The Combined Effect of Systemic Immune-Inflammation Index and Type 2 Diabetes Mellitus on the Prognosis of Patients Undergoing Percutaneous Coronary Intervention: A Large-Scale Cohort Study

Figures & data

Table 1 Baseline Characteristics for Patients Stratified by Primary Events

Variables	Overall (N=8602)	Non-MACE (N=8080)	MACE (N=522)	P value
Four subgroups				<0.001
SII-H/T2DM	1440 (16.7)	1311 (16.2)	129 (24.7)
SII-H/Non-T2DM	2516 (29.2)	2350 (29.1)	166 (31.8)
SII-L/T2DM	1687 (19.6)	1595 (19.7)	92 (17.6)
SII-L/Non-T2DM	2959 (34.4)	2824 (35.0)	135 (25.9)
Baseline characteristics
Age, years	58.41±10.19	58.35±10.17	59.29±10.41	0.041
Male	6611 (76.9)	6197 (76.7)	414 (79.3)	0.187
BMI, kg/m^2	25.90±3.19	25.90±3.19	26.00±3.14	0.463
Hypertension	5547 (64.5)	5197 (64.3)	350 (67.0)	0.224
Dyslipidemia	5741 (66.7)	5381 (66.6)	360 (69.0)	0.287
T2DM	3956 (46.0)	3661 (45.3)	295 (56.5)	<0.001
Smoking history	4899 (57.0)	4596 (56.9)	303 (58.0)	0.635
MI history	1617 (18.8)	1488 (18.4)	129 (24.7)	<0.001
PCI history	1958 (22.8)	1819 (22.5)	139 (26.6)	0.034
CABG history	337 (3.9)	310 (3.8)	27 (5.2)	0.159
Stroke history	903 (10.5)	836 (10.3)	67 (12.8)	0.085
PAD history	637 (7.4)	596 (7.4)	41 (7.9)	0.750
ACS	5070 (58.9)	4767 (59.0)	303 (58.0)	0.702
Laboratory tests
Platelet, *10^9/L	207.26±55.08	207.10±54.84	209.67±58.70	0.301
Neutrophil, *10^9/L	4.25±1.53	4.23±1.51	4.55±1.76	<0.001
Lymphocyte, *10^9/L	1.95±0.64	1.95±0.64	1.99±0.64	0.192
SII	423.81 [310.25, 591.46]	422.45 [310.04, 588.03]	450.41 [319.81, 628.96]	0.033
Ln SII	6.07±0.51	6.07±0.51	6.13±0.56	0.014
FBG, mmol/L	6.26±2.22	6.23±2.18	6.68±2.71	<0.001
HbA1c, %	6.60±1.21	6.59±1.21	6.79±1.24	<0.001
TG, mmol/L	1.52 [1.14, 2.08]	1.53 [1.14, 2.08]	1.46 [1.14, 2.09]	0.526
TC, mmol/L	4.20±1.07	4.20±1.07	4.19±1.07	0.852
HDL-C, mmol/L	1.04±0.28	1.04±0.28	1.03±0.26	0.792
LDL-C, mmol/L	2.50±0.90	2.50±0.90	2.49±0.90	0.728
hsCRP, mg/L	1.57 [0.79, 3.46]	1.56 [0.78, 3.40]	1.72 [0.91, 4.15]	0.002
Creatinine, μmol/L	75.16±15.44	75.10±15.43	76.01±15.44	0.195
eGFR, mL/min/1.73m^2	102.91±22.04	102.97±21.93	102.08±23.65	0.373
LVEF, %	63.12±7.12	63.19±7.07	62.09±7.83	0.001
Medications
DAPT	8407 (97.7)	7894 (97.7)	513 (98.3)	0.479
β-blocker	7739 (90.0)	7259 (89.8)	480 (92.0)	0.138
CCB	4241 (49.3)	3967 (49.1)	274 (52.5)	0.145
Statins	8258 (96.0)	7757 (96.0)	501 (96.0)	1.000
Nitrate	8417 (97.8)	7907 (97.9)	510 (97.7)	0.932
Angiography data
LM/three-vessel disease	3787 (44.0)	3506 (43.4)	281 (53.8)	<0.001
CTO	1430 (16.6)	1305 (16.2)	125 (23.9)	<0.001
SYNTAX score	10.00 [6.00, 16.00]	10.00 [5.50, 16.00]	11.00 [6.00, 17.50]	0.005
Number of stents	2.00 [1.00, 2.00]	2.00 [1.00, 2.00]	2.00 [1.00, 3.00]	0.001
Total length of stents, mm	36.00 [23.00, 55.00]	36.00 [23.00, 55.00]	40.00 [24.00, 57.75]	0.001
Average diameter of stents, mm	3.00 [2.75, 3.50]	3.00 [2.75, 3.50]	3.00 [2.71, 3.33]	0.004

Note: Values are expressed as mean ± SD or median (IQR) for continuous variables and percentage for categorical variables.

