Effects of Extended-Release Nicotinic Acid on Apolipoprotein (a) Kinetics in Hypertriglyceridemic Patients. Issue 9 (September 2015)

• Record Type: Journal Article
• Authors: Croyal, Mikaël; Ouguerram, Khadija; Passard, Maxime; Ferchaud-Roucher, Véronique; Chétiveaux, Maud; Billon-Crossouard, Stéphanie; de Gouville, Anne-Charlotte; Lambert, Gilles; Krempf, Michel; Nobécourt, Estelle
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 35:Issue 9(2015)
• Publication Date: 2015-09
• Subjects: Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.115.305835
• Languages: English
• ISSNs: 1079-5642

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective—</title> <p>To determine the mechanisms by which extended-release nicotinic acid reduces circulating lipoprotein (a) concentrations in hypertriglyceridemic patients.</p> </sec> <sec> <title>Approach and Results—</title> <p>Eight nondiabetic, obese male subjects (aged 48±12 years; body mass index, 31.2±1.8 kg/m<sup>2</sup>) with hypertriglyceridemia (triglycerides, 226±78 mg/dL) were enrolled in an 8 week, double blind, placebo-controlled cross-over study. At the end of each treatment phase, fasted subjects received a 10 µmol/L per kg bolus injection of [5, 5, 5-<sup>2</sup>H<sub>3</sub>]-L-Leucine immediately followed by constant infusion of [5, 5, 5-<sup>2</sup>H<sub>3</sub>]-L-Leucine (10 µmol L<sup>−1</sup> kg<sup>−1</sup> h<sup>−1</sup>) for 14 hours, and blood samples were collected. A liquid chromatography–tandem mass spectrometry method was used to study apolipoprotein (a) (Apo(a)) kinetics. The fractional catabolic rate of Apo(a) was calculated with a single compartmental model using the apolipoprotein B100 (ApoB100) containing very low density lipoprotein tracer enrichment as a precursor pool. Extended-release nicotinic acid decreased plasma triglycerides (−46%; <italic>P</italic>=0.023), raised high-density lipoprotein cholesterol (+20%; <italic>P</italic>=0.008), and decreased Apo(a) plasma concentrations (−20%; <italic>P</italic>=0.008). Extended-release nicotinic acid also decreased ApoB100 (22%; <italic>P</italic>=0.008) and proprotein convertase subtilisin/kexin type 9 (PCSK9, −29%; <italic>P</italic>=0.008) plasma concentrations. Apo(a) fractional catabolic rate and production rates were decreased by 37% (0.58±0.28 versus 0.36±0.19 pool/d; <italic>P</italic>=0.008) and 50% (1.4±0.8 versus 0.7±0.4 nmol/kg per day; <italic>P</italic>=0.008), respectively.</p> </sec> <sec> <title>Conclusions—</title> <p>Extended-release nicotinic acid treatment decreased Apo(a) plasma concentrations by 20%, production rates by 50%, and catabolism by 37%. ApoB100 and PCSK9 concentrations were also decreased by treatment, but no correlation was found with Apo(a) kinetic parameters.</p> </sec> </abstract>