The Experts below are selected from a list of 4008 Experts worldwide ranked by ideXlab platform
Wiebke Fenske - One of the best experts on this subject based on the ideXlab platform.
-
release and decay kinetics of Copeptin vs avp in response to osmotic alterations in healthy volunteers
The Journal of Clinical Endocrinology and Metabolism, 2018Co-Authors: Wiebke Fenske, Ingeborg Schnyder, Gilbert Koch, Carla Walti, Marc Pfister, Peter Kopp, Martin Fassnacht, Konrad Strauss, Mirjam ChristcrainAbstract:Context Copeptin is the C-terminal fragment of the arginine vasopressin (AVP) prohormone whose measurement is more robust than that of AVP. Similar release and clearance characteristics have been suggested promoting Copeptin as a surrogate marker. Objective To characterize the physiology of osmotically regulated Copeptin release and its half-life in direct comparison with plasma AVP. Design Ninety-one healthy volunteers underwent a standardized three-phase test protocol including (1) osmotic stimulation into the hypertonic range by hypertonic-saline infusion followed by osmotic suppression via (2) oral water load and (3) subsequent glucose infusion. Plasma Copeptin, AVP, serum sodium, and osmolality levels were measured in regular intervals. Results In phase 1, an increase in median osmotic pressure [289 (286; 291) to 311 (309; 314) mOsm/kg H2O] caused similar release kinetics of plasma Copeptin [4 (3.1; 6) to 29.3 (18.6; 48.2) pmol/L] and AVP [1 (0.7; 1.6) to 10.3 (6.8; 18.8) pg/mL]. Subsequent osmotic suppression to 298 (295; 301) mOsm/kg at the end of phase 3 revealed markedly different decay kinetics between both peptides-an estimated initial half-life of Copeptin being approximately 2 times longer than that of AVP (26 vs 12 minutes). Conclusion Copeptin is released in equimolar amounts with AVP in response to osmotic stimulation, suggesting its high potential as an AVP surrogate for differentiation of osmotic disorders. Furthermore, we here describe the decay kinetics of Copeptin in response to osmotic depression enabling to identify a half-life for Copeptin in direct comparison with AVP.
-
Copeptin in the diagnosis of vasopressin-dependent disorders of fluid homeostasis
Nature Reviews Endocrinology, 2016Co-Authors: Mirjam Christ-crain, Wiebke FenskeAbstract:Copeptin and arginine vasopressin (AVP) are derived from a common precursor molecule and have equimolar secretion and response to osmotic, haemodynamic and stress-related stimuli. Plasma concentrations of Copeptin and AVP in relation to serum osmolality are highly correlated. The physiological functions of AVP with respect to homeostasis of fluid balance, vascular tonus and regulation of the endocrine stress response are well known, but the exact function of Copeptin is undetermined. Quantification of AVP can be difficult, but Copeptin is stable in plasma and can be easily measured with a sandwich immunoassay. For this reason, Copeptin has emerged as a promising marker for the diagnosis of AVP-dependent fluid disorders. Copeptin measurements can enable differentiation between various conditions within the polyuria–polydipsia syndrome. In the absence of prior fluid deprivation, baseline Copeptin levels >20 pmol/l identify patients with nephrogenic diabetes insipidus. Conversely, Copeptin levels measured upon osmotic stimulation differentiate primary polydipsia from partial central diabetes insipidus. In patients with hyponatraemia, low levels of Copeptin together with low urine osmolality identify patients with primary polydipsia, and the ratio of Copeptin to urinary sodium can distinguish the syndrome of inappropriate antidiuretic hormone secretion from other AVP-dependent forms of hyponatraemia. The levels of Copeptin in the circulation correlate with those of arginine vasopressin (AVP) Currently available techniques for the measurement of Copeptin have advantages over those for AVP in terms of ex vivo stability of the marker, and the ease and speed of measurement In the differential diagnosis of polyuria–polydipsia syndrome, measurement of Copeptin has great potential, enabling direct identification of patients with nephrogenic diabetes insipidus, without prior thirsting Osmotically stimulated Copeptin levels can differentiate between patients with primary polydipsia and those with partial central diabetes insipidus In the differential diagnosis of hyponatraemia, low Copeptin levels identify primary polydipsia, and the ratio of Copeptin to urinary sodium could distinguish between AVP-dependent forms of hyponatraemia Copeptin is derived from the same precursor as arginine vasopressin (AVP). Unlike AVP, Copeptin is stable and readily assayed. In this Review, Christ-Crain and Fenske describe the use of Copeptin as a marker for differential diagnosis of conditions within the polyuria–polydipsia syndrome.
-
Copeptin as a biomarker and a diagnostic tool in the evaluation of patients with polyuria polydipsia and hyponatremia
Best Practice & Research Clinical Endocrinology & Metabolism, 2016Co-Authors: Mirjam Christcrain, Nils G Morgenthaler, Wiebke FenskeAbstract:Copeptin is part of the 164 amino acid precursor protein preprovasopressin together with vasopressin and neurophysin II. During precursor processing, Copeptin is released together with vasopressin. Copeptin concentrations respond as rapidly as vasopressin to changes in osmolality, a decrease in blood pressure or stress and there is a close correlation of vasopressin and Copeptin concentrations. For these reasons, Copeptin is propagated as a surrogate marker for vasopressin in the differential diagnosis of the polyuria–polydipsia syndromes and hyponatremia. Results of prospective studies show that a baseline Copeptin level without prior fluid deprivation >20 pmol/L is able to identify patients with nephrogenic diabetes insipidus, whereas osmotically stimulated Copeptin levels differentiate between patients with partial central diabetes insipidus and primary polydipsia with a high sensitivity and specificity >94%. In hyponatremia, low Copeptin levels point to primary polydipsia and high levels to hypovolemic hyponatremia. The Copeptin to urinary sodium ratio differentiates accurately between volume-depleted and normovolemic disorders.
