ABSTRACT
One of the major risk factors for cardiovascular disease involves elevated levels of cholesterol-containing lipoproteins in the blood. Individuals who are hyperlipidemic or dyslipidemic are at a much higher risk of heart and related diseases. The atherogenic profile consists of the triad: (1) elevated LDL, (2) low HDL, and (3) elevated triglycerides. This lipid profile is also seen in patients with metabolic syndrome. The processing, distribution, and synthesis of cholesterol involve complex processes that include a host of lipoproteins. LDL, HDL, and the liver are central to maintaining cholesterol homeostasis. Genetics, diet, physical activity, and other factors are critical in maintaining a healthy lipoprotein profile. When lifestyle changes are inadequate to correct lipoprotein abnormalities, drug intervention is needed.
Four major classes of lipid-modifying agents are commonly used. Statins block HMG-CoA-reductase and decrease the production of cholesterol, ultimately decreasing the formation of LDL. The decrease in cholesterol synthesis makes cells more dependent on LDL uptake from the blood, decreasing LDL levels further. A resulting increase in reverse cholesterol transport back to the liver causes an increase in HDL levels. Niacin decreases release of VLDL from the liver. It inhibits the lipase activity in adipose tissues, decreasing free fatty acid release and slowing the formation of lipoproteins in the blood. Fibrates stimulate lipoprotein lipase in the vascular lining, leading to the breakdown of triglycerides. Fibrates also increase the oxidation of free fatty acids in liver and muscle and suppress synthetic pathways, so less VLDL and triglycerides are produced. The fourth class of agents works in the gut. These agents block dietary cholesterol uptake or bind bile acids and increase their rate of excretion. This class of agents is often used in conjunction with one of the other three classes of drugs. Exercise and diet can improve the atherogenic profile by mechanisms similar to those of the lipid-modifying agents. Maintaining a good diet and an active lifestyle can reduce the need for or required dosage of these agents.
