Copeptin adds prognostic information after ischemic stroke

Abstract

OBJECTIVE: To evaluate and validate the incremental value of copeptin in the prediction of outcome and complications as compared with established clinical variables. METHODS: In this prospective, multicenter, cohort study, we measured copeptin in the emergency room within 24 hours from symptom onset in 783 patients with acute ischemic stroke. The 2 primary end points were unfavorable functional outcome (modified Rankin Scale score 3-6) and mortality within 90 days. Secondary end points were any of 5 prespecified complications during hospitalization. RESULTS: In multivariate analysis, higher copeptin independently predicted unfavorable outcome (adjusted odds ratio 2.17 for any 10-fold copeptin increase [95% confidence interval CI, 1.46-3.22], p < 0.001), mortality (adjusted hazard ratio 2.40 for any 10-fold copeptin increase [95% CI, 1.60-3.60], p < 0.001), and complications (adjusted odds ratio 1.93 for any 10-fold copeptin increase [95% CI, 1.33-2.80], p = 0.001). The discriminatory accuracy, calculated with the area under the receiver operating characteristic curve, improved significantly for all end points when adding copeptin to the NIH Stroke Scale score and the multivariate models. Moreover, the combination of copeptin with a validated score encompassing both the NIH Stroke Scale and age led to a net reclassification improvement of 11.8% for functional outcome and of 37.2% for mortality. CONCLUSIONS: In patients with ischemic stroke, copeptin is a validated blood marker that adds predictive information for functional outcome and mortality at 3 months beyond stroke severity and age. Copeptin seems to be a promising new blood marker for prediction of in-hospital complications. Authors Contribution:As principal investigators, Dr De Marchis (GMDM), Dr Katan (MK) and Dr Arnold (MA) had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Methods:In this prospective, multicenter cohort study we measured copeptin in the emergency room within 24 hours from symptom onset in 783 patients with acute ischemic stroke. The two primary endpoints were unfavorable functional outcome (modified Rankin Scale score 3-6) and mortality within 90 days. Secondary endpoints were any of five prespecified complications during hospitalization.

Predicting Functional Outcome and Symptomatic Intracranial Hemorrhage in Patients With Acute Ischemic Stroke

“…Also, it would be interesting to investigate whether the addition of imaging or specialized laboratory tests (eg, copeptin), 96 biomarkers, or genetic profiles can increase their accuracy. In this context, recently the addition of multimodal imaging did not increase the prognostic accuracy of the ASTRAL score, 97 but it improved the accuracy of the MRI-DRAGON score.…”

Plasma midregional pro-adrenomedullin improves prediction of functional outcome in ischemic stroke

“…[29] The mRS at three months is the most prevalent outcome assessment and the preferred outcome measure for treatment trials in acute stroke. [30,31] As opposed to other stroke biomarker studies, [4][5][6]32,33] we have excluded patients with minor stroke or transitory ischemic attack which results in a higher median NIHSS in our study. This contributes to the higher percentage of patients in this study who underwent recanalization therapy as compared to average rates in Austrian stroke units in recent years.…”

“…[3] Several proteins in peripheral blood which are related to an acute stress response have recently been shown to improve outcome prediction in ischemic stroke. [4][5][6][7] As derived from observations in patients with myocardial infarction and congestive heart failure (CHF), plasma midregional pro-adrenomedullin (MR-proADM) is an independent predictor of death. [8,9] We hypothesized that MR-proADM would also reflect the acute stress response in ischemic stroke and could therefore be used to predict functional outcome.…”

Copeptin in critical illness

“…In children with septic shock, vasopressin and copeptin levels may not robust markers for severity and clinical outcomes [14]. Copeptin is also increased in several acute neurological illnesses, such as acute ischemic stroke [15,16], spontaneous cerebral hemorrhage [17][18][19] and brain trauma [20]. Copeptin, measured within the first 24 h after stroke onset, improves neurologic prognostication after ischemic stroke adding predictive information for functional outcome and mortality at 3 months beyond age and stroke severity measured with the NIH Stroke Scale score [16].…”

“…Copeptin is also increased in several acute neurological illnesses, such as acute ischemic stroke [15,16], spontaneous cerebral hemorrhage [17][18][19] and brain trauma [20]. Copeptin, measured within the first 24 h after stroke onset, improves neurologic prognostication after ischemic stroke adding predictive information for functional outcome and mortality at 3 months beyond age and stroke severity measured with the NIH Stroke Scale score [16]. In patients with severe brain trauma, copeptin does not reflect the urinary sodium excretion or sodium plasma levels, indicating an uncoupling of copeptin-vasopressin release and renal water excretion, but is correlated with injury severity [21].…”