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CLINICAL STUDIES

Improvement of endothelial vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoproteins levels

^a Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Kumamoto, Japan

Manuscript received September 9, 1998; revised manuscript received January 6, 1999, accepted January 21, 1999.

Reprint requests and correspondence: Dr. Kiyotaka Kugiyama, Department of Cardiovascular Medicine,, Kumamoto University School of Medicine, Honjo 1-1-1, Kumamoto City, 860 Japan
kiyo{at}gpo.kumamoto-u.ac.jp

OBJECTIVES

This study sought to examine whether oral intake of alpha-tocopherol, an antioxidant, could improve endothelium-dependent vasorelaxation in patients with high remnant lipoproteins levels.

BACKGROUND

Remnant lipoproteins are known to be atherogenic and impair endothelium-dependent arterial relaxation, but the underlying mechanisms remain unclear. Oxidative stress is a common feature of various risk factors for atherosclerosis.

METHODS

Flow-mediated vasodilation of the brachial artery during reactive hyperemia was examined by high resolution ultrasound technique before and at the end of 4 weeks treatment with oral administration of alpha-tocopherol acetate (300 IU/day) or placebo, which was randomly assigned, in 40 patients with high serum levels of remnants and in 30 patients with low remnants levels in the fasting state (>75th percentile and <25th percentile, respectively, of the distribution of remnants levels in 150 consecutive hospitalized patients).

RESULTS

Before treatment, flow-mediated vasodilation was lower in patients with high remnants levels than in those with low levels (4.1 ± 0.3% vs. 6.0 ± 0.5%, p < 0.01). Treatment with alpha-tocopherol but not with placebo significantly increased flow-mediated dilation in patients with high remnants levels (7.5 ± 0.4% after alpha-tocopherol vs. 4.2 ± 0.4% after placebo, p < 0.01). In patients with low remnants levels, alpha-tocopherol was not effective. The beneficial effect with alpha-tocopherol in high remnants patients was associated with decrease in plasma levels of thiobarbituric acid reactive substances, an indicator of lipid peroxidation (6.6 ± 0.3 nmol/ml before alpha-tocopherol vs. 4.6 ± 0.3 after alpha-tocopherol, p < 0.05).

CONCLUSIONS

Alpha-tocopherol improved impairment of endothelium-dependent vasodilation in patients with high remnants levels. The increase in oxidative stress may at least partly contribute to endothelial vasomotor dysfunction in patients with high remnants levels.

Abbreviations and Acronyms   apo = apolipoprotein   LDL = low density lipoproteins   TBARS = thiobarbituric acid reactive substances   VLDL = very low density lipoproteins

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