Cohort Profile: The Henan Rural Cohort: a prospective study of chronic non-communicable diseases

With the rapid development of social mobility, change of lifestyle and environment and ageing of the population, chronic non-communicable diseases (NCDs) such as stroke, coronary heart disease, cancer, diabetes mellitus, hypertension, dyslipidaemia, obesity and chronic lung disease, have become leading causes of death globally.1 Although the steady increase in the prevalence of NCDs has slowed in some high-income countries, the global burden of NCDs is still rising due to its increasing prevalence in low- and middle-income countries, where 80% of all global NCD-related deaths occur.1 As a populous and large agricultural country, China is contributing the largest number of NCDs patients and deaths due to ageing, lifestyle changes and psychosocial stress.2–4 Although great efforts have been made to control NCDs in China, the prevalence of NCDs still continues to increase, especially in rural areas with limited resources.5–8 The latest report showed that the prevalence of NCDs had climbed from 15.3% in 2003 to 29.5% in 2013 in rural areas, and the increase of incidence rates in rural areas exceeds that of those in cities (the corresponding rates were 27.7% and 36.7%, respectively).9 In addition, rural NCD patients are facing the risks of disability and life-threatening conditions that result from complications of NCDs because of lack of medical service resources and coverage by health care systems.8,9 Therefore, it is urgent to understand the potential risk factors contributing to rural China’s current epidemic of NCDs, and then to adopt effective intervention measures to improve the prevention of NCDs and reduce the disease burden in Chinese rural residents. Inherited factors, multiple environmental exposures and behavioural factors likely contribute to the growing burden of NCDs in the Chinese rural population. However, the relative contribution of these various risk factors has not yet been clearly determined. Although some genome-wide association studies (GWAS) have identified a large number of common gene variants for some chronic diseases,10–13 the conclusions are not entirely appropriate for the Chinese people, especially for Chinese rural populations considering the diversities in ethnicity, economic level, education, dietary factors and behavioural/lifestyle factors. In addition to inherited and behavioural factors, unique environmental exposures, such as pesticides, metal elements and air pollution, are also thought to contribute to NCDs’ development and mortality.14–20 To address the urgent need for data on NCDs prevalence, risk factors and associated conditions in resource-constrained settings, the Henan Rural Cohort study was launched in Henan from July 2015 to September 2017 based on a standardized survey approach and stringent quality control measures.21 Henan province is located in central China, with a permanent resident population of approximate 94 million in 2010.22 It is an important province in agricultural production, with a rural population accounting for 79% of the total population. However, definitive data on prevalence of NCDs and their risk factors remain limited in Chinese rural areas. The purposes of the Henan Rural Cohort study were to: (1) determine the prevalence of stroke, coronary heart disease, cancer, diabetes mellitus, hypertension, dyslipidaemia, obesity, osteoporosis, mental disorders and other common NCDs in a rural Chinese adult population; (2) estimate the disease burden and complications of NCDs indicated above; (3) describe the temporal dynamics of NCD prevalence and their risk factors; (4) assess the effects of environmental exposures, lifestyle and genetics on NCDs; (5) develop and evaluate morbidity and mortality risk assessment tools for NCDs; (6) explore the underlying causes of NCDs and then aid in the development of strategies to prevent and control the diseases in resource-constrained settings. The Henan Rural Cohort was established in five rural regions (Suiping county, Yuzhou county, Xinxiang county, Tongxu county and Yima county) of Henan province in China, and the baseline survey was carried out between July 2015 and September 2017 (Figure 1). A multistage, stratified cluster sampling method was used to obtain samples in the general population. The target population was adults aged 18–79 years who were permanent residents and available for completing follow-up studies of mortality and morbidity. An individual was excluded if they had a severe physical or mental disease that made them unable to answer the questionnaire or if they had a severe medical condition that made them unable to report to the survey location. In the first stage, five rural counties were selected from different geographical regions (south, central, north, east, and west) in Henan province through simple cluster sampling. In the second stage, one to three rural communities (referred to as ‘townships’) in each county were selected by the local Centre for Disease Control and Prevention in consideration of the coherence of the residents, population stability and local medical conditions. In the final stage, all permanent residents in each administrative unit (rural village) of the selected township who were 18–79 years and signed