Relationship between glycemic status and progression of carotid intima-media thickness during treatment with combined statin and extended-release niacin in ARBITER 2.
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 (approximately 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.
Taylor
Allen J
AJ
Cardiology Service, Walter Reed Army Medical Center, 6900 Georgia Avenue, NW, Building 2, Room 4A34, Washington, DC 20307-5001, USA. allen.taylor@na.amedd.army.mil
Zhu
Daming
D
Sullenberger
Lance E
LE
Lee
Hyun J
HJ
Lee
Jeannie K
JK
Grace
Karen A
KA
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009525:Niacin / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D014463:Ultrasonography
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003692:Delayed-Action Preparations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D009525:Niacin