Table 1. Baseline clinical characteristics of the study population.
|
Total population, n = 2419
|
Without event, n = 1965
|
With event, n = 454
|
P
|
Age, years
|
60.08 ± 8.97
|
59.60 ± 8.72
|
62.16 ± 9.70
|
< 0.001
|
Male, n (%)
|
1737 (71.8)
|
1422 (72.4)
|
315 (69.4)
|
0.203
|
BMI, kg/m²
|
26.21 ± 3.45
|
26.13 ± 3.40
|
26.55 ± 3.61
|
0.019
|
Heart rate, bpm
|
69.77 ± 10.15
|
69.44 ± 10.00
|
71.17 ± 10.69
|
0.002
|
SBP, mmHg
|
130.30 ± 16.52
|
129.80 ± 15.99
|
132.44 ± 18.50
|
0.005
|
DBP, mmHg
|
77.05 ± 9.90
|
77.00 ± 9.68
|
77.25 ± 10.80
|
0.661
|
Smoking, n (%)
|
1381 (57.1)
|
1127 (57.4)
|
254 (55.9)
|
0.585
|
Drinking, n (%)
|
562 (23.2)
|
468 (23.8)
|
94 (20.7)
|
0.157
|
Family history of CAD, n (%)
|
254 (10.5)
|
203 (10.3)
|
51 (11.2)
|
0.572
|
Medical history, n (%)
|
|
|
|
|
Hypertension
|
1511 (62.5)
|
1210 (61.6)
|
301 (66.3)
|
0.061
|
Prior MI
|
527 (21.8)
|
348 (17.7)
|
179 (39.4)
|
< 0.001
|
Prior PCI
|
414 (17.1)
|
280 (14.2)
|
134 (29.5)
|
< 0.001
|
Prior CABG
|
55 (2.3)
|
23 (1.2)
|
32 (7.0)
|
< 0.001
|
Prior stroke
|
281 (11.6)
|
204 (10.4)
|
77 (17.0)
|
< 0.001
|
Prior PAD
|
84 (3.5)
|
63 (3.2)
|
21 (4.6)
|
0.137
|
Glycometabolic status
|
|
|
|
|
Non-diabetes
|
926 (38.3)
|
829 (42.2)
|
97 (21.4)
|
< 0.001
|
Pre-diabetes
|
645 (26.7)
|
531 (27.0)
|
114 (25.1)
|
0.406
|
Diabetes
|
848 (35.1)
|
605 (30.8)
|
243 (53.5)
|
< 0.001
|
Laboratory results
|
|
|
|
|
TGs, mmol/L
|
1.84 ± 1.32
|
1.69 ± 1.05
|
2.47 ± 2.00
|
< 0.001
|
TC, mmol/L
|
4.17 ± 1.06
|
4.14 ± 1.05
|
4.33 ± 1.07
|
0.001
|
LDL-C, mmol/L
|
2.50 ± 0.88
|
2.50 ± 0.89
|
2.50 ± 0.85
|
0.962
|
HDL-C, mmol/L
|
0.98 ± 0.23
|
0.99 ± 0.24
|
0.92 ± 0.21
|
< 0.001
|
Estimated RLP-C, mmol/L
|
0.69 ± 0.42
|
0.65 ± 0.35
|
0.90 ± 0.61
|
< 0.001
|
hs-CRP, mg/L
|
1.29 (0.58, 3.31)
|
1.22 (0.53, 3.06)
|
1.87 (0.77, 4.29)
|
< 0.001
|
Creatinine, μmol/L
|
76.00 ± 16.95
|
75.68 ± 16.49
|
77.42 ± 18.76
|
0.048
|
eGFR, ml/(min*1.73m²)
|
93.49 ± 20.36
|
94.09 ± 20.11
|
90.91 ± 21.22
|
0.003
|
Uric acid, μmol/L
|
346.22 ± 82.64
|
346.45 ± 81.45
|
345.21 ± 87.69
|
0.774
|
FBG, mmol/L
|
6.20 ± 1.94
|
6.01 ± 1.71
|
7.03 ± 2.57
|
< 0.001
|
HbA1c, %
|
5.90 (5.50, 6.60)
|
5.80 (5.50, 6.40)
|
6.40 (5.80, 8.00)
|
< 0.001
|
LVEF, %
|
65.00 (60.00, 68.00)
|
65.00 (61.00, 69.00)
|
63.00 (57.00, 67.00)
|
< 0.001
|
Initial diagnosis, n (%)
|
|
|
|
0.001
|
UA
|
2018 (83.4)
|
1662 (84.6)
|
356 (78.4)
|
|
NSTEMI
|
401 (16.6)
|
303 (15.4)
|
98 (21.6)
|
|
Medical treatment, n (%)
|
|
|
|
|
ACEI
|
734 (30.3)
|
577 (29.4)
|
157 (34.6)
|
0.029
|
ARB
|
948 (39.2)
|
753 (38.3)
|
195 (43.0)
|
0.068
|
Aspirin
|
2417 (99.9)
|
1963 (99.9)
|
454 (100.0)
|
0.496
|
Clopidogrel
|
2415 (99.8)
|
1963 (99.9)
|
452 (99.6)
|
0.109
|
β-Blocker
|
2199 (90.9)
|
1780 (90.6)
|
419 (92.3)
|
0.255
|
Statins
|
2366 (97.8)
|
1922 (97.8)
|
444 (97.8)
|
0.985
|
Oral hypoglycemic agents
|
437 (18.1)
|
314 (16.0)
|
123 (27.1)
|
< 0.001
|
Insulin
|
232 (9.6)
|
154 (7.8)
|
78 (17.2)
|
< 0.001
|
Angiographic data, n (%)
|
|
|
|
|
Left main disease
|
110 (4.5)
