Higher Copeptin Levels Research Articles

Assessment of stress markers in restrained individuals following physical stress with and without sham CED activation

IntroductionLaw enforcement and pre-hospital care personnel often confront individuals who must be physically restrained. Many are under the influence of illicit substances, and law enforcement officers may need to use a controlled electrical device (CED) to gain control of the individual and they are often placed into the prone maximum restraint (PMR) position. These techniques have previously been evaluated for their physiologic effects. The purpose of this study was to investigate the psychological effects of anticipating and experiencing a sham CED activation in healthy human subjects who were exercised and restrained compared with no sham activation by assessing the differences in a panel of several known biomarkers of stress. MethodsWe performed a randomized, crossover controlled human subject trial to study the stress associated with exercise, physical exhaustion, and restraint with and without an added psychological stress simulating the field use of a CED. Twenty five total subjects; each subject performed two different trials each consisting of a brief period of intense exercise on a treadmill to exhaustion followed by placement in the PMR with and without induced psychological stress. Blood samples were collected for analysis pre and post exercise, as well as 10 min after completion of the exercise. A panel of hormones and stress markers were measured. ResultsWe found no significant differences in any of the stress biomarkers measured between the two study groups. A trend towards higher levels of copeptin was measured in the sham CED activation arm. ConclusionDuring a brief period of intense exercise followed by the psychological stress of anticipated CED application, there did not appear to be statistically significant changes in the stress panel of biomarkers measured, only a trend towards significance for higher copeptin levels in the patients exposed to the psychological stress.

Serum Copeptin, NLPR3, and suPAR Levels among Patients with Autosomal-Dominant Polycystic Kidney Disease with and without Impaired Renal Function

Background: The pathophysiology of renal disease progression in autosomal-dominant polycystic kidney disease (ADPKD) involves not only cystogenesis but also endothelial dysfunction, leading to the activation of inflammatory and fibrotic pathways. This study evaluated the levels of biomarkers related to osmoregulation, immune system activation, and tubular injury in ADPKD patients with impaired or preserved renal function. Methods: This study included 26 ADPKD patients with modestly impaired renal function (estimated glomerular filtration rate [eGFR] 45–70 mL/min/1.73 m²; Group A), 26 age- and sex-matched ADPKD patients with relatively preserved renal function (eGFR >70 mL/min/1.73 m²; Group B), and 26 age- and sex-matched controls (Group C). Serum levels of copeptin, the inflammasome nucleotide-binding and oligomerization domain-like receptors pyrin domain-containing protein 3 (NLRP3), and soluble urokinase-type plasminogen activator receptor (suPAR) were measured with ELISA techniques. Results: Patients in Group A had higher levels of copeptin (median [interquartile range]: 50.44 [334.85] pg/mL), NLRP3 (5.86 [3.89] ng/mL), and suPAR (390.05 [476.53] pg/mL) compared to patients in Group B (32.38 [58.33], p = 0.042; 2.42 [1.96], p < 0.001; and 313.78 [178.85], p = 0.035, respectively) and Group C (6.75 [6.43]; 1.09 [0.56]; and 198.30 [28.53], respectively; p < 0.001 for all comparisons). Levels of all studied markers were also significantly higher in Group B patients compared to controls (p < 0.001), despite having similar eGFR. In patients with ADPKD, all studied biomarkers were correlated positively with asymmetric-dimethylarginine (ADMA) and endocan levels, and negatively with eGFR. ADMA and endocan levels were the only parameters independently associated with increased copeptin levels. Conclusions: This study showed that ADPKD patients with impaired and preserved renal function had higher copeptin, NLRP3, and suPAR levels than controls. Such findings support that cystogenesis and inflammation are associated with endothelial dysfunction, even in the early stages of ADKPD.

