Triglyceride glucose index for the detection of the severity of coronary artery disease in different glucose metabolic states in patients with coronary heart disease: a RCSCD-TCM study in China

doi:10.21203/rs.3.rs-1537070/v1

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Research Article

Triglyceride glucose index for the detection of the severity of coronary artery disease in different glucose metabolic states in patients with coronary heart disease: a RCSCD-TCM study in China

https://doi.org/10.21203/rs.3.rs-1537070/v1

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Background: The triglyceride glucose (TyG) index is a new marker associated with atherosclerosis. This study aimed to assess the association between the TyG index and the severity of coronary artery disease (CAD) in patients with coronary heart disease (CHD) and further explore the association between the TyG index and CAD severity in different glucose metabolic states.

Methods: This multi-centre retrospective study included 731 CHD patients between September 1, 2014 to September 30, 2020 in China. All patients were stratified into groups based on the tertiles of the TyG index (T1:5.48 ≤ TyG index ≤ 7.17; T2: 7.18 ≤ TyG ≤ 7.76; T3: 7.77 ≤ TyG ≤ 10.82) and the number of diseased vessels [1-vessel disease (VD), 2-VD and 3-VD] represented the severity of CAD. The relationship between the TyG index and CAD severity was analysed using logistic regression. The associations between the TyG index and CAD severity based on different glucose metabolic status were also assessed. Receiver operating characteristic (ROC) curves were performed to evaluate the accuracy of the TyG index for detecting the CAD severity.

Results: The baseline analysis results showed significant differences in clinical and biological characteristics of CHD patients according to the TyG index tertiles (P < 0.05 to < 0.001). The TyG index was significantly related to the risk of multiple diseased coronary arteries and more severe coronary stenoses (CS) (P < 0.001). The TyG index was significantly associated with the risk of 3-VD in patients with CHD. The odds ratio (OR) of 3-VD for the TyG index T3 compared to T1 was 2.27 (95% confidence interval [CI] 1.497-3.452; P for trend <0.001). Among different states of glucose metabolism, the association between the TyG index and 3-VD observed was significant in diabetes (OR: 1.662; 95% CI 1.166–2.369). A TyG index threshold for predicting 3-VD (95% [CI] 0.554-0.664; P < 0.001 ) was 7.0 and was 8.1 in diabetes state (95% [CI] 0.523-0.646; P < 0.001 ).

Conclusion: The TyG index is associated with CAD severity in CHD patients and an increased TyG index could identify CHD patients with a high risk of 3-VD. The association between the TyG index and CAD severity in the condition of diabetes is higher than in non-diabetes.

coronary heart disease

coronary artery disease severity

triglyceride glucose index

glucose metabolic states

Coronary heart disease (CHD) is one kind of chronic cardiovascular disease caused by hardening of the coronary arteries. The morbidity and mortality of CHD are on the rise due to aging, urbanisation, obesity, and unhealthy lifestyle habits, and it is increasingly becoming a serious public health problem^{[1, 2]}. Type 2 diabetes mellitus (T2DM) has widely been considered a prevalent comorbidity that affects the progression of CHD and the treatment choices for CHD patients^[3]. CHD patients with combined abnormal glucose metabolic state have a higher risk of adverse cardiovascular outcomes^[4–6]. Actually, T2DM increases the probability of developing CHD and the risk of death from CHD by at least two-fold^{[7, 8]}.

In patients with CHD, the severity of coronary artery disease (CAD) varies and depends on the patient's clinical symptoms and ancillary investigations. Previous studies have found that 42.4% of individuals who experienced sudden cardiac deaths determined to be caused by CHD had no clinical symptoms, but on autopsy these individuals were found to have severe CAD and myocardial infarction^{[9, 10]}. Coronary angiography (CAG) is now a common and accurate imaging test for the diagnosis of CAD and is known as the “gold standard” for CAD severity in China. CAG may accurately detect the number and the severity of artery stenoses in patients. Related to the CAG results, CAD was defined as diameter lumen stenosis of ≥ 50% in at least one major coronary artery and the number of diseased vessels expressed the severity of CAD.

