Rabea Asleh, Alexandros Briasoulis, Elliot M Berinstein, Joshua B Wiener, Mohan Palla, Sudhir S Kushwaha, Andrew P Levy

The objectives of the study were to compile and summarize the data from all of the clinical trials designed to examine the association between haptoglobin (Hp) genotype and incidence of cardiovascular (CV) events in patients with diabetes mellitus (DM) and to assess the impact of vitamin E treatment on CV outcomes according to the Hp genotype. The Hp genotype could serve as a predictive biomarker to DM patients who may benefit from vitamin E therapy. The electronic databases MEDLINE, PubMed, EMBASE and the Cochrane Library for Central Register of Clinical Trials were searched systematically using the following MESH terms: "haptoglobin genotype", "diabetes mellitus" and "cardiovascular events". Overall, 13 studies fit the inclusion criteria for this analysis, yielding a large study population that included 6,161 patients without Hp 2-2 and 4,684 patients with Hp 2-2. The analysis of these studies showed that the incidence of CV events in DM patients with the Hp 2-2 genotype was significantly increased as compared to non-Hp 2-2 patients in all three subgroups of case-control (OR: 2.2, 95% CI: 1.3-3.6; P=0.003), cohort (OR: 1.3, 95% CI: 1.2-1.5; P=0.001) and randomized controlled trials (OR: 1.6, 1.2-2.2; P=0.005). Among patients with the Hp 2-2 genotype, administration of vitamin E was associated with lower rates of CV events (OR: 0.66, 95% CI: 0.45-0.95; P=0.025). Further investigation into the association between Hp 2-2 and myocardial infarction, stroke, mortality and end-stage renal disease was also performed. The Hp genotype is a risk factor for CV events in patients with DM, and administration of vitamin E appears to offer a low cost and accessible means of reducing CV events and mortality in this population.