A total of 798 patients (mean age: 60.9 ± 8.3 years; 68.3% men) were finally enrolled in present study. During the 36-month follow-up period, seventeen patients (2.1% of total population) were lost to follow-up. Among the 798 participants, 180 (22.6%) experienced primary endpoint events, which consisted of 14 (1.8%) all-cause death, 37 (4.6%) non-fatal MI, and 129 (16.2%) ischemia-driven revascularization.
Baseline characteristic of study population
Baseline characteristics of the total population and groups stratified by the occurrence of primary endpoint events were presented in Table 1. TyG index was significantly higher in patients with primary endpoint event compared with those without. Patients with a primary endpoint event showed higher age and SBP, longer duration of diabetes, and higher prevalence of dyslipidemia, previous MI and previous PCI history. In terms of laboratory indicators, participants with endpoint event had higher levels of TGs, TC, hs-CRP, FBG and HbA1c, but lower levels of HDL-C, eGFR and LVEF. As for the angiographic findings, those with an endpoint event showed higher proportions of LM disease, multi-vessel disease and other characteristics of complex coronary artery lesion. The SYNTAX score was significantly higher in subset with adverse prognosis. Correspondingly, more LM lesions were disposed and more coronary artery stents were implanted in patients with endpoint event. Moreover, the rate of complete revascularization was significantly lower in participants with adverse prognosis.
Table 1. Baseline clinical characteristics of patients with and without adverse event.
|
Total population
(n = 798)
|
Without event
(n = 618)
|
With event
(n = 180)
|
P value
|
Age, years
|
60.9 ± 8.3
|
60.3 ± 8.1
|
62.9 ± 8.6
|
< 0.001
|
Sex, male, n (%)
|
545 (68.3)
|
430 (69.6)
|
115 (63.9)
|
0.149
|
BMI, kg/m2
|
26.7 ± 3.2
|
26.7 ± 3.2
|
26.6 ± 3.2
|
0.772
|
Heart rate, bpm
|
71.7 ± 10.2
|
71.5 ± 9.8
|
72.1 ± 11.4
|
0.502
|
SBP, mmHg
|
131.8 ± 17.1
|
130.8 ± 16.3
|
135.1 ± 19.5
|
0.007
|
DBP, mmHg
|
76.8 ± 10.1
|
76.4 ± 9.8
|
78.1 ± 11.1
|
0.052
|
Smoking, n (%)
|
417 (52.3)
|
332 (53.7)
|
85 (47.2)
|
0.124
|
Drinking, n (%)
|
184 (23.1)
|
149 (24.1)
|
35 (19.4)
|
0.191
|
Family history of CAD, n (%)
|
93 (11.7)
|
73 (11.8)
|
20 (11.1)
|
0.796
|
Duration of diabetes, years
|
8.2 ± 4.3
|
8.0 ± 4.1
|
9.1 ± 4.7
|
0.007
|
Medical history, n (%)
|
|
|
|
|
Hypertension
|
573 (71.8)
|
449 (72.7)
|
124 (68.9)
|
0.323
|
Dyslipidemia
|
710 (89.0)
|
537 (86.9)
|
173 (96.1)
|
0.001
|
Prior MI
|
175 (21.9)
|
118 (19.1)
|
57 (31.7)
|
< 0.001
|
Prior PCI
|
151 (18.9)
|
106 (17.2)
|
45 (25.0)
|
0.018
|
Prior stroke
|
109 (13.7)
|
80 (12.9)
|
29 (16.1)
|
0.276
|
Prior PVD
|
125 (15.7)
|
93 (15.0)
|
32 (17.8)
|
0.375
|
Laboratory results
|
|
|
|
|
TGs, mg/dL
|
138.2 (97.2, 198.5)
|
127.6 (91.3, 174.8)
|
209.1 (134.9, 299.5)
|
< 0.001
|
TC, mg/dL
|
157.2 ± 39.7
|
153.5 ± 39.4
|
170.2 ± 38.2
|
< 0.001
