Lipoproteins Test Health Article

Definition

Lipids are water insoluble molecules and must be transported in the plasma as macromolecular complexes containing protein called lipoproteins. The lipoproteins are large aggregates (micelles) composed of cholesterol, triglycerides, phospholipids, proteins, and small amounts of carbohydrates. Generally, the core of the lipoprotein contains hydrophobic lipids surrounded by a sheath of protein and lipids arranged with the hydrophilic ends directed outward. Carbohydrates and enzymes are present in the outer sheath. The proteins that become part of the lipoprotein are called apoproteins. Lipoproteins are grouped into four main classes depending upon their density. In order from least to greatest density these are: chylomicrons, very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL).

Purpose

Lipoproteins are measured to classify persons with severe hyperlipoproteinemia or hypolipoproteinemia. The hyperlipoproteinemias result from increased production or decreased clearance of lipoproteins from the blood and may be inherited or secondary to other diseases or conditions. Some common causes of secondary hyperlipoproteinemia include diabetes mellitus, hypothyroidism, biliary cirrhosis, estrogens and pancreatitis. The cholesterol content of the LDL (LDL cholesterol) and HDL (HDL cholesterol) are measured, along with total cholesterol and triglycerides, to evaluate the patient's risk for coronary heart disease. In addition, a subclass of LDL called lipoprotein(a) or Lp(a) may be measured in persons who have a family history of coronary artery disease (CAD) or predisposing risk factors for CAD.

Measurement

Measurement of lipoproteins may be performed by ultracentrifugation of the plasma. When plasma is subjected to very high centrifugal force, the lipoproteins can be separated in a gradient salt solution on the basis of their density. Since the density is directly related to protein content, the lipoproteins can also be separated by electrophoresis.

Electrophoresis is the separation of charged particles in an electrical field and is dependent on the amount and nature of the apoproteins within the lipoprotein. The electrophoretic positions of the lipoproteins are often used to describe them. Thus, HDL is also called alpha-1 lipoprotein, VLDL is called prebeta lipoprotein, and LDL is called beta lipoprotein. Chylomicrons do not migrate and are not given any designation. When one or more plasma lipid levels are extremely elevated or reduced, either of these methods may be used to determine which lipoproteins are abnormal. On the basis of these findings, abnormal lipoproteins are classified into patterns. Since severe disorders of lipoprotein metabolism are often inherited, the abnormal patterns are called phenotypes. There are five abnormal lipoprotein phenotypes (Type I through Type V), each characterized by the presence of an extremely high quantity of one or two lipoproteins. Persons with severe hyperlipoproteinemia often have skin and tissue infiltration of fat deposits, and persons with Type II and Type III are predisposed to premature atherosclerosis owing to high levels of plasma cholesterol. Lipoprotein phenotyping is not performed as a screening test to evaluate risk of coronary artery disease.

Immunological methods are used to measure the quantity of specific apoproteins present in the plasma. Testing for apoA-I and apoB-100 the principal apoproteins of HDL and LDL, respectively is often performed in persons with elevated lipids who have risk factors associated with coronary artery disease. Measurement of a form of LDL, called Lp(a) is performed on these persons as well as on those who have normal lipid levels, but a family history of CAD.

HDL cholesterol is routinely measured along with total cholesterol and triglycerides as a screening test for coronary artery disease. If the total cholesterol is 200 mg/dL or higher the LDL cholesterol is measured. The measurement of HDL cholesterol is based upon the measurement of cholesterol (see entry on lipid tests) under conditions that inhibit the reaction with all lipoproteins except HDL. The measurement of LDL cholesterol involves precipitating the HDL, VLDL, and cholymicrons using antibodies to apoproteins A, and E, followed by measurement of the LDL cholesterol in the supernatant. When the triglyceride concentration is below 400 mg/dL, the LDL cholesterol is often estimated using the Friedewald formula [LDL cholesterol = total cholesterol minus (HDL cholesterol + triglyceride/5)]. It should be noted that this formula will underestimate LDL cholesterol when triglycerides are above 400 mg/dL.