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INTRODUCTION

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Lipoproteins are complexes of lipids and proteins that are essential for the 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 has continued to increase. The development of safe, effective, and well-tolerated pharmacologic agents has greatly expanded the therapeutic armamentarium available to the physician to treat disorders of lipid metabolism. Therefore, the appropriate diagnosis and management of lipoprotein disorders is of critical importance in the practice of medicine. This chapter will review normal lipoprotein physiology, the pathophysiology of primary (inherited) disorders of lipoprotein metabolism, the diseases and environmental factors that cause secondary disorders of lipoprotein metabolism, and the practical approaches to their diagnosis and management.

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LIPOPROTEIN METABOLISM

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LIPOPROTEIN CLASSIFICATION AND COMPOSITION

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Lipoproteins are large macromolecular complexes that transport hydrophobic 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.

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Lipoproteins contain a core of hydrophobic lipids (triglycerides and cholesteryl esters) surrounded by hydrophilic lipids (phospholipids, unesterified cholesterol) and proteins that interact with body fluids. The plasma lipoproteins are divided into five major classes based on their relative density (Fig. 31-1 and Table 31-1): 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 slightly in density, size, and protein composition. The density of a lipoprotein is determined by the amount of lipid per particle. HDL is the smallest and most dense lipoprotein, whereas chylomicrons and VLDLs are the largest and least dense lipoprotein particles. Most plasma triglyceride is transported in chylomicrons or VLDLs, and most plasma cholesterol is carried as cholesteryl esters in LDLs and HDLs.

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Figure 31-1

The density and size distribution of the major classes of lipoprotein particles. Lipoproteins are classified by density and size, which are inversely related. VLDL, very low-density lipoprotein; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein; HDL, high-density lipoprotein.

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Table Graphic Jump Location
TABLE 31-1MAJOR LIPOPROTEIN CLASSES

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