-
Copeptin in the diagnosis of vasopressin dependent disorders of fluid homeostasis
Nature Reviews Endocrinology, 2016Co-Authors: Mirjam Christcrain, Wiebke FenskeAbstract:Copeptin and arginine vasopressin (AVP) are derived from a common precursor molecule and have equimolar secretion and response to osmotic, haemodynamic and stress-related stimuli. Plasma concentrations of Copeptin and AVP in relation to serum osmolality are highly correlated. The physiological functions of AVP with respect to homeostasis of fluid balance, vascular tonus and regulation of the endocrine stress response are well known, but the exact function of Copeptin is undetermined. Quantification of AVP can be difficult, but Copeptin is stable in plasma and can be easily measured with a sandwich immunoassay. For this reason, Copeptin has emerged as a promising marker for the diagnosis of AVP-dependent fluid disorders. Copeptin measurements can enable differentiation between various conditions within the polyuria-polydipsia syndrome. In the absence of prior fluid deprivation, baseline Copeptin levels >20 pmol/l identify patients with nephrogenic diabetes insipidus. Conversely, Copeptin levels measured upon osmotic stimulation differentiate primary polydipsia from partial central diabetes insipidus. In patients with hyponatraemia, low levels of Copeptin together with low urine osmolality identify patients with primary polydipsia, and the ratio of Copeptin to urinary sodium can distinguish the syndrome of inappropriate antidiuretic hormone secretion from other AVP-dependent forms of hyponatraemia.
-
a Copeptin based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis
Journal of The American Society of Nephrology, 2014Co-Authors: Wiebke Fenske, Mirjam Christcrain, Martin Fassnacht, Anna Horning, Jessica Simet, Gabor Szinnai, Jonas Rutishauser, Daniel G Bichet, Stefan StorkAbstract:Hyponatremia, the most frequent electrolyte disorder, is caused predominantly by the syndrome of inappropriate antidiuresis (SIAD). A comprehensive characterization of SIAD subtypes, defined by type of osmotic dysregulation, is lacking, but may aid in predicting therapeutic success. Here, we analyzed serial measurements of serum osmolality and serum sodium, plasma arginine vasopressin (AVP), and plasma Copeptin concentrations from 50 patients with hyponatremia who underwent hypertonic saline infusion. A close correlation between Copeptin concentrations and serum osmolality existed in 68 healthy controls, with a mean osmotic threshold±SD of 282±4 mOsM/kg H2O. Furthermore, saline-induced changes in Copeptin concentrations correlated with changes in AVP concentrations in controls and patients. With use of Copeptin concentration as a surrogate measure of AVP concentration, patients with SIAD could be grouped according to osmoregulatory defect: Ten percent of patients had grossly elevated Copeptin concentrations independent of serum osmolality (type A); 14% had Copeptin concentrations that increased linearly with rising serum osmolality but had abnormally low osmotic thresholds (type B); 44% had normal Copeptin concentrations independent of osmolality (type C), and 12% had suppressed Copeptin concentrations independent of osmolality (type D). A novel SIAD subtype discovered in 20% of patients was characterized by a linear decrease in Copeptin concentrations with increasing serum osmolality (type E or "barostat reset"). In conclusion, a partial or complete loss of AVP osmoregulation occurs in patients with SIAD. Although the mechanisms underlying osmoregulatory defects in individual patients are presumably diverse, we hypothesize that treatment responses and patient outcomes will vary according to SIAD subtype.
Andreas Bergmann - One of the best experts on this subject based on the ideXlab platform.
-
prognostic value of Copeptin one year outcome in patients with acute stroke
Stroke, 2010Co-Authors: Sandrine A Urwyler, Nils G Morgenthaler, Andreas Bergmann, Philipp Schuetz, Felix Fluri, Christian Zweifel, Roland Bingisser, Ludwig Kappos, Andreas J Steck, Stefan T EngelterAbstract:Background and Purpose— An accurate long-term outcome prediction may improve management of stroke patients. We investigated the ability of Copeptin to predict 1-year outcome in stroke patients. Methods— In this preplanned post hoc analysis, the National Institutes of Health Stroke Scale score and Copeptin levels were measured on admission in a cohort of patients with ischemic stroke. The primary end point was functional outcome (modified Rankin Scale score <3 or 3–6) after 1 year. The secondary end point was all-cause mortality. Results— Of 362 patients, 341 (94.2%) completed the 1-year follow-up, 146 (43%) patients had an unfavorable functional outcome, and 66 (20%) died. Multivariate logistic-regression analysis adjusted for age and National Institutes of Health Stroke Scale score showed that Copeptin was an independent predictor of functional outcome (odds ratio=4.00; 95% CI, 1.94–8.19) and death (odds ratio=2.68; 95% CI, 1.24–5.82). The area under the receiver operating characteristic curve of copepti...
