National Heart, Lung, and Blood Institute Task Force Report on Research in Prevention of Cardiovascular Disease

Establishing Priorities for Prevention Research
Specific Recommendations
      Top-Tier Priorities
      High-Priority Research
Utilization and Implementation of the Task Force Report
Conclusions
Task Force on Research in Prevention of Cardiovascular Disease

During the past 30 to 40 years, tremendous advances have been made in preventing cardiovascular disease (CVD). Since 1960, mortality from CVD has decreased more than 50 percent in the United States. This remarkable decline is a result of population-wide efforts to prevent CVD and advances in treating patients with CVD. Over the past four decades, dietary and smoking habits, treatment of hypertension and dyslipidemia, outpatient therapy for CVD, and inpatient treatment of acute CVD events have improved substantially.

Yet, some areas of prevention research have not been as successful. Currently in the United States, the prevalence of obesity and diabetes continues to increase, the knowledge gained from clinical trials is not always integrated successfully into community and clinical practice, and health disparities have not been significantly reduced for various racial and ethnic groups and individuals with low socioeconomic status. In addition, U.S. mortality rates for CVD are approximately double those of many other countries, indicating that the United States has additional opportunities for further reducing mortality, and morbidity, from CVD.

To identify fruitful areas of research for continuing the United States' history of success in preventing CVD, the National Heart, Lung, and Blood Institute (NHLBI) established in January 2001 the Task Force on Research in Prevention of Cardiovascular Disease. Its members represented specific areas of prevention research. This report documents the deliberations and recommendations of the Task Force.

The objective was to develop a research agenda and an action plan for the NHLBI and the National Heart, Lung, and Blood Advisory Council (NHLBAC). The Task Force's recommendations address the research agenda, not a broad public health agenda. By developing specific research priorities in the context of the research the NHLBI currently supports and existing gaps in its portfolio, the Task Force defines a strategic prevention research agenda for the next 2 to 5 years. The aim is to provide guidance for allocating NHLBI resources for Institute-initiated and investigator-initiated research on the prevention of CVD.

As requested by the NHLBI, the report is a short document focused on identifying appropriate next steps for continued implementation of the Institute's objectives in prevention research. The NHLBI published a more comprehensive document, entitled the NHLBI Report of the Task Force on Research in Epidemiology and Prevention of Cardiovascular Disease, in August 1994.

Establishing Priorities for Prevention Research
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Research on prevention of CVD is necessarily multidisciplinary. It encompasses prevention activities across the disease continuum, including research on behaviors leading to elevated risk factors for CVD, the initiation and progression of disease, and acute events and premature death. In its report, the Task Force emphasizes strategic clinical and population research applicable to the prevention of CVD.

The recent National Conference on Cardiovascular Disease Prevention highlighted national trends in risk factors, morbidity, and mortality related to CVD. Its findings are published as a special report in Circulation (2000;102:3137-47), entitled "Trends and Disparities in Coronary Heart Disease, Stroke, and Other Cardiovascular Diseases in the United States" (Cooper, R., et al.). The data reported show several disparities in the control of risk factors and in mortality rates among groups according to race, ethnicity, socioeconomic status, geography, age, and gender. Based on these findings, the National Conference recommended emphasis on applied prevention research to reduce these disparities in population subgroups and to address adverse trends in deleterious health behaviors. The Task Force adopted this recommendation in developing the specific research priorities presented in this report.

Establishing research priorities is difficult and the process used to establish priorities has inherent limitations. The Task Force used the following criteria to determine whether a particular area should be considered a priority for research on prevention of CVD:

• Is the research applicable to Areal-world@ clinical and community settings?
• Does the research area involve cutting-edge science?
• Is the area understudied?
• Is the opportunity timely?
• Is the potential impact large (i.e., is the burden of disease high and/or are the risk factors or risk behaviors highly modifiable)?
  
  The members of the Task Force, who represented a broad range of prevention science, initially presented research priorities within their areas of expertise and then collectively discussed the overall merit of each recommendation before ranking all recommendations by priority. The Task Force then distributed a draft report of its recommendations to leaders in prevention research to solicit their feedback. It also encouraged input from the global scientific community and then incorporated their responses in developing its final recommendations.
  
