stroke: incidence and cost in the united states · cost of stroke stroke severity includes a broad...
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Stroke:Stroke:Incidence and Cost in the United StatesIncidence and Cost in the United States
◆ 700,000 new cases yearly
◆ #3 cause of death
◆ $43 billion annual health cost
(1998)
◆ 4,400,000 stroke survivors at
high risk for recurrence
Most strokes can be prevented
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Cost of StrokeCost of Stroke
◆ Stroke severity includes a broad range; about half ofsurvivors unable to walk unaided.
◆ Acute inpatient costs average $38,000 but are only afraction of total economic burden (including rehab,long-term care).
◆ Average lifetime cost of stroke in the U.S. estimatedto be $60,000.
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Race and Stroke RiskRace and Stroke Risk
◆ Stroke risk increased 1.5-2.5 times.◆ Higher prevalence of hypertension.
Hispanic - Americans◆ Stroke occurs at younger age (about 6 years earlier
than in whites).◆ Small subcortical “lacunar” strokes are more
frequent.◆ Diabetes is an important risk factor.
African -Americans
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The Stroke Belt: Stroke Mortality in Black MenThe Stroke Belt: Stroke Mortality in Black Men
Fewer than 80 deaths per 100,000 people
80 to 129.9 per 100,000
130 or more per 100,000
No data or data unreliable
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Causes of StrokeCauses of Stroke
85%85%InfarctionInfarction
60%60%CerebrovascularCerebrovascularatherosclerosisatherosclerosis
20%20%Penetrating arteryPenetrating arterydisease (disease (lacuneslacunes))
15%15%CardiogenicCardiogenic embolism embolism
5%5%Other,Other,
unusualunusualcausescauses
HemorrhageHemorrhage - - Intracerebral Intracerebral - - Subarachnoid Subarachnoid15%15%
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Cervical Carotid and Vertebral ArteriesCervical Carotid and Vertebral Arteries
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Circle of Willis:Circle of Willis:Key Collateral CirculationKey Collateral Circulation
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Vascular Territories of the CerebralVascular Territories of the CerebralHemisphereHemisphere
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Functional AnatomyFunctional Anatomy
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Causes of Stroke:Causes of Stroke:Cerebrovascular AtherosclerosisCerebrovascular Atherosclerosis
85%85%InfarctionInfarction
60% 60%CerebrovascularCerebrovascularatherosclerosisatherosclerosis- Stenosis- Stenosis (flow reduction) (flow reduction)- Ulcerated plaque- Ulcerated plaque (artery-to-artery emboli) (artery-to-artery emboli)
20%20%Penetrating arteryPenetrating arterydisease (lacunes)disease (lacunes)
15%15%Cardiogenic embolismCardiogenic embolism
5%5%Other,Other,
unusualunusualcausescauses
HemorrhageHemorrhage - Intracerebral - Intracerebral - Subarachnoid - Subarachnoid15%15%
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Critical Internal CarotidCritical Internal Carotid Stenosis Stenosis
Critical InternalCarotid Stenosis
Critical InternalCarotid Stenosis
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Mechanisms of IschemiaMechanisms of Ischemia
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Nonstenotic Ulcerated PlaqueNonstenotic Ulcerated Plaque
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Carotid UltrasoundCarotid Ultrasound
Internal carotidInternal carotidarteryartery
Common carotidCommon carotidarteryartery
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Magnetic Resonance Angiography (MRA)Magnetic Resonance Angiography (MRA)
Cervical Carotid Artery Middle Cerebral Artery
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Major Risk Factors for CerebrovascularMajor Risk Factors for CerebrovascularAtherosclerosisAtherosclerosis
FACTOR
◆ Hypertension
◆ Smoking
◆ Diabetes
◆ Hyperlipidemia
◆ Obesity
INCREASED RISK
X 5-10
X 2
X 2
X 1.5
X 1.5
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Reduction in Stroke in SHEPReduction in Stroke in SHEP
0
2
4
6
8
10
36% reduction in stroke (p = 0.003)36% reduction in stroke (p = 0.003)
0 12 24 36 48 60
PlaceboPlacebo
Active TreatmentActive Treatment
Follow-up, months
Cum
ulat
ive
Str
oke
Rat
e pe
r 10
0 P
opul
atio
nC
umul
ativ
e S
trok
e R
ate
per
100
Pop
ulat
ion
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Therapeutic Goals for Antihypertensive RxTherapeutic Goals for Antihypertensive Rx