-
c terminal provasopressin Copeptin is a strong prognostic marker in patients with heart failure after an acute myocardial infarction results from the optimaal study
European Heart Journal, 2009Co-Authors: Adriaan A Voors, Joachim Struck, Andreas Bergmann, Iain B Squire, Stephan Von Haehling, Stefan D Anker, Hans L Hillege, Oliver Hartmann, Dirk J Van Veldhuisen, Kenneth DicksteinAbstract:Aims The aim of the present study was to compare the prognostic value of a novel and promising marker, Copeptin, with B-type natriuretic peptide (BNP), and N-terminal pro-BNP (NT-proBNP), on death or a composite cardiovascular endpoint in patients who developed heart failure after an acute myocardial infarction (AMI). Methods and results From a subset of 224 patients of the OPTIMAAL study, blood samples were drawn at a mean of 3 days after AMI when all patients had signs and/or symptoms of heart failure or a left ventricular ejection fraction <0.35. Endpoints of interest were mortality (primary endpoint of OPTIMAAL) and a composite cardiovascular endpoint, including death, MI, stroke, and/or resuscitated cardiac arrest. Mean age was 67 ± 10 years, and mean follow-up was 33 ± 7 months. Using univariable Cox proportional hazards survival analysis, higher levels of Copeptin, BNP, and NT-proBNP were all significantly related to both mortality and the composite cardiovascular endpoint (all P < 0.01). In a multivariable Cox proportional hazards model, including all three biomarkers and other relevant covariates, a doubling of Copeptin was related to a 1.83 (1.26–2.64) times increased risk of mortality ( P < 0.0001) and a 1.35 (1.05–1.72) times increased risk of the composite cardiovascular endpoint ( P = 0.018). Receiver operating characteristic curves indicated that Copeptin [area under curve (AUC) 0.81] was a stronger predictor of mortality compared with both BNP (AUC 0.66; P = 0.0063 vs. Copeptin) and NT-proBNP (AUC 0.67; P = 0.0016 vs. Copeptin). Finally, changes of Copeptin levels after 1 month significantly added prognostic information to the baseline value. Conclusion Copeptin is a strong and novel marker for mortality and morbidity in patients with heart failure after AMI. In this population, the predictive value of Copeptin was even stronger than BNP and NT-proBNP.
-
Use of Copeptin in the detection of myocardial ischemia.
Clinica Chimica Acta, 2009Co-Authors: Daniel Staub, Nils G Morgenthaler, Andreas Bergmann, Claudia Buser, Tobias Breidthardt, Mihael Potocki, Markus Noveanu, Tobias Reichlin, Christian MuellerAbstract:The role of the arginine-vasopressin (AVP) system in the response to myocardial ischemia is unclear. Copeptin, the C-terminal part of the AVP prohormone is secreted stoichiometrically with AVP.; A total of 253 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography (SPECT) were enrolled. We evaluated the response of Copeptin during exercise and determined whether measurement of Copeptin may be helpful in the detection of myocardial ischemia.; Myocardial ischemia on perfusion images was detected in 127 patients (50%). Median Copeptin levels increased significantly with exercise in patients with ischemia as well as in patients without ischemia (from 3.8 [IQR 2.8-6.6] to 12.3 [IQR 5.2-39.6] pmol/l, P>0.001; and from 3.6 [IQR 2.6-5.7] to 10.8 [IQR 5.0-24.5] pmol/l, P>0.001). Median exercise-induced changes in Copeptin (DeltaCopeptin) were similar in both groups (7.7 versus 5.1 pmol/l, P=0.150). The area under the ROC curve for the ability of DeltaCopeptin to detect myocardial ischemia was 0.552.; Copeptin levels increased threefold with exercise, irrespective of the presence or absence of myocardial ischemia. Therefore, myocardial ischemia does not seem to be a major trigger of the AVP system. Measurement of Copeptin does not seem helpful in the detection of exercise-induced myocardial ischemia.
-
circulating levels of Copeptin a novel biomarker in lower respiratory tract infections
European Journal of Clinical Investigation, 2007Co-Authors: Bert Muller, Nils G Morgenthaler, Andreas Bergmann, Philipp Schuetz, Roland Bingisser, Daiana Stolz, Christian Muller, Michael Tamm, Mirjam ChristcrainAbstract:Background Vasopressin has haemodynamic as well as osmoregulatory effects, and reflects the individual stress response. Copeptin is cosynthesized with vasopressin, directly mirroring vasopressin levels, but is more stable in plasma and serum. Both levels are increased in patients with septic shock. Lower respiratory tract infections (LRTI) are a precursor of sepsis. Thus, we investigated circulating levels and the prognostic use of Copeptin for the severity and outcome in patients with LRTI. Materials and methods Five hundred and forty-five consecutive patients with LRTI and 50 healthy controls were evaluated. Serum Copeptin levels were measured with a new chemiluminescens sandwich immunoassay. Results Of the 545 patients, 373 had community-acquired pneumonia (CAP), 60 acute exacerbations of chronic obstructive pulmonary disease (COPD), 59 acute bronchitis, 13 exacerbations of asthma and 40 other final diagnoses. Copeptin levels were significantly higher in patients with LRTI as compared to controls (P < 0·001) with highest levels in patients with CAP. Copeptin levels increased with increasing severity of CAP, as classified by the pneumonia severity index (PSI) (P < 0·001). In patients who died, Copeptin levels on admission were significantly higher as compared to levels in survivors [70·0 (28·8–149·0) vs. 24·3 (10·8–43·8) pmol L−1, P < 0·001]. The area under the receiver operating curve (AUC) for survival was 0·75 for Copeptin, which was significantly higher as compared to C-reactive protein (AUC 0·61, P = 0·01), leukocyte count (AUC 0·59, P = 0·01) and similar to procalcitonin (AUC 0·68, P = 0·21). Conclusions Copeptin levels are increased with increasing severity of LRTI namely in patients with CAP and unfavourable outcome. Copeptin levels, as a novel biomarker, might be a useful tool in the risk stratification of patients with LRTI.
