Relationship between glycemic status and progression of carotid intima-media thickness during treatment with combined statin and extended-release niacin in ARBITER 2

Allen J Taylor, Daming Zhu, Lance E Sullenberger, Hyun J Lee, Jeannie K Lee, Karen A Grace

Cardiology Service, Walter Reed Army Medical Center, Washington, DC, USA

Background: We previously reported in a placebo-controlled study that extended-release niacin slowed the progression of carotid atherosclerosis when added to statin monotherapy. This analysis examines the relationship between glycemic status and the effects of niacin on common carotid intima-media thickness (CIMT) and HDL cholesterol.

Methods: Post-hoc, subgroup analysis of ARBITER 2, a randomized, placebo-controlled trial of once-daily extended-release niacin (1000 mg) added to background statin therapy in 167 patients (mean age 67 years) with known coronary heart disease. The primary analysis was a comparison of the primary endpoint, the change in CIMT, between participants with either normal glycemic status, diabetes mellitus (DM) or the metabolic syndrome (MS).

Results: Baseline cardiovascular risk variables were significantly worse in those with abnormal glycemic status, particularly among subjects with MS. Niacin increased HDL-C to a similar degree (~20%) across normals, DM and MS. Placebo-treated patients had the greatest CIMT progression, regardless of glycemic status. The lowest progression rate was observed in niacin treated patients with normal glycemic status. Among all niacin treated subjects, there was a significant linear relationship between change in CIMT and change in HDL-C (r = –0.16; p = 0.05), which was of similar magnitude in subgroups with normal glycemic status (r = –0.23; p = 0.08) and DM (r = –0.22; p = 0.17). In those with MS, there was no relationship between changes in HDL and CIMT, (r = 0.11; p = 0.44), whereas blood glucose was positive correlated to change in CIMT (r = 0.30; p = 0.04). In multivariable linear models controlling for MS characteristics and blood glucose changes, only the change in HDL independently predicted change in CIMT.

Conclusions: During niacin treatment, increases in HDL-C are related to changes in CIMT in the setting of both normal glycemic status and diabetes mellitus.

Keywords: atherosclerosis, risk factors, lipids, diabetes mellitus