The National Institutes of Health (NIH) emphasizes lowering cholesterol as an important aspect of preventing coronary heart disease. In 1985, NIH’s National Heart, Lung, and Blood Institute (NHLBI) initiated the National Cholesterol Education Program (NCEP), which has undertaken a major effort to encourage individuals to measure, track, and reduce their cholesterol levels (notably total and low-density lipoprotein (LDL) cholestrol) with the objective of reducing mortality and morbidity from coronary heart disease. The focus on cholesterol reduction has come at a time when increased emphasis has also been given to modifying other risk factors associated with heart disease such as cigarette smoking and hypertension. One aspect of the efforts to broaden awareness of cholesterol as a risk factor has been to encourage individuals to “know your cholesterol number.” This advice has been heeded by the public. According to data compiled by the Centers for Disease Control and Prevention (CDC) from 47 states and the District of Columbia, the percentage of adults who reported having had their total cholesterol checked in the past 5 years ranged from 56 percent in New Mexico to 71 percent in Connecticut (median across the states sampled: 64 percent). The percentage of persons who had been told their cholesterol is high by a health professional ranged from 14 percent in New Mexico to 21 percent in Michigan (median across the states sampled: 17 percent). For a widespread cholesterol-lowering campaign to be credible, however, test results must be accurate across the diverse devices and settings in which cholesterol is measured. This is because the guidelines for treating elevated cholesterol are predicated on test results that place an individual into different risk categories. In this report, we discuss what is known about the accuracy of cholesterol testing, including how it is measured, factors that hinder accurate measurements, and efforts to improve the accuracy of cholesterol tests. Coronary heart disease is one of the leading causes of death for both men and women in the United States, accounting for 478,530 deaths in 1991, according to the American Heart Association (AHA). Of these deaths, 52 percent were men and 48 percent were women. Approximately 6.3 million people alive today in the United States have a history of heart attack, chest pain, or both; of this group, 44 percent are 60 years of age and older, 25 percent are 40 to 59 years old, and 31 percent are younger than 40. Further, 1.5 million Americans are expected to suffer a heart attack in 1994. The death rate from heart attack in the United States, however, declined 32 percent between 1981 and 1991. Reasons cited as contributing to this decline include improved medical care of patients and preventive measures in the population. AHA estimates that total costs associated with coronary heart disease are $56.3 billion per year. Of this figure, $37.2 billion is spent on hospital and nursing home services, $8.7 billion on physicians and nurses services, and $2.4 billion on drugs. Lost output associated with heart disease is valued at $8 billion. Because of the large sums being spent on treatment, to say nothing of the attendant psychological and social costs, prevention has been emphasized. NHLBI has established several education programs, such as NCEP, to inform the public about different risk factors associated with coronary heart disease and to provide guidelines for reducing risks that are modifiable. Other programs include the National High Blood Pressure Education Program, which began in 1972; the Smoking Education Program (1985); and the Obesity Education Initiative (1991). A consensus development conference of scientific experts brought together by NIH in 1984 concluded that the risk of coronary heart disease is positively related to increased levels of serum cholesterol and that lowering elevated cholesterol levels can reduce coronary heart disease risk for individuals. The conference experts based their conclusions on the accumulated evidence from a large body of epidemiological, animal, metabolic, and clinical studies. Of major importance was the results of the Lipid Research Clinics Coronary Primary Prevention Trial, a large randomized study completed in 1984 that provided evidence that treatment to lower high cholesterol levels in patients can reduce the risk of coronary heart disease. The conference experts further recommended plans for establishing the National Cholesterol Education Program, which began in 1985. NCEP has convened several expert panels and issued a series of guidelines, reports, and educational materials on the management and control of cholesterol for health care professionals and the general public. The program emphasizes two parallel approaches: (1) a clinical approach that attempts to identify and treat individuals who are at high risk and (2) a broader population approach that aims to reduce cholesterol levels for the entire population. Clinical guidelines for reducing elevated cholesterol levels in adults over 20 years of age were first issued by the Adult Treatment Panel in 1987 and were subsequently updated in a second expert panel report in 1993. These guidelines cover the classification of cholesterol, patient evaluation, and dietary and