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TRANSLATE-TIMI 70 was a placebo-controlled, double-blind, randomized phase 2 trial of vupanorsen, an N-acetyl galactosamine-conjugated antisense oligonucleotide that targets ANGPTL3 mRNA in the liver, at escalating doses in adults with hyperlipidemia on statin therapy. Read More

Chapter Summary

This chapter discusses the prevalence, genetics, pathophysiology, and management of lipoprotein abnormalities, which are interpreted in the context of the history of clinical cardiovascular events or subclinical cardiovascular disease (CVD) (see Fuster and Hurst’s Central Illustration). Evaluation requires a complete assessment of other major cardiovascular risk factors and detailed, multigenerational family trees that include cardiovascular history, age of onset of the first and recurrent events, untreated lipid and lipoprotein levels, and genetic analysis. Laboratory assessment begins with the standard lipid panel and may extend to measures of atherogenic lipoprotein concentrations (apolipoprotein B [apoB], and low-density lipoprotein [LDL] particle number), lipoprotein(a) (Lp[a]), and triglyceride-rich lipoproteins/remnant cholesterol. The evaluation must include assessment of secondary causes of dyslipidemia, such as obesity, poor diet, diabetes, hypothyroidism, renal disease (chronic kidney disease and nephrotic syndrome), liver disease (hepatosteatosis and primary biliary cirrhosis), and autoimmune conditions. Confirmation of underlying lipoprotein disorders may include genetic assessment of major genes in monogenic dyslipidemias and polygenic factors. A strategy to reduce cardiovascular risk involves implementation of lifestyle interventions (healthy diet, and aerobic and resistance exercise), aggressive surveillance and management of cardiovascular risk factors with therapies supported by clinical outcomes, and aggressive treatment of LDL cholesterol (LDL-C). Once LDL-C targets are achieved, strategies to lower triglyceride-rich lipoproteins and Lp(a) may be considered.

eFig 10-01 Chapter 10: Hypercholesterolemia, Hyperlipoprotein(a), Hypertriglyceridemia, and Low HDL


The term hyperlipidemia comprises multiple disorders of high levels of circulating blood fats. In general, hyperlipidemia increases the risk for atherosclerotic cardiovascular disease (ASCVD). Of the hyperlipidemias, excess concentrations of low-density lipoprotein (LDL) have been the most extensively studied. LDL is a causal risk factor for ASCVD that has been established from multiple sources encompassing natural selection studies (Mendelian randomization), prospective population studies, and randomized, controlled clinical trials.1

Cardiovascular disease (CVD) represents the leading cause of morbidity and mortality for adults in industrialized societies.2,3 Decades of progress in the fight against CVD is eroding as incident coronary heart disease (CHD) increases among adolescents and young adults.4 Lifestyle changes and comprehensive medical therapy has reduced the risk of recurrent cardiovascular events and mortality in high-risk and very high-risk patients.1,5–7 However, the risk of recurrent cardiovascular events after hospitalization for a myocardial infarction (MI) remains high even among many patients treated with high dosages of high-intensity statins.8–10

Despite multiple advances in LDL therapeutics, investigations are needed to improve understanding of lipoprotein associated risk beyond aggressive lowering of LDL cholesterol (LDL-C). Other hyperlipidemias characterized as ...

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