Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)

Scott M. Grundy, M.D., Ph.D.
Director, Center for Human Nutrition
University of Texas Southwestern Medical Center at Dallas
May 15, 2001

Press Conference Remarks

Release of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III)

Good morning. I am pleased to present to you the National Cholesterol Education Program's updated clinical guidelines for cholesterol testing and management. As Dr. Lenfant said, the executive summary of the Adult Treatment Panel (ATP) report will be published in tomorrow's JAMA. The Full Report will soon be published as a government publication and likely as a medical journal publication in the near future.

The Full Report is an evidence-based report. It is extensively referenced from the scientific literature. Recent clinical trials of cholesterol-lowering therapy are particularly featured in the report. The Full Report provides the scientific rationale for the recommendations contained in the Executive Summary.

The new guidelines—known as ATP III— build on previous ATP reports. Because of strong clinical trial evidence, it is now possible to expand the indications for cholesterol-lowering therapy in clinical practice. A brief comparison of ATP III with past reports may be instructive.

ATP I, published in 1988, outlined a strategy for preventing the development of coronary heart disease (CHD) in persons with high levels of serum cholesterol. It focused on preventing CHD in the first place–before any clinical signs of the disease. ATP I identified LDL cholesterol as the primary target of therapy, and it emphasized clinical management of patients with higher levels of LDL cholesterol.

ATP II, published in 1993, affirmed the importance of treating high LDL cholesterol to prevent CHD from developing. In addition, it added a new feature, namely, the intensive management of LDL cholesterol in patients who already have CHD. For these patients it set a lower LDL goal, specifically, a level equal to or less than 100 mg/dL.

ATP III maintains attention on intensive treatment of patients with CHD. But it also adds a new feature. The new focus is on prevention of CHD in persons with multiple risk factors. Many of these persons are at high risk and deserve more intensive intervention than recommended in ATP II.

In ATP III, LDL cholesterol remains the primary target of therapy. LDL is a major cause of CHD, as shown by research in experimental animals, laboratory investigations, epidemiology, genetic forms of hypercholesterolemia, and clinical trials. A key feature of ATP III is the definition of cut points for goals for LDL cholesterol and for initiation of LDL-lowering therapy.

A basic principle of prevention is that the intensity of risk reduction therapy should be adjusted to a person's risk of having a heart attack. For this reason, the first step in selection of LDL-lowering therapy is to assess a person's risk. Risk assessment is done through identification and weighting of risk factors. Besides elevated LDL cholesterol, the major risk factors that affect the treatment of LDL are cigarette smoking, high blood pressure, low HDL cholesterol, diabetes, advancing age, and a family history of early heart disease. Obesity and physical inactivity are also major risk factors for CHD; they are direct targets of treatment and do not change LDL treatment. Also, the risk associated with advancing age is greater in men than in women.

Counting these risk factors is the basis for a first-cut estimate of a person's short-term and long-term risk. The greater the number of risk factors, the higher the risk. The number of risk factors thus sets general goals of therapy. A refined estimate of short-term risk can be made using a tool based on newly analyzed data from the NHLBI's Framingham Heart Study. This tool calculates risk by assigning points to each risk factor according to its severity and adding them. The resulting score enables the physician to determine the likelihood of developing CHD in the next ten years.

ATP III identifies three levels of risk. Highest risk is found in patients with CHD or CHD risk equivalents. A person with a CHD risk equivalent has the same level of risk for a future heart attack or other coronary event as does one who has already suffered from CHD in some form. Several lines of evidence show that a person has a CHD risk equivalent when 10-year risk for heart attack or coronary death is over 20%; this means that over 20 of 100 such indiviudals will have an event within 10 years. The next highest level consists of persons with two or more risk factors. The lowest risk level pertains to those with 0-1 risk factor.

Patients at highest risk have the lowest treatment goal for LDL cholesterol. This is a level less than 100 mg/dL. CHD patients include those who have had a previous heart attack (myocardial infarction), unstable angina, stable angina, or previous coronary procedure like angioplasty or by-pass surgery. Those with CHD risk equivalents include patients with other forms of atherosclerotic disease such as artery disease in the legs, ballooning of the aorta, and disease of the carotid artery producing temporary or permanent stroke. This group was also listed in ATP II. A new addition to the list of CHD risk equivalents is diabetes. This is a major new addition and is justified by recent epidemiological and clinical trial data. A second new addition includes persons with multiple risk factors (other than diabetes) whose 10-year risk is greater than 20%. These persons are detected by Framingham scoring.

