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Case reports play an important role in disseminating information to the medical community. Given the wide variety of naturopathic clinical practice, case reports offer an excellent opportunity to share clinical insights from naturopathic doctors. Typically, unique and rare events or patterns are depicted regarding different aspects of a case, including: symptomatology, pathophysiology, treatment(s), and outcome, including adverse effects. In this paper we elaborate on what a case report is, why one is conducted, and provide a brief set of guidelines on how one is written. We hope to encourage clinicians to write case reports and to submit them for publication. The case report is a well-respected venue for sharing valuable knowledge and generating questions derived from practice. The production of this form of clinically relevant evidence should be actively encouraged within the naturopathic community.

The peer-reviewed medical literature contains articles that cover virtually all topics within medicine including research on therapies used by naturopathic doctors (NDs). The literature is growing at an incredible rate and there is plenty of opportunity for both dedicated researchers and clinicians to participate in this process. Complex studies such as randomized controlled trials, systematic reviews, and large observational trials can be daunting to the practitioner who has little training in research methodology and too little time. The role of the clinician in private practice is critical, however, for the introduction of important clinical information from the ground up. The strength of case reports and case series is primarily in their ability to inject new information into the medical consciousness and to generate hypotheses that can be tested in controlled studies.

Case reports provide a level of evidence that is often a starting point for further research. A classic example is the drastic teratological adverse effect of thalidomide on fetal development. A single case report opened the eyes of the medical community in the late 50s when thalidomide was being touted as an effective treatment for nausea and vomiting of pregnancy. This case report opened a floodgate of responses and the publication of further case reports that quickly led to the drug being pulled from the market (1). Ironically it is through the publication of case reports that thalidomide has been brought back into usage more recently as a treatment for certain dermatological pathologies (2).

Naturopathic medicine incorporates an incredibly wide array of modalities often combined in unique ways. The holistic, individualized and eclectic ‘nature’ of naturopathic medicine makes the case report an ideal place to showcase the benefits and also the potential adverse events that can occur within its bounds. The intent of this article is to provide an overview of a case report, the reasons for writing one, and guidelines for writing and publishing such a report. We hope that this paper offers motivation and some of the tools necessary to carry out this process. The clinician who sees patients regularly is intimately aware of what works in practice. This shared knowledge is a resource that can benefit clinicians, the profession and ultimately our patients. The case report is a well-respected medium that should be encouraged so that valuable information is not limited to a few practitioners, but can be widely disseminated amongst colleagues.

Like most colonized countries in the Western world, Australia has a history of natural medicine use that dates back to the first settlement (by the British in 1788). The Government physician on the first fleet was quick to cultivate a physick or medicinal plant garden to provide medicines for all manner of ailments experienced by the government authorities as well as the convicts who established the first settlement. Of course, the original inhabitants of the country, the aborigines, had their own unique natural healing methods that included herbal treatments, food therapy and shamanic practice. Over the first one hundred years of settlement in Australia, herbal medicine, homeopathy and traditional Chinese medicine formed the greater part of early health care for the inhabitants. “Naturopathy” as such, didn’t really become an entity until the late 1960s to early 1970s, although nature cure practitioners did exist during the early part of the 20th century. Today, naturopathic medicine is second only to chiropractic as the most popular form of natural medicine health care in Australia. It is estimated that around 64% of Australians currently use natural medicine health care, whether that is through consultations with natural medicine practitioners or self-medication. They spend over AUS$2 billion annually on natural medicine treatments. This is more than the amount spent on over-the-counter pharmaceutical drugs in Australia each year. Growth of natural medicine usage has been quite significant, increasing from around 22% in 1986 to 50% in 1995, through to more than 60% in 1998. A study conducted in 1997 suggested that there were three main reasons why Australians were turning to natural medicine health care. These were:

Unlike North America, naturopathic practitioners are not registered or licensed by State legislation. Statutory regulation exists for chiropractic and osteopathy and, in one state of Australia, for Chinese medicine. The naturopathic profession is self-regulated, meaning that professional associations monitor the practice and training of practitioners. In reality this means that anyone, regardless of their level of education or training can use the title “naturopath” and practice as a naturopathic physician. As more Australians use natural medicine treatments for the maintenance and improvement of their health (often in conjunction with prescribed or over-thecounter pharmaceutical drugs), there is an increasing level of concern by the medical profession and Government about drug interactions and safety of natural therapies. This has raised the question about the need for closer monitoring and regulation by Government, of natural medicine. Currently an enquiry is underway, in one Australian state (Victoria), into the safety of naturopathy and Western herbal Medicine, and the need for statutory legislation to regulate these practices.

