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CLINICAL STUDY: ENDOTHELIAL FUNCTION

Endothelial function fluctuates with diurnal variation in the frequency of ischemic episodes in patients with variant angina

Hiroaki Kawano, MD, PhD^*,*, Takeshi Motoyama, MD, PhD^*, Hirofumi Yasue, MD, PhD, Nobutaka Hirai, MD^*, Hesham M. Waly, MD, PhD, Kiyotaka Kugiyama, MD, PhD and Hisao Ogawa, MD, PhD^*

^* Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Kumamoto, Japan
Kumamoto Aging Research Institute, Kumamoto, Japan
Second Department of Internal Medicine, Yamanashi Medical School, Kohfu, Japan
Mansoura University Faculty of Medicine, Mansoura, Egypt

Manuscript received October 4, 2001; revised manuscript received March 26, 2002, accepted April 17, 2002.

^* Reprint requests and correspondence: Dr. Hiroaki Kawano, Department of Cardiovascular Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto City 860-8556, Japan.
koumei{at}gpo.kumamoto-u.ac.jp

OBJECTIVES: The aim of the present study was to investigate whether there is diurnal fluctuation in the endothelial function of patients with variant angina (VA).

BACKGROUND: Coronary spasm is induced by acetylcholine and is promptly relieved by nitroglycerin. Thus, it is possible that endothelial dysfunction is involved in the pathogenesis of coronary spasm. Furthermore, the frequency of ischemic episodes is known to display diurnal variation.

METHODS: Flow-mediated, endothelium-dependent vasodilation of the brachial arteries was measured in the early morning (6 AM), afternoon (2 PM) and evening (8 PM) in 20 patients with VA (mean age 54.5 years; 10 men and 10 women) and in 20 control subjects (mean age 54.2 years; 10 men and 10 women). All patients underwent 24-h ambulatory electrocardiographic monitoring during the study.

RESULTS: Flow-mediated vasodilation in patients with VA was deteriorated by the early morning and improved by the afternoon (patients with VA at 8 PM vs. 6 AM vs. 2 PM: 7.8 ± 2.1% (p < 0.01 vs. VA at 6 AM) vs. 5.4 ± 2.3% vs. 8.8 ± 1.9% (p < 0.01 vs. VA at 6 AM); control subjects: 9.5 ± 2.8% vs. 9.0 ± 2.2% vs. 9.9 ± 1.9%, respectively). The frequency of spontaneous ischemic episodes was highest from midnight to morning and was lowest from morning to late afternoon (4 PM to midnight: 7 episodes; midnight to 8 AM: 25 episodes; 8 AM to 4 PM: 3 episodes).

CONCLUSIONS: There is diurnal fluctuation in endothelial function, which is associated with variation in the frequency of ischemic episodes.

Abbreviations and Acronyms   ACh   acetylcholine   ANOVA   analysis of variance   ECG   electrocardiogram/electrocardiographic   NTG   nitroglycerin   VA   variant angina

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