Editors: Norris, John W.; Hachinski, Vladimir
Title: Stroke Prevention, 1st Edition
Copyright 2001 Oxford University Press
> Table of Contents > I - Primary Prevention > 7 - Prevention and Screening Programs
Prevention and Screening Programs
Philip B. Gorelick
Stroke is well-suited for prevention because it has a high prevalence, burden of illness and economic cost, effective preventive measures.1,2,3 Although stroke is preventable, recent surveys suggest that there is a lack of awareness stroke warning signs and risk factors by the public underutilization or possible misapplication of stroke prevention methods by physicians.5,6 This should not come as a surprise, because implementation rates of clinical prevention services lag far behind the dissemination of prevention service goals.7,8 A major barrier to the delivery of preventive services may be a perceived lack time to implement such measures in the ambulatory office setting.
With rising prosperity one sees increasing interest in future health, healthy living, and a healthy environment.9 Ironically, physicians are trained to care for the sick, but preventive training may not receive appropriate emphasis in medical school and postgraduate training programs. Furthermore, as resources for health care remain limited, politics and money increasingly determine health policy. The humanitarian argument that favors preventive medicine9 may not be the highest priority of health planners, who must juggle limited financial resources.
Screening: Concepts, Diagnostic Technology, and Values
Screening is a public health strategy designed to separate persons with higher from persons with lower probabilities of disease. Those who screen positive
Is the program effective judged on basis of a randomized trial?
If an effectiveness trial has not been carried out, (a) are there efficacious treatments for the primary disorder or prevention measures its sequelae? and (b) does the burden of disease warrant screening?
Is there a good screening test?
Does the program serve those who need it?
Can the health system accommodate the screening program?
Will those screened comply with advice and treatment plans?
To better understand screening in the context of prevention, one must appreciate the stages of chronic disease.12 Chronic disease usually has a long latent period before clinical symptoms are manifested. Risk factors or exposures thought to cause pathophysiologic changes that may eventually lead clinically active disease. In the natural history of chronic disease, the earliest period is susceptibility stage, in which one is susceptible to pathogenetic tissue change when exposed to risk factors. If the risk factor can be prevented from developing, disease may be thwarted or postponed. At this stage prevention possible through health promotion and intervention.
The second period is the presymptomatic stage, when pathogenetic damage has occurred but clinical symptoms have not yet appeared. Early detection, diagnosis, and treatment of modifiable risk factors may be the key to prevention at this stage. In the last two stages, clinical disease and disability or recovery, clinical disease is manifest and intervention aimed at limiting disability prevention of recurrent disease. Some have likened the first two stages to being upstream and the latter two stages to being downstream .1 The upstream/downstream analogy refers, in the former case, to point time before disease becomes overt but may be prevented, and in the latter case to the point of manifest disease and its sequelae. Ideally, one strives to prevent risk factor development, and thus, intervene at the earliest possible stage (i.e., the upstream stage).
Public health dogma advocates screening and early intervention for modifiable risk factors. Risk factor modification is most effective when the prevalent in the population; when there is a strong association between the favorable effects of treating the risk factor and the target disease; when there are valid, safe, and cost-effective screening procedures treatments. Thus, screening plays an important role in the public health model of disease prevention.
Effective screening depends on diagnostic technology. The purpose of diagnostic technology is to heighten the quality of health care.13,14 Many technologies, however, have entered the market without adequate assessment of their
Technical capability Does the diagnostic test meet accepted standards of showing what it is expected to?
Diagnostic accuracy What is the true positive rate (sensitivity), or ability of the test to detect disease correctly when present? What is the true negative rate (specificity), or the test's ability to exclude disease when not present? Accuracy reflects both sensitivity and specificity (true positive plus true negative results divided by the total number of tests administered). A gold-standard is used to determine the true state of the screened.
Diagnostic and therapeutic impact Does the technology change diagnosis, add significant information, or change patient management?
Key factors to be considered when evaluating a medical diagnostic test are listed in Table 7.1.15
The complexity of a diagnostic screening instrument may vary considerably. For example, consider the differences in complexity of the following screening techniques: manual pulse rate estimation, blood pressure cuff, biochemical assay, and magnetic resonance spectroscopy system. Furthermore, in the current medical environment of cost-containment, flawed or unnecessary screening tests can lead to inappropriate referral for treatment, false reassurance, or even disability. To assist in the evaluation of a screening instrument, a technology assessment is employed to identify reliable, useful, and positive impact tests.13
To better understand the usefulness of a screening test, some basic terms and measures (e.g., validity, sensitivity, specificity) are listed and defined in Table 7.2.13,15,16 Sox et al. and Rocca17 provide an in-depth review of these other concepts that relate to the interpretation and assessment of screening tests.
TABLE 7.1. Factors to be Considered When Evaluating a Medical Diagnostic Test15
TABLE 7.2. Commonly Used Definitions and Measures for Screening Tests13,15,16
Studies of diagnostic (screening) tests are evaluated according to evidencebased rules. One such system that has been used by the American Academy of Neurology18 rates quality of evidence by class designation and strength the recommendation (Table 7.3). Such rating systems are important because they emphasize the rigor by which a test was assessed in the context of a recommendation for use based on safety and efficacy.
