High level of plasma endothelin-1 predicts development of hypertension in normotensive subjects

Shun Ichi Kumagae, Hisashi Adachi, David R. Jacobs, Yuji Hirai, Mika Enomoto, Ako Fukami, Maki Otsuka, Yasuki Nanjo, Eishi Esaki, Eita Kumagai, Kuniko Yoshikawa, Kanako Yokoi, Kinuka Ogata, Eri Tsukagawa, Akiko Kasahara, Kyoko Murayama, Tsutomu Imaizumi

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Background: Endothelin-1 (ET-1) is a potent vasoconstrictor derived from the endothelium. However, most large scale cross-sectional studies in humans have indicated no relationship between plasma ET-1 levels and hypertension. The present study was designed to determine whether high plasma ET-1 levels predict the development of hypertension.MethodsA total of 1,492 subjects received a health examination in the Japanese cohort of Seven Countries Study in 1999, when, we examined blood pressure (BP), body mass index (BMI), and blood chemistries. Data on fasting ET-1 were obtained from 1,451 individuals. Seven years later, 1,261 subjects (494 males and 767 females) were re-examined (follow-up rate = 87%).ResultsOf 814 normotensives (BP 140/90mmHg without antihypertensive medications) at baseline, 222 subjects developed hypertension. We divided the baseline plasma ET-1 levels into quartiles. The odds ratio for the development of hypertension after 7 years was 1.79 (95% confidence interval (CI): 1.08-2.96) in the highest quartile vs. the lowest quartile of ET-1 level after adjustment for confounding factors.ConclusionA high level of plasma ET-1 predicted the development of hypertension in normotensive subjects.

Original languageEnglish (US)
Pages (from-to)1103-1107
Number of pages5
JournalAmerican journal of hypertension
Issue number10
StatePublished - Oct 27 2010

Bibliographical note

Funding Information:
Acknowledgments: We are grateful to the members of the Japan Medical Association of Ukiha, the elected officials and residents ofTanushimaru, and the team of cooperating physicians for their help in performing the health examinations.This study was supported in part by the Kimura Memorial Heart Foundation (Fukuoka, Japan).


  • Seven Countries Study
  • Tanushimaru
  • blood pressure
  • endothelium
  • epidemiology
  • hypertension
  • prospective study


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