First line chemotherapy regimens for colon cancer include FOLFOX (leucovorin, 5-fluorouracil, and oxaliplatin). This combination of medications, more significantly oxaliplatin, has been linked to peripheral neuropathy. For patients with previous active lifestyles, peripheral neuropathy can cause a decreased quality of life. In addition, there are many other side effects of FOLFOX including nausea, diarrhea, and weight loss. Significant peripheral neuropathy in patients undergoing FOLFOX therapy may occur spontaneously after oxaliplatin infusions are discontinued. Current literature supports the need to clinically evaluate peripheral neuropathy in patients undergoing FOLFOX chemotherapy, but few studies have shown an effective way to treat the peripheral neuropathy experienced by many patients. Standard of care for chemotherapyinduced peripheral neuropathy (CIPN) includes dose reduction and/or discontinuation of the suspected neurotoxin. Such dose-limiting effects are poor prognostic indicators and often negatively affect a patient’s long-term survival.

Patient H is a 43-year-old male diagnosed with stage IV colon cancer in December 2003. After H was diagnosed he was treated with 20 cycles of FOLFOX (December 2003-October 2004). The FOLFOX was tolerated moderately well. The oxaliplatin dose was 85 mg/ m2 throughout the 20 cycle course. In February 2004, before the fifth cycle of FOLFOX, the oncologist referred H to the Integrative Medicine clinic; the referral was due to H’s desire to continue with the chemotherapy protocol with goals including weight optimization and alleviation of side effects from the medications causing decrease in daily activities and decreased quality of life.

The Integrative Medicine clinic is staffed with an internist, naturopathic doctors, acupuncturists, massage therapists, and a nutritionist. H saw Dr. Ken Weizer, a board certified Naturopathic Doctor (ND). H presented with chief complaints of weight loss over two months totaling 10% of body weight, nausea, diarrhea, and peripheral neuropathy. On exam, chemotherapy-induced peripheral neuropathy (CIPN) presented as paresthesia in the fingertips for 2-3 days post chemotherapy before complete resolution. However, the CIPN by the ninth cycle of FOLFOX was lasting a full week after chemotherapy treatments and the paresthesia progressed to include all fingers and toes. The CIPN subsequently progressed from the tips of the fingers and toes to involving the entire digits with mild to moderate pain and was affecting the patient’s activities of daily living (ADL). The CIPN associated with oxaliplatin is cumulative and dose dependent. The CIPN was graded using a subjective pain scale and through patient interview with specifics determined regarding location, duration, and effects on ADLs. There is controversy regarding the most sensitive scale to evaluate peripheral neuropathy, and many of the scales do not take into account ADLs,3 therefore in H’s case, no objective scale was used to evaluate the neuropathy.

The authors assessed the diet and exercise habits and perceived barriers to following a healthy lifestyle of 471 college students. Sixty percent of the participants were female and 31% had BMIs > 25. Breakfast was the most commonly missed meal and 63% of students snacked one to two times per day. Fifty-eight percent of participants ate vegetables and 64% ate whole or canned fruit less than once per day. Men consumed more soda and alcohol and used higher fat dairy, ate more meat, and ate fewer vegetables and fruits than women. Over half of the subjects rated their diet as poor or fair with “lack of time” listed as the number one barrier to eating well. Men exercised more frequently and at greater intensity than women and were more confident with their body image. The most common barrier to exercise was “lack of time.” The results of this study have implications for the design of general and specific diet and physical activity interventions among college students.

