The science of cardiovascular medicine and pharmacologycontinues to evolve and advance at a dizzyingpace. The National Cholesterol Education ProgramAdult Treatment Panel III's (NCEP ATP III) recently updatedguidelines, published in the July 13, 2004, issue ofCirculation, are based on the latest advancements in lipidmedicine and preventive cardiovascular pharmacy.
It has been a mere 3 years since the NCEP guidelines werelast reviewed, but the recent clinical trials forced a reevaluationof the data. The updated recommendations have beenendorsed by 3 of the most respected organizations in medicine:the American College of Cardiology, the AmericanHeart Association (AHA), and the National Heart, Lung, andBlood Institute.
The summary of the data indicates that the lower thelow-density lipoprotein (LDL) cholesterol for high-riskpatients the better the cardioprotective benefits. These benefitsinclude a theoretical improvement in vascular stability.
The updated guidelines reflect the results of 5 major studieson statin intervention that displayed a log-linear correlationbetween LDL cholesterol level and coronary heartdisease (CHD) risk. Importantly, no lower threshold of LDLcholesterol was identified, indicating that lower LDL cholesterollevels in very-high-risk patients are an importantnew target for clinicians and patients to appreciate.
Scott Grundy, MD, PhD, chairman of the ATP III and anAHA representative to the NCEP, stated, "The lower the betterfor high-risk people." At the same time, he added,"There is strong supportive evidence that lower LDL cholesterolis better, but it has to be balanced against cost andside effects of achieving very low levels, which oftenrequires high doses of medication or combination therapy."He also emphasized that therapeutic lifestyle changes(TLCs) have a significant benefit and remain the foundationof lipid management and cholesterolemia prevention.
Highlights of the Guidelines
• Emphasis is placed on the importance of TLCs as foundationtherapy for lipid management to provide significantbenefit beyond the lowering of LDL cholesterol(reduce inflammation, decrease triglycerides, increasehigh-density lipoprotein [HDL] cholesterol, improveblood sugars, etc)
• Drug therapy is recommended for all high-risk patientswith LDL cholesterol levels of ≥100 mg/dL (the previousguideline indicated LDL cholesterol levels between100 and 129 mg/dL; the use of drug therapy was a therapeuticoption based on clinician judgment, but it hasbeen changed into a firm recommendation to go lower)
• The LDL cholesterol goal of <70 mg/dL has become thenew therapeutic option for very-high-risk patients(including those patients with established cardiovasculardisease and diabetes, patients who have had a recentmyocardial infarction [MI], persistent cigarette smokers,patients with poorly controlled hypertension, orpatients with multiple risk factors related to the metabolicsyndrome)
• The metabolic syndrome has been reemphasized as the"clinical leverage point" in stratifying patients intohigh-risk categories and treating early and more aggressively;all pharmacists should become aware of themetabolic syndrome criteria (Table)
• Utilizing the Framingham Score to estimate theabsolute risk of MI or cardiac death within 10 years forrisk categorization is an important way to targetlifestyle and drug therapy goals
• Moderately high-risk patients are defined as those withmultiple risk factors and an estimated 10% to 20% risk ofMI or cardiac death within 10 years; these individualsshould be treated if LDL cholesterol levels are ≥130 mg/dL;the new recommendation, however, is that drug therapy isoptional if levels are between 100 and 129 mg/dL
• Combination drug therapy may be required to get totarget goals in many patients (even in clinical trialsmany did not achieve the target with single drug therapy;in fact, in most secondary prevention trials achievingLDL cholesterol lowering to <100 mg/dL occurred injust slightly more than half the patients)
• The target LDL cholesterol target remains at 160 mg/dLfor low-risk patients; however, drug therapy usually isrequired for all patients if baseline LDL cholesterol is>190 mg/dL (this very high level indicates an addedgenetic predisposition)
• For every 1% reduction in LDL cholesterol level, a correspondingrelative risk reduction of CHD in a 1:1 ratiois realized; the data show that a 30% to 40% reductionin LDL cholesterol translates to a similar CHD riskreduction over 5 years of treatment
• Non-HDL cholesterol (a surrogate marker for lipoproteinB particles) continues to be an important secondarytarget for cholesterol-lowering therapy, and target endpoints are within 30 mg/dL of LDL cholesterol targetgoals; non-HDL cholesterol is calculated as follows:
Non-HDL Cholesterol =Total Cholesterol-HDL Cholesterol
• Older patients (aged 65-85 years) tolerate statins welland obtain risk reduction similar to younger patients;however, risk analysis is not reliable in older patients,and clinical judgment is stressed in the decision tointensify LDL-lowering therapy
• HDL-cholesterol-raising therapy is recommended forpatients with the metabolic syndrome and diabetes;therapeutic options include exercise, smoking cessation,and adjunctive treatment with fibric acid derivatives andnicotinic acid with statin medications; the importanceof recognizing the atherogenic combination of low HDLcholesterol and high triglycerides as 2 components ofthe metabolic syndrome cannot be understated
• All patients with CHD risk should be counseled andempowered with TLCs to minimize CHD riskLDL cholesterol targets have again been lowered, but thischange has to be tempered by the realization that lifestylechanges are foundational therapy for all patients. As medicineand pharmacy continue to advance, the question ofcareful risk benefit analysis for each individual must be considered.The key is an integration of dietary discretion, regularand persistent exercise, and pharmacology utilized carefullyand aggressively for our patients.
Dr. Duggal is medical director of Liberty Bay Internal Medicine inPoulsbo, Wash. He also is a clinical associate professor at theUniversity of Washington.