TABLE 7.3. Quality of Evidence and Strength Recommendation Ratings for Diagnostic Tests18
Approaches to Prevention
Two basic public health strategies have been advocated for prevention of chronic disease, the mass approach and the high-risk approach.9,19 The is advanced through health education, legislation, and economic measures that discourage exposure to risk factors or the development of factors. Lifestyle modification is used to achieve modest reductions in the levels of a risk factor community. It is believed that prevention of disease among the many persons in the community with mild or moderate levels of risk will yield large absolute benefit from a public health standpoint.
The high-risk approach is typically used by practicing physicians to identify individuals with high levels of a risk factor. Medication is usually prescribed to achieve substantial reductions in the risk factor. The high-risk approach can result in a substantial and expensive case-finding procedure if applied on a large scale and may fail to prevent a high percentage of disease among those in the community with lower levels of a risk factor.
The relation of hypertension and stroke may serve as an example the latter paradox. Although there may be a large relative benefit for stroke prevention by identification and treatment of persons with severe hypertension, the bulk strokes occur in those with less severe hypertension,20 who may not be identified and treated by the high-risk approach. One must also keep in mind, however, that measures that may bring large absolute benefit to the general community through modest reductions in risk factor levels for all may offer little the way of advantage for some individuals in the community (i.e., those with highest levels of the risk factor and highest risk of disease).9 The high-risk mass prevention approaches should be considered complementary strategies.1,2,3
Screening for Stroke Risk: Evidence-Based Examples
This section explores several evidence-based examples of screening for stroke risk. These examples have been chosen because they include risk-benefit or costeffectiveness.21
Asymptomatic Carotid Stenosis
Several recent clinical trials suggest that carotid endarterectomy is efficacious to reduce risk of cerebral ischemia in patients with asymptomatic carotid stenosis.22,23 Asymptomatic carotid stenosis is common, and community physicians may be uncertain if it is appropriate to obtain diagnostic studies, such as noninvasive carotid blood flow, or offer treatment, such as carotid endarterectomy, to patients with carotid bruit.24,25,26
One must first decide if noninvasive carotid artery tests are an adequate predictor of stenosis. Blakeley et al.27 carried out a meta-analytic review noninvasive carotid tests when carotid angiography was the reference standard. Sensitivity, specificity, receiver operator curves (ROC), and summary measures of effectiveness for each test were determined. Carotid duplex ultrasound, carotid doppler ultrasound, and magnetic resonance angiography had sensitivities between 0.82 and 0.86, with specificities of 0.98 test effectiveness measures at or exceeding 3.0 for predicting 100% occlusion. For carotid stenosis 70%, there were sensitivities at 0.83 to 0.86, specificities 0.89 0.94, test effectiveness approaching 3.0, and composite ROC at 0.91 to 0.92. These latter analyses included supraorbital doppler ultrasonography. The authors concluded that the noninvasive procedures were similarly successful at predicting carotid occlusion and 70% stenosis. Feinberg has cautioned however, about the tendency for noninvasive tests to overestimate carotid stenosis and their inability discriminate total occlusion from very high-grade stenosis in some cases.28
Models have been developed to assess the cost-effectiveness and efficacy of noninvasive screening for patients with asymptomatic carotid stenosis, or neck bruits. These models are based on various assumptions that may or may not be valid in a particular practice setting or for an individual case. Lee et al.29 based their model on the screening of 65-year-old men and simulated the Asymptomatic Carotid Atherosclerosis Study (ACAS) experience.23 Markov modeling was used to estimate annual transitions by different health states. The authors concluded that if 60% carotid stenosis was detected by ultrasonography and confirmed by cerebral angiography, carotid endarterectomy offered a modest absolute reduction in the rate of stroke, but at a cost greater than is usually considered acceptable. Obuchowski et al.30 developed a model based on literature estimates of the prevalence and incidence of carotid artery stenosis associated morbidity and mortality and used a Markov cohort simulation to estimate mean qualityadjusted life years and monetary costs. They concluded that asymptomatic patients
The Canadian Stroke Consortium does not recommend screening asymptomatic patients for carotid endarterectomy or, in general, performing carotid endarterectomy for asymptomatic carotid stenosis.31 This recommendation is based on the belief that widespread screening would detect relatively few patients who were suitable for surgery, and a large number of noninvasive potentially dangerous invasive diagnostic procedures would be necessary and the modest benefit of carotid endarterectomy could be nullified by limited generalizeability the procedure based on ACAS.23 Furthermore, serial carotid ultrasound studies may be of limited usefulness in predicting cerebrovascular events and death persons with asymptomatic carotid stenosis.32 From the standpoint of populationbased medicine, screening for asymptomatic carotid stenosis does not appear to be useful.33 For some high-risk individuals in the population with asymptomatic carotid stenosis, however, carotid endarterectomy may be indicated34 and may be diagnosed by high-quality, noninvasive studies only, as some have advocated.35
Major Cardiovascular Risk Factors
Prevention guidelines and consensus statements for stroke invariably target cardiovascular risk factors and promotion of a healthy lifestyle.36,37 Substantial clinical trial or observational epidemiologic evidence suggests that treatment of hypertension, hypercholesterolemia in coronary heart disease patients, atrial fibrillation with antithrombotic agents, and cessation of cigarette smoking or heavy alcohol consumption will reduce the risk of a first stroke.1,2,3 Furthermore, cardiovascular risk factor screening instruments, such as the one developed by Framingham Study investigators,38,39 that assess stroke risk based on age, blood pressure, antihypertensive therapy use, medical history of diabetes mellitus, cigarette smoking, cardiovascular disease, atrial fibrillation, and left ventricular hypertrophy are available and have been applied in populations at risk for stroke.40 Although treatment or modification of the aforementioned cardiovascular risk factors may reduce the risk of stroke, there is generally a paucity of information concerning the cost-effectiveness of mass screening for stroke prevention. As noted above, mass screening may be expensive and may fail to prevent a high percentage of strokes.9,19 The mass approach to prevention, however, may have special merit as attempts are made to shift a community's risk factor profile or likelihood of developing a risk factor(s) downward,1 yet formal mass screening may not be needed.
