Association of Systemic Immune Inflammation Index with All-Cause, Cardiovascular Disease, and Cancer-Related Mortality in Patients with Cardiovascular Disease: A Cross-Sectional Study

Figures & data

Table 1 Characteristics of the Study Population Based on SII Index Quartiles

SII Index	Total	Q1	Q2	Q3	Q4	P-value
Age, years	64.70 ± 0.29	64.24 ± 0.45	63.58 ± 0.54	64.91 ± 0.47	66.12 ± 0.55	0.006
Sex, %						0.005
Male	2997 (56.2%)	784 (15.1%)	736 (13.8%)	736 (13.8%)	717 (13.5%)
Female	2332 (43.8%)	549 (10.3%)	572 (10.7%)	596 (11.2%)	615 (11.5%)
Race/ethnicity, %						< 0.001
Mexican American	594 (11.1%)	133 (2.5%)	161 (3.0%)	161 (3.0%)	139 (2.6%)
Other Hispanic	326 (6.1%)	92 (1.7%)	86 (1.6%)	79 (1.5%)	69 (1.3%)
Non-Hispanic Black	1106 (20.8%)	417 (7.8%)	269 (5.0%)	236 (4.4%)	184 (3.5%)
Non-Hispanic White	3000 (56.3%)	600 (11.3%)	736 (13.8%)	797 (15.0%)	867 (16.3%)
Other race	303 (5.7%)	91 (1.7%)	80 (1.5%)	59 (1.1%)	73 (1.4%)
Family PIR	2.57 ± 0.04	2.67 ± 0.07	2.65 ± 0.06	2.60 ± 0.06	2.37 ± 0.06	< 0.001
Education level, %						0.664
High school	1892 (35.5%)	489 (9.2%)	484 (9.1%)	460 (8.6%)	459 (8.6%)
College	558 (10.5%)	160 (3.0%)	136 (10.2%)	141 (10.6%)	121 (2.3%)
Graduate	2879 (54.0%)	684 (12.8%)	712 (13.4%)	731 (13.7%)	752 (14.1%)
Marital status, %						<0.001
Having a partner	2876 (55.8%)	759 (14.2%)	798 (15.0%)	731 (13.7%)	688 (12.9%)
No partner	1988 (37.3%)	469 (8.8%)	453 (8.5%)	514 (9.6%)	552 (10.4%)
Unmarried	365 (6.8%)	105 (2.0%)	81 (1.5%)	87 (1.6%)	92 (1.7%)
Hypertension, %						0.010
No	1048 (19.7%)	257 (4.8%)	300 (5.6%)	254 (4.8%)	237 (4.4%)
Yes	4281 (80.3%)	1076 (20.2%)	1032 (19.4%)	1078 (20.2%)	1095 (20.5%)
DM, %						0.203
No	3214 (60.3%)	817 (15.3%)	819 (15.4%)	798 (15.0%)	780 (14.6%)
Yes	2115 (39.7%)	516 (9.7%)	513 (9.6%)	534 (10.0%)	552 (10.4%)
Smoker, %						0.339
No	2106 (39.5%)	567 (10.6%)	536 (10.1%)	526 (9.9%)	477 (9.0%)
Former	2167 (40.7%)	507 (9.5%)	552 (10.4%)	530 (9.9%)	578 (10.8%)
Now	1056 (19.8%)	259 (4.9%)	244 (4.6%)	276 (5.2%)	277 (5.2%)
Alcohol user, %						0.078
Never	830 (15.6%)	209 (3.9%)	209 (3.9%)	222 (4.2%)	190 (3.6%)
Former	1745 (32.7%)	406 (7.6%)	416 (7.8%)	427 (8.0%)	496 (9.3%)
Mild	1797 (33.7%)	469 (8.8%)	453 (8.5%)	457 (8.6%)	418 (7.8%)
Moderate	432 (8.1%)	114 (2.1%)	113 (2.1%)	95 (1.8%)	110 (2.1%)
Heavy	525 (9.9%)	135 (2.5%)	141 (2.6%)	131 (2.5%)	118 (2.2%)
CVD, %						< 0.001
No	4364 (81.9%)	1140 (21.4%)	1091 (20.5%)	1101 (20.7%)	1032 (19.4%)
Yes	965 (18.1%)	193 (3.6%)	241 (18.1%)	231 (4.3%)	300 (5.6%)
CHD, %						0.563
No	3337 (62.6%)	823 (15.4%)	823 (15.4%)	831 (15.6%)	860 (16.1%)
Yes	1992 (37.4%)	510 (9.6%)	509 (38.2%)	501 (9.4%)	472 (8.9%)
CHF, %						0.011
No	3796 (71.2%)	958 (18.0%)	980 (18.4%)	963 (18.1%)	895 (16.8%)
Yes	1533 (28.8%)	375 (7.0%)	352 (6.6%)	369 (6.9%)	437 (8.2%)
Angina pectoris						0.597