-
assay for the measurement of Copeptin a stable peptide derived from the precursor of vasopressin
Clinical Chemistry, 2006Co-Authors: Nils G Morgenthaler, Joachim Struck, Christine Alonso, Andreas BergmannAbstract:Background: Arginine vasopressin (AVP) is a key regulator of water balance, but its instability makes reliable measurement difficult and precludes routine use. We present a method for quantifying AVP release by use of Copeptin, a glycopeptide comprising the C-terminal part of the AVP prohormone. Methods: We measured Copeptin in 50-μL serum and plasma samples from healthy individuals and from critically ill patients with sepsis. Our sandwich immunoluminometric assay used 2 polyclonal antibodies to amino acids 132–164 of pre-provasopressin. Results: The assay yielded results within 3 h. The analytical detection limit was 1.7 pmol/L, and the interlaboratory CV was 2.25 pmol/L. The assay was linear on dilution of the analyte. Ex vivo Copeptin stability (<20% loss of analyte) for at least 7 days at room temperature and 14 days at 4 °C was shown for serum and EDTA-, heparin-, and citrate plasma. Copeptin (median, 4.2 pmol/L; range, 1–13.8 pmol/L) was detectable in 97.5% of 359 healthy individuals and was not associated with age. Median concentrations were considerably higher in men than women, increased significantly after exercise, and were influenced by fasting and water load. Copeptin was significantly ( P <0.001) increased in 60 critically ill patients with sepsis (median, 79.5 pmol/L; range, 10.6–228.0 pmol/L). The correlation between Copeptin and AVP for 110 samples was r = 0.78 ( P <0.0001). Conclusions: Copeptin is stable for days after blood withdrawal and can be quickly and easily measured. The Copeptin assay may be a useful alternative to direct measurement of AVP concentration.
Nils G Morgenthaler - One of the best experts on this subject based on the ideXlab platform.
-
Copeptin as a biomarker and a diagnostic tool in the evaluation of patients with polyuria polydipsia and hyponatremia
Best Practice & Research Clinical Endocrinology & Metabolism, 2016Co-Authors: Mirjam Christcrain, Nils G Morgenthaler, Wiebke FenskeAbstract:Copeptin is part of the 164 amino acid precursor protein preprovasopressin together with vasopressin and neurophysin II. During precursor processing, Copeptin is released together with vasopressin. Copeptin concentrations respond as rapidly as vasopressin to changes in osmolality, a decrease in blood pressure or stress and there is a close correlation of vasopressin and Copeptin concentrations. For these reasons, Copeptin is propagated as a surrogate marker for vasopressin in the differential diagnosis of the polyuria–polydipsia syndromes and hyponatremia. Results of prospective studies show that a baseline Copeptin level without prior fluid deprivation >20 pmol/L is able to identify patients with nephrogenic diabetes insipidus, whereas osmotically stimulated Copeptin levels differentiate between patients with partial central diabetes insipidus and primary polydipsia with a high sensitivity and specificity >94%. In hyponatremia, low Copeptin levels point to primary polydipsia and high levels to hypovolemic hyponatremia. The Copeptin to urinary sodium ratio differentiates accurately between volume-depleted and normovolemic disorders.
-
Copeptin helps in the early detection of patients with acute myocardial infarction primary results of the chopin trial Copeptin helps in the early detection of patients with acute myocardial infarction
Journal of the American College of Cardiology, 2013Co-Authors: Alan S. Maisel, Nils G Morgenthaler, Christian Mueller, Seanxavier Neath, Robert H Christenson, James Mccord, Richard M Nowak, Lori B Daniels, Gary M Vilke, Judd E HollanderAbstract:Objectives The goal of this study was to demonstrate that Copeptin levels Background Copeptin is secreted from the pituitary early in the course of AMI. Methods This was a 16-site study in 1,967 patients with chest pain presenting to an ED within 6 hours of pain onset. Baseline demographic characteristics and clinical data were collected prospectively. Copeptin levels and a contemporary sensitive cTnI (99th percentile 40 ng/l; 10% coefficient of variation 0.03 μg/l) were measured in a core laboratory. Patients were followed up for 180 days. The primary outcome was diagnosis of AMI. Final diagnoses were adjudicated by 2 independent cardiologists blinded to Copeptin results. Results AMI was the final diagnosis in 156 patients (7.9%). A negative Copeptin and cTnI at baseline ruled out AMI for 58% of patients, with a negative predictive value of 99.2% (95% confidence interval: 98.5 to 99.6). AMIs not detected by the initial cTnI alone were picked up with Copeptin >14 pmol/l in 23 (72%) of 32 patients. Non–ST-segment elevation myocardial infarctions undetected by cTnI at 0 h were detected with Copeptin >14 pmol/l in 10 (53%) of 19 patients. Projected average time-to-decision could be reduced by 43% (from 3.0 h to 1.8 h) by the early rule out of 58% of patients. Both abnormal Copeptin and cTnI were predictors of death at 180 days (p Conclusions Adding Copeptin to cTnI allowed safe rule out of AMI with a negative predictive value >99% in patients presenting with suspected acute coronary syndromes. This combination has the potential to rule out AMI in 58% of patients without serial blood draws. (Investigation of the Biomarker Copeptin in Patients With Acute Myocardial Infarction [ NCT00952744 ])
-
prognostic value of Copeptin one year outcome in patients with acute stroke
Stroke, 2010Co-Authors: Sandrine A Urwyler, Nils G Morgenthaler, Andreas Bergmann, Philipp Schuetz, Felix Fluri, Christian Zweifel, Roland Bingisser, Ludwig Kappos, Andreas J Steck, Stefan T EngelterAbstract:Background and Purpose— An accurate long-term outcome prediction may improve management of stroke patients. We investigated the ability of Copeptin to predict 1-year outcome in stroke patients. Methods— In this preplanned post hoc analysis, the National Institutes of Health Stroke Scale score and Copeptin levels were measured on admission in a cohort of patients with ischemic stroke. The primary end point was functional outcome (modified Rankin Scale score <3 or 3–6) after 1 year. The secondary end point was all-cause mortality. Results— Of 362 patients, 341 (94.2%) completed the 1-year follow-up, 146 (43%) patients had an unfavorable functional outcome, and 66 (20%) died. Multivariate logistic-regression analysis adjusted for age and National Institutes of Health Stroke Scale score showed that Copeptin was an independent predictor of functional outcome (odds ratio=4.00; 95% CI, 1.94–8.19) and death (odds ratio=2.68; 95% CI, 1.24–5.82). The area under the receiver operating characteristic curve of copepti...