Condition
◆ Uncomplicated
◆ Diabetic
◆ African-American
Goal BP
140/90
135/85
135/85
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Stroke Risk in SmokersStroke Risk in Smokers
10 20 30 40 10 20 30 400
0.5
1
1.5
2
2.5
1.21.2
1.41.4
1.61.6
1.91.9
1.21.21.41.4
1. 71. 7
2.02.0MenMen WomenWomen
Re
lativ
e R
isk
of S
tro
keR
ela
tive
Ris
k o
f S
tro
ke
Framingham DataFramingham DataJAMA 259:1025, 1988JAMA 259:1025, 1988 No. of Cigarettes Smoked/dayNo. of Cigarettes Smoked/day
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Stroke Free Survival in Smokers,Stroke Free Survival in Smokers,Nonsmokers and Former SmokersNonsmokers and Former Smokers
70
80
90
100
% F
ree
of S
troke
% F
ree
of S
troke
0 5 10 15 5 10 15 2020
MenMen WomenWomen
Years of follow-upSurvival free of stroke in cigarette smokers (dotted line), nonsmokers (solid line). and formerSurvival free of stroke in cigarette smokers (dotted line), nonsmokers (solid line). and formersmokers (dashed line), aged 60 years, using Cox proportional hazard regression model, in men and womensmokers (dashed line), aged 60 years, using Cox proportional hazard regression model, in men and women
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Stroke Facts in DiabetesStroke Facts in Diabetes
◆ Stroke risk 2 X higher
◆ Hypertension more prevalent in diabetics
◆ Strokes occur at younger age
◆ Risk of death after stroke 2 X higher
◆ Recovery from stroke less complete
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Lipid Lowering and Stroke Prevention:Lipid Lowering and Stroke Prevention:SummarySummary
Recent clinical trials of “statins”:
◆ Reduces stroke by 30% in patients with MI and angina .
◆ Reversed progression of plaque by ultrasound in early asymptomatic carotiddisease.
◆ Effective in “low-risk” (0.5%/yr stroke rate) patients with modestly elevatedcholesterol; not yet tested in high risk patients.
Lipid lowering with “statins” seems sensible to reduce stroke for those withatherosclerotic cerebrovascular disease and LDL cholesterol >130 mg%.
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Transient Ischemic Attack (TIA)Transient Ischemic Attack (TIA)
◆ “Warning strokes:” transient focal ischemia
◆ Duration: <24 hrs (usually 5 to 10 minutes)
◆ May occur with any cause of ischemic stroke
◆ TIA patients have 10 times the risk of ischemicstroke:● Risk highest in first 3 months after TIA
● 35% stroke risk with 3-5 years after TIA
◆ An opportunity to prevent stroke
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Common Manifestations of TIACommon Manifestations of TIA
Carotid system TIA
◆ Unilateral weakness
◆ Unilateral sensory symptoms
◆ Aphasia
◆ Monocular vision loss
Vertebrobasilar system TIA
◆ Bilateral weakness
◆ Bilateral sensory symptoms
◆ Diplopia◆ Vertigo◆ Ataxia without weakness◆ Dysphagiaonly in combination; not as isolated symptoms
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Established Therapies to Reduce StrokeEstablished Therapies to Reduce StrokeDue to Cerebrovascular AtherosclerosisDue to Cerebrovascular Atherosclerosis
◆ Control of risk factors(especially hypertension, lipids, smoking)
◆ Antiplatelet agents● aspirin
● ticlopidine / clopidogrel
◆ Carotid endarterectomy (selected patients)
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Antiplatelet Therapies for Stroke PreventionAntiplatelet Therapies for Stroke Prevention
35-40% stroke reduction;headache in 6%
200 mg bid
(25 mg bid)Phosphodiesterase
inhibitionDipyridamole
(with aspirin)
30% stroke reduction;non-toxic
75 mgADP receptor blockadeClopidogrel
35% stroke reduction;expensive, rash, diarrhea,
leukopenia (1%)250 mg bidADP receptor blockadeTiclopidine
25% stroke reduction50-1500 mgCyclo-oxygenase
inhibitionAspirin
CommentDaily DoseMechanismAgent
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Effect of Carotid Endarterectomy inEffect of Carotid Endarterectomy in CarotidCarotidStenosis: Symptomatic vs. AsymptomaticStenosis: Symptomatic vs. Asymptomatic
0
2
4
6
8
10
12
14
Str
oke
Rat
e (%
/yr)
Str
oke
Rat
e (%
/yr)
SymptomaticSymptomaticCarotid StenosisCarotid Stenosis
( >70% )( >70% )
AsymptomaticAsymptomaticCarotid StenosisCarotid Stenosis
( >60% )( >60% )
Medical Rx
Carotid Endarterectomy
SymptomaticSymptomaticCarotid StenosisCarotid Stenosis
( 50-69%)( 50-69%)
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Carotid Endarterectomy for StrokeCarotid Endarterectomy for StrokePrevention: SummaryPrevention: Summary
◆ Benefit is established for high-grade (>70%) symptomaticcarotid stenosis.
