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CLINICAL GUIDELINE, PART 2: Cholesterol Screening in Asymptomatic Adults, Revisited

Alan M. Garber, MD, PhD; Warren S. Browner, MD, MPH; and Stephen B. Hulley, MD, MPH
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From Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Department of Veterans Affairs Medical Center and the University of California, San Francisco, San Francisco, California. Acknowledgments: The authors thank Jin Yang for research assistance and Andrew Avins and members of the Clinical Efficacy Assessment Subcommittee of the Health and Public Policy Committee of the American College of Physicians for helpful comments. Grant Support: In part by grants R29 AG07651 from the National Institute on Aging and R01 HL46297 from the National Heart, Lung, and Blood Institute and by a Health Services Research and Development Senior Research Associate Award from the Department of Veterans Affairs. Much of this work was initiated while Dr. Garber was a Henry J. Kaiser Family Foundation Faculty Scholar in General Internal Medicine. Requests for Reprints: Alan M. Garber, MD, PhD, Stanford University School of Medicine, 204 Junipero Serra Boulevard, Stanford, CA 94305. Current Author Addresses: Dr. Garber: Stanford University School of Medicine, 204 Junipero Serra Boulevard, Stanford, CA 94305. Dr. Browner: San Francisco Veterans Affairs Medical Center, General Internal Medicine 111A1, 4150 Clement Street, San Francisco, CA 94121.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1996;124(5):518-531. doi:10.7326/0003-4819-124-5-199603010-00013
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Objective: To assess the role of serum lipid levels as screening tests in adults.

Design: Pooled analysis of clinical trials, supplemented by analysis of data from the Framingham Heart Study, to estimate the effect of cholesterol reduction in patient groups stratified by cardiac risk.

Study Selection: Published randomized, controlled trials of cholesterol reduction, meta-analyses of such trials, prospective cohort studies of the association between cholesterol levels and morbidity and death related to coronary heart disease, and cost-effectiveness analyses of cholesterol reduction.

Data Analysis: Two-stage logistic regression on cardiac risk factors and outcomes in the Framingham Heart Study. The first stage predicted the risk for death from coronary heart disease using standard risk factors but not cholesterol; the second stage predicted the risk for death from coronary heart disease and all causes as functions of age and cholesterol level, stratified by the risk predicted from the first stage.

Results: Randomized clinical trials show that cholesterol reduction confers survival benefits in patients with symptomatic coronary disease. In asymptomatic middle-aged men, who are at lower risk for death from coronary disease, cholesterol reduction prevents coronary disease but has not been shown to prolong life. The risk model based on analysis of the data from the Framingham Heart Study is consistent with the randomized trial data and shows that in the demographic groups excluded from trials, the hypothetical benefits of cholesterol reduction are greatest when the underlying risk for coronary disease is greatest.

Conclusions: Screening with total cholesterol levels is most likely to be useful when done in populations at high short-term risk for dying of coronary heart disease, such as survivors of myocardial infarction and middle-aged men with multiple cardiac risk factors. In these populations, cholesterol reduction appears to be both effective and cost-effective. In other populations, the benefits of reduction are much smaller or are uncertain.

[Note that sections in this paper are numbered so that they can be identified with cross-references as supporting evidence in the article “Guidelines for Using Serum Cholesterol, High-Density Lipoprotein Cholesterol, and Triglyceride Levels as Screening Tests for Preventing Coronary Heart Disease in Adults”; see pages 515-517.]


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Figure 1.
Cost-effectiveness of treating high blood cholesterol levels with lovastatin, 20 mg/d, drawn (solid lines) or extrapolated (dotted lines) from tabular data from Goldman and colleagues[120]

. The models assume only favorable effects on mortality, do not include screening costs, and define high blood cholesterol levels as at least 300 mg/dL (7.76 mmol/L) for primary prevention in persons without other risk factors (low-risk) and as at least 250 mg/dL (6.47 mmol/L) for secondary prevention in persons with previous coronary heart disease (CHD). (The cost of treating 35- to 54-year-old men with CHD is zero because savings from future CHD outweigh the costs of treatment.) The ordinate is a log scale; the dashed line is at $100 000 per year of life saved. Reproduced with permission from The Journal of the American Medical Association. 1993; 269:1416-9.

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