-
Use of Copeptin in the detection of myocardial ischemia.
Clinica Chimica Acta, 2009Co-Authors: Daniel Staub, Nils G Morgenthaler, Andreas Bergmann, Claudia Buser, Tobias Breidthardt, Mihael Potocki, Markus Noveanu, Tobias Reichlin, Christian MuellerAbstract:The role of the arginine-vasopressin (AVP) system in the response to myocardial ischemia is unclear. Copeptin, the C-terminal part of the AVP prohormone is secreted stoichiometrically with AVP.; A total of 253 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography (SPECT) were enrolled. We evaluated the response of Copeptin during exercise and determined whether measurement of Copeptin may be helpful in the detection of myocardial ischemia.; Myocardial ischemia on perfusion images was detected in 127 patients (50%). Median Copeptin levels increased significantly with exercise in patients with ischemia as well as in patients without ischemia (from 3.8 [IQR 2.8-6.6] to 12.3 [IQR 5.2-39.6] pmol/l, P>0.001; and from 3.6 [IQR 2.6-5.7] to 10.8 [IQR 5.0-24.5] pmol/l, P>0.001). Median exercise-induced changes in Copeptin (DeltaCopeptin) were similar in both groups (7.7 versus 5.1 pmol/l, P=0.150). The area under the ROC curve for the ability of DeltaCopeptin to detect myocardial ischemia was 0.552.; Copeptin levels increased threefold with exercise, irrespective of the presence or absence of myocardial ischemia. Therefore, myocardial ischemia does not seem to be a major trigger of the AVP system. Measurement of Copeptin does not seem helpful in the detection of exercise-induced myocardial ischemia.
-
c terminal provasopressin Copeptin is associated with left ventricular dysfunction remodeling and clinical heart failure in survivors of myocardial infarction
Journal of Cardiac Failure, 2008Co-Authors: Dominic Kelly, Joachim Struck, Nils G Morgenthaler, Iain B Squire, Sohail Q Khan, Paulene A Quinn, Joan E DaviesAbstract:Abstract Background Acute myocardial infarction (AMI) is associated with left ventricular (LV) dysfunction and clinical heart failure. Arginine vasopressin is elevated in heart failure and the C-terminal of provasopressin (Copeptin) is associated with adverse outcome post-AMI. The aim of this study was to describe the association between Copeptin with LV dysfunction, volumes, and remodeling and clinical heart failure post-AMI. Methods and Results We studied 274 subjects with AMI. Copeptin was measured from plasma at discharge and subjects underwent echocardiography at discharge and follow-up (median 155 days). Subjects were followed for clinical heart failure for a median of 381 days. Remodeling was assessed as the change (Δ) in LV volumes between echo examinations. Copeptin correlated directly with wall motion index score (WMIS) and inversely with LV ejection fraction (LVEF) at discharge (WMIS, r = 0.276, P r = −0.188, P = .03) and follow-up (WMIS, r = 0.244, P r = −0.270, P r = 0.215, P = .002; LVESV, r = 0.299, P r = 0.171, P = 0.015, ΔESV; r = 0.186, P = .008. Subjects with increasing LVESV had higher levels of Copeptin (median 6.30 vs. 5.75 pmol/L, P = .012). Subjects with clinical heart failure (n = 30) during follow-up had higher Copeptin before discharge (median 13.55 vs. 5.80, P 6.31 pmol/L. Conclusions Copeptin is associated with LV dysfunction, volumes, and remodeling and clinical heart failure post-AMI. Measurement of Copeptin may provide prognostic information and the AVP system may be a therapeutic target in post-MI LV dysfunction.
Joachim Struck - One of the best experts on this subject based on the ideXlab platform.
-
C-Terminal Provasopressin (Copeptin) as Prognostic Marker after Acute Non ST Elevation Myocardial Infarction - Leicester Acute Myocardial Infarction Peptide II (LAMP II) study.
Clinical Science, 2011Co-Authors: Hafid Narayan, Joachim Struck, Onkar S Dhillon, Paulene Quinn, Iain B Squire, Joan E DaviesAbstract:Background Copeptin, the 39 amino acid C-terminal portion of provasopressin, has been shown to be an independent predictor for adverse events following ST elevation myocardial infarction. We hypothesized that plasma Copeptin was an independent predictor for adverse outcomes following acute non ST elevation myocardial infarction (NSTEMI) and evaluated whether Copeptin added prognostic information to the GRACE score compared to NTproBNP. Methods Plasma Copeptin and NTproBNP were measured in 754 consecutive patients admitted to hospital with chest pain and diagnosed as having NSTEMI in this prospective observational study. The endpoint was all cause mortality at 6 months. Results: Upper median levels of Copeptin were strongly associated with all cause mortality at 6 months. Copeptin was a significant predictor of time to mortality (HR = 5.98 [3.75 to 9.53], p < 0.0005) in univariate analysis and remained a significant predictor in multivariate analysis (HR = 3.03 [1.32 to 6.98], p = 0.009). There were no significant differences between the area under ROC curves of Copeptin, NTproBNP and the GRACE score. Copeptin improved accuracy of risk classification when used in combination with the GRACE score as determined by net reclassification improvement whereas NTproBNP did not. The relative utility of the GRACE score was increased more by Copeptin than by NTproBNP over a wide range of risks. Conclusions: Plasma Copeptin is elevated after NSTEMI and higher levels are associated with worse outcomes. Copeptin used in conjunction with the GRACE score improves risk stratification enabling more accurate identification of high risk individuals.
