Table 1.
Baseline Characteristics of Study Population Stratified by Biomarker Trajectories
| All Patients (N = 688) [Median (IQR) or n (%)] | Subgroup −/− (n = 176) [Median (IQR) or n (%)] | Subgroup −/+ (n = 55) [Median (IQR) or n (%)] | Subgroup +/− (n = 163) [Median (IQR) or n (%)] | Subgroup +/+ (n = 294) [Median (IQR) or n (%)] | P Value* | |
|---|---|---|---|---|---|---|
| Age, yr | 62 (50–74) | 61 (49.5–72) | 64 (55–72.5) | 61 (50–71.5) | 64.5 (50–78) | 0.15 |
| Sex, M | 367 (53.3) | 80 (45.5) | 25 (45.5) | 97 (59.5) | 165 (56.1) | 0.03 |
| Race | 0.22 | |||||
| White | 491 (71.4) | 127 (72.2) | 41 (74.5) | 114 (69.9) | 209 (71.1) | |
| Black or African American | 153 (22.2) | 39 (22.2) | 13 (23.6) | 43 (26.4) | 58 (19.7) | |
| Other | 44 (6.4) | 10 (5.7) | 1 (1.8) | 6 (3.7) | 27 (9.2) | |
| Ethnicity | 0.63 | |||||
| Hispanic | 78 (11.3) | 20 (11.4) | 4 (7.3) | 16 (9.8) | 38 (12.9) | |
| Non-Hispanic | 610 (88.7) | 156 (88.6) | 51 (92.7) | 147 (90.2) | 256 (87.1) | |
| APACHE II score | 19 (15–23) | 17 (13–21) | 19 (14.5–25) | 18 (14–22.5) | 20 (16–24) | <0.001 |
| SOFA score | 6 (4–9) | 5 (3–7) | 7 (4.5–10) | 5 (4–7) | 7 (5–10) | <0.001 |
| Comorbidities | ||||||
| Charlson comorbidity index | 2 (1–4) | 2 (1–3.25) | 1 (1–3) | 2 (1–4) | 2 (1–4) | 0.89 |
| Hypertension | 406 (59.0) | 104 (59.1) | 32 (58.2) | 94 (57.7) | 176 (59.9) | 0.97 |
| Chronic respiratory disease | 155 (22.5) | 41 (23.3) | 12 (21.2) | 39 (23.9) | 63 (21.4) | 0.93 |
| Cancer | 134 (19.5) | 38 (21.6) | 10 (18.2) | 28 (17.2) | 58 (19.7) | 0.77 |
| Renal impairment | 50 (7.3) | 6 (3.4) | 6 (10.9) | 8 (4.9) | 30 (10.2) | 0.01 |
| Acute congestive heart failure | 70 (10.2) | 21 (11.9) | 3 (5.5) | 17 (10.4) | 29 (9.9) | 0.61 |
| Prior myocardial infarction | 75 (10.9) | 21 (11.9) | 6 (10.9) | 14 (8.6) | 34 (11.6) | 0.74 |
| Cerebral vascular disease | 75 (10.9) | 16 (9.1) | 9 (16.4) | 17 (10.4) | 33 (11.2) | 0.50 |
| Peripheral vascular disease | 58 (8.4) | 17 (9.7) | 5 (9.1) | 10 (6.1) | 26 (8.8) | 0.66 |
| Chronic dementia | 56 (8.1) | 7 (4.0) | 3 (5.5) | 20 (12.3) | 26 (8.8) | 0.03 |
| Hepatic cirrhosis | 40 (5.8) | 7 (4.0) | 5 (9.1) | 8 (4.9) | 20 (6.8) | 0.38 |
| Peptic ulcer disease | 34 (4.9) | 5 (2.8) | 4 (7.3) | 9 (5.5) | 16 (5.4) | 0.41 |
| AIDS and related syndromes | 15 (2.2) | 5 (2.8) | 1 (1.8) | 4 (2.5) | 5 (1.7) | 0.87 |
| Enrollment criteria | ||||||
| Hyperlactatemia | 399 (58.0) | 79 (44.9) | 33 (60) | 99 (60.7) | 188 (63.9) | <0.001 |
| Refractory hypotension | 373 (54.2) | 108 (61.4) | 29 (52.7) | 79 (48.5) | 157 (53.4) | 0.12 |
| Physiologic variables | ||||||
| Serum lactate, mmol/L | 2.00 (1.14–3.48) | 1.70 (0.90–2.98) | 1.91 (1.25–3.17) | 1.62 (1.04–3.10) | 2.71 (1.60–4.50) | <0.001 |
| Systolic blood pressure, mm Hg | 99 (84–120) | 101 (85–122) | 100 (84–117) | 99 (83–123) | 97 (83–119) | 0.46 |
| MAP, mm Hg | 70 (60–87) | 73 (63–88) | 72 (60–86) | 69 (59–87) | 69 (60–86) | 0.19 |
| Anemia | 104 (15.12) | 26 (14.8) | 11 (20) | 23 (14.1) | 44 (15.0) | 0.70 |
| Fluid overload > 10% over first 72 h | 45 (6.5) | 7 (3.9) | 4 (7.2) | 7 (4.3) | 27 (9.2) | 0.08 |
| [TIMP-2] · [IGFBP7], (ng/ml)2/1,000 | — | 0.1 (0.05–0.17) | 0.16 (0.08–0.22) | 0.85 (0.48–1.92) | 1.71 (0.84–4.1) | <0.001 |
Definition of abbreviations: APACHE II = Acute Physiologic Assessment and Chronic Health Evaluation II; IGFBP7 = insulin-like growth factor–binding protein 7; IQR = interquartile range; MAP = mean arterial pressure; SOFA = Sequential Organ Failure Assessment; TIMP-2 = tissue inhibitor of metalloproteinases-2.
Subgroups: −/− = [TIMP-2] · [IGFBP7] negative at both Hour 0 and Hour 6; −/+ = [TIMP-2] · [IGFBP7] negative at Hour 0 and [TIMP-2] · [IGFBP7] positive at Hour 6; +/− = [TIMP-2] · [IGFBP7] positive at Hour 0 and [TIMP-2] · [IGFBP7] negative at Hour 6; +/+ = [TIMP-2] · [IGFBP7] positive at both Hour 0 and Hour 6. Anemia was defined by Hb: <10 g/dl for males and <8 g/dl for females.
P values are shown for multiple comparison using ANOVA F test for continuous variables and the chi-square test or Fisher exact test for categorical variables.