The Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III) presents the National Cholesterol Education Program's (NCEP's) updated recommendations for cholesterol testing and management. It is similar to Adult Treatment Panel II (ATP II)1,2 in general outline and fundamental approach to therapy. It focuses on the role of the clinical approach to prevention of coronary heart disease (CHD).* This report continues to identify low-density lipoprotein (LDL) as the primary target of cholesterol-lowering therapy. Since ATP II, a number of controlled clinical trials with newer cholesterol-lowering drugs have been reported. These trials demonstrated remarkable reductions in risk for CHD, in both primary and secondary prevention. Their results enrich the evidence base upon which the new guidelines are founded.
1. Development of an evidence-based report
The ATP III panel extensively analyzed the results of recent clinical trials whose findings strongly influenced the development of the new guidelines. The panel's major goals were to review the literature objectively and to document and display the scientific evidence for ATP III recommendations. Prior to the appointment of the ATP III panel, the NCEP Coordinating Committee developed a list of important issues for the panel's consideration. This list was presented to the panel, discussed, and modified appropriately. The literature pertaining to each defined issue was identified by the panel members and by a MEDLINE search. Panel members produced a series of issue papers that carefully reviewed the literature; these issue papers became the foundation for writing the first draft of the report. Modifications of drafts were made following review and discussion of additional evidence arising from the literature search. ATP III contains both evidence statements and specific recommendations based on these statements. Each evidence statement is qualified according to category of evidence (A—D) and strength of evidence (1-3), as follows:⇓,⇓
Empirical data provide the foundation for recommendations; but research in the cholesterol field, as in almost any other, generally has addressed large questions and has not necessarily provided answers to every specific question of clinical intervention. Thus, in the panel's view, the general evidence (including type and strength) often fails to carry a one-to-one correspondence with needed specific recommendations. Consequently, ATP III recommendations are based on the panel's best interpretation of the relation between empirical evidence and issues of clinical intervention. The recommendations are crafted in language that best links general evidence to specific issues; they are not qualified quantitatively according to category and strength of evidence, which is implicit in the language of the recommendation. Finally, for complex issues, several evidence statements or recommendations may be grouped together.
This evidence-based report should not be viewed as a standard of practice. Evidence derived from empirical data can lead to generalities for guiding practice, but such guidance need not hold for individual patients. Clinical judgment applied to individuals can always take precedence over general management principles. Recommendations of ATP III thus represent general guidance that can assist in shaping clinical decisions, but they should not override a clinician's considered judgment in the management of individuals.
The ATP III panel played four important roles in forging this evidence-based report. First, it systematically reviewed the literature and judged which reports provided relevant information. Second, it synthesized the existing literature into a series of evidence statements. This synthesis also required a judgment as to the category and strength of evidence. Third, the panel developed recommendations based on the evidence statements; these recommendations represent a consensus judgment about the clinical significance of each evidence statement. Lastly, the panel created an integrated set of recommendations and guidelines based on individual recommendations.
2. Features of ATP III similar to those of ATP I and II
ATP III represents an update of recommendations for clinical management of high blood cholesterol and related abnormalities. It is constructed on the foundation of previous reports, ATP I3,4 and ATP II.1,2 The NCEP periodically produces ATP clinical updates as warranted by advances in the science of cholesterol management. Each report has a major thrust. ATP I outlined a strategy for primary prevention of CHD in persons with high LDL cholesterol (≥160 mg/dL) or in those with borderline-high LDL cholesterol (130-159 mg/dL) and multiple (2+) other risk factors. ATP II affirmed the importance of this approach and added a new feature: the intensive management of LDL cholesterol in persons with established CHD. For CHD patients, ATP II set a new, lower LDL-cholesterol goal of ≤100 mg/dL. ATP III maintains continuity with ATP I and ATP II. Before considering the new constituents of ATP III, some of the important features shared with previous reports are shown in Table I.2-1.
