A Population-Based, Prospective Study of Blood Pressure and Risk for End-Stage Renal Disease in China

Study Population

In 1991, a multistage, random-cluster sampling design was used to select a representative sample of the general Chinese population for the China National Hypertension Survey (10). A total of 950,356 men and women who were 15 yr and older were selected from all 30 provinces. In 1999, 17 of the 30 provinces participated in the China National Hypertension Survey Epidemiology Follow-up Study (CHEFS). Thirteen provinces were not included in the follow-up study because participants’ contact information was not available. However, sampling for the 1991 survey was conducted independently within each province, and participants who were included in the follow-up study were evenly distributed among the different geographic regions of the entire country, representing various stages of economic development. Overall, 169,871 participants (83,533 men and 86,338 women) who were 40 yr or older at the baseline examination were eligible for the follow-up study. From this population, a total of 158,666 (93.4%) participants or their proxies were identified and interviewed as part of the follow-up study. After exclusion of those with ESRD at baseline (n = 34) and those with missing BP measures (n = 267), data from 158,365 participants were included in this analysis.

Baseline Examination

Baseline data collection occurred during a single visit to a local field center. Information on demographic characteristics, medical history, and lifestyle risk factors were obtained using a standard questionnaire that was administered by trained staff. Physical activity was assessed using a questionnaire that asked participants about their work-related activities. Leisure-time physical activity was not ascertained because it was uncommon at the time of the baseline examination. Cigarette smoking was defined as smoking at least 1 cigarette per day for ≥1 yr. Data were collected on the amount and the type of alcohol consumed during the previous year.

Body weight and height were measured once during the visit by trained observers using a standard protocol, and body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. Overweight was defined in accordance with internationally recognized definitions as a BMI ≥25.0 kg/m² (13,14). Three BP measurements were obtained on a single occasion by trained nurses or doctors according to a standard protocol that was adapted from procedures that are recommended by the American Heart Association (15). BP was measured on the right arm in the sitting position using a standardized mercury sphygmomanometer after the participant had rested quietly for at least 5 min. In addition, participants were advised to avoid exercising; cigarette smoking; and consuming alcohol, coffee, or tea for at least 30 min before their BP measurement. The first and fifth Korotkoff sounds were recorded as SBP and DBP, respectively (15). The averages of all SBP and DBP measurements were used to define SBP and DBP, respectively.

Follow-Up Data Collection

Follow-up interviews were conducted in 1999 and 2000 and included tracking study participants or their proxies to a current address, performing in-depth interviews to ascertain disease status and vital information, and obtaining hospital records and death certificates. All ESRD events that were reported during the in-person/proxy interview were verified by obtaining medical records or death certificates from the local hospital, dialysis unit, public health department, or police department. ESRD was defined as renal replacement therapy (dialysis or renal transplantation) or death from renal failure. Trained study staff visited all hospitals and dialysis units where patients received their treatment. The participants’ hospital records, including medical history, physical examination findings, laboratory test results, discharge diagnosis, and/or autopsy findings were abstracted by study staff using a standard form. In addition, photocopies of selected sections of the participants’ inpatient record, discharge summary, and pathology reports were obtained.

An end-point assessment committee in each province reviewed and confirmed (or rejected) the hospital’s discharge diagnosis and cause of death on the basis of the abstracted information using prespecified criteria. All completed abstraction forms of hospital records, death certificates, and photocopies of hospital charts were sent to the Cardiovascular Institute of the Chinese Academy of Medical Sciences in Beijing, where a study-wide end-point assessment committee independently reviewed all ESRD cases. Each ESRD case was verified by two committee members, the results were compared, and discrepancies were adjudicated by discussion involving additional committee members. The underlying causes of ESRD were largely based on hospital discharge diagnoses that were assigned by nephrologists or internists. Patients’ hospital charts were reviewed to confirm a personal medical history of diabetes, hypertension, glomerulonephritis, or other causes for ESRD. Deaths were classified as being due to renal failure when one of the following International Classification of Diseases, 9th Revision, Clinical Modification codes was listed on the death certificate as the underlying cause: 403 to 404 (hypertensive renal disease); 250.4 (diabetes mellitus with nephropathy); 274.1 (gouty nephropathy); 275.4 (nephrocalcinosis), 593.3, 593.4, 593.5, 593.7, 593.8, 593.9 (other kidney disorders); 596 (bladder-neck obstruction); 600 (hyperplasia of prostate); 753.1 (cystic kidney disease); 580 to 589 (nephritis, nephritic syndrome, or nephrosis); 590 (infection of the kidney); 591 (hydronephrosis); and 592 (calculus of the kidney and ureter) (16).

This study was approved by the Tulane University Health Sciences Center Institutional Review Board and the Cardiovascular Institute and Fu Wai Hospital Ethics Committee. Written informed consent was obtained from all study participants at their follow-up visit.

Statistical Analyses

Study participants were grouped according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) classification of BP as measured at the baseline examination (normal BP: SBP <120 mmHg and DBP <80 mmHg; prehypertension: SBP between 120 and 139 mmHg or DBP between 80 and 89 mmHg; stage 1 hypertension: SBP between 140 and 159 mmHg or DBP between 90 and 99 mmHg; and stage 2 hypertension: SBP ≥160 mmHg or DBP ≥100 mmHg) (17). Participants who reported current use of antihypertensive medication were included in the stage 2 hypertension category. Person-years of follow-up for each study participant were calculated from the date of the baseline examination until the date of death, development of ESRD, or the follow-up interview, whichever occurred first. Cumulative incidence of ESRD was calculated by JNC-7 BP category using the Kaplan-Meier method with differences across categories assessed using the log-rank test (18,19). Age-standardized incidence rates were calculated by JNC-7 BP category using 5-yr age and gender-specific incidence rates and the age distribution of the Chinese population from year 2000 census data as the standard.

Cox proportional hazards models were used to examine the multivariate adjusted relationship of BP categorized by JNC-7 with the incidence of ESRD. Initial models included adjustment for age and gender. Subsequent models included additional adjustment for geographic region (north versus south China), urbanization (urban versus rural residence), education, BMI, physical activity, current cigarette smoking, alcohol drinking, and history of diabetes and cardiovascular disease (stroke or coronary heart disease). History of diabetes and cardiovascular disease was modeled as a time-dependent variable in extended Cox models (20). These analyses were conducted separately for all-cause ESRD, glomerulonephritis-related ESRD, non–glomerulonephritis-related ESRD, and unknown cause of ESRD. Population-attributable risks were calculated for each BP category (21).

To explore further the association of BP with ESRD, we determined the incidence and hazard ratios of ESRD for quintile of SBP (<108.5, 108.5 to 118.5, 118.5 to 128.5, 128.5 to 141, and ≥141 mmHg), DBP (<68, 68 to 74, 74 to 80, 80 to 87, and ≥87 mmHg), and pulse pressure (<37, 37 to 42.5, 42.5 to 50, 50 to 60, and ≥60 mmHg). In addition, multivariate adjusted hazard ratios that were associated with 1 SD higher BP were used to compare the association of SBP, DBP, and pulse pressures with ESRD. Analyses of BP as a continuous variable were performed with each BP component included in the regression model separately and with both SBP and DBP simultaneously included in the regression models (or, equivalently, both pulse pressure and SBP or pulse pressure and DBP). Methods that take into account the multistage sample clustering were used to estimate variance in the Cox proportional hazards models (22). Statistical analyses were conducted using SAS statistical software (version 9.1; SAS Institute, Cary, NC).