Association between copeptin and contrast-induced nephropathy in patients with ST-elevation myocardial infarction

ObjectiveThe aim of this study was to investigate the predictive value of copeptin levels in the development of contrast-induced nephropathy (CIN). MethodsA total of 274 patients diagnosed with ST-elevation myocardial infarction (STEMI) and who had undergone primary percutaneous coronary intervention were included in the study. The patients were divided into two groups according to the presence (CIN+) or absence (CIN-) of CIN. These groups were compared in terms of demographic characteristics, laboratory findings and risk factors. ResultsCopeptin levels (10.68±6.43 vs. 7.07±05.53 pmol/l; p<0.001) and peak creatinine (1.46±1.20 vs. 1.03±0.20 mg/dl; p=0.005) were significantly higher in the CIN+ group than in the CIN- group. Female gender was significantly more prevalent in the CIN- group compared to the CIN+ group (19% vs. 8.6%; p<0.05). Copeptin level at hospital admission (OR: 2.36, p=0.005) was found to be an independent predictor for CIN development. ConclusionCopeptin level is an independent predictor of CIN development in patients with acute STEMI that can be detected rapidly and easily. This result indicates that physicians should be aware of the possibility of CIN development in patients with high copeptin levels and preventive measures should start early.

Relationship between serum Copeptin level and severity outcome in patients with ischemic stroke: A meta-analysis

Copeptin is a c-terminal part of a neuroendocrine marker provasopressin. Literature survey suggests that plasma Copeptin level is associated with functional outcome and mortality in patients with acute stroke. It has emerged as a novel prognostic biomarker for predicting stroke outcome. The aim of the study was to quantitatively assess the prognostic significance of effect of Copeptin levels on patient survival using a meta-analysis approach. A literature survey was performed for published studies in stroke for the respective biomarker till 2017 using databases like Pubmed, Medline, Google scholar and OVID. The keyword search used was: “COPEPTIN” AND “PROGNOSIS” OR “OUTCOME” OR “MORTALITY” AND “BRAIN STROKE” OR “CEREBRAL INFARCTION”. Random effect model was used since heterogeneity was more than 50% otherwise fixed effect model could be used. A total of 13 studies from 2009 to March 2019 involving 2780 subjects were included in the present meta-analysis. The mean age of the subjects was 61.7 years. The pooled results suggested that the plasma Copeptin level was significantly higher in the subjects who died compared to those who survived brain stroke at the end of the last follow-up. Standardized mean difference (SMD 1.55; 95% CI, 1.11-1.99), p-value<0.0001 Finding of the meta-analysis is suggestive of high plasma Copeptin level being a contributing factor for predicting mortality rate in patients with acute stroke. Further prospective studies are required to validate the findings observed in this meta-analysis.

İzole Koroner Ektazide Kopeptin Düzeyi

Introduction: The level of copeptin was investigated in patients who underwent coronary angiography for suspected coronary artery disease and diagnosed with isolated coronary artery ectasia (CAE). Patients and Methods: A total of 308 patients were diagnosed as having coronary ectasia out of 3412 patients who underwent coronary angiography between May 2015 and July 2016. The evaluations were performed by two experienced physicians who were aware of the study design. Among these patients, 41 patients who did not have severe coronary artery disease (CAD) and who were diagnosed as having isolated CAE were included in the study. The control group comprised 33 age- and gender-matched individuals diagnosed as having normal coronary arteries following coronary angiography for suspected CAD. Patients with a previous coronary revascularization for severe CAD, known congestive heart disease and severe cardiac valve disease, and a left ventricular ejection fraction below 50% were excluded from the study. Blood samples were obtained from both groups and the serum copeptin levels were compared with each other. Results: Among patients with CAE, the frequency of isolated CAE was 14.9%. Among the total coronary angiography series, the frequency of isolated CAE was 1.34%. Most patients with isolated CAE were men (70%; women: 30%), and the mean age of the patients was 58 ± 9.2 years. In patients with isolated CAE, the frequencies of type I, type II, type III, and type IV CAE were found to be 4.3%, 17.4%, 32.6%, and 45.6%, respectively, according to Markis classification. The level of copeptin was found to be 7.8 ± 0.9 pmol/L in patients with normal coronary arteries and 9.7 ± 1.6 pmol/L in patients with isolated CAE (p< 0.028). Conclusion: The level of copeptin is increased in patients with isolated CAE. However, our results have to be supported by long-term randomized studies on isolated CAE patients with and high copeptin levels.

Serum Copeptin Levels Predict Clinical Outcomes After Successful Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction.

