Copeptin is associated with one-year mortality and functional outcome in patients with acute spontaneous basal ganglia hemorrhage
Highlights
► High plasma copeptin level is found in patients with intracerebral hemorrhage. ► Copeptin could emerge as a new biomarker in intracerebral hemorrhage. ► Copeptin independently predicts early neurological deterioration and long-term outcome in patients with intracerebral hemorrhage.
Introduction
Intracerebral hemorrhage (ICH) is a relatively common and devastating disease with little improvement in functional neurological outcome over the last decade despite advances in medical technology [2]. While acute diagnosis is relatively straightforward since the advent of computed tomography (CT) scanning, the ultimate prognosis remains difficult to predict early in the disease course, especially in light of the decision of many families to ‘withdraw care’ on patients deemed unlikely to have favorable long-term functional outcome by their physicians. This uncertainty has resulted in a wide spectrum of patient outcomes, from complete rehabilitation to persistent vegetative state, underscoring the need for adjunctive prognostic tools to guide initial management decisions in the setting of acute ICH. Thus, a readily measurable predictive biomarker predicting mortality or functional outcome in patients with ICH would be helpful for early prognostication and risk stratification [6], [19].
Arginine vasopressin (AVP), also termed antidiuretic hormone, is a nona peptide produced in the hypothalamus. AVP is released from the neurohypophysis into the blood to induce water conservation by the kidney, contributing to the regulation of osmotic and cardiovascular homeostasis [18], [20]. AVP is derived from a larger precursor peptide (pre-provasopressin) along with 2 other peptides, neurophysin II and copeptin [5]. Neurophysin II has a complex structure with many putative intramolecular disulfide bonds, and it may be associated with AVP during maturation and transport [17]. Copeptin, the C-terminal portion of provasopressin, is a 39-amino acid glycopeptide of unknown function [9], [21]. Copeptin may have a role during the intracellular processing of provasopressin, possibly contributing to correct structural formation of the precursor, which leads to efficient proteolytic maturation [1].
Copeptin is produced in equimolar amounts to AVP and can be easily determined [23]. In critically ill patients, copeptin values increased significantly with the severity of the disease [7], [10], [15], [22], [25], [27], [29], [30], [31]. Copeptin levels have also been found to be elevated in ICH; in these groups of patients, high copeptin levels were highly predictive for 90-day unfavorable functional outcome and 30-day mortality; in this context, a meaningful multivariate analysis was not allowed because of a small sample size [31]. Furthermore, it is found that copeptin was significantly associated with 1-week mortality after ICH in a logistic-regression model [8]. This follow-up study furthermore evaluated copeptin as a marker to predict functional outcome and mortality 1 year after admission and early neurological deterioration in acute ICH patients.
Section snippets
Study population
Our target group consisted of consecutive patients with spontaneous basal ganglia hemorrhage evaluated in the emergency room of Traditional Chinese Medical Hospital of Zhejiang Province within the first 6 h from stroke onset. Between July 2007 and December 2009, a total of 112 patients with spontaneous basal ganglia hemorrhage were initially evaluated. Exclusion criteria were existing previous neurological disease, head trauma, use of antiplatelet or anticoagulant medication, presence of other
Patient characteristics
89 patients were enrolled, including 54 men and 35 women. The mean age was 64.5 ± 10.9 years (range, 41–79 years). 79 patients (88.8%) presented with hypertension. 25 patients (28.1%) suffered from diabetes mellitus. On admission, the mean NIHSS score was 21.0 ± 6.6 (range, 6–31), the mean hematoma volume was 34.2 ± 18.3 mL (range, 5–65 mL), 51 patients (57.3%) complicated with IVH, 15 patients (16.9%) had hemorrhage growth. The mean admission time was 2.5 ± 1.6 h (range, 0.3–6.0 h), the mean
Discussion
This study demonstrated that the plasma copeptin levels on admission is considerably increased and markedly predicts long-term clinical outcome and helps to identify patients at risk of early neurological deterioration.
