This study is based on a health risk assessment study (HERAS) that aimed to characterize cardiovascular risk factors and explore surrogate markers of CVD in Korean adults. The study cohort consisted of 20,530 individuals aged ≥ 20 years who voluntarily visited the Health Promotion Center, Gangnam Severance Hospital, Yonsei University College of Medicine, for regular health examinations between November 2006 and June 2010. Among 20,530 participants initially assessed, 1,590 (7.7%) participants with a history of IHD or ischemic stroke, a previous diagnosis of type 2 diabetes or a fasting plasma glucose level ≥ 126 mg/dL were excluded. We also excluded participants who met at least one of the following criteria: age <30 years, missing data, current use of dyslipidaemia medication or aspirin, high-sensitivity C-reactive protein (hsCRP) level ≥ 10 mg/L (N = 2,485). After exclusion criteria were applied, 16,455 participants (8,426 men and 8,029 women) were included in our final analysis.
Each participant completed a lifestyle and medical history questionnaire that included information regarding cigarette smoking, alcohol consumption, and physical activity.
Smoking status was defined using the following categories: non-smoker, ex-smoker, and current smoker. Questions regarding alcohol intake included information regarding consumption frequency on a weekly basis. Regular alcohol consumption was defined as alcohol consumption ≥ two times per week. Participants were asked about their level of physical exercise on a weekly basis, and regular exercise was defined as exercise ≥ three times per week. Body weight and height were measured to the nearest 0.1 kg and 0.1 cm, respectively, in light indoor clothing without shoes. BMI was calculated as an individual’s weight in kilograms divided by the square of his/her height in metres (kg/m2). Systolic blood pressure and diastolic blood pressure were measured on the patient’s right arm using a standard mercury sphygmomanometer in the sitting position after 10 min of rest (Baumanometer, W.A. Baum Co Inc., Copiague, NY, USA). All blood samples were obtained from the antecubital vein after overnight fasting for 12 h. Fasting plasma glucose, total cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol levels were measured via enzymatic methods using a Hitachi 7600 automated chemistry analyser (Hitachi Co.; Tokyo, Japan). hsCRP concentrations were measured with a Roche/Hitachi 912 System (Roche Diagnostics, Indianapolis, IN, USA) using a latex-enhanced immunoturbidimetric method with a low limit of detection of 0.09 mg/L. Hypertension was defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or current use of hypertension medication. Chronic kidney disease (CKD) was defined either as renal tissue damage or reduced renal functioning, as determined by an eGFR value < 60 mL/min/1.73 m2 or proteinuria 1+ or greater .
The primary outcome assessed was IHD, which consisted of angina pectoris (ICD-10 codes I20) or acute myocardial infarction (ICD-10 codes I21) that occurred after initial study enrolment. To define baseline and post-survey outcomes, we linked a personal, 13-digit identification number that was assigned to each subject with Korea Health Insurance Review & Assessment (HIRA) data, which is a repository of claims data collected in the process of reimbursing healthcare providers, between November 2006 and December 2010. Participants that were found to have had IHD or ischemic stroke (ICD-10 codes I20, I21, and I63) at the time of their initial assessment were excluded before the final analysis.
The TyG index values were categorised into quartiles, as follows: Q1 (≤ 8.08), Q2 (8.09–8.45), Q3 (8.46–8.85), and Q4 (≥ 8.86). All data are presented as means with standard deviations or percentages. The baseline characteristics of the study population according to the TyG index quartiles were compared using an analysis of variance (ANOVA) model for continuous variables and the chi-squared test for categorical variables. Kaplan–Meier curves were used to assess the cumulative incidence of IHD. The log-rank test was used to determine whether the distributions of cumulative IHD incidence differed among groups. Pairwise comparisons of receiver-operating characteristic (ROC) curves were used to contrast area under the ROC curve (AUC) of IHD incidence based on TyG index, fasting plasma glucose, and serum triglyceride levels. Further, AUC values were used to test the sensitivity and specificity of biomarkers for predicting IHD. For multivariate analysis, after setting the lowest TyG index value quartile as a reference group, hazard ratios (HRs) and 95% confidence intervals (CIs) for incident IHD were calculated using the Cox proportional-hazards regression model after adjusting for potential confounding variables. All analyses were performed using SAS version 9.4 software (SAS Institute Inc., Cary, NC, USA). All statistical tests were two-sided, and statistical significance was set at P < 0.05.