Author + information
Niacin failed to improve clinical outcomes when added to standard low-density lipoprotein cholesterol targeted therapy in the AIM-HIGH clinical trial despite a significant increase in high-density lipoprotein cholesterol (HDL-C) levels. We measured the effect of niacin on HDL functionality using complementary assays that assess cholesterol efflux capacity and anti-oxidative properties in a randomized trial of niacin added to a statin.
Patients with carotid atherosclerosis were placed on simvastatin 20 mg daily and randomized to six months of therapy with either extended release niacin (n = 19) or placebo (n = 20) in the Carotid Atherosclerosis Regression and Magnetic Resonance Assessment study. HDL cholesterol efflux capacity was quantified using tritium labeled cholesterol efflux from J774 macrophages in the presence of apolipoprotein-B depleted patient plasma. HDL inflammatory index (HII) represents the ability of apolipoprotein-B depleted plasma to inhibit oxidation as measured by the fluorescence of a reporter lipid in the presence of oxidized LDL.
At baseline, HDL-C levels were associated with cholesterol efflux capacity (r = 0.57, P = 0.0002), but not HII (r = 0.20, P = 0.23). By contrast C-Reactive Protein (log-transformed) levels were linked with HII (r = 0.37, P = 0.02) but not cholesterol efflux capacity (r = – 0.15, P = 0.36). Cholesterol efflux capacity and HII were not correlated (r = – 0.15, P = 0.35). HDL-C levels increased in patients treated with niacin from 46 to 57 mg/dl (mean change: +29%), an effect not noted with simvastatin monotherapy (mean change: +2.3%). Combination therapy did not lead to improvement in either cholesterol efflux capacity (mean change: −0.8%, 95%CI −11 to +10), or HII (mean change: 9%, 95%CI −6 to + 24%). Similar results were noted in matched pairs analysis and comparisons in change across treatment groups.
Adding niacin to statin therapy led to increased HDL-C levels without improvement in two orthogonal measures of HDL functionality. These data suggest that niacin may not improve HDL functionality and provide a framework to prospectively evaluate the effects of therapeutics on various aspects of HDL function.
West, Room 2006
Sunday, March 10, 2013, 9:00 a.m.-9:15 a.m.
Session Title: Prevention: Novel Investigations in Lipidology
Abstract Category: 24. Prevention: Clinical
Presentation Number: 919-7
- 2013 American College of Cardiology Foundation