Cardiovascular Therapeutic Applications
Coronary heart disease (CHD), despite tremendous medical and technological advances and clearer insights into the pathogenesis of atherosclerosis, has been the leading cause of death in the United States for over a century [1-4]. Complications from atherosclerotic heart disease are the most common causes of morbidity and mortality in industrialized nations. In fact, the World Health Organization and others project that CHD will become the primary cause of death worldwide by the
year 2020 [5,6]. Several factors have been identified that increase the probability that an individual might develop atherosclerosis [1,7,8]. The major independent risk factors include elevated total and low-density lipoprotein cholesterol (LDL-C) levels, low serum high-density cholesterol (HDL-C) levels, cigarette smoking, hypertension, diabetes mellitus, insulin resistance, and advancing age. Other factors include obesity, physical inactivity, family history of premature cardiovascular disease, ethnicity, elevated serum triglyceride, homocysteine, and lipoprotein(a) [Lp(a)] levels, and the presence of prothrombotic factors such as fibrinogen and inflammatory markers such as C-reactive protein (CRP). These categories can be further subdivided into those that can be modified through various interventions (alterations in lifestyle and diet, or pharmacological agents) and those that cannot. Unmodifiable factors include advancing age, gender, ethnicity, and genetic predisposition. Of those factors that can be modulated, the abnormalities associated with lipid metabolism have been the most extensively studied and therefore, the best understood.