Does NCEP screening detect abnormal lipoprotein levels?
ACP J Club. 1991 Sept-Oct;115:57. doi:10.7326/ACPJC-1991-115-2-057
Bush TL, Riedel D. Screening for total cholesterol. Do the National Cholesterol Education Program's recommendations detect individuals at high risk of coronary heart disease? Circulation. 1991 April;83:1287-93.
To evaluate the ability of the National Cholesterol Education Program (NCEP) screening recommendations to detect individuals with lipid abnormalities.
Simulated application of the NCEP screening algorithm with data from the Lipid Research Clinics Prevalence Study (LRCPS).
10 North American clinics between 1972 and 1976.
60 502 persons (74% of those invited) answered a questionnaire and gave blood for lipoprotein analysis. A 15% random sample of the participants from visit 1 plus all with elevated total cholesterol (TC) were invited for visit 2; 5857 persons, 20 to 79 years of age, attended.
Description of test and criterion standard
The algorithm for NCEP screening is: All persons ≥ 20 years of age should have total cholesterol (TC) measured. If the level is ≥ 5.17 mmol/L (200 mg/dL), measurement of TC is repeated within 56 days. If the average of the 2 measurements is between 5.17 mmol/L (200 mg/dL) and 6.18 mmol/L (239 mg/dL) and if the participant has coronary heart disease or ≥ 2 risk factors, or if the level of TC at visit 1 is ≥ 6.20 mmol/L (240 mg/dL), a lipoprotein analysis is done. Other individuals are asked to return for screening after 1 year or 5 years.
Lipoprotein analysis, the standard with which TC was compared, was done for every participant at visit 2 of the LRCPS.
Main outcome measures
Identification of participants with low-density lipoprotein-cholesterol (LDLC) ≥ 4.13 mmol/L (160 mg/dL) or with high-density lipoprotein-cholesterol (HDLC) ≤ 0.9 mmol/L (35 mg/dL).
Of 5827 persons included in the analysis, 1163 (20%) had LDLC levels ≥ 4.13 mmol/L (160 mg/dL). 81 of these persons had initial or average TC < 5.17 mmol/L (200 mg/dL), and 167 had borderline TC levels with < 2 risk factors. Thus NCEP (TC) screening would have missed 21% of those with high LDLC (sensitivity, 79%).
718 persons (12%) had HDLC levels ≤ 0.9 mmol/L (35 mg/dL). 426 of these had TC levels < 5.17 mmol/L (200 mg/dL), and 49 persons had borderline TC levels with < 2 risk factors. Thus the sensitivity of NCEP screening for low HDLC was 34%. The sensitivity of TC for identifying participants at risk because of either high LDLC or low HDLC was 59%.
41% of those with lipoprotein abnormalities would not be detected using NCEP screening guidelines.
Source of funding: Not stated.
Address for article reprint: Dr. T.L. Bush, Department of Epidemiology, School of Hygiene and Public Health, The Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205.
Should HDL measurement be the first step in strategies for detecting and managing lipid disorders? The National Cholesterol Education Program (NCEP) Adult Treatment Panel guidelines treat a low HDL level as an independent risk factor for coronary disease and use the (calculated) LDLC level to determine treatment cutoff values, but lipoprotein fractionation is only recommended for individuals who are first found to have a high-risk TC level. Some experts claim that this strategy is misguided because HDLC and LDLC levels are stronger predictors of coronary risk than the TC level. Further, many persons with a low HDLC or elevated LDLC level have a "desirable" TC level. On the other hand, fractionation is costlier and often less accurate than TC measurement. Studies that demonstrated that HDLC and LDLC levels have a strong association with coronary risk used highly accurate, well-standardized assays; routine test results from clinical laboratories may not predict risk nearly as well. As the NCEP and others have argued, "accurate and standarized methodology (for HDL measurement) is not widely available in clinical laboratories in the United States...more harm than good could come from inaccuracies in reports of HDL-cholesterol levels" (1). The same concerns apply to the calculated LDLC level.
These two studies add fuel to the controversy over the role of TC in screening for lipoprotein disorders. Using meticulously standarized laboratory data from the Lipid Research Clinics program, Bush and Riedel conclude that the strategy of measuring TC first is too insensitive. They found that nearly half of adults at high risk for coronary heart disease on the basis of their LDLC or HDLC levels and other risk factors would have cholesterol levels too low to trigger fractionation when using the NCEP protocol. The study by Bachorik and colleagues, however, may have more relevance to what occurs in practice. Most Americans will be tested in a doctor's office, hospital, or at a field-testing site, where their lipoprotein levels are likely to be measured with a desktop analyzer or by a laboratory procedure that is far less accurate than the procedures used in the Lipid Research Clinics. Bachorik and colleagues show why it may be premature to use relatively inaccurate procedures for HDLC and LDLC measurement as the initial screening tests for lipid disorders.
Their study evaluates the relationship between the "screening" lipoprotein levels measured on a popular desktop analyzer and "gold standard" levels as measured by their CDC-standardized laboratory procedure. They found large disparities between screening values and laboratory values for both the HDLC and LDLC levels. The screening cholesterol measurements, whether obtained from capillary or venous blood, corresponded more closely to the gold standard values. The accuracy of the screening cholesterol was so much greater that it was as accurate as the screening LDLC level in predicting the "true" LDLC level. Their findings also suggest that the inaccurate LDLC levels would be no better than TC levels as an initial screening test for identifying individuals who should receive treatment.
Although Bachorik and colleagues studied a particular desktop analyzer, annual proficiency surveys of the College of American Pathologists confirm that most laboratories measure TC more accurately than HDLC or triglyceride levels. Only when measurements of HDLC and LDLC levels are both accurate and convenient will they be appropriate initial tests for the detection of lipoprotein disorders.
Alan M. Garber, MD, PhD
Stanford University School of Medicine Stanford, California