Introduction

Introduction
Diet related diseases including cardiovascular disease, cancer, and stroke are consistently among the top three leading causes of death (American Cancer Society, 2000). A new report, issued by the Institute of Medicine (IOM) of the National Academy of Sciences, suggests that to save the most lives from chronic disease, policy makers, health care providers and researchers should focus their efforts on helping people to stop smoking; maintain a healthy weight and diet; exercise regularly; and drink alcohol at low to moderate levels (American Cancer Society, 2003). Most college students may not achieve the nutrition and exercise guidelines designed to reduce the risk of chronic disease, typically consuming diets high in fat, sodium, and sugar and low in fruits and vegetables (Anding et al., 2001; Dinger & Waigandt, 1997; Grace, 1997; Hiza & Gerrior, 2002; TLHS, 2000). These poor eating habits may result from frequent snacking, excess dieting, and consumption of calorie dense but nutrient poor snacks and meals, such as those provided by fast food restaurants (Georgiou et al., 1997).

In addition, despite the recognized benefit of exercise, surveys of college students’ health habits indicate that only 35% have a regular schedule of physical activity and that a slightly higher proportion of men (40%) than women (32%) regularly exercise (Pinto et al., 1998). However, college students are at a time and place in their lives where their behavior is conducive to change. In fact, the students’ social role of learner is largely defined by a readiness to change (NIH, 1998). Therefore, college campuses serve as crucial settings to overcome perceived barriers to healthy diet and exercise habits, and implement effective interventions (Wallace et al., 2000). Ideally, if college students make positive changes in exercise and dietary habits, these changes could persist into adult years. The purpose of this survey was to assess the diet and exercise habits and perceived barriers to following a healthy lifestyle of college students and to determine if differences exist by gender. The results may have implications for the design of effective general and gender specific interventions for college students.

Triglycerides are a primary source of energy and their levels in the periphery vary significantly. Historically, it has been understood that high VLDL and triglyceride levels were the result of elevated total cholesterol and lower levels of HDL cholesterol (Ginsberg, 1999; Tulenk & Sumner, 2002), but recent studies have shifted elevated triglyceride levels from an association with CAD to an independent predictor of the disease (Cullen 2000; Ginsberg, 1999; NIH, 2002; Malloy & Kane, 2001;). Furthermore, this independent relationship suggests some triglyceride-rich lipoproteins are atherogenic (Cullen 2000; NIH, 2002), meaning VLDL levels may prove to be a significant risk factor in the future. With hypertriglyceridemia, triglycerides are transferred from VLDL and chylomicrons (cholesterol molecules formed from dietary substrates) to LDL, leading primarily to small dense LDL particles and more CAD (Tulenko & Sumner, 2002).

Triglycerides should be measured after fasting as non-fasting triglyceride and other postprandial measurements are difficult to homogenize and arduous to perform (Sullivan, 2002). Finally, the authors of the ATP-III report set the classification of triglyceride in the following categories: Normal (<150 mg/dL), borderline high (150-199 mg/dL), high (200-499mg/dL), and very high (≥500mg/dL). Chylomicrons are very similar in their structure to VLDL, but are released by the intestinal mucosa cells directly after consuming fat (Tulenka & Sumner, 2002). They are less dense due to their large size (100-500nm) and the amount of triglyceride that is transported in them. Chylomicrons are found in the blood and lymphatic fluid where they serve to transport fat from its port of entry in the intestine to the liver and to adipose tissue. They travel via the lymphatic system and their large size renders penetration of the endothelium improbable. Though chylomicrons are large and rich in triglyceride, they contain only a relatively small amount of protein (Hertz, 1999; Schumaker &, Lambertas, 1992). Once chylomicrons enter the blood. they acquire ApoE and ApoC-II. They gradually reduce in size by lipoprotein lipase which removes free-fatty acids from the triglyceride pool in the cell. Chylomicron remnants are reassembled with endogenous triglyceride and cholesterol esters to form VLDLs (Tulenka & Sumner, 2002). Partially degraded chylomicrons, called chylomicron remnants, probably carry some atherogenic potential (NIH, 2002). The ATP-III does not report guidelines for chylomicron levels. Recently, investigators from the INTERHEART study have demonstrated abnormal lipid levels, when combined with smoking, provide over 90% of the risk associated with CAD (Yusef et al., 2004) and can be generalized globally. The authors of the study suggest that the ApoB/ApoA1 ratio was the most important risk factor for CAD. Previous research suggests that ApoB/ApoA1 has not warranted as much attention of other subfractions of cholesterol and therefore needs further study (Sullivan, 2002). The relative lack of familiarity among professionals regarding the importance of ApoB and ApoA1 levels has been a primary cause of ApoB measurement not prevailing over cholesterol levels as the basis for treatment guidelines. Finally, Sullivan (2002) suggests the stage has not been reached where ApoA1 levels can supersede HDL levels as the basis for treatment guidelines (Sullivan, 2002). INTERHEART is a landmark study that will likely reveal a greater role of the ApoB/ApoA1 ratio in the progression of CAD.

