Use Of Copeptin Research Articles

6616 Copeptin Use To Reduce Hospital Stay In A Complicated DI Case

Abstract Disclosure: S.S. Kowsika: None. H. Moran: None. Introduction: While there is literature describing the use of copeptin for the diagnosis of polyuria-polydipsia syndrome, its utilization remains very limited in many hospitals. We present a case where the patient, initially misdiagnosed with central diabetes insipidus (DI), was appropriately diagnosed with partial nephrogenic DI through the use of copeptin. Case: A 48-year old female with a history of cardiac arrest, anoxic brain injury and diabetes insidious (DI) presented to the emergency department with hypernatremia (Na 154 mmol/L). The patient had been initiated on desmopresin (DDAVP) at an outside facility prior to her current admission. Despite receiving high doses of DDAVP, her sodium levels remained elevated, prompting further investigation. DDAVP administration was discontinued. A water deprivation test was subsequently performed, followed by IV administration of 2 mcg of DDAVP, which resulted in an increase in urine osmolality from 191 to 331 mosm/kg, which was less than the expected 50% increase observed in central DI. Additionally, a baseline copeptin level was obtained and noted to be 31 pmol/L, confirming the diagnosis of partial nephrogenic DI. The patient was started on Amiloride, leading to normalization of sodium levels. Discussion: Many patients with polyuria-polydipsia syndrome are frequently misdiagnosed and receive incorrect treatment, potentially worsening their clinical condition. Copeptin (Carboxy-Terminal-Pro-vasopressin) is the C-terminal peptide of pro-vasopressin, co-secreted with arginine vasopressin (AVP). It has been proposed as a direct test for diagnosing polyuria-polydipsia syndrome. Baseline Copeptin testing without stimulation can accurately diagnose nephrogenic DI if elevated (>21.4, pmol/L). To differentiate between central DI and chronic polyuria, prior thirsting with hypertonic saline or glucagon stimulation is necessary, with stimulated copeptin <4.9 pmol/L diagnosing central DI. Despite its diagnostic potential, Copeptin is underutilized in many settings. In this case, using Copeptin to accurately diagnose our patient led to appropriate treatment and the resolution of hypernatremia. Presentation: 6/1/2024

Abstract #1392363: Copeptin Role in the Diabetes Insipidus Work Up, a Case of Nephrogenic DI Diagnosed by Copeptin Levels After Indeterminate Results on Water Deprivation Test

The indirect water-deprivation test (WDT) is the gold standard for the diagnosis of diabetes insipidus (DI). This test can be technically cumbersome and inaccurate. Because Copeptin and Argine Vasopressin (AVP) are derived from the same precursor protein, pre-provasopressin, copeptin provides the advantage of a better diagnostic marker. We present a case of DI where copeptin elucidated the diagnosis. A 66 y/o male with past medical history of bipolar disorder (20 years taking lithium, last use 2 years prior), hypertension, chronic kidney disease stage 3, head trauma 10 years prior. He was sent to the ER from a psychiatry facility for urinary and fecal incontinence. History is significant for polyuria, and polydipsia (∼3 liters of water/day). No headaches, or vision changes. Unremarkable physical exam including mental status. Labs showed sodium of 152; urine osm 260; serum osm 309, and urinary sodium 68; baseline creatinine 1.5 with GFR 55. CT head w/o contrast was negative. Hypernatremia improved with D5W solution. Urine output was difficult to calculate given urinary incontinence. Endocrinology was consulted for DI work-up. The patient was transferred to the ICU for a WDT. Foley catheter was placed. The starting sodium level was 145. One hour later, sodium went up to 147 with plasma osm of 304. A copeptin level was sent. He received 2 mcg of DDAVP IV. The urine osm was checked every 30 min for 2 hours. Results showed urine osmolarity levels of 304, 320, 346 and 346 post-DDAVP. Sodium remained unchanged at a level of 148 pointing to nephrogenic DI. He was started on HCTZ 25 mg PO daily with normal sodium levels at 24 hours without IV fluids. Copeptin resulted at 26 pmol/L confirming a diagnosis of complete nephrogenic DI. Our patient had risk factors for central and nephrogenic DI. WDT was performed with an increase of < 15% in uOsm with persistently high sodium despite DDAVP ruling out central DI. This minimal response pointed to complete Nephrogenic DI; however, persistent urine osm >300 left partial central DI possible. The copeptin level of 26 confirmed the diagnosis of complete nephrogenic DI. Diagnostic accuracy of the classical WDT is only around 70%. Multiple studies have evaluated the accuracy of copeptin in the differential diagnosis of polyuria-polydipsia syndrome showing a single baseline copeptin level >21.4 pmol/L differentiated nephrogenic DI from other etiologies with a 100% sensitivity and specificity (1). The superiority of copeptin has also been confirmed when applies to hypertonic saline-stimulated testing (2). Copeptin is a more stable, reliable, and rapidly measurable blood biomarker of AVP. The use of copeptin should become standard of care for all DI work-up.

