This Article Extract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Garber, A. M. Articles by Browner, W. S. Search for Related Content PubMed PubMed Citation Articles by Garber, A. M. Articles by Browner, W. S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL

(Circulation. 1997;95:1642-1645.)
© 1997 American Heart Association, Inc.

Articles

Cholesterol Screening Guidelines

Consensus, Evidence, and Common Sense

Alan M. Garber, MD, PhD; Warren S. Browner, MD, MPH

From the Veterans Affairs Palo Alto Health Care System and Stanford University (A.M.G.), Stanford, Calif; and San Francisco Department of Veterans Affairs Medical Center and University of California, San Francisco (W.S.B.).

Correspondence to Alan M. Garber, MD, PhD, 204 Junipero Serra Blvd, Stanford, CA 94305. E-mail garber{at}camis.stanford.edu.

Key Words: cholesterol • tests • hypercholesterolemia

	Introduction

Top Introduction Evidence-Based and Consensus... ACP Guidelines: Approach and... Differences and Similarities References

 
In a previous issue of Circulation,¹ the Task Force on Risk Reduction criticized the updated American College of Physicians (ACP) Guidelines for Cholesterol Screening² for "advocating change in the NCEP [National Cholesterol Education Program]/AHA [American Heart Association] guidelines." Implicit in this claim are the beliefs that the NCEP guidelines represent the standard against which all cholesterol screening guidelines should be compared and that the ACP guidelines constitute a reaction to that standard. Neither belief is justified. Furthermore, the task force's comments reflect misunderstandings about the purpose, content, and scientific foundation of the ACP guidelines.

The ACP produced new cholesterol guidelines as part of a periodic review of all of its guidelines. The updated guidelines and background paper³ focused on the questions addressed in the original background paper and guidelines^{4 5} : Which adults should undergo screening for lipoprotein disorders? What tests should be used initially? These questions are more narrowly focused than the range of issues addressed in the NCEP report,⁶ which considered not only the initial screening test but also the sequence of follow-up testing, the criteria for initiation of treatment, and the choice of interventions. Because the effectiveness of screening depends on the steps taken after the result of the screening test is obtained, the ACP implicitly considered some of these issues, but the additional steps were not the subject of recommendations. Thus, the task force mistakenly inferred that the ACP recommended against certain practices proposed by the NCEP (eg, measuring lipoprotein levels in patients with elevated total cholesterol levels) that were not explicitly addressed because they fell outside of the purview of the guidelines.

	Evidence-Based and Consensus-Based Approaches to Guideline Development

Top Introduction Evidence-Based and Consensus... ACP Guidelines: Approach and... Differences and Similarities References

 
In the past, medical practice guidelines were often developed as the consensus opinion of experts. In keeping with this tradition, the NCEP assembled a group of experts from several professional organizations and sought their agreement about the best ways to detect and manage hypercholesterolemia in adults. This "consensus-based" type of recommendation can be contrasted with "evidence-based" guidelines and patient care recommendations. Evidence-based medicine is "a method of basing clinical decisions on the best available scientific evidence and using epidemiological and statistical methods to identify, appraise, and assimilate that evidence."⁷ The ACP has pursued such an approach in the development of its numerous (>200) practice guidelines. An evidence-based approach usually includes a comprehensive review of the pertinent data, a description of the search methods used to identify those data, and an evaluation of the quality of the information. Quantitative techniques are used to estimate the magnitude of the benefits and harms that would result from implementation of specific recommendations.

Consensus- and evidence-based approaches are not a strict dichotomy, and most current guidelines contain elements of each. Although it adhered to a consensus process, the NCEP reviewed a vast amount of evidence and used logic similar to that of the ACP in development of its treatment recommendations; the magnitude of the NCEP effort is manifest in the excellence of their report,⁶ which is useful even to those who do not agree with all of its recommendations. Unlike some groups that apply evidence-based approaches, the ACP did not rely solely on data from clinical trials. Furthermore, the ACP sought to gain many of the advantages of a consensus process by incorporating extensive internal and external reviews. Because much of the evidence reviewed by both the ACP and the NCEP was clear cut, the two sets of recommendations share many features, including advocacy of an aggressive approach to secondary prevention and testing patients at high risk.