|
LDL-C, mg/dL
|
94.2 ± 33.1
|
93.2 ± 33.9
|
97.6 ± 29.8
|
0.112
|
HDL-C, mg/dL
|
36.9 ± 8.7
|
37.3 ± 8.8
|
35.3 ± 8.0
|
0.005
|
hs-CRP, mg/L
|
1.6 (0.7, 4.1)
|
1.5 (0.6, 3.9)
|
2.0 (0.9, 4.4)
|
0.011
|
Creatinine, mg/dL
|
0.8 ± 0.2
|
0.8 ± 0.2
|
0.8 ± 0.2
|
0.384
|
eGFR, mL/ (min * 1.73m2)
|
96.5 ± 21.6
|
97.4 ± 21.7
|
93.5 ± 21.1
|
0.030
|
Uric acid, μmol/L
|
328.0 ± 75.6
|
328.3 ± 75.3
|
327.0 ± 76.6
|
0.842
|
FBG, mg/dL
|
127.7 (109.6, 157.0)
|
125.3 (108.1, 148.4)
|
141.5 (118.4, 173.3)
|
< 0.001
|
HbA1c, %
|
7.5 ± 1.3
|
7.3 ± 1.2
|
8.0 ± 1.3
|
< 0.001
|
TyG index
|
9.1 ± 0.6
|
9.0 ± 0.6
|
9.6 ± 0.7
|
< 0.001
|
LVEF, %
|
64.0 ± 6.6
|
64.3 ± 6.3
|
62.7 ± 7.5
|
0.010
|
Initial diagnosis, n (%)
|
|
|
|
0.149
|
UA
|
650 (81.5)
|
510 (82.5)
|
140 (77.8)
|
|
NSTEMI
|
148 (18.5)
|
108 (17.5)
|
40 (22.2)
|
|
Pre-admission medication, n (%)
|
|
|
|
|
ACEI
|
79 (9.9)
|
62 (10.0)
|
17 (9.4)
|
0.816
|
ARB
|
128 (16.0)
|
99 (16.0)
|
29 (16.1)
|
0.976
|
DAPT
|
253 (31.7)
|
194 (31.4)
|
59 (32.8)
|
0.725
|
Aspirin
|
427 (53.5)
|
325 (52.6)
|
102 (56.7)
|
0.334
|
Clopidogrel
|
264 (33.1)
|
203 (32.8)
|
61 (33.9)
|
0.794
|
β-Blocker
|
166 (20.8)
|
127 (20.6)
|
39 (21.7)
|
0.745
|
Statins
|
233 (29.2)
|
190 (30.7)
|
43 (23.9)
|
0.075
|
Proton pump inhibitor
|
8 (1.0)
|
7 (1.1)
|
1 (0.6)
|
0.796
|
Oral hypoglycemic agents
|
413 (51.8)
|
324 (52.4)
|
89 (49.4)
|
0.481
|
Metformin
|
170 (21.3)
|
138 (22.3)
|
32 (17.8)
|
0.189
|
Alpha-glucosidase inhibitor
|
185 (23.2)
|
140 (22.7)
|
45 (25.0)
|
0.512
|
Sulfonylurea
|
126 (15.8)
|
102 (16.5)
|
24 (13.3)
|
0.304
|
Dipeptidyl peptidase 4 inhibitor
|
15 (1.9)
|
12 (1.9)
|
3 (1.7)
|
0.811
|
Insulin
|
225 (28.2)
|
163 (26.4)
|
62 (34.4)
|
0.034
|
Post-discharge medication, n (%)
|
|
|
|
|
ACEI
|
234 (29.3)
|
177 (28.6)
|
57 (31.7)
|
0.433
|
ARB
|
384 (48.1)
|
294 (47.6)
|
90 (50.0)
|
0.566
|
DAPT
|
796 (99.7)
|
617 (99.8)
|
179 (99.4)
|
0.934
|
DAPT interruption in 12 months
|
12 (1.5)
|
9 (1.5)
|
3 (1.7)
|
0.838
|
Aspirin
|
797 (99.9)
|
617 (99.8)
|
180 (100.0)
|
0.589
|
Clopidogrel
|
797 (99.9)
|
618 (100.0)
|
179 (99.4)
|
0.226
|
β-Blocker
|
744 (93.2)
|
579 (93.7)
|
165 (91.7)
|
0.342
|
Statins
|
787 (98.6)
|
611 (98.9)
|
176 (97.8)
|
0.459
|
Statins interruption in 12 months
|
31 (3.9)
|
21 (3.4)
|
10 (5.6)
|
0.187
|
Proton pump inhibitor
|
790 (99.0)
|
613 (99.2)
|
177 (98.3)
|
0.554
|
Oral hypoglycemic agents
|
409 (51.3)
|
321 (51.9)
|
88 (48.9)
|
0.471
|
Metformin
|
167 (20.9)
|
135 (21.8)
|
32 (17.8)
|
0.238
|
Alpha-glucosidase inhibitor
|
181 (22.7)
|
137 (22.2)
|
44 (24.4)
|
0.521
|
Sulfonylurea
|
123 (15.4)
|
99 (16.0)
|
24 (13.3)
|
0.380
|
Dipeptidyl peptidase 4 inhibitor
|
15 (1.9)
|
12 (1.9)
|
3 (1.7)
|
0.811
|
Insulin
|
217 (27.2)
|
156 (25.2)
|
61 (33.9)
|
0.022
|
Angiographic data
|
|
|
|
|
LM disease, n (%)
|
44 (5.5)
|
22 (3.6)
|
22 (12.2)
|
< 0.001
|
One-vessel disease, n (%)
|
167 (20.9)
|
146 (23.6)
|
21 (11.7)
|
0.001
|
Two-vessel disease, n (%)