The triglyceride glucose (TyG) index, a combination of fasting plasma glucose (FPG) and triglyceride (TG) calculations, is considered to be a representative biomarker of insulin resistance (IR) ^{[11, 12]}. The risk of developing diabetes increases as the TyG index rises in the general population, and the TyG index may be a valuable indicator for observing glucose metabolic status^[13]. In addition, a large-scale population study in Korean were evaluated to indicate that TyG index was associated with atherosclerotic cardiovascular disease, and the TyG index has recently attracted a lot of attention as a new marker of atherosclerosis^[14]. The elevated TyG index has been shown in numerous studies to be an independent risk factor for atherosclerosis and is correlated with an increased chance of cardiovascular events (CVD)^[15–17]. In the meantime, the severity of CAD plays a crucial role in CVD, it is required to identify people at high risk of CAD severity among CHD patients, especially those with prediabetes or diabetes. However, the ability of the TyG index to detect the severity of CAD in patients with CHD has not been proven, and the influence of glucose metabolic status in this needs further studies.

This study aimed to investigate the association between the TyG index and the severity of CAD in CHD patients and the relationship between the TyG index and CAD severity in different states of glucose metabolic. Furthermore, the study determined whether the TyG index could detect the disease severity in patients with CHD.

Subjects

This large-scale multicenter retrospective study population comprised 107,301 CHD patients hospitalized in Tianjin between September 1, 2014 to September 30, 2020. The following patients were excluded: (1) those younger than 35 years or older than 75 years; (2) those with tumours, infectious or severe liver or kidney disease; (3) those who lacking data on hemoglobin A1c (HbA1c), FPG, TG, and coronary angiography (CAG). Finally, a total of 731 subjects were enrolled in the final analysis. The subjects inclusion process is illustrated in Fig. 1. Approval for the study was obtained from the Ethics Committee of Tianjin University of Traditional Chinese Medicine (TJUTCM-EC20190008) and registered with the China Clinical Trials Registry (ChiCTR-1900024535) and with Clinical Trials. gov (NCT04026724).

Data collection

The following data for the study analysis were acquired from medical records, including clinical history, anthropometric data, blood analysis and medical imaging data. Anthropometric data include weight, height, body mass index (BMI) and blood pressure; Personal information such as age, sex, smoking history and alcohol consumption history were recorded. The blood samples tested were fasting venous blood collected by specialist medical staff from all participants in the early morning. FPG, HbA1c, TG, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured using an automatic hematology analyzer. Coronary arteriography (CAG) was performed using a percutaneous femoral arteriography technique by an angiography machine with sufficient right and left anterior oblique views to diagnose of all coronary artery lesions.

Definitions

The TyG index is derived by arithmetic as follows: ln[TG (mg/dl) × FPG (mg/dl)/2]. BMI is calculated by dividing weight by the square of height and expressed in kg/m². CHD was defined as ≥ 50% diameter lumen stenosis in at least one major coronary artery. According to the Society for Cardiovascular Computed Tomography guidelines^[14], the number of diseased vessels expresses the severity of CAD. The number of branches per coronary artery lesion was the number of coronary vessels with ≥ 50% stenosis, classified as 1, 2 or 3 lesions according to whether the stenosis involved the left anterior descending, left circumflex and right coronary arteries; No other vascular lesions but the left main stem stenosis ≥ 50% was regarded as two lesions. Participants were divided into the following three groups: Participants with 1-vessel disease (VD), 2-VD, and 3-VD. Tandem stenoses were not considered. Advanced stenoses, if present, were used for further evaluation. Coronary stenoses (CS) was considered significant when one or more major branches of the coronary artery had ≥ 50% stenosis, moderate if 50–69%, and severe if ≥ 70%. According to the American Diabetes Association's Standards for the Medical Treatment of Diabetes ^[15]: Diabetes mellitus (DM) was defined by FPG ≥ 7.0 mmol/L or HbA1c ≥ 6.5%, Prediabetes mellitus (Pre-DM) was defined by 5.6 mmol/L ≤ FPG ≤ 6.9 mmol/L or 5.7% ≤ HbA1c ≤ 6.4%, and normal glucose regulation (NGR) was defined by FPG < 5.6 mmol/L or HbA1c < 5.7%.