Atrial Fibrillation and Echocardiography
Two other evidenced-based examples of the application screening technology in stroke merit mention. The first relates to screening and treatment for atrial fibrilation.
A second example relates to the application and cost-effectiveness of echocardiography after stroke. McNamara et al.44 developed a Markov model decision analysis for hypothetical patients with first stroke in normal sinus rhythm a simulated practice in the United States. The authors concluded that transesophageal echocardiography alone was a cost-effective option for cardiac imaging after stroke. Assumptions necessary for the model include no obvious clinical cause of stroke, lack antithrombotic medication use at the time the stroke, ischemic stroke subtype independent of the underlying condition, transesophageal echocardiography did not cause discomfort or diminish quality of life, risk of recurrent stroke was independent history cardiac disease, the first major complication after stroke was considered in the analysis, and new onset or recurrent strokes had similar relative effects on quality of life and on risk of death.
Screening and Cost-Effectiveness
The examples cited above suggest that screening for stroke risk may not be costeffective when taking into account diagnostic technology and treatment options. In some cases, however, screening may prove to be cost-effective for those at high risk, as has been demonstrated for prevention of coronary heart disease in the primary care setting.45
This may not translate to cost-effectiveness in the community at large, where case-finding may be an expensive proposition. No doubt, the aggregate cost of stroke in the United States is expensive more than $30 billion, with an average cost of approximately $50,000 per case.46 When societal concerns are weighed, which include resource constraint, mass screening for stroke has not been proven to be cost-effective as of yet and is difficult to sell those with financial incentives in the real world. In United States, the bulk of screening activities for stroke risk occur in the physician's office or local health clinic, with emphasis on identification of persons at high risk for cardiovascular disease.
It has been lamented that preventive action lags behind the state of public health science, and that under-investment in prevention remains a major drawback to
Gains in life expectancy from preventive interventions those at average risk have been reported to range from < 1 month slightly more that 1 year per person, with gains as high 5 years or more for those at especially high risk of chronic disease.52 The mean gain in life expectancy may be small for most members of the population (especially if disease is rare) but is much larger for those at higher risk. Such gains, however, may be followed by sobering realizations when one considers that the largest gains may occur shortly after administration of the intervention or when cost is taken into account.53
Those with favorable cardiovascular risk profiles may have lower average annual Medicare charges in older age.54 While this is good news, the costeffectiveness of preventions for those in middle-life may yield 100-fold differences in life years depending on the target at-risk group.55 Such results beg for the identification of more cost-effective interventions or new risk factors that can be modified in a more cost-effective manner.
Community-based cardiovascular disease prevention programs have focused on reduced risk factors, maintenance of reduction risk and surveillance of cardiovascular morbidity and mortality. Key endpoints have included coronary heart disease (CHD) and stroke. In community studies, modest program effects have been blamed primarily on contamination of the control communities with the educational message aimed at the intervention communities.56 In addition, insufficient sample size or inconsistent and insensitive outcome measures could contribute to insignificant effects.57 Changes in secular trends national cardiovascular health awareness, knowledge, and behavior may be largely attributed to national mass media campaigns.58
Stanford Five-City Project
This program, an outgrowth of a three-community study, is community-based intervention trial designed to test whether a comprehensive program of community organization and health education resulted in favorable changes cardiovascular risk factors, morbidity, and mortality in two treatment versus three
After 30 to 64 months of education, significant net reductions in community averages that favored treatment occurred for plasma cholesterol level (2%), blood pressure (4%), resting pulse rate (3%), and smoking rate (13%).60 Composite reductions occurred in total mortality risk scores (15%) and CHD risk (16%). Analysis of control cities over time showed improvements in respondents general cardiovascular disease risk factor knowledge and behaviors which was marked for cholesterol.61
When long-term effects were assessed, (1) blood pressure improvements were maintained in treatment but not control cities; (2) cholesterol levels continued to decline in treatment and control cities; (3) smoking rates leveled off or increased slightly in treatment cities but declined control cities (net differences not significant); and (4) CHD and all-caused mortality risk scores were maintained or continued to improve with treatment, whereas they leveled off or rebounded in control cities. Overall, sustained, but only modest program effects were noted.59
Minnesota Heart Health Program (MHHP)
The MHHP, a research and demonstration project, was conducted from 1980 to 1990 for the primary prevention of CHD and stroke.62,63,64 The intervention program included three communities in Minnesota and North Dakota. Of the three pairs of communities that were studied, each had one education and comparison site. Communities were matched on size, type, and distance from Minneapolis-St. Paul. A 5 6 year intervention program was initiated in November 1981 in Mankato (small rural area), and 22 and 28 months later FargoMoorhead (urban area) and Bloomington (large suburban area), respectively. Risk factors and health behaviors were measured over time. Morbidity mortality endpoints were also collected and analyzed.