Abbreviations: SD, standard deviation; IQR, interquartile range; MACE, major adverse cardiovascular events; SII, systematic immune-inflammation index; T2DM, type 2 diabetes mellitus; BMI, body mass index; MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; PAD, peripheral artery disease; ACS, acute coronary syndrome; FBG, fasting blood glucose; HbA1c, glycosylated hemoglobin A1c; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; hsCRP, high-sensitivity C-reactive protein; eGFR, estimated glomerular filtration rate; LVEF, left ventricular ejection fraction; DAPT, dual antiplatelet therapy; CCB, calcium channel blocker; LM, left main; SYNTAX, synergy between PCI with taxus and cardiac surgery.

Table 2 Baseline Characteristics for Patients Stratified by the Level of SII and Different Glycemic Metabolism Status

Variables	SII-H/T2DM (N=1,440)	SII-L/T2DM (N=2,516)	SII-H/Non-T2DM (N=1,687)	SII-L/Non-T2DM (N=2,959)	P value
Baseline characteristics
Age, years	59.68±10.29	59.34±9.63	57.28±10.60	57.64±10.23	<0.001
Male	1070 (74.3)	1867 (74.2)	1341 (79.5)	2333 (78.8)	<0.001
BMI, kg/m^2	26.18±3.19	26.31±3.12	25.43±3.24	25.68±3.16	<0.001
Hypertension	1039 (72.2)	1683 (66.9)	1091 (64.7)	1734 (58.6)	<0.001
Dyslipidemia	1004 (69.7)	1800 (71.5)	1042 (61.8)	1895 (64.0)	<0.001
Smoking history	818 (56.8)	1375 (54.7)	979 (58.0)	1727 (58.4)	0.034
MI history	271 (18.8)	526 (20.9)	281 (16.7)	539 (18.2)	0.005
PCI history	357 (24.8)	675 (26.8)	307 (18.2)	619 (20.9)	<0.001
CABG history	66 (4.6)	118 (4.7)	55 (3.3)	98 (3.3)	0.015
Stroke history	185 (12.8)	306 (12.2)	162 (9.6)	250 (8.4)	<0.001
PAD history	129 (9.0)	214 (8.5)	109 (6.5)	185 (6.3)	0.001
ACS	939 (65.2)	1331 (52.9)	1096 (65.0)	1704 (57.6)	<0.001
Laboratory tests
Platelet, *10^9/L	239.45±61.17	189.06±44.84	236.83±56.75	190.20±43.35	<0.001
Neutrophil, *10^9/L	5.57±1.90	3.75±1.02	5.13±1.44	3.52±0.97	<0.001
Lymphocyte, *10^9/L	1.74±0.58	2.16±0.68	1.68±0.55	2.03±0.59	<0.001
SII	676.04 [572.59,863.71]	342.63 [267.90,410.63]	662.33 [569.80,835.66]	337.12 [269.07,411.40]	<0.001
Ln SII	6.62±0.38	5.77±0.32	6.58±0.31	5.78±0.31	<0.001
FBG, mmol/L	7.94±3.04	7.35±2.42	5.21±0.59	5.11±0.55	<0.001
HbA1c, %	7.41±1.29	7.48±1.32	5.88±0.33	5.87±0.34	<0.001
TG, mmol/L	1.57 [1.20,2.15]	1.59 [1.19,2.21]	1.49 [1.13,2.02]	1.45 [1.09,1.99]	<0.001
TC, mmol/L	4.27±1.10	4.19±1.10	4.19±1.02	4.18±1.05	0.053
HDL-C, mmol/L	1.01±0.27	1.02±0.27	1.05±0.29	1.06±0.28	<0.001
LDL-C, mmol/L	2.55±0.92	2.48±0.91	2.49±0.86	2.50±0.91	0.080
hsCRP, mg/L	2.46 [1.18,6.62]	1.49 [0.78,3.10]	1.93 [0.90,4.75]	1.27 [0.65,2.47]	<0.001
Creatinine, μmol/L	77.41±17.98	74.20±15.59	75.94±15.19	74.44±13.90	<0.001
eGFR, mL/min/1.73m^2	99.52±23.84	103.83±23.03	102.35±21.21	104.10±20.49	<0.001
LVEF, %	61.94±7.83	63.15±6.86	63.19±7.27	63.63±6.83	<0.001
Medications
DAPT	1413 (98.1)	2469 (98.1)	1649 (97.7)	2876 (97.2)	0.083
β-blocker	1324 (91.9)	2308 (91.7)	1503 (89.1)	2604 (88.0)	<0.001
CCB	737 (51.2)	1272 (50.6)	825 (48.9)	1407 (47.5)	0.061
Statins	1367 (94.9)	2400 (95.4)	1634 (96.9)	2857 (96.6)	0.006
Nitrate	1402 (97.4)	2460 (97.8)	1660 (98.4)	2895 (97.8)	0.248
Angiography data
LM/three-vessel disease	730 (50.7)	1224 (48.6)	659 (39.1)	1174 (39.7)	<0.001
CTO	273 (19.0)	410 (16.3)	298 (17.7)	449 (15.2)	0.009
SYNTAX score	2.00 [1.00, 2.00]	2.00 [1.00, 3.00]	2.00 [1.00, 2.00]	2.00 [1.00, 2.00]	<0.001
Number of stents	11.00 [6.00, 17.50]	10.00 [6.00, 17.00]	10.00 [6.00, 16.00]	9.00 [5.00, 15.00]	<0.001
Total length of stents, mm	38.00 [23.00, 57.00]	38.00 [24.00, 58.00]	35.00 [23.00, 54.00]	33.00 [23.00, 54.00]	<0.001
Average diameter of stents, mm	3.00 [2.75, 3.50]	3.00 [2.75, 3.33]	3.00 [2.75, 3.50]	3.00 [2.75, 3.50]	<0.001

