Matters PRACTICE PRACTICE Matters

• Approximately 600,000 Americans have a stroke

each year; it is the third leading cause of death in

the United States and a leading cause of disability,

resulting in an approximated annual cost of

$30 billion.

• Approximately 15,000 veterans are annually

hospitalized for stroke, requiring 5% of VHA

resources.

• Antihypertensive agents can reduce stroke

incidence by 40%.

• For eligible patients with atrial fibrillation,

warfarin can reduce the risk of stroke by 60%.

• Carotid endarterectomy is effective in reducing

stroke in selected high-risk patients in centers

where complication rates for surgery are less

than 3% for asymptomatic patients and less than

6% for symptomatic patients.

• Specific cholesterol reducing agents (HMG-CoA)

can reduce stroke incidence by 30% in patients

with known coronary artery disease.

• Lifestyle modifications that focus on diet and exercise can reduce the risk of stroke and heart disease.

PRIMARY

STROKE

PREVENTION

A publication of the Management Decision and Research Center

A program within the Department of Veterans Affairs Health Services Research and Development Service

MAY 1999 VOL. 4 ISSUE 1
2 PRACTICE Matters

BACKGROUND

Prevention practices are the optimal clinicalapproach to reducing the risk of stroke. In this

issue of VA Practice Matters we highlight important

recent developments of research on stroke prevention aimed at helping the practicing physician.

PREVENTION AND

TREATMENT GOALS

Hypertension

I

n the United States, hypertension is the most

prevalent and treatable risk factor for stroke.

Due to national educational initiatives, the percentage of Americans aware of their hypertension has

increased from 51% in 1976 to over 70% in 1994,

and treatment has increased from 31% to 55%.

Over this same period, death from stroke declined

by 59%. However, 75% of all Americans with

hypertension are not achieving acceptable blood

pressure levels (less than 140/90 mm Hg).

Hypertension is more common among the

elderly, who are also at higher risk of cardiovascular

comorbidity. A number of lifestyle modifications

have been associated with decreased hypertension:

increased dietary calcium, magnesium and potassium; reduced saturated fat, cholesterol, sodium,

alcohol consumption and cigarette smoking; weight

reduction; increased aerobic activity; and stress

reduction.

Atrial fibrillation

Patients with atrial fibrillation (AF) have a fivefold increased risk of stroke, with approximately 80,000 strokes in the United States attributable to AF each year. Both the prevalence of AF, as

well as the risk of stroke among persons with AF,

increases dramatically with age, hence AF treatment

is particularly important to health care systems that

care for older patients. Cost-effectiveness analyses

suggest that stroke prevention among persons with

AF is likely to be not only cost-effective, but costsaving.

Well-managed anticoagulation with warfarin

reduces the risk of stroke by approximately 65-70%

in patients with AF. The corresponding risk reduction of aspirin therapy is approximately 20-35%.

On average, 25% of patients will have absolute

contraindications to warfarin therapy, 25% will have

relative contraindications, and 50% will have no

contraindications. Accordingly, up to 50-75% of all

AF patients should be receiving warfarin, but

several studies have shown that only half of eligible

patients receive it. Some subgroups of patients with

AF are at low risk and may do well with aspirin

alone, but many elders with AF have risk factors

(e.g. left ventricular hypertrophy, hypertension,

diabetes) that place them at higher risk for stroke.

In these patients, well-controlled warfarin anticoagulation is most effective in reducing stroke rates

and averting hospitalization costs.

Carotid artery stenosis

I

n the Cardiovascular Health Study some degree

of carotid stenosis was detectable in 75% of men

and 62% of women over 65, and this percentage

increased with age. However, less than 10% of

people had more than 50% stenosis. This relationship between prevalence and severity suggests that

general screening programs may not be the best

approach.

Several recent randomized trials have helped

define important indications for carotid endarterectomy (CE). When performed by surgeons at

institutions that achieve low complication rates, CE

can reduce stroke risk in symptomatic and asymptomatic patients by at least 50%. Several patient

groups appear to benefit most: those with ipsilateral

carotid artery distribution, transient ischemic attack

(TIA), or minor, non-disabling stroke, and proven

stenosis of 70% or more, but less than 100%. The

benefit of CE in patients with moderate stenosis

(50-69%) is less dramatic, but the identification of

subgroups of patients who may be at particularly

high risk is important. In addition, the overall CE

complication rates are generally higher than experienced by patients enrolled in the efficacy trials of

the 1990s. Therefore, to benefit from CE, patients

must have a high degree of stenosis and receive

surgery at institutions with low complication rates.

