Study population
This study was based on a rural community-based prospective cohort study of Xifeng County, which is located in northeast China. From June 2012 to August 2012, 4157 Chinese rural participants aged ≥35 years from 2 of the 19 towns were included by cluster random sampling (2 towns, Anmin and Helong). Individuals who are pregnant, malignancies or mental disorders were excluded from this study. The study was approved by Ethics Committee of China Medical University (Shenyang, China)(Num. AF-SOP-07-1. 0–01). All procedures were conducted in accordance with the ethical standards of this committee. All participants received written consent after learning the objectives, benefits and medical details of the study and the confidentiality agreement regarding personal information.
All study subjects were invited to return for follow-up from June 2017 to September 2017, 330 individuals refused or were lost to follow-up and 3827 (92.06%) participants (or their guardians) agreed and completed the follow-up study. In this study, we analyzed the baseline and follow-up data, and only the participants provided complete data on the variables were analyzed in the study. The inclusion process of subjects is shown in Fig. 1.
Stroke and BP level assessment
In our study, on the basis of the WHO multi-national monitoring of the trend of cardiovascular disease and the decision factor (MONICA) standard [12], the stroke event is defined as a local (or global) brain dysfunction that continues the rapid growth of the > 24 h, with no apparent non-vascular causes. The definition included patients presenting with clinical signs and symptoms of subarachnoid hemorrhage, intracerebral hemorrhage, thrombosis. Transient ischemic attacks (TIA) and silent brain infarctions (cases without clinical signs or symptoms) were not included, neither were events associated with trauma, hematologic disorders, or malignancy. All information was independently reviewed by the endpoint evaluation committee and its members were unaware of the baseline risk factors for the study participants.
BP measurement and definition
According to the American heart association protocol, the BP was measured three times at least 2 min after a rest of at least 5 min using a standardized automatic electronic blood pressure measuring instrument (HEM − 907), which has been confirmed by British hypertensive association [13]. Participants were advised to avoid sports and alcohol for at least 30 min before they were measured. During the measurement, the participants’ arms were supported at the heart level. The average of three BP was used for the final analysis and evaluation.
According to the American Heart Association (AHA) published its 2017 hypertension clinical practice guidelines, BP was divided into the normal (SBP<120 mmHg and DBP<80 mmHg), elevated (SBP:120–129 mmHg and DBP<80 mmHg), stage1 hypertension (SBP:130–139 mmHg or DBP:80–89 mmHg) and stage2 hypertension (SBP:≥140 mmHg or DBP:≥90 mmHg) [14].
Data collection and measurements at baseline
Detailed methods have been described previously [15]. The data was conducted by face-to-face with cardiologists and trained nurses using standard questionnaires during a single clinic visit. Prior to the investigation, we invited all qualified investigators to participate in an organized training course. The training included the purpose of this study, how to manage the questionnaire, the standard measurement method, the importance of standardization and the research procedure. The training was followed by rigorous test, and only those who scored high on the test were allowed to act as investigators. Our inspector provided further instructions and support when collecting data.
A standardized questionnaire, had been described in previously literature [7, 9, 11, 15, 16], was used to investigate the demographic characteristics, lifestyle risk factors, family income, history of heart disease and any drugs used in the 2 weeks before the survey. Currently smoking was defined as at least one cigarette per day and for at least 1 year [16]. Alcohol consumption was defined as the weekly consumption of beer, wine and hard liquor, converted into mL of alcohol. Current drinking was defined as more than 1 drink/day for women and more than 2 drinks/day for men during the last year [16]. Education levels were divided into primary or middle school, middle school, and high school or above. Labor strength is based on the classification of China physical labor intensity, divided into 4 levels: I (Light labor), II (Moderate labor), III (Heavy labor), IV (Extremely heavy labor). Diabetes was defined as a history of diabetes or fasting blood glucose (FPG) level ≥ 7.0 mmol/L [17]. The history of antihypertensive drugs was taken within 2 weeks of the patient’s self-report. The history of coronary heart disease (CHD) was defined as patient’s self-report. Weight and height were measured to the nearest 0.1 kg and 0.1 cm, respectively, with participants in light weight clothing and without shoes. Body mass index (BMI) was calculated as the participant’s weight in kilograms divided by their height in meters squared (kg/m2).
After a fasting of at least 12 h, all participants collected fasting blood samples. Then isolated from whole blood serum, and serum samples were frozen at − 20 °C for testing at a center, certified laboratory. In automatic analyzer (Olympus AU640 automatic analyzer, Olympus Corp., kobe, Japan), general blood biochemical indexes such as total cholesterol (TC), FPG, low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), were analyzed. All laboratory equipment has been calibrated and samples are repeated with blind samples. Dyslipiemia was defined as TG ≥ 1.7 mmol/L, TC ≥ 5.2 mmol/L, LDL-C ≥ 3.4 mmol/L or HDL-C < 1.0 mmol/L [18].
Statistical analysis
Descriptive statistics were calculated for all the variables, including continuous variables (expressed as the mean values and standard error) and categorical variables (expressed as numbers and proportions). The difference of baseline characteristics between different sex were evaluated using the student’ t test or the χ2-test, as appropriate.
To evaluate stroke risk associated with BP level, participants were stratified by BP, which was according to the 2017 ACC/AHA classification criteria: normal, elevated, stage1 hypertension and stage 2 hypertension. Cox proportional hazards model (Forward Stepwise) was used to identify independent associations between different BP level or an increment of 1- standard deviation (SD) /20 mmHg in SBP/DBP and stroke incidence. All the variables included in the analysis start including: age, sex, ethnicity, education level, current smoking, current drinking, BMI, labor strength, dyslipidemia, diabetes, atrial fibrillation, coronary heart disease and antihypertensive medication. Hazard Ratios (HR) and the corresponding 95% confidence interval (CI) were calculated, with the normal BP level (SBP/DBP <120/<80 mmHg) as the reference. In addition, sensitivity analyses were performed after excluding participants who were taking antihypertensive medications. Furthermore, an age group BP level and a sex BP level interaction were analyzed in Cox proportional hazards model.
The incidence rate was denoted by case load/100,000 person-years. χ2 test was used to test the rate difference between sex.
All the statistical analyses were performed using SPSS version 20.0 software, and a 2-sided value of P less than 0.05 were considered to be statistically significant.