Statistical analysis

Differences between groups were calculated using χ2 tests and the Kruskal-Wallis test. Mean ± standard deviation (SD) or median and interquartile range (IQR) are indicated for continuous data. Categorical variables are expressed as percentages. Risk factors for increased severity of CAD using spearman correlation analysis. The odds ratios(OR) value and 95% confidence intervals(CI) were calculated using spearman correlation analysis and logistic regression analysis to test the association of various factors in coronary artery lesions in CHD. The area under the curve (AUC) and 95% CI of the receiver operating characteristic (ROC) curve were calculated to determine whether the TyG index could be a useful tool for detecting the extent of coronary lesions in patients with CHD. It was considered to be statistically significant when the P-value < 0.05. All statistical analysis were performed using SPSS 24.0 (IBM Corp, New York, NY, USA).

Clinical and biological characteristics

The baseline characteristics of 731 participants were divided into three groups based on the TyG index: T1 (5.48 ≤ TyG ≤ 7.17), T2 (7.18 ≤ TyG ≤ 7.76) and T3 (7.77 ≤ TyG ≤ 10.82) in Table 1: Age, sex, SBP, DBP, history of smoking and drinking did not show significant differences (P > 0.05). Meanwhile, compared with participants in the lowest TyG index tertile (T1), participants in the highest tertile (T3) were associated with higher BMI, TC, TG, LDL-C, FPG and HbA1c but lower HDL-C (P < 0.001). Furthermore, CHD patients in the TyG T3 were composed of more abnormal glucose metabolism participants, more diseased vessels and more severe coronary stenosis participants than those in T1(P < 0.001).

Groups were divided into three according to the number of coronary lesions: 1-VD, 2-VD, 3-VD with the following baseline characteristics in Table 2: Patients in the 3-VD were composed of more male participants and more abnormal glucose metabolism participants (P < 0.001). The TyG index, FPG, TG, HbA1c, LDL-C were positively associated with the number of coronary vessels with ≥ 50% stenosis, while HDL-C was negatively associated with the number of diseased vessels (P < 0.005).

Table 1

Clinical and biological characteristics according to the TyG tertiles
Characteristics	T1(5.48–7.17) (n = 244)	T2 (7.18–7.76) n = 244	T3 (7.7–10.82) (n = 243)	P value
Age (years)	64(59, 69)	63.5(58, 68)	63(56, 67)	0.062
Sex(M/F)	1.32	1.57	1.38	0.634
SBP(mmHg)	142.0 ± 21.5	140.5(129, 159)	140(125, 156)	0.805
DBP(mmHg)	82(76, 91.75)	83(76.25, 90)	84.3 ± 12.9	0.750
BMI(kg/m²)	25.64 ± 3.67	26.63 ± 3.71	27.47(24.61, 29.67)	< 0.001
Drinking	86(34.0%)	90(35.6%)	77(30.4%)	0.468
Smoking	120(33.1%)	124(34.2%)	119(32.8%)	0.905
TC(mg/dL)	4.27(3.56, 5.04)	4.49(3.91, 5.28)	5.04(4.36, 6)	< 0.001
TG(mg/dL)	1.03 ± 0.26	1.58(1.3, 1.96)	2.52(1.87, 3.33)	< 0.001
HDL(mg/dL)	1.16(0.97, 1.37)	1.05(0.89, 1.22)	0.99(0.8, 1.16)	< 0.001
LDL(mg/dL)	2.57(1.99, 3.22)	2.74(2.19, 3.31)	2.98 ± 0.97	< 0.001
TyG index	6.88(6.65, 7.04)	7.42(7.3, 7.6)	8.17(7.94, 8.49)	< 0.001
FBG(mmol/L)	5.63(5.09, 6.18)	6.31(5.58, 7.6)	9.3(7.01, 12.48)	< 0.001
HbA1c(%)	5.8(5.5, 6.2)	6.1(5.7, 6.8)	6.9(6, 8.4)	< 0.001
Glucose metabolism
NGR	59(65.6%)	26(28.9%)	8(8.9%)	< 0.001
Pre-DM	131(49.4%)	97(36.6%)	37(14.0%)
DM	54(14.5%)	121(32.4%)	198(53.1%)
Coronary artery stenosis
1-VD	105(40.4%)	94(36.2%)	61(23.5%)	< 0.001
2-VD	87(32.7%)	86(32.3%)	93(35.0%)
3-VD	52(25.4%)	64(31.2%)	89(43.4%)
CS ≥ 50%	76(40.9%)	65(34.9%)	45(24.2%)	0.005
CS ≥ 70%	168(30.8%)	179(32.8%)	198(36.3%)	0.005