No	3955 (74.2%)	981 (18.4%)	992 (18.6%)	993 (18.6%)	989 (18.6%)
Yes	1374 (25.8%)	352 (6.6%)	340 (6.4%)	339 (6.4%)	343 (6.4%)
MI						0.620
No	3228 (60.6%)	795 (14.9%)	802 (15.0%)	842 (15.8%)	789 (14.8%)
Yes	2101 (39.4%)	538 (10.1%)	530 (9.9%)	490 (9.2%)	543 (10.2%)
Stroke, %						0.059
No	3456 (64.9%)	904 (17.0%)	846 (15.9%)	855 (16.0%)	851 (16.0%)
Yes	1873 (35.1%)	429 (8.1%)	486 (9.1%)	477 (9.0%)	481 (9.0%)
BMI, kg/m^2	30.21 ± 0.13	30.01 ± 0.20	30.11 ± 0.23	30.53 ± 0.28	30.16 ± 0.26	0.496
Waist circumference, cm	105.27 ± 0.31	104.97 ± 0.46	104.87 ± 0.56	106.03 ± 0.68	105.20 ± 0.56	0.524
SBP, mmHg	130.24 ± 0.40	129.99 ± 0.78	129.60 ± 0.76	130.98 ± 0.75	130.41 ± 0.75	0.608
DBP, mmHg	68.44 ± 0.28	69.10 ± 0.48	68.78 ± 0.52	68.94 ± 0.51	66.90 ± 0.48	0.003
FBG, mg/mL	119.46 ± 0.76	117.82 ± 1.17	119.38 ± 1.74	119.85 ± 1.47	120.75 ± 1.47	0.476
HbA1c, %	6.06 ± 0.02	6.01 ± 0.04	6.09 ± 0.05	6.06 ± 0.04	6.09 ± 0.04	0.415
CRP, mg/dL	2.16 ± 0.13	1.54 ± 0.16	1.96 ± 0.27	2.31 ± 0.17	2.85 ± 0.33	0.001
Mean Energy	1880.65 ± 15.67	1903.52 ± 31.80	1920.30 ± 29.73	1903.72 ± 29.03	1791.66 ± 24.27	< 0.001
Intake, kcal
AST, U/L	25.45 ± 0.26	27.74 ± 0.50	25.31 ± 0.50	24.67 ± 0.56	24.16 ± 0.52	< 0.001
ALT, U/L	24.06 ± 0.36	25.80 ± 0.59	24.39 ± 0.68	23.11 ± 0.71	23.02 ± 1.06	0.008
Albumin, g/L	41.42 ± 0.07	41.61 ± 0.13	41.81 ± 0.12	41.48 ± 0.14	40.74 ± 0.15	< 0.001
Hb, g/dL	14.02 ± 0.04	14.03 ± 0.06	14.16 ± 0.07	14.11 ± 0.06	13.76 ± 0.07	< 0.001
Plt, 1000 cells/ul	236.69 ± 1.49	191.22 ± 1.80	223.03 ± 1.95	245.12 ± 2.16	287.15 ± 2.86	< 0.001
Lym, 1000 cells/ul	2.10 ± 0.04	2.77 ± 0.16	2.11 ± 0.03	1.92 ± 0.02	1.61 ± 0.02	< 0.001
Neu, 1000 cells/ul	4.55 ± 0.03	3.27 ± 0.04	4.05 ± 0.03	4.79 ± 0.04	6.08 ± 0.07	< 0.001
BUN, mg/dL	17.33 ± 0.14	16.52 ± 0.24	16.96 ± 0.26	17.43 ± 0.27	18.41 ± 0.33	< 0.001
UA, mg/dL	5.92 ± 0.03	5.93 ± 0.05	5.82 ± 0.05	5.91 ± 0.06	6.02 ± 0.06	0.071
Scr, mg/dL	1.06 ± 0.01	1.06 ± 0.02	1.01 ± 0.01	1.06 ± 0.02	1.14 ± 0.02	< 0.001
eGFR, mL/min/1.73m^2	74.15 ± 0.41	75.97 ± 0.80	76.43 ± 0.88	73.64 ± 0.86	70.49 ± 0.83	< 0.001
TC, mg/dL	186.40 ± 0.99	185.63 ± 1.72	186.11 ± 1.79	186.37 ± 1.83	187.52 ± 1.76	0.895
TG, mg/dL	151.62 ± 2.08	148.61 ± 4.37	153.30 ± 4.17	153.72 ± 3.42	150.59 ± 2.98	0.753
HDL-C, mg/dL	50.25 ± 0.33	50.62 ± 0.66	49.70 ± 0.57	49.99 ± 0.59	50.74 ± 0.53	0.437
All-cause mortality, %						<0.001
No	2981 (55.9%)	870 (16.3%)	777 (14.6%)	756 (14.2%)	578 (10.8%)
Yes	2348 (44.1%)	463 (8.7%)	555 (10.4%)	576 (10.8%)	754 (14.1%)
CVD mortality, %						<0.001
No	4364 (81.9%)	1140 (21.4%)	1091 (20.5%)	1101 (20.7%)	1032 (19.4%)
Yes	965 (18.1%)	193 (3.6%)	241 (4.5%)	231 (4.3%)	300 (5.6%)
Cancer-related mortality, %						0.004
No	4936 (92.6%)	1249 (23.4%)	1249 (23.4%)	1246 (23.4%)	1192 (22.4%)
Yes	393 (7.4%)	84 (1.6%)	83 (1.6%)	86 (1.6%)	140 (2.6%)

