Higher serum total bilirubin predicts high risk of 3-year adverse outcomes in patients undergoing primary percutaneous coronary intervention

Figures & data

Figure 1 Study population selection.

Abbreviation: TB, total bilirubin.

Table 1 Clinical information, laboratory tests and procedural characteristics

Variable	TB>0.60 mg/dL	TB≤0.60 mg/dL	p-value
	n=980	n=1,522
Age (years)	59.7±11.2	60.1±11.0	0.258
Male, n (%)	764 (78)	938 (61.6)	<0.001
Admission characteristics
Systolic BP (mmHg)	107±28.3	100.8±27.9	<0.001
Diastolic BP (mmHg)	78.1±12.0	76.6±11.6	<0.001
Urgent PCI, n (%)	57(5.8)	40(2.6)	<0.001
Cardiogenic shock, n (%)	3 (0.3)	1 (0.1)	0.142
Heart rate (/min)	72.9±11.4	71.6±10.8	0.022
Laboratory test
Fasting glycemia (mmol/L)	6.1±3	6±3	0.004
Creatinine (mmol/L)	73±24.1	72.2±37	0.001
Uric acid (mmol/L)	309.4±95.2	299±83.9	0.007
TB (mg/dL), median[IQR]	0.7 [0.6–0.9]	0.4 [0.3–0.5]	<0.001
Total cholesterol (mmol/L)	4.2±1	4.3±1.1	0.145
Triglycerides (mmol/L)	1.8±1	2±1.4	0.005
HDL-C (mmol/L)	1.1±0.3	1.1±0.3	0.446
LDL-C (mmol/L)	2.7±0.8	2.7±0.9	0.100
History of disease, n (%)
Stroke	51 (5.2)	82 (5.4)	0.842
Peripheral vascular disease	4 (0.4)	2 (0.1)	0.167
Previous PCI	64 (6.5)	105 (6.9)	0.720
Previous CABG	14 (1.4)	6 (0.4)	0.005
Myocardial infarction	103 (10.5)	129 (8.5)	0.087
COPD	11 (1.1)	11 (0.7)	0.314
Atrial fibrillation	28 (2.9)	21 (1.4)	0.015
Heart failure	124 (12.7)	169 (11.1)	0.030
Risk factors, n (%)
Hypertension	449 (45.8)	780 (51.2)	0.008
Diabetes mellitus	182 (18.6)	333 (21.9)	0.046
Smoking	334 (34.1)	475 (31.2)	0.134
Medication, n (%)
Aspirin	967 (98.7)	1,502 (98.7)	0.640
Clopidogrel	943 (96.2)	1,460 (95.9)	0.549
β-blocker	638 (65.1)	1,060 (69.6)	0.018
ACEI	506 (51.6)	835 (54.9)	0.483
CCB	201 (20.5)	390 (25.6)	0.003
Statin	864 (88.2)	1,411 (92.7)	<0.001
Angiographic and procedural characteristics
Total stent length (mm)	48.6±30.6	51.3±33.9	0.277
Stent diameter (mm)	3.1±1.3	3.1±0.4	0.056
Stent type, n (%)			0.760
SES	630(64.3)	997(65.5)
PES	202(20.6)	296(19.5)
Mixture	148(15.1)	229(15.1)
3 or more diseased vessels, n (%)	231 (23.5)	366(24.0)	0.749
Location of target lesions, n (%)
Left main stem	32 (3.3)	52 (3.4)	0.331
LAD	823 (84)	1,246 (81.9)	0.063
LCX	476 (48.6)	736 (48.4)	0.539
RCA	475 (48.5)	761 (50)	0.326
Coronary bypass graft	2 (0.2)	2 (0.1)	0.180
Total chronic occlusions, n (%)	143 (14.6)	182 (12)	0.056
Ostial lesions, n (%)	129 (13.2)	145 (9.5)	0.004
Bifurcation lesion, n (%)	156 (15.9)	290 (19.1)	0.045
Restenotic lesion, n (%)	13 (1.3)	21 (1.4)	0.839
LVEF (%)	60.4 (8.5)	61.1 (6.8)	0.783
Type of patients			0.018
ACS	798 (81.4)	1,294 (85)
SA	182 (18.6)	228 (15)

Abbreviations: ACS, acute coronary syndrome; BP, blood pressure; CABG, coronary artery bypass graft; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; PCI, percutaneous coronary intervention; SA, stable angina; TB, total bilirubin.

Table 2 In-hospital and follow-up outcomes in total population

Clinical outcomes	TB>0.60 mg/dL	TB≤0.60 mg/dL	p-value
	n=980	n=1,522
In-hospital outcomes, n (%)
Cardiovascular death	11 (1.1)	7 (0.5)	0.055
Nonfatal MI	6 (0.6)	9 (0.6)	0.947
MACE	16 (1.6)	15 (1)	0.153
Follow-up outcomes, n (%)
MACE	125 (12.8)	125 (8.2)	<0.001
Cardiovascular death	62 (6.3)	52 (3.4)	<0.001
Nonfatal MI	55 (5.6)	62 (4.1)	0.075
TVR	57 (5.8)	66 (4.3)	0.095
Any revascularization	85 (8.7)	114 (7.5)	0.286
In-stent restenosis	62 (6.3)	83 (5.5)	0.362
Angina	112 (11.4)	175 (11.5)	0.958
Stroke	17 (1.7)	21 (1.4)	0.479

Abbreviations: MACE, major adverse cardiovascular events; MI, myocardial infarction; TB, total bilirubin; TVR, target vessel revascularization.