Use of copeptin in interpretation of the water deprivation test.

Currently, the water deprivation test remains the standard method for distinguishing primary polydipsia (PP) from cranial diabetes insipidus (cDI) and nephrogenic diabetes insipidus (nDI). There is increasing interest in a direct estimate of antidiuretic hormone using plasma copeptin as a stable and reliable surrogate marker. We present our experience of measuring copeptin during the water deprivation test. Forty-seven people (17 men) underwent a standard water deprivation test between 2013 and 2021. Plasma copeptin was measured at the start of the test and at the end of the period of water deprivation (maximum osmotic stimulation). Results were classified using prespecified diagnostic criteria. As it is known that a significant proportion of tests will reveal indeterminate results, a final diagnosis was obtained by including relevant pre- and post-test clinical criteria. This diagnosis was then used to plan individual treatment. Basal and stimulated copeptin were significantly higher in the nephrogenic DI group than other categories (p< .001). There was no significant difference in basal or stimulated copeptin between PP, cDI or partial DI. Nine results were indeterminate where the serum and urine osmolality did not give a unified diagnosis. Stimulated copeptin was helpful in reclassifying these patients into the final diagnostic groups. Plasma copeptin has additional clinical utility in interpretation of the water deprivation test and may continue to have a place alongside newer stimulation tests.

Measuring copeptin, a surrogate for vasopressin in patients with hypertension – Can it identify those who are volume Responsive?

BackgroundAmong hypertensive patients, plasma renin activity is lower and the response to diuretic monotherapy greater in volume responsive hypertensive patients. We hypothesized that hormones influencing extracellular volume such as vasopressin / antidiuretic hormone (ADH) might permit the development of a simple test to identify those with volume-related hypertension. Such a test might be of particular benefit to the Black population which is purported to have a higher incidence of volume-related and responsive hypertension. Thus, using copeptin, a surrogate marker for ADH, we studied if there were differences in this hormone between those with and without volume responsive hypertension. MethodsSerum copeptin was measured in biobanked blood samples from the Genetic Epidemiology of Responses to Antihypertensives (GERA) I study and analyzed with other variables from the study dataset. ResultsThere was no relationship between PRA and copeptin values nor could the response in blood pressure be predicted by the copeptin values. However, baseline copeptin levels were higher in Black than in White subjects (7.5 pmol/L vs 5.4 pmol/L, P < 0.001) while plasma sodium and calculated plasma osmolality were slightly lower in keeping with the concept that Black subjects have more volume-related hypertension. In addition, after hydrochlorothiazide (HCTZ), copeptin was significantly lower in Black (6.2 pmol/L, P = 0.004) but unchanged in White subjects (5.2 pmol/L, P = 0.901) and there were also changes in sodium. ConclusionThe current study suggests differences in ADH physiology between hypertensive Black and White patients. However, the use of copeptin to identify volume responsive patients could not be confirmed.

Copeptin in Patients with Pregnancy-Induced Hypertension.

