Study population
NCRCHS is a prospective cohort study in a general population in Northeast China. The methods of the study, including research design, personnel recruitment, and data collection, have been elaborated in previous publications [16-17]. Briefly, using multistage, randomly stratified, cluster-sampling, 11956 participants aged at least 35 years were recruited from rural areas of Liaoning province between January 2013 and August 2013. Subsequently, participants were invited to attend follow-up visits in 2015 and 2018, and 6017 hypertensive participants were consented and eligible for the follow-up study. A total of 5249 participants of hypertension completed at least one follow-up visit. In the current study, we excluded baseline history of coronary heart disease (n=355) and stroke (n=590), and missing physical indicators (n=60). Eventually, data from 4244 participants were available for analysis. The Ethics Committee of the First Hospital of China Medical University (Shenyang, China) approved the study. All participants provided written informed consent.
Data collection
Data was collected during a single clinic visit by cardiologists and trained nurses using a standard questionnaire by face-to-face interview. Before the survey was performed, we invited all eligible investigators to attend the organized training. The training contents included the purpose of this study, how to administer the questionnaire, the standard method of measurement, the importance of standardization, and the study procedures. A strict test was evaluated after this training, only those who scored perfectly on the test could become investigators. During data collection, our inspectors had further instructions and support.
All participants were asked about the current status of smoking, drinking and the history of diseases. Base on the recommendations of the Working Group on Obesity in China, participants were stratified according to the BMI levels as underweight group (BMI<18.5 kg/m2), normal weight group (18.5 kg/m2≤BMI<24 kg/m2), overweight (24 kg/m2≤BMI<30 kg/m2), or obesity (BMI≥30 kg/m2). WHtR was calculated as WC divided by height. According to the reports from Ashwell, we categorized WHtR as WHtR<0.40, 0.40≤WHtR≤0.50, 0.50<WHtR≤0.60, WHtR>0.60. The group with 0.40≤WHtR≤0.50 was used as the reference group [18-20].
According to American Heart Association protocol, blood pressure was measured three times at 2-min intervals after at least 5 min of rest using a standardized automatic electronic sphygmomanometer (HEM-907; Omron). The participants were advised to avoid caffeinated beverages and exercise for at least 30 min before the measurement. During the measurement, the participants were seated with the arm supported at the level of the heart. The mean of three blood pressure measures was calculated and used in all analyses. Hypertension was defined as a mean SBP at least 140 mmHg and/or a mean DBP at least 90 mmHg, and/or use of antihypertensive medication in the previous 2 weeks [21-22]. Diabetes mellitus was defined as FBG at least 7.0 mmol/l and/or self-reported physician-confirmed diagnosis [23]. Fasting blood samples were collected in the morning after at least 10 h of fasting. Blood samples were obtained from an antecubital vein into BD Vacutainer tubes containing ethylenediaminetetraacetic acid. Serum was subsequently isolated from the whole blood, and all serum samples were frozen at -80℃ for testing at a central, certified laboratory. Triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and other blood biochemical indexes were analyzed enzymatically using the an Olympus AU640 autoanalyzer (Olympus, Kobe, Japan). All blinded duplicate samples were used for these analyses.
Judgment and definition of clinical outcomes
For all participants, all available clinical information on possible diagnoses or mortality was collected, including data from medical records and death certificates. Subsequently, materials were independently reviewed and adjudicated on by an endpoint assessment committee. CVD was defined as stroke or Coronary heart disease (CHD). Stroke was defined as rapidly developing signs of focal or global cerebral function disturbance lasting more than 24 h (unless interrupted by surgery or death) with no apparent nonvascular causes, based on the WHO Multinational Monitoring of Trends and Determinants in CVD criteria [24]. CHD was defined as a diagnosis of angina requiring hospitalization, miocardial infarction (MI) requiring hospitalization, CHD-related mortality, or any revascularization procedure [25].
Statistical analysis
Descriptive statistics were calculated for all variables, including continuous variables (reported as means and SDs) and categorical variables (reported as frequencies and percentages). As appropriate, differences between categories were evaluated using the t test, or the x2 test. Kaplan–Meier method was used to calculate the cumulative incidence for adverse events, and log-rank test was used to compare differences. Besides, to evaluate the improvement in risk prediction for adverse outcomes by adding WHtR to the conventional model (including age, sex, current smoking, current drinking, SBP, DBP, TC, HDL-C, LDL-C, triglyceride, and diabetes), we calculated the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) for CVD prediction models respectively (conventional model vs. conventional model+ WHtR). The calculation method is IDI=(Pnew, events-Pold, events)-(Pnew, non-events-Pold, non-events). With the larger value of IDI, the new model has the better prediction ability.
SPSS software version 22.0 (SPSS Inc., Chicago, Illinois, USA) and statistical software packages R (http://www. R-project.org, The R Foundation) were used for statistical analyses. P values were considered to be statistically significant if less than 0.05.