|
64 (3.3)
|
46 (10.1)
|
< 0.001
|
Multi-vessel disease
|
1631 (67.4)
|
1225 (62.3)
|
406 (89.4)
|
< 0.001
|
Chronic total occlusion
|
345 (14.3)
|
202 (10.3)
|
143 (31.5)
|
< 0.001
|
Diffuse lesion
|
605 (25.0)
|
431 (21.9)
|
174 (38.3)
|
< 0.001
|
Bifurcation lesion
|
492 (20.3)
|
368 (18.7)
|
124 (27.3)
|
< 0.001
|
Number of stents
|
1.96 ± 1.29
|
1.87 ± 1.14
|
2.33 ± 1.76
|
< 0.001
|
Bold values indicate statistically significant associations.
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; CAD, coronary artery disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; PAD, peripheral arterial disease; TGs, triglycerides; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; RLP-C, remnant-like particle cholesterol; hs-CRP, high-sensitivity C-reactive protein; eGFR, estimated glomerular filtration rate; FBG, fasting blood glucose; HbA1c, glycosylated hemoglobin A1c; LVEF, left ventricular ejection fraction; UA, unstable angina; NSTEMI, non-ST-segment elevation myocardial infarction; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker.
Table 2. Multiple Cox analysis on predictive value of estimated RLP-C for composite and each component of adverse events in the total population.
|
As a nominal variable*
|
As a continuous variable**
|
|
β
|
HR
|
95% CI
|
P
|
β
|
HR
|
95% CI
|
P
|
Composite adverse events
|
0.673
|
1.960
|
1.558-2.465
|
< 0.001
|
0.256
|
1.291
|
1.119-1.490
|
< 0.001
|
All-cause death
|
0.792
|
2.207
|
0.612-7.959
|
0.226
|
0.604
|
1.829
|
0.837-3.995
|
0.130
|
Non-fatal MI
|
0.633
|
1.883
|
1.195-2.966
|
0.006
|
0.285
|
1.330
|
1.002-1.764
|
0.048
|
Ischemia-driven revascularization
|
0.608
|
1.836
|
1.395-2.416
|
< 0.001
|
0.189
|
1.208
|
1.016-1.438
|
0.033
|
Bold values indicate statistically significant associations.
Multiple Cox analysis was adjusted for confounders that are significant (P < 0.05) in simple Cox analysis (details shown in Suppl. materials: Table S1).
* The HR was examined regarding the lower median of estimated RLP-C as reference.
** The HR was examined by per 1-SD increase of estimated RLP-C.
HR, hazard ratio; CI, confidence interval; MI, myocardial infarction.
Table 3. C-statistics for discrimination ability of the various predictive model for composite adverse events in the total population.
|
ROC curve analysis
|
Category-free NRI
|
IDI
|
|
AUC
|
95% CI
|
P
|
index
|
P
|
index
|
P
|
Baseline model*
|
0.798
|
0.781-0.814
|
reference
|
-
|
reference
|
-
|
reference
|
+ estimated RLP-C
|
0.811
|
0.795-0.826
|
< 0.001
|
0.084
|
0.048
|
0.017
|
0.030
|
Bold values indicate statistically significant associations.
* Baseline model includes traditional risk factors: age, sex (female), smoking, hypertension, prior MI, prior PCI, eGFR, HbA1c, TC, HDL-C, LVEF, left main disease and multi-vessel disease.
ROC, receiver operating characteristics; AUC, area under the curve; CI, confidence interval; NRI, net reclassification improvement; IDI, integrated discrimination improvement; RLP-C, remnant-like particle cholesterol.