Pregnancy-induced hypertension (PIH) occurs in 6–8% of pregnancies, and increases the risk of many severe obstetric complications. The etiology of PIH has not been fully explained, and hence, treatment is only palliative in nature, and prevention is not fully effective. It has been proposed that PIH development is influenced by the arginine vasopressin pathway, whose surrogate biomarker is copeptin. The aim of this study is a prospective assessment of the relationship between the level of copeptin in pregnant women and the occurrence of PIH, and to identify its usefulness in predicting complications. The study involved a group of 21 pregnant women who developed PIH and 37 women with uncomplicated pregnancies as a control group. Blood samples were collected at the three trimesters of gestation (<13 HBD, between 13 and 26 and >26 HBD) and then frozen. Copeptin levels [pg/mL] were measured in serum samples obtained in the first, second and third trimesters of gestation from women in the PIH and control groups. The concentration of copeptin in the second and third trimesters of pregnancy was statistically significantly higher in the PIH group (p < 0.05). For copeptin determined in the first trimester, which could be used to screen for PIH, the area under the ROC curve was 0.650. The highest risk of PIH occurred in patients with high concentrations of copeptin in the first trimester of pregnancy and obesity OR = 5.5 (95% CI 1.0–31.3). The risk of PIH was augmented in patients with high levels of copeptin and an abnormal Doppler result of the uterine arteries OR = 28.4 (95% CI 5.3–152). In conclusion, copeptin levels were found to be elevated in pregnant women before the diagnosis of PIH; however, copeptin should not be used as a stand-alone marker. The combination of copeptin concentration with the other risk factors (diabetes, maternal age and preeclampsia in previous pregnancy) did not improve the diagnostic values of the use of copeptin in the PIH risk assessment, but the combination of copeptin concentration with BMI may be useful in clinical practice. Measurement of copeptin together with a Doppler examination of uterine arteries in the first trimester of pregnancy may be a useful marker in predicting the development of PIH.

The Emerging Role of Copeptin.

Direct measurement of the nonapeptide vasopressin has been limited by analyte instability ex vivo and in vivo rapid degradation, low serum concentrations requiring a sensitive assay and inherent secretory pulsatility. Copeptin is a 39 amino acid glycopeptide cleavage product of vasopressin synthesis with high stability, providing a marker of vasopressin secretion. Copeptin measurement has applications in diagnosis of diabetes insipidus and other diseases with altered vasopressin secretion. This review summarises our current understanding of serum copeptin measurement in diabetes insipidus and possible future applications of copeptin assays. As vasopressin is a stress hormone, there is emerging evidence on the use of copeptin for diagnosis and prognostication of disorders such as syndrome of inappropriate anti-diuretic hormone secretion, diabetes mellitus, critical illness, stroke, cardiovascular disease, respiratory disease, renal disease and thermal stress. Copeptin concentration measurement is likely to improve the diagnostic reliability of diabetes insipidus and, as a marker of stress, may have diagnostic or prognostic utility in specific clinical circumstances. Further studies are needed to determine if goal-directed therapy using plasma copeptin concentrations may improve patient outcomes.

Postoperative Copeptin as a Biomarker for Development of Diabetes Insipidus Following Hypothalamic-Pituitary Surgery

ObjectiveCopeptin is a surrogate marker of arginine vasopressin release with better stability and simplicity of measurement. Postoperative copeptin levels may guide clinicians in stratifying patients who need close monitoring of fluid balance. The objective is to determine whether copeptin is a predictive marker of postoperative diabetes insipidus (DI). MethodsThis is a prospective diagnostic study. Patients who underwent neurosurgical intervention of the sellar-suprasellar regions were recruited. Serum copeptin levels were measured before and after surgery, within 24 hours. Logistic regression analysis and diagnostic performance measures were calculated to determine the relationship between postoperative copeptin levels and DI. ResultsOf 82 patients, 26 (31.7%) developed postoperative DI, with 7 patients (8.5%) having permanent DI. The samples for copeptin measurement were taken at 13 ± 2.1 hours postoperatively. From the receiver operating characteristic analysis, low postoperative copeptin levels (<2.5 pmol/L) demonstrated an acceptable ability to predict DI (area under the curve, 0.72; 95% CI, 0.60-0.84). Discriminative power was stronger in the permanent DI group (area under the curve, 0.82; 95% CI, 0.64-1.00). Postoperative copeptin levels <2.5 pmol/L were associated with DI (specificity > 91%). However, postoperative copeptin levels >20 pmol/L were rarely associated with DI, with a negative predictive value of 100%. ConclusionsIn patients undergoing sellar-suprasellar interventions, low postoperative copeptin levels within the first postoperative day predict postoperative DI, whereas high levels exclude it. Copeptin measurement should be applied in the clinical practice of postoperative care in patients following hypothalamic-pituitary surgery. This study may expand the potential use of copeptin, including in the Asian population.

