Hypertension is a disease of unknown etiology. Most investigators agree that retention of excess sodium (Na) underlies the sustained increase in blood pressure (BP) that characterizes hypertension. In children, BP elevation accompanies somatic growth in height and weight. While BP is known to be correlated to various somatic measurements, physiological mechanisms that underlie the observed associations remain unclear. Additionally, few investigations have examined whether any characteristics of somatic growth relate to the rise of BP or to the early onset of pre-hypertension or hypertension. Our preliminary data strongly suggest that the process of somatic growth is well synchronized with that of BP development. With the compelling data evidence, we propose to conduct an epidemiological study to delineate the relations among somatic growth, Na retention, and BP using data from an existing cohort of children. We hypothesize that a strong relationship of somatic growth with BP during the period of pubertal growth is mediated at least partially by increases in retention of Na. Along this line, we will examine the effects of somatic changes on measures of Na retention, and the effects of somatic growth characteristics on post-pubertal BP and the onset of pre- hypertension and hypertension. The study addresses some of the critically important but previously unanswered questions about the mechanisms of BP change during puberty. The hypotheses are derived from strong and compelling preliminary data evidence. If successfully carried out, the research may uncover early risk factors for hypertension, affording opportunities of timely interventions. To assess the post-pubertal BP and onset of pre-hypertension and hypertension, we seek to extend the follow-up period for 350 subjects in the cohort for five additional years till the subjects become adults. The existing cohort and the new extension will afford a rare opportunity to assess the linkage between somatic growth patterns in puberty and post-pubertal BP, with accommodation of Na retention. To implement, we have proposed an integrated analytical plan. By focusing on the beginnings of hypertension, before BP reaches hypertensive levels, this research provides a new approach for investigating mechanisms. While scientifically significant, the study is also cost effective because it fully utilizes the existing longitudinal data.

Public Health Relevance

This study uses longitudinal data to examine the effects of pubertal growth and sodium retention on post-pubertal blood pressure. The research may provide crucial insight on the physiological mechanisms that underlie the elevation of blood pressure. Its public health relevance is that it may facilitate the identification of somatic growth patterns that signal future risk of hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL095086-02
Application #
7748985
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Thrasher, Terry N
Project Start
2009-01-01
Project End
2012-12-31
Budget Start
2010-01-01
Budget End
2010-12-31
Support Year
2
Fiscal Year
2010
Total Cost
$385,000
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Tu, Wanzhu; Pratt, J Howard (2016) Small Potassium Channels: Speculation on a Role to Regulate Aldosterone Production and Blood Pressure. Hypertension 68:542-3
Wu, Jingwei; Tu, Wanzhu (2016) Development of a pediatric body mass index using longitudinal single-index models. Stat Methods Med Res 25:872-84
Tu, Wanzhu; Decker, Brian S; He, Zangdong et al. (2016) Triamterene Enhances the Blood Pressure Lowering Effect of Hydrochlorothiazide in Patients with Hypertension. J Gen Intern Med 31:30-6
He, Zangdong; Tu, Wanzhu; Wang, Sijian et al. (2015) Simultaneous variable selection for joint models of longitudinal and survival outcomes. Biometrics 71:178-187
Tu, Wanzhu; Wagner, Erin K; Eckert, George J et al. (2015) Associations between menarche-related genetic variants and pubertal growth in male and female adolescents. J Adolesc Health 56:66-72
Hannon, Tamara S; Gupta, Sandeep; Li, Zhuokai et al. (2015) The effect of body mass index on blood pressure varies by race among obese children. J Pediatr Endocrinol Metab 28:533-8
Tu, Wanzhu; Eckert, George J; Hannon, Tamara S et al. (2014) Racial differences in sensitivity of blood pressure to aldosterone. Hypertension 63:1212-8
Watson, S E; Li, Z; Tu, W et al. (2014) Obstructive sleep apnoea in obese adolescents and cardiometabolic risk markers. Pediatr Obes 9:471-7
Tu, Wanzhu; Pratt, J Howard (2013) A consideration of genetic mechanisms behind the development of hypertension in blacks. Curr Hypertens Rep 15:108-13
Yu, Zhangsheng; Eckert, George J; Liu, Hai et al. (2013) Adiposity has unique influence on the renin-aldosterone axis and blood pressure in black children. J Pediatr 163:1317-22.e1

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