Blood Pressure Follow-up Study in Two Chinese Cohorts(C-BPCS) (C-BPCS)

Effect of the Interaction Between Environmental Factors and Genetic Predisposition on Long-term Blood Pressure in Chinese Population

Essential hypertension is a complex trait which results from interaction between environmental factors and genetic factors. The aim of this study is to investigate the effects of interaction between environmental factors and genetic factors on long-term blood pressure (BP) based on two established cohorts including "the cohort of Hanzhong adolescent hypertension study" and "the cohort of Mei county adult salt-sensitive hypertension study". Firstly, the Hanzhong cohort-based follow-up study is designed to observe the track of BP during the whole life time, and to explore the effects of many risk factors (such as salt-sensitivity, obesity et al) on long-term BP and the occurrence of hypertension, and also to analyze the relationship of different polymorphisms of sodium and potassium metabolism-related gene with BP changes and target organ damages. In addition, by using DNA samples collected from subjects of "Mei county adult salt-sensitive hypertension study"in which all participants had completed a chronic salt loading and potassium intervention trial, we attempt to examine the single nucleotide polymorphisms (SNPs) of sodium and potassium metabolism-related genes, as well as the relationship between these SNPs and BP responses to dietary sodium/potassium intervention, long-term BP change, the risk of hypertension and target organ damages were analyzed. This study would enable us to further explore the etiology of essential hypertension as well as to identify new genetic markers for predicting early hypertension and target organ damage.

Study Overview

• Status: Unknown
• Conditions: Hypertension
• Intervention / Treatment: Other: Incidence and risk factors of hypertension

Detailed Description

This study is a longitudinal cohort follow-up study. The main contents include:(1)Questionnaire design: questionnaire is designed according to the research contents and purposes. The standard questionnaires will be used to collect the general information, dietary habits, lifestyle, medical history and family history etc.(2)Anthropometric measurements: blood pressure, height, body weight,waist and hip, pulse will be acquired by medical practitioners who received professional trainings based on World Health Organization (WHO) standards, and passed relevant examinations.(3) Blood and urine samples collection: morning fasting blood, nocturia, and 24-hour urine specimen will be collected by medical staffs, and blind tubes will be set up according to 5% of the total samples. Blood biochemistries including serum total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, fasting glucose, creatinine and hsCRP can be measured using automatic biochemical analyzer. The sodium and potassium concentrations in the urine will be measured by flame photometry. The total sodium and potassium excretions in urine in 24h were calculated by multiplying the concentration and 24-h volume of urine. (4) Auxiliary examinations: Auxiliary examinations including carotid intima-media thickness, endothelium-dependent vasodilation (FMD), measurements of brachial-ankle pulse wave velocity (baPWV) and electrocardiographic parameters. The measurement will be done in hospitals by medical practitioners who received professional trainings and passed relevant examinations. (5) Single nucleotide polymorphisms detection: based on our previous studies, sodium and potassium metabolism-related gene polymorphisms will be detected using MassARRAY technology. (6) Data processing and statistics: we should input the data to the database, and utilize softwares such as SPSS, STATA, Haploview and FBAT to analyze. (7) Quality control: ① Questionnaire is strictly designed and amended by epidemiologist and clinical experts. ② A standardized "Investigator Handbook" will be stipulated according to the guidelines. ③ Staff members are required to do a rigorous training and pass the exam. ④ The investigation process will be strictly supervised by the principal investigator. ⑤ Data entry use the parallel double entry method. ⑥ During laboratory testing, blank control and blind detection are applied to ensure the quality. ⑦ Data analysis is performed by 2-3 postgraduates, inconsistent data need to be double checked.

• Study Type: Observational
• Enrollment (Anticipated): 5298

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Recruiting
      • First Affiliated Hospital of Xi'an JiaoTong University
      • Contact: Jianjun Mu, doctor; Phone Number: 0086-029-85323804; Email: mujjun@163.com
      • Contact: Chao chu, master; Phone Number: 0086-029-85323800; Email: iaacd@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

In March and April, 1987, investigators established the cohort of Hanzhong Adolescent Hypertension Study. A total of 4,623 adolescents aged 6-15 years old in over 20 schools of three towns (Qili, Laojun and Shayan) in Hanzhong, Shaanxi, China were recruited.

