Participants in our study were recruited from the "Early screening and comprehensive intervention project for high-risk groups of CVD" in Inner Mongolia. During 2015–2017, multistage stratified cluster sampling method was used to recruit the study population. In the first stage, six cities (Hohhot, Wuhai, Chifeng, Erdos, Hulun Buir, and Xingan League) were randomly selected from Inner Mongolia province, based on geographic, economic, and ethnic distribution factors. In the second stage, we selected one district or county from each of these cities according to the size of the district or county and population stability. In the third stage, two or three urban residential communities or rural villages were selected from each district or county, according to the size of communities or villages.
This study was approved by the ethics committee of Inner Mongolia Medical University (YKD202101133) and all enrolled participants provided their written informed consent. A total of 70,380 participants in the province of Inner Mongolia were finally enrolled.
Residents aged 35–75 years who had lived in Inner Mongolia for more than 6 months from 2015 to 2017 were included in the study. We excluded patients with malignant neoplasms and other diseases (hemorrhagic stroke, chronic obstructive pulmonary disease) that might influence the association between RC and ICVD. A total of 65,236 participants were finally included in the study.
Field investigation included a questionnaire survey, physical examination, and biochemical examination. In-person interviews were conducted by trained investigators using a standardized questionnaire. We collected information on social demographic characteristics such as age, ethnic group, disease history, medication history, and lifestyle factors including smoking. Data of height, weight, and blood pressure were obtained in physical examination.
Two consecutive blood pressure measurements were taken and the mean blood pressure value of the two readings was used. For each participant, blood pressure measurement was performed on the right upper arm after 5 minutes of rest, with the participant in a seated position, using an electronic sphygmomanometer (Omron HEM-7430). Fasting blood samples were collected after at least 10 hours of overnight fasting. Venous blood specimens were collected in Vacutainer tubes containing ethylenediaminetetraacetic acid. Serum total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) were measured using an automatic biochemical analyzer (Cardiochek PA). All laboratory equipment was calibrated.
Definitions of variables
Current smoker was defined as smoking at least one cigarette per day in the past 12 months. body mass index (BMI) was calculated as weight in kilograms divided by height squared, in meters, and obesity was defined as BMI ≥28 kg/m2. Patients with diabetes were defined as those who self-reported diabetes, those taking hypoglycemic agents, those receiving insulin injections, or those with measured fasting plasma glucose level ≥7.0 mmol/L. Hypertension was defined as an average systolic blood pressure (SBP) of at least 140 mmHg or an average diastolic blood pressure (DBP) of at least 90 mmHg, or self-reported use of antihypertensive medication in the past 2 weeks. Of patients with dyslipidemia, those who reported taking lipid-lowering medications (including Western medicine, Chinese patent medicine, and traditional Chinese medicine) during the previous 2 weeks were considered to be treated for dyslipidemia. Calculated RC was TC minus HDL-C and LDL-C, as previously reported.
A history of ICVD was defined as any self-reported history of coronary heart disease (CHD) events (including myocardial infarction, coronary artery bypass grafting, and percutaneous coronary intervention) and IS.
There is no physiological cut-point for discordance among different lipid or lipoprotein measures. Therefore, we defined discordance using clinical cut-points of LDL-C (2.6 and 3.4 mmol/L, respectively) and quartiles of RC. The population was divided into: (i) LDL-C ≤ clinical cut-point and RC ≤ one of the quartiles (concordant low RC), (ii) LDL-C ≤ clinical cut-point but RC > one of the quartiles (discordantly high RC), (iii) LDL-C > clinical cut-point but RC ≤ one of the quartiles (discordantly low RC), and (iiii) LDL-C > clinical cut-point but RC > one of the quartiles (concordant high RC). We used several cut-points to define discordance and to assess the robustness of our findings.
Numerical variables with a normal distribution are expressed using mean ± standard deviation; otherwise, variables are described using median and interquartile range. Categorical variable data are described using percentage. Differences between the baseline characteristics of ICVD and non-ICVD were compared with the chi-square and Mann–Whitney U tests. We constructed logistic regression models to assess the association between RC levels (given a non-normal distribution) and the risk of ICVD (including CHD events and IS). Model 1 was adjusted by age and sex; Model 2 was additionally adjusted for smoking, obesity, hypertension, diabetes, and use of lipid-lowering therapy. To further explore the interaction between LDL-C and RC in ICVD, the odds ratios (ORs) and 95% confidence intervals (CIs) of different combinations of LDL-C and RC and ICVD were calculated using the same models. A two-sided significance level was set at P<0.05. We used SAS version 9.4 for all statistical analyses (SAS Institute Inc., Cary, NC, USA).