It is well known that copeptin is increased in other central nervous system diseases such as ischemic stroke, aneurysmal subarachnoid hemorrhage or head trauma; in these groups of patients, high copeptin levels in peripheral blood were associated with mortality and poor
Conclusions
In this study, copeptin was significantly associated with early neurological deterioration and 1-year mortality and unfavorable outcome after ICH. If this finding can be validated and confirmed in larger studies, the measurement of copeptin levels may allow together with other clinical parameters to improve risk stratification for ICH patients in the future.
References (31)
- et al.
Change in plasma copeptin level after acute spontaneous basal ganglia hemorrhage
Peptides
(2011) Antidiuretic hormone. Normal and disordered function
Endocrinol Metab Clin North Am
(2001)- et al.
A new glycopeptide in pig, ox, and sheep pituitary
Biochem Biophys Res Commun
(1979) - et al.
Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients
Peptides
(2005) - et al.
Prognostic value of copeptin: one-year outcome in patients with traumatic brain injury
Peptides
(2012) - et al.
Properties of human vasopressin precursor constructs: inefficient monomer folding in the absence of copeptin as a potential contributor to diabetes insipidus
Biochemistry
(2004) - et al.
Guidelines for the management of spontaneous intracerebral hemorrhage in adults
Stroke
(2007) - et al.
Early hemorrhage growth in patients with intracerebral hemorrhage
Stroke
(1997) - et al.
Circadian secretion pattern of copeptin, the C-terminal vasopressin precursor fragment
Clin Chem
(2010) - et al.
Structure–function relationships of the vasopressin prohormone domains
Cell Mol Neurobiol
(1998)
Biological markers in spontaneous intracerebral hemorrhage
Neurologia
Copeptin is associated with mortality in patients with traumatic brain injury
J Trauma
A glycopeptide from the posterior lobe of pig pituitaries. I. Isolation and characterization
Eur J Biochem
Copeptin: a novel, independent prognostic marker in patients with ischemic stroke
Ann Neurol
Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level
Neuro Endocrinol Lett
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Prognostic molecular markers for motor recovery in acute hemorrhagic stroke: A systematic review
2021, Clinica Chimica ActaCitation Excerpt :For instance, the odds of having a poor outcome when NLR, and platelet to lymphocyte ratio were combined (OR = 5.44) increased up to 118%, which means more than double the improvement compared to the isolated biomarkers (OR = 2.30 and 2.49, respectively) [68]. In addition, other sorts of biomarkers have arisen as independent prognostic factors for motor recovery after a stroke, such as NIHSS [2,3,6,7,29,31,33,36,37,42–45,49,50,52,54,56,57,67,69,71,74,77,80] and hematoma volume [2,3,6,29,33,36,37,43–45,49,51,52,54,56,57,67,71,74,79], which might improve accuracy to predict functional recovery. This approach was seen in studies that observed better accuracy to predict functional motor recovery when combining molecular biomarkers with NIHSS [2–4,6–8] or with hematoma volume [2–4,8].
Prognostic value of copeptin in patients with aneurysmal subarachnoid hemorrhage
2019, Journal of NeuroimmunologyIdentification of Plasma Biomarkers of Human Intracerebral Hemorrhage Subtypes through Microarray Technology
2016, Journal of Stroke and Cerebrovascular DiseasesSerum YKL-40 levels as a prognostic factor in patients with intracerebral hemorrhage
2014, Clinical BiochemistryCitation Excerpt :The recent report has shown that circulating C-reactive protein level is an independent predictor for mortality of ICH and has a high prognostic power compared with blood white cell count [40]. However, some recent papers include other biomarkers like copeptin and S100b in multivariable models and do not identify circulating C-reactive protein level as an independent prognostic predictor of ICH [38,39]. In the current study using a multivariate model including serum YKL-40 level, plasma C-reactive protein level did not emerge as an independent predictor for 3-month mortality and unfavorable outcome of ICH.