Note: Q1, 4.056–349.500; Q2, 349.501–508.800; Q3, 508.801–736.154; Q4, 376.155–11,700.000.

Abbreviations: SII index, systemic immune inflammation index; CVD, cardiovascular disease; CHD, coronary heart disease; CHF, congestive heart failure; MI, myocardial infarction; DM, diabetes mellitus; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fast glucose; HbA1c, glycohemoglobin; CRP, C-reactive protein; AST, aspartate aminotransferase; ALT, alanine aminotransferase; Hb, hemoglobin; Plt, platelet; Lym, lymphocyte; Neu, neutrophils; BUN, blood urea nitrogen; UA, uric acid; Scr, serum creatinine; eGFR, estimated glomerular filtration rate; TC, total cholesterol; TG, triglyceride; HDL-C, high density lipoprotein-cholesterol.

Table 2 Cox Regression Analysis of SII Index for All-Cause, CVD, and Cancer-Related Mortality in CVD Patients

Mortality	Model 1	P for Trend	Model 2	P for Trend	Model 3	P for Trend
	HR (95% CI)		HR (95% CI)		HR (95% CI)
All-cause		<0.001		<0.001		0.005
Q1	1.00		1.00		1.00
Q2	1.259 (1.032, 1.537)*		1.194 (0.976, 1.460)		1.202 (0.981, 1.474)
Q3	1.191 (0.976, 1.454)		1.150 (0.940, 1.407)		1.184 (0.967, 1.450)
Q4	1.762 (1.454, 2.315)***		1.521 (1.248, 1.854) ***		1.365 (1.115, 1.672)**
CVD		0.004		0.081		0.314
Q1	1.00		1.00		1.00
Q2	1.174 (0.864, 1.594)		1.108 (0.813, 1.511)		1.116 (0.815, 1.527)
Q3	1.060 (0.778, 1.445)		1.016 (0.743, 1.389)		1.017 (0.740, 1.398)
Q4	1.609 (1.197, 2.161)**		1.355 (0.999, 1.838)		1.220 (0.891, 1.670)
Cancer-related		0.137		0.403		0.005
Q1	1.00		1.00		1.00
Q2	0.869 (0.543, 1.389)		0.825 (0.513, 1.326)		1.202 (0.981, 1.474)
Q3	1.005 (0.641, 1.576)		0.960 (0.609, 1.514)		1.184 (0.967, 1.450)
Q4	1.347 (0.868, 2.092)		1.152 (0.731, 1.816)		1.365 (1.115, 1.672) **

