The science of cardiovascular medicine and pharmacology continues to evolve and advance at a dizzying pace. The National Cholesterol Education Program Adult Treatment Panel III's (NCEP ATP III) recently updated guidelines, published in the July 13, 2004, issue of Circulation, are based on the latest advancements in lipid medicine and preventive cardiovascular pharmacy.

It has been a mere 3 years since the NCEP guidelines were last reviewed, but the recent clinical trials forced a reevaluation of the data. The updated recommendations have been endorsed by 3 of the most respected organizations in medicine: the American College of Cardiology, the American Heart Association (AHA), and the National Heart, Lung, and Blood Institute.

The summary of the data indicates that the lower the low-density lipoprotein (LDL) cholesterol for high-risk patients the better the cardioprotective benefits. These benefits include a theoretical improvement in vascular stability.

The updated guidelines reflect the results of 5 major studies on statin intervention that displayed a log-linear correlation between LDL cholesterol level and coronary heart disease (CHD) risk. Importantly, no lower threshold of LDL cholesterol was identified, indicating that lower LDL cholesterol levels in very-high-risk patients are an important new target for clinicians and patients to appreciate.

Scott Grundy, MD, PhD, chairman of the ATP III and an AHA representative to the NCEP, stated, "The lower the better for high-risk people." At the same time, he added, "There is strong supportive evidence that lower LDL cholesterol is better, but it has to be balanced against cost and side effects of achieving very low levels, which often requires high doses of medication or combination therapy." He also emphasized that therapeutic lifestyle changes (TLCs) have a significant benefit and remain the foundation of lipid management and cholesterolemia prevention.

Highlights of the Guidelines

• Emphasis is placed on the importance of TLCs as foundation therapy for lipid management to provide significant benefit beyond the lowering of LDL cholesterol (reduce inflammation, decrease triglycerides, increase high-density lipoprotein [HDL] cholesterol, improve blood sugars, etc)

• Drug therapy is recommended for all high-risk patients with LDL cholesterol levels of ≥100 mg/dL (the previous guideline indicated LDL cholesterol levels between 100 and 129 mg/dL; the use of drug therapy was a therapeutic option based on clinician judgment, but it has been changed into a firm recommendation to go lower)

• The LDL cholesterol goal of <70 mg/dL has become the new therapeutic option for very-high-risk patients (including those patients with established cardiovascular disease and diabetes, patients who have had a recent myocardial infarction [MI], persistent cigarette smokers, patients with poorly controlled hypertension, or patients with multiple risk factors related to the metabolic syndrome)

• The metabolic syndrome has been reemphasized as the "clinical leverage point" in stratifying patients into high-risk categories and treating early and more aggressively; all pharmacists should become aware of the metabolic syndrome criteria (Table)


• Utilizing the Framingham Score to estimate the absolute risk of MI or cardiac death within 10 years for risk categorization is an important way to target lifestyle and drug therapy goals

• Moderately high-risk patients are defined as those with multiple risk factors and an estimated 10% to 20% risk of MI or cardiac death within 10 years; these individuals should be treated if LDL cholesterol levels are ≥130 mg/dL; the new recommendation, however, is that drug therapy is optional if levels are between 100 and 129 mg/dL

• Combination drug therapy may be required to get to target goals in many patients (even in clinical trials many did not achieve the target with single drug therapy; in fact, in most secondary prevention trials achieving LDL cholesterol lowering to <100 mg/dL occurred in just slightly more than half the patients)

• The target LDL cholesterol target remains at 160 mg/dL for low-risk patients; however, drug therapy usually is required for all patients if baseline LDL cholesterol is >190 mg/dL (this very high level indicates an added genetic predisposition)

• For every 1% reduction in LDL cholesterol level, a corresponding relative risk reduction of CHD in a 1:1 ratio is realized; the data show that a 30% to 40% reduction in LDL cholesterol translates to a similar CHD risk reduction over 5 years of treatment

• Non-HDL cholesterol (a surrogate marker for lipoprotein B particles) continues to be an important secondary target for cholesterol-lowering therapy, and target end points are within 30 mg/dL of LDL cholesterol target goals; non-HDL cholesterol is calculated as follows:

Non-HDL Cholesterol = Total Cholesterol-HDL Cholesterol

• Older patients (aged 65-85 years) tolerate statins well and obtain risk reduction similar to younger patients; however, risk analysis is not reliable in older patients, and clinical judgment is stressed in the decision to intensify LDL-lowering therapy

• HDL-cholesterol-raising therapy is recommended for patients with the metabolic syndrome and diabetes; therapeutic options include exercise, smoking cessation, and adjunctive treatment with fibric acid derivatives and nicotinic acid with statin medications; the importance of recognizing the atherogenic combination of low HDL cholesterol and high triglycerides as 2 components of the metabolic syndrome cannot be understated

• All patients with CHD risk should be counseled and empowered with TLCs to minimize CHD risk LDL cholesterol targets have again been lowered, but this change has to be tempered by the realization that lifestyle changes are foundational therapy for all patients. As medicine and pharmacy continue to advance, the question of careful risk benefit analysis for each individual must be considered. The key is an integration of dietary discretion, regular and persistent exercise, and pharmacology utilized carefully and aggressively for our patients.

Dr. Duggal is medical director of Liberty Bay Internal Medicine in Poulsbo, Wash. He also is a clinical associate professor at the University of Washington.