It has been well recognized that the development of cardiovascular disease (CVD) is driven by multiple contributing factors including glycemic abnormality and lipid disorder (1,2). Hypertriglyceridemia (HTG) is a common dyslipidemia and the association of triglyceride (TG) with CVD risk remains controversial

© Journal of Thoracic Disease. All rights reserved. J Thorac Dis 2018;10(11):6137-6146jtd.amegroups.com

Original Article

Triglyceride glucose index for predicting cardiovascular outcomes in patients with coronary artery disease

Jing-Lu Jin1, Ye-Xuan Cao1, Li-Guo Wu2, Xiang-Dong You2, Yuan-Lin Guo1, Na-Qiong Wu1, Cheng-Gang Zhu1, Ying Gao1, Qiu-Ting Dong1, Hui-Wen Zhang1, Di Sun1, Geng Liu1, Qian Dong1, Jian-Jun Li1

1Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese

Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China; 2Department of Cardiology, TangXian People’s Hospital,

Baoding 072350, China

Contributions: (I) Conception and design: JJ Li; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection

and assembly of data: D Sun, YX Cao, HW Zhang, XD You, NQ Wu, CG Zhu, YL Guo, Y Gao, Q Dong, G Liu, QT Dong; (V) Data analysis and

interpretation: JL Jin, JJ Li; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Professor Jian-Jun Li, MD, PhD. Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital,

National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing

100037, China. Email: lijianjun938@126.com

Background: Triglyceride glucose (TyG) index is a novel marker for metabolic disorders and recently it has been reported to be associated with cardiovascular disease (CVD) risk in apparently healthy individuals. However, the prognostic value of TyG index in patients with stable coronary artery disease (CAD) is not determined. Methods: We conducted a nested case-control study among 3,745 patients with stable CAD. Patients were followed up for 11,235 person-years. The cardiovascular events (CVEs) were defined as all-cause death, non-fatal myocardial infarction (MI), stroke and post-discharge revascularization [percutaneous coronary intervention (PCI) coronary artery bypass grafting (CABG)]. In total, 290 (7.7%) patients with CVEs and 1,450 controls were matched according to age, gender, previous history of PCI or CABG and the duration of follow-up. TyG index was calculated as formula: ln[fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. Results: Multivariable Cox proportional hazards models revealed that TyG index was positively associated with CVEs risk (hazard ratio: 1.364, 95% confidence interval: 1.100–1.691, P=0.005). The Kaplan-Meier analysis indicated that patients within the highest quartile of TyG index presented the lowest event-free survival (P=0.029). Moreover, a 1-standard deviation (SD) increment in TyG index was associated with 23.2% [hazard ratio (HR): 1.232, 95% confidence interval (95% CI): 1.084–1.401] higher risk of CVEs, which was superior to other triglyceride or glycemic related markers. Conclusions: The present study, firstly, showed that TyG index was positively associated with future CVEs, suggesting that TyG may be a useful marker for predicting clinical outcomes in patients with CAD.

Keywords: Triglyceride glucose index (TyG index); stable coronary artery disease; outcome

Submitted Jun 01, 2018. Accepted for publication Sep 30, 2018.

doi: 10.21037/jtd.2018.10.79

View this article at: http://dx.doi.org/10.21037/jtd.2018.10.79

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© Journal of Thoracic Disease. All rights reserved. J Thorac Dis 2018;10(11):6137-6146jtd.amegroups.com

Jin et al. TyG index and outcomes in CAD

Introduction

It has been well recognized that the development of cardiovascular disease (CVD) is driven by multiple contributing factors including glycemic abnormality and lipid disorder (1,2). Hypertriglyceridemia (HTG) is a common dyslipidemia and the association of triglyceride (TG) with CVD risk remains controversial (3,4). However, judging from a credible body of evidence, we can conclude that HTG is an independent risk factor of developing glucose metabolism disorders (5). Plasma TG levels are strongly associated with raised glucose levels because of the interactions between fat, muscle and function of pancreatic β-cells (6,7). Moreover, accumulation of TG in the liver may cause fatty liver disease, which can increase the risk of type 2 diabetes mellitus (T2DM) (8). Prospective studies have revealed that plasma TG is an independent risk factor for developing T2DM (9,10). Additionally, it has been demonstrated that lowering TG, such as fibrates do, can significantly attenuate the process of developing insulin resistance (11). Furthermore, it also has been reported that both fasting glucose and TG within the high normal range may predict CVD risk (12,13). Hence, evaluating the joint value of TG and fasting glucose in patients with stable