We believe that the critical differences between the cholesterol screening recommendations of the NCEP and ACP result from two features that distinguish evidence- and consensus-based approaches to guideline development: adherence to quantitative inferences drawn from clinical and epidemiological data, and burden of proof. The NCEP report drew heavily on the biological and clinical plausibilities of potential benefit in arguing for aggressive approaches to the detection of hypercholesterolemia. In applying an evidence-based approach to guideline development, the ACP also argued that there might be a benefit from cholesterol detection and treatment but, unlike the NCEP, tried to quantify the benefit. The background paper for the ACP guidelines contained a review of epidemiological data and a description of the results (eg, magnitude of cholesterol reduction, odds ratios for coronary heart disease [CHD] death and total mortality) of every identified randomized, controlled clinical trial of cholesterol reduction that reported clinical outcomes, along with the results of every major reported meta-analysis. To quantify benefits in the large segments of the population excluded from the clinical trials, we estimated the hypothetical reduction in risk of CHD and total mortality resulting from cholesterol reduction in various demographic groups and at various risk levels. The body of evidence supporting the ACP guidelines was culled from an extensive effort to identify relevant information (largely based on Medline searches for clinical trials of cholesterol reduction and epidemiological studies of cholesterol as a risk factor, articles cited in other articles and book chapters, government reports, and citations from reviews and experts who reviewed draft manuscripts). The ACP guidelines are not based on a repudiation of the rationale the NCEP offered but rather represent an attempt to carry it a step further by answering a quantitative question that the NCEP did not answer directly: How great are the likely benefits of cholesterol reduction in specific population groups?

The second feature that distinguishes consensus-based from evidence-based guidelines is the burden of proof for establishing effectiveness: Evidence-based guidelines nearly always place that burden on those who advocate a preventive intervention. Consensus-based guidelines, particularly when they are produced by advocates for a particular set of approaches, may require less direct evidence or only a rationale that supports a potential benefit. Evidence-based approaches to guideline development often require clinical trial evidence of benefit or other directly applicable data. In the absence of acceptable evidence, they may refrain from making recommendations.

The areas in which cholesterol screening recommendations differ clearly illustrate the consequences of adopting either a consensus- or an evidence-based approach. The NCEP and the Canadian Consensus Conference on Cholesterol,⁸ both of which are consensus groups, recommended universal cholesterol testing in adults, whereas every major group in North America that rated the quality of evidence or attempted to quantify benefits (ie, the US Preventive Services Task Force⁹ ; the Canadian Task Force on the Periodic Health Examination¹⁰ ; the groups that created the official guidelines for the provinces of Ontario,¹¹ Quebec,¹² and Saskatchewan¹³ ; and many provider groups, such as Kaiser-Permanente, and other state or provincial authorities) made screening recommendations similar to those of the ACP.

There are many reasons for the ascendancy of evidence-based approaches to guideline development. Forceful recommendations to carry out screening and other preventive measures in the absence of equally strong evidence that they are beneficial, particularly when the magnitude of the potential benefit is small, can subsequently be proven wrong. The first Adult Treatment Panel of the National Cholesterol Education Program, for example, made stronger recommendations concerning the treatment of elevated cholesterol levels in asymptomatic adults than the subsequent panel¹⁴ and may have led to the increased use of gemfibrozil.¹⁵ Recent analyses of clinical trial data have concluded that gemfibrozil and other fibrates increase mortality.¹⁶ Like most groups that produce guidelines today, we believe that the most appropriate course is to prudently interpret existing data rather than to anticipate the results of future studies. If such studies confirm current hopes about the effectiveness of screening, the ACP should review its guidelines and revise them as appropriate.