-
c terminal provasopressin Copeptin is a strong prognostic marker in patients with heart failure after an acute myocardial infarction results from the optimaal study
European Heart Journal, 2009Co-Authors: Adriaan A Voors, Joachim Struck, Andreas Bergmann, Iain B Squire, Stephan Von Haehling, Stefan D Anker, Hans L Hillege, Oliver Hartmann, Dirk J Van Veldhuisen, Kenneth DicksteinAbstract:Aims The aim of the present study was to compare the prognostic value of a novel and promising marker, Copeptin, with B-type natriuretic peptide (BNP), and N-terminal pro-BNP (NT-proBNP), on death or a composite cardiovascular endpoint in patients who developed heart failure after an acute myocardial infarction (AMI). Methods and results From a subset of 224 patients of the OPTIMAAL study, blood samples were drawn at a mean of 3 days after AMI when all patients had signs and/or symptoms of heart failure or a left ventricular ejection fraction <0.35. Endpoints of interest were mortality (primary endpoint of OPTIMAAL) and a composite cardiovascular endpoint, including death, MI, stroke, and/or resuscitated cardiac arrest. Mean age was 67 ± 10 years, and mean follow-up was 33 ± 7 months. Using univariable Cox proportional hazards survival analysis, higher levels of Copeptin, BNP, and NT-proBNP were all significantly related to both mortality and the composite cardiovascular endpoint (all P < 0.01). In a multivariable Cox proportional hazards model, including all three biomarkers and other relevant covariates, a doubling of Copeptin was related to a 1.83 (1.26–2.64) times increased risk of mortality ( P < 0.0001) and a 1.35 (1.05–1.72) times increased risk of the composite cardiovascular endpoint ( P = 0.018). Receiver operating characteristic curves indicated that Copeptin [area under curve (AUC) 0.81] was a stronger predictor of mortality compared with both BNP (AUC 0.66; P = 0.0063 vs. Copeptin) and NT-proBNP (AUC 0.67; P = 0.0016 vs. Copeptin). Finally, changes of Copeptin levels after 1 month significantly added prognostic information to the baseline value. Conclusion Copeptin is a strong and novel marker for mortality and morbidity in patients with heart failure after AMI. In this population, the predictive value of Copeptin was even stronger than BNP and NT-proBNP.
-
gender and renal function influence plasma levels of Copeptin in healthy individuals
Clinical Science, 2009Co-Authors: Sanjay S Bhandari, Joan E Davies, Iain B Squire, Ian Loke, Joachim StruckAbstract:The present study sought to identify confounding factors for the interpretation of Copeptin levels in healthy individuals. The natriuretic peptides are recognized as diagnostic and prognostic tools in HF (heart failure). Interpretation of BNP (brain natriuretic peptide) and NTproBNP (N-terminal pro-BNP) levels is multifaceted as their secretion is influenced by many variables. A newly identified glycopeptide called Copeptin is comparable with the natriuretic peptides in the diagnosis and prognosis of HF and as a prognostic biomarker after AMI (acute myocardial infarction). Copeptin, derived from the C-terminal portion of the precursor to AVP (arginine vasopressin), is secreted stoichiometrically with vasopressin, hence it can be used as a surrogate marker of the AVP system. In the present study, 706 healthy volunteers were recruited from a local HF screening study. Participants with a history of cardiovascular disease and those with echocardiographic abnormalities were excluded from the study. Copeptin and NTproBNP levels were assayed using in-house immunoluminometric assays. Median Copeptin levels were significantly higher in the male volunteers compared with the females [median (range): 4.3 (0.4-44.3) compared with 3.2 (1.0-14.8) pmol/l; P<0.001]. In males, Copeptin was correlated with eGFR (estimated glomerular filtration rate; r(s)=-0.186, P<0.001). In females, the correlation of Copeptin with eGFR was weak (r(s)=-0.097, P=0.095). DT (deceleration time) and left atrial size correlated with higher Copeptin levels (r(s)=0.085, P=0.029 and r(s)=0.206, P<0.001 respectively). Only gender (P<0.001), eGFR (P<0.001), left atrial size (P=0.04) and DT (P=0.02) remained independently predictive of plasma Copeptin. The present study suggests that gender and renal function specific partition values should be used to interpret Copeptin values in future studies of this biomarker in HF or ischaemic heart disease.
-
c terminal provasopressin Copeptin is associated with left ventricular dysfunction remodeling and clinical heart failure in survivors of myocardial infarction
Journal of Cardiac Failure, 2008Co-Authors: Dominic Kelly, Joachim Struck, Nils G Morgenthaler, Iain B Squire, Sohail Q Khan, Paulene A Quinn, Joan E DaviesAbstract:Abstract Background Acute myocardial infarction (AMI) is associated with left ventricular (LV) dysfunction and clinical heart failure. Arginine vasopressin is elevated in heart failure and the C-terminal of provasopressin (Copeptin) is associated with adverse outcome post-AMI. The aim of this study was to describe the association between Copeptin with LV dysfunction, volumes, and remodeling and clinical heart failure post-AMI. Methods and Results We studied 274 subjects with AMI. Copeptin was measured from plasma at discharge and subjects underwent echocardiography at discharge and follow-up (median 155 days). Subjects were followed for clinical heart failure for a median of 381 days. Remodeling was assessed as the change (Δ) in LV volumes between echo examinations. Copeptin correlated directly with wall motion index score (WMIS) and inversely with LV ejection fraction (LVEF) at discharge (WMIS, r = 0.276, P r = −0.188, P = .03) and follow-up (WMIS, r = 0.244, P r = −0.270, P r = 0.215, P = .002; LVESV, r = 0.299, P r = 0.171, P = 0.015, ΔESV; r = 0.186, P = .008. Subjects with increasing LVESV had higher levels of Copeptin (median 6.30 vs. 5.75 pmol/L, P = .012). Subjects with clinical heart failure (n = 30) during follow-up had higher Copeptin before discharge (median 13.55 vs. 5.80, P 6.31 pmol/L. Conclusions Copeptin is associated with LV dysfunction, volumes, and remodeling and clinical heart failure post-AMI. Measurement of Copeptin may provide prognostic information and the AVP system may be a therapeutic target in post-MI LV dysfunction.
