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

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.

Methods: A 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%).

Results: Of 814 normotensives (BP <140/90 mm Hg 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.

Conclusion: A high level of plasma ET-1 predicted the development of hypertension in normotensive subjects.