SLCO1B1 Pharmacogenomic Genotyping for Statin Dosing or Selection
Background: Heart disease is the leading cause of death for both men and women, and for people of most racial/ethnic groups in the United States (CDC, 2016). High blood pressure and high low-density lipoprotein cholesterol (LDL-C) are risk factors for heart disease. From 2009 to 2012, more than 100 million U.S. adults who are 20 years of age or older had total cholesterol levels at or above the recommended 200 milligrams per deciliter (mg/dL) upper limit. Almost 31 million had levels at or above 240 mg/dL, the level at which treatment to decrease cholesterol is recommended to begin (Mozaffarian et al., 2016). As cholesterol increases, the LDL-C fraction of total cholesterol contributes to plaque formation and atherosclerosis of artery walls. Over time, plaques can suddenly rupture and trigger clots within an artery opening, or the accumulation of atherosclerosis can narrow or close an artery, both resulting in cardiovascular disease, stroke, and other complications. Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG CoA] reductase inhibitors) effectively lower LDL-C and the risk of major cardiovascular events, and are the most commonly prescribed class of drugs in the United States (Talameh and Kitzmiller, 2014).
Statins have been used for decades for primary and secondary prevention of cardiovascular disease, decreasing cardiovascular events by approximately 25%. Although statins have a good overall safety record, some patients experience adverse effects that result in use of lower statin doses, noncompliance, and possibly discontinuation of use, leading to loss of full or any benefit. Management of statin-related side effects accounts for up to 25% of the workload of lipid clinics (Maghsoodi and Wierzbicki, 2016).
The most common adverse effect is statin-related myopathy, which comprises a spectrum of skeletal muscle conditions. No standardized definitions exist for classifying statin-related myopathies, but those of the American College of Cardiology, the American Heart Association, and the National Heart, Lung, and Blood Institute (Pasternak et al., 2002) are the most widely used (Hamann et al., 2013), as follows:
- Myopathy – A general term referring to any disease of muscles
- Myalgia – Muscle ache or weakness, no creatine kinase (CK) elevation
- Myositis – Muscle symptoms with increased CK levels
- Rhabdomyolysis – Muscle symptoms, CK substantially greater than 10 times the upper limit of normal, and elevated creatinine (usually with brown urine and urinary myoglobin)
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