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CLINICAL STUDIES

Improvement of endothelial function and insulin sensitivity with vitamin C in patients with coronary spastic angina

Possible role of reactive oxygen species

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

Manuscript received March 9, 1999; revised manuscript received December 10, 1999, accepted February 3, 2000.

Reprint requests and correspondence: Dr. Hirofumi Yasue, Department of Cardiovascular Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-8556, Japan
yasue{at}gpo.kumamoto-u.ac.jp

OBJECTIVES

This study was designed to examine the effect of antioxidant supplementation on the endothelial function and insulin sensitivity in patients with coronary spastic angina (CSA).

BACKGROUND

Insulin resistance may play a key role in coronary heart disease, and there is a possible link between acetylcholine-induced coronary vasoconstriction and hyperinsulinemia in patients with CSA. Endothelial dysfunction is present in the systemic arteries in CSA patients, and reactive oxygen species may cause inactivation of nitric oxide in these patients.

METHODS

We measured flow-mediated dilation of the brachial artery using ultrasound technique in 22 patients with CSA and 20 control subjects. We also evaluated glucose tolerance using a 75-g oral glucose tolerance test and insulin sensitivity using steady-state plasma glucose (SSPG) methods in the same patients.

RESULTS

The incidence of impaired glucose tolerance was higher in the CSA group than in the control group. Vitamin C infusion augmented flow-mediated dilation and decreased SSPG levels in the CSA group (from 3.27 ± 0.77% to 7.00 ± 0.59% [p < 0.001 by analysis of variance (ANOVA)] and from 177.3 ± 13.3 to 143.1 ± 14.9 mg/dl [p = 0.047 by ANOVA], respectively) but not in the control group (from 6.47 ± 0.66% to 6.80 ± 0.60% and from 119.8 ± 11.7 mg/dl to 118.1 ± 11.3 mg/dl, respectively). The steady-state plasma insulin levels were not affected by vitamin C infusion in either group.

CONCLUSIONS

Vitamin C improves both endothelial function and insulin sensitivity in patients with CSA. Thus, reactive oxygen species and/or decreased nitric oxide bioactivity may play an important role in the genesis of both endothelial dysfunction and insulin resistance in patients with CSA.

Abbreviations and Acronyms   Ach = acetylcholine   ANOVA = analysis of variance   CSA = coronary spastic angina   FMD = flow-mediated dilation   HDL = high-density lipoprotein   NO = nitric oxide   OGTT = oral glucose tolerance test   SSPG = steady-state plasma glucose   SSPI = steady-state plasma insulin

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