|
287 (36.0)
|
233 (37.7)
|
54 (30.0)
|
0.058
|
Three-vessel disease, n (%)
|
344 (43.1)
|
239 (38.7)
|
105 (58.3)
|
< 0.001
|
Chronic total occlusion, n (%)
|
117 (14.7)
|
67 (10.8)
|
50 (27.8)
|
< 0.001
|
Diffuse lesion, n (%)
|
237 (29.7)
|
169 (27.3)
|
68 (37.8)
|
0.007
|
Bifurcation lesion, n (%)
|
186 (23.3)
|
124 (20.1)
|
62 (34.4)
|
< 0.001
|
In-stent restenosis, n (%)
|
58 (7.3)
|
38 (6.1)
|
20 (11.1)
|
0.024
|
SYNTAX score
|
12.0 ± 5.5
|
11.1 ± 5.1
|
15.2 ± 6.0
|
< 0.001
|
Procedural results
|
|
|
|
|
Target vessel territory, n (%)
|
|
|
|
|
LM
|
25 (3.1)
|
14 (2.3)
|
11 (6.1)
|
0.009
|
LAD
|
513 (64.3)
|
393 (63.6)
|
120 (66.7)
|
0.449
|
LCX
|
335 (42.0)
|
249 (40.3)
|
86 (47.8)
|
0.073
|
RCA
|
398 (49.9)
|
300 (48.5)
|
98 (54.4)
|
0.164
|
DES implantation, n (%)
|
785 (98.4)
|
608 (98.4)
|
177 (98.3)
|
0.964
|
DCB use, n (%)
|
15 (1.9)
|
10 (1.6)
|
5 (2.8)
|
0.313
|
Complete revascularization, n (%)
|
414 (51.9)
|
333 (53.9)
|
81 (45.0)
|
0.036
|
Number of stents
|
2.1 ± 1.3
|
2.0 ± 1.2
|
2.4 ± 1.5
|
0.001
|
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; CAD, coronary artery disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; PVD, peripheral vascular disease; COPD, chronic obstructive pulmonary disease; TGs, triglycerides; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; eGFR, estimated glomerular filtration rate; FBG, fasting blood glucose; HbA1c, glycosylated hemoglobin A1c; TyG, triglyceride glucose; LVEF, left ventricular ejection fraction; UA, unstable angina; NSTEMI, non-ST-segment elevation myocardial infarction; ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; DAPT, dual antiplatelet therapy; LM, left main artery; SYNTAX, synergy between PCI with taxus and cardiac surgery; LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery; DES, drug-eluting stent; DCB, drug-coated balloon.
ROC curve analysis showed that the AUC of TyG index for predicting primary endpoint was 0.745 (95% CI 0.702-0.788, P < 0.001). The TyG index of 9.18 was determined as the optimal cutoff point for predicting primary endpoint with a sensitivity of 77.2% and a specificity of 62.8%. Baseline characteristics of groups according to the optimal cutoff point of TyG index were summarized in Table 2. Compared with patients in lower TyG index group, those with higher TyG index levels seemed to be younger, manifest higher levels of BMI and heart rate, and higher proportion of dyslipidemia. Laboratory indexes including TGs, TC, LDL-C, hs-CRP, uric acid, FBG and HbA1c were significantly higher in patients with higher TyG index, while HDL-C levels were relatively lower. In higher TyG index group, more patients were diagnosed as NSTEMI and prescribed insulin for treatment. Participants with higher TyG index also showed higher SYNTAX score compared to those with lower TyG index.
Table 2. Baseline clinical characteristics of patients stratified by the optimal cutoff point of TyG index.
