Effects of Extended-Release Nicotinic Acid on Apolipoprotein (a) Kinetics in Hypertriglyceridemic Patients
Objective—To determine the mechanisms by which extended-release niacin reduces circulating lipoprotein (a) concentrations in hypertriglyceridemic patients.
Approach and Results—Eight nondiabetic, obese male subjects (aged 48±12 years; body mass index, 31.2±1.8 kg/m2) 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 [5,5,5-2H3]-l-Leucine immediately followed by constant infusion of [5,5,5-2H3]-l-Leucine (10 µmol L−1 kg−1 h−1) 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 niacin decreased plasma triglycerides (−46%; P=0.023), raised high-density lipoprotein cholesterol (+20%; P=0.008), and decreased Apo(a) plasma concentrations (−20%; P=0.008). Extended-release niacin also decreased ApoB100 (22%; P=0.008) and proprotein convertase subtilisin/kexin type 9 (PCSK9, −29%; P=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; P=0.008) and 50% (1.4±0.8 versus 0.7±0.4 nmol/kg per day; P=0.008), respectively.
Conclusions—Extended-release niacin 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.
- Received April 30, 2015.
- Accepted June 24, 2015.
- © 2015 American Heart Association, Inc.