	ACP Guidelines: Approach and Content

Top Introduction Evidence-Based and Consensus... ACP Guidelines: Approach and... Differences and Similarities References

 
Like nearly all published guidelines, the current ACP guidelines reflect the belief that cholesterol screening, by identifying individuals who would benefit from interventions to lower cholesterol, is an important strategy with which to prevent and ameliorate the toll of CHD. The background paper reviewed evidence demonstrating that the benefits of treating hypercholesterolemia can be substantial, especially in individuals who have existing CHD or are at a high risk of developing CHD for other reasons, such as family history or cigarette smoking. This conclusion is well accepted and was cited by the NCEP. Persons who have had a myocardial infarction or who have vascular disease are at one end of the risk spectrum; in this population, treatment of an elevated cholesterol level prevents the morbidity and mortality caused by CHD and prolongs survival. Consequently, the ACP strongly recommends that cholesterol levels be measured for the secondary prevention of CHD in all adults with a history of CHD or vascular disease.

It is in the area of screening people without symptomatic CHD or vascular disease—primary prevention—that the NCEP screening recommendations differ from those of the ACP and other groups. Screening can be effective only if treatment is effective. Clinical trials of cholesterol reduction for primary prevention in middle-aged men have shown that cholesterol reduction reduces the incidence of CHD, but until the West of Scotland Study was performed,¹⁷ none showed a survival benefit. Results of primary prevention trials in women or younger or older men have not been reported. Approaches to guideline development that require direct evidence of benefit from clinical trials would recommend neither treatment nor screening in these excluded groups, particularly because there are several reasons to question whether their benefits would be as large as they are for high-risk middle-aged men. The control group of the West of Scotland Study, for example, died as a result of CHD at a rate 100-fold as great as that for young women. Secondary prevention trials include even higher-risk populations: the control group of the Scandinavian Simvastatin Survival Study (4S) died as a result of CHD at a rate 400-fold as great as that for young women.¹⁸ Among younger people, who have little CHD to prevent, harms that occurred too infrequently to be detected in these trials could exceed the benefits of treatment. Although our analysis of individual-level data from the Framingham Heart Study used assumptions favorable to treatment, it confirmed this conclusion. In young men, the short-term risk of CHD from an elevated cholesterol level is only slightly elevated, particularly in the absence of multiple risk factors for CHD. In young women, the incidence of CHD is so low that the increase in risk from an elevated cholesterol level is nearly unmeasurable. Thus, there is little potential short-term gain from the detection and treatment of hypercholesterolemia in most young men or women, particularly those who have no other risk factors for CHD.

The assumption underlying much of the document of the Task Force is that detection and treatment of hypercholesterolemia in young adults provide substantial long-term benefits. Nowhere is the difference in adherence to evidence-based processes more apparent than here. It might be worth detecting an elevated cholesterol level if diet—a safe intervention—could provide even a modest reduction in the longer-term risk of CHD. No published clinical trial has directly tested the effects of cholesterol reduction in young adults, but numerous studies of experimental diets conducted in metabolic wards, in institutionalized populations, or among survivors of myocardial infarction have shown that diet can substantially lower cholesterol levels. However, in community settings, large, well-designed trials of diets that would be recommended to most individuals found to have high cholesterol levels have consistently reported that cholesterol reduction averages only 2%.¹⁹ Thus, despite individual exceptions, most asymptomatic people will fail to attain "desirable" cholesterol levels with diet alone, so for most young people, sustained and large reductions in cholesterol levels will require more aggressive therapy.

