Lipid Based Cardiovascular Risk Reduction: Practical Strategies for Special Populations
Highlights from a Roundtable Symposium
Activity Date: October 2002  — Activity Info: Volume 2, (18)
Goals & Objectives | Faculty | Introduction | Full Activity Content | CME Test & Evaluation (CME Expired) | Order Copy of Activity


The National Cholesterol Education program (NCEP) issued new guidelines for managing hypercholesterolemia that focus on lowering low-density lipoprotein cholesterol (LDL-C) as a primary means of reducing coronary heart disease (CHD) risk.1 As established in previous versions of the Adult Treatment Panel (ATP) guidelines, specific LDL-C target levels are set as treatment goals. Establishing such objective goals not only for LDL-C but also general guidelines for other lipid entities, such as triglycerides and high-density lipoproteins, provides clinicians and patients with objective and practical guides to management. In many cases, dietary modification and exercise will be adequate for achieving the target lipid values. However, more patients now require a more aggressive approach involving drug therapy because the new guidelines set below 100 mg/dL LDL-C as the optimal level. In some high-risk cases (eg, patients hospitalized with coronary events), the guidelines recommend immediate use of drug therapy as opposed to an initial trial of diet therapy.

The NCEP guidelines are based on an extensive review of over 1600 primary references. The evidence ranges from the Lipid Research Clinic Program, which provided the first conclusive evidence that reducing LDL-C with cholestyramine reduced risk of CHD (a 2% risk reduction for every 1% LDL-C reduction),2 through more recent studies showing that 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins)3-5 or fibric acid derivatives also showed benefit in primary and secondary prevention.6,7

The new NCEP guidelines are unprecedented in their reliance on the clinical evidence base and are unequivocal in their treatment goals for various lipids. As a result of these treatment goals, the number of patients who qualify for drug treatment nearly tripled, from 13 million to 36 million.8 To assist clinicians in applying the new guidelines to this expanded population, the review article, roundtable discussion, and case study in this issue of Advanced Studies in Medicine will address key issues related to the management of dyslipidemia.

In the roundtable discussion, James M. McKenney, PharmD, an NCEP panelist, pointed out a major shift in the new guidelines: the recognition of certain high-risk patient categories that warrant a more aggressive approach. For example, if patients have type 1 or type 2 diabetes mellitus or have 2 or more risk factors (ie, Framingham-type risk factors) that confer a 10-year risk of more than 20%, they are now considered CHD "risk equivalents." These patients should be managed the same as patients with documented CHD. An LDL-C of 100 mg/dL is the new standard for patients in this newly enlarged high-risk category (Table 1).

According to Dr McKenney, shifting the emphasis from "knowing your number" to "knowing your risk" is a fundamental effect of risk-based treatment. Several recent studies support this concept of aggressively lowering lipids levels in patients in the highest risk categories—including those patients with mild forms of dyslipidemia. The 2001 Diabetes Atherosclerosis Intervention Study, for example, showed that treatment with fenofibrate reduced the progression of atherosclerosis (and presumably CHD risk) in all diabetic patients, including patients with mildly elevated lipid levels.9

The exciting Heart Protection Study offers similar evidence of the broad protective effects of statin therapy in all patients at high risk, again including patients with average-to-low cholesterol levels.10,11 However, this study's results are highly relevant to practicing clinicians because of the size of the undertaking (over 20 000 patients observed for 5 years) and a statistical strength that will allow analysis of specific subsets of previously understudied patient types (eg, women, older people) and outcomes (eg, stroke).

As discussed in this issue's roundtable, the preliminary results from the Heart Protection Study support the concept of aggressively treating all high-risk patients with statins, including patients with LDL-C levels below 130 mg/dL with statins. This study enrolled volunteers aged 40 years to 80 years who were at high risk of CHD (eg, due to prior myocardial infarction, stroke, peripheral vascular disease, or diabetes) but for whom the benefits and safety of cholesterol-lowering therapy were substantially uncertain. Volunteers were given either 40 mg simvastatin or matching placebo tablets and were followed for an average of 5 1/2 years. (The study also evaluated the effects of antioxidant vitamins.) Overall, according to the preliminary data presented at the AHA's 2002 meeting, the statin therapy reduced the risk of heart attacks and stroke by about one third. The benefits were evident not only in women and in people older than 70 years (Table 2), but also in people with "low" cholesterol levels.