  The research priorities presented in this report are not intended to be restrictive to the NHLBI or investigators, nor are they intended to preclude or discourage the submission of creative proposals in other areas of prevention research for consideration in the peer review process. Two areas, for example, which the Task Force chose not to address are research on surveillance and international studies.

The Task Force recognizes that ongoing surveillance of trends in CVD is vital for adapting current research strategies to current trends. The initiation of creative strategies for ongoing surveillance of CVD, similar to the Surveillance, Epidemiology, and End Results (SEER) registry system, is important, but the Task Force considers this research area to be outside the scope of its charge.

Similarly, the Task Force recognizes that international efforts are needed to reduce the global burden of CVD. Within the scope of this report, the Task Force limits its recommendations to the many opportunities for reducing the burden of CVD in the United States.

Specific Recommendations
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The Task Force presents its recommendations in two categories based on priority. Although all the recommendations have substantial merit, the Task Force's priority-ranking process yielded two distinct groups: top-tier priorities and high-priority research. To clarify the specific recommendations, the Task Force provides examples of specific research studies. These examples should not be viewed as the only areas of research pertinent to the specific recommendation.

Top-Tier Priorities
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Evaluate approaches to enhance implementation of efficacious preventive interventions in medical systems at all stages of clinical practice

Substantial evidence shows that established therapies for preventing CVD are not being adequately applied in practice. Models of health systems are needed to encourage and expand adoption of national standards for screening and management of behavioral and pharmacological risk factors for both primary and secondary prevention. The utility of novel methods for increasing adherence to national guidelines for prevention needs to be evaluated, and the cost-effectiveness and acceptability of these methods need to be determined. Both activities are critical for reducing the burden of CVD, especially among subpopulations that are not currently benefiting from uniformly applied guidelines.

Examples of research in this area include the testing of certain tools or specific organizational changes to encourage adherence to a national guideline. For example, studies may evaluate the effectiveness of intervention methods in coronary care unitsCto increase the proportion of patients who meet national goals for secondary prevention at the time of hospital dischargeCand systemic approaches to improve prevention in primary care settings.

Support studies to facilitate reduction of the epidemic of obesity in American children and adults

Current trends for obesity in American children and adults are alarming, and the incidence of Type 2 diabetes mellitus, a risk factor associated with obesity, has increased dramatically. Morbidity and mortality rates of ischemic heart disease attributable to obesity are likely to rise because of increased rates of diabetes, hypertension, and dyslipidemia. Effective interventions to prevent obesity are urgently needed, through dietary and exercise approaches for multiple population subgroups and particularly for prediabetic individuals and ethnic minorities. Although efficacy studies demonstrate that individuals lose weight when calories are restricted, regardless of the macronutrient content of the diet, the different levels of fat content or the glycemic index have rarely been compared in effectiveness studies or settings that are generalizable. Studies of the effects of other dietary components (e.g., the effect of fiber on weight loss), the treatment of obesity in both adults and children, and the maintenance of weight loss are also needed. Importantly, effective diet and exercise interventions would also benefit cardiovascular health in ways other than weight loss.

Examples of research in this area include studies to compare the effects on weight loss of self-selected high-fat versus low-fat diets or diets containing similar nutrient content but with a high versus low proportion of vegetables. Studying the effects of such dietary interventions in different populations (e.g., prediabetic, diabetic, ethnic minorities) also may be important. Studies of the effects of dietary components other than fat and of exercise, to treat and prevent obesity and maintain weight loss, are important. Research to improve measurements of exercise and diet would also be beneficial.

Initiate studies to understand the effects of preventive strategies on the early natural history of atherosclerosis, and integrate subclinical measures as appropriate

Strategies of primary prevention need to be focused on the prevention of disease as early as possible in the natural history of CVD. Using measures of subclinical disease as outcomes will enable investigators to evaluate the efficacy of interventions on early disease (i.e., clinically silent atherosclerosis or left ventricular hypertrophy). A number of noninvasive diagnostic tools (e.g., ultrasound, ultrafast computerized tomography, magnetic resonance imaging, electrocardiography, Doppler) are available for detecting the onset of CVD. However, subclinical measures should not be viewed as direct replacements for Ahard," CVD endpoints, but as endpoints for interventions to reduce the early burden of disease (e.g., atherosclerosis). Because many markers of subclinical disease are available, the selection of marker(s) to be used should be based on the design of the study and the demographics of the population to be studied (i.e., children, young adults, middle-aged populations, and higher-risk groups).