Note: Values are expressed as mean ± SD or median (IQR) for continuous variables and number (%) for categorical variables.

Abbreviations: SD, standard deviation; IQR, interquartile range; MACE, major adverse cardiovascular events; SII, systematic immune-inflammation index; T2DM, type 2 diabetes mellitus; BMI, body mass index; MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; PAD, peripheral artery disease; ACS, acute coronary syndrome; FBG, fasting blood glucose; HbA1c, glycosylated hemoglobin A1c; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; hsCRP, high-sensitivity C-reactive protein; eGFR, estimated glomerular filtration rate; LVEF, left ventricular ejection fraction; DAPT, dual antiplatelet therapy; CCB, calcium channel blocker; LM, left main; SYNTAX, synergy between PCI with taxus and cardiac surgery.

Table 3 Relation of the SII Level and Primary Endpoint in Patients with Different Glycemic Metabolism Status

Variables	Events/Subjects	Univariate Analysis		Multivariate Analysis
		HR (95% CI)	P value	HR (95% CI)*	P value
Whole cohort
SII-L	301/5475	Reference	NA	Reference	NA
SII-H	221/3127	1.30 (1.09–1.55)	0.003	1.21 (1.01–1.46)	0.037
Ln SII (per 1-unit)		1.23 (1.05–1.45)	0.013	1.12 (0.94–1.33)	0.201
T2DM cohort
SII-L	166/2516	Reference	NA	Reference	NA
SII-H	129/1440	1.39 (1.10–1.74)	0.005	1.31 (1.03–1.67)	0.028
Ln SII (per 1-unit)		1.36 (1.11–1.66)	0.003	1.29 (1.03–1.61)	0.024
Non-T2DM cohort
SII-L	135/2959	Reference	NA	Reference	NA
SII-H	92/1687	1.20 (0.92–1.57)	0.174	1.11 (0.84–1.46)	0.476
Ln SII (per 1-unit)		1.03 (0.80–1.34)	0.800	0.93 (0.70–1.22)	0.585

Notes: *Model adjusted for age, male, hypertension, dyslipidemia, prior MI, prior PCI/CABG, hsCRP, creatinine, LM/three-vessel disease, CTO, number of stents, SYNTAX score, total length of stents and average diameter of stents.

