Background
Methods
Study design, inclusion and exclusion criteria
Analysis of serum biomarkers
Main outcome measurements
Statistical analyses
Results
Patient characteristics
Factor | Level | Total | Non-adverse outcome at 30d | Adverse outcome at 30d | p-value |
---|---|---|---|---|---|
N
| 278 | 249 (89.6%) | 29 (10.4%) | ||
Demographics | |||||
Age in years median (IQR) | 71.5 (57, 82) | 71 (57, 82) | 76 (67, 83) | 0.078 | |
Gender, n (%) | Male | 165 (59.4%) | 147 (59.0%) | 18 (62.1%) | 0.75 |
Female | 113 (40.6%) | 102 (41.0%) | 11 (37.9%) | ||
BMI, median (IQR) | 24.8 (22.0, 27.7) | 24.6 (21.8, 27.5) | 26.6 (24.4, 29.5) | 0.053 | |
Comorbidities | |||||
Coronary Heart Disease, n (%) | 52 (18.7%) | 44 (17.7%) | 8 (27.6%) | 0.2 | |
Congestive Heart Failure, n (%) | 35 (12.6%) | 31 (12.4%) | 4 (13.8%) | 0.84 | |
Chronic Kidney Disease, n (%) | 67 (24.1%) | 51 (20.5%) | 16 (55.2%) |
< 0.001
| |
Diabetes mellitus, n (%) | 41 (14.7%) | 36 (14.5%) | 5 (17.2%) | 0.69 | |
Tumor, n (%) | 33 (11.9%) | 27 (10.8%) | 6 (20.7%) | 0.12 | |
COPD, n (%) | 73 (26.3%) | 61 (24.5%) | 12 (41.4%) | 0.051 | |
Vital signs | |||||
Pulse rate, bpm, median (IQR) | 94 (82, 107) | 94 (82.5, 106) | 97 (75, 114) | 0.75 | |
Temperature, °C, median (IQR) | 38 (37.2, 38.9) | 38 (37.2, 39) | 37.4 (36.7, 38.4) |
0.014
| |
Systolic BP, mmHg, median (IQR) | 130 (118, 146) | 131 (120, 147) | 124 (102, 139) |
0.044
| |
Clinical scores | |||||
PSI-Score | 1, 2 | 73 (26.3%) | 70 (28.1%) | 3 (10.3%) |
< 0.001
|
3 | 56 (20.1%) | 55 (22.1%) | 1 (3.4%) | ||
4, 5 | 149 (53.6%) | 124 (49.8%) | 25 (86.2%) | ||
CURB-65-Score | 0, 1 | 125 (45.0%) | 120 (48.2%) | 5 (17.2%) |
< 0.001
|
2, 3 | 139 (50.0%) | 123 (49.4%) | 16 (55.2%) | ||
4, 5 | 14 (5.0%) | 6 (2.4%) | 8 (27.6%) | ||
Markers of oxidative stress and inflammation | |||||
Tyrosine, median (IQR) | 81.7 (63.2, 118.0) | 81.6 (61.8, 117.0) | 84.0 (66.4, 122.0) | 0.33 | |
Tyr-NO2, median (IQR) | 1.5 (0.8, 11.7) | 1.5 (0.9, 12.3) | 1.4 (0.5, 4.0) | 0.29 | |
Ratio Tyr-NO2/Tyrosine, median (IQR) | 2.0 (1.0, 7.6) | 2.1 (1.0, 8.3) | 1.9 (0.9, 3.5) | 0.19 | |
CRP, median (IQR) | 136 (63, 252) | 132 (61, 246) | 176 (106, 336) |
0.032
| |
PCT, median (IQR) | 0.45 (0.16, 3.20) | 0.40 (0.15, 2.96) | 0.64 (0.21, 6.30) | 0.13 |
Association of markers of oxidative stress with clinical parameters and markers of inflammation
Tyrosine | Tyr-NO2 | Tyrosine/Tyr-NO2 ratio | |
---|---|---|---|
Demographics | |||
