For patients with known cardiovascular disease (secondary prevention), cholesterol lowering leads to a consistent reduction in total mortality and recurrent cardiovascular events in men and women and in middle-aged and older patients. Among patients without cardiovascular disease (primary prevention), the data are less conclusive, with rates of cardiovascular events, heart disease mortality, and all-cause mortality differing among studies. Nonetheless, treatment guidelines have been designed to assist clinicians in selecting patients for cholesterol-lowering therapy based on their overall risk of developing cardiovascular disease.
The two main lipids in blood are cholesterol and triglyceride. They are carried in lipoproteins, globular particles that also contain proteins known as apoproteins. Cholesterol is an essential element of all animal cell membranes and forms the backbone of steroid hormones and bile acids; triglycerides are important in transferring energy from food into cells. Why lipids are deposited into the walls of large and medium-sized arteries—an event with potentially lethal consequences—is not known.
Lipoproteins are usually classified on the basis of density, which is determined by the amounts of triglyceride (which makes them less dense) and apoproteins (which makes them more dense). The least dense particles, known as chylomicrons, are normally found in the blood only after fat-containing foods have been eaten. They rise as a creamy layer when nonfasting serum is allowed to stand. The other lipoproteins are suspended in serum and must be separated using a centrifuge. The densest (and smallest) family of particles consists mainly of apoproteins and cholesterol and is called high-density lipoproteins (HDL). Somewhat less dense are the low-density lipoproteins (LDL). Least dense are the large, very-low-density lipoproteins (VLDL), consisting mainly of triglyceride. In fasting serum, most of the cholesterol is carried on LDL particles and is therefore referred to as LDL cholesterol; most of the triglyceride is found in VLDL particles. Specific apoproteins are associated with each lipoprotein class.
Chylomicrons are made in the gut and travel via the portal vein into the liver and via the thoracic duct into the circulation (eFigure 28–1). They are normally completely metabolized, transferring energy from food into muscle and fat cells. The liver manufactures VLDL particles from its own stores of fat and carbohydrate. VLDL particles transfer triglyceride to cells; after losing enough, they eventually become LDL particles, which provide cholesterol for cellular needs. Excess LDL particles are taken up by the liver, and the cholesterol they contain is then excreted into the bile. HDL particles are made in the liver and intestine and appear to facilitate the transfer of apoproteins among lipoproteins. They also participate in reverse cholesterol transport, either by transferring cholesterol into other lipoproteins or directly into the liver.
Metabolism of chylomicrons. (TG, triglyceride; CE, cholesteryl esters; A-I, A-II, B-48, and C proteins, apolipoproteins.) See text for details. (Reproduced, with permission, from Greenspan FS, Strewler GJ [editors]. Basic & Clinical Endocrinology, ...