Systematic Evidence ReviewNumber 4

Prepared for:Agency for Healthcare Research and QualityU.S. Department of Health and Human Services

2101 East Jefferson Street

Rockville, MD 20852 http://www.ahrq.gov

Contract No. 290-97-0011 Task Order No. 3Technical Support of the U.S. Preventive Services Task Force

Prepared By: Research Triangle Institute University of North Carolina

Evidence-based Practice Center

Michael P. Pignone, M.D., M.P.H.

Christopher J. Phillips, M.D., M.P.H.

Carole M. Lannon, M.D., M.P.H.

Cynthia D. Mulrow, M.D., M.Sc.

Steven M. Teutsch, M.D., M.P.H.

Kathleen N. Lohr, Ph.D.

B. Lynn Whitener, Dr.P.H., M.S.L.S.

AHRQ Publication No. 01-S004

April 2001

On December 6, 1999, under Public Law 106-129, the Agency for Health Care Policy Research (AHCPR) was reauthorized and renamed the Agency for Healthcare Research and Quality(AHRQ). The law authorizes AHRQ to continue its research on the cost, quality, and outcomes of health care, and expands its role to improve patient safety and address medical errors. This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service.

The Agency for Healthcare Research and Quality (AHRQ) sponsors the development of Systematic Evidence Reviews (SERs) through its Evidence-based Practice Program. With guidance from the third U.S. Preventive Services Task Force* (USPSTF) and input from Federal partners and primary care specialty societies, two Evidence-based Practice Centers -- one at the Oregon Health Sciences University and the other at Research Triangle Institute-University of North Carolina -- systematically review the evidence of the effectiveness of a wide range of clinical preventive services, including screening, counseling, immunizations, and chemoprevention, in the primary care setting. The SERs -- comprehensive reviews of the scientific evidence on the effectiveness of particular clinical preventive services--serve as the foundation for the recommendations of the third USPSTF, which provide age- and risk-factor-specific recommendations for the delivery of these services in the primary care setting. Details of the process of identifying and evaluating relevant scientific evidence are described in the "Methods" section of each SER.

The SERs document the evidence regarding the benefits, limitations, and cost-effectiveness of a broad range of clinical preventive services and will help to further awareness, delivery, and coverage of preventive care as an integral part of quality primary health care.

AHRQ also disseminates the SERs on the AHRQ Web site (http://www.ahrq.gov/uspstfix.htm) and disseminates summaries of the evidence (summaries of the SERs) and recommendations of the third USPSTF in print and on the Web. These are available through the AHRQ Web site (http://www.ahrgq.gov/uspstfix.htm), through the National Guideline Clearinghouse (http://www.ncg.gov), and in print through the AHRQ Publications Clearinghouse (1-800-358-9295).

We welcome written comments on this SER. Comments may be sent to: Director, Center for Practice and Technology Assessment, Agency for Healthcare Research and Quality, 6010 Executive Blvd., Suite 300, Rockville, MD 20852.

John M. Eisenberg, M.D.

Director Agency for Healthcare Research and Quality

Douglas B. Kamerow, M.D.

Director, Center for Practice and Technology Assessment Agency for Healthcare Research and Quality

Lipid disorders are an important risk factor for coronary heart disease (CHD). Screening and treatment of lipid disorders in persons at high risk for future CHD events have gained wide acceptance, especially for patients with known CHD, but the proper role in persons with low to medium risk is controversial.

To examine the evidence about the benefits and harms of screening and treatment of lipid disorders in adults, adolescents, and children for the US Preventive Services Task Force.

We identified English-language articles on drug therapy, diet and exercise therapy, and screening for lipid disorders from comprehensive searches of the MEDLINE database from January1994 through July 1999. We used published systematic reviews, hand searching of relevant articles, the second Guide to Clinical Preventive Services, and extensive peer review to identify important older articles and ensure completeness.

We included all randomized trials of at least 1 year's duration that examined drug or diet therapy among patients without previously known CHD and that measured clinical endpoints, including total mortality, CHD mortality, or nonfatal myocardial infarctions. We also included randomized trials of diet or exercise therapy that measured change only in total cholesterol. To examine the question of screening, we included articles that addressed the epidemiology and natural history of lipid levels and lipid disorders or that measured the accuracy, reliability, acceptability, and feasibility of screening. We also included any articles that examined adverse effects and harms of screening or therapy for lipid disorders.

We extracted the following data from the included articles: demographic details about subjects; inclusion and exclusion criteria; and study design, duration, interventions, and outcome measures. We evaluated the internal and external validity of each article and judged the overall quality of evidence by examining aggregate internal and external validity and coherence of the results.