In 2003-2004, investigators established the cohort of Mei county adult salt sensitive hypertension Study. This study was a family-based dietary intervention study conducted in a Han Chinese population from rural areas of northern China. A total of 675 subjects from 126 families were recruited in this cohort.

Description

Inclusion Criteria:

1. Hanzhong cohort of Adolescent Hypertension Study:

   • adolescents aged 6-15 years old in over 20 schools of three towns (Qili, Laojun and Shayan) in Hanzhong, Shaanxi, China.

2. Mei county cohort of adult salt-sensitive hypertension study:

   • Han individuals in rural northern China
   • adults aged 18-60 years
   • individuals who had a mean systolic BP (SBP) between 130-160 mmHg and/or a diastolic BP (DBP) between 85-100 mmHg and no use of antihypertensive medications were identified as the proband
   • the probands'parents,siblings, spouses, and offspring were recruited for the study.

Exclusion Criteria:

During the follow-up period, the exclusion criteria are as follows:

• Secondary hypertension
• a history of severe cardiovascular disease
• chronic kidney disease or liver disease
• unable to complete the examination
• unable/refuse to sign the informed consent form

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hanzhong cohort; A total of 4623 adolescents aged 6-15 years old in Hanzhong rural areas were recruited in 1987.During the follow-up period, the information about the incidence and risk factors of hypertension will be collected.	Other: Incidence and risk factors of hypertension; During the follow-up period,General information(age, sex, BMI, blood pressure, the history of drink and smoke, medical history, etc).Blood biochemistry parameters（Lipid, hsCRP levels, etc）and other laboratory examination parameters(arterial stiffness,IMT, FMD) will be collected.
Mei county cohort; A total of 675 individuals from 126 families were recruited in this family-based dietary intervention study. A community-based BP screening was conducted among adults aged 18-60 years in the study villages. The probands who had a mean systolic BP (SBP) between 130-160 mmHg and/or a diastolic BP (DBP) between 85-100 mmHg and no use of antihypertensive medications and their parents, siblings, spouses, and offspring were recruited in this study. During the follow-up period, the information about the incidence and risk factors of hypertension will be collected.	Other: Incidence and risk factors of hypertension; During the follow-up period,General information(age, sex, BMI, blood pressure, the history of drink and smoke, medical history, etc).Blood biochemistry parameters（Lipid, hsCRP levels, etc）and other laboratory examination parameters(arterial stiffness,IMT, FMD) will be collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood pressure value(mmHg)	The follow-up study of these two cohorts will last approximately 18 months (Jul 2016 to Dec 2017). During this period, each subject will receive a three-day follow-up examination. Three BP(mmHg) measurements will be obtained using a mercury sphygmomanometer on the first day of the three-day follow-up period.	First day of the three-day follow-up period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular hypertrophy（g/m^2）	The follow-up study of these two cohorts will last approximately 18 months (Jul 2016 to Dec 2017). During this period, each subject will receive a three-day follow-up examination. Left ventricular mass index (LVMI,g/m^2）will be measured using echocardiography during the three-day follow-up period.	During the three-day follow-up period
Increased arterial stiffness（mm/s）	The follow-up study of these two cohorts will last approximately 18 months (Jul 2016 to Dec 2017).During this period, each subject will receive a three-day follow-up examination. Brachial-ankle pulse wave velocity（baPWV,mm/s）will be measured with Noninvasive automatic waveform analyzer during the three-day follow-up period.	During the three-day follow-up period
Carotid artery wall thickening（mm）	The follow-up study of these two cohorts will last approximately 18 months (Jul 2016 to Dec 2017).During this period, each subject will receive a three-day follow-up examination. Carotid Intima media thickness (IMT,mm）will be measured using Color Doppler Ultrasound Diagnostic System during the three-day follow-up period.	During the three-day follow-up period
Microalbuminuria（mg/24h）	The follow-up study of these two cohorts will last approximately 18 months (Jul 2016 to Dec 2017).During this period, each subject will receive a three-day follow-up examination. On the second day,24-hour urinary will be collected and the concentrations of microalbuminuria in the urine sample will be measured with Hitachi biochemical analyzer.The 24-h microalbuminuria（mg/24h）of each subject is calculated as the concentration of microalbuminuria multiplied by the 24-h urine volume of each individual.	Second day of the three-day follow-up period