Most patients with CHD and/or CHD risk equivalents will require LDL-lowering drugs in addition to an LDL-lowering diet. A drug can be started simultaneously with diet when the LDL cholesterol is above 130 mg/dL. However, the physician must use clinical judgment to decide whether to add an LDL-lowering drug when the LDL cholesterol is between 100 and 129 mg/dL. Most lipid experts favor drug treatment in this category, but some do not.

Persons at next highest risk are those with multiple risk factors. The LDL-cholesterol goal in this group is less than 130 mg/dL. The treatment plan in this group is modified according to a person's LDL levels and 10-year risk. Everyone with two risk factors should get lifestyle therapies, which consist of an LDL-lowering diet, weight control, and increased physical activity. However, the recommended use of drugs is not as broad. If cost were not an issue, everyone with two risk factors would receive drugs to lower their LDL cholesterol to below 130 mg/dL. But to use drugs in everyone with two risk factors might make prevention too costly in some people at low risk.

Consequently, persons with multiple risk factors are divided into higher and lower risk categories. When 10-year risk is between 10 and 20%, drug therapy is justified when the LDL goal of less than 130 cannot be reached by an LDL-lowering diet. However, when 10-year risk is less than 10%, drugs at current prices must be used more selectively.

In persons of still lower risk, that is, in those with 0-1 risk factor, drugs are to be given serious consideration when LDL levels are very high, over 190. However, physicians have the option to consider drugs in such persons when levels are in the range of 160 to 189 mg/dL.

ATP III puts increased emphasis on lifestyle therapies, called therapeutic lifestyle changes—or TLC. There are four components to these changes.

Although many patients with elevated LDL cholesterol can be effectively managed with therapeutic lifestyle changes, drug therapy will be required in addition in many others. Fortunately, we have several classes of drugs for LDL-lowering therapy. First, there are the HMG CoA reductase inhibitors called statins. These drugs lower LDL cholesterol by 25 to 50%. They are largely safe. We now have five major clinical trials that demonstrate the effectiveness and safety of statins for reducing risk for CHD. Not only do they reduce risk for heart attacks, but they also lower risk for strokes and total deaths. These beneficial results have been confirmed in several other studies using statin therapy.

Other classes of drugs are the bile acid sequestrants, nicotinic acid, and fibrates. These drugs are often used in combined drug therapy to enhance the effects of statins.

Another new area of emphasis for ATP III is a condition called the metabolic syndrome. This syndrome consists of a combination of metabolic risk factors occurring in one person. It is closely associated with insulin resistance in which the normal action of insulin is impaired. The risk factors of the metabolic syndrome are overweight and obesity, high triglycerides, low HDL, high blood pressure, high blood glucose, and a tendency to form blood clots. The metabolic syndrome may have a genetic foundation, but it is made worse by overweight and physical inactivity. About one-fourth of American adults have the metabolic syndrome. When the metabolic syndrome occurs with elevated LDL cholesterol, risk for CHD is greatly increased.

After the goals for LDL cholesterol have been achieved, physicians should turn their attention to the metabolic syndrome, if it is present. First line therapy is weight reduction and increased physical activity. This will help to control insulin resistance and will reduce all metabolic risk factors. In addition, each of these risk factors can be treated directly. Drugs can be used to treat high blood pressureCif it is present. Aspirin can help to reduce blood clotting, particularly in persons with established CHD. Finally, drugs can be considered for treatment of high triglycerides or low HDL. Since LDL must be lowered first, the addition of other lipid lowering drugs usually will mean combination therapy with statins.

ATP III guidelines are meant to extend to both sexes, all age groups, and to all racial/ethnic groups. However, there are special considerations for different subgroups. In young adults, cholesterol testing is needed to find persons at high long-term risk. Lifestyle changes are particularly important in this age range. The guidelines apply to both men and women. ATP III does not recommend use of estrogen replacement therapy to lower cholesterol and reduce CHD risk in post-menopausal women. Recent clinical trials have failed to show that estrogen use reduces women's risk for heart disease. Since clinical trials have shown that the elderly benefit from LDL-lowering therapy, they should not be excluded from treatment if they qualify according to the guidelines. In fact, because of the high risk associated with advancing age, many older persons—both with and without CHD—are candidates for intensive LDL-lowering treatment. In ATP III, the guidelines apply equally to all racial and ethnic groups.

Finally, ATP III has tried to place more emphasis on adherence. Lack of adherence is an overriding factor in failure to achieve the benefits of cholesterol lowering in clinical practice. ATP III has made a major effort to assemble the best possible strategies for improving adherence to both dietary therapy and drug treatment. Thank you.

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