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CHAPTER SUMMARY AND CENTRAL ILLUSTRATION

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Safety and Pharmacodynamic Effects of VERVE-101, an Investigational DNA Base Editing Medicine Designed to Durably Inactivate the PCSK9 Gene and Lower LDL Cholesterol - Interim Results of the Phase 1b Heart-1 Trial

The Heart-1 trial was a phase 1b, open-label clinical trial designed to assess the safety and pharmacodynamic effects of an investigational CRISPR-based gene editing therapy that inactivates the PCSK9 gene in the liver. Read More

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Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a): A Randomized Dose-Ascending Clinical Trial

This phase 1 randomized dose-ascending trial assessed the safety and tolerability of lepodisiran, a long-acting short interfering RNA targeting lipoprotein(a) production. Read More

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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

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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

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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

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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

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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 ...

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