Continued on page 4
PRACTICE Matters 3

EXPERT OPINION

epidemiological studies (randomized controlled

Observational epidemiological studies have ledto risk factor profiles for stroke. Experimental

clinical trials) have proven that modification and

treatment of various precursor conditions can

effectively reduce the risk of ischemic stroke.

Much of current attention should focus on

controlling modifiable risk factors for stroke.

These include hypertension, cardiac disease, atrial

fibrillation, diabetes, hyperlipidemia, asymptomatic

carotid stenosis, physical inactivity, cigarette smoking and alcohol abuse. Exciting findings suggest

additional risk factors: new cardiac risk factors

(patent foramen ovale, left atrial enlargement, and

valve strands), elevated homocysteine,

anticardiolipid antibodies, chronic infections or

inflammatory conditions (chlamydia, periodontal

disease), and markers of subclinical disease (white

matter hyperintensities, aortic arch atheroma, and

carotid intimal-medial plaque thickness).

This issue of VA Practice Matters highlights the

latest knowledge on modifiable stroke risk factors.

Evidence through well-controlled, randomized

clinical trials shows that proper treatment of hypertension, atrial fibrillation, carotid artery stenosis,

and hypercholesterolemia can reduce stroke risk.

Multiple studies, however, have documented less

than adequate control of many of these conditions

in the community. As health care providers, it is

our duty to try to reduce the risk of stroke just as

efficiently as has been done in clinical trials. Any

improvement in our awareness and treatment of

these risk factors should lead to a substantial reduction in the number of persons killed or disabled by

stroke each year.

Ralph L. Sacco, MD, MS

Associate Professor of Neurology and Public Health

Associate Chairman of Neurology

Associate Director of the Stroke Division

Neurological Institute

Columbia-Presbyterian Medical Center, NY, NY

RECOMMENDATIONS

symptoms of recurrent stroke.

a

Research evidence indicates key areas of emphasis for physicians in primary stroke prevention

nd treatment are to:

• Identify patients with hypertension and control

BP to levels of 140/90 by a combination of

lifestyle modifications and medication.

• Address full spectrum of lifestyle and risk factor

modifications (e.g. smoking, diet, physical activity).

• Screen patients for atrial fibrillation, assess risk

for bleeding, provide well-monitored anticoagulation for those at acceptable risk (50-75%

of those with AF) and provide aspirin for the

remaining cohort.

• Identify carotid artery stenosis for patients with

symptoms of anterior circulation ischemia (TIA

or minor stroke) and refer for CE if factors

related to surgery are favorable (<3% complication rates in institutions).

• Educate patients to recognize symptoms of

stroke and TIA, and take appropriate steps upon

VA Practice Matters is a publication for VA decision makers and practitioners that summarizes the results of important research to help

inform policy and to promote the application

of research for improved health care delivery

and decision making within VA. It is produced

by HSR&D’s Information Dissemination Program in collaboration with topic experts in the

field. For more information or to provide us

with your suggestions, please contact:

Information Dissemination Program

Management Decision and Research Center (152-M)

150 South Huntington Avenue

Boston, MA 02130

Phone: COM (617) 278-4433

or FTS 839-4433

FAX: (617) 278-4438

Email: geraldine.mcglynn@med.va.gov

VA Practice Matters is also available on the VA R&D

internet at www.va.gov/resdev/prt, and on our Fax on

Demand system by dialling (617) 278-4492 and

following the voice prompts.
4 PRACTICE Matters

Previous research has found a relationship between

high homocysteine levels in the blood with heart

disease and associated stroke events. For example,

patients with vascular disease had significantly higher

levels of homocysteine than normal subjects. Recent

findings suggest that folate supplements can reduce

homocysteine levels, and are associated with lower

rates of heart disease and stroke events. However,

more research is needed to elucidate safe, effective

levels of folate supplementation for homocysteine

reduction, and whether or not it leads to reduced

cardiovascular and cerebrovascular events.