Notes: Model 1: age and sex. Model 2: model 1 variables plus race/ethnicity, education level, marital status, family poverty–income ratio, hypertension, diabetes mellitus, smoker, alcohol user; Model 3 was adjusted for model 2 variables plus body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, mean energy intake, hemoglobin, fast glucose, glycosylated hemoglobin, alanine transaminase, aspartate aminotransferase, albumin, blood urea nitrogen, uric acid, serum creatinine, estimated glomerular filtration rate, total cholesterol, triglyceride, and high-density lipoprotein-cholesterol. Q1, 4.056–349.500; Q2, 349.501–508.800; Q3 508.801–736.154; Q4, 376.155–11,700.000; *P < 0.05, **P < 0.01, ***P < 0.001.

Abbreviations: SII index, systemic immune inflammation index; CVD, cardiovascular disease; HR, hazard ratio; CI, confidence interval.

Table 3 Subgroups Analysis for the Associations of SII Index with All-Cause Mortality in CVD Patients

	Q1	Q2	Q3	Q4	P for Trend	P for Interaction
	OR (95% CI)	OR (95% CI)	OR (95% CI)	OR (95% CI)
Age						0.107
< 60	1.00	1.440 (0.705, 2.941)	0.816 (0.350, 1.902)	1.767 (0.794, 3.929)	0.356
≥ 60	1.00	1.178 (0.952, 1.459)	1.188 (0.960, 1.472)	1.330 (1.076, 1.645)	0.012
Gender						0.309
Male	1.00	1.237 (0.962, 1.591)	1.278 (0.997, 1.638)	1.442 (1.128, 1.844)**	0.005
Female	1.00	1.304 (0.894, 1.901)	1.016 (0.697, 1.480)	1.253 (0.859, 1.830)	0.534
Hypertension						0.501
No	1.00	1.173 (0.658, 2.091)	1.118 (0.640, 1.955)	1.209 (0.666, 1.955)	0.603
Yes	1.00	1.191 (0.954, 1.486)	1.189 (0.952, 1.486)	1.383 (1.110, 1.723)**	0.006
DM						0.045
No	1.00	1.167 (0.886, 1.538)	1.130 (0.856, 1.491)	1.202 (0.904, 1.597)	0.292
Yes	1.00	1.168 (0.853, 1.600)	1.128 (0.824, 1.544)	1.504 (1.117, 2.024)	0.010
BMI						0.049
< 30 kg/m^2	1.00	1.064 (0.820, 1.379)	1.088 (0.837, 1.414)	1.332 (1.030, 1.721)*	0.025
≥ 30 kg/m^2	1.00	1.378 (0.978, 1.940)	1.132 (0.805, 1.591)	1.313 (0.933, 1.847)	0.315

Notes: Q1, 4.056–349.500; Q2, 349.501–508.800; Q3 508.801–736.154; Q4, 376.155–11,700.000; *P < 0.05; **P < 0.01. Analyses was adjusted for age and sex, race/ethnicity, education level, marital status, family poverty–income ratio, hypertension, diabetes mellitus, smoker, alcohol user, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, mean energy intake, hemoglobin, fast glucose, glycosylated hemoglobin, alanine transaminase, aspartate aminotransferase, albumin, blood urea nitrogen, uric acid, serum creatinine, estimated glomerular filtration rate, total cholesterol, triglyceride, and high-density lipoprotein-cholesterol.