Research scientists have also demonstrated that HDL has at least three distinct subclasses based on particle size. Different subclasses include nascent HDL, HDL2, and HDL3 with nascent HDL being the smaller and more dense followed by HDL3 and HDL2. One study found gender differences were most pronounced for large HDL, with women having a twofold higher (8 vs. 4 micromole/L) concentration of large HDL particles than men. Additionally, the observed differences in males and females large HDL particle size also decreased with age (Freedman et al., 2004). The authors of a similar study found that the antioxidative activity of large HDL was significantly higher than that of small HDL (Kontush, Chantepie, & Chapman, 2003). Numerous small studies suggest greater predictive power for each of the HDL components including the observation that large HDL particles are more cardioprotective. All subclasses of HDL have been demonstrated to have a role in reverse cholesterol transport, but HDL2 seems to have the most protective effect, with recent evidence suggesting that HDL3 may play a role in LDL oxidation that is just as vital (Yoshikawa, Sakuma, Hibino, Sato, & Fujinami, 1997). Finally HDL seems to have an antioxidant, anti-inflammatory, anti-adhesive, anti-aggregatory, and profibinolytic effect that aids in the control of CAD beyond reverse cholesterol transport mechanisms (Tulenko & Sumner, 2002).

The ATP-III recommended ranges for HDL are low (<40 mg/dL) and high (>60 mg/dL). This is a significant change as previous reports also set recommended levels for HDL, but the low designation was set at less than 35 mg/dL (NIH, 2002). Additionally, the third report has removed specific HDL levels for men and women, and made one recommendation of greater than 50 mg/dL.

Another subclass of lipoprotein is VLDL which can be divided into VLDL1 (large and less dense), VLDL2 (smaller and more dense), and VLDL3 (smallest and most dense). Hypertriglyceridemia is associated with an excess of VLDL1 while hypercholesterolemia is associated with excess VLDL2. VLDL is triglyceride rich and contains C-II, ApoE, and ApoB-100. Lipoprotein lipase reduces the size of VLDL through the release of triglyceride creating a smaller, dense and more cholesterol rich lipoprotein. About two-thirds of VLDL passes down the lipoprotein metabolism cascade terminating as LDL (Tulenka & Sumner, 2002). VLDL1 is a key component is what has been called the atherogenic lipoprotein profile, which when combined with small dense LDL, and low HDL, it is theorized to be a significant lipid risk factor for CAD (Austin et al., 1988). Most triglycerides are consumed from food, but during times of decreased caloric intake, the liver produces triglyceride endogenously (Kwiterovich, 1989). The ATP-III reports that VLDL levels should be less than 31 mg/dL.

Previous studies have identified a LDL cholesterol “disconnect” between LDL concentration and the number or size of LDL particles among patients with low levels of LDL cholesterol (Otvos, Jeyarajah, & Cromwell, 2002). The term disconnect suggests a differing risk profile depending on the type of LDL cholesterol measure that is used. Typically many individuals who are considered to have normal levels of LDL cholesterol will screen abnormal using phenotype designation. This difference, or disconnect, may help to explain why myocardial infarction can occur in some people who have normal cholesterol and/or LDL levels. Furthermore, since cholesterol is carried via lipoproteins within the blood in spherical particles, between any two individuals there can be tremendous differences in both the number, size and composition of these particles (Garvey 2003; Tulenko & Sumner, 2002). The implication of this disconnect is that CAD risk between two patients with identical LDL particle number and particle size would be the same, despite differing LDL concentration values (Garvey, 2003; Otvos et al., 2002; Tulenko & Sumner, 2002).

