Effect of atorvastatin, cholesterol ester transfer protein inhibition, and diabetes mellitus on circulating proprotein subtilisin kexin type 9 and lipoprotein(a) levels in patients at high cardiovascular risk

Journal of Clinical Lipidology
Benoit J ArsenaultGilles Lambert

Abstract

Proprotein subtilisin kexin type 9 (PCSK9) and lipoprotein (a) [Lp(a)] levels are causative risk factors for coronary heart disease. The objective of the study was to determine the impact of lipid-lowering treatments on circulating PCSK9 and Lp(a). We measured PCSK9 and Lp(a) levels in plasma samples from Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events trial patients with coronary heart disease and/or type II diabetes (T2D) mellitus. Patients received atorvastatin, which was titrated (10, 20, 40, or 80 mg/d) to achieve low-density lipoprotein cholesterol levels <100 mg/dL (baseline) and were subsequently randomized either to atorvastatin + torcetrapib, a cholesterol ester transfer protein inhibitor, or to atorvastatin + placebo. At baseline, both plasma PCSK9 and Lp(a) were dose-dependently increased with increasing atorvastatin doses. Compared with patients without T2D, those with T2D had higher PCSK9 (357 ± 123 vs 338 ± 115 ng/mL, P = .0012) and lower Lp(a) levels (28 ± 32 vs 32 ± 33 mg/dL, P = .0005). Plasma PCSK9 levels significantly increased in patients treated with torcetrapib (+13.1 ± 125.3 ng/mL [+3.7%], P = .005), but not in patients treated with placebo (+2.6 ± 127.9 ng/mL [...Continue Reading

Citations

May 8, 2018·Clinical Pharmacology and Therapeutics·Benoit J ArsenaultRishi Puri
Aug 14, 2018·European Journal of Clinical Investigation·Christopher AdlbrechtAlberto Bouzas-Mosquera
Sep 11, 2018·Current Opinion in Lipidology·Stéphane Ramin-MangataGilles Lambert
Oct 28, 2018·Nature Reviews. Endocrinology·Robert M StoekenbroekG Kees Hovingh
Mar 30, 2019·Current Opinion in Lipidology·Stefano SpolituLale Ozcan
Feb 14, 2019·Journal of the American Heart Association·Paul Nestel
May 22, 2019·European Heart Journal·Sotirios TsimikasJoseph L Witztum
Oct 28, 2019·Stroke; a Journal of Cerebral Circulation·Karina GasbarrinoStella S Daskalopoulou
Nov 10, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xinyi WangHao Xu
Jul 31, 2020·Advanced Drug Delivery Reviews·Josefin SoppertHeidi Noels
Apr 4, 2021·Journal of Clinical Medicine·Kari A MäkeläKarl-Heinz Herzig
Dec 14, 2019·Atherosclerosis·Stéphane Ramin-MangataBertrand Cariou

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