Association of Systemic Inflammatory Response Index and Pan-Immune-Inflammation-Value with Long-Term Adverse Cardiovascular Events in ST-Segment Elevation Myocardial Infarction Patients After Primary Percutaneous Coronary Intervention

Figures & data

Table 1 Comparison of Baseline Characteristics and Laboratory Parameters Between Patients with Non Acute Myocardial Infarction Patients (Non-AMI) and ST-Segment Elevation Myocardial Infarction (STEMI) at Admission

Baseline Characteristics	Control Group, n=122	STEMI Group, n=42	P -value^b
Demographics
Age, years	59(52,67)	63(55,69)	0.081
Male gender, n (%)	70(57)	32(76)	0.030
Smoking, n (%)	38(31)	24(57)	0.003
Hypertension, n (%)	75(61)	26(62)	0.961
Diabetes mellitus, n (%)	21(17)	8(19)	0.788
BMI (kg/m^2)	25.18±3.43	24.21±2.01	0.083^a
Laboratory parameters
Hemoglobin (g/L)	137.98±14.52	135.14±15.70	0.287^a
Total cholesterol (mmol/L)	4.382±0.925	4.696±1.112	0.074^a
Triglyceride (mmol/L)	1.450(0.980,2.223)	1.450(0.950,2.010)	0.545
HDL cholesterol (mmol/L)	1.180(1.020,1.370)	1.120(0.990,1.190)	0.048
LDL cholesterol (mmol/L)	2.287±0.737	2.760±0.848	0.001^a
Serum creatinine (μmol/L)	70.89±18.04	85.02±44.43	0.051^a
White blood cell count (x10^9/L)	6.300(5.028,7.493)	10.835(7.535,12.248)	<0.001
Admission SII value	377.59(285.87,557.22)	648.91(509.74,1060.47)	<0.001
Admission SIRI value	0.942(0.600,1.275)	2.037(1.119,3.520)	<0.001
Admission PIV value	159.14(106.13,249.75)	375.54(188.14,612.48)	<0.001

Notes: ^aUnpaired Student’s t test. ^bMann–Whitney U-test and chi-square test.

Abbreviations: BMI, body mass index; HDL cholesterol, high-density lipoprotein cholesterol; LDL cholesterol, low-density lipoprotein cholesterol; SII, systemic immune-inflammation index; SIRI, systemic inflammation response index; PIV, Pan-Immune-Inflammation Value.

Figure 1 Study flow chart. 468 patients were diagnosed with ST-segment elevation acute myocardial infarction on admission. (A). 42 patients who also had routine blood tests on admission, 6–12 h after PCI, 24–48 h after PCI, and at discharge were screened; (B). A total of 216 patients with both routine blood tests on admission, 12 h after PCI, and at discharge were screened.

Abbreviation: PCI, percutaneous coronary intervention.

Figure 2 Trajectory of dynamic change in white blood cell count from admission to discharge in patients with ST-segment elevation acute myocardial infarction. (A). Trajectories of white blood cell counts in 42 patients with ST-segment elevation myocardial infarction during admission, 6–12 hours after PCI, 24–48 hours after PCI, and at discharge; (B). Trajectories of white blood cell counts in 216 patients with ST-segment elevation myocardial infarction during admission, 12 hours after PCI, and at discharge. (N, number of patients with white blood cells determinations; ^#Mean ± SD; *Median (interquartile range)).

Abbreviation: PCI, percutaneous coronary intervention.

Table 2 Dynamic Trajectories of SII, SIRI, and PIV from Admission to Discharge in Patients with STEMI

STEMI, n=42	Admission	6–12 Hours After PCI	12–48 Hours After PCI	Discharge	P -value
SII value	648.91(509.74,1060.48)	1097.18(655.87,2071.41)	663.22(444.89,1143.78)	631.70(384.34,848.61)	<0.001
SIRI value	2.037(1.119,3.520)	3.870(2.356,6.347)	2.368(1.563,3.384)	1.679(1.044,2.265)	<0.001
PIV value	375.54(188.14,612.48)	669.38(416.82,1252.67)	445.65(311.02,767.90)	246.29(173.17,420.23)	<0.001
STEMI, n=216	Admission	12hours after PCI		Discharge	P -value
SII value	673.55(358.45,1198.96)	1064.09(674.04,1926.75)		566.58(400.23,801.19)	<0.001
SIRI value	1.988(0.906,3.847)	4.480(2.626,7.087)		1.431(0.8829,2.131)	<0.001
PIV value	378.10(180.63,776.54)	864.71(455.76,1412.71)		281.73(284.72,476.47)	<0.001

Note: Mann–Whitney U-test.

