Background
Methods
Study design and ethical statements
Data source: NHIS-HEALS database and study population
Exposure: history of anemia
Study endpoint: mortality due to infection
Covariates
Statistical analysis
Results
Study population
Variable | Total Cohort (n = 512,905) | ASD | PS-matched cohort (n = 98,078) | ASD | ||
---|---|---|---|---|---|---|
Anemia group n = 49,042 | Non-anemic group n = 463,863 | Anemia group n = 49,039 | Non-anemic group n = 49,039 | |||
Age, year | 54.9 (10.8) | 53.5 (9.5) | 0.134 | 54.9 (10.8) | 54.7 (9.8) | 0.017 |
Sex, male | 12,778 (26.1) | 265,068 (57.1) | 0.708 | 12,778 (26.1) | 12,458 (25.4) | 0.015 |
Residence | ||||||
Seoul (Capital city) | 8214 (16.7) | 79,819 (17.2) | 8213 (16.7) | 8280 (16.9) | ||
Other metropolitan city | 12,838 (26.2) | 127,430 (27.5) | 0.035 | 12,838 (26.2) | 13,065 (26.6) | 0.011 |
Other area | 27,990 (57.1) | 256,614 (55.3) | 0.125 | 27,988 (57.1) | 27,694 (56.5) | 0.012 |
Body mass index, kg/m2 | ||||||
18.5–24.9 (normal) | 34,312 (70.0) | 286,642 (61.8) | 34,311 (70.0) | 33,639 (68.6) | ||
Below 18.5 (Underweight) 25.0–29.9 (Overweight) | 2302 (4.7) | 9561 (2.1) | 0.125 | 2300 (4.7) | 2016 (4.1) | 0.027 |
11,384 (23.2) | 153,504 (33.1) | 0.234 | 11,384 (23.2) | 12,229 (24.9) | 0.041 | |
Above 30.0 (Obese) | 982 (2.0) | 13,741 (3.0) | 0.069 | 982 (2.0) | 1094 (2.2) | 0.016 |
Unknwon | 62 (0.1) | 415 (0.1) | 0.010 | 62 (0.1) | 61 (0.1) | < 0.001 |
Annual income level | ||||||
0–20% | 9698 (19.8) | 70,879 (15.3) | 9698 (19.8) | 9101 (18.6) | ||
20–40% | 7819 (15.9) | 62,101 (13.4) | 0.070 | 7818 (15.9) | 7515 (15.3) | 0.017 |
40–60% | 7811 (15.9) | 73,151 (15.8) | 0.004 | 7811 (15.9) | 7969 (16.3) | 0.009 |
60–80% | 9492 (19.4) | 98,521 (21.2) | 0.048 | 9492 (19.4) | 9690 (19.8) | 0.010 |
80–100% | 14,222 (29.0) | 159,211 (34.3) | 0.117 | 14,220 (29.0) | 14,764 (30.1) | 0.024 |
Underlying disability | ||||||
Mild to moderate | 228 (0.5) | 1824 (0.4) | 0.011 | 227 (0.5) | 216 (0.4) | 0.003 |
Severe | 196 (0.4) | 1050 (0.2) | 0.028 | 195 (0.4) | 162 (0.3) | 0.011 |
Smoking status | ||||||
Never smoker | 39,738 (81.0) | 291,628 (62.9) | 39,735 (81.0) | 40,063 (81.7) | ||
Previous smoker | 2112 (4.3) | 41,404 (8.9) | 0.228 | 2112 (4.3) | 2064 (4.2) | 0.005 |
Current smoker | 5189 (10.6) | 112,137 (24.2) | 0.442 | 5189 (10.6) | 4951 (10.1) | 0.016 |
Unknown | 2003 (4.1) | 18,694 (4.0) | 0.003 | 2003 (4.1) | 1961 (4.0) | 0.004 |
Alcohol consumption (frequency) | ||||||
No drink | 35,365 (72.1) | 250,644 (54.0) | 35,362 (72.1) | 35,364 (72.1) | ||
2–3 per a month | 5535 (11.3) | 71,024 (15.3) | 0.127 | 5535 (11.3) | 5671 (11.6) | 0.009 |
1–2 per a week | 4054 (8.3) | 78,927 (17.0) | 0.318 | 4054 (8.3) | 4053 (8.3) | < 0.001 |
3–4 per a week | 1508 (3.1) | 33,906 (7.3) | 0.245 | 1508 (3.1) | 1410 (2.9) | 0.012 |
Almost everyday drink | 1384 (2.8) | 20,995 (4.5) | 0.103 | 1384 (2.8) | 1388 (2.8) | < 0.001 |
Unknown | 1196 (2.4) | 8367 (1.8) | 0.041 | 1196 (2.4) | 1153 (2.4) | 0.006 |
Exercise frequency | ||||||
No exercise | 31,266 (63.8) | 254,500 (54.9) | 31,264 (63.8) | 30,689 (62.6) | ||