Although drug therapy reduces cholesterol levels more consistently and substantially, the assumption that early treatment will have a net benefit has not been established. Even if treatment initiated in young adulthood is completely safe, it is not likely to provide great benefits. The risk of CHD falls dramatically within 2 years of the initiation of cholesterol-lowering therapy, even if started in persons who already have symptomatic CHD; the full potential benefits of cholesterol reduction appear to be achieved within 5 years of the start of therapy.²⁰ Because the purpose of cholesterol reduction in young adults is to prevent the occurrence of CHD in the distant future, the rapid reduction in CHD risk implies that initiation of screening (and treatment) 5 years before the risk of CHD becomes substantial will produce essentially all of the benefits without the additional expense and potential harm of early initiation of screening. With the recognition that the incidence of CHD begins to rise at age 40 in men and age 50 in women, the ACP concluded that cholesterol screening was appropriate beginning at age 35 in men and age 45 in women without other CHD risk factors or at earlier ages if other risk factors were present.

Although the Task Force claimed that the ACP guidelines will miss some persons who might benefit from cholesterol reduction, such as young men and women with familial hypercholesterolemia who have no family history, xanthomas, xanthelasma, or other clinical evidence of the disorder, it is not evident that universal screening should be recommended to detect rare conditions (the situation they describe, although too uncommon for reliable statistics, is far less frequent than the overall 1:500 prevalence of familial hypercholesterolemia), particularly when there is no direct evidence that earlier initiation of treatment improves health outcomes.

The Task Force proposed another reason to perform cholesterol screening in the young: to promote desirable behavioral change, regardless of the cholesterol level. Available studies, however, show that screening causes persons to lower their cholesterol levels by only 2% to 4% during brief follow-up; these modest effects are likely to diminish over time.^{21 22 23 24 25} Thus, existing data do not indicate that cholesterol screening is a particularly effective way to promote behavioral change. Had this been a reason to screen, the NCEP might have recommended that this form of behavioral reinforcement be applied far more frequently than every 5 years.

Noting the lack of relevant clinical trials and ambiguity in the epidemiological data, the ACP refrained from making a recommendation for or against cholesterol screening for primary prevention in the age range of 65 to 75. However, it recommended against screening for primary prevention in men and women age 75 or older. In this group, which is well outside the age range included in primary prevention trials, evidence from epidemiological studies suggests that cholesterol may no longer be a risk factor for CHD.

When direct information about effectiveness is unavailable, such as for cholesterol reduction in young people or the elderly, different approaches may lead thoughtful persons to adopt differing positions. But we are concerned that the Task Force report and the LaRosa commentary that it recapitulates go beyond differences in opinion or interpretation and make statements about the ACP guidelines and the scientific literature that may be misleading. For example, the Task Force claims that the ACP overlooked evidence, such as the fact that cholesterol levels in young adults predict midlife CHD, that was cited and discussed in the background paper. The statement that the ACP displayed ignorance of the fact that a substantial portion of preventable CHD first manifests itself as sudden death or disabling myocardial infarction was not only incorrect but also irrelevant. The comment would be germane if the ACP had restricted cholesterol measurement to patients with CHD, but the ACP recommends screening for primary prevention in many circumstances.

The Task Force misleadingly conflates the results of primary and secondary prevention trials and misrepresents their findings. For example, it claimed that "data from both primary and secondary prevention trials ... demonstrate that cholesterol lowering is just as effective in persons older than 60 years as in younger populations." In support of this statement, the Task Force cites the 4S trial, a secondary prevention study, and the West of Scotland Study. The 4S trial reported the effects of simvastatin in individuals older and younger than age 60; in those younger than 60, the relative risk of a "major coronary event" in treated patients was 0.61, whereas in those older than 60, the relative risk was 0.73, suggesting, if anything, that the relative risk reduction diminishes with age. Although this does not imply that the absolute reduction in risk declines to the oldest age included in the trial (70 years), it reinforces the findings of epidemiological studies that the association between cholesterol and CHD declines with advancing age. The West of Scotland Study, the cited primary prevention trial, did not present the results claimed by the Task Force (the top age of enrollment was 64), but it also reported that the relative risk reduction from the intervention was less in the older participants. The results of these trials support the ACP guidelines—they suggest that cholesterol reduction may not be as beneficial, particularly for primary prevention, at advanced ages (75 and older). The key point, however, is that all of the participants in these two important trials fell into categories for which the ACP guidelines indicate that cholesterol measurement is appropriate: they had or were at high risk of developing CHD.

