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

Content Update

CLEAR Outcomes: Bempedoic Acid and Cardiovascular Outcomes in Statin Intolerant Patients

The CLEAR Outcomes trial was a phase 3 clinical trial designed to assess the impact of bempedoic acid, an ATP citrate lyase inhibitor, on cardiovascular outcomes in patients who are intolerant of statins. Read More

Content Update

OCEAN(a) DOSE: Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease

The OCEAN(a) DOSE trial was a phase 2 clinical trial designed to assess the impact of olpasiran, a small interfering RNA (siRNA) on lipoprotein(a) (Lp(a)) concentrations in patients with established atherosclerotic cardiovascular disease (ASCVD). Read More

Content Update

SPORT Trial: Supplements, Placebo, or Rosuvastatin

The SPORT Study was a single-center, prospective, randomized, single-blind clinical trial designed to compare the efficacy of a low-dose statin, placebo and six common supplements in impacting lipid and inflammatory biomarkers. Read More

Content Update

DANCAVAS: Five-Year Outcomes of the Danish Cardiovascular Screening Trial

The DANCAVAS (Danish Cardiovascular Screening) trial was designed to assess the impact of population-based cardiovascular health screening with respect to the risk of death. Read More

Content Update

TRANSLATE-TIMI 70 Review

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.