Data are presented as mean ± standard deviation or median (tertile) or number (proportion, %).

M, male; F, female; TyG, triglyceride glucose; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; NGR, normal glucose regulation; Pre-DM, prediabetes; DM, diabetes; 1-VD, 1-vessel disease; 2-VD, 2-vessel disease; 3-VD, 3-vessel disease; CS, coronary stenoses

Table 2

Clinical and biological characteristics according to number of coronary vessels with ≥ 50% stenosis
Characteristics	1- VD (n = 265)	2- VD (n = 269)	3- VD (n = 207)	P value
Age(years)	63(57, 68)	63(58, 69)	64(58, 69)	0.599
Sex(M/F)	1.10	1.56	1.77	0.027
SBP(mmHg)	139.5(126, 154)	141(128, 159.25)	141.2 ± 21.3	0.222
DBP(mmHg)	83(76.25, 90)	84.5(77, 93)	81(75, 90)	0.098
BMI(kg/m²)	26.47 ± 3.75	26.63 ± 3.90	26.5(24.12, 29.1)	0.935
Drinking	91(36.0%)	91(36.0%)	71(28.0%)	0.982
Smoking	123(33.9%)	131(36.1%)	109(30.0%)	0.448
TC(mg/dL)	4.45(3.78, 5.21)	4.73(3.95, 5.62)	4.64(3.87, 5.67)	0.062
TG(mg/dL)	1.42(1.05, 2.04)	1.51(1.1, 2.17)	1.64(1.19, 2.33)	0.012
HDL-C(mg/dL)	1.1(0.92, 1.32)	1.06(0.89, 1.23)	0.99(0.83, 1.19)	< 0.001
LDL-C(mg/dL)	2.63(2.02, 3.2)	2.83(2.19, 3.54)	2.75(2.2, 3.5)	0.009
TyG index	7.32(6.93, 7.75)	7.48(7.02, 7.98)	7.6(7.17, 8.21)	< 0.001
FBG(mmol/L)	5.98(5.28, 7.34)	6.53(5.6, 8.82)	7.14(5.81, 10.37)	< 0.001
HbA1c(%)	5.95(5.5, 6.48)	6.1(5.7, 7.2)	6.3(5.7, 7.4)	< 0.001
Glucose metabolism
NGR	45(48.4%)	31(33.3%)	17(18.3%)	< 0.001
Pre-DM	113(42.6%)	93(35.1%)	59(22.3%)
DM	102(27.3%)	142(38.1%)	129(34.6%)
Drug therapy
Antihypertensive	196(34.9%)	214(38.1%)	151(26.9%)	0.182
Antilipidemic	198(36.3%)	208(38.2%)	139(25.5%)	0.028
Antiplatelet	246(34.7%)	260(36.7%)	202(28.5%)	0.032

Data are presented as mean ± standard deviation or median (tertile) or number (proportion, %).