1–2 per a week | 8461 (17.3) | 109,692 (23.6) | 0.127 | 8460 (17.3) | 8635 (17.6) | 0.009 |
3–4 per a week | 3543 (7.2) | 43,539 (9.4) | 0.318 | 3543 (7.2) | 3801 (7.8) | 0.020 |
5–6 per a week | 1132 (2.3) | 12,043 (2.6) | 0.245 | 1132 (2.3) | 1163 (2.4) | 0.004 |
Almost everyday | 3372 (6.9) | 31,328 (6.8) | 0.103 | 3372 (6.9) | 3427 (7.0) | 0.004 |
Unknown | 1268 (2.6) | 12,761 (2.8) | 0.041 | 1268 (2.6) | 1324 (2.7) | 0.007 |
Charlson comorbidity index | 1.5 (1.9) | 1.3 (1.6) | 0.136 | 1.5 (1.9) | 1.5 (1.8) | 0.019 |
Myocardial infarction | 509 (1.0) | 3925 (0.8) | 0.019 | 509 (1.0) | 460 (0.9) | 0.010 |
Congestive heart failure | 1814 (3.7) | 12,412 (2.7) | 0.054 | 1813 (3.7) | 1688 (3.4) | 0.014 |
Peripheral vascular disease | 2183 (4.5) | 15,702 (3.4) | 0.052 | 2182 (4.4) | 2026 (4.1) | 0.015 |
Cerebrovascular disease | 2608 (5.3) | 19,873 (4.3) | 0.054 | 2607 (5.3) | 2526 (5.2) | 0.007 |
Dementia | 271 (0.6) | 1757 (0.4) | 0.023 | 271 (0.6) | 261 (0.5) | 0.003 |
Chronic pulmonary disease | 12,497 (25.5) | 104,209 (22.5) | 0.069 | 12,495 (25.5) | 12,513 (25.5) | < 0.001 |
Rheumatic disease | 3631 (7.4) | 24,377 (5.3) | 0.072 | 3630 (7.4) | 3537 (7.2) | 0.007 |
Peptic ulcer disease | 16,890 (34.4) | 139,279 (30.0) | 0.093 | 16,888 (34.4) | 16,696 (34.0) | 0.008 |
Mild liver disease | 7800 (15.9) | 76,669 (16.5) | 0.017 | 7798 (15.9) | 7813 (15.9) | < 0.001 |
Diabetes without chronic complication | 2923 (6.0) | 26,396 (5.7) | 0.011 | 2923 (6.0) | 2949 (6.0) | 0.002 |
Diabetes with chronic complication | 2038 (4.2) | 16,010 (3.5) | 0.035 | 2038 (4.2) | 1920 (3.9) | 0.012 |
Hemiplegia or paraplegia | 276 (0.6) | 1901 (0.4) | 0.020 | 276 (0.6) | 257 (0.5) | 0.005 |
Renal disease | 595 (1.2) | 1971 (0.4) | 0.072 | 592 (1.2) | 455 (0.9) | 0.026 |
vAny malignancy | 6889 (14.0) | 50,533 (10.9) | 0.091 | 6888 (14.0) | 6784 (13.8) | 0.006 |
Moderate or severe liver disease | 277 (0.6) | 1341 (0.3) | 0.037 | 275 (0.6) | 242 (0.5) | 0.009 |
Metastatic solid tumour | 454 (0.9) | 2075 (0.4) | 0.050 | 453 (0.9) | 401 (0.8) | 0.011 |
AIDS/HIV | 0 (0.0) | 1 (0.0) | < 0.001 | 0 (0.0) | 0 (0.0) | < 0.001 |
Mortality due to infection and history of anemia
Variable | Infectious mortality (n, %) | Cox regression | P-value |
---|---|---|---|
HR (95% CI) | |||
Before PS matching | |||
Non-anemic group | 2008/463,863 (0.4) | 1 | |
Anemia group | 437/49,042 (0.9) | 2.14 (1.93, 2.37) | < 0.001 |
After PS matching | |||
Non-anemic group | 256/49,039 (0.5) | 1 | |
Anemia group | 437/49,039 (0.9) | 1.77 (1.52, 2.06) | < 0.001 |
Variable | Multivariable model | P-value |
---|---|---|
HR (95% CI) | ||
Anemia (vs non-anemic group, model 1) | 1.47 (1.33, 1.64) | < 0.001 |
Subgroup analysis (model 2) | ||
Non-anemic group | 1 | |
Mild anemia (n = 36,383, 7.1%) | 1.38 (1.23, 1.55) | < 0.001 |
Moderate anemia (n = 11,787, 2.3%) | 2.02 (1.62, 2.50) | < 0.001 |
Severe anemia (n = 872, 0.2%) | 1.55 (0.50, 4.82) | 0.448 |
Age, year | 1.16 (1.15, 1.37) | < 0.001 |
Sex, male | 2.16 (1.96, 2.39) | < 0.001 |
Residence at diagnosis of sepsis | ||