Table 3 Factors related to TB by multiple linear regression analysis

Parameters	β (95%CI)	p-value
Age (years)	0.001 (0.0002–0.002)	0.012
Male	0.078 (0.051–0.104)	<0.001
Diabetes mellitus	−0.015 (−0.042–0.011)	0.263
Hypertension	−0.024 (−0.046 to–0.003)	0.027
Smoking	−0.024 (−0.050–0.001)	0.063
Atrial fibrillation	0.124 (0.047–0.202)	0.002
Heart failure	0.072 (0.039–0.105)	<0.001
Myocardial infarction history	0.021(−0.019–0.061)	0.307
3 or more diseased vessels	−0.016 (−0.041–0.009)	0.215
Lesion of left main stem	−0.048 (−0.107–0.011)	0.114
Restenosis lesions	−0.018 (−0.109–0.074)	0.705
Heart rate (/min)	0.002 (0.0005–0.003)	0.002
ACS	0.008 (−0.023–0.040)	0.605

Abbreviations: ACS, acute coronary syndrome; TB, total bilirubin.

Table 4 Associations between total bilirubin >0.60 mg/dL and clinical outcomes in total population

Clinical outcomes	Model 1	Model 2	Model 3
	OR (95%CI)	OR (95%CI)	OR (95%CI)
In-hospital outcomes
Cardiovascular death	2.46 (0.95–6.36)	2.64 (1.00–6.93)	NA
Nonfatal MI	1.04 (0.37–2.92)	1.10 (0.38–3.14)	NA
MACE	1.67 (0.82–3.39)	1.73 (0.84–3.55)	NA
Follow-up outcomes
MACE	1.63 (1.26–2.12)	1.60 (1.23–2.09)	1.60 (1.22–2.10)
Cardiovascular death	1.91 (1.31–2.79)	1.94 (1.32–2.86)	1.81 (1.22–2.70)
Nonfatal MI	1.40 (0.97–2.03)	1.38 (0.95–2.02)	1.40 (0.96–2.06)
TVR	1.36 (0.95–1.96)	1.60 (1.23–2.09)	1.26 (0.86–1.85)
Any revascularization	1.17 (0.88–1.57)	1.09 (0.81–1.47)	1.12 (0.83–1.51)
In-stent restenosis	1.17 (0.83–1.64)	1.12 (0.79–1.58)	1.15 (0.8–1.64)
Angina	0.99 (0.77–1.28)	0.99 (0.77–1.28)	1.01 (0.78–1.31)

Abbreviations: MACE, major adverse cardiovascular events; MI, myocardial infarction; TVR, target vessel revascularization.

Figure 2 Correlation of total bilirubin (TB) with major adverse cardiovascular and cerebrovascular events. (A) Categorical TB with tertiles; (B) binary, continuous, logarithmic and quadratic TB.

Figure 3 Plot of dose–response relationship between serum total bilirubin and MACE during follow-up (p nonlinear=0.208, p overall=0.025).

Abbreviations: CL, confidence limit; MACE, major adverse cardiovascular events.

Table 5 Dose–response relationship between total serum bilirubin and long-term MACE

Serum total bilirubin (mg/dL)	MACE
	OR	95% CI
0.21	0.81	0.50–1.33
0.44	0.88	0.79–0.97
0.52	1.0 (Reference)
0.6	1.16	1.01–1.32
1.06	1.41	1.01–1.97
p overall	0.025
p nonlinear	0.208

Abbreviation: MACE, major adverse cardiovascular events.

Figure 4 Associations between total bilirubin >0.60 mg/dL and clinical outcomes in ACS and SA patients.

Abbreviations: ACS, acute coronary syndrome; MACE, major adverse cardiovascular events; MI, myocardial infarction; SA, stable angina; TVR, target vessel revascularization. Logistic regression model adjusted for age, sex, diabetes mellitus and hypertension.

Table S1 In-hospital and follow-up outcomes in ACS and SA patients

Clinical outcomes	ACS patients			SA patients
	TB>0.60 mg/dL	TB<=0.60 mg/dL	p	TB>0.60 mg/dL	TB<=0.60 mg/dL	p
	n=798	n=1,294		n=182	n=228
In-hospital outcomes, n(%)
Cardiovascular death	9 (1.1)	7 (0.5)	0.134	2 (1.1)	0 (0)	0.113
Nonfatal MI	5 (0.6)	6 (0.5)	0.617	1 (0.5)	3 (1.3)	0.432
MACE	13 (1.6)	12 (0.9)	0.151	3 (1.6)	3 (1.3)	0.781
Follow-up outcomes, n(%)
MACE	99 (12.4)	105 (8.1)	0.001	26 (14.3)	20 (8.8)	0.079
Cardiovascular death	47 (5.9)	43 (3.3)	0.004	15 (8.2)	9 (3.9)	0.066
Nonfatal MI	47 (5.9)	57 (4.4)	0.129	8 (4.4)	5 (2.2)	0.206
TVR	43 (5.4)	54 (4.2)	0.152	14 (7.7)	12 (5.3)	0.316
Any revascularization	67 (8.4)	99 (7.7)	0.528	18 (9.9)	15 (6.6)	0.221
In-stent restenosis	49 (6.1)	71 (5.5)	0.525	13 (7.1)	12 (5.3)	0.429
Angina	96 (12)	144 (11.1)	0.435	16 (8.8)	31 (13.6)	0.129
Stroke	13 (1.6)	15 (1.2)	0.364	4 (2.2)	6 (2.6)	0.777

Abbreviations: ACS, acute coronary syndrome; MACE, major adverse cardiovascular events; MI, myocardial infarction; SA, stable angina; TB, total bilirubin; TVR, target vessel revascularization.