Associations between CAD severity and risk factors

Spearman correlation was used to inspect the association between CAD severity and various possible risk factors (Table 3). The number of coronary lesions showed significant associations with the TyG index (r = 0.189, P < 0.001 ) and the state of glucose metabolism (r = 0.175, P < 0.001 ), and the relationship between the TyG index and CAD severity was higher than the associations between other risk factors and CAD severity.

Table 3

Associations between CAD severity and risk factors
Variables	r	P value
Age	0.037	0.312
Sex(male)	-0.096	0.009
Smoking	0.068	0.068
Drinking	0.017	0.649
SBP	0.017	0.646
DBP	-0.035	0.340
BMI	0.028	0.449
TC (mmol/L)	0.075	0.043
TG (mmol/L)	0.108	0.003
HDL-C (mmol/L)	-0.145	< 0.001
LDL-C (mmol/L)	0.099	0.007
FBG(mmol/L)	0.124	0.016
HbA1c(%)	0.173	< 0.001
TyG index	0.189	< 0.001
Glucose metabolism	0.175	< 0.001

TyG, triglyceride glucose; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol

Associations between the TyG index and CAD severity and CS degree

Logistic regression models were constructed to show that an elevated TyG index was significantly associated with an increased risk of multiple diseased coronary arteries and more severe coronary stenoses (Table 4) (P < 0.005 ). After further adjustment, the odds of 3-VD lesions all increased 2.125 times that of 1-VD lesions (95% confidence interval [CI] 1.572–2.871). Statistical results showed that stenosis ≥ 70% lesions were1.680 times more than the stenosis of 50–69% (95% [CI] 1.276–2.212). The TyG index was related to the risk of developing CS before and after multivariate adjustment (P < 0.001 ).

Binary logistic regressions were used to assess the impact of the TyG index on 3-VD (Table 5). When the TyG index was shown to be a continuous variable, it had significantly associated with the presence of 3-VD in the crude model (OR: 1.621; 95% CI: 1.280–2.053). After further adjustment for confounding factors, the odds of developing of diseased vessels increased by 68.3% (OR: 1.683; 95% CI: 1.320–2.144) and 72.5% (OR: 1.725; 95% CI: 1.345–2.212). When the TyG index served as a classified variable, compared to the T1, 3-VD risk of CHD patients for the T3 was 2.3 times (95% [CI] 1.497–3.452, P for trend < 0.001).

Table 4

Association between the TyG index and the number of coronary vessels with ≥ 50% stenosis and the degree of coronary stenosis
Variables	Unadjusted OR (95% CI)	P value	Model 1 OR (95% CI)	P value	Model 2 OR (95% CI)	P value
Number of coronary vessels with ≥ 50% stenosis
1-VD	Reference		Reference		Reference
2-VD	1.508(1.156–1.968)	0.002	1.535(1.172–2.011)	0.002	1.514(1.146–1.999)	0.003
3-VD	2.025(1.526–2.686)	< 0.001	2.125(1.591–2.838)	< 0.001	2.125(1.572–2.871)	< 0.001
Degree of coronary stenosis
50–69%	Reference		Reference		Reference
≥ 70%	1.702(1.305–2.219)	< 0.001	1.710(1.306–2.240)	< 0.001	1.680(1.276–2.212)	< 0.001
OR, odds ratios; CI, confidence interval; 1-VD, 1-vessel disease; 2-VD, 2-vessel disease; 3-VD, 3-vessel disease;
Model 1 adjusted for age, sex;
Model 2 adjusted for age, sex, BMI, SBP, DBP, smoking, drinking, antihypertensive drug therapy, antilipidemic drug therapy and antiplatele drug therapy