	Differences and Similarities

Top Introduction Evidence-Based and Consensus... ACP Guidelines: Approach and... Differences and Similarities References

 
These and other inaccuracies in the Task Force statement should not divert our attention from legitimate reasons for disagreement about screening. Expert groups can and do differ in their interpretation of data and of the evidence needed before concluding that cholesterol screening programs will be beneficial in different segments of the adult population. All agree on the importance of identifying and treating individuals with high cholesterol levels who have or who are at high short-term risk of developing CHD. The most important practical disagreement may be regarding young people, for whom any benefit remains unproved and speculative (and attempts to quantify benefit consistently demonstrate that it will be very small at best) and for whom the harmful effects of treatment may cumulate over 30 to 50 years. The evidence is insufficient to recommend cholesterol testing for low-risk groups, much less to mandate it, as the NCEP does. This conclusion is based on a careful analysis of existing data and resulted from a quantitative application of the same concept—that intervention should be targeted toward those at greatest risk—that underlies the NCEP treatment recommendations.

Although they were not an explicit factor in the development of the ACP recommendations, cost-effectiveness considerations lend further support to targeted screening. Both the NCEP report and the ACP background paper note that cholesterol-lowering therapy is most cost-effective when directed toward high-risk populations. The cost of statins, the most popular class of cholesterol-lowering drugs, is too high to ignore; the average wholesale price for a year of treatment with 40 mg/d lovastatin or 20 mg/d simvastatin, exceeds $1000.²⁶ When used in high-risk men and women, reduced costs of treating CHD may offset a substantial fraction of these costs,²⁷ making the drugs highly-cost effective, but the cost-effectiveness ratio reaches $1 million per year of life saved when used in young men or women with very high cholesterol levels but without other risk factors.^{3 28} When comparing the consequences of the NCEP and ACP guidelines, the relevant comparison is not between treating young adults for high cholesterol and not treating at all, as is typical for cost-effectiveness analyses. Rather, the difference is between initiating treatment at, say, age 25 or waiting until age 35 (or age 45 in women). By delaying of the initiation of therapy, the ACP guidelines avoid 10 or 20 years of costs and potential risks while preserving nearly all of the benefit. Seeking and treating hypercholesterolemia at ages younger than those recommended by the ACP produce a cost-effectiveness ratio that far exceeds generally accepted levels.

The ACP guidelines are advisory to physicians, who should exercise judgment and discretion—indeed, common sense—in applying any set of recommendations to their patients. Physicians are under pressure to handle more problems in increasingly brief office visits and to prioritize the issues and preventive strategies that they will address with each patient. A preventive intervention, even one that begins with something as simple and nominally inexpensive as a cholesterol test, should be recommended only if there is adequate evidence that it is likely to be beneficial. Based on current information, the ACP joined with nearly all major groups applying evidence-based criteria in concluding that cholesterol screening in low-risk young men and women and in asymptomatic older men and women does not meet this standard.

	References

Top Introduction Evidence-Based and Consensus... ACP Guidelines: Approach and... Differences and Similarities References

 
1. Task Force on Risk Reduction. Cholesterol screening in asymptomatic adults: no cause to change. Circulation.. 1996;93:1067-1068. [Free Full Text]

2. Garber AM, Browner WS. American College of Physicians guidelines for using serum cholesterol, high-density lipoprotein cholesterol, and triglyceride levels as screening tests for preventing coronary heart disease in adults. Ann Intern Med.. 1996;124:515-517. [Abstract/Free Full Text]

3. Garber AM, Browner W, Hulley S. Cholesterol screening in asymptomatic adults, revisited. Ann Intern Med.. 1996;124:518-531. [Abstract/Free Full Text]

4. Garber AM, Sox HC, Littenberg B. Screening asymptomatic adults for cardiac risk factors: the serum cholesterol level. Ann Intern Med.. 1989;110:622-639.

