Inflammatory and stress markers predicting pneumonia, outcome, and etiology in patients with stroke

Abstract

ObjectivePrognosis of stroke is negatively affected by complications, in particular stroke-associated pneumonia (SAP). We hypothesized that inflammatory and stress biomarkers predict SAP during hospitalization and outcome 3 months after stroke.MethodsWe pooled the clinical data of 2 acute stroke studies with identical assessment: the STRoke Adverse outcome is associated WIth NoSoKomial Infections (STRAWINSKI) and PREDICT studies. Measurement of biomarkers (ultrasensitive procalcitonin [PCTus]; midregional pro-adrenomedullin; midregional pro-atrial natriuretic peptide [MRproANP]; ultrasensitive copeptin [CPus]; C-terminal pro-endothelin) was performed from serum samples drawn on the first 4 days of hospital admission.ResultsThe combined cohort consists of 573 cases with available backup samples to perform the analysis. SAP was associated with increased admission and maximum levels of all biomarkers. Furthermore, all biomarkers were associated with death and correlated with functional outcome 3 months after stroke. The multivariate logistic regression model retained ultrasensitive CPus and PCTus beyond clinical risk factors for predicting SAP, improving the receiver operating characteristic area under the curve (AUC) from 0.837 to 0.876. In contrast, the biomarkers did not improve the prediction of death and functional outcome in the multivariate model. Cardioembolic strokes were significantly associated with higher values of all biomarkers, whereas discrimination was best for MRproANP (AUC = 0.811 for maximum value).ConclusionsThe tested biomarkers are associated with SAP and poor functional outcome. However, these biomarkers only slightly improve prediction of SAP and do not improve long-term outcome prediction over clinical parameters. MRproANP showed the best discrimination for identifying cardioembolic stroke, warranting further studies to confirm our finding.Clinical trial registrationclinicaltrials.govNCT01264549 and NCT01079728.

Stroke-induced immunosuppression: implications for the prevention and prediction of post-stroke infections

“…Recently, PCT and copeptin were studied as SAP predictors along with other biomarkers by pooling data from two clinical trials (PREDICT [ 62 ] and STRAWINSKI [ 63 ]). Of all the studied biomarkers, the results showed that only PCT and copeptin were independent predictors of SAP when adjusting for clinical variables such as dysphagia, chronic obstructive pulmonary disease (COPD), hypercholesterolemia, and the National Institute of Health Stroke Scale (NIHSS) at admission [ 64 ]. In contrast, at earlier time points, Hu et al [ 65 ] did not find PCT to be useful for the prediction of SAP, only when the clinical suspicion of SAP is already high.…”

A Combined Clinical and Serum Biomarker-Based Approach May Allow Early Differentiation Between Patients With Minor Stroke and Transient Ischemic Attack as Well as Mid-term Prognostication

“…Hence, the diagnosis of an ischemic stroke is currently linked to the detection of a persistent and not only transient neuronal damage either by cerebral imaging in terms of an ischemic lesion or by persisting neurological symptoms for more than 24 h ( 3 ). Besides the differentiation between ischemic and hemorrhagic stroke within the (hyper)acute phase of stroke ( 5 , 6 ), serum biomarkers might also be helpful in predicting complications of stroke like pneumonia ( 11 , 13 ), in functional prognostication ( 12 , 14 , 15 ), as well as in the allocation of diagnostic and rehabilitative resources. However, so far, no single biomarker or panel of biomarkers succeeded translation from bench to bedside, i.e., to facilitate diagnosis, treatment, or prognostication ( 7 ).…”

Copeptin and Stress

“…Based on this, it has been recently included in a validated biomarker-based clinical score with age, NIHSS and thrombolysis, "the CoRisk score", for the prediction of 90-day death and disability after ischemic stroke (AUC 0.819) [114]. Data from a recent pooled analysis indicate copeptin is an independent predictor of stroke-associated pneumonia, although of only slightly additive value as compared with clinical parameters or commonly applied prediction scores [115,116], and that its plasma levels are higher in cardioembolic stroke than other etiologies [115]. Furthermore, assessing copeptin levels in the emergency setting could be helpful in guiding the safe discharge of patients with transient ischemic attack (TIA) and their subsequent management as outpatients [117]: in a prospective observational study on 237 consecutive patients referring to the emergency department for TIA, copeptin emerged as an independent predictor for stroke recurrence within 7 days (negative predictive value 97.4% at a cut-off value of 13.8 pmol/L, HR 3.9, 95% CI 1.01-14.4, p = 0.039), particularly when combined with demonstrated large artery atherosclerosis (HR 7.8, 95% CI 2.5-24.7, p = 0.002; AUC 0.83).…”