◆ Value in moderate (50-69%) symptomatic stenosis is modestand similar to that for asymptomatic carotid stenosis.
◆ Reduces stroke in asymptomatic carotid stenosis, butmagnitude of benefit is small (1%/yr).
◆ Whether catheter arteriography should routinely precedeendarterectomy is controversial.
◆ Role of carotid angioplasty/stenting undergoing evaluation intrials.
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Causes of Stroke:Causes of Stroke:Penetrating Artery Disease (Lacunes)Penetrating Artery Disease (Lacunes)
85%85%InfarctionInfarction
60%60%CerebrovascularCerebrovascularatherosclerosisatherosclerosis
20%20%Penetrating arteryPenetrating arterydisease (disease (lacuneslacunes))
15%15%CardiogenicCardiogenic embolism embolism
5%5%Other,Other,
unusualunusualcausescauses
HemorrhageHemorrhage - - Intracerebral Intracerebral - - Subarachnoid Subarachnoid15%15%
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Lacunar StrokeLacunar Stroke
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Lacunar InfarctsLacunar Infarcts(Small Subcortical Strokes): Summary(Small Subcortical Strokes): Summary
◆ Diagnosis: Clinical syndrome (e.g., pure motor orpure sensory) plus CT/MRI confirmation
◆ Risk factor management: Hypertension, diabetes
◆ Carotid stenosis: Present in only 10%
◆ Rate of occurrence: High (10% yr)
◆ Antiplatelet agents probably effective
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Causes of Stroke: CardiogenicCauses of Stroke: CardiogenicEmbolismEmbolism
85%85%InfarctionInfarction
60%60%CerebrovascularCerebrovascularatherosclerosisatherosclerosis
20%20%Penetrating arteryPenetrating arterydisease (disease (lacuneslacunes))
15%15%CardiogenicCardiogenic embolism* embolism*
5%5%Other,Other,
unusualunusualcausescauses
HemorrhageHemorrhage - - Intracerebral Intracerebral - - Subarachnoid Subarachnoid15%15%
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Sources of Cardiogenic EmbolismSources of Cardiogenic Embolism
Nonvalvular atrialNonvalvular atrialfibrillationfibrillation
(45%)(45%)
Acute MIAcute MI(15%((15%(
Other,lessOther,lesscommon sourcescommon sources
(10%)(10%)ProstheticProsthetic
cardiac valvescardiac valves(10%)(10%)
Rheumatic heartRheumatic heartdiseasedisease(10%)(10%)
VentricularVentricularaneurysmaneurysm
(10%)(10%)
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AtrialAtrial Fibrillation (AF) Predisposes to Fibrillation (AF) Predisposes toStrokeStroke
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Stroke Prevention in Atrial FibrillationStroke Prevention in Atrial Fibrillation
◆ Mean Onset Age 64, > 2 Million People
◆ 35% Have Stroke During Lifetime
◆ 5% /Yr Stroke Rate
◆ >75,000 Strokes/Yr in U.S.
AF is a marker of 2 million Americans with a six-fold increased risk of stroke.
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Stroke: Other, Unusual CausesStroke: Other, Unusual Causes
*Dissection, migraine, oral contraceptive use in smokers, meningovascular syphilis, cocaine and amphetamine use, associated with prothrombotic states (e.g., sickle cell anemia)
85%85%InfarctionInfarction
60%60%CerebrovascularCerebrovascularatherosclerosisatherosclerosis
20%20%Penetrating arteryPenetrating arterydisease (lacunes)disease (lacunes)
15%15%Cardiogenic embolismCardiogenic embolism
5%5%Other,Other,
unusualunusualcausescauses
HemorrhageHemorrhage - Intracerebral - Intracerebral - Subarachnoid - Subarachnoid15%15%
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Hemorrhagic StrokeHemorrhagic Stroke
85%85%InfarctionInfarction
60%60%CerebrovascularCerebrovascularatherosclerosisatherosclerosis
20%20%Penetrating arteryPenetrating arterydisease (disease (lacuneslacunes))
15%15%CardiogenicCardiogenic embolism embolism
5%5%Other,Other,
unusualunusualcausescauses
HemorrhageHemorrhage - - Intracerebral Intracerebral - - Subarachnoid Subarachnoid15%15%
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Types of CNS HemorrhageTypes of CNS Hemorrhage
Arteriovenousmalformation
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Hypertensive Intracerebral Hemorrhage Hypertensive Intracerebral Hemorrhage
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Aneurysmal Subarachnoid HemorrhageAneurysmal Subarachnoid Hemorrhage
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Evaluation of TIA and Ischemic Stroke*Evaluation of TIA and Ischemic Stroke*
