Prediction of 72-hour mortality in patients with extremely high serum C-reactive protein levels using a novel weighted average of risk scores

Abstract

The risk factors associated with mortality in patients with extremely high serum C-reactive protein (CRP) levels are controversial. In this retrospective single-center cross-sectional study, the clinical and laboratory data of patients with CRP levels ≥40 mg/dL treated in Saitama Medical Center, Japan from 2004 to 2017 were retrieved from medical records. The primary outcome was defined as 72-hour mortality after the final CRP test. Forty-four mortal cases were identified from the 275 enrolled cases. Multivariate logistic regression analysis (MLRA) was performed to explore the parameters relevant for predicting mortality. As an alternative method of prediction, we devised a novel risk predictor, “weighted average of risk scores” (WARS). WARS features the following: (1) selection of candidate risk variables for 72-hour mortality by univariate analyses, (2) determination of C-statistics and cutoff value for each variable in predicting mortality, (3) 0–1 scoring of each risk variable at the cutoff value, and (4) calculation of WARS by weighted addition of the scores with weights assigned according to the C-statistic of each variable. MLRA revealed four risk variables associated with 72-hour mortality—age, albumin, inorganic phosphate, and cardiovascular disease—with a predictability of 0.829 in C-statistics. However, validation by repeated resampling of the 275 records showed that a set of predictive variables selected by MLRA fluctuated occasionally because of the presence of closely associated risk variables and missing data regarding some variables. WARS attained a comparable level of predictability (0.837) by combining the scores for 10 risk variables, including age, albumin, electrolytes, urea, lactate dehydrogenase, and fibrinogen. Several mutually related risk variables are relevant in predicting 72-hour mortality in patients with extremely high CRP levels. Compared to conventional MLRA, WARS exhibited a favorable performance with flexible coverage of many risk variables while allowing for missing data.

Correlation between the 72-hour fatality ratios and out-of-hospital cardiac arrest ratios in patients with extremely high outlier values of 57 laboratory test items: A single-center retrospective inception cohort study

“…[ 7 ] The 72-hour fatality ratio in patients with CRP levels ≥ 40 mg/dL was 16.0%, and old age, low albumin level, high inorganic phosphorus level, and complications of cardiovascular disease were predictive indicators. [ 8 ] The 72-hour fatality ratio in patients with RPG levels ≥ 500 mg/dL was 4.6%, and low albumin level, high CK level, and the presence of malignancy were predictive indicators. [ 9 ]…”

“…AST = aspartate aminotransferase, BUN = blood urea nitrogen, CK = creatine kinase, CRP = C-reactive protein, HCO 3 − = bicarbonate ion, LD = lactic dehydrogenase, N/A = not applicable, Na = sodium, T-Bil = total bilirubin. JSLM2018 [12] ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ Hamano et al [13] ✔ ✔ ✔ ✔ ✔ ✔ Chen et al [14] ✔ ✔ ✔ ✔ Cheng et al [15] ✔ ✔ ✔ Onishi et al [16] ✔ ✔ Niki et al [17] ✔ ✔ Forrest et al [18] ✔ Kawai et al [19] ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ Tyler et al [20] ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ Saito et al [7] ✔ ✔ ✔ Saito et al [8] ✔ ✔ Watanabe et al [9] ✔ "B" indicates laboratory test items with 72-h mortality rates that were below the lower limit of the linear confidence region of the regression line and lower rates than the out-of-hospital cardiac arrest rate. "C" indicates selected item that were classified as neither "A" nor "B" in this study.…”

“…JSLM2018 [12] Panic data and critical values N/A ✔ ✔ ✔ ✔ ✔ ✔ Hamano et al [13] Advanced cancer 7-90 d ✔ ✔ ✔ ✔ Chen et al [14] Advanced cancer 7 d Cheng et al [15] Metastatic or advanced cancer 14 d ✔ ✔ Onishi et al [16] Terminal illness 14 d ✔ ✔ ✔ ✔ Niki et al [17] Terminal cancer 2 or 3 wk ✔ ✔ ✔ ✔ Forrest et al [18] Inoperable non-small-cell lung cancer Survival mo ✔ Kawai et al [19] Terminally ill cancer 30 d ✔ ✔ Tyler et al [20] Intensive care unit Death in the ICU ✔ ✔ ✔ Saito et al [7] AST more than 3000 U/L 72 h ✔ ✔ Saito et al [8] CRP more than 40 mg/dL 72 h Watanabe et al [9] RPG more than 500 mg/dL 72 h ✔ "A" indicates laboratory test items with 72-h mortality rates that were above the upper limit of the linear confidence region of the regression line and higher rates than the out-of-hospital cardiac arrest rate. AST = aspartate aminotransferase, BUN = blood urea nitrogen, CK = creatine kinase, CRP = C-reactive protein, HCO 3 − = bicarbonate ion, LD = lactic dehydrogenase, N/A = not applicable, Na = sodium, T-Bil = total bilirubin.…”

“…[ 3 ] However, the nature of extremely high outlier values of various laboratory tests (panic values or not) and the role of these values in the actual prognosis have not been sufficiently examined. Several studies have identified the following as the predictors of 72-hour mortality for patients in intensive care units (ICUs), [ 4 ] after emergency department visits, [ 5 ] and those with trauma [ 6 ] : aspartate aminotransferase (AST) level ≥ 3000 U/L, [ 7 ] C-reactive protein (CRP) level ≥ 40 mg/dL, [ 8 ] and random plasma glucose level ≥ 500 mg/dL. [ 9 ] In other words, to the best of our knowledge, no previous studies have analyzed the association between each extremely high outlier value of laboratory test items and short-term prognosis or out-of-hospital cardiac arrest (OHCA) from a cross-disease perspective.…”

Biomarkers as Prognostic Predictors and Therapeutic Guide in Critically Ill Patients: Clinical Evidence

“…CRP is a clinical marker frequently used to evaluate the presence of infection and sepsis and is frequently used in the diagnosis of intra-abdominal infections [ 22 ], as a marker of discrimination of patients with pneumonia and those with tracheal infections [ 23 ], as an aid to differentiate bacterial infection from viral and, in critical patients, elevated CRP values have been associated with increased risk of organ failure and mortality [ 24 ]. Elevated CRP concentrations have been successfully used as a biomarker of infection in septic patients with community-acquired pneumonia (CAP) or ventilator-associated pneumonia (VAP) and as a marker of bacterial load and appropriate antibiotic therapy.…”