The intervention program emphasized hypertension prevention and control, healthy eating habits to lower cholesterol and blood pressure, cessation of smoking, and regular physical activity. The intervention was carried out at the individual, group, and community levels. Social learning theory, persuasive
Overall, in the 30- to 74-year-old men and women enrollees, there were only modest program effects that were generally within chance levels, given a background of secular trends for health promotion and declining risk factors.64 In the education communities, there were 2394 cases of CHD and 818 stroke, versus 2526 and 739 cases, respectively, in the comparison communities.63 The CHD event rate decreased by 1.8% per year in men (p = .03) and by 3.6% year in women (p = .007). There were no significant trends for stroke. In addition, there were minimal effects of sustained intervention on risk factor levels, and no significant intervention effect on CHD or stroke morbidity or mortality.
Pawtucket Heart Health Program (PHHP)
Similar to the Stanford Five-City Project and the MHHP, the PHHP was designed to test the hypothesis that population risk factor intensity or prevalence and projected cardiovascular disease risk would decrease more in Pawtucket, the intervention city, than in a comparison city.65 The theoretical base of the education program featured social learning theory. The program targeted risk factors, behavior change, and community activation.
There were small, insignificant differences in blood cholesterol and pressure that favored Pawtucket. A downward trend in smoking was slightly greater in the control city. In cross-sectional surveys, but not in the cohort surveys, body mass index increased significantly in the control city. Projected cardiovascular disease rates were 16% less in Pawtucket during the intervention program, but this declined to 8% post-education. Overall, cardiovascular risk reduction was feasible, but maintenance of statistically significant differences between the intervention and control cities was not.
North Karelia Project (NKP)
The NKP was launched in 1972 Finland response to high CHD rates and levels of cardiovascular disease risk factors. Given the status secular trends for cardiovascular disease by decade, the NKP was carried out in a community with very high cardiovascular disease rates in comparison to, for example, the MHHP, where rates stayed within the medium range.63 The aim of NKP66,67,68,69,70 was to carry out a systematic and comprehensive intervention to reduce mortality morbidity rates of CHD and related cardiovascular diseases in the entire population, and particularly middle-aged men. Reduction of risk factors, such as smoking, high serum cholesterol, and hypertension, were the main targets. There was a comprehensive educational and service-oriented program to modify risk factors based on local community action and service structure. Practical skills,
The study showed that a community-wide intervention was feasible and could lead to risk factor changes.70 Cardiovascular mortality decreased more in North Karelia than in the rest of Finland.69 Based on potential sources bias and theoretical issues regarding causal inference, it may be difficult to conclude what excess proportion of the mortality decline was attributable to program.70
Hypertension Control Program in Rural Northeastern Japan
Hypertension is the most important modifiable risk factor for stroke.1,2,3 In Japan, stroke rates have been traditionally high, and hypertension has been a prevalent risk factor. In the early 1960s a community-based hypertension control program was begun in two rural communities northeastern Japan.71 In one of the communities, the municipal government began to charge participants for blood pressure screenings after 1968 and failed to replace the public health nurse she retired in 1973. In the other community, the program had continuous support. the full intervention, community residents 30 years of age were offered blood pressure screenings. High risk individuals were referred to local clinics for antihypertensive medication and were rescreened annually. The remainder of the community was rescreened at four-year intervals. Treatment of hypertension carried out by local physicians, who used thiazide diuretics and, secondarily, betaadrenergic blocking agents. Calcium channel blockers and angiotensin-converting enzyme inhibitors were used infrequently before the mid-1980s. Health education for hypertensives was carried out at screening sites and also included adult classes, nurse home visits, volunteers for health education ( healthy diet volunteers), and community-wide media to encourage participation in blood pressure screening and reduced salt intake.72 Because the traditional Japanese diet was high in salt (20g/day), education on how to reduce intake was a major focus of the program.
In the minimal intervention community, blood pressure rescreening occurred at two-year intervals. Program components were similar to the full educational intervention but did not include adult classes or community-wide media education. About 75% of the referred hypertensives attended a clinic outside the community.
Six-year stroke incidence rates, adjusted for sex and age, did not differ between the two groups in the period 1964 to 1969. Subsequently, stroke incidence declined in men, more so in the full intervention than the minimal intervention group (42% decrease vs. 5% increase for 1970 to 1975; 53% vs. 19% decrease for 1976 to 1981; and 75% vs. 29% decrease for 1982 1987). For women,
For men and women aged 40 to 69 years, age-adjusted blood pressures, prevalence of hypertension, and hypertensive end-organ defects were nearly identical in the study communities. For men, the full intervention group showed a 3 4 mm Hg lower mean systolic blood pressure in the early 1970s and 1980s. This was not maintained in the mid-1980s. For women, a difference systolic blood pressure was found only in the early 1980s. Unexpectedly, among those with hypertension, the proportion previously undetected was greater and the treated and controlled was lower in the full intervention group. For the most part, there were no major differences in the prevalence of diabetes mellitus or atrial fibrillation in either community.
The investigators concluded that active use of existing health resources, high participation in blood pressure screenings and follow-up exams, communitywide health education for hypertension control augmented the decline in stroke incidence and prevalence among men. Control of hypertension in the community has been shown to yield benefits for cardiovascular disease prevention in other studies,73,74 but in one study it had little impact on stroke risk.75 Many hypertensive persons in the community, however, have blood pressures that are not well-controlled, and there is a trend for falling awareness, treatment, control of hypertension in the United States.76,77
Community Intervention Trial for Smoking Cessation (COMMIT)
Cigarette smoking is a well-documented risk factor for stroke.1,2,3 Furthermore, the risk of stroke reverses substantially within two to five years after smoking cessation. COMMIT was a community-level, multichannel, four-year intervention designed to increase quit rates.78,79 The trial included two matched pairs of community, one randomly assigned to intervention and the other as a control. The intervention focused on public education through media and communitywide events, work-sites and other organizations, health care providers organizations, and cessation resources. Mandated activities were carried out primarily by community volunteers, local staff, or agencies and were implemented by community task forces. The target smoking group was between 25 and 64 years old and included heavy smokers (>25 cigarettes per day) and light to moderate smokers.