Abbreviations: STEMI, ST-segment elevation myocardial infarction; SII, systemic immune-inflammation index; SIRI, systemic inflammation response index; PIV, Pan-Immune-Inflammation Value.

Figure 3 Trajectory of the dynamic changes of inflammatory markers SII, SIRI, and PIV from admission to discharge in patients with ST-segment elevation myocardial infarction. Trajectory of SII (A), SIRI (B), and PIV (C) dynamics in 42 patients with ST-segment elevation myocardial infarction (Mann–Whitney U-test P < 0.05, Friedman test and Bonferroni post hoc test adjusted P < 0.05). Box-and-whisker plot showing dynamic change trends for SII (D), SIRI (E), and PIV(F) in 216 patients with ST-segment elevation myocardial infarction (Friedman test and Bonferroni post hoc test adjusted P < 0.05). Boxes indicate 25–75% interquartile range; horizontal lines in boxes, median width; whiskers, 10–90% range; dots, detected outliers that reside outside the whisker range. Bolded values indicate higher levels of inflammatory markers SII, SIRI, and PIV in patients with STEMI at admission compared to the non acute myocardial infarction (control group). In patients with STEMI, the expression levels of inflammatory markers SII, SIRI, and PIV were higher 6–12 or 12 hours after PCI compared to admission and discharge.

Abbreviations: SII, systemic immune-inflammation index; SIRI, systemic inflammation response index; PIV, pan-immune-inflammation value, PCI, percutaneous coronary intervention.

Table 3 Clinical Outcomes at 1-Year Follow-Up After PCI for ST-Segment Elevation Myocardial Infarction (STEMI)

MACEs	Outcomes at 1 Year
Death, n (%)	14(16.47)
Acute reinfarction, n (%)	18(21.18)
UA revascularization, n (%)	27(31.76)
Heart failure, n (%)	21(24.71)
Reinfarction and Heart failure, n (%)	2(2.35)
UA revascularization and Heart failure, n (%)	3(3.53)

Abbreviations: PCI, percutaneous coronary intervention; MACEs, major adverse cardiac events; UA, unstable angina.

Table 4 Basic Clinical Characteristics Between MACEs Groups and Non-MACEs Groups in Patients with STEMI