Diabetes insipidus complicating apoplexy during pregnancy: the potential use of copeptin.

Pituitary apoplexy during pregnancy is rare but important to recognise, particularly in the hyperoestrogenaemic state when known lactotroph hyperplasia occurs. Untreated, the complication rates from pituitary adenomas depend upon the size of the adenoma before pregnancy. A history of thirst plus polydipsia during pregnancy raises suspicion for diabetes insipidus and a 24-h urine collection quantifying polyuria with an inappropriately low urine osmolality confirms the diagnosis. Further evaluation for assessing diabetes insipidus in pregnancy may be facilitated by the use of a copeptin.

Clinical use of copeptin in migraine patients admitted to the emergency department

PurposeThe purpose of this study was to investigate the clinical use of copeptin to evaluate migraine attacks in the Emergency Department. An additional aim was to detect changes in serum copeptin levels in migraine patients during attack and attack-free periods. MethodsThis prospective case–control study included 52 migraine patients and 51 healthy individuals with similar demographic characteristics. Blood samples were collected from migraine patients both in attack and attack-free periods. ResultsThe mean copeptin levels in the patients group in the attack and attack-free periods were 689.28 and 576.68 pg/ml, respectively, whereas they were 608.68 pg/ml in the control group. There was a significant difference in the mean copeptin level in the attack period and attack-free periods (p = 0.026). The sensitivity and specificity of copeptin in detecting headache episodes in migraine patients were 58.8% and 60.7%, respectively, at a cut-off value of 388.67 pg/ml. ConclusionThis is the first study to investigate the diagnostic efficacy of serum copeptin levels in migraine patients. Although the diagnostic efficacy of serum copeptin levels for migraines was unsatisfactory, it could be helpful at management of migraine patients in ED.

Copeptin and its role in the diagnosis of diabetes insipidus and the syndrome of inappropriate antidiuresis.

Copeptin is secreted in an equimolar amount to arginine vasopressin (AVP) but can easily be measured in plasma or serum with a sandwich immunoassay. The main stimuli for copeptin are similar to AVP, that is an increase in osmolality and a decrease in arterial blood volume and pressure. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation. Copeptin has, therefore, been evaluated as diagnostic biomarker in vasopressin‐dependent disorders of body fluid homeostasis. Disorders of body fluid homeostasis are common and can be divided into hyper‐ and hypoosmolar circumstances: the classical hyperosmolar disorder is diabetes insipidus, while the most common hypoosmolar disorder is the syndrome of inappropriate antidiuresis (SIAD). Copeptin measurement has led to a “revival” of the direct test in the differential diagnosis of diabetes insipidus. Baseline copeptin levels, without prior thirsting, unequivocally identify patients with nephrogenic diabetes insipidus. In contrast, for the difficult differentiation between central diabetes insipidus and primary polydipsia, a stimulated copeptin level of 4.9 pmol/L upon hypertonic saline infusion differentiates these two entities with a high diagnostic accuracy and is clearly superior to the classical water deprivation test. On the contrary, in the SIAD, copeptin measurement is of only little diagnostic value. Copeptin levels widely overlap in patients with hyponatraemia and emphasize the heterogeneity of the disease. Additionally, a variety of factors lead to unspecific copeptin elevations in the acute setting further complicating its interpretation. The broad use of copeptin as diagnostic marker in hyponatraemia and specifically to detect cancer‐related disease in SIADH patients can, therefore, not be recommended.

An exploratory pilot study with copeptin as a biomarker for individualizing treatment for nocturnal polyuria.