informed consent were selected as the study sample. All participants were asked to bring their unique national identity (ID) cards to the health examination centre in the local community. The response rate for participation at each survey site will be related to these known denominators. The procedure of study was approved by the Zhengzhou University Life Science Ethics Committee. Locations of the five survey sites in the Henan Rural Cohort. The map of China was downloaded from the National Administration of Surveying, Mapping And Geoinformation (serial number was 8012790168). The map of Henan province was generated by the Map Institution of Henan Province. The National Electronic Disease Surveillance System (NEDSS) and the New Rural Cooperative Medical System (NRCMS) in China were the major means to provide basic health care information and to prevent and control diseases in rural China. The systems enable us to collect clinical data, to track the incidence and prognosis of disease and deaths (including registration of all-cause mortality). Follow-up surveys will be conducted every 3 years having begun in 2018. All surviving study participants will be invited for re-survey with repeat interviews, including the same questionnaire interview, physical examination and blood, urine and stool collection procedures as those used in the baseline survey. Self-reported chronic diseases and history of medication use, such as stroke, coronary heart disease, cancer, diabetes mellitus, hypertension, dyslipidaemia, mental disorder and other diseases, are being further identified and confirmed through the sound NEDSS and NRCMS in China. The diagnoses of these conditions are based on well-accepted international standards. Causes of death are classified according to the 10th version of the International Statistical Classification of Diseases (ICD-10) and Related Health Problems. All deaths during follow-up will be checked for cause-specific mortality through the death registries. The local household registration system enables us to locate participants who move to other areas, and will minimize the expected rate of loss to less than an estimated 10% in follow-up. Figure 2 shows the overall study plan. Study plan of the Henan Rural Cohort. After an overnight fast of at least 8 h, all participants came to the health examination centre in the local community. Following informed written consent, the collections of data, blood, urine and partial stool samples (10%), anthropometric measurements and clinical examinations were performed by well-trained physicians, nurses and technicians. A pilot study was conducted 6 months before the formal investigation. The aim was to evaluate whether the questionnaire was easily understood, each item was clear etc. We modified the questionnaire for the language and inclusive items if necessary. In addition, the completion time was determined before the formal investigation. After the pilot study, the validity and reliability of the questionnaire were assessed by a small simple survey. A total of 76 participants were asked to complete the questionnaire on the same day. One week later, the second survey was conducted in the same participants, and the response rate was 100%. The internal consistency was assessed by Cronbach’s alpha coefficient (α = 0.729). The test-retest reliability was examined by intraclass correlation coefficients (ICC) using a two-way mixed model, and the value was 0.841, which suggested that the questionnaire has high test-retest reliability. Data were collected by face-to-face interview. A standard questionnaire including information on general demographic characteristics (name, sex, age, education level, marital status, occupation, income, medical services etc.), lifestyles (dietary intake, smoking and drinking status, physical activity levels etc.), sleep situation, personal history of diseases (stroke, coronary heart disease, cancer, diabetes mellitus, hypertension, dyslipidaemia etc.), family history of diseases (stroke, coronary heart disease, cancer, diabetes mellitus, hypertension, dyslipidaemia etc.), menstrual and reproductive history (for women) and mental status was completed by well-trained investigators. Table 1 describes the detailed information of the questionnaire interview. Summary of data collected in the Henan Rural Cohort The main diseases of personal disease history and family history included stroke, coronary heart disease, cancer, diabetes mellitus, hypertension, dyslipidaemia, pulmonary emphysema, chronic obstructive pulmonary disease, gastric disease, intestinal disease, liver disease, gall bladder disease, pancreatic disease, splenic disease, kidney disease, skin disease and gout. Anthropometric measurements included height, waist circumference, hip circumference, weight, body fat percentage (BFP), visceral fat index (VFI), basal metabolic rate (BMR), resting blood pressure, heart rate, hand grip and lung function. Height was measured with subjects’ shoes off in an upright position against a calibrated wall. Waist circumference at the level of 1.0 cm above the navel and hip circumference at the maximal level of the hip were measured with light clothing. Body weight, BFP, VFI and BMR were measured with the subjects in light clothing and shoes off using OMRON V. BODY HBF-371 according