The Systemic Inflammation Index Predicts Poor Clinical Prognosis in Patients with Initially Diagnosed Acute Coronary Syndrome Undergoing Primary Coronary Angiography

Figures & data

Figure 1 Flowchart of the study cohort.

Table 1 Baseline Characteristics of 757 Patients with Initially Diagnosed Acute Coronary Syndrome

	ALL(N=757)	SII<713.9(N=490)	SII≥713.9(N=267)	P value
Clinical characteristics
Age(years)	62.69(52.42–72.96)	63.10(53.71–72.49)	61.93(50.24–73.62)	0.133
Male sex, n(%)	428(56.5%)	259(52.9%)	169(63.3%)	0.006
Hypertension, n(%)	507(67.0%)	332(67.8%)	175(65.5%)	0.571
Diabetes mellitus, n(%)	220(29.1%)	146(29.8%)	74(27.7%)	0.559
New diagnosis dyslipidemia, n(%)	173(22.9%)	103(21.0%)	70(26.2%)	0.123
Current smoker, n(%)	250(33.0%)	144(29.4%)	106(39.7%)	0.005
Laboratory parameters
Hemoglobin(g/L)	141.41(126.50–156.32)	140.82(126.06–155.58)	142.51(127.35–157.76)	0.135
White blood cell(10^9/L)	7.26(4.97–9.55)	6.57(4.87–8.27)	8.54(5.89–11.19)	<0.001
Neutrophil(10^9/L)	4.98(3.07–6.89)	4.23(3.01–5.45)	6.35(4.18–8.52)	<0.001
Monocyte(10^9/L)	0.41(0.24–0.58)	0.38(0.24–0.52)	0.47(0.26–0.68)	<0.001
Lymphocyte(10^9/L)	1.73(1.13–2.33)	1.81(1.21–2.41)	1.59(1.03–2.15)	<0.001
Platelet(10^9/L)	226.15(169.19–283.11)	216.28(164.65–267.91)	244.27(182.53–306.01)	<0.001
Total cholesterol(mg/dL)	191.76(147.54–235.98)	191.71(149.43–233.99)	191.83(144.17–239.49)	0.972
Triglycerides(mg/dL)	158.51(66.38–250.64)	156.85(65.99–247.71)	161.57(67.06–256.08)	0.501
High-density lipoprotein(mg/dL)	44.57(30.17–58.97)	45.02(30.72–59.32)	43.76(29.18–58.34)	0.251
Low-density lipoprotein(mg/dL)	122.43(88.67–156.19)	122.64(88.89–156.39)	122.05(88.21–155.89)	0.821
Albumin(g/L)	41.87(38.42–45.32)	42.16(38.79–45.53)	41.33(37.80–44.86)	0.001
Fibrinogen(g/L)	2.93(2.24–3.62)	2.86(2.22–3.50)	3.06(2.31–3.81)	<0.001
Glycosylated hemoglobin(%)	5.49(4.13–6.85)	5.49(4.08–6.90)	5.48(4.20–6.76)	0.976
Fasting blood glucose(mmol/L)	6.44(4.23–8.65)	6.37(4.18–8.56)	6.57(4.32–8.82)	0.220
Medications
ACEI, n(%)	21(2.8%)	16(3.3%)	5(1.9%)	0.356
ARB, n(%)	188(24.8%)	134(27.3%)	54(20.2%)	0.034
β-blockers, n(%)	98(12.9%)	70(14.3%)	28(10.5%)	0.143
CCB, n(%)	238(31.4%)	169(34.5%)	69(25.8%)	0.017
Diuretics, n(%)	43(5.7%)	27(5.5%)	16(6.0%)	0.870
Glucose-lowering Drugs, n(%)	195(25.8%)	129(26.3%)	66(24.7%)	0.664
Lymphocyte-based inflammatory indices
SII	675.46(403.90–947.02)	512.14(390.36–633.92)	975.19(767.78–1182.60)	<0.001
PLR	140.94(94.37–187.51)	127.67(88.65–166.69)	165.30(115.85–214.75)	<0.001
NLR	3.10(1.77–4.43)	2.48(1.68–3.28)	4.23(2.86–5.60)	<0.001
MLR	0.25(0.14–0.36)	0.22(0.14–0.30)	0.31(0.18–0.44)	<0.001
FAR	0.071(0.052–0.090)	0.068(0.051–0.085)	0.075(0.054–0.096)	<0.001

Abbreviations: SII, systemic inflammatory index; PLR, platelet-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; MLR, mononuclear-to-lymphocyte ratio; FAR, fibrinogen-to-albumin ratio; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; CCB, calcium channel blockers.