|
Total population
(n = 798)
|
Lower TyG index
(< 9.18; n = 429)
|
Higher TyG index
(≥ 9.18; n = 369)
|
P value
|
Age, years
|
60.9 ± 8.3
|
62.1 ± 7.9
|
59.5 ± 8.5
|
< 0.001
|
Sex, male, n (%)
|
545 (68.3)
|
303 (70.6)
|
242 (65.6)
|
0.127
|
BMI, kg/m2
|
26.7 ± 3.2
|
26.3 ± 3.2
|
27.1 ± 3.2
|
< 0.001
|
Heart rate, bpm
|
71.7 ± 10.2
|
70.9 ± 9.6
|
72.5 ± 10.8
|
0.028
|
SBP, mmHg
|
131.8 ± 17.1
|
131.3 ± 16.8
|
132.2 ± 17.5
|
0.443
|
DBP, mmHg
|
76.8 ± 10.1
|
76.2 ± 10.1
|
77.6 ± 10.1
|
0.051
|
Smoking, n (%)
|
417 (52.3)
|
227 (52.9)
|
190 (51.5)
|
0.688
|
Drinking, n (%)
|
184 (23.1)
|
106 (24.7)
|
78 (21.1)
|
0.233
|
Family history of CAD, n (%)
|
93 (11.7)
|
44 (10.3)
|
49 (13.3)
|
0.185
|
Duration of diabetes, years
|
8.2 ± 4.3
|
8.3 ± 4.3
|
8.2 ± 4.2
|
0.681
|
Medical history, n (%)
|
|
|
|
|
Hypertension
|
573 (71.8)
|
303 (70.6)
|
270 (73.2)
|
0.426
|
Dyslipidemia
|
710 (89.0)
|
347 (80.9)
|
363 (98.4)
|
< 0.001
|
Prior MI
|
175 (21.9)
|
90 (21.0)
|
85 (23.0)
|
0.484
|
Prior PCI
|
151 (18.9)
|
82 (19.1)
|
69 (18.7)
|
0.881
|
Prior stroke
|
109 (13.7)
|
60 (14.0)
|
49 (13.3)
|
0.772
|
Prior PVD
|
125 (15.7)
|
72 (16.8)
|
53 (14.4)
|
0.348
|
Laboratory results
|
|
|
|
|
TGs, mg/dL
|
138.2 (97.2, 198.5)
|
99.2 (78.4, 127.1)
|
204.7 (164.4, 276.0)
|
< 0.001
|
TC, mg/dL
|
157.2 ± 39.7
|
145.9 ± 35.0
|
170.4 ± 40.8
|
< 0.001
|
LDL-C, mg/dL
|
94.2 ± 33.1
|
88.2 ± 30.5
|
101.1 ± 34.6
|
< 0.001
|
HDL-C, mg/dL
|
36.9 ± 8.7
|
38.7 ± 9.3
|
34.8 ± 7.3
|
< 0.001
|
hs-CRP, mg/L
|
1.6 (0.7, 4.1)
|
1.3 (0.6, 4.2)
|
1.9 (0.9, 3.9)
|
0.009
|
Creatinine, mg/dL
|
0.8 ± 0.2
|
0.8 ± 0.2
|
0.8 ± 0.2
|
0.655
|
eGFR, mL/ (min * 1.73m2)
|
96.5 ± 21.6
|
96.6 ± 21.3
|
96.5 ± 22.0
|
0.992
|
Uric acid, μmol/L
|
328.0 ± 75.6
|
322.2 ± 74.9
|
334.8 ± 75.9
|
0.019
|
FBG, mg/dL
|
127.7 (109.6, 157.0)
|
115.4 (102.3, 133.1)
|
149.9 (125.3, 177.8)
|
< 0.001
|
HbA1c, %
|
7.5 ± 1.3
|
7.1 ± 1.2
|
7.8 ± 1.3
|
< 0.001
|
TyG index
|
9.1 ± 0.6
|
8.6 ± 0.4
|
9.7 ± 0.4
|
< 0.001
|
LVEF, %
|
64.0 ± 6.6
|
64.0 ± 6.8
|
64.0 ± 6.4
|
0.986
|
Initial diagnosis, n (%)
|
|
|
|
0.022
|
UA
|
650 (81.5)
|
362 (84.4)
|
288 (78.0)
|
|
NSTEMI
|
148 (18.5)
|
67 (15.6)
|
81 (22.0)
|
|
Pre-admission medication, n (%)
|
|
|
|
|
ACEI
|
79 (9.9)
|
44 (10.3)
|
35 (9.5)
|
0.716
|
ARB
|
128 (16.0)
|
66 (15.4)
|
62 (16.8)
|
0.586
|
DAPT
|
253 (31.7)
|
136 (31.7)
|
117 (31.7)
|
0.999
|
Aspirin
|
427 (53.5)
|
226 (52.7)
|
201 (54.5)
|
0.613
|
Clopidogrel
|
264 (33.1)
|
141 (32.9)
|
123 (33.3)
|
0.889
|
β-Blocker
|
166 (20.8)
|
92 (21.4)
|
74 (20.1)
|
0.629
|
Statins
|
233 (29.2)
|
127 (29.6)
|
106 (28.7)
|
0.786
|
Proton pump inhibitor
|
8 (1.0)
|
4 (0.9)
|
4 (1.1)
|
0.830
|
Oral hypoglycemic agents
|
413 (51.8)
|
220 (51.3)
|
193 (52.3)
