Haptoglobin genotype does not predict extent of coronary artery calcification in a prospective cohort of patients with type 2 diabetes

Abstract

The protein haptoglobin (Hp) binds free hemoglobin extravasated from the vasa vasorum and mitigates its proinflammatory and proatherogenic effects [ [1] Moreno P.R. Purushothaman K.R. Sirol M. Levy A.P. Fuster V. Neovascularization in human atherosclerosis. Circulation. 2006; 113: 2245-2252 Crossref PubMed Scopus (377) Google Scholar ]. There are two common alleles for Hp (1 and 2) and the three genotypes, Hp 1-1, Hp 2-1, and Hp 2-2, which are structurally distinct. In diabetes mellitus (DM) the Hp 2-2 genotype confers less protection against hemoglobin-driven oxidative stress [ [2] Melamed-Frank M. Lache O. Enav B.I. et al. Structure–function analysis of the antioxidant properties of haptoglobin. Blood. 2001; 98: 3693-3698 Crossref PubMed Scopus (277) Google Scholar ] and is an independent predictor of adverse cardiovascular events [ [3] Levy A.P. Hochberg I. Jablonski K. et al. Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study. J Am Coll Cardiol. 2002; 40: 1984-1990 Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar ]. It is unknown whether this association is related to increased coronary atherosclerotic burden or to increased plaque vulnerability. Coronary artery calcification (CAC) is a direct measure of total calcified atherosclerotic burden [ [4] Sangiorgi G. Rumberger J.A. Severson A. et al. Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology. J Am Coll Cardiol. 1998; 31: 126-133 Abstract Full Text Full Text PDF PubMed Scopus (847) Google Scholar ] and can be readily quantified on cardiac computed tomography (CCT). The present study was designed to investigate the hypothesis that type-2 diabetics with the Hp 2-2 genotype have increased coronary plaque burden compared with diabetics with other Hp genotypes.