drug treatments. In 1990, NCEP outlined population strategies to lower total and LDL cholesterol by encouraging all Americans to be aware that elevated cholesterol is a potential risk factor for coronary heart disease, have their cholesterol measured at regular intervals, and modify their diet. NCEP published another report in 1991 that addressed cholesterol issues in children and adolescents. It emphasized strategies for encouraging the nation’s youths to reduce their intake of saturated fat and cholesterol as well as identifying and treating those whose high serum cholesterol levels put them at increased risk for heart disease as adults. The recommendations made in NCEP reports are disseminated and implemented through 40 agencies, such as AHA, that conduct health education and information activities. The current NCEP adult treatment guidelines emphasize classification and treatment decisions based on a person’s risk status, which is defined not only by serum cholesterol levels (including total cholesterol and its low-density lipoprotein (LDL) and high-density lipoprotein (HDL) components) but also by what other coronary risk factors are present. Those with symptoms of coronary heart disease or with at least two other coronary heart disease risk factors are considered candidates for more intensive treatment. Hypertension (>140/90 mm Hg, or on antihypertensive medication) Current cigarette smoking Diabetes Family history of myocardial infarction or sudden death before age 55 in father or male sibling, before age 65 in mother or female sibling Age: male >45 years of age or female >55 years of age or postmenopausal and not on estrogen replacement therapy Low HDL cholesterol (<35 mg/dL) A negative risk factor is HDL cholesterol >60 mg/dL. The guidelines recommend that all adults have their total cholesterol measured at least once every 5 years and that HDL cholesterol be measured at the same time. As shown in figure 1.1, adults without evidence of existing coronary heart disease are classified initially into three levels based on total cholesterol levels—desirable (below (<) 200 mg/dL), borderline high (200-239 mg/dL), and high (equal to or above (>) 240 mg/dL). An HDL cholesterol level of less than 35 mg/dL is considered low and a contributing risk factor for coronary heart disease. The cutpoints for total cholesterol are based largely on epidemiological data that have shown that the risk of heart disease increases as cholesterol levels rise. For example, in 361,000 men screened for the Multiple Risk Factor Intervention Trial, those at or above the 90th percentile of total cholesterol, about 263 mg/dL, had a four times greater risk of death from coronary heart disease than those in the bottom 20 percent (< 182 mg/dL). As indicated in figure 1.1, individuals are recommended for a followup lipoprotein analysis depending on an assessment of their total cholesterol and HDL cholesterol levels in conjunction with the presence or absence of other coronary heart disease risk factors. Thus, those who would be candidates for a subsequent lipoprotein analysis include individuals with (1) high total cholesterol (‡ 240 mg/dL), (2) borderline-high cholesterol (200-239 mg/dL) and low HDL cholesterol (<35 mg/dL), or (3) borderline-high cholesterol (200-239 mg/dL), higher HDL cholesterol (>35 mg/dL), and two or more risk factors. Lipoprotein analysis includes measurement of fasting levels of total cholesterol, HDL cholesterol, and triglycerides and the calculation of LDL cholesterol, which is derived by a mathematical formula. The subsequent classification of adults based on LDL cholesterol levels is shown in figure 1.2. NCEP also classifies LDL cholesterol into three levels—desirable (<130 mg/dL), borderline-high risk (130-159 mg/dL), and high risk (>160 mg/dL). Decisions for beginning diet or drug treatment are then based on these levels in combination with other risk factors (see table 1.1). Thus, candidates for diet therapy without known symptoms of coronary heart disease include those with high LDL cholesterol (>160 mg/dL) or those with borderline-high LDL cholesterol (130-159 mg/dL) plus two or more risk factors. NCEP recommends diet therapy as a first line of treatment for most patients except those at particularly high risk who may warrant drug intervention immediately, such as individuals with existing coronary heart disease. NCEP’s recommended step I and step II diets are designed to reduce consumption of saturated fat and cholesterol and to promote weight loss in overweight patients. If diet therapy is ineffective at lowering LDL cholesterol levels, then drug treatment is advised. NCEP has developed a series of guidelines for administering different types of drugs that are available to lower cholesterol. It should be noted that initiating drug treatment commits patients to long-term therapy, which may be for the rest of their lives. Some perspective on what these treatment categories and recommendations mean for Americans can be seen in recently collected, nationally representative data from the first phase of the National Health and Nutrition Examination Survey (NHANES III). These data indicate that the average total serum cholesterol level is 205 mg/dL for men 20 years old and older and 207 mg/dL for women 20 years old and older.