to the operating instructions. Electronic sphygmomanometers (Omron HEM-7071A, Japan) were used to measure resting blood pressure and heart rate on the right arm supported at heart-level sitting position in triplicate. The average of the three measures was used for the statistical analysis. To ensure accurate readings, the participants were asked to rest for at least 5 min, and with no tea or alcohol consumption, cigarette smoking or excessive physical activity for at least 30 min or longer before the measurement. Slow vital capacity (SVC), forced vital capacity (FVC), forced expiratory volume in one s (FEV1), maximum voluntary ventilation (MVV) and bronchodilator test (BD) were the main elements of the lung function tests. Clinical examinations included bone mineral density, 12-lead resting electrocardiogram (ECG), chest X-ray and abdominal B-type ultrasound inspection (for potential conditions in the liver, gall bladder, pancreas, spleen and kidney, and the uterus, ovaries and fallopian tubes for women). Table 2 shows details of the equipment for anthropometric and clinical examinations. Summary of anthropometric and clinical measures collected at baseline in the Henan Rural Cohort After at least 8 h of overnight fasting, venous blood samples were collected for routine blood measurements, biochemical indexes, metal elements, hormone levels, pesticide levels, DNA, RNA, microRNA extraction and so on. A total of 15.0 ml fasting venous blood was collected into one ethylenediamine tetraacetic acid dipotassium (EDTA-K2) anticoagulation tube of 10.0 ml and one vacuum tube without anticoagulation of 5.0 ml. Plasma and serum samples were separated from whole blood through centrifugation for 10 min at the relative centrifugal force 2000 g at room temperature. Serum samples were forwarded to measure biochemical indexes that included fasting blood glucose, insulin, blood lipids, hepatic function, kidney function, high-sensitivity C-reactive protein (hsCRP), etc. In addition, repeat measures were obtained on a random sub-sample (10%) of participants, providing estimation of reliability. Figure 3 displays the detail of the flow diagram of blood separation and detection of main blood biochemical indexes. A total of 30.0 ml mid-stream morning urine was collected to detect routine urine substances, urinary albumin (UALB), urine creatinine (Ucr) etc. The details of equipment for biochemical indexes are in Table 2. Partial stool samples (10%) were also collected to measure gut microbiota. Whole blood, plasma, white cell, serum, blood clot, urine, stool samples, DNA, RNA and mircoRNA were stored in -80°C cryogenic refrigerator. Flow diagram of blood separation and detection of main blood biochemical indexes. On the same day of questionnaire completion, trained investigators checked the integrity and logical errors of the questionnaire, and if there were any problems, they contacted the participants by phone and amended the responses. The questionnaire was entered into the computer database twice by two trained investigators independently using EpiData3.1 software. Within 4–6 weeks of the baseline survey, resurvey and repeat measures were obtained on a random sub-sample (2.5%) of participants, providing estimates of reliability and checks against any serious organizational failure. An ecological study on metal elements and pesticides was also implemented during the period. Samples of farmland soil, surface water and drinking water were collected to evaluate the levels of external exposure to metal elements and pesticides by the grid method at the grid centre in the five survey fields. Meanwhile, data for internal exposure (including metal elements, organochlorine and organophosphorus pesticides) was also measured in plasma samples of participants. Furthermore, vole, sparrow, meat of livestock, vegetable and fruit samples were obtained to measure metal elements and pesticide residues at each site. In addition, the dynamics of environmental exposure, especially of air pollutants, were also obtained from the local department of environmental protection together with the Food and Drug Administration. Table 3 summarizes the detail of samples collected and measurement indexes in the ecological study. Summary of samples collected and measurement indexes in the ecological study in the Henan Rural Cohort (collected during 2015–17) A total of 41 893 invitations were sent out to those who met the inclusion criteria, and 39 259 people (93.7%) responded and were recruited.23,24Table 4 shows the baseline characteristics of the participants. Among the participants, 60.5% (n = 23 769) were women, with a mean age 54.9 years. About 39.8% graduated from middle school and 15.4% obtained high school or higher education. Most of the participants (89.8%) were married. The proportion of the participants who had less than 2000 RMB per capita monthly income was 92.6%. Among men, 47.9% were current smokers and 20.5% were former smokers. Among women, only 0.3% were current smokers and 0.1% were former smokers. The rates of current alcohol use, high fat diet, more vegetable and fruit intake, high salt diet and physical inactivity for men and women were 41.7% vs 2.6%, 25.0% vs 15.2%, 42.7% vs 41.1%, 19.9% vs 16.5% and 35.7% vs 30.2%, respectively. The mean height, weight, waist circumference, hip