The ATP-III (NCEP) report establishes the following ranges for LDL cholesterol levels: optimal (<100mg/dL), near optimal/above optimal (100-129 mg/dL), borderline high (130-159 mg/dL), high (160-189 mg/dL), and very high (≥190 mg/dL) (NIH, 2002). When risk is very high (two or more additional risk factors of existing heart disease), an LDL goal of <70 mg/dL is a therapeutic option, but lifestyle changes should still be pursued. This therapeutic option extends also to patients at very high risk who have a baseline LDL <100 mg/dL (Grundy et al., 2004). The metabolic balance of lipoproteins which is both vital and dangerous also uses reverse cholesterol transport to lower cholesterol in the periphery (Trigatti, 2005). HDL is synthesized by intestinal mucosal cells and the liver. It contains a small amount of phospholipids and ApoA1 (Tulenko & Sumner, 2002). Research has consistently identified an inverse relationship between HDL levels and CAD incidence. The mechanism for this relationship is still unclear, leading some researchers to suggest that low HDL levels are simply a marker for other lipid abnormalities. While the role of decreased HDL levels in atherosclerosis is still vague, it is considered an independent risk factor for CAD (NIH, 2002). It also has been identified as the greatest predictor, along with ApoA1 as the most important risk factor in patients with existing CAD (Bolibar, von Eckardstein, Assman, &Thompson, 2000; Devroey, 2004). HDL absorbs cholesterol in peripheral cells which enter the core of the cell through the action of lecithin-cholesterol acyltransferase. Inclusion of HDL in risk assessment can greatly enhance risk stratification (Kannel & Wilson, 1992).

LDL ranges in size from the largest and least dense (LDL1), intermediate density and size (LDL2) to the smallest and most dense (LDL3). The ATP-III report states that small LDL particles are formed in large part, although not exclusively, as a response to elevation of triglycerides via the production of very-low density lipoproteins (VLDL) and specifically VLDL1 (Malloy & Kane, 2001; NIH, 2002).

The presence of small, dense LDL particles is associated with more than a three-fold increase in the risk of CAD and is independent of LDL levels (Austin, Breslow, Hennekens, Buring, Willett, & Kraus, 1988). Tulenka & Sumner (2002) further suggest that not all LDL particles are the same and that variations in disease outcomes may by attributable to differences in particle size and number even when LDL levels are the same between patients. The authors of the Physicians Health Study demonstrated that each decrease of eight angstroms in LDL peak particle size was associated with a significant 38% increase in the seven-year risk of myocardial infarction after adjustment for age and smoking status (Lemarche, Lemieux, & Depres, 1999).

The correlation between particle size and CAD may exist because of the physiological properties of smaller particles. Researchers suggests smaller and denser LDL particles are more susceptible to in vitro oxidation and have been shown to be degraded less rapidly (Hsueh & Law, 1998). In addition, smaller particles diffuse more easily into the sub-endothelial space in the periphery. A stronger diffusion gradient would push more particles into the arterial wall, attract more macrophages, and develop more foam cells.

Using gel electrophoresis, previous studies have computed and investigated both LDL peak particle size and the mean LDL particle size (Hsueh & Law, 1998). Mean LDL particle size is determined by computing the relative abundance of each of the LDL subclasses within one individual through a densitometric scan (Hsueh & Law, 1998; Lemarche et al., 1999). The results of these studies have led to the development of two different categories of LDL classification that rely on both peak particle size and LDL subclass distribution (Tulenko & Sumner, 2002). These two designations are Phenotype A and Phenotype B. Phenotype A consists of a predominance of LDL particles of >25.5 nanometers and Phenotype B is defined as the predominance of small LDL particles with diameters However, Cromwell and Otvos (2004) believe it is not clear that small LDL particles are more atherogenic than large ones simply because individuals with small LDL particles also have a higher LDL particle number. The authors further state that LDL particle number measured by nuclear magnetic resonance has consistently been shown to be a strong, independent predictor of CAD. In other words, small dense particles may have been found to be more atherogenic due to a higher number of particles that are typically associated with small dense particles. Also, the combination of the two (high particle number, and small dense particles) may place individuals at more risk than either risk factor alone.