The aim of the present study was to investigate the use of random copeptin concentrations as possible biomarkers for the differential diagnosis of nocturnal polyuria (NP). In all, 111 patients with and without nocturia were enrolled in the study. Patients with a neurogenic bladder and/or those who had undergone bladder or urethral surgery were excluded from the study. All patients completed a 72-hour frequency-volume chart and a renal function profile. A random blood sample was obtained during the day for measurement of plasma copeptin concentrations, osmolality, and serum sodium and creatinine concentrations. The effect of the use of different definitions for NP was evaluated. The median age of the study participants was 61 years, and 48% were female. Copeptin was significantly correlated with urinary and plasma osmolality, as well as free water clearance (r=0.43, 0.56 and -0.38 respectively; P < .001 for all). Study participants were divided into 3 groups: controls (n = 51), those with NP (n = 41), and those with global polyuria (n = 19). Copeptin concentrations were significantly lower in subjects with global polyuria than in those with NP and the control group (2.96 vs 3.97 and 3.94 pM, respectively; P = .008 and .005). There was no significant difference in random daytime copeptin concentrations between the NP and control groups (P = .972). The results differed when other definitions for NP were used (e.g. NPi33 or NUP10). We could not confirm our hypothesis that patients with NP have lower copeptin concentrations, although random blood sampling is not ideal. Further research is required to determine the use of copeptin in NP, perhaps in the identification of the desmopressin response.

YIA-CS2-5 - Usefulness of Copeptin for Predicting Long-term Clinical Outcomes in Patients with Heart Failure

Background: Copeptin, a surrogate marker of proarginine vasopression, is expected to be a useful marker for diagnosis and predicting clinical outcomes in cardiovascular disease. However, its usefulness in patients with heart failure (HF) has not been adequately evaluated yet in real-world clinical practice. Methods and Results: In consecutive 107 patients hospitalized for HF in Kyoto University Hospital between April 2011 and July 2012, median serum copeptin level on admission was 15.5 (6.7–32.0) pmol/L. As compared with the low-copeptin group (<18 pmol/L, N = 60), the high-copeptin group (≧18 pmol/L, N = 47) included more male patients and those with prior myocardial infarction, prior HF, low ejection fraction and chronic kidney disease. During median 4.5 (1.0–5.5) years clinical follow-up, the cumulative incidence of a composite of all-cause death and HF re-admission (all-cause death/re-admission for HF) was significantly higher in the high-copeptin group than in the low-copeptin group (63.4% versus 33.0% at 1 year, 77.1% versus 62.2% at 3 years, and 85.2% versus 77.2% at 5 years, respectively, log-rank P = .03). After adjustment for confounders, the higher-copeptin level was still an independent predictor for all-cause death/re-admission for HF (hazard ratio [95% confidence interval]: 1.77 [1.04–3.01], P = .03). Conclusion: Copeptin was suggested to be a potential useful marker for predicting long-term clinical outcomes in patients with HF.

Use of copeptin for rapid rule-out of acute myocardial infarction.

Copeptin is currently understood as a quantitative marker of endogenous stress. It rises rapidly in multiple acute disorders including acute myocardial infarction. As a single variable, it has only modest diagnostic accuracy for acute myocardial infarction. However, the use of copeptin within a dual-marker strategy together with conventional cardiac troponin increases the diagnostic accuracy and particularly the negative predictive value of cardiac troponin alone for acute myocardial infarction. The rapid rule-out of acute myocardial infarction is the only application in acute cardiac care mature enough to merit consideration for routine clinical care. However, the dual-marker approach seems to provide only very small incremental value when used in combination with sensitive or high-sensitivity cardiac troponin assays. This review aims to update and educate regarding the potential and the procedural details, as well as the caveats and challenges of using copeptin in clinical practice.