There was a modest impact of the intervention on light to moderate smokers, but the quit rate of heavy smokers did not increase.78 Smoking prevalence was not affected significantly beyond existent favorable secular trends.79 It has been
Work-site health promotion has been advocated as part of community intervention programs because a large percentage of the community may be employed, more than a third of one's waking hours are spent at work, and the potential public health benefits of work-site health promotion may be substantial.81 Work-site interventions may address multiple risk factors or single risk factors. Work-site interventions may be aimed at organizational and environmental change or individual change (e.g., screening, educational, behavioral counseling, and incentives). Behavioral counseling may be an effective strategy for reduction of some cardiovascular disease risk factors.81,82
Community Prevention Programs in Perspective
Secular trends for improvements in cardiovascular risk factor profiles have been substantial and are believed largely to account for the generally insignificant differences between intervention and comparison communities. These secular trends became prominent from the 1960s through 1980s. With recent realization that stroke rates may be on the rise83 and that high stroke rates exist in some areas of the world where cardiovascular risk factor frequency is high and presumably adequate treatment is lacking,84 there concern that stroke rates may be moving backward in the direction of past decades, when stroke rates were high.85 This has led to a battle cry to redouble efforts to control cardiovascular risk factors in the community and to identify new risk factors treatments. Thus, there is a need to continue advocate for public health policy mass and high-risk approaches to community prevention.
Future Targets of Screening and Prevention
Since atherosclerosis seems to begin in childhood and cardiovascular risk factors or their precursors may manifest in this time period, interest has been increasing in cardiovascular screening and prevention of children, adolescents, young adults.86,87,88,89,90,91,92,93,94,95,96,97 Risk factor variables such as ponderal index; systolic blood pressure and total cholesterol;96 triglycerides, insulin, and blood pressure92 may cluster in children or young adults and predict susceptibility to cardiovascular disease later in life. Evidence from tracking studies suggests, for example, that young adult men in the top quintile of blood pressure distribution are likely to remain top quintile.97 Thus, a number of risk factors or precursors may manifest early in life that could be modified by lifestyle changes (e.g., weight loss, exercise, diet). These windows of opportunity need to be investigated determine if stroke and other cardiovascular diseases can be prevented or postponed by early-life modification of these factors.3 Low-cost, high-yield population
Beyond biological aging, much illness and disability in the elderly is related to risk factors that are present in midlife.99 If the foundation for subclinical disease is being established in childhood and young adulthood, our public health policy for screening and prevention should begin to explore health promotion leading causes of chronic illness the elderly during this early time period.
1. Gorelick PB. Stroke prevention. An opportunity for efficient utilization of health care resources during the coming decade. Stroke 1994;25:220 224.
2. Gorelick PB. Stroke prevention. Arch Neurol 1995;52:347 355.
3. Gorelick PB. Stroke prevention: Windows of opportunity and failed expectations? A discussion of modifiable cardiovascular risk factors and a prevention proposal. Neuroepidemiology 1997; 16:163 173.
4. Pancioli AM, Broderick J, Kothari R, Brott T, Tuchfarber A, Miller Khoury Jauch E. Public perception of stroke warning signs and knowledge potential risk factors. JAMA 1998;279:1288 1292.
5. Brass LM, Krumholz HM, Scinto JM, Radford M. Warfarin use among patients with atrial fibrillation. Stroke 1997;28:2328 2389.
6. Goldstein LB, Bonito AJ, Matchar DB, Duncan PW, Samsa GP. National survey of physician practices for secondary and tertiary prevention of ischemic stroke: Medical therapy in patients with carotid artery stenosis. Stroke 1996;27:1473 1478.
7. Kottke TE, Brekke ML, Solberg LI. Making time for preventive services. Mayo ClinProc 1993;68:785 791.
8. Kottke TE, Solberg LI, Brekke ML, Cabrera A, Marquez MA. Delivery rates for preventive services in 44 Midwestern clinics. Mayo Clin Proc 1997;72:515 523.
9. Rose G. The Strategy of Preventive Medicine. New York: Oxford University Press, 1994:1 138.
10. Retcher SW. Evidence-based screening: What kind of evidence is needed? ACP J Club May/June 1998:A12-A14.
11. Sackett DL, Haynes RB, Tugwell P. Clinical Epidemiology. A Basic Science for Clinical Medicine. Boston: Little Brown, 1985:139, 302 310.
12. Mausner JS, Kramer S. Mausner and Bahn Epidemiology An Introductory Text. Philadelphia: WB Saunders, 1985; 1 42.
13. Sox H, Stern S, Owens D, Abrams HL. Assessment of Diagnostic Technology in Health Care. Rationale, Methods, Problems and Directions. Washington, DC: Institute of Medicine, National Academy Press, 1989:8 54.
14. Silverman WA. Doing more good than harm. In: Warren KS, Mosteller F, (eds). Doing More Good than Harm: The Evaluation of Health Care Interventions. New York: Annals of the New York Academy Sciences, vol 703, 1993:5 11.
