Study population
This study was a single-center, retrospective, observational cohort study. From January 2016 to December 2016, a total of 3428 consecutive patients with Type 2 diabetes and ACS, who were admitted to Tianjin Chest Hospital for coronary angiography, were enrolled in this study.
Type 2 diabetes included those with history of type 2 diabetes, currently using insulin or hypoglycemic drugs, or fasting blood glucose(FBG)≥7.0 mmol/L or the 2-h plasma glucose of the oral glucose tolerance test≥11.1mmol/L. ACS was defined as unstable angina pectoris(UAP), non-ST-segment elevation myocardial infarction(NSTEMI) or ST-segment elevation myocardial infarction(STEMI). Those with severe valvular disease or congenital heart disease requiring cardiac surgery(n=42 ), acute infection(n=76), malignancy(n=14 ), severe hepatic dysfunction(n=18), severe kidney dysfunction(n=172), nutritional derangements(n=8), other severe medical illnesses or lacking complete clinical data(n=285) were excluded. Finally, a total of 2815 patients participated in the research. Patients were followed up from January 2017 to December 2019 by telephone or outpatient clinical visit, and 2531(89.9%) patients completed the 3-year clinical follow-up. The patients were divided into 3 tertiles according to the admission TyG index levels: tertile 1(n=844, TyG index≤8.848),tertile 2(n=843, 8.849≤TyG index≤9.382)and tertile 3(n=844, TyG index≥9.383).This study was approved by the local research ethics committee and strictly adhered to the Declaration of Helsinki. Given the retrospective nature of the present research, no informed consent was required.
Data collection and Definition
Clinical data were collected from all medical recorded by trained clinicians who blind to the purpose of the study. These included age, gender, duration of diabetes, newly diagnosed diabetes, smoking history, history of hypertension, family history of CAD, previous myocardial infarction (MI), previous percutaneous coronary intervention (PCI), previous coronary artery bypass graft (CABG) , previous stroke, height, weight, systolic and diastolic blood pressure(SBP and DBP), heart rate(HR) ,left ventricle eject fraction(LVEF) and medication at discharge. Peripheral venous blood samples were collected early in the morning after an overnight fast on admission and analyzed shortly after sampling. The hemoglobin, FBG, Hemoglobin A1c(HbA1c), total cholesterol (TC), triglyceride (TG), low density lipoprotein-C(LDL-C), high density lipoprotein-C(HDL-C), serum creatinine, serum uric acid, high-sensitivity C-reactive protein(hs-CRP) and N-terminal proB-type natriuretic peptide (NT-proBNP) were analyzed. The renal function was assessed by using the baseline estimated glomerular filtration rate (eGFR). Body mass index (BMI) was defined as weight (kg)/height (m2). Angiographic significant stenosis was defined as >50% diameter stenosis. Multivessel disease was defined as 2 vessels with significant angiographic stenosis. The GRACE score was calculated according to 8 variables including age, SBP, HR, cardiac arrest during presentation, Killip class, ST-segment deviation, serum creatinine, positive cardiac biomarkers. The TyG index was calculated as ln (fasting TG level (mg/dL) ×FBG level (mg/dL)/2).
End points
The primary end point was new-onset major adverse cardiovascular event (MACE), defined as the composite of all-cause death, non-fatal MI and non-fatal stroke. All-cause death referred to death attributed to cardiovascular or non-cardiovascular causes. Non-fatal MI referred to MI that did not result in death. Non-fatal stroke referred to stroke that did not result in death. The secondary end points included all-cause death, non-fatal MI, non-fatal stroke.
Statistical analysis
Continuous variables were expressed as mean ± standard deviation when normally distributed, and as medians with interquartile ranges for results not normally distributed. Categorical variables were presented as frequencies. Baseline demographic characteristics, clinical presentation, laboratory findings, extent of CAD, revascularization, and medication data were compared between groups using analysis of variance or Kruskal-Wallis tests for continuous variables, and with chi-square test or Fisher’s exact test for categorical variables.
Multivariate linear regression analyses based on stepwise method was performed to reveal the factors associated with the TyG index. Kaplan-Meier event-free survival curves associated with TyG index tertiles were compared using log-rank tests. Possible factors associated with MACE were determined by using univariate Cox regression analysis. Then, variables with significant association (P values <0.10) with MACE were included in multivariate Cox proportional hazards regression analysis as two models. The area under the receiver operating characteristic (ROC) curves was used to indicate the predictive value of the TyG index for MACE. To evaluate whether an increased TyG index had incremental predictive value for MACE, C-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were compared between models. A 2-sided analysis with a P value <0 .05 was considered significant. All analyses were performed using SPSS version 20.0 (IBM Corp, Armonk, New York) and SAS version 9.1.3 (Cary, NC, USA).