circumference, BMI, BFP, VFI, BMR, grip-left, grip-right, systolic blood pressure, diastolic blood pressure and heart rate (HR) were 159.7 cm, 63.5 kg, 84.1 cm, 94.5 cm, 24.8 kg/m2, 30.1%, 9.4, 1374.2 kcal, 28.4 kg, 29.9 kg, 126.0 mmHg, 77.7 mmHg and 75.7 beats/minute, respectively. The mean sleep global score estimated according to the Pittsburgh Sleep Quality Index (PSQI) was 3.8. The baseline characteristics of the participants in the Henan Rural Cohort (collected during 2015–17) Continuous data are presented as mean and standard deviation mean ± SD, and categorical data are presented as number and percentage n Table 5 biochemical characteristics of the participants. The mean fasting blood glucose, insulin, total and were and respectively. In addition, the mean and of blood routine hepatic function, kidney function and urine are in Table The levels of biochemical of the participants in the Henan Rural Cohort (collected during 2015–17) Continuous data are presented as mean and standard deviation [mean ± SD, and categorical data are presented as number and percentage [n high-sensitivity C-reactive white blood blood total total urinary urine The detection of was conducted in of the participants. Table 6 shows the prevalence of common The overall prevalence was for stroke, for coronary heart disease, for cancer, for diabetes mellitus, for hypertension, for dyslipidaemia, for for general obesity, for abdominal obesity, for metabolic for for and for respectively. The prevalence of the common chronic NCDs in the Henan Rural Cohort (collected during 2015–17) data are presented as number and percentage [n waist circumference cm for women, and cm for BMI, body The detection of and was conducted in 30 participants. for the the genome-wide in in the population, a study was conducted in a sub-sample (10%) of the participants. of common variants in a number of participants also will be implemented to risk factors, to explore and to develop the risk to the morbidity and mortality of the common are to the Henan Rural Cohort study. the study population is in that has rapid economic and social which will provide important in the and measurement of prevalence and risk factors of the NCDs that in low- and middle-income the large number of including whole blood, plasma, serum, white and blood as as DNA, RNA and microRNA samples, were collected at resources will the effective and of information the and variants for the detailed information on diet, personal and family disease menstrual and reproductive history (for and mental status and anthropometric measures was also collected at the baseline survey, which will the of studies of biochemical and as as the of the of and environmental risk factors, on the the samples of farmland soil, surface and drinking and in the will the of an ecological study to explore the effects of external exposure on the disease diagnoses and follow-up are to database through the NEDSS and of health status and of medical The of the Henan Rural Cohort study its on information for some lifestyle and medical factors. However, higher test-retest effective of study and as as the sound NEDSS and NRCMS in China, will ensure the and reliability of the the proportion of the participants aged years was and information on exposures was not available for the of is increasing that exposures have on chronic disease risk in adult and a approach be more However, the high prevalence and incidence of the common NCDs in and adults in the of rapid will provide us with for the the were based on only a of China, which not be a of the Chinese rural population. However, the rural population of Henan province for of rural Chinese population, and the based on large rural study, to some the prevalence of the common NCDs in Chinese rural areas. The Henan Rural Cohort and to the of data and Although the study database is not available in the because of some information at and for potential be in and further information are invited to the corresponding to: or The Henan Rural Cohort is a study with its major to understand the effects of environmental exposures, lifestyle and genetics on NCDs in areas that are rapid economic and social A total of 39 259 participants aged 18–79 years were for the Henan Rural Cohort which was in Tongxu and Yima counties of Henan province in China from July 2015 to September Follow-up surveys will be conducted every 3 years in 2018. The a of individual factors, health personal disease family menstrual and reproductive history (for sleep and mental status, anthropometric clinical samples and In addition, external exposure levels of pesticides, metal elements and air were also collected and measured in study. An ecological study has been and and samples of farmland soil, surface drinking meat of livestock, and and were collected to evaluate the effects of environmental exposures on are the corresponding with any was supported by the National and of China National Science of China Henan Science for Science and of Henan and and of Zhengzhou University The had no in the study data collection and to or of the We all study participants and of Xinxiang Medical Yuzhou for Disease Control and Yima for Disease Control and for Disease Control and Prevention and Tongxu for Disease Control and In addition, the to and for their of the and to of