Vasopressin and Related Peptides; Potential Value in Diagnosis, Prognosis and Treatment of Clinical Disorders

Vasopressin (AVP) and its receptors play a pivotal role in maintaining body homeostasis under physiological and pathophysiological conditions. As a consequence, the vasopressin system has emerged as an important target for both diagnostic and therapeutic applications in a number of medical conditions. Stoichiometric generation of AVP with copeptin, which is relatively accessible in the blood for measurements, makes copeptin a valuable surrogate of AVP. In this review, we present the regulation of release of AVP and activation of V1a, V1b, and V2 vasopressin receptors under physiological and pathological conditions. We make a survey of the role of AVP in: the regulation of the cardiovascular system; body fluid osmolality; natraemia; endocrine regulation; food intake; metabolism; circadian rhythmicity, immunological processes; and in the formation of learning, memory, cognition, and emotional and social behaviours. We also discuss the significance of the inappropriate functioning of the vasopressin system for: the development of cardiovascular diseases; disturbances of the water-electrolyte balance; energy metabolism; inflammatory processes; pain; neurogenic stress; memory disorders; depression; anxiety; autism; and schizophrenia. The structure and biological properties of peptide and non-peptide agonists and antagonists of V1a, V1b and V2 vasopressin receptors are presented and the potential use of copeptin and the current and likely indications for AVP agonists and antagonists in the diagnosis and therapeutics of multiple pathological conditions is discussed.

Usefulness of copeptin as a potential biomarker in TBE

Objective: The aim of the study was to evaluate the usefulness of copeptin for differentiation of hyponatremia in the course of tick-borne encephalitis (TBE) and for being a prognostic marker of the severity of TBE.Materials and methods: One hundred and fourteen patients with TBE were included in the study. The control group consisted of 62 patients diagnosed with viral meningitis.Results: Copeptin concentration did not differ in patients with hyponatremia and normonatremia. Urinary sodium excretion to plasma copeptin (copeptin/UNa Secretion) ratio was significantly lower in Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Secretion patients than in patients with hyponatremia of other origin. Mean copeptin concentration in TBE patients was higher than in control group (VM) patients. There were no differences between patients with severe and mild course of TBE.Conclusions: Copeptin/UNa ratio may be used as a potential biomarker of SIADH in patients with TBE. Copeptin concentration is significantly higher in patients with TBE than in viral meningitis of other origin, especially in patients aged 18–34 and >49 years old. Copeptin does not differentiate TBE of mild and severe course.

Utilidad de copeptina en el diagnóstico de síndrome coronario agudo en el departamento de urgencias de un hospital de tercer nivel

ObjectivesThis study was conducted in order to evaluate the usefulness of copeptin (a stable fragment of the precursor of arginine vasopressin) in the differential diagnosis of acute chest pain of probable coronary origin. Material and methodsThe study includes 82 patients who were initially evaluated according to the protocol of a patient with suspected acute coronary syndrome (ACS) in our Emergency Department, including the determination of troponin and copeptin with specimens taken on admission (time 0) and at 6h. ResultsStatistically significant differences were observed in copeptin concentrations at time 0 among patients diagnosed with non–ST-segment elevation (NTEACS): 42.1±38.7pmol/L and non-NSTEACS patients: 15.6±21.2pmol/L (P<. 01). However, the differences did not reach statistical significance at 6h (P=.093).The analysis of the area under the ROC curve for Copeptin in NSTEACS patients at time 0 was 0.713, with a confidence interval of 95% from 0.592 to 0.834 and a significance level of P=.001. ConclusionsThe concentration of copeptin represents an additional value in the differentiation between NSTEACS patients and non-NSTEACS patients, as well as between ACS patients and patients with stable angina. The cut-off point of 10pmol/L provides the best values for sensitivity, negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR–) in the diagnosis of NSTEACS patients.

Incremental value of copeptin in suspected acute myocardial infarction very early after symptom onset.

