Lipoproteins are complexes of lipids and proteins that are essential for transport of cholesterol, triglycerides, and fat-soluble vitamins. Previously, lipoprotein disorders were the purview of specialized lipidologists, but the demonstration that lipid-lowering therapy significantly reduces the clinical complications of atherosclerotic cardiovascular disease (ASCVD) has brought the diagnosis and treatment of these disorders into the domain of the internist. The number of individuals who are candidates for lipid-lowering therapy continues to increase. Therefore, the appropriate diagnosis and management of lipoprotein disorders is of critical importance in the practice of medicine. This chapter reviews normal lipoprotein physiology, the pathophysiology of disorders of lipoprotein metabolism, the effects of diet and other environmental factors that influence lipoprotein metabolism, and the practical approaches to the diagnosis and management of lipoprotein disorders.
LIPOPROTEIN CLASSIFICATION AND COMPOSITION
Lipoproteins are large macromolecular complexes composed of lipids and proteins that transport poorly soluble lipids (primarily triglycerides, cholesterol, and fat-soluble vitamins) through body fluids (plasma, interstitial fluid, and lymph) to and from tissues. Lipoproteins play an essential role in the absorption of dietary cholesterol, long-chain fatty acids, and fat-soluble vitamins; the transport of triglycerides, cholesterol, and fat-soluble vitamins from the liver to peripheral tissues; and the transport of cholesterol from peripheral tissues to the liver and intestine.
Lipoproteins contain a core of hydrophobic lipids (triglycerides and cholesteryl esters) surrounded by a shell of hydrophilic lipids (phospholipids, unesterified cholesterol) and proteins (called apolipoproteins) that interact with body fluids. The plasma lipoproteins are divided into five major classes based on their relative density (Fig. 27-1 and Table 27-1): chylomicrons, very-low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs), low-density lipoproteins (LDLs), and high-density lipoproteins (HDLs). Each lipoprotein class comprises a family of particles that vary in density, size, and protein composition. Because lipid is less dense than water, the density of a lipoprotein particle is primarily determined by the amount of lipid per particle. Chylomicrons are the most lipid-rich and therefore least dense lipoprotein particles, whereas HDLs have the least lipid and are therefore the most dense lipoproteins. In addition to their density, lipoprotein particles can be classified according to their size, determined either by nondenaturing gel electrophoresis or by nuclear magnetic resonance profiling. There is a strong inverse relationship between density and size, with the largest particles being the most buoyant (chylomicrons) and the smallest particles being the most dense (HDL).
The density and size distribution of the major classes of lipoprotein particles. Lipoproteins are classified by density and size, which are inversely related. HDL, high-density lipoprotein; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein; VLDL, very-low-density lipoprotein.
TABLE 27-1MAJOR LIPOPROTEIN CLASSES