Modifiable

Hypertension

Dyslipidemia

Diabetes

Atrial fibrillation

SCD

Goldstein L, et al. Circulation. 2001;103:163-182.

Broderick J, et al. Stroke. 1998;29:415-421.

Brown WV. Clin Cornerstone. 2004;6(suppl 3):S30-S34.

TIA/prior stroke

Carotid stenosis

Cigarette smoking Obesity

Physical inactivity

HRT

Non-Modifiable

Age

Gender

Race/Ethnicity

Genetics

Low birth weight

Potentially Modifiable

Metabolic syndrome

Excess alcohol

Drug abuse

OCPs

Sleep-disordered breathing

Migraine

Hyperhomocysteinemia

Lipoprotein (a)

Hypercoagulability

Inflammation

Infection

Data from Prospective Studies Collaboration, Lancet 2002;360:1903

Hypertension

• Regular BP

screening

• Treatment

• Targets of

therapy

Class I A

Diabetes and Stroke Prevention

• Kenyan prevalence of DM 3.9% (2-12%)

• The prevalence of diabetes in persons with stroke is about 15-33%.

• DM a risk factor for stroke, but relationship to recurrent stroke unclear.

• DM is a clear RF in lacunar strokes

Diabetes Mellitus BP Control Class I A

ACEI/ARB Class I A

Statin, especially in those with additional risk

factors

Class I A

Fibrate Class IIb B

Addition of a fibrate to a statin in DM is not useful

for decreasing stroke risk.

Class III B

Aspirin Class IIb B

Blood lipids and Stroke Prevention

Modest relationship between elevated total cholesterol or LDL with increased risk of ischemic stroke

Higher serum triglycerides linked to ischemic stroke and large artery atherosclerosis

Link between LDL and ICH

Meta-analysis: the larger the reduction in LDL-C the larger the reduction in stroke

SPARCL – Stroke Prevention by Aggressive Reduction in Cholesterol Levels

4371 persons with LDL-C = 2.6-4.9 mmol/L

Randomized to 80 mg atorvastatin vs. placebo

Endpoint: fatal and nonfatal stroke = 11.2% vs. 13.1%

5 yr absolute RR, 2.2%, HR 0.84; 85% CI (0.71 to 0.99;

P=0.03)

5 yr absolute RR in cardiovascular events was 3.5%

(HR, 0.80; 95% CI, 0.69-0.92; P=0.002).

Recommendations/targets ↑LDL, ↓HDL

N Engl J Med. 2006;355(6):549

Dyslipidemia

Statins Class I A

Fibric acid derivatives Class IIb C

Niacin Class IIb C

Bile acid sequestrants

Ezetimibe

Class IIb C

Atrial Fibrillation Screening

CHADS2VASc

HASBLED

Class IIa B

• Warfarin

• Dabigatran (RE-LY)

• Rivaroxaban (ROCKET AF)

Class I A

Class I B

Aspirin Class I A

High-risk patients with AF unsuitable for

anticoagulation→→→ Clopidogrel + Aspirin

Class IIb B

• Asymptomatic Carotid Stenosis

• OCPs

• Sickle Cell disease

• TCD screening

• Transfusion

• Hydroxyurea

• BMT

• Other Stroke risks

Primary Stroke prevention

• Diet and nutrition

• Physical inactivity

• Obesity and body fat distribution

• Alcohol consumption

• Cigarette smoking

Primary Stroke prevention

Hyperhomocysteinemia

B-complex vitamins,

pyridoxine (B6 ), Cobalamin

(B12 ) and folic acid

effectiveness not well

established

IIb; B

Elevated Lipoprotein (a)

Niacin IIb; B

Hypercoagulability

Role of screening IIb;C

Specific treatments for primary

stroke prevention in asymptomatic

patients

IIb;C

Low-dose aspirin not indicated for

primary stroke prevention in

persons who are persistently aPL

positive.

III;B

Inflammation and Infection

hs-CRP or Lp-PLA2 ~↑ risk of stroke IIb B

Chronic inflammatory disease RA /SLE

≡↑stroke risk

I B

↑hs-CRP →→? Statin IIb B

Annual influenza vaccination IIa B

HIV?