-
assay for the measurement of Copeptin a stable peptide derived from the precursor of vasopressin
Clinical Chemistry, 2006Co-Authors: Nils G Morgenthaler, Joachim Struck, Christine Alonso, Andreas BergmannAbstract:Background: Arginine vasopressin (AVP) is a key regulator of water balance, but its instability makes reliable measurement difficult and precludes routine use. We present a method for quantifying AVP release by use of Copeptin, a glycopeptide comprising the C-terminal part of the AVP prohormone. Methods: We measured Copeptin in 50-μL serum and plasma samples from healthy individuals and from critically ill patients with sepsis. Our sandwich immunoluminometric assay used 2 polyclonal antibodies to amino acids 132–164 of pre-provasopressin. Results: The assay yielded results within 3 h. The analytical detection limit was 1.7 pmol/L, and the interlaboratory CV was 2.25 pmol/L. The assay was linear on dilution of the analyte. Ex vivo Copeptin stability (<20% loss of analyte) for at least 7 days at room temperature and 14 days at 4 °C was shown for serum and EDTA-, heparin-, and citrate plasma. Copeptin (median, 4.2 pmol/L; range, 1–13.8 pmol/L) was detectable in 97.5% of 359 healthy individuals and was not associated with age. Median concentrations were considerably higher in men than women, increased significantly after exercise, and were influenced by fasting and water load. Copeptin was significantly ( P <0.001) increased in 60 critically ill patients with sepsis (median, 79.5 pmol/L; range, 10.6–228.0 pmol/L). The correlation between Copeptin and AVP for 110 samples was r = 0.78 ( P <0.0001). Conclusions: Copeptin is stable for days after blood withdrawal and can be quickly and easily measured. The Copeptin assay may be a useful alternative to direct measurement of AVP concentration.
Mirjam Christcrain - One of the best experts on this subject based on the ideXlab platform.
-
release and decay kinetics of Copeptin vs avp in response to osmotic alterations in healthy volunteers
The Journal of Clinical Endocrinology and Metabolism, 2018Co-Authors: Wiebke Fenske, Ingeborg Schnyder, Gilbert Koch, Carla Walti, Marc Pfister, Peter Kopp, Martin Fassnacht, Konrad Strauss, Mirjam ChristcrainAbstract:Context Copeptin is the C-terminal fragment of the arginine vasopressin (AVP) prohormone whose measurement is more robust than that of AVP. Similar release and clearance characteristics have been suggested promoting Copeptin as a surrogate marker. Objective To characterize the physiology of osmotically regulated Copeptin release and its half-life in direct comparison with plasma AVP. Design Ninety-one healthy volunteers underwent a standardized three-phase test protocol including (1) osmotic stimulation into the hypertonic range by hypertonic-saline infusion followed by osmotic suppression via (2) oral water load and (3) subsequent glucose infusion. Plasma Copeptin, AVP, serum sodium, and osmolality levels were measured in regular intervals. Results In phase 1, an increase in median osmotic pressure [289 (286; 291) to 311 (309; 314) mOsm/kg H2O] caused similar release kinetics of plasma Copeptin [4 (3.1; 6) to 29.3 (18.6; 48.2) pmol/L] and AVP [1 (0.7; 1.6) to 10.3 (6.8; 18.8) pg/mL]. Subsequent osmotic suppression to 298 (295; 301) mOsm/kg at the end of phase 3 revealed markedly different decay kinetics between both peptides-an estimated initial half-life of Copeptin being approximately 2 times longer than that of AVP (26 vs 12 minutes). Conclusion Copeptin is released in equimolar amounts with AVP in response to osmotic stimulation, suggesting its high potential as an AVP surrogate for differentiation of osmotic disorders. Furthermore, we here describe the decay kinetics of Copeptin in response to osmotic depression enabling to identify a half-life for Copeptin in direct comparison with AVP.
-
Copeptin as a biomarker and a diagnostic tool in the evaluation of patients with polyuria polydipsia and hyponatremia
Best Practice & Research Clinical Endocrinology & Metabolism, 2016Co-Authors: Mirjam Christcrain, Nils G Morgenthaler, Wiebke FenskeAbstract:Copeptin is part of the 164 amino acid precursor protein preprovasopressin together with vasopressin and neurophysin II. During precursor processing, Copeptin is released together with vasopressin. Copeptin concentrations respond as rapidly as vasopressin to changes in osmolality, a decrease in blood pressure or stress and there is a close correlation of vasopressin and Copeptin concentrations. For these reasons, Copeptin is propagated as a surrogate marker for vasopressin in the differential diagnosis of the polyuria–polydipsia syndromes and hyponatremia. Results of prospective studies show that a baseline Copeptin level without prior fluid deprivation >20 pmol/L is able to identify patients with nephrogenic diabetes insipidus, whereas osmotically stimulated Copeptin levels differentiate between patients with partial central diabetes insipidus and primary polydipsia with a high sensitivity and specificity >94%. In hyponatremia, low Copeptin levels point to primary polydipsia and high levels to hypovolemic hyponatremia. The Copeptin to urinary sodium ratio differentiates accurately between volume-depleted and normovolemic disorders.