BackgroundSerum copeptin has been demonstrated to be useful in early risk stratification and prognostication of patients with acute myocardial infarction (AMI). However, the prognostic value of copeptin after percutaneous coronary intervention (PCI) for clinical outcomes remains uncertain. We investigated the prognostic role of serum copeptin levels immediately after successful PCI as a prognostic marker for major adverse cardiac events (MACE; comprising death, repeat PCI, recurrent MI, or coronary artery bypass grafting) in patients with AMI.MethodsA retrospective study was performed in 149 patients with AMI who successfully received PCI. Serum copeptin levels were analyzed in blood samples collected immediately after PCI. The association between copeptin levels and MACE during the follow-up period was evaluated.ResultsMACE occurred in 34 (22.8%) patients during a median follow-up of 30.1 months. MACE patients had higher copeptin levels than non-MACE patients did. Multiple logistic regression analysis showed that the increase in serum copeptin levels was associated with increased MACE incidence (odds ratio=1.6, P=0.005).ConclusionsA high level of serum copeptin measured immediately after PCI was associated with MACE in patients with AMI during long-term follow-up. Serum copeptin levels can serve as a prognostic marker in patients with AMI after successful PCI.

Plasma copeptin and chronic kidney disease risk in 3 European cohorts from the general population.

The prevalence of chronic kidney disease (CKD) is increasing worldwide. The identification of factors contributing to its progression is important for designing preventive measures. Previous studies have suggested that chronically high vasopressin is deleterious to renal function. Here, we evaluated the association of plasma copeptin, a surrogate of vasopressin, with the incidence of CKD in the general population. We studied 3 European cohorts: DESIR (n = 5,047; France), MDCS-CC (n = 3,643; Sweden), and PREVEND (n = 7,684; the Netherlands). Median follow-up was 8.5, 16.5, and 11.3 years, respectively. Pooled data were analyzed at an individual level for 4 endpoints during follow-up: incidence of stage 3 CKD (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2); the KDIGO criterion "certain drop in eGFR"; rapid kidney function decline (eGFR slope steeper than -3 ml/min/1.73 m2/yr); and incidence of microalbuminuria. The upper tertile of plasma copeptin was significantly and independently associated with a 49% higher risk for stage 3 CKD (P < 0.0001); a 64% higher risk for kidney function decline, as defined by the KDIGO criterion (P < 0.0001); a 79% higher risk for rapid kidney function decline (P < 0.0001); and a 24% higher risk for microalbuminuria (P = 0.008). High copeptin levels are associated with the development and the progression of CKD in the general population. Intervention studies are needed to assess the potential beneficial effect on kidney health in the general population of reducing vasopressin secretion or action. INSERM and Danone Research Centre for Specialized Nutrition.

Copeptin Plasma Levels are Associated with Decline of Renal Function in Patients with Type 2 Diabetes Mellitus

Chronic kidney disease (CKD) is a leading complication of type 2 diabetes mellitus (T2DM) and is considered as a public health problem. Copeptin is a surrogate marker of arginine vasopressin (AVP) system and is proposed as a biomarker of decline renal function. Evaluate whether plasma copeptin levels may be used as a biomarker of decline renal function in patients with T2DM. A total of 480 patients with T2DM and different stages of CKD were included. Plasma levels of copeptin, cystatin-C, and other biochemical parameters were measured. The correlation between copeptin and glomerular filtration rate (GFR), estimated based on plasma cystatin-C levels, was investigated. Plasma copeptin levels were gradually increased from the stage 1-5 of CKD in the patients with T2DM. In univariate linear regression analysis, high plasma levels of copeptin were associated with lower GFR (Standardized β=-0.535, R2=0.287, p<0.0001). This association remained significant even after being adjusted for glucose levels and years of T2DM diagnosis, mean blood pressure, pharmacological treatment, gender, and age. The results show that high plasma copeptin levels are associated with the decline of renal function in patients with T2DM and, therefore, copeptin may be considered as a biomarker of renal function. Further evaluation of plasma copeptin levels to predict morbidity and mortality of T2DM patients, with or without CKD, has been taken into our consideration.

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.

Are Markers of Cardiac Dysfunction Useful in the Assessment of Cardiovascular Risk in Dialysis Patients?