Aspirin for Primary Stroke Prevention

Aspirin in CV risk 6%-10% I A

Aspirin not useful in low risk patients III A

Aspirin not useful in DM or DM+

asymptomatic PAD in the absence of

other established CVD

III B

Assessing the Risk of First Stroke

Stroke risk assesment I A

Stroke risk-assessment tools

Framingham stroke profile

IIa B

Stroke or TIA survivors have an increased risk of a subsequent stroke

Recurrent strokes are more likely than initial strokes to result in disability and death

~ 20%-40% of strokes are preceded by a TIA or non disabling stroke

Rothwell et al. Lancet Neurol 2006; 5: 323-331

Evaluate the Event

Implement Interventions Initiate Medications

Modify Stroke Risk Factor: Continuous Monitoring

TIA Stroke Risk Assessment

High Risk

1. Symptom onset within the last 48 hours with any one of the following :

Motor deficit lasting more than 5 minutes

Speech deficit lasting more than 5 minutes

ABCD2 score ≥ 4

2. Atrial fibrillation with TIA

TIA Stroke Risk Assessment Medium Risk

Symptom onset between 48 hours and 7 days with any one of the following :

Motor deficit lasting more than 5 minutes

Speech deficit lasting more than 5 minutes

ABCD2 score ≥ 4

Low Risk 1. Symptom onset > 7 days

2. Symptom onset ≤ 7 days without the presence of high risk symptoms Speech deficit, motor deficit, ABCD2 score ≥ 4, atrial fibrillation with TIA

› CT or MRI

Rule out mimics, identify stroke type

› Carotid Imaging (carotid duplex, CTA or MRA)

Identify stenosis

› ECG

? Cardiac cause - afib

Holter monitor

› Echocardiogram

If suspect cardiac cause

› Labs - CBC, UECr, RBS, PTT, INR, fasting lipids

Cigarette Smoking

Alcohol

Physical activity

Modifiable Behavioral Risk Factors

Interventions:

Diet

Exercise

Pharmacologic

Metabolic Syndrome and Stroke

63 Year old male, DM, Hypertension, non smoker, teetotaler

4 months ago developed sudden onset right hemiparesis, initial power 2/5, Improved to 4/5. Speech normal

Preceded by episodic right sided numbness and mild weakness that usually resolved

Referred Re: one week of worsening right hemiparesis

On Insulin, Amlodipine, Aspirin

Symptomatic Extra-cranial Carotid

Disease

Carotid Endarterectomy: Conventional Gold Standard Surgical Treatment

Carotid Endarterectomy vs Medical Rx

Trial Mean Follow-up Surgical Arm* Medical Arm*

ECST

3 y

2.8%

16.8%

NASCET

2.7 y

9%

26%

VACS

11.9 mo

7.9%

25.6%

ECST indicates European Carotid Surgery Trial; NASCET, North American Symptomatic Carotid Endarterectomy Trial; and

VACS, Veterans Affairs Cooperative Study Program.

*Risk of fatal or nonfatal ipsilateral stroke.

CREST: Hazard Ratio for CAS vs CEA

Periprocedural HR

(95% CI)

4-Year Study Period

HR

(95% CI)

MI 0.45 (0.18-1.11) ---

Any periprocedural

stroke or postprocedural

ipsilateral stroke 1.74 (1.02-2.98) 1.29 (0.84-1.98)

Any periprocedural

stroke, death, or

postprocedural

ipsilateral stroke

1.89 (1.11-3.21) 1.37 (0.90-2.09)

Any periprocedural

stroke, MI, death, or

postprocedural

ipsilateral stroke

1.26 (0.81-1.96) 1.08 (0.74-1.59)

Risk Factor – Symptomatic Extracranial Carotid

Disease

Recommendations

Class/Level of

Evidence

TIA or ischemic stroke within 6 months and ipsilateral

severe carotid artery stenosis, CEA if perioperative

morbidity and mortality risk is estimated to be <6%.

Class I; A

Ipsilateral moderate carotid stenosis, CEA depending on

patient-specific factors if the perioperative morbidity and

mortality risk is estimated to be <6%.

Class I; B

Stenosis <50%, no indication for carotid revascularization Class III; A

Recommendations for Interventional Approaches to Patients

With Stroke Caused by Large-Artery Atherosclerotic Disease

Risk Factor – Symptomatic Extracranial

Carotid Disease

Recommendations

CEA surgery within 2 weeks reasonable if there

are no contraindications to early

revascularization.

Class IIa; B

CAS an alternative to CEA for symptomatic

patients at average or low risk of

complications of endovascular intervention.