Basic Clinical Characteristics	MACEs Group, n=85	Non-MACEs Group, n=131	P -value^b
Demographics
Age, years	64.00(55.00,69.50)	61.00(50.00,69.00)	0.108
Male gender, n (%)	69(81.18)	112(85.50)	0.400
Smoking, n (%)	59(69.41)	85(64.89)	0.491
Hypertension, n (%)	55(64.71)	77(58.78)	0.383
Diabetes mellitus, n (%)	21(24.71)	19(14.50)	0.059
BMI (kg/m^2)	24.09(22.49,25.28)	24.45(23.03,25.95)	0.068
Killip class ≥ II, n (%)	39(45.88)	28(21.37)	<0.001
Time from pain-to-balloon (h)	3.0(2.5,5.0)	3.0(2.0,5.0)	0.421
In-hospital day	12(10,15.5)	11(10,13)	0.026
Prior medications
Beta-blocker, n (%)	66(77.65)	113(86.26)	0.101
ACEI/ARBs, n (%)	50(58.82)	92(70.23)	0.084
CCB, n (%)	6(7.06)	12(9.16)	0.585
Laboratory parameters
CK-MB peak (ng/dL)	128.20(52.42,297.29)	83.00(27.80,274.33)	0.101
Troponin I peak (ng/dL)	13.549(7.099,40.425)	11.070(2.360,25.200)	0.035
Hemoglobin (g/L)	139(125.5,148.5)	140(129,148)	0.788
Albumin (g/L)	36.768±4.588	37.102±3.482	0.573^a
Total cholesterol (mmol/L)	4.490(3.940,5.135)	4.500(3.830,5.110)	0.779
Triglyceride (mmol/L)	1.520(1.115,2.120)	1.520(1.000,2.020)	0.862
HDL cholesterol (mmol/L)	1.090(0.930,1.180)	1.090(0.930,1.250)	0.599
LDL cholesterol (mmol/L)	2.640(2.265,3.035)	2.640(2.160,3.070)	0.438
C-reactive protein (mg/L)	12.70(4.38,39.66)	7.60(3.20,13.90)	0.003
Serum creatinine (μmol/L)	72.00(62.00,95.50)	72.00(63.00,83.00)	0.437
Fibrinogen (g/L)	3.350(2.850,3.880)	2.880(2.480,3.610)	0.001
D-dimer (mg/L)	0.520(0.295,0.985)	0.370(0.220,0.560)	<0.001
Lipoprotein (a) (mg/L)	125.00(82.60,286.20)	86.90(44.00,172.00)	0.001
Uric acid (umol/L)	392.00(281.50,487.50)	360.00(292.00,428.00)	0.127
Carotid artery calcification	35(41.18)	66(50.38)	0.185
LVEF on admission (%)	58.00(53.50,60.00)	60.00(58.00,61.00)	<0.001
LVDd (mm)	46.00(44.00,49.00)	46.00(42.00,49.00)	0.166
Localization of MI, n (%)
Left main coronary artery, n (%)	5(5.88)	3(2.29)	0.319
Left anterior descending artery, n (%)	39(45.88)	71(54.20)	0.232
Left circumflex artery, n (%)	14(16.47)	17(12.98)	0.474
Right coronary artery, n (%)	27(31.76)	40(30.53)	0.849
Angiographic characteristics
Number of diseased artery ≥ 2, n (%)	68(80.00)	75(57.25)	0.001
Mean stent diameter (mm)	3.000(2.750,3.375)	3.000(2.750,3.250)	0.517
Total stent length (mm)	36.00(29.00,57.50)	33.00(24.00,47.00)	0.009
No-reflow, n (%)	26(30.59)	16(12.21)	0.001
Gensini score	80.00(52.00,93.00)	52.00(38.00,80.00)	<0.001
Inflammation indicators
Admission SII value	845.80(493.30,1550.26)	596.67(282.98,1046.38)	0.002
12hours after PCI SII value	1499.82(901.97,2202.86)	915.40(604.86,1468.45)	<0.001
Discharge SII value	695.82(420.00,1031.74)	526.72(395.42,679.09)	<0.001
Admission SIRI value	2.724(1.335,5.050)	1.623(0.870,2.888)	<0.001
12hours after PCI SIRI value	6.115(4.293,10.646)	3.295(2.243,5.269)	<0.001
Discharge SIRI value	1.610(1.048,3.053)	1.272(0.868,1.806)	<0.001
Admission PIV value	507.48(299.20,1046.60)	314.22(148.77,612.48)	<0.001
12hours after PCI PIV value	1186.14(700.38,2305.88)	645.89(372.84,1098.48)	<0.001
Discharge PIV value	381.54(179.27,781.58)	260.32(86.66,352.78)	<0.001
SII change between Admission and 12hours after PCI	450.78(−51.65,1250.11)	312.51(−246.02,954.29)	0.115
SII change between Discharge and 12hours after PCI	−646.36(−1333.45,-212.46)	−388.47(−933.40,-77.82)	0.033
SII change between Discharge and Admission	−16.413(−610.544,308.691)	−131.54(−437.92,196.99)	0.400
SIRI change between Admission and 12hours after PCI	3.758(1.177,6.271)	1.317(0.254,2.974)	<0.001
SIRI change between Discharge and 12hours after PCI	−4.236(−7.644,-2.156)	−2.124(−3.675,-1.004)	<0.001
SIRI change between Discharge and Admission	−0.277(−2.626,0.596)	−0.384(−1.696,0.355)	0.939
PIV change between Admission and 12hours after PCI	628.16(232.20,1360.62)	204.42(17.64,613.76)	<0.001
PIV change between Discharge and 12hours after PCI	−652.11(−1907.21,-298.96)	−370.94(−764.42,-100.30)	<0.001
PIV change between Discharge and Admission	−15.604(−489.620,198.766)	−80.02(−275.51,73.73)	0.459

Notes: ^aUnpaired Student’s t test. ^bMann–Whitney U-test and Chi-square test/Fisher’s exact test.

Abbreviations: MACEs, major adverse cardiovascular events; BMI, body mass index; ACEI/ARBs, angiotensinogen converting enzyme inhibitor/angiotensinogen receptor blockers; CCB, calcium channel blocker; CK-MB, creatine kinase, myocardial; HDL cholesterol, high-density lipoprotein cholesterol; LDL cholesterol, low-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction; LVDd, Left ventricular end diastolic diameter; SII, systemic immune-inflammation index; SIRI, systemic inflammation response index; PIV, Pan-Immune-Inflammation Value; PCI, percutaneous coronary intervention.