Cardiovascular morbidity and mortality of dialysis patients are major problems in this group of patients. The purpose of this study was also to evaluate whether any of the studied markers are better than troponin in early detection of the occurrence of ventricular arrhythmias and prolongation of QT interval. This study included 45 patients undergoing hemodialysis. ECG Holter and echocardiographic examination were performed before and after dialysis. The concentrations of markers: copeptin, GDF-15, HFABP and troponin were measured with the use of ELISA tests. We observed significantly higher QT (p=0.004), QTc (0.018), right atrium volume (p=0.006) and concentrations of copeptin (p<0.0001) and H-FABP (p<0.0001) as well as smaller left atrium volume (p<0.0001) and width of inferior vena cava (p<0.0001) after dialysis than before it. Significantly longer QT and higher copeptin levels were seen in patients with ventricular arrhythmia. A trend between the increase in copeptin concentration and H-FABP level and the presence of ventricular arrhythmias was also noted. Generally, we failed to find any strong predictor of post-dialysis ventricular arrhythmia or the prolongation of QT, however, it seems that copeptin may have prognostic value, but this has to be analyzed in large studies.

Association of Stress Biomarkers With 30-Day Unplanned Readmission and Death.

The theory that posthospitalization stress might increase the risk of postdischarge complications has never been investigated. To assess whether serum levels of stress biomarkers at discharge are associated with readmission and death after an acute-care hospitalization. We prospectively included 346 patients aged ≥50 years admitted to the department of general internal medicine at a large community hospital between April 8, 2013 and September 23, 2013. We measured the serum levels of several biomarkers at discharge: midregional pro-adrenomedullin, copeptin, cortisol, and prolactin. All patients were followed for up to 90 days after discharge (none was lost to follow-up). The main outcome was first unplanned readmission or death within 30 days after hospital discharge. We assessed the additional value of biomarkers to 2 validated readmission prediction scores: the LACE index (Length of stay, Admission Acuity, Charlson Comorbidity Index, and number of Emergency department visits within preceding 6 months) and the HOSPITAL score (Hemoglobin level at discharge, discharge from Oncology service, Sodium level at discharge, any Procedure performed during index hospitalization, Index admission Type, number of Admissions within preceding 12 months, and Length of stay). Forty patients (11.6%) had a 30-day unplanned readmission or death. High serum copeptin and cortisol levels were associated with an increase in the odds of unplanned readmission or death (odds ratios [95% confidence interval] 2.69 [1.29-5.64] and 3.43 [1.36, 8.65], respectively). We found no significant association with midregional pro-adrenomedullin or prolactin. Furthermore, these stress biomarkers increased the performance of two readmission prediction scores (LACE index and HOSPITAL score). High serum levels of copeptin and cortisol at discharge were independently associated with 30-day unplanned readmission or death, supporting a possible negative effect of hospitalization stress during the postdischarge period. Stress biomarkers improved the performance of prediction models and therefore could help better identify high-risk patients.

Predictive value of plasma copeptin level for the risk and mortality of heart failure: a meta-analysis.

Epidemiologic studies are inconsistent regarding the association between plasma copeptin level and heart failure (HF). The aim of this study was to perform a meta‐analysis to determine whether high level of copeptin is correlated with incidence of HF and mortality in patients with HF. We searched PUBMED and EMBASE databases for studies conducted from 1966 through May 2016 to identify studies reporting hazard ratio (HR) estimates with 95% confidence intervals (CIs) for the association between plasma copeptin level and HF. A random‐effects model was used to combine study‐specific risk estimates. A total of 13 studies were included in the meta‐analysis, with five studies on the incidence of HF and eight studies on the mortality of patients with HF. For incidence of HF, the summary HR indicated a borderline positive association of high plasma copeptin level with HF risk (HR, 1.60; 95% CI, 0.90–2.85). Furthermore, an increase of 1 standard deviation in log copeptin level was associated with a 17% increase in the risk of incident HF (HR, 1.17; 95% CI, 1.02–1.33). For all‐cause mortality of patients with HF, we also found a significant association between elevated plasma copeptin level and increased mortality of HF (HR, 1.76; 95% CI, 1.33–2.33). Our dose–response analysis indicated that an increment in copeptin level of 1 pmol/l was associated with a 3% increase in all‐cause mortality (HR, 1.03; 95% CI, 1.01–1.05). In conclusion, our results suggest that elevated plasma copeptin level is associated with an increased risk of HF and all‐cause mortality in patients with HF.

