ABSTRACT
CONTENTS Introduction .........................................................................................................183 Targets for Therapy ............................................................................................184 Goals for Therapy...............................................................................................185 Therapeutic Lifestyle Changes .........................................................................186 Pharmacotherapy................................................................................................187 Statins....................................................................................................................189 Bile Acid Binding Resins ...................................................................................194 Nicotinic Acid......................................................................................................197 Fibrates .................................................................................................................199 Cholesterol Absorption Inhibitors ...................................................................200 Other Therapies...................................................................................................202 Selection of Drug ................................................................................................204 Monitoring ...........................................................................................................204 Summary ..............................................................................................................205 References ............................................................................................. 205
Cholesterol is an essential component of mammalian cell membranes and also serves as a source of steroid hormones and bile acids. Although vital for cellular growth and metabolism, its deposition into the arterial wall produces atherosclerosis.1 Cholesterol is transported primarily as cholesteryl ester, which is water insoluble, and therefore must be transported in the water world of the bloodstream in specialized particles called lipoproteins. At least three major classes of lipoproteins are involved in transport
of cholesterol. Very low-density lipoprotein (VLDL) is a triglyceride-rich particle that transports triglycerides (TGs) and cholesterol from the liver. Low-density lipoprotein (LDL) is a cholesterol-rich particle produced by the delipidation of VLDL. LDL transports cholesterol to various tissues including the arterial wall and returns cholesterol to the liver via the LDL receptor. HDL also has a major role in returning cholesterol to the liver as part of the general process known as “reverse cholesterol transport.” There is overwhelming evidence that elevation in LDL-cholesterol (LDL-C) leads to the development of atherosclerosis. There is also strong evidence that elevations in TG and subnormal levels of HDL increase atherosclerotic risk. Atherosclerosis is the single most common cause of mortality in the United States accounting for almost 1.5 million deaths each year.2 Nearly half of these deaths result from coronary artery disease (CAD). Thus treatment of the lipoprotein disorders forms the cornerstone for CAD risk reduction.