Examples of research in this area include studies to improve behavioral factors and pharmacological interventions in youth and asymptomatic middle-aged adults. Rather than designing a study focused primarily on process indicators, investigators also could integrate markers of subclinical disease as outcomes.

Identify determinants of disparities and barriers to optimal prevention of CVD according to age, gender, and ethnicity

Health disparities across racial, ethnic, age, and gender groups are well documented. To eliminate these disparities, optimal strategies are needed for delivering preventive care to all population subgroups. Significant barriers to optimal prevention of CVD have been identified and include level of income, access to care, and treatment. Existing systems for primary and secondary prevention of CVD have not eliminated health disparities. New strategies must be developed to overcome the known barriers to prevention.

Examples of research in this area include the development of procedures for use in real-world settings to increase the treatment of, and adherence to, interventions for lowering blood pressure among individuals in low socioeconomic and African American populations. Other strategies involve development of better methods of primary prevention of CVD targeted to underserved populations. Techniques for accurately monitoring health outcomes are also needed to track changes in health disparities.

Test approaches using subclinical measures or other markers of CVD risk in clinical practice, to enhance effectiveness of interventions

Clinical populations are increasingly aware of the availability of subclinical measures, risk equations, and genetic markers for risk of CVD. Yet, adherence to primary and secondary CVD prevention measures is relatively low. Subclinical measures or other markers could be used as motivational tools to enhance adherence to pharmacological and lifestyle interventions. They could also be used to stratify individuals according to their risk of CVD and appropriate levels of intervention (initiation and intensity). Unfortunately, the utility of using subclinical measures or other markers in high-risk populations or in the general population has not been established. Although some measures have been shown to be independent predictors of CVD events, methods to integrate them into clinical practice and clinical prevention have not been delineated. Additional research is needed to describe more clearly the cost- and risk-benefit of using these measures and markers in nonresearch settings.

Examples of research in this area are efforts to determine appropriate uses for subclinical disease or risk markers in clinical practice. The clinical use of many subclinical markers depends on the results of ongoing studies (e.g., of the predictive power of calcium in the coronary artery, of many genetic markers). However, clinical guidelines for the application of other measures (e.g., Framingham risk scores, selected genetic markers, carotid ultrasound for atherosclerosis, Doppler studies of peripheral artery disease) could be developed now. Some potentially important areas of investigation include determining whether a high-risk or general-population approach is cost effective and warranted, whether abbreviated study protocols are possible and as effective for detecting disease as more elaborate research protocols, and which actions should be recommended when patients present the results of for-profit screening (e.g., ultrafast computerized tomography data) to their regular physician.

Identify persons more susceptible to environmental change by designing studies to determine the effects of preventive interventions in persons with a variation in the candidate genes for CVD risk factors

The draft sequence of the human genome is now available, and an enormous effort is under way to identify variations in genetic sequences across individuals. Information is needed to better characterize variation in disease, modifier, and susceptibility genes across different environments so that the influence of environmental factors on levels of risk factors and disease can be evaluated in different populations. Two important areas to be explored are genetic effects on age-related changes in measures of subclinical disease and the effect of age on specific genes (i.e., genotypeBage interaction). Determining whether responses to differing environments and/or treatments depend on genetic variation is also fundamental.

Examples of research in this area include studies that incorporate genetics related to lipids. Areas of inquiry could include identifying genes, genetic variants, and environmental factors that contribute to the variation in lipids among populations; assessing geneBenvironment interactions related to the development of hyperlipidemia; determining the efficacy of lifestyle or pharmacological interventions according to individual genetic variations; and evaluating the utility of genetic screening tests for predicting the efficacy of treatment.

Incorporate psychosocial factors into intervention trials, for research on the prevention of CVD

Psychosocial risk factors for CVD (e.g., hostility, depression, social isolation) and physical risk factors for CVD (e.g., abnormal lipid and lipoprotein levels, high blood pressure, smoking) tend to cluster in individuals and in groups of individuals (e.g., with low socioeconomic status). Instead of acting independently, risk factors probably interact to increase an individual's risk of disease, and psychosocial risk factors may contribute to the risk of CVD via effects on physical risk factors. Because psychosocial risk factors appear to cause some people to engage in behaviors (e.g., smoking, poor dietary intake) that contribute to increased levels of physical risk factors, studying the combined and interactive effects of both types of risk factors on risk of CVD is important.