Hypernatremia and Copeptin Levels in the Elderly Hospitalized Patient

Elderly patients have a high prevalence of hypernatremia. The aim of this study was to determine demographic and clinical characteristics of the elderly hypernatremic patient hospitalized in the internal medicine ward and to enhance understanding of the role of antidiuretic hormone (ADH) secretion in the pathogenesis of hypernatremia. Case-control study performed in an internal medicine ward in a university-affiliated hospital. Thirtythree elderly hypernatremic patients (admission sodium, >150 mEq/L; age, >70 years) were compared with 34 normonatremic patients. Demographic, functional (mental status and activities of daily living), clinical data (Acute Physiology and Chronic Health Evaluation [APACHE] II score), and serum copeptin levels as a marker of ADH secretion, were collected at admission. Mortality and change in the functional status were followed up to 30 days from discharge. Patients with hypernatremia presented with significantly lower baseline functional and cognitive states and higher APACHE II score (21.3 ± 8.6 vs. 15.4 ± 6.7; P<.01). Mortality within 30 days after discharge was higher in the hypernatremic group (58% vs. 32%; P<.05). Higher copeptin levels were found in the hypernatremic group compared to the normonatremic group (100.2 ± 60.6 pmol/L vs. 66.5 ± 57.2 pmol/L; P<.05). High levels of copeptin were associated with higher in-hospital (P<.05) and 30-day (P<.01) mortality. Sodium levels were found correlated with copeptin levels; yet, an even stronger correlation was found between copeptin levels and APACHE II score (r = 0.52; P<.001). Hypernatremia in the elderly at admission is associated with a high mortality rate. Copeptin level in the elderly seems to be a good single disease severity marker. ADH is strongly secreted in elderly hypernatremic patients. ADH = antidiuretic hormone APACHE = Acute Physiology and Chronic Health Evaluation.

Copeptin as a biomarker for prediction of prognosis of acute ischemic stroke and transient ischemic attack: a meta-analysis.

This meta-analysis aimed to investigate the predictive effect of copeptin as a biomarker for the prognosis of acute ischemic stroke and transient ischemic attack. Electronic databases including PubMed, Medline, EMBASE, Web of Science and Cochrane Central were searched for studies assessing the association of copeptin level on admission with prognosis of acute ischemic stroke and transient ischemic attack. The Newcastle-Ottawa Quality assessment scale for cohort study was used to evaluate quality. A total of 1976 acute ischemic stroke patients from 6 studies were included, and 59% of patients were male. Patients with poor outcomes and nonsurvivors had a higher copeptin level at admission (P<0.0001). Copeptin combined with an admission National Institutes of Health Stroke Scale score significantly improved the discriminatory accuracy of functional outcome and mortality compared with the National Institutes of Health Stroke Scale alone. Elevation in plasma copeptin level carried a higher risk of all-cause mortality (odds ratio=4.16; 95% CI: 2.77-6.25) and poor functional outcome (odds ratio=2.56; 95% CI: 1.97-3.32) after acute ischemic stroke. In addition, copeptin improved the prognostic value of the ABCD2 (age, blood pressure, clinical features of transient ischemic attack, duration of symptoms and presence of diabetes mellitus) score for a recurrent cerebrovascular event in transient ischemic attack. Copeptin seems to be a promising independent biomarker for predicting the functional outcome and all-cause mortality within 3 months or 1 year after acute ischemic stroke, and it could also be a powerful tool for early risk stratification for patients with transient ischemic attack.

Higher copeptin levels are associated with worse outcome in patients with hypertrophic cardiomyopathy.

Correlation of increased copeptin levels with various cardiovascular diseases has been described. The clinical use of copeptin levels in patients with hypertrophic cardiomyopathy (HCM) has not been investigated before. In this study, we aimed to investigate the prognostic value of copeptin levels in patients with hypertrophic cardiomyopathy (HCM). HCM was defined as presence of left ventricular wall thickness ≥15 mm in a subject without any concomitant disease that may cause left ventricular hypertrophy. Levels of copeptin and plasma N-terminal probrain natriuretic peptide (NT-proBNP) were evaluated prospectively in 24 obstructive HCM patients, 36 nonobstructive HCM patients, and 36 age- and sex-matched control subjects. Blood samples were collected in the morning between 7 and 9 am after overnight fasting. Patients were followed for 24 months. Hospitalization with diagnosis of heart failure/arrhythmia, implantable cardioverter-defibrillator implantation, and cardiac mortality were accepted as adverse cardiac events. Copeptin and NT-proBNP levels were higher in the HCM group compared with controls (14.1 vs 8.4 pmol/L, P < 0.01; and 383 vs 44 pg/mL, P < 0.01, respectively). Copeptin and NT-proBNP levels were higher in the obstructive HCM subgroup compared with the nonobstructive HCM subgroup (18.3 vs 13.1 pmol/L, P < 0.01; and 717 vs 223 pg/mL, P < 0.01, respectively). In multivariable logistic regression analysis, copeptin and NT-proBNP levels remained as independent predictors of heart failure (P < 0.01 for both) and adverse cardiac events (P < 0.01 for both). Copeptin and NT-proBNP levels were significantly higher in patients with obstructive HCM, and higher levels were associated with worse outcome.

