Elevated Plasma Transforming Growth Factor β1 Levels Predict the Development of Hypertension in Normotensives: The 14-Year Follow-Up Study

BACKGROUND Transforming growth factor beta 1 (TGF-beta 1) is a multifunctional cytokine. There is growing evidence that TGF-beta 1 is involved in the pathogenesis of hypertension and the development of target organ damage in hypertensives. Although several studies have shown that TGF-beta 1 induced vascular hypertrophy and remodelling in various vascular diseases, there are no longitudinal data on hypertension in the epidemiological studies. The present study tested the hypothesis whether elevated TGF-beta 1 levels can predict the development of hypertension. METHODS In 2002-2004, 528 subjects received health examinations in Uku town, southwestern Japan. We examined blood pressure (BP), body mass index, and blood test. Data on fasting plasma TGF-beta 1 were obtained from 528 individuals. Of these, 149 normotensives (BP < 140/90 mm Hg without antihypertensive medications) at baseline were followed-up for 14 years. RESULTS The receiver-operating characteristic curve was used and the calculated cutoff value was 8.9 ng/ml. Of 149 normotensives at baseline, 59 subjects developed hypertension. Plasma TGF-beta 1 levels were significantly associated with the development of hypertension after adjustment for confounding factors. To further examine the association between them, we performed logistic regression analysis. We divided the baseline plasma TGF-beta 1 levels into 2 groups using a cutoff value. The significant high odds ratio [3.582 (95% confidence interval, 1.025-12.525)] for the development of hypertension was found in the highest group of TGF-beta 1 level vs. the lowest group after adjustment for confounders. CONCLUSIONS This is the first report demonstrating the causal relationship between them. Elevated plasma TGF-beta 1 levels predicted the development of hypertension in normotensives in a population of community-dwelling Japanese.