Table 5

Association between the TyG index and 3-VD
Variables	Unadjusted Model OR(95% CI)	P value	Model 1 OR(95% CI)	P value	Model 2 OR(95% CI)	P value
TyG	1.621(1.280–2.053)	< 0.001	1.683(1.320–2.144)	< 0.001	1.725(1.345–2.212)	< 0.001
T1(5.48–7.17)	Reference		Reference		Reference
T2(7.18–7.76)	1.313(0.864–1.995)	0.203	1.313(0862-1.999)	0.205	1.270(0.828–1.949)	0.273
T3(7.7–10.82)	2.134(1.427–3.191)	< 0.001	2.226(1.482–3.345)	< 0.001	2.273(1.497–3.452)	< 0.001
P-trend		< 0.001		< 0.001		< 0.001
OR, odds ratios; CI, confidence interval; TyG, triglyceride glucose
Model 1 adjusted for age, sex;
Model 2adjusted for age, sex, SBP, DBP, smoking, drinking, antihypertensive drug therapy, antilipidemic drug therapy and antiplatele drug therapy

Association between the TyG index and 3-VD in different glucose metabolism states

Binary logistic regression analysis results showed the effect of glucose metabolic status on the relationship between the TyG index and 3-VD (Table 6). There is no statistically significant association between the TyG index and the presence of 3-VD in the NGR and Pre-DM states (P > 0.05 ), while there was a statistically significant association between the TyG index and the presence of 3-VD after multivariate adjustment in the DM state (OR: 1.662; 95% CI 1.166–2.369, P < 0.001 ).

Table 6

Association between the TyG index and 3-VD in different glucose metabolism states
Variables	3-VD(%)	Unadjusted Model OR(95% CI)	P value	Model 1 OR(95% CI)	P value	Model 2 OR(95% CI)	P value
NGR	17(18.3)	1.625(0.597–4.423)	0.342	1.429(0.508–4.021)	0.498	2.026(0.624–6.573)	0.240
Pre-DM	59(22.3)	1.085(0.627–1.879)	0.771	1.117(0.639–1.952)	0.698	1.142(0.624–2.091)	0.666
DM	129(34.6)	1.470(1.057–2.045)	0.022	1.587(1.127–2.235)	0.008	1.662(1.166–2.369)	0.005

OR, odds ratios; CI, confidence interval; 3-vessel disease; NGR, normal glucose regulation; Pre-DM, prediabetes; DM, diabetes;

Model 1 adjusted for age, sex;

Model 2adjusted for age, sex, SBP, DBP, smoking, drinking, antihypertensive drug therapy, antilipidemic drug therapy and antiplatele drug therapy

Detection of CAD severity by theTyG index

ROC curve analysis was used to determine the threshold values of the TyG index corresponding to the risk of 3-VD and to evaluate its accuracy in detecting the severity of CAD (Fig. 2 and Fig. 3). The statistical results showed that TyG > 7.0 was the threshold for the number of vascular lesions to be three lesions, the area under the curve for the TyG index was 0.60 (95% [CI] 0.554–0.664; P < 0.001 ). In condition of DM, the TyG index threshold for predicting 3-VD was 8.1, the curve was 0.584 (95% [CI] 0.523–0.646; P < 0.001 ). Accordingly, patients with CHD have an increased threshold for the TyG index predicting 3-VD in diabetes.

This is the first study revealed a significant association between the TyG index and CAD severity in CHD patients and assessed this association according to the states of glucose metabolism. In the present study, the TyG index was significantly associated with CAD severity and the risk of 3-VD in patients with CHD. Among different states of glucose metabolism, the association between the TyG index and 3-VD observed was significant in diabetes. Furthermore, the accuracy of TyG index in detecting the CAD severity was also evaluated. A TyG index threshold for predicting 3-VD in CHD patients was 7.0 and was 8.1 in diabetes state.

Previous literature has suggested that the TyG index could identify individuals in asymptomatic patients with T2DM who are at high risk of coronary disease^[20]. The study mainly compared patients with the severity of CS in diabetic patients; the evidence was provided to the TyG index was related to the degree of coronary artery stenoses in patients with T2DM and without cardiovascular disease. In line with the study, the results of our research analysis supported the notion that increased TyG index is associated with the number of vessels and the degree of CS, and our study builds on this with a more in-depth study of the severity of CAD in patients with CHD in different states of metabolic status.