Plasma copeptin in children and adolescents with type 1 diabetes mellitus in comparison to healthy controls

In a cohort of children and adolescents with type 1 diabetes mellitus the trial tested the hypothesis that copeptin levels are associated with kidney function, biometrical data and quality of diabetes control. Patients and methodsA total of 141 subjects were recruited to participate in the trial: 80 patients with type 1 diabetes (13.0±3.4years, HbA1c 7.85±1.42%) and 61 healthy controls (12.4±2.8years). Clinical and socio-economic data were assessed. A sandwich immunoassay (B.R.A.H.M.S. GmbH/Thermo Fisher Scientific, Hennigsdorf/Berlin, Germany) was used for measuring plasma copeptin levels. ResultsThe mean concentration of copeptin in the diabetic patients was 4.75±3.46pmol/l. There was a strong inverse correlation between copeptin and GFR (r=−0.86, p=0.021), as well as with total cholesterol (r=−0.23, p=0.041), LDL-cholesterol (r=−0.24, p=0.036), but not with serum creatinine, albuminuria, HbA1c, blood glucose, MAGE, CRP, systolic or diastolic blood pressure or age, diabetes duration, weight, height and BMI. Comparing patients with a diabetes duration of ⩾7years (n=45) with those with a diabetes duration <7years (n=35), patients with a longer duration of diabetes had higher copeptin levels (5.24±2.26 vs 4.13±2.86, p=0.045). Performing multivariate analyses only GFR could be identified as a parameter associated with copeptin (R-square=0.05, β=−0.23, p=0.032). In the healthy controls mean copeptin concentration was 5.56±3.15pmol/l. The copeptin concentration and GFR were inversely correlated as well (r=−0.61, p=0.034). However, other correlation and multivariate analyses revealed no further significant results. Comparing patients with type 1 diabetes mellitus with the healthy controls, the diabetes patients revealed no significant difference with respect to copeptin (p=0.24), serum creatinine (49.8±11.9 vs 50.4±11.0μmol/l, p=0.53) or GFR (102.4±23.3 vs 104.5±19.1ml/min, p=0.47). On the other hand, patients with type 1 diabetes had lower concentrations of CRP (1.66±3.91 vs 3.21±3.04μg/ml, p=0,013), triglycerides (0.88±0.53 vs 1.13±0.60mmol/l, p=0.010), and a lower ratio of LDL-/HLD-cholesterol (1.73±0.69 vs 2.32±0.80, p<0.001), as well as lower body weight (51.3±18.0 vs 60.3±15.7kg, p=0.002) and BMI (19.7±3.8 vs 23.2±2.9kg/m2, p<0.001). In contrast to the controls, the diabetes patients had higher blood glucose levels at the time of examination (8.2±3.8 vs 4.7±0.5mmol/l, p<0.001), higher HDL-cholesterol levels (1.59±0.34 vs 1.26±0.24mmol/l, p<0.001), as well as higher education and higher educational levels of the mothers. ConclusionsThe present trial revealed a clear association between GFR and copeptin in children and adolescents with type 1 diabetes mellitus. Hence, copeptin can be considered as a marker of renal function.

Copeptin and the risk of incident stroke, CHD and cardiovascular mortality in older men with and without diabetes: The British Regional Heart Study.