3. New features of ATP III
While ATP III maintains attention to intensive treatment of patients with CHD, its major new feature is a focus on primary prevention in persons with multiple risk factors. Many of these persons have a relatively high risk for CHD and will benefit from more intensive LDL-lowering treatment than is recommended in ATP II. Table I.3-1. shows the new features of ATP III.
4. Relation of ATP III to NCEP's public health approach
To reduce the burden of coronary atherosclerosis in society, LDL-cholesterol concentrations and other CHD risk factors must be kept as near to an optimal level as possible through the public health (population) approach. Lowering LDL-cholesterol levels in the whole population and keeping them low requires adoption of a low saturated fat and low cholesterol diet, maintenance of a healthy weight, and regular physical activity. NCEP has separately produced a Population Panel Report5,6 that outlines a strategy for the public health approach. The population approach for controlling CHD risk factors will, in the long term, have the greatest impact on reducing the magnitude of cardiovascular disease in the United States. Nonetheless, for persons in whom LDL-cholesterol concentrations are significantly elevated, a clinical strategy is also required. NCEP's recommendations for the clinical approach are contained in the Adult Treatment Panel reports. The clinical and population approaches are complementary.7 ATP III updates NCEP's clinical guidelines for cholesterol management. It also attempts to provide a bridge between clinical management and population strategy. Clinical professionals are integral to the public health approach. The clinical approach alone cannot overcome the burden of atherosclerotic disease in the general population. A parallel and simultaneous effort must be made to promote changes in population life habits to retard atherogenesis. The clinical approach can, however, delay or prevent the onset of CHD and prolong the lives of many persons at increased risk.
5. Relation of ATP III to other clinical guidelines
Since the publication of ATP II, other bodies have published guidelines for CHD risk reduction. For persons with established CHD, ATP III recommendations largely match other guidelines. Recent clinical trials confer a strong scientific base for the benefit of cholesterol-lowering therapy in secondary prevention, making it easier to achieve common ground with other guidelines. There is less congruence on guidelines for primary prevention through clinical therapy. Several recent guidelines place almost exclusive priority for treatment on persons at high risk in the short term, (i.e., ≤10 years). This priority is dictated largely by cost considerations, particularly the costs of cholesterol-lowering drugs. ATP III likewise identifies individuals at high short-term risk who need intensive intervention. However, an important feature of the ATP III guidelines (as in ATP I and ATP II) is extension of the clinical approach to the reduction of long-term (i.e., >10-year) risk. By so doing, ATP III links clinical therapy to the public health approach and goes beyond the more restrictive recommendations of some guideline committees. The panel concluded that clinical guidelines should not be truncated to include only persons at high short-term risk. High serum cholesterol itself is a major cause of the build-up of coronary atherosclerosis, and hence of the development of CHD in the long term. For this reason, ATP III stresses the need for long-term prevention of coronary atherosclerosis, as well as short-term prevention of acute coronary syndromes resulting from advanced atherosclerosis.
A comment is required about the relationship of ATP III to what is commonly called global risk assessment for CHD. In recent clinical guidelines, assessment of absolute risk (global risk) for experiencing acute coronary syndromes over the short term (≤10 years) has assumed increasing importance for primary prevention. These estimates provide a guide for selecting persons for clinical intervention. Accordingly, ATP III can be considered the“ cholesterol component” of integrated, short-term risk reduction. At the same time, ATP III can be viewed as a broad-based approach to reducing CHD risk through short-term and long-term control of high serum cholesterol and related disorders of lipid and lipoprotein metabolism. Thus, on the one hand, high serum cholesterol can be identified in the context of global risk assessment that employs all other risk factors. Alternatively, risk assessment can be performed for persons in whom high serum cholesterol and related lipid disorders are detected independently. Thus, ATP III guidelines are designed to be flexible for use in various approaches to primary prevention.
↵ * In ATP III, CHD is defined as symptomatic ischemic heart disease, including myocardial infarction, stable or unstable angina, demonstrated myocardial ischemia by noninvasive testing, and history of coronary artery procedures.