Patients presenting very early after chest pain onset may provide a diagnostic challenge even when using a high-sensitivity cardiac troponin (hs-cTnT). We hypothesized that in these patients the incremental value of copeptin in the early diagnosis of acute myocardial infarction (AMI) may be substantial. We aimed to investigate the incremental value of copeptin in a pre-specified subgroup analysis of patients presenting with suspected AMI to the emergency department within 2 hours of symptom onset in a multicenter study. Copeptin was measured in a blinded fashion. Two independent cardiologists adjudicated the final diagnosis using all available clinical informations, including high-sensitivity cardiac troponin T (hs-cTnT). Overall, 2000 patients were enrolled, of whom 519 (26%) arrived within 2 hours of symptom onset. Of these, 102 patients (20%) had an AMI. The additional use of copeptin did not increase diagnostic accuracy as quantified by the area under the receiver-operating characteristic curve (AUC) of hs-cTnT (0.87 (95% confidence interval (CI): 0.83-0.90) for hs-cTnT alone to 0.86 (95% CI: 0.82-0.90) for the combination; p = NS). Copeptin (using 9 pmol/L as a cut-off) increased the negative predictive value (NPV) of hs-cTnT (using 14 ng/L as a cut-off) alone from 93% (95% CI: 90-95%) to 96% (95% CI: 93-98%). The NPV for the combination of hs-cTnT and copeptin was lower in patients arriving in the first 2 hours than in those arriving after 2 hours: 96% (95% CI: 93-98%) versus 99% (95% CI: 99-100%), respectively. The additional use of copeptin on top of hs-cTnT seems to lead to a small increase in NPV, but no increase in AUC. Routine use of copeptin in early presenters does not seem warranted.

Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis.

The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment.

The potential of serum copeptin as a prognostic marker of mortality in patients with sepsis, severe sepsis, or septic shock

Background The present study sought to investigate the correlation of copeptin with the severity of septic status and to analyze the usefulness of copeptin as a predictor of mortality in patients with sepsis, severe sepsis, and septic shock. Patients and methods This prospective observational study was conducted in Alexandria Main University Hospital. The participants were 60 patients who had sepsis, severe sepsis, and septic shock consecutively admitted to the internal medicine ward and the ICU from October 2014 to August 2015. All patients were subjected to full history taking, clinical examination, as well as routine laboratory workup including serum Na+, serum K+, and serum lactate and imaging parameters. Serum copeptin was measured on the first or second day of admission. APACHE II scores were assigned on the basis of the most pessimistic clinical and laboratory data obtained during the first 24 h following admission. Patients were followed up for 10 days after admission, and the 10-day mortality rate was calculated. In addition, 20 age-matched and sex-matched healthy participants were enrolled as controls. Results Measured serum copeptin was significantly increased in groups I, II, and III in comparison with the control group (P Conclusion Our data demonstrate that serum copeptin levels increase progressively with the severity of sepsis and may be considered an independent predictor of mortality in severe sepsis and septic shock with superiority of APACHE II scoring.

Copeptin, Troponin-I, Pro-BNP and hs-CRP levels in Diagnosing Acute Coronary Syndromes

Background: Chest pain is a frequent symptom patients present with to the emergency room. Copeptin, the Cterminal fragment of arginine-vasopressin, is a marker of stressful situations. Recent studies showed that normal levels of copeptin combined with a normal troponin accurately excluded the diagnosis of acute coronary syndrome (ACS). In this prospective, single center study we evaluated if negative levels of copeptin, pro-BNP and hs-CRP combined with negative troponin (cTn-I) can accurately rule out the diagnosis of ACS and also other life-threatening causes of chest pain. Results: Of 120 enrolled patients (69.2% males, median age 60 yrs), 31.7% were diagnosed with ST elevation myocardial infarction (STEMI), 17.5% with non ST‐elevation myocardial infarction (NSTEMI), 17.5% with unstable angina (USAP), 12.5% stable angina pectoris (SAP) and 20.8% normal coronary arteries (NCA). Copeptin levels were significantly higher in ACS patients with STEMI and NSTEMI than in those with other diagnoses (0.855 ± 0.279 vs. 0.516 ± 0.127, p<0.001). In the correlation analyses, copeptin and cTn-I, and copeptin and pro-BNP were positively correlated (r values 0.397; p<0.001). Diagnostic accuracy of copeptin over 0.583, had 91% sensitivity and 79% specificity the myocardial infarction (95% CI 0.86 to 0.91). Conclusions: The combined use of copeptin, pro-BNP, hs-CRP and cTn-I significantly improved the diagnostic accuracy of troponin alone both in myocardial infarctions and in other life-threatening diseases. Measurement of these markers might be therefore considered not only as a rule-out strategy but also as a warning sign of lifethreatening disease.