Age | r 0.1748, p = 0.0230 | r 0.0856, p = 0.2684 | r 0.0158, p = 0.8383 |
Gender | r − 0.0253, p = 0.7441 | r 0.0458, p = 0.5545 | r 0.0508, p = 0.5116 |
BMI | r − 0.0870, p = 0.2608 | r − 0.0100, p = 0.8973 | r 0.0039, p = 0.9594 |
Comorbities | |||
Coronary heart disease | r 0.0263, p = 0.7059 | r − 0.0020, p = 0.9775 | r − 0.0224, p = 0.7483 |
Chronic heart failure | r 0.0586, p = 0.4005 | r 0.1123, p = 0.1064 | r 0.0681, p = 0.3285 |
Chronic Kidney Disease | r 0.0178, p = 0.7981 | r 0.0104, p = 0.8809 | r 0.0083, p = 0.9050 |
Diabetes mellitus | r − 0.0156, p = 0.8225 | r 0.1052, p = 0.1305 | r 0.1205, p = 0.0830 |
COPD | r 0.0430, p = 0.5378 | r − 0.0559, p = 0.4228 | r − 0.0832, p = 0.2321 |
Tumor | r 0.0816, p = 0.2413 | r 0.0392, p = 0.5741 | r 0.0149, p = 0.8310 |
Vital signs | |||
Heart rate | r − 0.0761, p = 0.2893 | r − 0.0981, p = 0.1714 | r − 0.0592, p = 0.4096 |
Systolic BP | r-0.0305, p = 0.6716 | r − 0.0113, p = 0.8753 | r 0.0066, p = 0.9270 |
Temperature | r − 0.0226, p = 0.7532 | r 0.2403, p = 0.0007 | r 0.2804, p = 0.0001 |
Clinical scores | |||
PSI | r 0.1264, p = 0.0689 | r 0.0932, p = 0.1805 | r 0.0464, p = 0.5060 |
CURB-65 | r 0.1243, p = 0.0737 | r 0.1008, p = 0.1474 | r 0.0508, p = 0.4662 |
qSOFA | r 0.0307, p = 0.6594 | r 0.1132, p = 0.1034 | r 0.1074, p = 0.1226 |
Biomarkers | |||
CRP | r − 0.2662, p = 0.0001 | r − 0.0994, p = 0.1540 | r − 0.0338, p = 0.6286 |
PCT | r − 0.1607, p = 0.0207 | r 0.0519, p = 0.4579 | r 0.1158, p = 0.0967 |
WBC | r − 0.0586, p = 0.4018 | r 0.0080, p = 0.9091 | r 0.0397, p = 0.5703 |
Association between markers of oxidative stress and short-term adverse outcome
Entire Cohort (n = 278) | Adverse outcome at 30d | 6 year Mortality |
---|---|---|
OR (95% CI); p-value | HR (95% CI); p-value | |
Tyrosinea | ||
Univariate | 3.30 (0.63 to 17.36), p = 0.159 | 1.88 (0.90 to 3.91), p = 0.093 |
Multivariateb | 0.84 (0.15 to 4.65), p = 0.841 | 1.58 (0.72 to 3.47), p = 0.256 |
AUROC | 0.55 (0.44 to 0.66) | 0.60 (0.54 to 0.67) |
Tyr-NO2a | ||
Univariate | 0.65 (0.35 to 1.20), p = 0.167 | 0.96 (0.73 to 1.27), p = 0.778 |
Multivariateb | 0.44 (0.20 to 0.96), p = 0.039 | 0.81 (0.6 to 1.1), p = 0.181 |
AUROC | 0.43 (0.31 to 0.56) | 0.50 (0.42 to 0.58) |
Ratio Tyr-NO2/Tyrosine | ||
Univariate | 0.91 (0.81 to 1.02), p = 0.098 | 0.99 (0.95 to 1.02), p = 0.457 |
Multivariateb | 0.98 (0.97 to 0.99), p = 0.043 | 1.00 (0.99 to 1.00), p = 0.216 |
AUROC | 0.42 (0.30 to 0.53) | 0.48 (0.40 to 0.56) |