Historically, total cholesterol concentration was used to assess an individual’s risk of CAD (Bowden & Kingery, 2004). Because cholesterol contributes to the buildup of atherosclerotic plaques, an individual’s blood cholesterol concentration could be a way to measure risk for heart disease. Clinical studies are consistent in supporting the projection that for serum cholesterol levels in the 250-300 mg/dl range, each 1% reduction in serum cholesterol level reduces CAD rates by approximately 2% (NIH, 1989a). However, the degree of stenosis and CAD varies between individuals with the same total cholesterol and other lipid levels (Bowden, Kingery, Rust, 2004, Kmietowicz, 1998; Telenko & Sumner, 2002).

Total cholesterol tends to reflect average dietary habits that affect LDL, and can reasonably provide an assessment of CVD risk between participants. Yet, the differences in risk between individuals can be strongly influenced by many additional factors. Therefore the measurement of total cholesterol alone cannot adequately reflect individual risk of CAD (NIH, 2002) and should rarely be used as the sole lipid measure in cholesterol screenings. Other studies have also demonstrated the process of heart disease to consist of many factors that are independent of total cholesterol (Katerndahl & Lawler, 1999). These other risk factors fall into two three broad categories, consisting of blood markers, behavior, and biology. New blood tests that identify increased cardiovascular risk include various subfractions of cholesterol. Many of these new markers relate to the physiological functions of cholesterol and the interaction between these markers and the cholesterol in the periphery.

The generally accepted ranges for total cholesterol levels (NIH, 2002) consist of desirable (<200mg/dL), borderline high (200-239mg/dL), and high (≥240mg/dL). If a patient’s cholesterol level is in the high category, a LDL cholesterol measure should be performed. If the patient is in the borderline high range, another total cholesterol measurement should be taken within eight weeks and the average of the two readings used to guide future decisions (NIH, 2002).

Cholesterol Subfractions
LDL cholesterol accounts for 60-75% of the total serum cholesterol and is the terminal end of in the pathway of lipoprotein metabolism called cholesterol transport. Numerous epidemio-logical, physiological, and animal models have linked high LDL levels to CAD (American Heart Association, 2004; Assman, Cullen & Schulte, 1998; NIH, 1989a; Smith et al., 2004; Stone, 2005). High levels of LDL cholesterol are able to penetrate the porous endothelium of arteries and begin to accumulate if plasma concentrations are abnormal. This natural plaque is eventually converted to unstable plaque increasing the likelihood of rupture and possible thrombosis (NIH, 2002). Accordingly, the greatest absolute diminution of risk can be achieved by the reduction of LDL which may directly lower platelet aggregation, vascular reactivity, and lower cytokine release leading to a further reduction in risk for myocardial infarction (Sullivan, 2002). In fact, when elevated LDL levels are combined with comorbidity factors of smoking and hypertension, this complex explains over 90% of myocardial infarction cases occurring in middle age (Wilhelmsen, 1997). The landmark INTERHEART data suggests that 90% of risk comes from combination of abnormal levels of apolipoproteins found in LDL and smoking. LDL contains ApoB-100 which has been linked to atherogenesis (Yusef, Hawken, Ounpuu, Dans, Avesum, Lanas et al., 2004).

Finally, it should be noted that although LDL lowering therapy is believe to offer the greatest benefit for CAD risk reduction, LDL alone is insufficient to predict CAD incidence and risk stratification. The best risk prediction strategy requires measurement of other cholesterol components and particle size and concentration (Wald, Law, Watt, Wu et al., 1994).

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.