Examples of research in this area include studies that use sophisticated, multivariate statistical techniques (e.g., PATH analysis, Structural Equation Modeling) to evaluate data on psychosocial and physical risk factors which are available from extant studies [e.g., Coronary Artery Risk Development in Young Adults (CARDIA), Atherosclerosis Risk in Communities (ARIC), Multiple Risk Factor Intervention Trial (MRFIT), Hypertension Detection and Follow-up Program (HDFP), Nurses' Health Study (NHS), Health Professionals Follow-up Study (HPFS)]. Related studies could determine whether the targeting of psychosocial risk factors results in improved outcomes for interventions to reduce physical risk factors (e.g., smoking).

Evaluate the efficacy of preventive strategies on risk factors, quality of life, and functional status in elderly persons and the effectiveness of strategies for use in clinical practice

Recent census data suggest that the oldest age group (75 years and older) continues to increase as a proportion of the U.S. population. Although manifesting a broad spectrum of comorbidity, functioning, and treatment of disease, this heterogeneous group has been the focus of relatively few intervention studies of CVD. Too little is known about the best strategies to use in this group to compress morbidity, preserve (or enhance) functioning, and optimize outcomes.

Examples of research in this area include randomized trials of various combinations of strategies (e.g., management of blood pressure and lipid levels by drugs, diet, and exercise) to reduce the risk of CVD in representative groups of very elderly patients. Little is known about the effectiveness of lowering patients' lipid levels using statins for those 75 years of age and older. Studies of lipid management are needed in this age group and should include randomized trials and observational studies to assess a spectrum of outcomes.

High-Priority Research
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Obtain consent and DNA when possible from participants in prevention studies

Using current resources, tools, and technologies, high-throughput genotyping and re-sequencing of candidate genes are feasible. The relevance of gene mutations and sequence variations in the onset and progression of disease across genetically heterogeneous population groups needs to be determined. By knowing whether and how the effectiveness of interventions differs across different genetic subgroups, investigators will be able to tailor interventions to individuals. To improve understanding of the potential genetic basis of prevention, DNA should be collected whenever possible in all prevention-oriented observational studies and trials.

Understand the origins of psychosocial factors in childhood, including gene-environment interactions

Psychosocial and physical risk factors for CVD, and their tendency to co-occur in individuals and groups of individuals, likely have their origins in childhood, including the prenatal period. Some diseases are caused by mutations of a single gene (e.g., Huntington's chorea, sickle cell anemia), but the development of risk factors for CVD probably involves interactions of multiple genes with environmental factors. Knowledge of the variation (polymorphisms) in genes that are strong candidates for interacting with environmental factors, to contribute to the development of disease, is rapidly increasing. Identifying persons at highest risk of CVD should therefore be possible with far greater accuracy. This knowledge would enable investigators to target high-risk groups for more effective and efficient primary prevention.

Examples of research in this area are studies to evaluate candidate polymorphisms of genes that regulate serotonergic function among children in both positive and adverse (e.g., lower socioeconomic) environments, as predictors of the development of CVD in individuals and groups of individuals.

Determine the effects of dietary patterns and specific nutrients on CVD risk factors other than LDL cholesterol (e.g., blood pressure, other lipoproteins, and other risk factors) across population subgroups

Many studies address the effects of diet on lipoproteins, especially low-density lipoproteins (LDL). However, other lipoproteins appear to be involved in atherogenesis, including high-density lipoproteins (HDL) and triglyceride-rich remnant particles. In addition, diet has other, nonlipoprotein effects (e.g., on coagulation, blood pressure, and antioxidant level), which may be important. The effects of dietary patterns and specific nutrients on multiple lipid and nonlipid endpoints need to be studied. The effects of dietary patterns in specific population subgroups, especially diabetic and prediabetic patients, also should be addressed.

An example of research in this area is a randomized efficacy study to compare two low-saturated-fat diets (high total fat versus very low total fat) for their effects on lipids, lipoproteins, and coagulation in different groups of individuals (who are obese and nonobese, have normal or high triglyceride levels at baseline, exhibit normal insulin sensitivity).

