Guidelines for Cholesterol Management
Anumber of clinical trials evaluating risk factors associated with coronary heart disease (CHD), including the role of lipoproteins and lipid metabolism, have established that lowering cholesterol reduces death and myocardial infarction in patients with CHD. The reduced incidence of cardiac events is also well documented in patients without established cardiac disease.
In an attempt to reduce morbidity and mortality associated with coronary heart disease, the National Institutes of Health released new guidelines for the detection, evaluation, and management of high blood cholesterol in adults in May 2001. The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults (known as the Adult Treatment Panel III [ATP III]) includes over 800 references evaluating current scientific information on cholesterol. Leading clinicians and researchers comprising the multidisciplinary expert panel of the NCEP thoroughly reviewed the clinical and scientific rationale for the new guidelines and its recommendations.
ATP guidelines were first issued in 1988 and last updated in 1993. ATP III continues to identify elevated LDL ( low-density lipoprotein) cholesterol as the primary target of cholesterol-lowering therapy. Lowering LDL can reduce the short-term risk of heart disease by as much as 40%. The optimal level of LDL cholesterol is set at <100 mg/dL. The categorical low for HDL cholesterol is raised from <35 mg/dL to <40 mg/dL. The new guidelines also pay more attention to elevated triglyceride levels.
Risk Detection and Prevention
The main conclusion of the report is that Americans with elevated blood cholesterol are not being adequately treated; an estimated 65% of those who should receive cholesterol-lowering therapy are not getting any treatment. Main features of the ATP III report are reviewed below.
Metabolic Syndrome: Elevated low-density lipoprotein cholesterol is the primary target of therapy. Extensive research shows elevated LDL cholesterol is a major cause of coronary heart disease and that LDL-lowering therapy reduces the risk for CHD. An important nuance of ATP III vs. ATP II is recognition of the metabolic syndrome, which manifests as hypertension, abdominal obesity, hyperglycemia, elevated triglyceride (TG) levels, and low levels of high-density lipoprotein (HDL) cholesterol. This set of findings addresses lipid abnormalities thought to arise from insulin resistance that go beyond elevated LDL cholesterol. Treatment includes weight management, increasing the patient’s level of physical activity, and antihypertensive therapy. Aspirin to reduce prothrombotic state in CVD patients, and treatment for elevated triglycerides and/or low high-density lipoprotein cholesterol are also recommended.
| Table 1. ATP III Classification of LDL, Total, and HDL Cholesterol (mg/dL)* | |
| LDL Cholesterol | |
| <100
100-129 130-159 160-189 >=190 |
Optimal
Near or above optimal Borderline high High Very high |
| Total Cholesterol | |
| <200
200-239 >=240 |
Desirable
Borderline high High |
| HDL Cholesterol | |
| <40
>=60 |
Low
High |
| *ATP = Adult treatment panel; LDL = low-density lipoprotein; HDL = high-density lipoprotein | |
Risk Assessment
Since assessing risk is the first step in risk management, a method of prospectively estimating absolute risk in patients without clinical coronary disease is emphasized. When counting the major risk factors and estimating the 10-year CHD risk, patients with an absolute 10-year risk of 20% for developing clinical coronary disease are considered candidates for very aggressive therapy (LDL cholesterol treatment goal of <100 mg/dL and a recommendation to initiate drug therapy at an LDL level of >130 mg/dL). Somewhat less aggressive therapy is recommended for patients with an estimated absolute risk of 10%-20% (pharmacotherapy is suggested to keep low-density lipoprotein levels <130 mg/dL). The risk is calculated on a modified Framingham Risk Prediction Score. An important new feature is that diabetes patients are also candidates for aggressive therapy. Diabetes is no longer considered one risk factor, but rather equivalent to coronary heart disease. Interactions between age and smoking, age and total cholesterol, and systolic blood pressure with treatment were also considered in calculating absolute risk.
Other Risk Factors
ATP III recognizes the role of other risk factors in risk assessment aside from the major ones related to cholesterol levels, cigarette smoking, hypertension, and family history of premature CHD (CHD in male first-degree relative <55 years; CHD in female first-degree relative <65 years; age [men >=45 years; women >=55 years]). Lifestyle risk factors include obesity, physical inactivity, and atherogenic diet; the emerging risk factors consist of homocysteine, prothrombotic and proinflammatory factors, lipoprotein (a), impaired fasting glucose, and evidence of subclinical atherosclerotic disease. When making therapeutic decisions, the presence of these factors may modify clinical treatment.
Older Adults and Women
Many authorities have questioned the importance and effectiveness of treating hypercholesterolemia in the elderly. Although data from clinical trials have shown that older adults benefit from lipid-lowering therapy, ATP III recommends lifestyle modifications in older adults. Careful attention should be given to individual circumstances such as overall health and concomitant illnesses. Age in and of itself is considered a risk factor, but also a modifying factor of increasing levels of total cholesterol. For example, among women aged 40-49 years, a cholesterol level of 200-239 mg/dL adds six points to the prediction score, whereas among women aged 60-69 years, only two points are added. The Framingham Prediction Scores incorporate both these issues regarding age. The sidebar on page 33 reviews special considerations that should be taken in account for different population age groups.
| Table 2. New Features of ATP III: Multiple Risk Factors |
| • Raises persons with diabetes without coronary heart disease, most of whom have multiple risk factors, to the risk level of CHD risk equivalent
• Uses Framingham projections of 10-year absolute coronary heart disease risk (i.e., the percent possibility of having a CHD event in 10 years) to identify certain patients with multiple (2+) risk factors for more intensive treatment • Identifies persons with multiple metabolic risk (metabolic syndrome) as candidates for intensified therapeutic lifestyle changes |
Implementing Treatment in Routine Clinical Practice
Since it is well established that abnormal cholesterol levels cause major morbidity and mortality and that aggressive treatment saves lives, the NCEP guidelines recommend immediate initiation of drug therapy (as opposed to therapy started after a trial in which diet is modified) in high-risk patients with a baseline low-density lipoprotein level >130 mg/dL. This also applies to patients who are hospitalized for major coronary events, since patients who do not start cholesterol-lowering drugs early are less likely to be prescribed them later.
Benefit and Cost-Effectiveness
Lifestyle modifications are the most cost-effective way to decrease coronary heart disease risk, according to ATP III; however, many high-risk patients are candidates for drug therapy. As drug prices decrease (due to competition, generic alternatives), ATP III acknowledges it will become cost-effective to treat lower-risk persons as well.
Conclusion
When cholesterol-lowering agents are being considered, side effects and drug interactions need to be incorporated into the overall risk/benefit equation. The necessary lab data to monitor for safety and effectiveness (e.g., lipid profile, liver enzymes) should not be overlooked when determining the cost-effectiveness of drug therapy. In the long-term care setting, the quality of life vs. length of life dilemma is often grappled with when therapy for hypercholesteremia is discussed. The economic impact of drug treatment is a weighty one, regardless of whether the patient pays out-of-pocket, has insurance or government assistance, or belongs to a managed care organization. Finally, compliance to drug therapy is affected by all of the factors listed in this review. Thus, the NCEP guidelines are welcomed to assist in evaluating the appropriateness of drug therapy to ultimately reduce the morbidity and mortality associated with coronary disease.
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