Figure 4 Differential values of the inflammatory markers SII, SIRI, and PIV between the major cardiovascular adverse events (MACEs) and non-MACEs groups at different time points and between different time points (Mann–Whitney U-test P < 0.05). (A). Differential values of SII between MACEs and non-MACEs groups; (B). Differential values of SIRI between MACEs and non-MACEs groups; (C). Differential values of PIV between MACEs and non-MACEs groups; (D). Differential values of SII changes between MACEs and non-MACEs groups; (E). Differential values of SIRI changes between MACEs and non-MACEs groups; (F). Differential values of PIV changes between MACEs and non-MACEs groups.

Abbreviations: SII, systemic immune-inflammation index; SIRI, systemic inflammation response index; PIV, pan-immune-inflammation value.

Table 5 Univariate and Multivariable Cox Proportional Hazard Regression Analysis of MACEs Occurrence Within 1 Year of Hospital Discharge in Patients with ST-Segment Elevation Myocardial Infarction (STEMI) After PCI

	Univariate Analysis				Multivariable Analysis
	P-value	HR	95% CI		P-value	HR	95% CI
In-hospital day	<0.001	1.067	1.035	1.101
Killip class ≥ II, n (%)	<0.001	2.392	1.558	3.670	0.009	1.859	1.169	2.957
Troponin I peak (ng/dL)	0.062	1.007	1.000	1.014
Lipoprotein (a) (mg/L)	0.027	1.001	1.000	1.002
C-reactive protein (mg/L)	<0.001	1.011	1.005	1.017
Fibrinogen (g/L)	0.001	1.312	1.123	1.534
D-dimer (mg/L)	0.009	1.382	1.082	1.766
Number of diseased artery ≥ 2, n (%)	0.001	2.476	1.454	4.215
Total stent length (mm)	0.004	1.018	1.006	1.030	0.019	1.016	1.003	1.029
PIV change between Discharge and 12hours after PCI	<0.001	1.000	0.999	1.000
PIV change between Admission and 12hours after PCI	<0.001	1.000	1.000	1.000
SIRI change between Discharge and 12hours after PCI	<0.001	0.907	0.878	0.937
SIRI change between Admission and 12hours after PCI	<0.001	1.106	1.069	1.143
SII change between Discharge and 12hours after PCI	0.018	1.000	1.000	1.000
Admission SII value	0.005	1.000	1.000	1.000
12hours after PCI SII value	<0.001	1.000	1.000	1.000
Discharge SII value	<0.001	1.001	1.000	1.001
Admission SIRI value	<0.001	1.090	1.041	1.142
12hours after PCI SIRI value	<0.001	1.099	1.071	1.127	<0.001	1.079	1.050	1.108
Discharge SIRI value	<0.001	1.178	1.112	1.248
Admission PIV value	0.002	1.000	1.000	1.001
12hours after PCI PIV value	<0.001	1.000	1.000	1.000
Discharge PIV value	<0.001	1.001	1.000	1.001
Gensini score	<0.001	1.019	1.012	1.025	<0.001	1.014	1.007	1.022
No-reflow, n (%)	0.001	2.196	1.383	3.487
LVEF on admission (%)	<0.001	0.940	0.918	0.962

Abbreviations: MACEs, major adverse cardiac events; PCI, percutaneous coronary intervention; SII, systemic immune-inflammation index; SIRI, systemic inflammation response index; PIV, Pan-Immune-Inflammation Value; LVEF, left ventricular ejection fraction; HR, hazard ratio; CI, confidence interval.

Table 6 Correlation Between General Clinical Characteristics, Angiographic Characteristics and SIRI in Patients with ST-Segment Elevation Myocardial Infarction (STEMI)

		N	12 Hours After PCI SIRI value Median (Interquartile Range, 25–75 Percentiles)	P -value
Sex	Male	181	4.496(2.665,7.095)	0.837
	Female	35	4.256(2.512,6.994)
Age (y)	≥63 (median)	111	4.557(2.613,4.682)	0.688
	<63	105	4.109(2.642,7.101)
Hypertension	Yes	132	4.716(2.466,7.101)	0.463
	No	84	4.132(2.718,6.640)
Diabetes mellitus	Yes	40	4.542(3.275,6.859)	0.318
	No	176	4.359(2.514,7.097)
Killip class at admission	I	149	4.109(2.543,6.037)	0.002
	≥ II	67	5.110(3.268,9.411)
In-hospital day	<11	81	4.550(2.270,6.256)	0.164
	≥11	135	4.464(2.777,7.349)
Number of diseased arteries	1	73	4.109(2.532,7.084)	0.377
	≥ 2	143	4.545(2.665,7.100)
No-reflow	Not occurred	174	3.986(2.387,6.119)	<0.001
	Occurred	42	5.467(4.174,8.390)

Abbreviations: PCI, percutaneous coronary intervention; SIRI, systemic inflammation response index.