Acknowledgments

This Stroke Prevention issue of VA Practice Matters was prepared by the QUERI Stroke Executive Committee using recent research and reviews, with major contributions from Eugene

Oddone, MD, Director of HSR&D Center for

Health Services Research in Primary Care,

VAMC Durham; Lawrence Goldstein, MD,

Neurology, VAMC Durham; Lawrence M. Brass,

MD, Chief of Neurology Service, VAMC West

Haven; John Booss, MD, Director of Neurology, VAMC West Haven; Linda Alley, PhD, RN,

Associate Director, HSR&D, VAMC Atlanta;

Amy Rosen, PhD, Senior Research Scientist,

VAMC Bedford; Ralph Sacco, MD, MS, Associate Chairman of Neurology, Associate Director

of the Stroke Division, Columbia-Presbyterian

Medical Center, NY; and Lyla Kaplan, MS,

QUERI Stroke Project Coordinator, VAMC

Durham. Other contributors/reviewers were:

John G. Demakis, Director, VA Health Services

Research and Development Service; Robert J.

Sullivan Jr., MD, MPH, Director, National Center for Health Promotion and Disease Prevention, Durham; Valerie Lawrence, MD, MSc, Staff

Physician, Audie L. Murphy Memorial Veterans

Hospital, San Antonio; Margaret Baumann, MD,

Associate Chief of Staff for Geriatrics and Extended Care, Hines VA Hospital, Hines. The

issue was edited by Geraldine McGlynn, M.Ed.

of VA’s Management Decision and Research

Center.

PREVENTION AND TREATMENT GOALS

Continued from page 2

Cholesterol

The National Cholesterol Education Programindicates that blood cholesterol levels below 200

mg/dl are “desirable”, whereas levels above 240 mg/dl

are “high.” More than half of Americans have blood

cholesterol levels over 200 mg/dl and a quarter have

levels over 240 mg/dl. Recent studies have shown that

HMG-CoA reductase inhibitors (statins) lower lipid

levels and are associated with a 30% relative reduction

in risk of stroke in patients with known coronary

artery disease. This benefit is similar to the benefit

statins confer on reducing myocardial infarctions (MI)

in asymptomatic patients. Despite these promising

findings, hypercholesterolemia has not been confirmed as an independent risk factor for stroke in those

older than 70, and further research needs to establish

the effectiveness of statins for the elderly. Furthermore, there are no studies of statins and stroke risk in

patients with elevated serum cholesterol levels but no

known coronary artery disease.

Physicians need to be aware of the patient’s total

cholesterol level, and levels of both low and high

density lipoprotein (LDL and HDL) cholesterol

and triglycerides. Moreover, concomitant risk

factors such as hypertension, age, and family history

of coronary artery disease should be considered.

Lifestyle

Targeting modifiable risk factors can reduce therisk of stroke. Research evidence indicates

decreased risk with cessation of cigarette smoking,

reducing hypercholesterolemia and obesity, and

increasing physical activity. Moderate alcohol

consumption (two drinks per day) appears to confer

a lower risk for first stroke compared to either no or

heavy alcohol intake.
Participants or Observations/

Reference Type of Study Interventions Outcomes

May 1999

Evidence Chart for Primary Stroke Prevention

 Hypertension

Psaty BM. Health outcomes Meta-analysis of 18 Association between High dose beta-blocker therapy prevented

associated with antihypertensive randomized trials. administration of diuretics stroke (relative risk [RR], 0.71) and congestive

therapies. JAMA 1997; 277(9): or beta blockers and heart failure (RR, 0.58). High dose diuretic

739-45. subsequent stroke rate. therapy prevented stroke (RR, 0.49) and

congestive heart failure (RR, 0.17).

 Atrial Fibrillation

Atrial Fibrillation Investigators. The Meta-analysis of 3 Association between Relative stroke risk reduction of 21% in

efficacy of aspirin in patients with randomized trials. 1,985 aspirin and stroke risk patients with AF.

atrial fibrillation. Arch Int Med patient-years assigned to reduction.

1997;157(11):1237-40. the aspirin and 1,867

patient-years assigned to

the placebo group.