There is strong, direct evidence that drug therapy reduces CHD events and CHD mortality in middle-aged men (35 to 70 years of age) with abnormal lipids and a potential risk of CHD events greater than 1%per year. Drug therapy may also reduce total mortality in patients at higher risk (greater than 1.5% per year). Less direct evidence suggests that drug therapy is also effective in other adults, including older men (over the age of 70 years) and middle-aged and older women (ages 45 years and older) with similar levels of risk. Trials of diet therapy for primary prevention have led to long-term reductions in cholesterol of 3% to 6%but have not demonstrated a reduction in CHD events overall. Exercise programs that maintain or reduce body weight can produce short-term reductions in total cholesterol of 3% to 6% but longer-term results in unselected populations have found small reductions or no effect.

Screening middle-aged and older men and women for lipid disorders can accurately identify persons at increased CHD risk who may benefit from therapy. The evidence is insufficient about benefits and harms of screening and treating persons at low absolute risk, including most men under 35 years of age, women under 45 years, and children and adolescents. To identify accurately persons with abnormal lipids, at least 2 measurements of total cholesterol and high-density lipoprotein cholesterol (HDL) are required. The role of measuring triglycerides and the optimal screening interval are unclear from the available evidence.

Strong evidence shows the effectiveness of therapy for lipid disorders in middle-aged men; indirect evidence shows effectiveness in older men and women of sufficient risk. Screening for lipid disorders with total cholesterol and HDL and performing a global assessment of CHD risk can accurately identify those at sufficient risk who can benefit from treatment.

Key Word: Cardiovascular diseases - cholesterol - hyperlipidemia - preventive health services - evidence-based medicine - MEDLINE - methods - lipids - mass screening - mortality - drug therapy

This document is in the public domain and may be used and reprinted without permission except those copyrighted materials noted for which further reproduction is prohibited without the specific permission of copyright holders.

Suggested Citation:
Pignone MP, Phillips CJ, Lannon CM, et al. Screening for Lipid Disorders, Systematic Evidence Review No.4 (Prepared by the Research Triangle Institute -- University or North Caroline Evidence-based Practice Center, under contract No. 290-98-0011<). AHRQ Publication No. AHRQ 01-S004. Rockville, MD:

This study was supported by Contract 290-97-0011 from the Agency for Healthcare Research and Quality (Task No. 3 to support the US Preventive Services Task Force). We acknowledge the ongoing guidance and assistance of David Atkins, M.D., M.P.H., Director of the Clinical Preventive Services program at AHRQ, Dana Best, M.D., the Task Order Officer for this project, and Jacqueline Besteman, J.D., M.A., the Program Officer in the Center for Practice and Technology Assessment for the entire AHRQ Evidence-based Practice Center program.. We also acknowledge the assistance of Eve Shapiro, Managing Editor, under contract to the AHRQ Office of Health Care Information.

The investigators deeply appreciate the considerable support and contributions of faculty and staff from the University of North Carolina at Chapel Hill: Timothy S. Carey, M.D., M.P.H.; Co-Director of the RTI-UNC EPC; Russell P. Harris, M.D., M.P.H., Co-Director of the RTI-UNC EPC's Clinical Prevention Center; Anne Jackman, M.S.W.; Barbara E. Starrett, M.H.A.; Alyssa Wood, M.F.A., and Carol Krasnov. They are equally grateful to Linda Lux, M.P.A., Anjolie Idicula, B.A., and Sonya Sutton, B.S.P.H. of Research Triangle Institute for substantive project assistance and to Nicole Walker and Sheila White for, respectively, valuable contract assistance and superior secretarial support.

We appreciate the efforts of the following external peer reviewers who provided insightful and constructive suggestions for improvements in the systematic evidence review: Andy Avins, M.D., Department of Veterans Affairs (VA) Medical Center, San Francisco, CA; Robert Baron, M.D., University of California-San Francisco, San Francisco, Calif.; Warren Browner, M.D., for the American College of Physicians and American Society of Internal Medicine, VA Medical Center, San Francisco, Calif.; James Cleeman, M.D., National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Md.; Theodore Ganiats, MD, for the American Academy of Family Practice, , University of California-San Diego, La Jolla, Calif.; Wayne Giles, M.D., M.S. ,Centers for Disease Control and Prevention, Atlanta, Ga.; Matthew Gillman, M.D., S.M., Harvard Medical School and Harvard Pilgrim Health Care, Boston, Mass., ; Jeffrey Harris, M.D., Centers for Disease Control and Prevention, Atlanta, Ga., ; Marc Jacobson, M.D., for the American Academy of Pediatrics, , Schneider Children's Hospital, New Hyde Park, NY; David Katz, MD, MPH, Yale University School of Public Health, New Haven, Conn.; Michel Labrecque, M.D., M.Sc., for the Canadian Task Force on Preventive Health Care, Universite Laval, Rimouski, Quebec, Canada; Haq Nawaz, MD, MPH, for the American College of Preventive Medicine, Yale-Griffin Prevention Research Center, Derby, Conn., ; Thomas Newman, M.D. M.P.H., University of California-San Francisco, San Francisco, Calif., ; Thomas Nolan, M.D., for the American College of Obstetricians and Gynecologists, , Louisiana State University, New Orleans, La., ; and Hanna Rubins, MD, from the Department of Verterans Affairs.