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.

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.

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

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.

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.