Cardiovascular (CV) disease continues to be the leading cause of death in the United States. The role of dyslipidemia in the pathogenesis of CV disease has been well documented, but lipid-lowering treatments were limited until the discovery of 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase in-hibitors in the 1970s. HMG-CoA reductase inhibitors, commonly referred to as statins, have since gained popularity for their ability to effectively lower cholesterol levels in patients with CV disease.
Cholesterol is a naturally occurring compound that is essential for the body's normal physiologic processes.1 Dietary cholesterol is ingested mainly through animal products, such as dairy products, meats, and eggs, but is also found in small amounts in plants and fungi. The body can also produce cholesterol on its own in the liver. The biosynthesis of cholesterol is mainly via the entry of acetyl-CoA into the HMG-CoA reductase pathway. The body uses cholesterol to form cell membranes and synthesize steroid hormones. Because cholesterol is largely hydrophobic and is insoluble in blood, it is carried along with fats within molecules coated with proteins, called lipoproteins. Low-density lipoprotein (LDL) cholesterol is commonly referred to as the "bad cholesterol" and is thought to be one of the main contributors to CV disease. High-density lipoprotein (HDL) cholesterol is commonly referred to as the "good cholesterol" because it is believed that HDL works to remove excess cholesterol from the blood and sends it back to the liver for removal from the body.2
In the United States, more than 30% of the population has elevated LDL cholesterol, a known risk factor for CV disease.3 In addition, CV disease is the leading cause of death in adult women in the United States.4 Hypercholesterolemia has been directly linked to numerous CV diseases, including angina pectoris, myocardial infarction (MI), transient ischemic attack (TIA), stroke, and peripheral artery disease.
Statins are naturally occurring compounds that are used by microorganisms to defend themselves from other organisms by inhibiting the production of mevalonate, a required precursor for the production of cholesterol, which is a key ingredient of cell walls. Research using the mold Aspergillus terreus led to development of the first commercially marketed statin, lovastatin.5 Today, many different statins and statin combinations are marketed in the United States for the treatment of hypercholesteremia. Some statins are fermentation-derived and some are synthetic, but each molecule's unique chemical structure affects its potency and other chemical characteristics, such as lipophilicity and side-effect profile. Statins work to lower LDL cholesterol by competitively inhibiting HMG-CoA reductase. The effect of this decreased intracellular cholesterol level causes hepatocytes to increase production of LDL receptors, which increases clearance of LDL cholesterol from the body. Statins have a favorable side-effect profile; the most commonly occurring adverse events are elevated liver enzymes and myopathy. Rarely, statins may induce rhabdomyolysis that can precipitate acute renal failure.1
Statins have become the most commonly prescribed medication for the treatment of hypercholesterolemia because of their efficacy in lowering LDL cholesterol and their favorable safety profile. The rate of statin use among high-risk patients in the United States increased from 4% in 1992 to 19% in 2002.6 Commonly, initiation of treatment with statins lowers LDL cholesterol by an average of 1.8 mmol/L, which yields a 60% decrease in cardiac events and a 17.5% decrease in risk of stroke.7 In addition, A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID) showed that achieving lower-than-target LDL values through aggressive treatment with rosuvastatin produced disease regression within the coronary arteries.8
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