The TyG index is a proven independent predictor of coronary artery calcification progression^{[15, 21]}. A large-scale population study whose date form 5,593,134 Korean participants were evaluated to indicate that TyG index as a simple and low-cost marker was associated with atherosclerotic cardiovascular disease^[14]. The TyG index is also associated with carotid arterial stenosis and our previous study revealed that the relationship between the TyG index and carotid artery plaque is significant in CHD patients^{[22, 23]}. Additionnally, the elevated TyG index plays a potentially valuable role in early recognizing the individuals at high risk of CVD^[24].

Patients with IR result in the disappearance of the normal coordinated hypoglycaemic response and the loss of, for example, inhibition of endogenous glucose production, inhibition of endogenous glucose lipolysis, cellular uptake of available blood glucose, and net glycogen synthesis^[25]. Triglycerides stored in adipose tissue increase as IR begins to lipolysis and produce more fatty acids before raising blood glucose levels^[26]. The TyG index, a product calculated from FPG and TG, has also become a simple surrogate marker for IR and is inversely related to IR as determined using the euglycemic-hyperinsulinemic clamp test^[27]. Among the traditional risk factors, FBG and TG levels have been associated with an increased risk of T2DM^{[28, 29]}. In addition to the well-known fact that IR accelerates the decline in pancreatic β cell function leading to the development of diabetes on the one hand. The above theory could explain the relationship between IR and diabetes in another way. Previous evidence reported that patients with metabolism disorder had more severe coronary artery lesion in the coronary artery stenosis population^[30]. IR, a severe metabolic syndrome that can cause diabetes, is a collection of pathological conditions associated with systemic inflammation, endothelial dysfunction, oxidative stress and prothrombotic states^[31]. Moreover, IR is also considered a pivotal risk factor for cardiometabolic diseases^[32]. IR plays an essential role in the atherosclerotic process with associated clustering of risk factors increasing the risk of atherogenic damage. Compared with the homeostasis model assessment of insulin resistance (HOMA-IR), the TyG index is better for predicting subclinical atherosclerosis^[33]. It may be ascribed to the myocardium generating damage and atherosclerotic plaque generation due to IR^[34]. Based on the above rationale, we can better understand the association between the TyG index and CAD severity that emerged in the analysis of the study.

In this retrospective cohort study, we observed that the prevalence and incidence of abnormalities in clinical and biological characteristics were higher than in the general population. The results showed that an elevated TyG index was also associated with more severe dyslipidemia, progressively impaired glucose metabolic status and progression of coronary stenoses. CHD patients were detected 2-VD with stenosis ≥ 50% in 36.9% and 3-VD in 28.0%. This may be due to the fact that our study was a hospital-based study in which subjects had CHD with more risk factors, such as diagnosed diabetes, dyslipidemia, and hypertension. The results of epidemiological studies have identified multiple important risk factors responsible for the progression of CAD, such as hypertension, hyperlipidemia, IR and obesity^{[35, 36]}. Our results corroborate this view that CHD patients showed more abnormal biochemical parameters and glucose metabolic status with developing severity of CAD.

This study demonstrated that the number of coronary lesions was associated with levels of the TyG index and the associativity was higher than the relationship between other risk factors and CAD severity and CS degree regardless of the confounders such as age, sex, BMI, SBP, DBP, smoking, drinking and drug therapy, further emphasizing the consistency of this association. IR has been present for an extended period before the diagnosis of diabetes and it is a critical pathophysiological pathway leading to DM^[37]. The TyG index can similarly indicate IR in non-diabetic individuals^[38]. This theory is consistent with our results: The TyG index could be of value for detecting the severity of CAD across all CHD patients.

