Association of stress biomarkers with 30-day unplanned readmission and death
BACKGROUND
The theory that posthospitalization stress might increase the risk of postdischarge complications has never been investigated.
OBJECTIVE
To assess whether serum levels of stress biomarkers at discharge are associated with readmission and death after an acute-care hospitalization.
DESIGN
We prospectively included 346 patients aged ≥50 years admitted to the department of general internal medicine at a large community hospital between April 8, 2013 and September 23, 2013. We measured the serum levels of several biomarkers at discharge: midregional pro-adrenomedullin, copeptin, cortisol, and prolactin. All patients were followed for up to 90 days after discharge (none was lost to follow-up). The main outcome was first unplanned readmission or death within 30 days after hospital discharge. We assessed the additional value of biomarkers to 2 validated readmission prediction scores: the LACE index (Length of stay, Admission Acuity, Charlson Comorbidity Index, and number of Emergency department visits within preceding 6 months) and the HOSPITAL score (Hemoglobin level at discharge, discharge from Oncology service, Sodium level at discharge, any Procedure performed during index hospitalization, Index admission Type, number of Admissions within preceding 12 months, and Length of stay).
RESULTS
Forty patients (11.6%) had a 30-day unplanned readmission or death. High serum copeptin and cortisol levels were associated with an increase in the odds of unplanned readmission or death (odds ratios [95% confidence interval] 2.69 [1.29-5.64] and 3.43 [1.36, 8.65], respectively). We found no significant association with midregional pro-adrenomedullin or prolactin. Furthermore, these stress biomarkers increased the performance of two readmission prediction scores (LACE index and HOSPITAL score).
CONCLUSION
High serum levels of copeptin and cortisol at discharge were independently associated with 30-day unplanned readmission or death, supporting a possible negative effect of hospitalization stress during the postdischarge period. Stress biomarkers improved the performance of prediction models and therefore could help better identify high-risk patients. Journal of Hospital Medicine 2017;12:523-529. © 2017 Society of Hospital Medicine
© 2017 Society of Hospital Medicine
RESULTS
Among the 530 patients admitted to the ward, 184 were excluded (120 meeting exclusion criteria, 64 unable to give consent, Figure). Among the 346 patients included, 11.6% (n = 40) had a 30-day unplanned readmission or death (37 were readmitted, 2 died during readmission, 3 died without readmission). Within 90 days, 26.6% (n = 92) had a readmission or death (84 were readmitted, 10 died during or after readmission, 8 died without readmission).
Clinical Characteristics
Table 1 lists the patients’ baseline characteristics. Median age was 73 years (IQR, 64-82 years). Of the 346 patients included, 172 (49.7%) were men. Median CCI was 7 (IQR, 5-9); according to this index, 310 patients (89.6%) had at least 2 comorbidities. Median length of stay was 7 days (IQR, 4-12 days).
Primary Diagnoses of Admission, Unplanned Readmission, and Death
The 3 main causes of index admission were cardiovascular disorder (n = 92), infectious disorder (n = 70), and neurologic disorder (n = 66). Table 2 lists the causes of readmissions and deaths. A same-diagnosis category between index admission and readmission was found in 17 (45.9%) of the 37 readmitted patients and in 3 (60%) of the 5 patients who died.
Biomarkers and 30-Day Unplanned Readmission or Death
AUROC was 0.53 (95% confidence interval [CI], 0.43-0.63) for ADM, 0.60 (95% CI, 0.50-0.70) for copeptin, 0.59 (95% CI, 0.44-0.73) for cortisol, and 0.56 (95% CI, 0.45-0.66) for prolactin. The difference between admission and discharge levels was not associated with unplanned readmission or death for any of the biomarkers (Supplemental Table 2).
ADM and readmission or death. Median ADM level was not different between patients with and without readmission or death (1.0 nmol/L in each case; P = 1.00). The best cutoff level for ADM was 2 nmol/L (sensitivity, 16.7%; specificity, 91.8%). At this level, ADM was associated with a nonstatistically significant 130% increased odds of 30-day readmission or death (P = 0.09; Table 3, Supplemental Table 3). Conversely, the association with the 90-day outcome was significant (P = 0.02; Table 3, Supplemental Table 4).
Copeptin and readmission or death. Patients with 30-day readmission or death had a higher median copeptin level at discharge than patients without (10.4 pmol/L vs 7.3 pmol/L; P = 0.03). At a copeptin level higher than 9 pmol/L (to convert to pg/mL, divide by 0.249; sensitivity, 66.7%; specificity, 59.7%), both 30-day readmission or death (adjusted odds ratio [OR], 2.69; 95% CI, 1.29-5.64; P = 0.009) and 90-day readmission or death (adjusted OR, 2.76; 95% CI, 1.56-4.88; P < 0.001) were nearly 3 times as likely (Table 3, Supplemental Tables 3 and 4).
Cortisol and readmission or death. Median cortisol was not statistically different between patients with and without the primary outcome (431 nmol/L vs 465 nmol/L; P = 0.72). At a cortisol level higher than 590 nmol/L (to convert to μg/dL, divide by 27.59; sensitivity, 54.6%; specificity, 76.4%), 30-day outcome was more than 3 times as likely (adjusted OR, 3.43; 95% CI, 1.36-8.65; P = 0.009; Table 3, Supplemental Table 3). At 90 days, only the model that adjusted for age and LACE index points remained statistically significant (P = 0.02; Table 3, Supplemental Table 4).
Prolactin and readmission or death. Median prolactin was not statistically different between patients with and without the primary outcome (15.1 μg/L vs 14.1 μg/L; P = 0.24). The best cutoff level for prolactin was 23 μg/L (to convert to mIU/L, divide by 0.05; sensitivity, 27.8%; specificity, 82.9%). Prolactin was associated with a nonstatistically significant increased odds of 30-day (P = 0.16) and 90-day (P = 0.24) readmission or death (Table 3, Supplemental Tables 3 and 4).
Additive Value of Biomarkers to HOSPITAL Score and LACE Index
The AUROC for the original HOSPITAL score, 0.70 (95% CI, 0.60-0.80), nonsignificantly increased to 0.76 after adding the biomarkers (P > 0.14). For the LACE index, AUROC was 0.59 (95% CI, 0.49-0.68), with a significant 0.10 increase with cortisol (P = 0.04) and a near significant increase with copeptin (P = 0.08). Calibration remained almost unchanged after adding the biomarkers to both models (Supplemental Table 5). NRIoverall was positive for all biomarkers, with statistical significance for copeptin added to the HOSPITAL score (0.47; 95% CI, 0.13-0.79) and for cortisol added to the LACE index (0.62; 95% CI, 0.15-1.06).
DISCUSSION
In this prospective cohort study, 30-day and 90-day unplanned readmission or death was nearly 3 times as likely for patients with high copeptin levels on discharge from an acute-care medical hospitalization, and 30-day readmission or death was more than 3 times as likely for patients with high cortisol levels. High ADM and prolactin levels were not consistently associated with readmission or death. Adding such biomarkers to readmission prediction models improved their performance.
