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Hyperlipidemia is an elevation of one or more of the following: cholesterol, cholesterol esters, phospholipids, or triglycerides. Although cholesterol has received much negative press, in normal quantities, it is essential for life. Cholesterol and triglycerides, as the major plasma lipids, are essential substrates for cell membrane formation, steroidal hormone synthesis, and production of bile acids. Effective management of hypercholesterolemia requires understanding the biochemistry of cholesterol and the importance of cholesterol in normal physiology. In recent years, studies have consistently shown that abnormalities of plasma lipoproteins can result in a predisposition to coronary artery disease, pancreatitis, xanthomas, or neurologic disease. Accumulating evidence has linked elevated total and low-density lipoprotein cholesterol (LDL-C) and reduced high-density lipoprotein cholesterol (HDL-C) to the development of coronary heart disease.
Lipids, being water immiscible, are not present in the free form in plasma, but are transported as lipoproteins. Hyperlipoproteinemia describes the increased concentration of the lipoprotein macromolecules that transport lipids in the plasma.(1) Lipoproteins have a lipid core made up of cholesterol esters and triglyceride with an outer hydrophilic shell of phospholipids and unesterified cholesterol. The outer shell has at least one protein that provides a very important ligand for attaching to receptors on cell surfaces. This protein, in very simple perspective, is the delivery address for that specific lipoprotein.(2) Density, composition, and electrophoretic mobility have been used to divide the lipoproteins into four classes: chylomicrons, VLDL, LDL, and HDL.
Chylomicrons are large triglyceride-rich particles containing apolipoprotein B-48, B-100, and E, that transport cholesterol to the liver from cholesterol in the diet and/or from cholesterol synthesized in the intestines. Chylomicrons are normally not present in the plasma after a 12-14 hour fast and are catabolized by the enzyme lipoprotein lipase (LPL). If lipoprotein lipase levels are low, triglyceride levels can be very high.
VLDL or very low-density lipoproteins are formed primarily in the liver, and to a lesser extent, the intestines. VLDL has been subdivided into three classes, and it carries about 10-15 percent of serum cholesterol and most of the triglyceride in the fasting state. VLDL is a precursor of LDL, and VLDL "remnants" may also be atherogenic. VLDL serves to distribute cholesterol and triglycerides to the cells. As VLDL complexes circulate, they become progressively smaller. Metabolism occurs through the action of two enzymes, lipoprotein lipase and hepatic lipase. Drugs that enhance these enzymes hasten the process and are effective in lowering triglyceride levels. Current therapies directed at preventing atherosclerosis do not focus on VLDL, but instead affect elements that are produced by VLDL.(2)
LDL, or low-density lipoprotein, has been further divided into LDL1 and LDL2. LDL2 carries 60-70 percent of the total serum cholesterol. This is considered the "bad" lipoprotein, since the likelihood of atherosclerosis is directly related to the concentration of LDL in the blood. Lowering LDL is the primary target for therapy of hypercholesterolemia.
HDL, or high-density lipoprotein, functions in transporting cholesterol from peripheral cells to the liver. It is often known as the "good" cholesterol, since high levels mean that much of the peripheral cholesterol is being transferred to the liver for disposal.
The most common classification for hypercholesterolemia is the Fredrickson-Levy-Lee Classification of Hyperlipoproteinemia illustrated below:
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