coronary artery disease (CAD) may be clinically in need. Triglyceride glucose (TyG) index is a novel marker,

which has been demonstrated to have a high sensitivity and specificity in identifying metabolic syndrome (14). Previous studies have shown that TyG index is associated with carotid atherosclerosis, coronary artery calcification and high risk of CVD. Unfortunately, no data is currently available with regard to the effects of TyG index on clinical outcomes in patients with stable CAD (15-17). Therefore, the primary objective of the study was to investigate the prognostic role of TyG index in a large Chinese cohort with stable CAD.

Methods

Study design and population

Our study complied with the Declaration of Helsinki and was approved by the hospital’s ethical review board (Fu Wai Hospital & National Center for Cardiovascular Diseases, Beijing, China, approval number: 2013–442). Informed written consents were obtained from all patients enrolled in this study.

As described in Figure 1, from March 2011 to October 2014, 5,437 consecutive patients were scheduled for coronary

5,437 eligible patients from March 2011 to October 2014

3,745 patients enrolled in the study

3,448 patients without CVEs297 patients with CVEs

290 patients with CVEs 1,450 patients in control group

7 CVEs patients without controls

972 non-CAD patients

183 patients did not complete 36 months

following-up 198 patients were excluded for heart failure or ACS; 103 patients were excluded for liver or renal insufficiency; 72 patients were excluded for thyroid dysfunction; 164 patients were excluded for other mentioned exclusion criteria.

matched

Figure 1 Flowchart of the study. CAD, coronary artery disease; ACS, acute coronary syndrome; CVEs, cardiovascular events.

 

 

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Journal of Thoracic Disease, Vol 10, No 11 November 2018

angiography because of angina-like chest pain and/or positive treadmill exercise test or clinically suspected CAD in our division. Among these patients, 972 were excluded because they were not angiography-proven CAD. Patients with acute coronary syndrome (ACS), heart failure (left ventricular ejection fraction, LVEF <45%), severe liver and/or renal insufficiency, thyroid dysfunction, malignant disease, extreme body mass index (BMI >45 kg/m 2), s u s p e c t e d f a m i l i a l H T G [ p l a s m a T G ≥5 0 0 m g / d L (5.65 mmol/L) or more than one first-degree relative with TG ≥500 mg/dL] were also excluded. Patients were prospectively followed up at 6, 12, 24, 36 months by means of interviewing directly or using telephone conducted by trained nurses or doctors who were blinded to the clinical data. The cardiovascular events (CVEs) were all-cause death, non-fatal myocardial infarction (MI), stroke and post-discharge revascularization [percutaneous coronary intervention (PCI) coronary artery bypass grafting (CABG)]. Cardiovascular death was defined as death primarily caused by acute MI, congestive heart failure, stroke, malignant arrhythmia and other structural or functional cardiac diseases. Non-fatal MI was diagnosed as positive cardiac troponins along with typical chest pain or typical electrocardiogram serial changes. Stroke was diagnosed by the presence of typical symptoms or imaging. Finally, we identified 3,745 patients with stable CAD who completed our follow-up for the present analysis. During a follow-up of per 11,235 person-years, 297 CVEs occurred and individually matched to 5 randomly selected controls on age, gender, previous history of PCI and CABG, and the duration of follow-up.

Hypertension was defined as a self-reported hypertension, currently taking anti-hypertensive drugs or recorded systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg for three or more consecutive times. T2DM was defined as fasting serum glucose ≥7.0 mmol/L or the 2-h serum glucose of the oral glucose tolerance test ≥11.1 mmol/L or currently using hypoglycaemic drugs or insulin. BMI was calculated as weight divided by height squared. Information of other disease, family history and current therapy of every patient was collected from self-reported medical history.