Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: a prospective double-blinded clinical trial.

OBJECTIVE: Clinical trials of vitamin E have failed to demonstrate a decrease in cardiovascular events. However, these studies did not address possible benefit to subgroups with increased oxidative stress. Haptoglobin (Hp), a major antioxidant protein, is a determinant of cardiovascular events in patients with Type 2 diabetes mellitus (DM). The Hp gene is polymorphic with 2 common alleles, 1 and 2. The Hp 2 allelic protein product provides inferior antioxidant protection compared with the Hp 1 allelic product. We sought to test the hypothesis that vitamin E could reduce cardiovascular events in DM individuals with the Hp 2-2 genotype, a subgroup that comprises 2% to 3% of the general population. METHODS AND RESULTS: 1434 DM individuals > or = 55 years of age with the Hp 2-2 genotype were randomized to vitamin E (400 U/d) or placebo. The primary composite outcome was myocardial infarction, stroke, and cardiovascular death. At the first evaluation of events, 18 months after initiating the study, the primary outcome was significantly reduced in individuals receiving vitamin E (2.2%) compared with placebo (4.7%; P=0.01) and led to early termination of the study. CONCLUSIONS: Vitamin E supplementation appears to reduce cardiovascular events in individuals with DM and the Hp 2-2 genotype (ClinicalTrials.gov NCT00220831).

Effect of cilazapril with or without low dose thiazide on LDL peroxidation in [correction of peroxidationin] hypertensive patients.

BACKGROUND: This study aims to address the question, "Does equivalent blood pressure (BP) reduction by cilazapril alone or in combination with low dose of both cilazapril and hydrochlorothiazide have an equal effect on lowering oxidation of plasma LDL?" METHODS: Fifteen patients with untreated arterial hypertension were enrolled. Patients received 5 mg/d cilazapril (C5) for 6 weeks and were treated with a combination of 2.5 mg/d cilazapril and 12.5 mg/d hydrochlorothiazide (C2.5,HCTz) for an additional 2 months to achieve the same BP reduction as in the initial period. Treatment with a combination of 5 mg/d cilazapril and 12.5 mg/d hydrochlorothiazide (C5,HCTz) was administered for an additional 6 weeks. RESULTS: Treatment with C5 or in combination with C2.5,HCTz lowered systolic BP by the same magnitude (P <.05). Treatment with C5,HCTz decreased systolic BP an additional 7% and diastolic BP by 6% (P <.05). The LDL of 15 hypertensive patients demonstrated a 16.7% shorter lag time to initiation of peroxidation and 8.5% higher malonyldialdehyde levels at point of maximal peroxidation than LDL from 10 healthy controls (P <.05). Treatment with C5 decreased LDL tendency to peroxidation (lag time was prolonged by 43%, P <.05; malonyldialdehyde levels decreased by 8.3%). The combined treatment of C2.5,HCTz achieved the same BP reduction, but did not increase LDL resistance to peroxidation. Treatment with C5,HCTz achieved the same reduction in malonyldialdehyde levels in LDL than C5 therapy, but prolonged lag time by 17% (P <.05). CONCLUSIONS: The decreased tendency of LDL to peroxidation in hypertensive patients treated by cilazapril is due to the inherent effect of cilazapril, and not to a reduction in BP.