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C H A P T E R 4 7 Lipid-lowering agents

Risk factors Strong evidence exists that atheroma development occurs more quickly in individuals with elevated cholesterol and lipid levels. People who consume high-fat diets are more likely to develop high lipid levels. However, indi- viduals without increased lipid levels can also develop atheromas leading to CAD, so other factors evidently contribute to this process. Although the exact mecha- nism of atherogenesis (atheroma development) is not understood, certain risk factors increase the likelihood that a person will develop CAD. Metabolic syndrome occurs when a person has several risk factors: increased insulin resistance, high blood pressure, altered lipid levels and a proinflammatory and prothrombotic state, which seem to increase the risk of CAD development dramatically. Unmodifiable and modifiable risk factors are presented in Box 47.1. Different ethnic groups also have different risk factors, as discussed in Box 47.2, as do different genders, as discussed in Box 47.3. Treatment Because an exact cause of CAD is not known, success- ful treatment involves manipulating a number of these risk factors (see Table 47.2). Overall treatment and pre- vention of CAD should include the following measures: decreasing dietary fats (decreasing total fat intake and limiting saturated fats seems to have the most impact on serum lipid levels); losing weight, which helps to decrease insulin resistance and the development of type 2 diabetes; eliminating smoking; increasing exercise levels; decreas- ing stress; and treating hypertension, diabetes and gout. ■■ CAD is the leading cause of death in the Western world. It is associated with the development of atheromas or plaques in arterial linings that lead to narrowing of the lumen of the artery and hardening of the artery wall, with loss of distensibility and responsiveness to stimuli for contraction or dilation. ■■ The cause of CAD is not known, but many contributing risk factors have been identified, including increasing age, male gender, genetic predisposition, high-fat diet, sedentary lifestyle, smoking, obesity, high stress levels, bacterial infections, diabetes, hypertension, gout and menopause. The presence of many of these factors constitutes metabolic syndrome. ■■ Treatment and prevention of CAD are aimed at manipulating the known risk factors to decrease CAD development and progression. KEY POINTS

Cultural considerations

BOX 47.2

FAT AND BIOTRANSFORMATION (METABOLISM) Fats are taken into the body as dietary fats, then broken down in the stomach to fatty acids, lipids and choles- terol (Figure 47.1). The presence of these products in the duodenum stimulates contraction of the gallbladder and the release of bile. Bile acids , which contain high levels of cholesterol (a fat), act like a detergent in the small intestine and break up the fats into small units, called micelles, which can be absorbed into the wall of the small intestine. (Imagine ads for dishwashing detergents that break up the grease and fats in the dishwashing water; bile acids do much the same thing.) The bile acids are then reabsorbed and recycled to the gallbladder, where they remain until the gallbladder is again stimu- lated to release them to facilitate fat absorption. Fats and water do not mix and cannot be absorbed directly into the plasma. To allow absorption, micelles are carried on a chylomicron , a package of fats and proteins. This packaging is done by brush enzymes in Variations in lipoprotein levels Australia and New Zealand both have high incidences of coronary artery disease. Certain risk factors are known to place particular cultural groups at higher risk than national averages. Amongst the ethnic groups in New Zealand, death rates of Pacific people are higher than in Ma– ori in hypertensive disease, cerebrovascular disease and cardiomyopathy (males).The CHD death rate in Ma– ori men has fallen since 1996, but risen in women while rates in Pacific people have increased in both men and women. (Source: www.heartfoundation. org.nz.Technical Report 82: Cardiovascular Disease in New Zealand, 2004: A Summary of Recent Statistical Information.) In Australia, Indigenous Australians have been reported to have three times the rate of death from major coronary events than other Australians. (AIHW 2010. Australia’s health 2010. Cat. no. AUS 122. Canberra: AIHW.) There are identified cultural variations in lipid levels as well. Cultural variations in key lipid parameters have been identified in the specific ethnic groups below; however, currently no data exist for Pacific Islander, Ma– ori people or Indigenous Australians in relation to lipid profiles. Cultural variations in key lipid parameters include the following: • Serum cholesterol levels: whites > African Americans, Native Americans • High-density lipoprotein (HDL) levels: African Americans, Asians > whites • Low-density lipoprotein (LDL) levels: African Americans < whites • HDL: cholesterol ratio: African Americans < whites