Data source and study subjects
The design and inclusion criteria of the community-based prospective cohort study, named the Northeast China Rural Cardiovascular Health Study (NCRCHS), have been described previously [8, 9]. In all, 11,956 participants older than thirty-five years were enrolled from three countries in LiaoNing Province (Dawa, Zhangwu and Liaoyang) between 2012 and 2013. The Ethics Committee of China Medical University approved this study (Shenyang, China AF-SDP-07-1, 0-01). During 2015 and 2017, we invited participants at baseline to attend the follow-up study. In total, 1,256 out of 11,956 subjects were excluded due to a lack of contact information. Ultimately, 86.6% of the participants (10,349) finished the follow-up visits (median 4.66 follow-up years). All participants signed the written informed consent. We consider covariables that have complete information from the baseline visit in the present analysis. We excluded those participants who already were diagnosed CVD (n=821) and who were lack of experiment data (n=89). In the present study, 9439 participants were included.
Study variables
At baseline, participants were asked to finish a standardized questionnaire that contained detailed information about socioeconomic factors, lifestyle, demographic characteristics, and chronic disease history. Regular exercise was defined as yes or no. Self-reported history of cerebrovascular diseases, such as ischemic stroke, hemorrhagic stroke, and cardiovascular diseases, such as coronary heart disease and chronic heart failure at baseline, was recorded and confirmed by their medical records. Educational level included ≤ primary school, middle school, and ≥ high school. Annual income of the family was categorized into ≤ 5000 CNY/year, 5000-20000 CNY/year and >20000 CNY/year. Waist circumference was measured as previously described (8). Obesity was defined using BMI criteria with the cutoff ≥25 kg/m2 [BMI = weight (kg)/height (m) 2]. Blood pressure was measured automatically followed the standard criteria using an electronic sphygmomanometer (HEM-907; Omron, Tokyo, Japan). After fasting for at least 12 hours, participants were gathered together to take blood samples by trained nurses. Fasting plasma glucose (FPG) and lipid profiles, such as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol and triglyceride, were analyzed enzymatically. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was performed to calculate estimated glomerular filtration rate (eGFR) [10].
Diagnosis of CVD
The median follow-up was 4.66 years. In the present study, an incident cardiovascular disease was defined as a composite of new onset stroke or CHD during follow-up period. The specific incidences of stroke and CHD were also determined. For all participants reporting possible diagnoses or death, all available clinical information was collected including medical records and death certificates. All materials were independently reviewed and adjudicated by the end-point assessment committee. Stroke was defined according to the WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) criteria [11, 12], as rapidly developing signs of focal or global disturbance of cerebral function, lasting more than 24 hours (unless interrupted by surgery or death) with no apparent non-vascular causes. Hemorrhagic stroke was defined as stroke cases with diagnosis of subarachnoid hemorrhage or intracerebral hemorrhage and ischemic stroke was defined as stroke cases with diagnosis of thrombosis or embolism. Transient ischemic attack and chronic cerebral vascular disease were excluded. CHD was defined as a diagnosis of hospitalized angina, hospitalized myocardial infarction, CHD death or any revascularization procedure [13].
Statistical analysis
Mean values ± standard deviations were used to describe continuous variables, and categorical variables were reported as numbers together with percentages. ANOVA, t-test, nonparametric test or the χ2-test were performed to evaluate differences among categories as appropriate. Cox proportional hazards models were used to identify the associations of obesity categories with the risk of newly onset CHD, stroke and CVD incidence with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated. Multivariable hazard ratio was adjusted for gender, age, ethnicity, educational status, marriage status, annual income, physical activity, cigarette smoking status, alcohol intake status, family history of stroke, family history of CHD, family history of hypertension, antihypertension medication, SBP, DBP, TC, TG, HDL-C, LDL-C, eGFR, FPG. SPSS version 17.0 software was used to calculate all the statistical analyses, and statistical significance was defined as P≤0.05.