Evaluate behavioral strategies in adolescents, including successful strategies from other disciplines (e.g., research on drug abuse)

Adolescence is a time when individual health behaviors emerge from family health behaviors. It is also a time when the influence of peers on health behaviors increases and behavioral interventions are most difficult. Effective lifestyle and behavioral interventions for adolescents need to be developed and assessed.

An example of research in this area is a randomized clinical trial to determine whether behavioral strategies to build self-esteem and self-efficacy, which have been useful in preventing drug abuse, can be used to prevent other adverse health behaviors, such as tobacco use, poor diet, and physical inactivity.

Understand the social and cultural antecedents of diet and exercise behavior

The reasons for adopting, or failing to adopt, a healthy diet and/or physical activity are complex. Providing information and knowledge of appropriate health behaviors is important and necessary, but is not sufficient for promoting heart-healthy behaviors at a population level. To enhance success in promoting healthy lifestyles, the fundamental social and cultural antecedents of healthy behaviors need to be better understood. Results from this basic research can be incorporated into the next generation of innovative interventions.

Examples of research in this area are studies to gain a better understanding of the reasons for food selection (e.g., cost, commercial media campaigns, availability, convenience) among diverse populations. Specific studies could examine the effects of cultural traditions and social influences on food choices by individuals of various ethnic and socioeconomic groups.

Evaluate newer options for hormone replacement therapy for prevention of CVD

The accumulation of evidence suggests that the traditional form of hormone replacement therapy (0.625mg/day of conjugated estrogen combined with medroxyprogesterone acetate), which is being tested in the Women's Health Initiative (WHI), may not be optimal for preventing CVD. While clinicians await the results of the WHI and additional ongoing studies, other options for hormone replacement could be evaluated. Studies that compare the efficacy of alternative compounds, such as low-dose estrogen, natural progesterone, selective estrogen receptor modulators (SERM), and other tissue-specific estrogens (including soy isoflavones), on surrogate markers and intermediate CVD endpoints are needed. These studies would enable investigators to identify the optimal therapy for testing in future large-scale, clinical studies of CVD endpoints and to make informed choices about therapy for menopause.

An example of research in this area is a randomized clinical trial to compare the effects of low-dose estrogen or other alternative compounds on markers of inflammation and vascular activation and on subclinical or clinical outcomes of CVD.

Understand community-wide and neighborhood-level determinants of health behaviors

The major risk factors for epidemic CVD (i.e., incidence at the societal level) are social and include low socioeconomic status, poor diet, physical inactivity, tobacco use, and adverse physical environment. Major NHLBI studies in the 1980s demonstrated that community-level risk of CVD changes over time. The determinants of these changes and the reasons for improvement by some communities, but not others, are not clear. Factors that indicate a community's acceptance of change also are not known. The determinants of changes in health behaviors tend to operate in neighborhoods and entire communities. Important variables may include availability of recreation facilities or fast food, media and marketing, transportation systems, and cultural factors.

Examples of research in this area include studies with small- or large-scale objectives. Small-scale studies could focus on the effects of in-store marketing of tobacco on initiation of smoking among youth or the effects of television marketing of snack foods on individuals' caloric consumption. Large-scale studies could include long-term observational studies in several communities to document differences in social variables and changes in risk factors for CVD. A study of exercise levels in recently constructed, planned communities that emphasize cohesive neighborhoods and public transit would be informative. The goal of these efforts would be to identify successful techniques for promoting healthy behaviors at a population level.

Evaluate potentially generalizable interventions in selected community settings (worksites, churches, schools)

A major challenge in the prevention of CVD is to address social, community-level causes of disease. Large-scale, community-wide intervention studies are expensive. However, studies of intervention programs in selected community settings, such as schools, worksites, and churches, may suggest programs that can be generalized to other settings and populations. The NHLBI is already supporting research in this area. Additional studies on the dissemination of interventions (e.g., incentives for schools to adopt and implement effective curricula related to the prevention of CVD) would be helpful. Also, because declining levels of physical activity are contributing to the epidemic of obesity in the United States, ways to increase total daily energy expenditures should be emphasized and extended to the worksite. Focusing only on leisure-time exercise is not sufficient.

Examples of research in this area include studies of interventions to promote increased physical activity, and particularly to prevent obesity, among diverse population subgroups. Development of a comprehensive health promotion curriculum for grades K through 12 in collaboration with a school system may improve long-term adoption and effectiveness of interventions.