5. Eddy DM. Common Screening Tests. Philadelphia, Pa: American College of Physicians; 1991.

6. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA.. 1993;269:3015-3023. [Abstract/Free Full Text]

7. Smith R. Editor's choice: celebrating evidence-based everything. BMJ.. 1995;310:1081i.

8. Canadian Consensus Conference on Cholesterol. Final report. Can Med Assoc J.. 1988;139:1-8.

9. United States Preventive Services Task Force. Guide to Clinical Preventive Services. 2nd Ed. Baltimore, Md: Williams & Wilkins; 1996.

10. Canadian Task Force on the Periodic Health Examination. Periodic health examination, 1993 update; 2: lowering the blood total cholesterol level to prevent coronary heart disease. Can Med Assoc J.. 1993;148:521-538. [Medline] [Order article via Infotrieve]

11. Toronto Working Group on Cholesterol Policy. Asymptomatic hypercholesterolemia: a clinical policy review. J Clin Epidemiol.. 1990;43:1028-1121. [Medline] [Order article via Infotrieve]

12. Conseil d'Evaluation des Technologies de la Sante du Quebec (CETS). Cholesterol and Coronary Disease: Intervention Strategies in the Light of Present Knowledge. Montreal, Canada: CETS; 1993.

13. Health Services Utilization and Review Commission. Cholesterol Testing and Treatment in Adults. Saskatoon, Canada: Saskatchewan Health Services Utilization and Research Commission; 1995 (HSURC final report).

14. National Cholesterol Education Program. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: the Expert Panel. Arch Intern Med.. 1988;148:36-69. [Abstract/Free Full Text]

15. Wysowski DK, Kennedy DL, Gross TP. Prescribed use of cholesterol-lowering drugs in the United States, 1978 through 1988. JAMA.. 1990;263:2185-2188.[Abstract/Free Full Text]

16. Gould AL, Rossouw JE, Santanello NC, Heyse JF, Furberg CD. Cholesterol reduction yields clinical benefit: a new look at old data. Circulation.. 1995;91:2274-2282. [Abstract/Free Full Text]

17. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med.. 1995;333:1301-1307. [Abstract/Free Full Text]

18. Scandinavian Simvastatin Study Group. Baseline serum cholesterol and treatment effect in the Scandinavian Simvastatin Survival Study. Lancet.. 1995;345:1274-1275. [Medline] [Order article via Infotrieve]

19. Ramsay LE, Yeo WW, Jackson PR. Dietary reduction of serum cholesterol concentration: time to think again. BMJ.. 1991;303:953-957.

20. Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ.. 1994;308:367-373. [Abstract/Free Full Text]

21. Robertson I, Phillips A, Mant D, Thorogood M, Fowler G, Fuller A, Yudkin P, Woods M. Motivational effects of cholesterol measurement in general practice health checks. Br J Gen Pract.. 1992;42:469-472. [Medline] [Order article via Infotrieve]

22. Elton PJ, Ryman A, Hammer M, Page F. Randomised controlled trial in northern England of the effect of a person knowing their own cholesterol concentration. J Epidemiol Community Health.. 1994;48:22-25. [Abstract/Free Full Text]

23. Barratt A, Reznik R, Irwig L, Cuff A, Simpson JM, Oldenburg B, Horvath J, Sullivan D. Work-site cholesterol screening and dietary intervention: the Staff Health Heart Project. Am J Public Health.. 1994;84:779-782. [Abstract/Free Full Text]

24. Family Heart Study Group. Randomised controlled trial evaluating cardiovascular screening and intervention in general practice: principal results of British Family Heart Study. BMJ.. 1994;308:313-320. [Abstract/Free Full Text]

25. Hanlon P, McEwen J, Carey L, Gilmour H, Tannahill C, Tannahill A, Kelly M. Health checks and coronary risk: further evidence from a randomised controlled trial. BMJ.. 1995;311:1609-1611. [Abstract/Free Full Text]

26. 1996 Drug Topics Red Book. Montvale, NJ: Medical Economics Company; 1996.

