Abstract 11821: HDL-Induced Cholesterol Efflux Capacity From Niacin Therapy in Diabetes is Haptoglobin Genotype-Dependent
Objectives: One possible explanation for the recent failure of HDL raising therapies such as niacin to reduce cardiovascular disease (CVD) may be that raising HDL is beneficial only in individuals with preserved HDL function. There exists two common alleles at the Haptoglobin (Hp) genetic locus, 1 and 2, with a 2-3 fold increased rate of CVD in individuals with diabetes mellitus (DM) and the Hp 2-2 genotype. We recently demonstrated that Hp 2-2 DM individuals have pro-inflammatory dysfunctional HDL. We therefore sought to test the hypothesis in AIM HIGH that benefit from niacin on HDL function would be Hp genotype-dependent.
Methods: Stored serum samples from all 1140 DM participants in AIM HIGH were Hp typed. Cholesterol efflux capacity was evaluated at baseline and at one year of treatment in 70 Hp 1-1 and 70 Hp 2-2 DM individuals randomly selected in equal proportions from the niacin and placebo groups.
Results: At baseline, efflux capacity of serum from Hp 1-1 was significantly greater than that from Hp 2-2 participants (11.1% vs. 9.6%, p=0.001). In the 4 treatment groups evaluated for efflux capacity (Hp 1-1 and Hp 2-2 ± niacin), a significant increase in efflux capacity at one year into the study was only found in the niacin treated Hp 1-1 group (14% increase in median efflux, p<0.02 comparing efflux at baseline and after 1 year on niacin). There was no difference in efflux between Hp 2-2 individuals treated with placebo and niacin. With regard to the primary AIM HIGH composite clinical endpoint, although the directions of association were as expected, niacin therapy was not associated with a differential response in Hp 1-1 or Hp 2-2 DM individuals (Hp 1-1 DM: OR 0.84; 95% CI [0.42-1.69]) and Hp 2-2 DM: OR 1.30; 95% CI [0.78-1.81]); p=0.47 for interaction).
Conclusions: Benefit from niacin on cholesterol efflux capacity appears to be Hp genotype-dependent. A larger sample size is needed to determine if this translates into a meaningful change in clinical events.
Author Disclosures: R. Asleh: None. D. Farbstein: None. S. Blum: None. M. Vardi: None. H. Shalom: None. S. Saraf: None. K. O`Brien: None. S. Marcovina: None. B.H. Roberts: None. D. Herrington: None. J.G. Robinson: Research Grant; Significant; Amarin, Amgen, Astra-Zeneca, Daiichi-Sankyo, Genentech/Hoffman La Roche, Glaxo-Smith Kline, Merck, Regeneron/Sanofi, Zinfandel/Takeda.. Consultant/Advisory Board; Significant; Amgen, Hoffman LaRoche, Merck, Pfizer, Sanofi. A.P. Levy: Employment; Modest; Professor Levy is an employee of the Technion Faculty of Medicine, which owns patents related to the use of haptoglobin typing to predict the risk of diabetic vascular complications..
- © 2014 by American Heart Association, Inc.