-
Copeptin in the diagnosis of vasopressin dependent disorders of fluid homeostasis
Nature Reviews Endocrinology, 2016Co-Authors: Mirjam Christcrain, Wiebke FenskeAbstract:Copeptin and arginine vasopressin (AVP) are derived from a common precursor molecule and have equimolar secretion and response to osmotic, haemodynamic and stress-related stimuli. Plasma concentrations of Copeptin and AVP in relation to serum osmolality are highly correlated. The physiological functions of AVP with respect to homeostasis of fluid balance, vascular tonus and regulation of the endocrine stress response are well known, but the exact function of Copeptin is undetermined. Quantification of AVP can be difficult, but Copeptin is stable in plasma and can be easily measured with a sandwich immunoassay. For this reason, Copeptin has emerged as a promising marker for the diagnosis of AVP-dependent fluid disorders. Copeptin measurements can enable differentiation between various conditions within the polyuria-polydipsia syndrome. In the absence of prior fluid deprivation, baseline Copeptin levels >20 pmol/l identify patients with nephrogenic diabetes insipidus. Conversely, Copeptin levels measured upon osmotic stimulation differentiate primary polydipsia from partial central diabetes insipidus. In patients with hyponatraemia, low levels of Copeptin together with low urine osmolality identify patients with primary polydipsia, and the ratio of Copeptin to urinary sodium can distinguish the syndrome of inappropriate antidiuretic hormone secretion from other AVP-dependent forms of hyponatraemia.
-
a Copeptin based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis
Journal of The American Society of Nephrology, 2014Co-Authors: Wiebke Fenske, Mirjam Christcrain, Martin Fassnacht, Anna Horning, Jessica Simet, Gabor Szinnai, Jonas Rutishauser, Daniel G Bichet, Stefan StorkAbstract:Hyponatremia, the most frequent electrolyte disorder, is caused predominantly by the syndrome of inappropriate antidiuresis (SIAD). A comprehensive characterization of SIAD subtypes, defined by type of osmotic dysregulation, is lacking, but may aid in predicting therapeutic success. Here, we analyzed serial measurements of serum osmolality and serum sodium, plasma arginine vasopressin (AVP), and plasma Copeptin concentrations from 50 patients with hyponatremia who underwent hypertonic saline infusion. A close correlation between Copeptin concentrations and serum osmolality existed in 68 healthy controls, with a mean osmotic threshold±SD of 282±4 mOsM/kg H2O. Furthermore, saline-induced changes in Copeptin concentrations correlated with changes in AVP concentrations in controls and patients. With use of Copeptin concentration as a surrogate measure of AVP concentration, patients with SIAD could be grouped according to osmoregulatory defect: Ten percent of patients had grossly elevated Copeptin concentrations independent of serum osmolality (type A); 14% had Copeptin concentrations that increased linearly with rising serum osmolality but had abnormally low osmotic thresholds (type B); 44% had normal Copeptin concentrations independent of osmolality (type C), and 12% had suppressed Copeptin concentrations independent of osmolality (type D). A novel SIAD subtype discovered in 20% of patients was characterized by a linear decrease in Copeptin concentrations with increasing serum osmolality (type E or "barostat reset"). In conclusion, a partial or complete loss of AVP osmoregulation occurs in patients with SIAD. Although the mechanisms underlying osmoregulatory defects in individual patients are presumably diverse, we hypothesize that treatment responses and patient outcomes will vary according to SIAD subtype.
-
circulating levels of Copeptin a novel biomarker in lower respiratory tract infections
European Journal of Clinical Investigation, 2007Co-Authors: Bert Muller, Nils G Morgenthaler, Andreas Bergmann, Philipp Schuetz, Roland Bingisser, Daiana Stolz, Christian Muller, Michael Tamm, Mirjam ChristcrainAbstract:Background Vasopressin has haemodynamic as well as osmoregulatory effects, and reflects the individual stress response. Copeptin is cosynthesized with vasopressin, directly mirroring vasopressin levels, but is more stable in plasma and serum. Both levels are increased in patients with septic shock. Lower respiratory tract infections (LRTI) are a precursor of sepsis. Thus, we investigated circulating levels and the prognostic use of Copeptin for the severity and outcome in patients with LRTI. Materials and methods Five hundred and forty-five consecutive patients with LRTI and 50 healthy controls were evaluated. Serum Copeptin levels were measured with a new chemiluminescens sandwich immunoassay. Results Of the 545 patients, 373 had community-acquired pneumonia (CAP), 60 acute exacerbations of chronic obstructive pulmonary disease (COPD), 59 acute bronchitis, 13 exacerbations of asthma and 40 other final diagnoses. Copeptin levels were significantly higher in patients with LRTI as compared to controls (P < 0·001) with highest levels in patients with CAP. Copeptin levels increased with increasing severity of CAP, as classified by the pneumonia severity index (PSI) (P < 0·001). In patients who died, Copeptin levels on admission were significantly higher as compared to levels in survivors [70·0 (28·8–149·0) vs. 24·3 (10·8–43·8) pmol L−1, P < 0·001]. The area under the receiver operating curve (AUC) for survival was 0·75 for Copeptin, which was significantly higher as compared to C-reactive protein (AUC 0·61, P = 0·01), leukocyte count (AUC 0·59, P = 0·01) and similar to procalcitonin (AUC 0·68, P = 0·21). Conclusions Copeptin levels are increased with increasing severity of LRTI namely in patients with CAP and unfavourable outcome. Copeptin levels, as a novel biomarker, might be a useful tool in the risk stratification of patients with LRTI.