Step I:Step I: •• CBC, platelet count, PT, PTT, RPR CBC, platelet count, PT, PTT, RPR•• Chemistry profile (glucose, cholesterol) Chemistry profile (glucose, cholesterol)•• ECG ECG•• CT Scan CT Scan
•• Carotid ultrasound Carotid ultrasound•• Echocardiography Echocardiography•• Rhythm (Holter) monitoring if suspicious Rhythm (Holter) monitoring if suspicious symptoms symptoms
•• Arteriography or MR angiography Arteriography or MR angiography•• Magnetic resonance imaging Magnetic resonance imaging•• Special coagulation testing Special coagulation testing•• Transesophageal echocardiography Transesophageal echocardiography
Step II:Step II:
Step III:Step III:
* for patients > 50 years old* for patients > 50 years old
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Acute Stroke Treatment: Salvaging theAcute Stroke Treatment: Salvaging theIschemic PenumbraIschemic Penumbra
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NINDS tPA StudyNINDS tPA Study(NEJM 1995: 333: 1581)(NEJM 1995: 333: 1581)
◆ First proven effective intervention for acute stroke
◆ Double blind, randomized, 624 patients
◆ tPA 0.9 mg/kg (max 90mg) infused over 1 hour
◆ Treatment started <3hrs from stroke onset
◆ CT documenting absence of hemorrhage
◆ No anticoagulants or antiplatelet Rx for 24 hrs
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NINDS tPA StudyNINDS tPA StudyKey OutcomesKey Outcomes
tPA Placebo
GoodOutcome
• Barthel95-100
50% 38%
• Rankin0,1
39% 26%
Death 17% 21%• Brain
hemorrhage 6% 1%
DifferenceAbsolute
12%*
13%
- 4%
+5%
* 12 extra pts./100 given tPA regained normal function
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Thrombolytic TherapyThrombolytic Therapy
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AngioplastyAngioplasty
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CT AngiographyCT Angiography
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Initial Management of Acute StrokeInitial Management of Acute Stroke
◆ Determine ischemic vs. hemorrhagic by (CT)◆ Consider thrombolytic Rx if <3 hrs from onset◆ Assess stroke mechanism◆ Systemic management issues:
● blood pressure● oxygenation● glucose● dysphagia / aspiration precautions● D.V.T. prophylaxis● fluid status● seizures
◆ Consider aspirin if ischemic stroke, no contraindications
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Stroke Prevention: High Risk PatientsStroke Prevention: High Risk Patients
◆ Prior TIA or minor stroke
◆ Atrial Fibrillation
◆ Hypertension*
◆ Asymptomatic Stenosis
◆ Smoking*
X 10
X 6
X 5-10
X 3
X 2
Relative Risk
*Patients who have both uncontrolled hypertension and whosmoke have a 10-20 fold risk!
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Summary Diagram of Causes of StrokeSummary Diagram of Causes of Stroke
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Stroke Syndromes: SummaryStroke Syndromes: Summary
• Half million new strokes each year• Effective preventive therapy available to prevent most strokes• Emphasis must be on prevention
85%85%InfarctionInfarction
60%60%CerebrovascularCerebrovascularatherosclerosisatherosclerosis
20%20%Penetrating arteryPenetrating arterydisease (disease (lacuneslacunes))
15%15%CardiogenicCardiogenic embolism embolism
5%5%Other,Other,
unusualunusualcausescauses
HemorrhageHemorrhage - - Intracerebral Intracerebral - - Subarachnoid Subarachnoid15%15%
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Established Therapies to Prevent StrokeEstablished Therapies to Prevent Stroke
◆ Risk factor control (hypertension, smoking,
hyperlipidemia).
◆ Antiplatelet agents for cerebrovascular disease.
◆ Anticoagulation for atrial fibrillation and otherselected heart diseases.
◆ Endarterectomy for high-grade symptomaticcarotid stenosis (less benefit for moderatesymptomatic and asymptomatic stenosis).
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Situation Recommended Reasonable Options
1 Cerebrovascular diseases - TIA or stroke ASA 50-1300 mg/d Clopidogrel; Ticlopidine
ASA + ER-DP
- TIA or stroke on ASA Clopidogrel TiclopidineASA + ER-DP Warfarin INR 1.5-2.5
Atrial Fibrillation - lone AF < 65 yr ASA 325 mg/d - - low risk 65-75 yr ASA 325 mg/d Warfarin INR 2-3 - > 75 yr or high risk Warfarin INR 2-3 ASA if warfarin is
contraindicated
*ASA=aspirin; ER-DP=Extended release Dipyridamole
o
Antithrombotic Therapy for Stroke Prevention: SummaryAntithrombotic Therapy for Stroke Prevention: Summary