Does the new emphasis on risk-driven management mean we should abandon cholesterol measurement altogether? Clearly the answer is no. The cholesterol numbers from the laboratory remain the best guide for identifying risk in patients with no personal or familial history of cardiovascular disease. The numbers provide patients, regardless of their risk factor, and physicians with a tangible guide for treatment and a tool for monitoring progress and encouraging compliance with diet and/or drug treatment. On a population level, the numbers serve as a reminder of what must be done to achieve these newly heightened goals. In the Lipid Treatment Assessment Project, for example, only 38% of the approximately 5000 patients treated in the primary-care setting achieved NCEP-defined cholesterol treatment targets.12 The treatment success rate was only 18% among patients with CHD. One reason for the underaggressive therapy was the clinicians' unwillingness to increase the statin dose.

A main topic of discussion in this issue's roundtable was how to increase success rates in high-risk patients. Increasing the statin dose is one underutilized strategy; combination drug treatment is another. Adding a bile acid resin or niacin to a low-dose statin may provide the extra push toward attaining the LDL-C goal while minimizing the risk of adverse effects sometimes associated with high-dose statin therapy (eg, myositis and liver enzyme elevations). Importantly, the new generation of high-affinity bile acid sequestrants, such as colesevelam, do not provoke the range of gastrointestinal adverse effects associated with the older agents in this class. In a recent clinical trial discussed in this issue's roundtable, colesevelam combined with low-

dose atorvastatin provided a reduction in LDL-C that was essentially equivalent to that provided by 80 mg atorvastatin.13 Additional benefits in terms of high-density lipoprotein increases and triglyceride reduction were also noted.

The new NCEP guidelines and the major clinical trials published in 2001 provide guidance on achieving lipid goals in specific patient types. The discussion and background information provided in this issue of Advanced Studies in Medicine will help to clarify the clinical implications of this new information-especially as it relates older people, women, and patients with diabetes.


1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.
2. Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial results, II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA. 1984;251:365-374.
3. Pedersen TR, Olsson AG, Faergeman O, et al. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation. 1998;97:1453-1460.
4. The West of Scotland Coronary Prevention Study Group. Baseline risk factors and their association with outcomes in the West of Scotland Coronary Prevention Study. Am J Cardiol. 1997;79:756-762.
5. Sacks FM, Moye LA, Davis BR, et al. Relationship between plasma LDL concentrations during treatment with pravastatin and recurrent coronary events in the Cholesterol and Recurrent Events trial. Circulation. 1998;97:1446-1452.
6. Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia. N Engl J Med. 1987;317:1237-1245.
7. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999; 341:410-418.
8. NCEP issues major new cholesterol guidelines [news release]. Bethesda, Md: National Heart, Lung, and Blood Institute, National Institutes of Health; May 15, 2001.
9. Diabetes Atherosclerosis Intervention Study Investigators. Effect of fenofibrate on progression of coronary artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomized study. Lancet. 2001; 357:905-910.
10. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360(9326):7-22.
11. Plutzky J. The heart protection study and other developments in atherosclerosis. American Heart Association Scientific Sessions 2001; Day 5, November 15, 2001. American Heart Association Web site. Available at: cfm?story_id=2549. Accessed July 9, 2002.
12. Pearson TA, Laurora I, Chue H, Kafonek S. The Lipid Treatment Assessment Project (L-TAP). Arch Intern Med. 2000;160:459-467.
13. Hunninghake D, Insull W, Toth P, et al. Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively. Atherosclerosis. 2001;158:407-416

*Professor of Medicine and Pediatrics; Director, Lipid Clinic; Chief, Lipid Research, Johns Hopkins University Hospital, Baltimore, Maryland.

Home | Contact Us | View Account | Need Help?