Aims/hypothesisThis study aimed to examine the association between copeptin (a surrogate marker of arginine vasopressin) and incident stroke, CHD and cardiovascular mortality in older men with and without diabetes.MethodsWe conducted a prospective study of 3536 men aged 60–79 years who were followed for an average of 13 years. During this period, there were 437 major CHD events (fatal and non-fatal myocardial infarction [MI]), 323 stroke events (fatal and non-fatal) and 497 cardiovascular disease (CVD) deaths. Prevalent diabetes was defined on the basis of a history of doctor-diagnosed diabetes or fasting blood glucose ≥7.0 mmol or HbA1c ≥6.5% (48 mmol/mol) (n = 428).ResultsNo association was seen between copeptin and incident stroke or CVD mortality in men without diabetes after adjustment for conventional cardiovascular risk factors, renal dysfunction, and insulin and N-terminal pro B-type natriuretic peptide levels. In contrast, elevated copeptin levels were associated with an increased risk of stroke and CVD mortality in men with diabetes after these adjustments. Compared with those in the lowest tertile of copeptin, men in the top tertile had adjusted relative HRs for stroke and CVD death of 2.34 (95% CI 1.04, 5.27) and 2.21 (1.12, 4.36), respectively. The risk of stroke and CVD mortality remained increased after the exclusion of men with prevalent stroke or MI. Higher levels of copeptin were associated with increased risk of CHD in the diabetic and non-diabetic groups, but these associations were attenuated after exclusion of individuals with a previous stroke or MI.Conclusions/interpretationCopeptin was independently associated with an increased risk of incident stroke and CVD mortality in men with diabetes, but not in men without diabetes. Targeting the arginine vasopressin system might have beneficial effects on CVD mortality and stroke risk in older men with diabetes.

ENDOCRINE AND METABOLIC ALTERATIONS MAY UNDERLIE MORTALITY OF SEVERE SEPSIS AND SEPTIC SHOCK PATIENTS ADMITTED TO ICU.

The study evaluated endocrinal and metabolic response to sepsis and its applicability for the prediction of outcome of septic patients. Patients were 39 adult with severe infections and within 24 h after onset or suspected clinical tissue hypoperfusion. At enrollment patients were evaluated for acute physiology and chronic health evaluation II score (APACHE II) and Glasgow Coma Scale (GCS). Global hemodynamic parameters including systolic blood pressure (SBP), heart rate (HR) and central venous pressure (CVP) were recorded and monitored. All patients were managed at ICU due to Surviving Sepsis Campaign guidelines. ELISA estimated serum copeptin, macrophage migration inhibitory factor (MIF) and total cortisol (TC) and blood lactate levels. Study outcome was survival rate via 28 days (28-D SR) and best predictor for it. The results showed that 22 patients passed total hospital stay uneventfully for a total survival rate of 56.4%. Seventeen patients died; 10 during ICU stay and 7 during word stay. At admission serum markers levels were significantly higher in survivors and non-survivors compared to controls and in non-survivors compared to survivors. Survival showed negative significant correlation with age, high blood lactate and serum copeptin, TC and MIF levels. Survival showed positive significant correlation with SBP, CVP and urine output. ROC curve and Regression analyses defined high at admission serum copeptin and blood lactate levels as significant predictors for mortality of septic patients.

Association Between Circulating Copeptin Level and Mortality Risk in Patients with Intracerebral Hemorrhage: a Systemic Review and Meta-Analysis.

Copeptin has been identified as a biomarker of disease severity and is associated with mortality risk in several common diseases. This study sought to determine the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. PubMed, Web of Science, and Wanfang Medicine Database were searched for studies assessing the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. The pooled hazard ratio (HR) of mortality was calculated and presented with 95% confidence interval (95% CI). Data from 1332 intracerebral hemorrhage patients were derived from 9 studies. Meta-analysis showed that intracerebral hemorrhage patients with poor prognosis had much higher copeptin levels than those survivors (standardized mean difference = 1.68, 95% CI 1.26-2.11, P < 0.00001). Meta-analysis of 8 studies with HRs showed that high circulating copeptin level was associated with higher risk of mortality in patients with intracerebral hemorrhage (HR = 2.42, 95% CI 1.60-3.65, P < 0.0001). Meta-analysis of 6 studies with adjusted HRs showed that high circulating copeptin level was independently associated with higher risk of mortality in patients with intracerebral hemorrhage (HR = 1.67, 95% CI 1.26-2.22, P = 0.0003). Our study suggests that there is an obvious association between circulating copeptin level and mortality in patients with intracerebral hemorrhage. High circulating copeptin level is independently associated with higher risk of mortality in patients with intracerebral hemorrhage.

Copeptin in patients with heart failure and preserved ejection fraction: a report from the prospective KaRen-study

IntroductionUnderlying mechanisms of heart failure (HF) with preserved ejection fraction (HFPEF) remain unknown. We explored copeptin, a biomarker of the arginine vasopressin system, hypothesising that copeptin in HFPEF is elevated,...