CLINICAL GUIDELINE, PART 1: Guidelines for Using Serum Cholesterol, High-Density Lipoprotein Cholesterol, and Triglyceride Levels as Screening Tests for Preventing Coronary Heart Disease in Adults

Previous American College of Physicians Guidelines for Screening Low-Risk, Asymptomatic Adults for Cardiac Risk Factors: Serum Cholesterol and Triglyceride Levels

The College previously recommended screening for cardiac risk factors with a total serum cholesterol measurement at least once in early adulthood (at 20 years of age) and at intervals of 5 or more years up to 70 years of age. Screening with triglyceride levels was not recommended. Screening was interpreted broadly, encompassing cholesterol measurement in persons with other illnesses (what some would term “case-finding”).

Current Recommendations and Rationales

1. Patients in whom screening for lipoprotein abnormalities is appropriate should have testing with a total cholesterol level

Tests for the total cholesterol level are convenient and relatively inexpensive. Epidemiologic studies suggest that a low HDL cholesterol level is also an independent risk factor for coronary heart disease [4.5]. An HDL cholesterol level less than 35 mg/dL (0.9 mmol/L) can be considered a factor that places an individual patient at increased risk for coronary heart disease, even if the total cholesterol level is not elevated, and an HDL cholesterol level of 60 mg/dL (1.6 mmol/L) or greater can be considered to be protective against coronary heart disease. Thus, the HDL cholesterol level can aid in risk stratification. Evidence is insufficient, however, to recommend the HDL cholesterol level as an initial screening test because its effect on management is uncertain. The triglyceride level is not recommended for initial screening because there is insufficient evidence that it is a risk factor for coronary heart disease independent of the total and HDL cholesterol levels [4.7].

Total and HDL cholesterol levels should be used only if the laboratory measuring them uses well-accepted procedures to ensure accuracy. For example, the tests either should be standardized against a reference laboratory that participates in the National Heart Lung and Blood Institute-Centers for Disease Control and Prevention Lipid Standardization Program or should meet comparable criteria.

See the related article on pp 505-508 and an editorial comment on pp 513-514.

An individual patient's total cholesterol, HDL cholesterol, and triglyceride levels fluctuate from day to day and week to week. Thus, even in a highly accurate laboratory, the lipoprotein levels measured in specimens obtained from the same patient at different times may differ substantially. Thus it is important to base treatment decisions on the average of measurements from two or more specimens, just as the treatment of high blood pressure is based on the average of several measurements.

2. in patients who are screened for the primary prevention of coronary heart disease, the total cholesterol level should be measured once. Measurement should be repeated periodically if the measured value is near a treatment threshold

Total cholesterol levels are moderately stable over time; therefore, if the total cholesterol level is low (about 160 mg/dL [4.1 mmol/L] or less), the screening test need not be regularly repeated [4.8]. For lipoprotein levels that are closer to a treatment threshold, too little information is available to precisely recommend the frequency of screening. However, retesting about every 5 years is a reasonable rule of thumb.

3. Screening for total cholesterol levels is not recommended for young men (younger than 35 years of age) or women (younger than 45 years of age) unless the history or physical examination suggests a familial lipoprotein disorder or at least two other characteristics increase the risk for coronary heart disease

Because the short-term risk for developing coronary heart disease is low in this group, even among persons with an elevated blood cholesterol level, the potential benefits of cholesterol reduction are small [3.2, 3.3, 3.7, 3.13-3.16]. Furthermore, even if treatment caused no adverse effects, treating patients at such ages would not be cost-effective [4.10]. Because the hypothetical benefits of cholesterol reduction are larger when the underlying risk for coronary heart disease is greater, the potential benefits of cholesterol reduction may justify screening in men and women at younger ages (about 5 to 10 years earlier) if they have at least two risk factors for coronary heart disease or are thought to have familial hypercholesterolemia [4.2], but even in these groups, the potential benefit is small. No randomized clinical trials have provided direct information on the effects of cholesterol reduction in these groups (see Table 1 of the background paper [1]).

4. Screening for total cholesterol levels in the primary prevention of coronary heart disease is appropriate but not mandatory for men 35 to 65 years of age and for women 45 to 65 years of age

With the possible exception of a recent trial of pravastatin in a high-risk population, primary prevention trials have not proven that cholesterol reduction prolongs life in middle-aged men with no history of coronary heart disease [2.5-2.10]. However, these trials have established that cholesterol reduction prevents coronary heart disease and suggest that it prevents death from coronary heart disease [2.4]. Clinical trials in middle-aged women provide no directly applicable evidence. A woman's risk for developing symptoms of coronary heart disease is similar to that of a man about a decade younger, and the association between cholesterol levels and death from coronary heart disease is not as well established for women as for men. Therefore, screening should be considered in order to identify men 35 to 65 years of age and women 45 to 65 years of age who can avert coronary heart disease by lowering an elevated cholesterol level. In this age group, as in others, the presence of additional cardiac risk factors, including a history or physical examination suggestive of familial hypercholesterolemia, is likely to shift the balance toward greater net benefit of therapy [2.8, 3.5, 3.13-3.16] and a more favorable cost-effectiveness ratio [4.10, 4.11]. In all cases, physicians should exercise discretion in deciding whether to recommend measurement of total and HDL cholesterol levels to a patient and should consider the uncertainty about the long-term effects of treatment, the patient's overall cardiac risk, and the patient's preferences.

5. Evidence is insufficient to recommend or discourage screening for the primary prevention of coronary heart disease in men and women 65 to 75 years of age

Although the hypothetical effect of cholesterol reduction on coronary heart disease end points is substantial in this age group [3.4, 3.13], no direct evidence from clinical trials supports this effect [3.1]. In addition, the risk of drug therapy in particular may be heightened by chronic diseases and interactions with other drugs.

6. Screening is not recommended for men and women 75 years of age and older

No clinical trial data are available for this group; because observational data do not confirm that cholesterol is a risk factor for coronary heart disease, there is no evidence of hypothetical benefit [3.4].

7. All patients with known coronary heart disease (history of myocardial infarction, angina pectoris, other evidence of coronary disease) or whose history of other kinds of vascular disease (such as stroke or claudication) places them at high risk for coronary heart disease should have lipid analysis, including but not limited to measurement of total cholesterol levels

Convincing evidence from randomized controlled clinical trials and observational studies suggests that cholesterol reduction can prevent recurrent myocardial infarction and death from coronary heart disease and all causes in persons with a history of coronary heart disease (see Table 1 and Table 2 of the background paper [1]) [2.4, 2.5, 2.7-2.10]. Persons with severe atherosclerotic vascular disease have a similarly high risk for coronary heart disease and are therefore likely to gain similar benefits from cholesterol reduction [2.5]. Cost-effectiveness studies suggest that cholesterol reduction is either highly cost-effective or cost-saving when used for the secondary prevention of coronary heart disease [4.10, 4.11]. Lipid analysis usually includes measurement of HDL and LDL cholesterol levels, which can be used to refine risk classification and help guide the choice of therapy and which can serve as a baseline to monitor response to cholesterol-lowering interventions.

Conclusion

Recommendations for screening will probably change as further data become available, and particularly as evidence accumulates about the long-term risks and benefits of new cholesterol-lowering drugs (especially the 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors), of other treatments to prevent heart disease (such as aspirin and anti-oxidants), and of treatments specifically for women (such as postmenopausal estrogen replacement).

The accompanying background paper [1] describes the supporting evidence for these recommendations; this evidence is also summarized in Table 1. Key features of other North American screening guidelines are shown in Table 2.