Seoul (Capital city) | 1 | |
Other metropolitan city | 1.18 (1.02, 1.37) | 0.027 |
Other area | 1.24 (1.08, 1.41) | 0.002 |
Body mass index, kg/m2 | ||
18.5–24.9 (normal) | 1 | |
Below 18.5 (Underweight) | 2.33 (2.04, 2.66) | < 0.001 |
25.0–29.9 (Overweight) | 0.74 (0.67, 0.81) | < 0.001 |
Above 30.0 (Obese) | 1.07 (0.83, 1.37) | 0.625 |
Unknwon | 0.33 (0.05, 2.36) | 0.270 |
Annual income level | ||
0–20% | 1 | |
20–40% | 0.91 (0.80, 1.03) | 0.143 |
40–60% | 0.84 (0.74, 0.96) | 0.008 |
60–80% | 0.74 (0.65, 0.83) | < 0.001 |
80–100% | 0.65 (0.58, 0.73) | < 0.001 |
Underlying disability | ||
Mild to moderate | 1.19 (0.88, 1.59) | 0.258 |
Severe | 1.63 (1.12, 2.37) | 0.011 |
Smoking status | ||
Never smoker | 1 | |
Previous smoker | 1.34 (1.16, 1.54) | < 0.001 |
Current smoker | 1.50 (1.35, 1.67) | < 0.001 |
Unknown | 1.08 (0.83, 1.39) | 0.580 |
Alcohol consumption (frequency) | ||
No drink | 1 | |
2–3 per a month | 0.73 (0.63, 0.85) | < 0.001 |
1–2 per a week | 0.91 (0.80, 1.05) | 0.199 |
3–4 per a week | 0.82 (0.69, 0.99) | 0.034 |
Almost everyday drink | 1.01 (0.87, 1.18) | 0.867 |
Unknown | 0.93 (0.66, 1.31) | 0.688 |
Exercise frequency | ||
No exercise | 1 | |
1–2 per a week | 0.81 (0.71, 0.92) | 0.001 |
3–4 per a week | 0.74 (0.61, 0.89) | 0.002 |
5–6 per a week | 0.72 (0.52, 0.99) | 0.044 |
Almost everyday | 0.79 (0.68, 0.92) | 0.002 |
Unknown | 1.22 (0.95, 1.58) | 0.128 |
Charlson comorbidity index, 1 point (model 2) | 1.13 (1.11, 1.15) | < 0.001 |
Myocardial infarction | 1.19 (0.91, 1.55) | 0.198 |
Congestive heart failure | 1.18 (1.01, 1.3) | 0.038 |
Peripheral vascular disease | 1.22 (1.06, 1.40) | 0.007 |
Cerebrovascular disease | 1.29 (1.13, 1.47) | < 0.001 |
Dementia | 1.48 (1.07, 2.04) | 0.018 |
Chronic pulmonary disease | 1.26 (1.15, 1.37) | < 0.001 |
Rheumatic disease | 1.29 (1.13, 1.47) | < 0.001 |
Peptic ulcer disease | 0.91 (0.83, 0.99) | 0.028 |
Mild liver disease | 1.24 (1.13, 1.37) | < 0.001 |
Diabetes without chronic complication | 1.25 (1.10, 1.43) | 0.001 |
Diabetes with chronic complication | 1.36 (1.16, 1.59) | < 0.001 |
Hemiplegia or paraplegia | 1.13 (0.79, 1.64) | 0.503 |
Renal disease | 0.92 (0.60, 1.40) | 0.692 |
Any malignancy | 1.15 (1.03, 1.28) | 0.014 |
Moderate or severe liver disease | 2.30 (1.55, 3.43) | < 0.001 |
Metastatic solid tumour | 0.66 (0.37, 1.18) | 0.162 |
AIDS/HIV | 0.00 (0.00-) | 0.997 |
Variable | Multivariable model | P-value |
---|---|---|
HR (95% CI) | ||
Male (n = 277,846, event = 1571) | ||
Anemia group (vs non-anemic group) | 1.57 (1.37, 1.83) | < 0.001 |
Subgroup analysis | ||
Non-anemic group | 1 | |
Mild historical anemia | 1.49 (1.28, 1.72) | < 0.001 |
Moderate historica anemia | 2.49 (1.6, 3.51) | < 0.001 |
Severe historica anemia | 2.06 (0.51, 8.26) | 0.308 |
Female (235,059, event = 874) | ||
Anemia group (vs non-anemic group) | 1.36 (1.15, 1.61) | < 0.001 |
Subgroup analysis | ||
Non-anemic group | 1 | |
Mild historica anemia | 1.23 (1.01, 1.49) | 0.038 |
Moderate historica anemia | 1.84 (1.39, 2.43) | < 0.001 |
Severe historica anemia | 0.99 (0.14, 7.07) | 0.994 |