Niacin Therapy Increases High-Density Lipoprotein Particles and Total Cholesterol Efflux Capacity But Not ABCA1-Specific Cholesterol Efflux in Statin-Treated Subjects

Abstract

Objective: We investigated relationships between statin and niacin/statin combination therapy and the concentration of high-density lipoprotein particles (HDL-P) and cholesterol efflux capacity, 2 HDL metrics that might better assess cardiovascular disease risk than HDL-cholesterol (HDL-C) levels.

Approach: In the Carotid Plaque Composition Study, 126 subjects with a history of cardiovascular disease were randomized to atorvastatin or combination therapy (atorvastatin/niacin). At baseline and after 1 year of treatment, the concentration of HDL and its 3 subclasses (small, medium, and large) were quantified by calibrated ion mobility analysis (HDL-PIMA). We also measured total cholesterol efflux from macrophages and ATP-binding cassette transporter A1 (ABCA1)-specific cholesterol efflux capacity.

Results: Atorvastatin decreased low-density lipoprotein cholesterol by 39% and raised HDL-C by 11% (P=0.0001) but did not increase HDL-PIMA or macrophage cholesterol efflux. Combination therapy raised HDL-C by 39% (P<0.0001) but increased HDL-PIMA by only 14%. Triglyceride levels did not correlate with HDL-PIMA (P=0.39), in contrast to their strongly negative correlation with HDL-C (P<0.0001). Combination therapy increased macrophage cholesterol efflux capacity (16%, P<0.0001) but not ABCA1-specific efflux. ABCA1-specific cholesterol efflux capacity decreased significantly (P=0.013) in statin-treated subjects, with or without niacin therapy.

Conclusions: Statin therapy increased HDL-C levels but failed to increase HDL-PIMA. It also reduced ABCA1-specific cholesterol efflux capacity. Adding niacin to statin therapy increased HDL-C and macrophage efflux, but had much less effect on HDL-PIMA. It also failed to improve ABCA1-specific efflux, a key cholesterol exporter in macrophages. Our observations raise the possibility that niacin might not target the relevant atheroprotective population of HDL.

Keywords: atherosclerosis; cardiovascular diseases; macrophages; niacin; triglycerides.

© 2015 American Heart Association, Inc.

Figures

Figure 1. Effects of lipid-altering therapies on lipid parameters

For each therapy, the change from baseline on lipid parameters is provided. The differences in change from baseline between therapies were compared using a linear regression model controlling for baseline values, and the P value for the difference is indicated. A, atorvastatin therapy; A+N, atorvastatin plus niacin therapy.

Figure 2. HDL particle distribution according to therapy

S-HDL-PIMA, M-HDL-PIMA, and L-HDL-PIMA were measured by calibrated-IMA. HDL-PIMA was obtained by summing the different HDL-PIMA subspecies. For each HDL-PIMA subspecies, P values comparing on treatment and baseline measurements for the same therapy are provided. P values comparing differences in changes between two therapies are also indicated. The box plots show the distribution of the data (median, interquartile ranges), while the dots represent outliers. A, atorvastatin therapy; A+N, atorvastatin plus niacin therapy.

Figure 3. Effect of lipid-altering therapies on cholesterol efflux capacity

(A) Macrophage cholesterol efflux. (B) ABCA1-specific efflux. (C) ABCA1-specific efflux combining all subjects (n=126). P values comparing on treatment and baseline measurements for the same therapy are provided. P values comparing differences in changes between two therapies are also indicated. The box plots show the distribution of the data (median, interquartile ranges), while the dots represent outliers. A, atorvastatin therapy; A+N, atorvastatin plus niacin therapy.