002
p=0.0001
p=0.21
p=0.20
Clopidogrel Plus Aspirin Versus Warfarin in Patients
With Stroke and Aortic Arch Plaques.
The Aortic Arch Related Cerebral Hazard Trial
Patients were randomized 1:1 to either aspirin 75 to 150
mg/d plus clopidogrel 75 mg/d (A+C), or warfarin with a
target INR 2.5 (2–3).
Primary end point: ischemic
stroke,
hemorrhagic
stroke,
peripheral embolism, myocardial
infarction, vascular death, and
incranial hemorrhage
Amarenco et al, Stroke 2014
Extracranial atherosclerosis: Aortic arch
Intracranial atherosclerosis
5-10% of stroke
15-29% of stroke/TIA
30-50% of stroke
white people
black people
Asian people
Pu et al. Frontiers in Neurology 2014
WASID: Comparison of Warfarin and Aspirin for
Symptomatic Intracranial Arterial Stenosis
N Engl J Med 2005; 352: 1305-1316
Symptomatic basilar artery stenosis
Neurology 2006; 67: 1275-1278
Symptomatic basilar artery stenosis
aspirin
55
warfarin
57
18 (33%)
9 (16%)
Ischemic stroke, brain hemorrhage, non-stroke
vascular death
HR: 2.28, 95% CI 1.02-5.08 (p=0.044)
Neurology 2006; 67: 1275-1278
Nuovi anticoagulanti orali
Indicazione: fibrillazione atriale non valvolare
•
•
•
•
Apixaban
Dabigatran
Edoxaban
Rivaroxaban
Clopidogrel plus aspirin versus aspirin alone for reducing
embolisation in patients with acute symptomatic cerebral
or carotid artery stenosis (CLAIR study): a randomised,
open-label, blinded-endpoint trial
Wong et al, Lancet Neurology 2010
SAMMPRIS trial
Stenting vs aggressive medical therapy
Aggressive medical therapy
- Aspirin 325 mg + clopidogrel 75 mg per 90 days
- Target arterial pressure < 130 mmHg
- Target LDL cholesterol < 70 mg/dL
Chimowitz et al, N Engl J Med 2011
Rank of stroke prevention strategies
in order of importance
Spence, F1000 Prime Report 2013
Correzione dei fattori di rischio
• Correzione dello stile di vita
• Terapia anti-ipertensiva
• Attento controllo del diabete
• Se colesterolo LDL superiore a 100 mg/dL:
atorvastatina 80 mg/die (ictus non cardioembolico)
Carotid atherosclerotic plaque stenosis: the
stabilizing role of statins
Artom et al, Eur J Clin Invest. 2014
MRI of endothelial permeability
Willdgruber et al, Theranostics 2013
Fibrin-tergeted molecular MRI of thrombus formation
3D TOF images
FTCA: fibrin targeted contrast agent
Willdgruber et al, Theranostics 2013
Imaging of the vulnerable plaques in human coronary
atherosclerosis (F-FDG PET; PET/TC)
Willdgruber et al, Theranostics 2013