|
0.773
|
Metformin
|
170 (21.3)
|
101 (23.5)
|
69 (18.7)
|
0.096
|
Alpha-glucosidase inhibitor
|
185 (23.2)
|
100 (23.3)
|
85 (23.0)
|
0.927
|
Sulfonylurea
|
126 (15.8)
|
67 (15.6)
|
59 (16.0)
|
0.886
|
Dipeptidyl peptidase 4 inhibitor
|
15 (1.9)
|
7 (1.6)
|
8 (2.2)
|
0.578
|
Insulin
|
225 (28.2)
|
109 (25.4)
|
116 (31.4)
|
0.059
|
Post-discharge medication, n (%)
|
|
|
|
|
ACEI
|
234 (29.3)
|
114 (26.6)
|
120 (32.5)
|
0.066
|
ARB
|
384 (48.1)
|
204 (47.6)
|
180 (48.8)
|
0.729
|
DAPT
|
796 (99.7)
|
429 (100.0)
|
367 (99.5)
|
0.214
|
DAPT interruption in 12 months
|
12 (1.5)
|
7 (1.6)
|
5 (1.4)
|
0.749
|
Aspirin
|
797 (99.9)
|
429 (100.0)
|
368 (99.7)
|
0.462
|
Clopidogrel
|
797 (99.9)
|
429 (100.0)
|
368 (99.7)
|
0.462
|
β-Blocker
|
744 (93.2)
|
400 (93.2)
|
344 (93.2)
|
0.993
|
Statins
|
787 (98.6)
|
423 (98.6)
|
364 (98.6)
|
0.958
|
Statins interruption in 12 months
|
31 (3.9)
|
14 (3.3)
|
17 (4.6)
|
0.327
|
Proton pump inhibitor
|
790 (99.0)
|
426 (99.3)
|
364 (98.6)
|
0.568
|
Oral hypoglycemic agents
|
409 (51.3)
|
217 (50.6)
|
192 (52.0)
|
0.683
|
Metformin
|
167 (20.9)
|
98 (22.8)
|
69 (18.7)
|
0.151
|
Alpha-glucosidase inhibitor
|
181 (22.7)
|
97 (22.6)
|
84 (22.8)
|
0.959
|
Sulfonylurea
|
123 (15.4)
|
64 (14.9)
|
59 (16.0)
|
0.676
|
Dipeptidyl peptidase 4 inhibitor
|
15 (1.9)
|
7 (1.6)
|
8 (2.2)
|
0.578
|
Insulin
|
217 (27.2)
|
104 (24.2)
|
113 (30.6)
|
0.043
|
Angiographic data
|
|
|
|
|
LM disease, n (%)
|
44 (5.5)
|
19 (4.4)
|
25 (6.8)
|
0.148
|
One-vessel disease, n (%)
|
167 (20.9)
|
92 (21.4)
|
75 (20.3)
|
0.698
|
Two-vessel disease, n (%)
|
287 (36.0)
|
163 (38.0)
|
124 (33.6)
|
0.197
|
Three-vessel disease, n (%)
|
344 (43.1)
|
174 (40.6)
|
170 (46.1)
|
0.117
|
Chronic total occlusion, n (%)
|
117 (14.7)
|
55 (12.8)
|
62 (16.8)
|
0.113
|
Diffuse lesion, n (%)
|
237 (29.7)
|
123 (28.7)
|
114 (30.9)
|
0.493
|
Bifurcation lesion, n (%)
|
186 (23.3)
|
93 (21.7)
|
93 (25.2)
|
0.240
|
In-stent restenosis, n (%)
|
58 (7.3)
|
28 (6.5)
|
30 (8.1)
|
0.384
|
SYNTAX score
|
12.0 ± 5.5
|
11.6 ± 5.5
|
12.6 ± 5.6
|
0.010
|
Procedural results
|
|
|
|
|
Target vessel territory, n (%)
|
|
|
|
|
LM
|
25 (3.1)
|
14 (3.3)
|
11 (3.0)
|
0.819
|
LAD
|
513 (64.3)
|
274 (63.9)
|
239 (64.8)
|
0.791
|
LCX
|
335 (42.0)
|
185 (43.1)
|
150 (40.7)
|
0.480
|
RCA
|
398 (49.9)
|
211 (49.2)
|
187 (50.7)
|
0.674
|
DES implantation, n (%)
|
785 (98.4)
|
425 (99.1)
|
360 (97.6)
|
0.163
|
DCB use, n (%)
|
15 (1.9)
|
5 (1.2)
|
10 (2.7)
|
0.109
|
Complete revascularization, n (%)
|
414 (51.9)
|
229 (53.4)
|
185 (50.1)
|
0.360
|
Number of stents
|
2.1 ± 1.3
|
2.1 ± 1.3
|
2.1 ± 1.3
|
0.700
|
The groups were stratified by the optimal cutoff point of TyG index determined by ROC curve analysis.