Abbreviations: HR, hazard ratio; CI, confidence interval; NA, not applicable; SII, systematic immune-inflammation index; T2DM, type 2 diabetes mellitus; SYNTAX, synergy between PCI with taxus and cardiac surgery.

Figure 1 Kaplan–Meier curves for the cumulative incidence of MACE according to different SII levels (A), glycemic metabolism status (B).

Table 4 Predictive Value of the SII Level and Different Glycemic Metabolism Status for Primary and Secondary Endpoints

Variables	Events/Subjects	Univariate Analysis		Multivariate Analysis
		HR (95% CI)	P value	HR (95% CI)*,^†	P value
MACE
SII-H/T2DM	129/1440	Reference	NA	Reference	NA
SII-L/T2DM	166/2516	0.72 (0.57–0.91)	0.005	0.77 (0.61–0.98)	0.036
SII-H/Non-T2DM	92/1687	0.60 (0.46–0.78)	<0.001	0.66 (0.50–0.87)	0.003
SII-L/Non-T2DM	135/2959	0.50 (0.39–0.63)	<0.001	0.58 (0.45–0.74)	<0.001
MI+All-cause mortality
SII-H/T2DM	41/1440	Reference	NA	Reference	NA
SII-L/T2DM	51/2516	0.71 (0.47–1.07)	0.097	0.84 (0.54–1.29)	0.421
SII-H/Non-T2DM	36/1687	0.75 (0.48–1.17)	0.206	0.97 (0.61–1.56)	0.906
SII-L/Non-T2DM	39/2959	0.46 (0.30–0.71)	<0.001	0.61 (0.38–0.98)	0.042
All-cause mortality
SII-H/T2DM	29/1440	Reference	NA	Reference	NA
SII-L/T2DM	26/2516	0.51 (0.30–0.86)	0.012	0.66 (0.38–1.17)	0.158
SII-H/Non-T2DM	22/1687	0.65 (0.37–1.13)	0.123	0.86 (0.48–1.54)	0.602
SII-L/Non-T2DM	25/2959	0.42 (0.24–0.71)	0.001	0.64 (0.36–1.14)	0.127
MI
SII-H/T2DM	357/1440	Reference	NA	Reference	NA
SII-L/T2DM	282/2516	0.46 (0.39–0.54)	<0.001	0.65 (0.55–0.76)	<0.001
SII-H/Non-T2DM	376/1687	0.95 (0.82–1.09)	0.46	0.98 (0.84–1.14)	0.775
SII-L/Non-T2DM	344/2959	0.47 (0.41–0.55)	<0.001	0.64 (0.54–0.75)	<0.001
TVR
SII-H/T2DM	96/1440	Reference	NA	Reference	NA
SII-L/T2DM	126/2516	0.74 (0.56–0.96)	0.024	0.76 (0.58–1.00)	0.047
SII-H/Non-T2DM	65/1687	0.57 (0.41–0.77)	<0.001	0.58 (0.42–0.81)	0.001
SII-L/Non-T2DM	106/2959	0.52 (0.40–0.69)	<0.001	0.57 (0.43–0.76)	<0.001

Notes:*Model adjusted for age, male, hypertension, dyslipidemia, prior MI, prior PCI/CABG, hsCRP, creatinine, LM/three-vessel disease, CTO, number of stents, SYNTAX score, total length of stents and average diameter of stents. ^†P for trend for the risk of MACE: <0.001.

Abbreviations: MACE, major adverse cardiovascular events; SII, systematic immune-inflammation index; T2DM, type 2 diabetes mellitus; MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; hsCRP, high-sensitivity C-reactive protein; SYNTAX, synergy between PCI with taxus and cardiac surgery; NA, not applicable; HR, hazard ratio; CI, confidence interval.

Figure 2 Incidence rate for MACE (A) and Kaplan–Meier curves for the cumulative incidence of MACE (B) according to four groups.

Figure 3 Hazard ratios (95% CI) for MACE according to four groups.

Notes: Adjusted for age, male, hypertension, dyslipidemia, prior MI, prior PCI/CABG, hsCRP, creatinine, LM/three-vessel disease, CTO, number of stents, SYNTAX score, total length of stents and average diameter of stents.

Figure 4 Forest plot of MACE according to different subgroups.

Notes: Adjusted for age, male, hypertension, dyslipidemia, prior MI, prior PCI/CABG, hsCRP, creatinine, LM/three-vessel disease, CTO, number of stents, SYNTAX score, total length of stents and average diameter of stents.