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Epidemiology and Management of Hyperlipidemia
Samantha Karr, PharmD, FCCP, BCPS, BCACP, BC-ADM
Participating Faculty

Epidemiology and Management of Hyperlipidemia

Samantha Karr, PharmD, FCCP, BCPS, BCACP, BC-ADM
Cardiovascular disease (CVD) is the leading cause of death among adults in the United States, and people with hyperlipidemia are at roughly twice the risk of developing CVD as compared to those with normal total cholesterol levels.1 Patients with familial hypercholesterolemia (FH) have an even greater risk of developing CVD at an earlier age; therefore, early detection and treatment are imperative to reduce cardiovascular events and premature death. Statins are the mainstay treatment for hyperlipidemia; however, the limitations of statins include treatment resistance, intolerance due to adverse events, and a lack of adherence which contribute to poor outcomes. As such, many patients require adjunct therapies to properly control hyperlipidemia including niacin, bile acid sequestrants, fibric acids, and ezetimibe. FH can be even more challenging to treat, often requiring the use of lomitapide, mipomersen, proprotein convertase subtilisin/kexin type 9 inhibitors, or low-density lipoprotein cholesterol apheresis, in addition to high dose conjunction with statins or other agents.2 The approach to determining the appropriate treatment options has also undergone important changes. Guidelines for the management of patients with hyperlipidemia vary in their recommendations, with the American College of Cardiology/American Heart Association recommending that treatment decisions be based on the intensity of response associated with various statins, while multiple other guidelines (eg, National Lipid Association (NLA) and the American Association of Clinical Endocrinologists and American College of Endocrinology) still support attaining prespecified lipid values to reduce cardiovascular risk.3-5 This article will review the epidemiology of hyperlipidemia and FH, risk factors associated with the development of disease, as well as the efficacy and safety of statins and adjunct treatment options.
Am J Manag Care. 2017;23:-S0

Hyperlipidemia involves an imbalance of cholesterol levels, including low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in the blood. LDL-C and HDL-C regulate the amount of cholesterol in the body and an imbalance can increase the risk of cardiovascular events, including myocardial infarction and stroke. Other forms of hyperlipidemia include hypertriglyceridemia as well as mixed hyperlipidemia, in which both cholesterol and triglyceride levels are elevated. Elevated LDL-C can lead to a buildup of plaques within the arteries and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease or stroke. As HDL-C functions to remove cholesterol from the body, increased levels of HDL-C (≥60 mg/dL) can help decrease the risk of ASCVD.6

In the United States, more than 100 million, or roughly 53% of adults, have elevated LDL-C levels.7 Yet, fewer than 50% of patients with high LDL-C receive treatment to reduce their levels, and among those receiving treatment, fewer than 35% achieve adequate control.1,7 Further, approximately 31 million American adults have total cholesterol levels that exceed 240 mg/dL, placing them at about twice the risk of ASCVD compared to those with total cholesterol levels that are at goal.1

Risk Factors for Hyperlipidemia
Several factors are associated with an increased risk of hyperlipidemia. Modifiable risk factors include a diet high in saturated or trans fats, physical inactivity, smoking, and obesity.1 Secondary causes of elevated LDL-C include diseases such as biliary obstruction, chronic kidney disease, type 2 diabetes mellitus, high blood pressure, and hypothyroidism.1 Medications such as diuretics, cyclosporine, and glucocorticoids can also contribute to elevated LDL-C levels.3 Data related to the role of race and gender in the development of hyperlipidemia have been conflicting; however, some risk factors may be more prevalent in specific races, such as obesity in non-Hispanic blacks, and thus an increased incidence of hyperlipidemia within that population.8 Predictions of 10-year and lifetime ASCVD risk, based on patient-specific risk factors, are available in the literature. Clinical tools such as the American College of Cardiology/American Heart Association (ACC/AHA) ASCVD risk calculator,9 can be useful in evaluating individual patient risk; however, clinicians using these resources should note that there are some limitations when using these risk predictors. The ACC/AHA has stated that the risk predictor could be used to predict stroke as well as coronary heart disease (CHD) events in non-Hispanic white and African American women and men 40 to 79 years of age. Beyond these parameters, the ASCVD risk calculator may not be a reliable predictor due to lack of sufficient data in other races or age groups. In addition, the calculator is not a reliable risk predictor for those with total cholesterol over 320 mg/dL, which would include patients with familial hypercholesterolemia (FH).

Genetics can also play a role in the development of elevated cholesterol in the form of FH. FH is an autosomal dominant trait characterized by significant elevations in total cholesterol and LDL-C from birth and premature ASCVD.10-13 DNA testing has revealed that FH is the result of genetic mutations in the LDL receptor (LDLR); gain-of-function mutations of the proprotein convertase subtilisin/kexin type 9 (PCSK9), which leads to decreased LDL metabolism; or genetic mutations in the apolipoprotein (apo) B gene, which reduces binding of LDL particles to the LDLR.14,15 Of the 3 types of genetic mutations listed above, the majority of individuals with FH have a mutation in the LDLR.16 A lack of enough properly functioning LDLRs results in a reduction of cleared LDL-C, and thus an increase in circulating LDL-C. Compared with patients without FH, those with FH have greater risk of developing coronary heart disease.17 A recent analysis by the National Health and Nutrition Examination Survey (NHANES) noted that although the prevalence of FH did not differ based on gender, the prevalence of FH did vary among ethnic groups, with the lowest prevalence among Mexican Americans and the highest prevalence among whites, blacks, and other Hispanics.18

There are 2 types of FH: homozygous (HoFH) and heterozygous FH (HeFH). In the United States, HeFH is more common, affecting approximately 1 in 500 people, and is associated with LDL-C levels of 200 to 450 mg/dL.19,20 Patients with HeFH often develop coronary artery disease before the age of 60 years.15 HoFH is rarer, affecting roughly 1 in 300,000 to 1,000,000 people, but is associated with much higher LDL-C levels compared with HeFH (450 to >1000 mg/dL).11,19,21 If left untreated, patients with HoFH may die before the age of 20 years.15

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