Table 4. Multiple Cox analysis on predictive value of estimated RLP-C for composite and each component of adverse event in subgroups with different glycometabolic status.
|
As a nominal variable*
|
As a continuous variable**
|
|
β
|
HR
|
95% CI
|
P
|
β
|
HR
|
95% CI
|
P
|
Non-diabetic population
|
|
|
|
|
|
|
|
|
Composite adverse events
|
0.177
|
1.193
|
0.681-2.092
|
0.538
|
-0.044
|
0.957
|
0.548-1.670
|
0.876
|
All-cause death
|
-1.067
|
0.344
|
0.001-229.549
|
0.748
|
1.421
|
4.143
|
0.240-71.536
|
0.328
|
Non-fatal MI
|
0.173
|
1.189
|
0.382-3.703
|
0.766
|
0.088
|
1.092
|
0.309-3.855
|
0.892
|
Ischemia-driven revascularization
|
0.256
|
1.292
|
0.664-2.513
|
0.451
|
-0.208
|
0.812
|
0.421-1.568
|
0.535
|
Pre-diabetic population
|
|
|
|
|
|
|
|
|
Composite adverse events
|
0.289
|
1.335
|
0.852-2.092
|
0.208
|
-0.107
|
0.898
|
0.577-1.397
|
0.633
|
All-cause death
|
1.058
|
2.882
|
0.337-24.651
|
0.334
|
0.124
|
1.132
|
0.305-4.202
|
0.853
|
Non-fatal MI
|
0.297
|
1.346
|
0.532-3.404
|
0.530
|
0.141
|
1.152
|
0.535-2.483
|
0.718
|
Ischemia-driven revascularization
|
0.271
|
1.312
|
0.750-2.293
|
0.341
|
-0.321
|
0.725
|
0.405-1.297
|
0.278
|
Diabetic population
|
|
|
|
|
|
|
|
|
Composite adverse events
|
1.446
|
4.247
|
2.941-6.135
|
< 0.001
|
0.326
|
1.385
|
1.183-1.620
|
< 0.001
|
All-cause death
|
0.452
|
1.571
|
0.247-9.996
|
0.632
|
-0.284
|
0.753
|
0.329-1.723
|
0.502
|
Non-fatal MI
|
1.804
|
6.072
|
2.669-13.815
|
< 0.001
|
0.331
|
1.392
|
0.975-1.988
|
0.069
|
Ischemia-driven revascularization
|
1.304
|
3.683
|
2.397-5.657
|
< 0.001
|
0.283
|
1.327
|
1.100-1.600
|
0.003
|
Bold values indicate statistically significant associations.
Multiple Cox analysis was adjusted for confounders that are significant (P<0.05) in simple Cox analysis (details shown in Suppl. materials: Table S1).
* The HR was examined regarding the lower median of estimated RLP-C as reference.
** The HR was examined by per 1-SD increase of estimated RLP-C.
HR, hazard ratio; CI, confidence interval; MI, myocardial infarction.
Table 5. C-statistics for discrimination ability of the various predictive model for composite adverse events in subgroups with different glycometabolic status.
|
ROC curve analysis
|
Category-free NRI
|
IDI
|
|
AUC
|
95% CI
|
P
|
index
|
P
|
index
|
P
|
Non-diabetic population
|
|
|
|
|
|
|
|
Baseline model*
|
0.836
|
0.810-0.859
|
reference
|
-
|
reference
|
-
|
reference
|
+ estimated RLP-C
|
0.838
|
0.813-0.861
|
0.311
|
0.022
|
0.517
|
0.002
|
0.169
|
Pre-diabetic population
|
|
|
|
|
|
|
|
Baseline model*
|
0.781
|
0.747-0.812
|
reference
|
-
|
reference
|
-
|
reference
|
+ estimated RLP-C
|
0.781
|
0.747-0.812
|
0.581
|
0.017
|
0.842
|
0.001
|
0.642
|
Diabetic population
|
|
|
|
|
|
|
|
Baseline model*
|
0.788
|
0.759-0.815
|
reference
|
-
|
reference
|
-
|
reference
|
+ estimated RLP-C
|
0.836
|
0.809-0.860
|
< 0.001
|
0.155
|
0.010
|
0.040
|
< 0.001
|
Bold values indicate statistically significant associations.
* Baseline model includes traditional risk factors: age, sex (female), smoking, hypertension, prior MI, prior PCI, eGFR, HbA1c, TC, HDL-C, LVEF, left main disease and multi-vessel disease.
ROC, receiver operating characteristics; AUC, area under the curve; CI, confidence interval; NRI, net reclassification improvement; IDI, integrated discrimination improvement; RLP-C, remnant-like particle cholesterol.