Abbreviations: SII index, systemic immune inflammation index; CVD, cardiovascular disease; HR, hazard ratio; CI, confidence interval.

Table 4 Subgroups Analysis for the Associations of SII Index with CVD Mortality in CVD Patients

	Q1	Q2	Q3	Q4	P for Trend	P for Interaction
	OR (95% CI)	OR (95% CI)	OR (95% CI)	OR (95% CI)
Age						0.003
< 60	1.00	3.020 (1.490, 6.120) **	1.892 (0.903, 3.964)	2.763 (1.321, 5.779) **	0.043
≥ 60	1.00	0.963 (0.786, 1.178)	0.970 (0.793, 1.187)	1.188 (0.977, 1.444)	0.063
Gender						0.056
Male	1.00	1.038 (0.808, 1.334)	1.132 (0.881, 1.454)	1.314 (1.028, 1.679) *	0.017
Female	1.00	1.274 (0.931, 1.744)	0.908 (0.662, 1.247)	1.311 (0.968, 1.776)	0.306
Hypertension						0.028
No	1.00	0.865 (0.516, 1.448)	0.586 (0.335, 1.024)	0.854 (0.510, 1.432)	0.362
Yes	1.00	1.100 (0.891, 1.357)	1.121 (0.909, 1.383)	1.354 (1.103, 1.663) **	0.004
DM						0.134
No	1.00	1.240 (0.954, 1.611)	1.180 (0.906, 1.537)	1.413 (1.091, 1.830)	0.019
Yes	1.00	0.923 (0.689, 1.237)	0.873 (0.650, 1.173)	1.203 (0.905, 1.599)	0.242
BMI						0.021
< 30 kg/m^2	1.00	1.000 (0.786, 1.272)	1.040 (0.815, 1.328)	1.177 (0.927, 1.495)	0.145
≥ 30 kg/m^2	1.00	1.290 (0.923, 1.803)	0.985 (0.708, 1.370)	1.470 (1.070, 2.020)	0.072

Notes: Q1, 4.056–349.500; Q2, 349.501–508.800; Q3 508.801–736.154; Q4, 376.155–11,700.000; *P < 0.05; **P < 0.01. Analyses was adjusted for age and sex, race/ethnicity, education level, marital status, family poverty–income ratio, hypertension, diabetes mellitus, smoker, alcohol user, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, mean energy intake, hemoglobin, fast glucose, glycosylated hemoglobin, alanine transaminase, aspartate aminotransferase, albumin, blood urea nitrogen, uric acid, serum creatinine, estimated glomerular filtration rate, total cholesterol, triglyceride, and high-density lipoprotein-cholesterol.

Abbreviations: SII index, systemic immune inflammation index; CVD, cardiovascular disease; HR, hazard ratio; CI, confidence interval.

Table 5 Subgroups Analysis for the Associations of SII Index with Cancer-Related Mortality in CVD Patients

	Q1	Q2	Q3	Q4	P for Trend	P for Interaction
	OR (95% CI)	OR (95% CI)	OR (95% CI)	OR (95% CI)
Age						0.104
< 60	1.00	0.926 (0.372, 2.301)	0.870 (0.351, 2.158)	2.186 (0.975, 4.897)	0.043
≥ 60	1.00	0.837 (0.602, 1.163)	0.848 (0.611, 1.177)	1.310 (0.967, 1.774)	0.046
Gender						0.095
Male	1.00	0.732 (0.498, 1.075)	0.861 (0.591, 1.252)	1.330 (0.943, 1.875)	0.038
Female	1.00	1.227 (0.714, 2.110)	1.030 (0.598, 1.776)	1.689 (1.016, 2.805)	0.062
Hypertension
No	1.00	0.920 (0.456, 1.860)	1.101 (0.544, 2.229)	1.030 (0.513, 2.071)	0.796	0.255
Yes	1.00	0.855 (0.603, 1.213)	0.898 (0.635, 1.271)	1.558 (1.136, 2.136)	0.002
DM						0.406
No	1.00	0.914 (0.617, 1.355)	0.859 (0.576, 1.279)	1.483 (1.032, 2.131)	0.025
Yes	1.00	0.874 (0.525, 1.455)	0.991 (0.607, 1.617)	1.539 (0.967, 2.451)	0.044
BMI						0.001
< 30 kg/m^2	1.00	0.849 (0.549, 1.311)	1.044 (0.677, 1.609)	1.960 (1.335, 2.877)	<0.001
≥ 30 kg/m^2	1.00	0.899 (0.574, 1.408)	0.738 (0.473, 1.152)	0.909 (0.583, 1.418)	0.504