Utilization and Implementation of the Task Force Report
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The recommended priorities for research in prevention of CVD, presented in this report, reflect the consensus of the Task Force. These recommendations may be used by the NHLBI to help guide the Institute's decision making process, to accept investigator-initiated grants in excess of $500,000, to stimulate and encourage submission of research project grant applications in targeted areas of research, and to provide direction for the development of specific NHLBI initiatives (i.e., Requests for Applications, Requests for Proposals, Program Announcements).

Conclusions
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The Task Force believes that research on the prevention of CVD offers tremendous opportunities for scientific discovery. The priorities it set forth are intended to promote further activity in high-yield, high-priority research areas in the short-term. However, the Task Force emphasizes that this report is not intended to constrain the Institute from recognizing meritorious research that may lie outside the topics described above.

Substantial benefits will be gained from funding the next generation of innovative research on prevention of CVD. Significant advances to reduce the U.S. burden of CVD have been made in the past decades. With this report, the Task Force hopes to energize continued progress in research on prevention of CVD. Its recommendations should be viewed as an effort to achieve a balance among many important research areas. These include primary and secondary prevention; genetic, environmental, and combined approaches; prevention in childhood through older adulthood; risk factors for CVD; subclinical disease and clinical outcomes of CVD; and community, as well as clinical, settings.

The Task Force believes that the next generation of studies to prevent CVD will provide the foundation for future efforts to further reduce the still-unacceptable high burden of CVD in the United States.

Task Force on Research in Prevention of Cardiovascular Disease Task Force
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Cochairs

Gregory Burke, M.D.
Professor and Chairman
Department of Health Sciences
Wake Forest University School of Medicine
Winston-Salem, North Carolina

Lori Mosca, M.D., Ph.D.
Director, Preventive Cardiology
New York Presbyterian Hospital
Associate Professor of Medicine
Columbia University New York, New York

Members

Donna Arnett, Ph.D.
Associate Professor
Division of Epidemiology
University of Minnesota School of Public Health
Minneapolis, Minnesota

Luther T. Clark, M.D.
Director, Cardiovascular Medicine
Department of Medicine
SUNY Health Science Center at Brooklyn
Brooklyn, New York

Stephen R. Daniels, M.D., Ph.D.
Professor of Pediatrics and Environmental Health
Children's Hospital Medical Center
University of Cincinnati College of Medicine
Cincinnati, Ohio

Stephen P. Fortmann, M.D.
C. F. Rehnborg Professor of Preventive Medicine
Stanford University School of Medicine
Palo Alto, California

Harlan M. Krumholz, M.D.
Associate Professor of Medicine
Yale University School of Medicine
New Haven, Connecticut

Redford B. Williams, Jr., M.D.
Director, Behavioral Medicine Research Center
Department of Psychiatry & Behavioral Sciences
Duke University Medical Center
Durham, North Carolina

NHLBI Staff

Coordination:

Carl Roth, Ph.D., LL.M.
Associate Director for Scientific Program Operation

Nancy Eng
Program Analyst
Office of Science and Technology

Resource:

Jeffrey Cutler, M.D., M.P.H.
Director, Clinical Applications and Prevention Program
Division of Epidemiology and Clinical Applications

Teri Manolio, M.D., Ph.D.
Director, Epidemiology and Biometry Program
Division of Epidemiology and Clinical Applications

Peter Savage, M.D.
Acting Director
Division of Epidemiology and Clinical Applications

Denise Simons-Morton, M.D., Ph.D.
Deputy Director, Clinical Applications and Prevention Program
Division of Epidemiology and Clinical Applications

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October 2001

The National Heart, Lung, and Blood Institute (NHLBI) provides leadership for a national program in diseases of the heart, blood vessels, lung, and blood; sleep disorders; and blood resources management. It plans, conducts, fosters, and supports an integrated and coordinated program of basic research, clinical investigations and trials, observational studies, and demonstration and education projects related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases, and sleep disorders. Research is conducted in the Institute's own laboratories and by other scientific institutions and individuals supported by research grants and contracts. The Institute also supports research training and career development for new and established researchers in basic and clinical research relating to these topics, and oversees management of the Women's Health Initiative.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
National Institutes of Health
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