Coronary heart disease (CHD) remains the leading cause of death in the United States in both men and women. In 1998, Berenson et al¹ noted that coronary fatty streaks can be found in as much as 50% of children aged 2 to 15 years, increasing to 85% by the age of 39 years. With the ubiquitous prevalence of this disease into adulthood, it is little surprise that CHD is the number one cause of mortality in the United States. It is therefore imperative that we devise strategies for early diagnosis and treatment to stem this epidemic. 

In this supplement of JAOA—The Journal of the American Osteopathic Association, Robert J. Chilton, DO, Kelly Anne Spratt, DO, and Margo A. Denke, MD, discuss the pathophysiology, diagnosis, and therapeutic options for the treatment of patients with dyslipidemia relative to CHD. 

In the first article, Dr Chilton reviews new concepts pertaining to the pathophysiology of CHD. He highlights the influence of an inflammatory response with the concept of evolving from a vulnerable plaque to a vulnerable patient. The concept of a vulnerable patient expands on the emerging data that suggest a vulnerable plaque is a pro-inflammatory condition to now include a vulnerable myocardium (prone to fatal arrhythmia) and vulnerable blood (prone to thrombosis). This milieu helps define a vulnerable patient and expands the possibility of therapeutic options for the treatment and prevention of CHD. 

In the second article, Dr Spratt discusses several recent clinical trials (ie, the Heart Protection Study [HPS], the Aggressive Lipid Lowering Initiation Abates New Cardiac Events [ALLIANCE], the Pravastatin or Atorvastatin Evaluation and Infection Therapy [PROVE-IT], and the Reversal of Atherosclerosis with Aggressive Lipid Lowering [REVERSAL] that have been published since the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III)² guidelines were established in 2001. 

These newer trials have complemented some older studies (ie, the Post Coronary Artery Bypass Graft [Post-CABG], the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering [MIRACL]) that have suggested that lowering low-density lipoprotein cholesterol (LDL-C) below the recommended goal of less than 100 mg/dL in patients with CHD or its risk equivalent may garner additional benefit. These assertions have recently been endorsed by the National Heart, Lung, and Blood Institute, American Heart Association, and the American College of Cardiology Foundation by recommending modifications to footnote the ATP III algorithm.³ Highlighted recommendations for those at high risk include an option to treat patients at very high risk—even those with a baseline LDL-C level of less than 100 mg/dL—to an LDL-C goal of less than 70 mg/dL. In patients at high risk who have associated high triglyceride concentrations or low high-density lipoprotein cholesterol (HDL-C) levels, consideration can be given to combining niacin or a fibrate with an LDL-C–lowering medication. 

For persons at moderately high risk (two plus risk factors and 10% to 20% 10-year risk), the recommended goal is still an LDL-C level of less than 130 mg/dL, but an LDL-C goal of less than 100 mg/dL is an option and extends to individuals with a baseline LDL-C of between 100 mg/dL and 129 mg/dL. To further the concept that a lower LDL-C level is better will be tested in the near future when the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL), Treating to New Targets (TNT), and Study to Evaluate Additional Reductions of Cholesterol and Homocysteine (SEARCH) are published. 

In the third article, Drs Spratt and Denke discuss the therapeutic options for treating patients with dyslipidemia. The discussion divides the various options into those that primarily target endogenous cholesterol (ie statins, fibric acids, and niacin) and those that target exogenous cholesterol (ie, bile acid sequestrants and the newest option, the cholesterol uptake inhibitor ezetimibe). 

In the fourth article, Dr Denke introduces the concept of coadministration therapy in the treatment of patients with dyslipidemia. Evidence cited in the previous articles suggest that many patients are currently not being treated to their therapeutic goal, whereas newer data suggest that these goals may be lowered even further. Coadministration therapy should be considered to meet the lower therapeutic goals, maintain a low risk profile, and limit side effects. The addition of a bile acid sequestrant to a statin will decrease the LDL-C below the level achieved with either agent alone. The coadministration of a fibrate (fenofibrate) and a statin may benefit those with dyslipidemia represented with multiple lipid abnormalities (ie, elevated triglyceride concentrations and LDL-C levels with low HDL-C levels). The use of the older fibrate gemfibrozil should be generally avoided when coadministration with a statin is suggested. 

The coadministration of niacin with a statin would also lower LDL-C levels to a greater extent than either medication alone but have a high side effect profile. The last combination discussed is the coadministration of the cholesterol absorption inhibitor ezetimibe plus a statin. This combination, as with coadministration of a statin plus a bile acid sequestrant or niacin, can add additional LDL-C lowering capacity beyond that achieved with either medication alone. However, the coadministration of a statin and ezetimibe may be better tolerated than coadministration of a statin and either niacin or a bile acid sequestrant because they both generally have a larger side effect profile. Outcome data on the coadministration of niacin and a bile acid sequestrant,^4,5 niacin and a statin,⁶ and niacin and a fibrate⁷ are limited. Because of a lack of outcome data on any other coadministration therapy, the efficacy of these coadministration regimens have yet to be proven. However, using the surrogate goal of improved LDL-C reduction does give us hope that lower may be better in preventing CHD. 

With the anticipation of new clinical trials and the potential coadministration therapy allowing patients to achieve more rigorous LDL-C goals, the future for the treatment of CHD appears to be promising. This supplement highlights some of the emerging ideas into the diagnosis and evaluation of CHD while suggesting a potential role for more aggressive lipid-lowering options.