15. Nuwer M. On the process for evaluating proposed new diagnostic EEG tests. Brain Topogr 1992;4(4):243 247.
16. Ahlbom A, Norell S. Introduction to Modern Epidemiology. Chestnut Hills, MA: Epidemiology Resources, 1990:24 27, 57 60.
17. Rocca WA. Clinical trials in neurology: Reliability and validity of rating scales. In: Gorelick PB, Alter MA, eds. Handbook of Neuroepidemiology. New York: Marcell Dekker, 1994:63 74.
18. American Academy of Neurology, Therapeutics and Technology Assessment Subcommittee. Assessment Workbook. 1997.
19. Dunbabin DW, Sandercock PAG. Preventing stroke by modification of risk factors. Stroke 1990;21(suppl IV):IV-36-IV-39.
20. Joseph LN, Kase CS, Beiser AS, Wolf PA. Mild blood pressure elevation and stroke: The Framingham Study. 23rd International Conference on Stroke and Cerebral Circulation, Orlando, Florida, February 5 7, 1998 (abstract).
21. Ringel SP, Hughes HL. Evidence-based medicine, critical pathways, practice guidelines, and managed care: Reflections on the prevention care of stroke. Arch Neurol 1996;53:867 871.
22. Hobson RW, Weiss DG, Fields WS, Goldstone J, Moore Towne JB, Wright CB, Veterans Affairs Cooperative Study Group. Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. N Engl J Med 1993;328:221 227.
23. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA 1995;273:1421 1428.
24. Feussner JR, Matchar D. When and how to study the carotid arteries. Ann Intern Med 1988;109:805 818.
25. Health and Public Policy Committee, American College of Physicians. Diagnostic evaluation of the carotid arteries. Ann Intern Med 1988;109:835 837.
26. Sauve J-S, Laupacis A, Ostbye T, Feagan B, Sackett DL. Does the patient have a clinically important carotid bruit? JAMA 1993; 270: 2843 2845.
27. Blakeley DD, Oddone EZ, Hasselbad V, Simel DL, Matcher DB. Noninvasive carotid artery testing: A meta-analytic review. Ann Intern Med 1995; 122:360 367.
28. Feinberg AW. Commentary. ACP J Club July/August 1995:17.
29. Lee TT, Solomon NA, Heidenreich PA, Oehlert J, Garber AM. Cost-effectiveness of screening for carotid stenosis in asymptomatic patients. Ann Intern Med 1997; 126: 337 346.
30. Obuchowski NA, Modic MT, Magdenic M, Masaryk TJ. Assessment of the efficacy of noninvasive screening for patients with asymptomatic neck bruits. Stroke 1997;28: 1330 1339.
31. Perry JR, Szalai JP, Norris JW, for the Canadian Stroke Consortium. Consensus against both endarterectomy and routine screening for asymptomatic carotid artery stenosis. Arch Neural 1997;54:25 28.
32. Lewis RF, Abrahamowicz M, Cote R, Battista RN. Predictive power of duplex ultrasound in asymptomatic carotid disease. Ann Intern Med 1997; 127:13 20.
33. Lanska DJ, Kryscio RJ. Endarterectomy for asymptomatic internal carotid artery stenosis. Neurology 1997;48:1481 1490.
34. Sarasin FP, Bounameaux H, Bogousslavsky J. Asymptomatic severe carotid stenosis: Immediate surgery or watchful waiting? A decision analysis. Neurology 1995;45: 2147 2153.
35. Strandess DE. Angiography before carotid endarterectomy-no. Arch Neurol 1995; 52:832 833.
36. Organizing Committees (Program, Advisory and Local): Asia Pacific Consensus Forum on Stroke Management. Stroke 1998;29:1730 1736.
37. National Stroke Association Prevention Advisory Board. National Stroke Association stroke prevention guidelines. Journal of Stroke and Cerebrovascular Diseases 1998;7: 162 164.
38. Wolf PA, D'Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: A risk profile from the Framingham Study. Stroke 1991;22:312 318.
39. D'Agostino RB, Wolf PA, Belanger AJ, Kannel WB. Stroke risk profile: Adjustment for antihypertensive medication. The Framingham Study. Stroke 1994;25:40 43.
40. Sitzer M, Skutta Siebler Sitzer G, Siegrist J, Steinmetz H. Modifiable stroke risk factors in volunteers willing to participate a prevention program. Neuroepidemiology 1998; 17:179 187.
41. National Stroke Association. Check Your Pulse Americal 1998.
42. Gustafsson C, Asplund K, Britten M, Norrving B, Olsson Marke L-A. Costeffectiveness of primary stroke prevention in atrial fibrillation: Swedish national perspective. BMJ 1992;305:1457 1460.
43. Gage BF, Cardinalli AB, Albers GW, Owens DK. Cost-effectiveness of warfarin and aspirin for prophylaxis of stroke in patients with nonvalvular atrial fibrillation. JAMA 1995;274:1839 1845.
44. McNamara RL, Lima JAC, Whelton PK, Powe NR. Echocardiographic identification of cardiovascular sources of emboli to guide clinical management stroke: A costeffectiveness analysis. Ann Intern Med 1997;127:775 787.
45. Field K, Thorogood M, Silagy C, Normand O'Neill C, Muir J. Strategies for reducing coronary risk factors in primary care: Which is most cost effective? BMJ 1995;310:1109 1112.