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Investigators: Principal Investigator: Jianjun Mu, doctor, First Affiliated Hospital Xi'an Jiaotong University

Publications and helpful links

General Publications

• Mu J, Zheng S, Lian Q, Liu F, Liu Z. Evolution of blood pressure from adolescents to youth in salt sensitivies: a 18-year follow-up study in Hanzhong children cohort. Nutr J. 2012 Sep 14;11:70. doi: 10.1186/1475-2891-11-70.
• Liu F, Zheng S, Mu J, Chu C, Wang L, Wang Y, Xiao H, Wang D, Cao Y, Ren K, Liu E, Yuan Z. Common variation in with no-lysine kinase 1 (WNK1) and blood pressure responses to dietary sodium or potassium interventions- family-based association study. Circ J. 2013;77(1):169-74. doi: 10.1253/circj.cj-12-0900. Epub 2012 Oct 12.
• Niu ZJ, Yao S, Zhang X, Mu JJ, Du MF, Zou T, Chu C, Liao YY, Hu GL, Chen C, Wang D, Ma Q, Yan Y, Jia H, Wang KK, Sun Y, Yan RC, Man ZY, Ren DF, Wang L, Gao WH, Li H, Wu YX, Li CH, Gao K, Zhang J, Yang TL, Wang Y. Associations of genetic variations in NEDD4L with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults. J Clin Hypertens (Greenwich). 2022 Oct;24(10):1381-1389. doi: 10.1111/jch.14566. Epub 2022 Aug 30.
• Yuan Y, Mu JJ, Chu C, Zheng WL, Wang Y, Hu JW, Ma Q, Yan Y, Liao YY, Chen C. Effect of metabolically healthy obesity on the development of arterial stiffness: a prospective cohort study. Nutr Metab (Lond). 2020 Jul 2;17:50. doi: 10.1186/s12986-020-00474-8. eCollection 2020.
• Yuan Y, Chu C, Zheng WL, Ma Q, Hu JW, Wang Y, Yan Y, Liao YY, Mu JJ. Body Mass Index Trajectories in Early Life Is Predictive of Cardiometabolic Risk. J Pediatr. 2020 Apr;219:31-37.e6. doi: 10.1016/j.jpeds.2019.12.060. Epub 2020 Feb 12.
• Yuan Y, Hu JW, Wang Y, Wang KK, Zheng WL, Chu C, Ma Q, Yan Y, Liao YY, Mu JJ. Association between atherogenic index of plasma and subclinical renal damage over a 12-year follow-up: Hanzhong adolescent hypertension study. Eur J Clin Nutr. 2020 Feb;74(2):278-284. doi: 10.1038/s41430-019-0530-x. Epub 2019 Nov 14.

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: March 22, 2016
• First Submitted That Met QC Criteria: April 11, 2016
• First Posted (Estimate): April 12, 2016

Study Record Updates

• Last Update Posted (Actual): October 2, 2017
• Last Update Submitted That Met QC Criteria: September 28, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: blood pressure; Proteinuria; Vascular Stiffness; Hypertrophy, Left Ventricular; Carotid Artery Diseases
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: XJTU1AF-CRF-2015-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The achievements will be evaluated by papers published in specialized journals with a peer-reviewed system, and the original dates can be disclosed according to requirements.