Hart RG. Prevention of stroke in Review of 13 randomized Patients with atrial Stroke risk for patients with AF averages

patients with nonvalvular atrial trials of antithrombotic fibrillation (AF) who 5%/y, with wide variation as a function of

fibrillation. Neurology 1998;51:674- therapy. received antithrombitic coexistent thromboembolic risk factors. Low

81. Carotid Artery Steno therapy. risk = about 1%/y, Moderate = about 3%/y,

sis and High = about 6%/y. Prior stroke or

transient ischemic attack are highest risk =

about 12%/y. Well-monitored adjusted-dose

warfarin (INR 2-3) = 70% stroke risk

reduction. Aspirin = 20% stroke risk

reduction.

 Carotid Artery Stenosis

Goldstein LB. Comparison and Meta-analysis of Compared rates of nonfatal Event rates after 30 days for medically treated

meta-analysis of randomized trials of NASCET, ECST and stroke, nonfatal MI, or patients = .20 versus 0.08 for NASCET; 0.12

endarterectomy for symptomatic VACS. death for surgically or versus 0.07 for ECST; and 0.15 versus 0.07

carotid artery stenosis. Neurology medically treated patients for VACS.

1995;45(11): 1965-70. in the perioperative period

(30 days).

Wennberg DE. Variation in carotid “Trial” hospitals in Mortality rates in patients Mortality risk reduction in patients at trial

endarterectomy mortality in the NASCET and ACAS n=86 undergoing CE in trial hospitals compared with high volume nonMedicare population: trial hospitals, patients, and Medicare hospitals and non-trial trial hospitals was 15%, compared with

volume, and patient characteristics. “non-trial” hospitals hospitals. average-volume hospitals was 25%, compared

JAMA 1998;279:1278-1281. n=2613 patients. with low-volume hospitals was 43%.

 Cholesterol

Blauw GJ. Stroke, statins, and Meta-analysis of 13 trials. Stroke rate in middle-aged Treatment with an HMG-CoA reductase

cholesterol. Stroke 1997; 28(5): 946- patients receiving HMG- inhibitor led to an overall risk reduction of

50. CoA reductase inhibitor 31%.

compared to patients

receiving placebo.

Hebert PR. Cholesterol lowering Meta-analysis of 16 trials. 29,000 patients receiving Average reductions in total and low-density

with statin drugs, risk of stroke and statins with averaged 3.3 lipoprotein cholesterol were 22% and 30%,

total mortality. JAMA year follow up. respectively. Reductions in risks of stroke of

1997;278:313-21. 29% and total mortality of 22%.

Crouse JR. HMG-CoA reductase Meta-analysis of primary HMG-CoA reductase 30% stroke reduction and CHD in secondary

inhibitor therapy and stroke risk and secondary prevention inhibitors effect on prevention.

reduction. Atherosclerosis trials. reducing cholestorol levels

1998;138:11-24. and coronary heart disease.

 Lifestyle

Shinton R. Lifelong exposures and 125 men and women who Stroke and concomitant Cigarette smoking was estimated to have

the potential for stroke prevention: had just had their first risk factors. caused 49% of the strokes. Cigarette smoking

the contribution of cigarette stroke and were aged 35- combined with lack of exercise caused 62%

smoking, exercise, and body fat. 74 and 198 controls and smoking combined with obesity caused

Jl of Epidemiol Community Health matched for age and sex. 72%.

1997;51(2):138-43.

Perry IJ. Prospective study of serum 107 men with stroke and Association between serum tHcy concentrations were significantly higher

total homocysteine concentration 118 control men. total homocysteine (tHcy) in cases than controls (p = 0.004). Relative risk

and risk of stroke in middle-aged concentration taken of stroke increased in the second, third and

British men: Lancet between 1978-1980 and fourth quarters of the tHcy distribution

1995;346(8987):1395-8. subsequent first stroke. relative to the first (trend p = 0.005).

PRACTICE Matters
Primary Stroke Prevention

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Information Dissemination Program

Management Decision and Research Center (152-M)

150 South Huntington Avenue, Boston, MA 02130

Phone: COM (617) 278-4433 or FTS 839-4433

FAX: (617) 278-4438 Email: geraldine.mcglynn@med.va.gov

PRACTICE Matters