Table 2 Receiver Operating Characteristic Curve Analysis

Biomarkers	Cut-Off value	AUC(95% CI)	P value	Sensitivity	Specificity
SII	713.9*10^9/L	0.709(0.660–0.757)	<0.001	0.636	0.712
NLR	2.718	0.675(0.626–0.723)	<0.001	0.757	0.514
MLR	0.265	0.615(0.563–0.667)	<0.001	0.521	0.665
FAR	0.071	0.584(0.531–0.636)	0.002	0.557	0.610
PLR	127.5	0.558(0.506–0.610)	0.032	0.643	0.460

Abbreviations: SII, systemic inflammation index; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; MLR, monocyte to lymphocyte ratio; FAR, fibrinogen-to-albumin ratio; AUC, area under curve.

Figure 2 Receiver operating characteristic (ROC) curve analysis with the area under the curve of SII, NLR, PLR. MLR and FAR in predicting.

Table 3 Clinical Outcomes in Initially Diagnosed Acute Coronary Syndrome Patients According to SII Score

	SII<713.9 (N=490)	SII≥713.9 (N=267)	P value
Primary endpoint: composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke	51(10.4%)	89(33.3%)	<0.001
Secondary endpoints
Cardiac death	1(0.2%)	0(0%)	0.999
Nonfatal myocardial infarction	41(8.4%)	79(29.6%)	<0.001
Nonfatal stroke	9(1.8%)	10(3.7%)	0.143
Congestive heart failure for hospitalization	14(2.9%)	37(13.9%)	<0.001
Revascularization(PCI or CABG)	115(23.5%)	92(34.5%)	0.002

Abbreviations: PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting.

Figure 3 Kaplan-Meier survival curve analysis showing: (A) MACEs, (B) cardiac death, (C) non-fatal myocardial infarction, (D) non-fatal stroke, (E) rehospitalization for congestive heart failure, (F) Revascularization.

Table 4 Cox Regression Analysis

	Univariable Cox Regression		Multivariable Cox Regression
	HR(95% CI)	P-value	HR(95% CI)	P-value
Age	0.985(0.969–1.001)	0.069
Gender	0.824(0.586–1.158)	0.265
Hypertension	1.171(0.811–1.690)	0.401
Diabetes mellitus	1.259(0.855–1.854)	0.243
New Diagnosis dyslipidemia	1.529(1.051–2.224)	0.026	1.645(1.125–2.407)	0.010
Current smoking	1.328(0.944–1.868)	0.104
Total cholesterol	1.000(0.996–1.004)	0.973
Triglycerides	0.999(0.997–1.001)	0.432
High-density lipoprotein	1.004(0.994–1.015)	0.430
Low-density lipoprotein	0.999(0.994–1.003)	0.552
Fasting blood glucose	0.990(0.917–1.070)	0.802
Glycosylated hemoglobin	0.912(0.797–1.042)	0.176
Fibrinogen	1.435(1.156–1.780)	0.001	1.168(0.859–1.589)	0.323
Albumin	0.964(0.920–1.011)	0.128
ACEI	0.850(0.271–2.669)	0.781
ARB	0.794(0.527–1.195)	0.268
β-blokers	1.081(0.666–1.755)	0.751
CCB	1.003(0.703–1.432)	0.985
Diuretics	1.007(0.471–2.155)	0.985
Glucose-lowering Drugs	1.087(0.749–1.579)	0.660
SII(≥713.9)	3.898(2.755–5.516)	<0.001	2.808(1.776–4.439)	<0.001
NLR(≥2.718)	2.729(1.853–4.018)	<0.001	1.305(0.796–2.141)	0.292
PLR(≥127.5)	1.775(1.251–2.519)	0.001	1.062(0.725–1.555)	0.758
MLR(≥0.265)	2.182(1.562–3.047)	<0.001	1.375(0.953–1.983)	0.088
FAR(≥0.071)	1.709(1.223–2.388)	0.002	1.260(0.792–2.004)	0.328

Abbreviations: ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; CCB, calcium channel blockers; SII, systemic inflammatory index; PLR, platelet-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; MLR, mononuclear-to-lymphocyte ratio; FAR, fibrinogen-to-albumin ratio.

