Perspectives in clinical gastroenterology and hepatology
Management of Dyslipidemia as a Cardiovascular Risk Factor in Individuals With Nonalcoholic Fatty Liver Disease

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Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the United States and is associated with an increased risk of cardiovascular disease (CVD) and cardiovascular (CV) mortality, independent of traditional cardiovascular risk factors. CVD is one of the most common causes of death among individuals with NAFLD and management of NAFLD must extend beyond liver disease to include CVD risk modification. Clinicians should assess CVD risk with the Framingham Risk Score and screen for CVD risk factors including dyslipidemia, diabetes mellitus, hypertension, tobacco use, and the metabolic syndrome. CVD risk factors, particularly dyslipidemia, require aggressive medical management to reduce the high risk of CVD events and death in individuals with NAFLD.

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Dyslipidemia in Nonalcoholic Fatty Liver Disease

Dyslipidemia is frequent in individuals with NAFLD. A substudy from the Multi-Ethnic Study of Atherosclerosis assessed the relationship between radiographically diagnosed NAFLD and dyslipidemia.6 NAFLD was associated independently with increased triglyceride levels, increased low-density lipoprotein (LDL) particle concentration, decreased LDL particle size, and decreased high-density lipoprotein (HDL) levels after controlling for insulin resistance. These findings have been replicated in

Cardiovascular Disease and Nonalcoholic Fatty Liver Disease

CVD events are a frequent cause of morbidity and mortality in individuals with NAFLD (Table 1). Three community-based studies have shown that individuals with radiographically diagnosed NAFLD have an increased risk of CVD events and mortality compared with individuals without NAFLD.13, 14, 15 Hamaguchi et al16 assessed 1637 subjects in a community-based cohort from Japan for NAFLD by ultrasonography. Nineteen percent of the cohort was found to have NAFLD. Cardiovascular (CV) events occurred in

Cardiovascular Risk Stratification in Nonalcoholic Fatty Liver Disease

Several different methods are used in the general population to estimate CVD risk including the Framingham Risk Score (FRS). The FRS is a validated measure of CV risk in the general population. Incorporating age, sex, cholesterol, HDL, smoking status, and hypertension, the FRS predicts an individual's 10-year risk of myocardial infarction or CVD death. Furthermore, the FRS has been validated as a predictor of CVD in NAFLD and should be used to risk-stratify individuals and guide treatment of

Management of Dyslipidemia and Cardiovascular Disease Risk in Nonalcoholic Fatty Liver Disease

Lifestyle modification, encompassing weight loss and increased physical activity, is the cornerstone of dyslipidemia management in NAFLD. However, for groups with increased CVD risk, lifestyle modification should be accompanied by lipid-lowering therapy. Guidelines set forth by the NCEP Adult Treatment Panel III provide guidance on which groups should be targeted for lipid-lowering therapy and outline treatment goals (Figure 1).12 These guidelines were not designed specifically to address

Diabetes Mellitus

DM is associated with an increased risk of CVD. Because DM is highly prevalent among individuals with NAFLD, comprehensive management is essential for CVD risk reduction. A detailed discussion of the management of DM in individuals with NAFLD is beyond the scope of this review. However, primary and secondary prevention of CVD events in individuals with DM should focus on multifactorial risk reduction, including treatment of hypertension and dyslipidemia.51 In addition, specific treatments of DM

Fatty Liver and Newly Approved Lipid-Lowering Agents

Statins are effective LDL-lowering agents; however, in an important subset of individuals, statins cannot lower LDL to goal treatment levels. Therefore, the search for medications to improve LDL lowering is ongoing. Two new lipid-lowering agents recently were approved. Mipomersen, an anti-sense oligonucleotide, binds to and degrades hepatic apolipoprotein B messenger RNA, decreasing circulating LDL levels. Mipomersen is effective at LDL lowering in individuals with hyperlipidemia, homozygous

Future Directions

NAFLD is an increasing epidemic in the United States and is associated with CV mortality. Many individuals with NAFLD will die of CVD before the development of end-stage liver disease. Thus, the careful management of CVD risk factors including dyslipidemia in individuals with NAFLD is essential to reduce CVD-related mortality. Gastroenterologists and hepatologists should play an active role in comprehensive CVD risk assessment including screening for dyslipidemia, DM, the MetS, cigarette

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    This article has an accompanying continuing medical education activity on page e60. Learning Objectives—At the end of this activity, the successful learner will be able to evaluate patients with NAFLD for cardiovascular disease risk and formulate a comprehensive treatment plan to address cardiovascular disease risk factors.

    Conflicts of interest This author discloses the following: Dr Chalasani has served as a consultant in the past 12 months to Lilly, Salix, Aegerion, Merck, Abbott, and Mochida in the area of drug hepatotoxicity. He has also received research grant support from Gilead, Genfit, Takeda, Cumberland Pharmaceuticals, Intercept pharmaceuticals, and Enterome. The remaining author discloses no conflicts.

    Funding Supported in part by a National Institutes of Health grant (K24 DK069290A to N.C.) and an AASLD Clinical and Translational Research Award (K.E.C.).

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