Improvement of endothelial vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoproteins levels.
OBJECTIVE
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.
Kugiyama
K
K
Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Kumamoto City, Japan. kiyo@gpo.kumamoto-u.ac.jp
Motoyama
T
T
Doi
H
H
Kawano
H
H
Hirai
N
N
Soejima
H
H
Miyao
Y
Y
Takazoe
K
K
Moriyama
Y
Y
Mizuno
Y
Y
Tsunoda
R
R
Ogawa
H
H
Sakamoto
T
T
Sugiyama
S
S
Yasue
H
H
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D001053:Apolipoproteins / Q000097:blood; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000503:physiopathology; D015228:Hypertriglyceridemia / Q000188:drug therapy* / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D014666:Vasomotor System / Q000187:drug effects* / Q000503:physiopathology; D014810:Vitamin E / Q000008:administration & dosage*
D000975:Antioxidants; D001053:Apolipoproteins; D008055:Lipids; D008074:Lipoproteins; D014810:Vitamin E; D002784:Cholesterol