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; CAD, coronary artery disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; PVD, peripheral vascular disease; COPD, chronic obstructive pulmonary disease; TGs, triglycerides; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; eGFR, estimated glomerular filtration rate; FBG, fasting blood glucose; HbA1c, glycosylated hemoglobin A1c; TyG, triglyceride glucose; LVEF, left ventricular ejection fraction; UA, unstable angina; NSTEMI, non-ST-segment elevation myocardial infarction; ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; DAPT, dual antiplatelet therapy; LM, left main artery; SYNTAX, synergy between PCI with taxus and cardiac surgery; LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery; DES, drug-eluting stent; DCB, drug-coated balloon.
Correlation between the TyG index and cardiovascular risk factors
The Spearman rank correlation analysis was performed to determine the correlation between the TyG index and traditional or commonly-used risk factors for cardiovascular disease. The TyG index was positively correlated with BMI, FBG, HbA1c, TGs, TC, LDL-C, uric acid, and hs-CRP, while negatively correlated with age and HDL-C (Table 3).
Table 3. Correlations between the TyG index and traditional cardiovascular risk factors.
|
Correlation coefficient
|
P value
|
Age
|
-0.194
|
< 0.001
|
Sex, female
|
0.069
|
0.051
|
BMI
|
0.184
|
< 0.001
|
FBG
|
0.588
|
< 0.001
|
HbA1c
|
0.352
|
< 0.001
|
TGs
|
0.906
|
< 0.001
|
TC
|
0.333
|
< 0.001
|
LDL-C
|
0.197
|
< 0.001
|
HDL-C
|
-0.273
|
< 0.001
|
Uric acid
|
0.093
|
0.008
|
eGFR
|
0.010
|
0.785
|
hs-CRP
|
0.123
|
0.001
|
LVEF
|
0.001
|
0.981
|
SYNTAX score
|
0.049
|
0.166
|
BMI, body mass index; FBG, fasting blood glucose; HbA1c, glycosylated hemoglobin A1c; TGs, triglycerides; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; hs-CRP, high-sensitivity C-reactive protein; LVEF, left ventricular ejection fraction; SYNTAX, synergy between PCI with taxus and cardiac surgery.
Clinical outcomes and Kaplan-Meier analysis
During the 36-month follow-up period, 180 (22.6%) endpoint events including 14 (1.8%) all-cause death, 37 (4.6%) non-fatal MI, and 129 (16.2%) ischemia-driven revascularization were documented to perform the present analyses. The incidence of adverse prognosis was compared between groups stratified by the optimal cutoff point of TyG index determined by ROC curve analysis. The incidence of primary endpoint, non-fatal MI and ischemia-driven revascularization increased significantly in patients with higher TyG index compared with those with lower TyG index (all Chi-square P < 0.001). However, the all-cause death rate was similar between the two groups (Chi-square P = 0.172) (Table 4).
Table 4. Primary endpoint event rate according to the optimal cutoff point of TyG index.
|
Lower TyG index
(< 9.18; n = 429)
|
Higher TyG index
(≥ 9.18; n = 369)
|
P value
|
Primary endpoint, n (%)
|
41 (9.6)
|
139 (37.7)
|
< 0.001
|
All-cause death, n (%)
|
5 (1.2)
|
9 (2.4)
|
0.172
|
Non-fatal MI, n (%)
|
9 (2.1)
|
28 (7.6)
|
< 0.001
|
Ischemia-driven revascularization, n (%)
|
27 (6.3)
|
102 (27.6)
|
< 0.001
|
The groups were stratified by the optimal cutoff point of TyG index determined by ROC curve analysis.
TyG, triglyceride glucose; MI, myocardial infarction.
Kaplan-Meier curves for incidence of primary endpoint and each component of it according to the optimal cutoff point of TyG index were shown in Figure 2. Kaplan-Meier curves for primary endpoint showed a significant difference between the lower and higher TyG index group (Figure 2A, Log-rank P < 0.001). The difference was mainly driven by the increased incidence of non-fatal MI and ischemia-driven revascularization (Figure 2C and 2D, both Log-rank P < 0.001). Kaplan-Meier curves for all-cause death between the lower and higher TyG index group failed to reach statistical significance (Figure 2B, Log-rank P = 0.167).
Cox proportional hazard analyses to evaluate the prognostic implication of TyG index
In multivariate Cox proportional hazard analysis, four models (Model 1-4 as described above) including variables that had statistical significance (P < 0.2) and/or clinical importance were constructed to evaluate the predictive potential of TyG index for primary endpoint. After adjusting for confounding variables, higher TyG index levels remained to be an independent risk predictor of primary endpoint, despite of regarding TyG index as nominal variable or continuous variable (all P < 0.001 in Model 1-4) (Table 5). The detailed information of Model 4 was shown in Table S1.