46. Matchar DB. The value of stroke prevention and treatment. Neurology 1998;51(Suppl 3):S31-S35.
47. Atwood K, Colditz GA, Kawachi I. From public health science to prevention policy: Placing science in its social and political contexts. Am J Public Health 1997;87:1603 1606.
48. Gordon RL, Gerzoff RB, Richards TB. Determinants of US local health department expenditures, 1992 through 1993. Am J Public Health 1997;87:91 95.
49. Richmond JB, Kotelchuck M. Co-ordinating and development of strategies policy for public health promotion in the United States. In: Holland WW, Detels L, Knox G, eds. Oxford Textbook of Public Health. Oxford: Oxford Medical Publications, 1991.
50. Brownson RC, Newschaffer CJ, Ali-Abarghoui F. Policy research for disease prevention: Challenges and practical recommendations. Am J Public Health 1997;87: 735 739.
51. Russell LB. The knowledge base for public health strategies (annotation). Am J Public Health 1997;87:1597 1588.
52. Wright JC, Weinstein MC. Gains in life expectancy from medical interventions standardizing data on outcome. TV Engl J Med 1998;339:380 386.
53. Detsky AS, Redelmeier DA. Measuring health outcomes putting gains into perspective. W Engl J Med 1998;339:402 404.
54. Daviglus ML, Greenland P, Dyer AR, Garside DB, Manheim L, Lowe LP, Rodin MB, Lubitz J, Stamler J. Benefit of a favorable cardiovascular risk-factor profile in middle age with respect to medicare costs. N Engl J Med 1998;339:1122 1129.
55. Russell LB. Prevention and Medicare costs. N Engl J Med 1998;339:1158 1160.
56. Feinlieb M. New directions for community intervention studies (editorial). Am J Public Health 1996;86:1696 1698.
57. Fishbein M. Great expectations, or do we ask too much from community-level interventions (editorial)? Am J Public Health 1996;86:1075 1076.
58. Niknian M, Lefebvre C, Carleton RA. Are people more health conscious? A longitudinal study of one community. Am J Public Health 1991;81:203 205.
59. Winkleby MA, Taylor LB, Jatulis D, Fortmann SP. The long-term effects of a cardiovascular disease prevention trial: The Stanford Five City Project. Am J Public Health 1996;86:1773 1779.
60. Farquhar JW, Fortmann SP, Flora JA, Taylor CB, Haskell WL, Williams PT, Maccoby N, Wood PD. Effects of community wide education on cardiovascular disease risk factors: The Stanford Five City Project. JAMA 1990;264:359 365.
61. Frank E, Winkleby M, Fortmann SP, Farquhar JW. Cardiovascular disease risk factors: Improvements in knowledge and behavior the 1980s. Am J Public Health 1993;83:590 593.
62. Murray DM. Design and analysis of community trials: Lessons from the Minnesota Heart Health Program. Am J Epidemiol 1995;142:569 575.
63. Luepker RV, Rastam L, Hannam PJ, Murray DM, Gray C, Baker WL, Crow R, Jacobs AR, Pirie PL, Mascioli SR, Mittlemark MB, Blackburn H. Community education for cardiovascular disease prevention: Morbidity and Mortality results from the Minnesota Heart Health Program. Am J Epidemiol 1996; 144:351 362.
64. Luepker RV, Murray DM, Jacobs DR, Mittelmark MB, Bracht N, Carlaw R, et al. Community education for cardiovascular disease prevention: Risk factor changes in the Minnesota Heart Health Program. Am J Public Health 1994;84:1383 1393.
65. Carleton RA, Lasator TM, Assaf AR, Feldman HA, McKinlay S, and the Pawtucket Heart Health Program Writing Group. The Pawtucket Heart Health Program: Community changes in cardiovascular risk factors and projected disease risk. Am J Public Health 1995;85:772 785.
66. Salonen JT, Puska P. Kotte TE, Tuomilheto J. Changes in smoking, serum cholesterol and blood pressure levels during a community-based cardiovascular disease prevention program: The North Karelia Project. Am J Epidemiol 1981; 14:81 94.
67. Paska P, Toumilehto J, Nissinen A, Salonen JT, Vartiainen E, Pietinen Koskela K, Korhonen HJ. The North Karelia Project: 15 years of community-based prevention of coronary heart disease. Ann Med 1989;21:169 173.
68. Salonen JT, Puska P, Mustaniemi H. Change in morbidity and mortality during comprehensive community program to control cardiovascular diseases during 1972 7 in North Karelia. BMJ 1979;2:1178 1183.
69. Tuomilehto J, Geboeas Salonen JT, Nissinen A, Kuulasmaa K, Puska P. Decline in cardiovascular mortality in North Karelia and other parts of Finland. BMJ 1986;293: 1068 1071.
70. Salonen JT. Did the North Karelia project reduce coronary mortality (letter). Lancet 1987;2:269.
71. Shimamoto T, Komachi Y, Inada H, Doi M, Iso Sato S, et al. Trends for coronary heart disease and stroke and their risk factors in Japan. Circulation 1989;79:503 515.
72. Iso H, Shimamoto T, Naito Y, Sato S, Kitamura A, lida M, et al. Effects of a longterm hypertension control program on stroke incidence and prevalence in a rural community in Northeastern Japan. Stroke 1998;29:1510 1518.