Class I; B

82 Year old male, DM, non smoker, teetotaler

2 days of severe dizziness+ Gait ataxia. Tendency to fall right side

Clinically cerebellar dysfunction

MRI Brain→Right cerebellar infarct

On Metformin, Aspirin, Cinnarizine

82 Year old male, DM, non smoker, teetotaler

2 days of severe vertigo+ Gait ataxia. Tendency to fall right side

Clinically cerebellar dysfunction

MRI Brain→Right cerebellar infarct

On Metformin, Aspirin, Cinnarizine

Extracranial Vertebrobasilar Disease

• Persons with occlusive disease of the proximal and cervical portions of the vertebral artery (VA) are at relatively high risk for posterior or vertebrobasilar circulation ischemia.

• Symptomatic VA stenosis carries a high recurrent risk in the first 7 days after symptoms onset than patients with recently symptomatic carotid stenosis.

• ? Medical therapy

• ? Role of invasive treatment

Intracranial Atherosclerosis

High risk of subsequent stroke.

The WASID trial

Aspirin >>>Warfarin

BP, cholesterol control

?Angioplasty+/- Stenting

EC/IC bypass NOT recommended

Atrial Fibrillation and Stroke

• Persistent and paroxysmal Afib are potent risk factors for first and recurrent stroke

• Subclinical atrial fibrillation

• VKA anticoagulation, Dabigatran, Rivaroxaban

• CHADS2VASc

Risk Factor – Atrial Fibrillation

Ischemic stroke or TIA with paroxysmal

(intermittent) or permanent AF → VKA

Dabigatran

Rivaroxaban

Class I A

Unable to take oral anticoagulants→ Aspirin

Clopidogrel + Aspirin risk of bleeding ≡

warfarin

Class I A

Class III B

AF at high risk for stroke, temporary interruption

of oral anticoagulation →→ LMWH

Class IIa C

Recommendations for Patients With

Cardioembolic Stroke Types

Acute MI and LV Thrombus

Risk Factor – Acute MI and LV

Thrombus

Class/Lev

el of

Evidence

Ischemic stroke or TIA →→oral

anticoagulation (target INR 2.5;

range 2.0 to 3.0) >=3 months.

Class I B

Risk Factor – Cardiomyopathy Class/Level

of

Evidence

Prior stroke/TIA in sinus rhythm with

cardiomyopathy (LVEF 35%), ?the benefit of

warfarin

Class IIb B

Warfarin, Aspirin (81 mg daily), clopidogrel (75

mg daily), or Aspirin (25 mg twice daily) plus ER

dipyridamole (200 mg twice daily)

Class IIb B

Recommendations for Patients With Cardioembolic Stroke Types

Risk Factor – Native Valvular Heart Disease Class/Level

of Evidence

Rheumatic mitral valve disease+/- AF →→ long-term

warfarin

Class IIa C

Antiplatelet agents should not be routinely added to

warfarin.

Class III C

Native aortic or nonrheumatic mitral valve disease -

AF, antiplatelet therapy

Class IIb C

Mitral annular calcification →→ antiplatelet therapy Class IIb C

MVP →→ long-term antiplatelet therapy may be

considered.

Class IIb C

Recommendations for Patients With Cardioembolic Stroke Types

Risk Factor – Prosthetic Heart Valves Class/Level of

Evidence

Mechanical prosthetic heart valves →→

warfarin INR target of 3.0 (range, 2.5 to 3.5).

Class I; B

Mechanical prosthetic heart valves with

event despite adequate therapy with oral

anticoagulants→→→add aspirin 75-100

mg/d

Class IIa; B

Bioprosthetic heart valves with no other

source of thromboembolism ?Warfarin

Class IIb; C

Recommendations for Patients With Cardioembolic

Stroke Types

Class/Level of Evidence

Aspirin (50-325 mg/d)

Aspirin 25 mg + ER Dipyridamole 200 mg BD

Clopidogrel 75 mg

ASA + Clopidogrel

Class IA-IIB

Recommendations for Antithrombotic Therapy for Noncardioembolic Stroke or TIA

Pregnancy

PFO

Sickle Cell Disease

Cerebral Venous Sinus Thrombosis

Post-menopausal HRT

Hyperhomocysteinemia

Inherited Thrombophilias

APL syndrome

Stroke Patients With Other Specific Conditions

THE END