Table 5. Predictive value of TyG index for primary endpoint in different Cox proportional hazards models.
|
TyG index as a nominal variable*
|
TyG index as a continuous variable**
|
|
HR
|
95% CI
|
P value
|
HR
|
95% CI
|
P value
|
Crude model
|
4.610
|
3.253-6.533
|
< 0.001
|
3.367
|
2.677-4.235
|
< 0.001
|
Model 1
|
4.858
|
3.367-7.011
|
< 0.001
|
3.459
|
2.731-4.381
|
< 0.001
|
Model 2
|
3.774
|
2.553-5.580
|
< 0.001
|
2.900
|
2.194-3.832
|
< 0.001
|
Model 3
|
3.994
|
2.699-5.991
|
< 0.001
|
3.031
|
2.294-4.005
|
< 0.001
|
Model 4
|
4.062
|
2.732-6.040
|
< 0.001
|
3.208
|
2.400-4.289
|
< 0.001
|
Model 1: adjusted for age, sex (female), BMI, SBP, DBP, smoking, drinking, duration of diabetes, dyslipidemia, prior MI, PCI, stroke and PVD.
Model 2: adjusted for variables included in Model 1 and diagnosis (NSTEMI), TC, HDL-C, eGFR, HbA1c, LVEF.
Model 3: adjusted for variables included in Model 2 and SYNTAX score, LM treatment, DCB use, complete revascularization and number of stents.
Model 4: adjusted for variables included in Model 3 and DAPT at discharge, DAPT interruption in 12 months, statins at discharge, statins interruption in 12 months, oral hypoglycemic agents (metformin, alpha-glucosidase inhibitor, sulfonylurea, dipeptidyl peptidase 4 inhibitor) at discharge and insulin at discharge.
* The HR was examined regarding lower TyG index as reference (stratified by the optimal cutoff point of TyG index determined by ROC curve analysis).
** The HR was examined by per 1-unit increase of TyG index.
TyG, triglyceride glucose; HR, hazard ratio; CI, confidence interval.
The predictive value of TyG index for each component of primary endpoint was also evaluated by using model 4. The results showed that a 1-unit increase of TyG index was independently associated with higher risk of non-fatal MI and ischemia-driven revascularization [HR (95% CI) for non-fatal MI: 3.332 (1.730-6.415), P < 0.001; HR (95% CI) for ischemia-driven revascularization: 3.021 (2.167-4.211), P < 0.001]. However, higher TyG index levels failed to be a predictor of all-cause death, which was consistent with the results of Kaplan-Meier curves (Table 6).
Table 6. Predictive value of TyG index for primary endpoint and each component in univariate and multivariate analysis.
|
Univariate analysis
|
Multivariate analysis***
|
|
HR
|
95% CI
|
P value
|
HR
|
95% CI
|
P value
|
TyG index as a nominal variable*
|
|
|
|
|
|
|
Primary endpoint
|
4.610
|
3.253-6.533
|
< 0.001
|
4.062
|
2.732-6.040
|
< 0.001
|
All-cause death
|
2.103
|
0.705-6.276
|
0.183
|
0.872
|
0.179-4.258
|
0.866
|
Non-fatal MI
|
3.744
|
1.767-7.935
|
0.001
|
2.260
|
0.894-5.715
|
0.085
|
Ischemia-driven revascularization
|
4.920
|
3.218-7.521
|
< 0.001
|
4.980
|
3.075-8.067
|
< 0.001
|
TyG index as a continuous variable**
|
|
|
|
|
|
|
Primary endpoint
|
3.367
|
2.677-4.235
|
< 0.001
|
3.208
|
2.400-4.289
|
< 0.001
|
All-cause death
|
1.358
|
0.610-3.024
|
0.454
|
0.429
|
0.111-1.659
|
0.220
|
Non-fatal MI
|
4.449
|
2.684-7.373
|
< 0.001
|
3.332
|
1.730-6.415
|
< 0.001
|
Ischemia-driven revascularization
|
2.874
|
2.216-3.727
|
< 0.001
|
3.021
|
2.167-4.211
|
< 0.001
|
* The HR was examined regarding lower TyG index as reference (stratified by the optimal cutoff point of TyG index determined by ROC curve analysis).
** The HR was examined by per 1-unit increase of TyG index.
*** The multivariate analysis was performed by using Model 4 (adjusted for age, sex, BMI, SBP, DBP, smoking, drinking, duration of diabetes, dyslipidemia, prior MI, PCI, stroke, PVD, diagnosis (NSTEMI), TC, HDL-C, eGFR, HbA1c, LVEF, SYNTAX score, LM treatment, DCB use, complete revascularization, number of stents, DAPT at discharge, DAPT interruption in 12 months, statins at discharge, statins interruption in 12 months, oral hypoglycemic agents (metformin, alpha-glucosidase inhibitor, sulfonylurea, dipeptidyl peptidase 4 inhibitor) at discharge and insulin at discharge.
TyG, triglyceride glucose; MI, myocardial infarction; HR, hazard ratio; CI, confidence interval.