Table 5 The Association of High SII (≥713.9*10⁹/L) and Future Adverse Events in Initially Diagnosed Acute Coronary Syndrome Patients

	Model I		Model II		Model III		Model IV
MACEs	3.898(2.755–5.516)	P<0.001	3.878(2.732–5.504)	P<0.001	3.899(2.742–5.545)	P<0.001	3.946(2.764–5.633)	P<0.001
Cardiac death	Ref		Ref		Ref		Ref
Nonfatal myocardial infarction	4.300(2.937–6.294)	P<0.001	4.256(2.898–6.250)	P<0.001	4.251(2.889–6.255)	P<0.001	4.320(2.921–6.390)	P<0.001
Nonfatal stroke	2.538(1.030–6.254)	P=0.043	2.646(1.063–6.584)	P=0.036	2.781(1.108–6.983)	P=0.029	2.691(1.071–6.761)	P=0.035
Congestive heart failure	5.697(3.076–10.550)	P<0.001	5.461(2.936–10.154)	P<0.001	5.565(2.981–10.390)	P<0.001	5.407(2.855–10.238)	P<0.001
Revascularization(PCI or CABG)	1.800(1.366–2.370)	P<0.001	1.772(1.342–2.340)	P<0.001	1.770(1.337–2.342)	P<0.001	1.766(1.331–2.342)	P<0.001

Notes: MACEs include cardiac death, nonfatal myocardial infarction, and nonfatal stroke. Model I: Confounding factors were not controlled. Model II: adjusted with age and gender. Model III: adjusted with age, gender, smoking, history of hypertension, diabetes, and a new diagnosis of dyslipidemia. Model IV: adjusted with age, gender, smoking, history of hypertension, diabetes, a new diagnosis of dyslipidemia, ACEI, ARB, β-blockers CCB, diuretics, and glucose-lowering Drugs.

Abbreviations: PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting.

Figure 4 Subgroup analysis of the predictive value of high SII vs low SII for MACEs in initially diagnosed acute coronary syndrome patients.

Table 6 Evaluation of Predictive Models for Cardiovascular Events

	C-index(95% CI)	P value	NRI(95% CI)	P value	IDI(95% CI)	P value
MACEs
Traditional risk factors	0.584(0.531–0.636)			P=ref		P=ref
Traditional + SII	0.729(0.683–0.775)	P<0.001	0.084(0.020–0.149)	P.011	0.106 (0.071–0.141)	P<0.001
Cardiac death
Traditional risk factors	0.531(0.480–0.583)
Traditional + SII	0.701(0.647–0.756)	P<0.001	Ref	Ref	Ref	Ref
Nonfatal STROKE
Traditional risk factors	0.537(0.418–0.657)			P=ref		P=ref
Traditional + SII	0.574(0.427–0.722)	P=0.268	0.002 (−0.003–0.029)	P=0.731	0.025(−0.003–0.052)	P=0.076
Nonfatal myocardial infarction
Traditional risk factors	0.599(0.543–0.655)			P=ref		P=ref
Traditional + SII	0.751(0.707–0.794)	P<0.001	0.099(0.021–0.176)	P=0.013	0.081(0.051–0.111)	P<0.001
Congestive heart failure
Traditional risk factors	0.587(0.506–0.669)			P=ref		P=ref
Traditional + SII	0.749(0.681–0.816)	P<0.001	0.004(−0.006–0.034)	P=0.278	0.148(−0.062–0.278)	P=0.198
Revascularization(PCI or CABG)
Traditional risk factors	0.592(0.547–0.638)			P=ref		P=ref
Traditional + SII	0.632(0.588–0.676)	P<0.001	0.010(−0.012–0.032)	P=0.367	0.016(0.003–0.028)	0.012

Notes: MACEs include cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

Abbreviations: PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; NRI, net reclassification improvement; IDI, integrated discrimination improvement. Traditional cardiovascular risk factors model: age, gender, hypertension, diabetes mellitus, new diagnosis dyslipidemia, and current smoker.