Table 7 The Optimal Cut-off Value and Area Under the Receiver Operating Characteristic Curve (ROC) of Inflammatory Markers SII, SIRI and PIV and Their Dynamically Fluctuating Changes Between Each Time Point to Predict the Occurrence of Major Adverse Cardiac Events (MACEs) Within 1 Year of Discharge in Patients with ST-Segment Elevation Myocardial Infarction (STEMI) After PCI

Inflammation Indicators	AUC	Cut-Off value	P -value
Admission SII value	0.627	419.33	0.001
12hours after PCI SII value	0.678	1418.45	<0.001
Discharge SII value	0.650	736.84	<0.001
Admission SIRI value	0.647	1.93	<0.001
12hours after PCI SIRI value	0.764	4.15	<0.001
Discharge SIRI value	0.642	2.53	<0.001
Admission PIV value	0.640	306.25	<0.001
12hours after PCI PIV value	0.738	622.71	<0.001
Discharge PIV value	0.642	352.78	<0.001
SII change between Admission and 12hours after PCI	0.563	343.29	0.123
SII change between Discharge and 12hours after PCI	0.586	−849.46	0.032
SII change between Discharge and Admission	0.534	297.88	0.400
SIRI change between Admission and 12hours after PCI	0.667	3.06	<0.001
SIRI change between Discharge and 12hours after PCI	0.708	−3.45	<0.001
SIRI change between Discharge and Admission	0.503	−2.25	0.943
PIV change between Admission and 12hours after PCI	0.670	290.48	<0.001
PIV change between Discharge and 12hours after PCI	0.669	−1227.76	<0.001
PIV change between Discharge and Admission	0.530	181.92	0.488

Abbreviations: AUC, area under the receiver operating characteristic curve; SII, systemic immune-inflammation index; SIRI, systemic inflammation response index; PIV, Pan-Immune-Inflammation Value; PCI, percutaneous coronary intervention.

Figure 5 Receiver operating characteristic (ROC) curves. (A). ROC curve for SIRI at 12 hours after PCI to predict the major cardiovascular adverse events (MACEs); (B). ROC curve for PIV at 12 hours after PCI to predict the MACEs.

Abbreviations: SIRI, systemic inflammation response index; PIV, pan-immune-inflammation value.

Figure 6 Kaplan–Meier survival analysis. (A). Patients with a high SIRI value (SIRI ≥ 4.15) had a much lower event-free survival at long-term follow-up than patients with a low SIRI value (SIRI < 4.15); (B). Patients with a high PIV (PIV ≥ 622.71) had a much lower event-free survival at long-term follow-up than patients with a low PIV (PIV < 622.71).

Abbreviations: SIRI, systemic inflammation response index; PIV, pan-immune-inflammation value.

Figure 7 Kaplan–Meier survival analysis. (A). Patients with a high SIRI value (SIRI ≥ 4.15) had a much higher mortality rate at long-term follow-up than patients with a low SIRI value (SIRI < 4.15); (B). Patients with a high SIRI value (SIRI ≥ 4.15) had a much higher new-onset nonfatal acute myocardial infarction (AMI) rate at long-term follow-up than patients with a low SIRI value (SIRI < 4.15); (C). Patients with a high SIRI value (SIRI ≥ 4.15) had a much higher congestive heart failure (HF) rate at long-term follow-up than patients with a low SIRI value (SIRI < 4.15); (D). Patients with a high SIRI value (SIRI ≥ 4.15) had a much higher revascularization in unstable angina (UA) rate at long-term follow-up than patients with a low SIRI value (SIRI < 4.15); (E). Patients with a high PIV (PIV ≥ 622.71) had a much higher mortality rate at long-term follow-up than patients with a low PIV (PIV < 622.71); (F). Patients with a high PIV (PIV ≥ 622.71) had a much higher new-onset nonfatal acute myocardial infarction (AMI) rate at long-term follow-up than patients with a low PIV (PIV < 622.71); (G). Patients with a high PIV (PIV ≥ 622.71) had a much higher congestive heart failure (HF) rate at long-term follow-up than patients with a low PIV (PIV < 622.71); (H). Patients with a high PIV (PIV ≥ 622.71) had much a higher revascularization in unstable angina (UA) rate at long-term follow-up than patients with a low PIV (PIV < 622.71).

Abbreviations: SIRI, systemic inflammation response index; PIV, pan-immune-inflammation value.

Data Sharing Statement

Data from this study are available from the corresponding author upon request.