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J Am Coll Cardiol, 2000; 35:1860-1866
© 2000 by the American College of Cardiology Foundation
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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

Osamu Hirashima, MDa, Hiroaki Kawano, MDa, Takeshi Motoyama, MDa, Nobutaka Hirai, MDa, Masamichi Ohgushi, MDa, Kiyotaka Kugiyama, MDa, Hisao Ogawa, MDa and Hirofumi Yasue, MDa

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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