Further evaluation of the risk stratification value of TyG index for primary endpoint was performed in various subclasses of the study population. Increased TyG index (per 1-unit) was consistently related to primary endpoint in various subgroups, including age ≤ 65 or > 65 years, female or male, BMI ≤ 28 or > 28 kg/m2, with or without hypertension, UA or NSTEMI, HbA1c ≤ 7 or > 7 %, LDL-C ≤ 70 or > 70 mg/dL, with or without pre-admission medication including statins, oral hypoglycemic agents and insulin (Figure 3). Interestingly, the predictive value of TyG index seemed to be more prominent in patients with BMI > 28 kg/m2 [HR (95% CI): BMI > 28 kg/m2 5.513 (3.631-8.370) vs. BMI ≤ 28 kg/m2 2.178 (1.524-3.111), P for interaction < 0.001] and without pre-admission insulin therapy [HR (95% CI): without insulin 4.011 (2.827-5.691) vs. with insulin 2.255 (1.461-3.479), P for interaction = 0.024] (Figure 3).
Incremental effect of TyG index on predictive value for adverse prognosis
The addition of TyG index had a significant incremental effect on the AUC obtained from baseline risk model that consisted of risk factors including age, sex (female), smoking, SBP, prior MI, prior PCI, TC, HDL-C, eGFR, LVEF, SYNTAX score, LM treatment, complete revascularization, number of stents and statins at discharge (AUC: baseline risk model, 0.800 vs. baseline risk model + TyG index, 0.856, P for comparison < 0.001) (Table 7, Figure 4D). Moreover, the addition of TyG index significantly improved the reclassification and discrimination ability beyond the baseline risk model with a category-free NRI of 0.346 and an IDI of 0.087 (both P < 0.001) (Table 8). Adding TGs to the baseline risk model also had a significant incremental effect on prognostic prediction (AUC: baseline model 0.800 vs. baseline model + albumin 0.842, P for comparison < 0.001; category-free NRI: 0.318, P < 0.001; IDI: 0.067, P < 0.001) (Table 7 and 8, Figure 4C). However, the addition of glycemic index including FBG or HbA1c did not have a significant incremental effect on the AUC of the baseline risk model (Table 7, Figure 4A and 4B). A significant but relatively minor incremental effect on the reclassification and discrimination ability was found after adding HbA1c to the baseline risk model (Table 8).
Table 7. C-statistics for discrimination ability of various models.
|
AUC
|
95% CI
|
P value
|
Z value
|
P for comparison
|
Baseline risk model*
|
0.800
|
0.771-0.827
|
< 0.001
|
Reference
|
Reference
|
+ FBG
|
0.807
|
0.778-0.834
|
< 0.001
|
1.860
|
0.063
|
+ HbA1c
|
0.811
|
0.782-0.838
|
< 0.001
|
1.653
|
0.098
|
+ TGs
|
0.842
|
0.815-0.867
|
< 0.001
|
3.757
|
< 0.001
|
+ TyG index
|
0.856
|
0.829-0.879
|
< 0.001
|
4.046
|
< 0.001
|
* The baseline risk model includes age, sex (female), smoking, SBP, prior MI, prior PCI, TC, HDL-C, eGFR, LVEF, SYNTAX score, LM treatment, complete revascularization, number of stents and statins at discharge.
FBG, fasting blood glucose; HbA1c, glycosylated hemoglobin A1c; TGs, triglycerides; TyG, triglyceride glucose; AUC, area under the curve; CI, confidence interval.
Table 8. Category-free NRI and IDI for the incremental predictive values of various models.
|
Category-free NRI
|
IDI
|
|
Index
|
95% CI
|
P value
|
Index
|
95% CI
|
P value
|
Baseline risk model*
|
-
|
-
|
Reference
|
-
|
-
|
Reference
|
+ FBG
|
0.076
|
-0.146-0.190
|
0.358
|
0.005
|
-0.005-0.019
|
0.408
|
+ HbA1c
|
0.145
|
0.050-0.234
|
0.020
|
0.014
|
0.001-0.038
|
0.020
|
+ TGs
|
0.318
|
0.143-0.399
|
< 0.001
|
0.067
|
0.028-0.108
|
< 0.001
|
+ TyG index
|
0.346
|
0.230-0.430
|
< 0.001
|
0.087
|
0.039-0.128
|
< 0.001
|
* The baseline risk model includes age, sex (female), smoking, SBP, prior MI, prior PCI, TC, HDL-C, eGFR, LVEF, SYNTAX score, LM treatment, complete revascularization, number of stents and statins at discharge.
FBG, fasting blood glucose; HbA1c, glycosylated hemoglobin A1c; TGs, triglycerides; TyG, triglyceride glucose; NRI, net reclassification improvement; IDI, integrated discrimination improvement; CI, confidence interval.