According to the American Heart Association [AHA] (2002), more Americans die from CAD every year than the next five leading causes of death combined. One in every 2.5 deaths in the year 2000 was from heart disease (Kohlman-Trigoboff, 2005). Though there has been a decrease in mortality rate in the US, CAD has become a leading cause of global mortality, accounting for almost 17 million deaths annually with nearly 80% of mortality and disease burden occurring in developing countries (Smith, Jackson, Pearson, Fuster, Yusuf, & Faergeman, et al., 2004).

The etiology of CAD is multi-factorial, involving numerous factors including genetics, diet, and environment with several risk factors significantly increasing an individual’s susceptibility to the disease. These risk factors include cigarette smoking, obesity, sedentary lifestyle, dietary habits, homocysteine, high blood pressure, high blood cholesterol and others. However, much of the research into CAD, which has being quite extensive and spanning a number of decades, has focused on the general relationship between plasma lipids and CAD (Gotto, 1997; Kannel, Castelli, Gordon, & McNamara, 1971; McGee, Reed, Stemmerman, Rhoads, Yano, & Feinlab, 1985; NCEP, 2002; NIH, 1989a;). Researchers have suggested that approximately twenty-five percent of the adult population ages twenty and older has blood cholesterol levels that are considered high (National Institutes of Health [NIH], 1989b). In addition, researchers have demonstrated that a total cholesterol level in the “high” category (>200 mg/dL) accompanied with high blood pressure (>130/85) increases an individual’s risk of coronary heart disease by a factor of six (NIH, 1989b). Therefore, establishing specific guidelines for cholesterol levels is both important and necessary to enhance the health of individuals.

Lipoprotein metabolism is a process that is not completely understood with fragmentary findings (Tulenka & Sumner, 2002). Attempting to have a clearer understanding of the relationship between cholesterol levels and CAD, individuals who have abnormal lipid levels can make the lifestyle changes necessary to reduce the risk of CAD and its associated complications. Similarly, adequately informed health professionals are better able to educate the public about cholesterol and heart disease and more equipped to implement effective health intervention programs.

Understanding the pathophysiology of CAD in population studies underlie the vital role of cholesterol metabolism. Protective mechanisms of the endothelium are evident in reverse cholesterol transport performed by high-density lipoprotein (HDL) and conversely low-density lipoprotein (LDL), specifically small, dense LDL, may penetrate the subendothelial space if concentrations are high in the plasma. Penetration of the endothelial space can cause acute and chronic endothelial damage, leading to CAD. Because movement into the arterial wall is likely driven by diffusion, hyper-cholesterolemia increases the infiltration of cholesterol into the endothelial space (Bowden, 2001; Wada & Karino, 1999). In response to this accumulation of cholesterol, macrophages respond to inflammatory markers from inflammatory cells, cytokines, growth factors and cellular responses (Sullivan, 2002) and absorb the cholesterol resulting in the formation of foam cells. Formations of foam cells are critical in the development of plaque in the endothelium (Ockene & Ockene, 1992). As the CAD progresses, lesions may begin to cause chronic injury to the endothelium. This process results in a positive-feedback cycle due to cytokine release that sends even more macrophages to the area, resulting in more foam cells, and eventually results in stenosis and occlusion of blood flow. Fatty streaks are first evident in this disease process followed by fibrous plaques that can develop necrotic cores which develop fissures leading to plague rupture. Hyperlipidemic concentrations also increase platelet aggregability, which attenuate the severity of the thrombotic process (Sullivan, 2002). Therefore, cholesterol metabolism plays a significant role in the development of plaque, stenosis, and eventually, myocardial infarction.