27. Pederson TR, Kjekshus J, Berg K, Olsson AG, Wilhelmsen L, Wedel H, Pyorala K, Miettinen T, Haghfelt T, Faergeman O, Thorgeirsson G, Jonsson B, Schwartz JS. Cholesterol lowering and the use of healthcare resources: results of the Scandinavian Simvastatin Survival Study. Circulation.. 1996;93:1796-1802. [Abstract/Free Full Text]

28. Goldman L, Weinstein M, Goldman P, Williams L. Cost-effectiveness of HMG Co-A reductase inhibition for primary and secondary prevention of CHD. JAMA.. 1991;265:1145-1151.[Abstract/Free Full Text]

This article has been cited by other articles:

				E. L. Navas-Nacher, L. Colangelo, C. Beam, and P. Greenland Risk Factors for Coronary Heart Disease in Men 18 to 39 Years of Age Ann Intern Med, March 20, 2001; 134(6): 433 - 439. [Abstract] [Full Text] [PDF]

				S. M. Grundy Early Detection of High Cholesterol Levels in Young Adults JAMA, July 19, 2000; 284(3): 365 - 367. [Full Text] [PDF]

				J. A. Milner and R. G. Allison The Role of Dietary Fat in Child Nutrition and Development: Summary of an ASNS Workshop J. Nutr., November 1, 1999; 129(11): 2094 - 2105. [Full Text]

				B. M. Psaty, C. D. Furberg, L. H. Kuller, D. E. Bild, P. M. Rautaharju, J. F. Polak, E. Bovill, and J. S. Gottdiener Traditional Risk Factors and Subclinical Disease Measures as Predictors of First Myocardial Infarction in Older Adults: The Cardiovascular Health Study Arch Intern Med, June 28, 1999; 159(12): 1339 - 1347. [Abstract] [Full Text] [PDF]

				L. P. Lowe, P. Greenland, K. J. Ruth, A. R. Dyer, R. Stamler, and J. Stamler Impact of Major Cardiovascular Disease Risk Factors, Particularly in Combination, on 22-Year Mortality in Women and Men Arch Intern Med, October 12, 1998; 158(18): 2007 - 2014. [Abstract] [Full Text] [PDF]

				R. N. Lemaitre, C. D. Furberg, A. B. Newman, S. B. Hulley, D. J. Gordon, J. S. Gottdiener, R. H. McDonald Jr, and B. M. Psaty Time Trends in the Use of Cholesterol-Lowering Agents in Older Adults: The Cardiovascular Health Study Arch Intern Med, September 14, 1998; 158(16): 1761 - 1768. [Abstract] [Full Text] [PDF]

				S. M. Grundy, G. J. Balady, M. H. Criqui, G. Fletcher, P. Greenland, L. F. Hiratzka, N. Houston-Miller, P. Kris-Etherton, H. M. Krumholz, J. LaRosa, et al. Primary Prevention of Coronary Heart Disease: Guidance From Framingham : A Statement for Healthcare Professionals From the AHA Task Force on Risk Reduction Circulation, May 19, 1998; 97(18): 1876 - 1887. [Full Text] [PDF]

				J. I. Cleeman and S. M. Grundy National Cholesterol Education Program Recommendations for Cholesterol Testing in Young Adults : A Science-Based Approach Circulation, March 18, 1997; 95(6): 1646 - 1650. [Full Text]

				J. C. LaRosa and T. A. Pearson Cholesterol Screening Guidelines : Consensus, Evidence, and the Departure From Common Sense Circulation, March 18, 1997; 95(6): 1651 - 1653. [Full Text]

This Article Extract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Garber, A. M. Articles by Browner, W. S. Search for Related Content PubMed PubMed Citation Articles by Garber, A. M. Articles by Browner, W. S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL