As a cohort study, Beijing Health Management Cohort (BHMC) study aims to explore the important chronic diseases and general factors among participants at work or in retirement in Beijing. At the 2011-2012 baseline survey, 8917 participants took the diagnostic test of arterial stiffness. Of 8917 participants, 2555 participants with cardiovascular diseases, cancer or atherosclerosis and without information about HbA1c were excluded. 3314 participants failed to take the final diagnostic test at the end point of the cohort study in 2018-2019 survey. 3048 participants finishing the follow-up were enrolled in the study (Figure 1). We obtained the ethical approval from the Ethics Committee of the Capital Medical University (number 2013SY26) and informed consents from all of the participants.
The physical examination and measurement was conducted by trained medical professionals in the whole process based on the 1964 Declaration of Helsinki and the updated version.
Participants were required to take off shoes and heavy clothes to take the anthropometric measurement. Body mass index (BMI) is the measure of dividing the weight (kg) by the square of the height (m2). After at least 5 minutes’ rest and 30 minutes’ against caffeine, mean arterial pressure (MAP) was calculated as diastolic blood pressure (DBP) plus one third of pulse pressure, and the latter was measured as systolic blood pressure (SBP) minus DBP. Participants were supposed to keep calm in the sitting position, and the technology should be put at the height of heart, as well as the tested right arm. Such test should be conducted at least three times with 1-2 minutes’ intervals, and the mean of the records was applied.
After at least 12 hours’ overnight fast, the blood samples were collected from participants, and the following main indexes were tested by a chemistry analyzer, Beckman LX 20, Beckman, Brea, CA, USA: HbA1c, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), FBG and PBG. All analyses, such as samples transportation and the enzymatic method, were performed according to the manufacturer’s recommendations.
Demographic data can be obtained according to the questionnaire. Briefly, information about age, gender, and behavioral factors, including physical activity intensity (low, moderate and high intensity), education level (lower than high-school education and over or equal to high-school education), excessive salt intake (>6g/day), drinking status (past/current alcohol drinker), smoking status (past/current smoker), sleep duration (<6h/day, 6-8h/day and >8h/day) and medication history of hypertension and hyperlipidemia, was collected mainly.
Definition of arterial stiffness
We defined arterial stiffness as baPWV >1800m/s or ABI <0.9 [22-24] in this study. And the above two criteria were tested with an automatic arterial stiffness analyzer. The requirement of the participants was similar with that when testing the blood pressure. We calculated ABIs as the ratio of SBP at the ankle to that on the upper arm on each side, and the minimum ratio was applied. BaPWV was calculated based on pressure in ankles and upper arms and the distance tailored to the height of each participant by the analyzer automatically, and the maximum record was applied.
We stratified the study population into quartiles based on HbA1c level (Q1 group: participants with HbA1c ≤5.29%, Q2 group: participants with HbA1c range of 5.30-5.52%, Q3 group: participants with HbA1c range of 5.53-5.81%, Q4 group: participants with HbA1c >5.81%). TyG index was calculated as the ln[fasting TG (mg/dl) × FBG (mg(dl)/2].
Continuous variables are summarized with mean ± standard deviation or median with interquartile range (IQR). Categorical variables are presented as numbers and proportions. We used ANOVA test for non-paired samples of normally distributed parameters and the Kruskal-Wallis test for non-parametric variables. The Chi-Squared test was applied for the comparison of categorical variables among four groups.
Three-step stepwise multivariable-adjusted Cox proportional hazard regression models were conducted to explore the potential association between these parameters and the risk of the arterial stiffness. Model 1 was adjusted for age and gender. Model 2 was adjusted for variables in model 1, as well as education level, smoking status, drinking status, physical activity intensity, sleep duration, excessive salt intake and medication history. Model 3 was adjusted for variables in model 2 plus BMI, MAP, LDL-C, HDL-C and TG. As for TyG index, we excluded TG from model 3 considering the calculation.
Sensitivity analysis was performed by treating the four parameters (HbA1c, FBG, PBG and TyG index) as continuous variable in Cox analysis. The restricted cubic spline was used to assess the dose-response relationship between the average HbA1c, PBG, FBG and TyG index and the risk of arterial stiffness.
For all analyses, a two-tailed P value <0.05 was considered to be statistically significant. All statistical analyses were performed using R version 3.5.1 (R Foundation for Statistical Computing, Vienna, Austria), SAS version 9.4 (SAS Institute, Cary, North Carolina, USA) and Stata version 15 (College Station TX StataCorp LLC).