Dyslipidemic drugs are used in the management of patients with elevated blood lipids, a major risk

factor for atherosclerosis and vascular disorders such as coronary artery disease, strokes, and peripheral
arterial insufficiency. These drugs have proven efficacy and are being used increasingly to reduce
morbidity and mortality from coronary heart disease and other atherosclerosis-related cardiovascular
disorders. To understand clinical use of these drugs, it is necessary to understand characteristics of
blood lipids, metabolic syndrome, and types of blood lipid disorders.

Blood Lipids

Blood lipids, which include cholesterol, phospholipids, and triglycerides, are derived from the diet or
synthesized by the liver and intestine. Most cholesterol is found in body cells, where it is a component of
cell membranes and performs other essential functions. In cells of the adrenal glands, ovaries, and
testes, cholesterol is required for the synthesis of steroid hormones (e.g., cortisol, estrogen,
progesterone, testosterone). In liver cells, cholesterol is used to form cholic acid which is conjugated
with other substances to form bile salts; bile salts promote absorption and digestion of fats. In addition,
a small amount of cholesterol is found in blood serum. Serum cholesterol is the portion of total body
cholesterol involved in formation of atherosclerotic plaques. Unless a person has a genetic disorder of
lipid metabolism, the amount of cholesterol in the blood is strongly related to dietary intake of
saturated fat. Phospholipids are essential components of cell membranes, and triglycerides provide
energy for cellular metabolism.

Blood lipids are transported in plasma by specific proteins called lipoproteins. Each lipoprotein contains
cholesterol, phospholipid, and triglyceride bound to protein. The lipoproteins vary in density and
amounts of lipid and protein. Density is determined mainly by the amount of protein, which is more
dense than fat. Thus, density increases as the proportion of protein increases. The lipoproteins are
differentiated according to these properties, which can be measured in the laboratory. For example,
high-density lipoprotein (HDL) cholesterol contains larger amounts of protein and smaller amounts of
lipid; low-density lipoprotein (LDL) cholesterol contains less protein and larger amounts of lipid. Other
plasma lipoproteins are chylomicrons and verylow-density lipoproteins (VLDL).

Metabolic Syndrome

Metabolic syndrome is a group of cardiovascular risk factors linked with obesity. The Third Report of the
National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults (NCEP III) clustered several elements of metabolic syndrome: elevated waist
circumference (central adiposity), elevated triglycerides, reduced high-density lipoprotein cholesterol,
elevated blood pressure, and elevated fasting glucose. These risk factors frequently produce an additive
effect on cardiovascular, cerebrovascular, and peripheral vascular disease and are principal contributors
to the significant morbidity and mortality of these conditions. Improvements in insulin resistance and
lipid profiles are essential lifestyle modifications and constitute firstline treatment of metabolic
syndrome. This chapter specifically addresses management of components of metabolic syndrome
related to dyslipidemia; additional discussion of other factors is found in Chapters 26 and 50.

Dyslipidemia
Dyslipidemia (also called hyperlipidemia) is associated with atherosclerosis and its many
pathophysiologic effects (e.g., myocardial ischemia and infarction, stroke, peripheral arterial occlusive
disease). Ischemic heart disease has a high rate of morbidity and mortality. Elevated total cholesterol
and LDL cholesterol and reduced HDL cholesterol are the abnormalities that are major risk factors for
coronary artery disease. Elevated triglycerides also play a role in cardiovascular disease. For example,
high blood levels reflect excessive caloric intake (excessive dietary fats are stored in adipose tissue;
excessive proteins and carbohydrates are converted to triglycerides and also stored in adipose tissue)
and obesity. High caloric intake also increases the conversion of VLDL to LDL cholesterol, and high
dietary intake of triglycerides and saturated fat decreases the activity of LDL receptors and increases
synthesis of cholesterol. Very high triglyceride levels are associated with acute pancreatitis. Dyslipidemia
may be primary (i.e., genetic or familial) or secondary to dietary habits, other diseases (e.g., diabetes
mellitus, alcoholism, hypothyroidism, obesity, obstructive liver disease), and medications (e.g., beta
blockers, cyclosporine, oral estrogens, glucocorticoids, sertraline, thiazide diuretics, antihuman
immunodeficiency virus protease inhibitors). Types of dyslipidemia (also called hyperlipoproteinemias
because increased blood levels of lipoproteins accompany increased

blood lipid levels) are described in Box 55-2. Although hypercholesterolemia is usually emphasized,
hypertriglyceridemia is also associated with most types of hyperlipoproteinemia.