It is well known that 3-VD, the three major vessels lesions of the coronary arteries involving left anterior descending, left circumflex and right coronary arteries, is the type of CHD with the highest risk of death and adverse events and is a clinical indication for coronary artery bypass grafting (CABG). This study showed that the TyG index of CHD patients was significantly associated with the risk of 3-VD. In the meantime, the CHD patients in the DM state had their TyG index significantly related to 3-VD. The present study's findings showed that the incidence of three branch lesions is higher in the DM state than in the NGR and Pre-DM states (34.6%>22.3%>18.3%). Studies have indicated that DM usually exists with dyslipidemia and increases CHD risk^{[3, 39]}. DM may increase cardiovascular risk in individuals by accelerating the development of atherosclerosis, including through polygenic risk^{[40, 41]}. Unfortunately, we did not find a statistical association between the TyG index and the presence of 3-VD in CHD patients without diabetes. This may be associated with higher levels of the TyG index in 3-VD but lower levels of the TyG index in NGR and Pre-DM states, which needs to be further explored in future studies.

The strengths of our study are that we explored the association between the TyG index and the severity of CAD in different glucose metabolic states, which to our knowledge is the first conducted. In addition, this study utilized sensitivity analysis to reconfirm our study and provide a specific reference for clinical control of the TyG index to prevent more severe CAD. There are also some limitations. First, we cannot manifest the existence of a causal relationship due to the inherent limitations of retrospective studies. Second, our study population was relatively small. Third, the participants in the current study were inpatients, and thus there may be some limitations to the generalizability of the results to populations.

In conclusion, the study demonstrated that a higher TyG index is associated with a higher risk of the severity of CAD and the degree of CS using a cohort dataset. The TyG index is associated with CAD severity in CHD patients and the elevated TyG index could identify CHD patients with a high risk of 3-VD. The relationship between the TyG index and CAD severity in the condition of diabetes is higher than in non-diabetes. Physicians should take steps to keep the TyG index below 7.0 in CHD patients and below 8.1 in CHD patients in the condition of DM to better prevent worsening of the severity of CAD.

TyG: Triglyceride glucose; CAD: Coronary artery disease; CVD: cardiovascular events; CHD: Coronary heart disease; CS: Coronary stenoses; NGR: Normal glucose regulation; Pre-DM: Prediabetes; DM: diabetes; T2DM: Type 2 diabetes; 1-VD: 1-vessel disease; 2-VD: 2-vessel disease; 3-VD: 3-vessel disease; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; BMI: Body mass index; FPG: Fasting plasma glucose; HbA1c: Hemoglobin A1c; TC: Total cholesterol; TG: Triglycerides; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; HOMA-IR: Homeostasis model assessment of insulin resistance; IR: Insulin resistance; OR: Odds ratios; CI: Confdence interval; CAG: Coronary angiography; CABG: Coronary artery bypass grafting

Acknowledgements

We thank all the participants in the study and the members of the survey teams, and the groups providing financial support.

Authors’ contributions

All authors have made substantial contributions. CY, LL, CL, and JS participated in the study design and statistical analysis; JS, ZL, and MH analyzed the data together and drafted the manuscript; YW, TY, GP, MM, YN, and ZL participated in data collection. All authors have read and approved the final manuscript.

Funding

This study was supported by the National Basic Research Program of China (973 project, Grant Number: 2014CB542902).

Availability of data and materials

The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.

Ethics approval and consent to participate

This study was approved by the ethics committee of Tianjin University of Traditional Chinese Medicine (TJUTCM-EC20190008) and registered in the Chinese Clinical Trial Registry (ChiCTR-1900024535) and in ClinicalTrials.gov (NCT04026724).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests

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Triglyceride glucose index for the detection of the severity of coronary artery disease in different glucose metabolic states in patients with coronary heart disease: a RCSCD-TCM study in China

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Abstract

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Data collection

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Associations between CAD severity and risk factors

Associations between the TyG index and CAD severity and CS degree

Association between the TyG index and 3-VD in different glucose metabolism states

Detection of CAD severity by theTyG index

Discussion

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