Notes: Q1, 4.056–349.500; Q2, 349.501–508.800; Q3 508.801–736.154; Q4, 376.155–11,700.000. Analyses was adjusted for age and sex, race/ethnicity, education level, marital status, family poverty–income ratio, hypertension, diabetes mellitus, smoker, alcohol user, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, mean energy intake, hemoglobin, fast glucose, glycosylated hemoglobin, alanine transaminase, aspartate aminotransferase, albumin, blood urea nitrogen, uric acid, serum creatinine, estimated glomerular filtration rate, total cholesterol, triglyceride, and high-density lipoprotein-cholesterol.

Abbreviations: SII index, systemic immune inflammation index; CVD, cardiovascular disease; CI, confidence interval; HR, hazard ratio.

Figure 1 The RCS curve of the association between SII index and all-cause (A), CVD (B and C) cancer-related mortality in CVD patients.

Abbreviations: RCS, restricted cubic spline; SII index, systemic immune inflammation index; CVD, cardiovascular disease.

Figure 2 Kaplan-Meier survival curve for all-cause (A), CVD (B and C) cancer-related mortality in CVD patients.

Abbreviation: CVD, cardiovascular disease.

Figure 3 The RCS curve of the association between SII index and all-cause (A), CVD (B and C) cancer-related mortality in CHD patients.

Abbreviations: RCS, restricted cubic spline; SII index, systemic immune inflammation index; CVD, cardiovascular disease; CHD, coronary heart disease.

Figure 4 Kaplan-Meier survival curve for all-cause (A), CVD (B and C) cancer-related mortality in CHD patients.

Abbreviations: CVD, cardiovascular disease; CHD, coronary heart disease.

Figure 5 The RCS curve of the association between SII index and all-cause (A), CVD (B and C) cancer-related mortality in CHF patients.

Abbreviations: RCS, restricted cubic spline; SII index, systemic immune inflammation index; CVD, cardiovascular disease; CHF, congestive heart failure.

Figure 6 Kaplan-Meier survival curve for all-cause (A), CVD (B and C) cancer-related mortality in CHF patients.

Abbreviations: CVD, cardiovascular disease; CHF, congestive heart failure.

Figure 7 The RCS curve of the association between SII index and all-cause (A), CVD (B and C) cancer-related mortality in angina pectoris patients.

Abbreviations: RCS, restricted cubic spline; SII index, systemic immune inflammation index; CVD, cardiovascular disease.

Figure 8 Kaplan-Meier survival curve for all-cause (A), CVD (B and C) cancer-related mortality in angina pectoris patients.

Abbreviation: CVD, cardiovascular disease.

Figure 9 The RCS curve of the association between SII index and all-cause (A), CVD (B and C) cancer-related mortality in MI patients.

Abbreviations: RCS, restricted cubic spline; SII index, systemic immune inflammation index; CVD, cardiovascular disease; MI, myocardial infarction.

Figure 10 Kaplan-Meier survival curve for all-cause (A), CVD (B and C) cancer-related mortality in MI patients.

Abbreviations: CVD, cardiovascular disease; MI, myocardial infarction.

Figure 11 The RCS curve of the association between SII index and all-cause (A), CVD (B and C) cancer-related mortality in stroke patients.

Abbreviations: RCS, restricted cubic spline; SII index, systemic immune inflammation index; CVD, cardiovascular disease.

Figure 12 Kaplan-Meier survival curve for all-cause (A), CVD (B and C) cancer-related mortality in stroke patients.

Abbreviation: CVD, cardiovascular disease.