73. Krishan I, Davis CS, Nobrega FT, Smoldt RK. The Mayo Three-Community Hypertension Control Program, IV: Five-year outcomes of intervention in entire communities. Mayo Clin Proc 1981;56:3 10.
74. Kotchen JM, McKean HE, Jackson-Thayer S, Moore RW, Straus R, Kotchen TA. Impact of a rural high blood pressure control program on hypertension control and cardiovascular disease mortality. JAMA 1986;255:2177 2182.
75. Whisnant JP. Effectiveness versus efficacy of treatment hypertension for stroke prevention. Neurology 1996:46:301 307.
76. Berlowitz DR, Ash AS, Mickey EC, Friedman RH, Clickman M, Kader B, Moskowitz MA. Inadequate management of blood pressure in a hypertensive population. N Engl JMed 1998;339:1957 1963.
77. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and treatment of High Blood Pressure. NIH Publication No. 98 4080, November 1997:3.
78. The COMMIT Research Group: Community Intervention Trial for Smoking Cessation: I. Cohort results from a four-year community intervention. Am J Public Health 1995;85:183 192.
79. The COMMIT Research Group: Community Intervention Trial for Smoking Cessation (COMMIT): II. Changes in Adult cigarette smoking prevalence. Am J Public Health 1995;85:193 200.
80. Cromwell J, Bartosch WJ, Fiore MC, Hasselblad Baker T. Cost-effectiveness of the clinical practice recommendations in the AHCPR guideline for smoking cessation. JAMA 1997;278:1759 1766.
81. Gomel M, Oldenburg B, Simpson JM, Owen N. Work-site cardiovascular risk reduction: A randomized trial of health risk assessment, education, counseling, and incen-tives. Am J Public Health 1993;83:1231 1238.
82. Gomel MK, Oldenburg B, Simpson JM, Chilvers M, Owen N. Composite cardiovascular risk outcomes of a work-site trial. Am J Public Health 1997;87:673 676.
83. Brown RD, Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO. Stroke incidence, prevalence and survival: Secular trends in Rochester, Minnesota, through 1989. Stroke 1996;27:373 380.
84. Feigin VL, Wiebers DO, Nikitin YP, O'Fallon WM, Whisnant JP. Stroke epidemiology in Novosibirsk, Russia: A population-based study. Mayo Clin Proc 1995;70:847 852.
85. Gillum RF. Secular trends in stroke mortality African Americans: The role of urbanization, diabetes and obesity. Neuroepidemiology 1997;16:180 184.
86. Hurbert HB, Faker ED, Garrison RJ. Life styles correlates of risk factor change in young adults: An eight-year study of coronary heart disease risk factors in the Framingham offspring. Am J Epidemiol 1987;125:812 831.
87. Hovell MF, Slymen DJ, Jones JA, Hofstetter CR, Burkham-Kreitner S, Conway TL, Rubin B, Noel D. An adolescent tobacco-use prevention trial in orthodontic offices. Am J Public Health 1996;86:1760 1766.
88. Blum RW, Beuhring T, Wunderlich M, Resnick MD. Don't ask, they won't tell: The quality of adolescent health screenings in five practice settings. Am J Public Health 1996;86:1767 1772.
89. Barnett HL. Preventive screening for health risks among adolescents (annotation). Am J Public Health 1996;86:1701.
90. Khoury MJ and the Genetics Working Group. From genes to public health: The applications of genetic technology in disease prevention. Am J Public Health 1996;86: 1717 1722.
91. Raitakari OT, Leino M, Raikkonen K, Porkka KVK, Taimela S, Rasanen L, Vikari JSA. Clustering of risk habits in young adults: The Cardiovascular Risk Young Finns Study. Am J Epidemiol 1995;142:36 44.
92. Guillaume M, Lapidus L, Beckers F, Lamberta A, Bjorntorp P. Cardiovascular risk factors in children from the Belgian province of Luxembourg: The Luxembourg Child Study. Am J Epidemiol 1996; 144:867 880.
93. Twisk JWR, Kemper HCG, van Mechelen KW, Post GB. Tracking of risk factors for coronary heart disease over a 14-year period: A comparison between lifestyle and biologic risk factors with data from the Amsterdam Growth and Health Study. Am J Epidemiol 1997; 145:888 898.
94. Lewis CE, Smith DE, Wallace DD, Williams OD, Bild Jacobs DR. Seven-year trends in body weight and associations with lifestyle behavioral characteristics black and white young adults: The CARDIA Study. Am J Public Health 1997;87:635 642.
95. Vartiainen E, Paavola M, McAlister A, Puska P. Fifteen-year follow-up of smoking prevention effects in the North Karelia Youth Project. Am J Public Health 1998;88: 81 85.
96. Meyers L, Coughlin SS, Webber LS, Srinivasan SR, Berenson GS. Prediction of adult cardiovascular multfactorial risk status from childhood risk factor levels: The Bogalusa Heart Study. Am J Epidemiol 1995;142:918 924.
97. Tate RB, Manfreda J, Krahn AD, Cuddy TE. Tracking of blood pressure over a 40-year period in the University of Manitoba Follow-Up Study, 1948 1988. Am J Epidemiol 1995;142:946 954.
98. Hornberger J. A cost-benefit analysis of a cardiovascular disease prevention trial, using folate supplementation as an example. Am J Public Health 1998;88:61 67.
99. Reed DW, Foley DJ, White LR, Heimovitz H, Burchfiel CM, Masak K. Predictors of healthy aging in men with high life expectancies. Am J Public Health 1998;88:1463 1468.