Higher Copeptin Levels Research Articles

Evaluating Serum Copeptin as a Promising Biomarker for Predicting Acute Ischaemic Stroke Severity: A Hospital-Based Study on Strokes.

Stroke is the second cause of mortality and the foremost leading cause of disability globally. Many potential biomarkers have been described to contribute to prognosticating the severity in the acute phase of stroke as well as help with risk stratification. Copeptin, an inactive peptide that is produced in an equimolar ratio to arginine vasopressin and adequately mirrors an individual's stress response to acute illnesses like acute ischaemic stroke as evidenced by elevated or increasing levels is being explored in this study to determine its relationship with acute stroke severity and infarct size on admission. This is a cross-sectional study of 80 neuroimaging-confirmed acute ischaemic patients who presented within seven days of symptom onset and 80 control subjects. The ischaemic stroke cases had stroke severity and infarct volume determined on admission by the National Institute of Health Stroke Scale (NIHSS) and neuroimaging (brain CT/MRI). A baseline serum copeptin level was measured in the study subjects. Spearman correlation and Kruskal Wallis test were used to determine the relationship between serum copeptin level with admission NIHSS and infarct size respectively. The receiver operating characteristic (ROC) curve was calculated to determine the sensitivity and specificity of copeptin to predict severity and outcome. The mean age of the study group was 61.3 ± 12.7 years with 55.0% males and 45.0% females. The serum level of copeptin was significantly higher in the stroke cases with a median of 28.6 pmol/L (interquartile range (IQR)- 15.4-31.6 pmol/L) versus 8.8 pmol/L (IQR- 3.2- 10.7 pmol/L) among the stroke-free controls (p= 0.001) at a statistically significant level. There was a weak correlation between copeptin and NIHSS calculated at admission to measure stroke severity (r- 0.02, p= 0.873). Patients with infarct sizes in the fourth quartile (infarct sizes greater than 18.78 cm3) had higher copeptin levels, though this was not statistically significant (H= 2.88; p= 0.410). Admission serum copeptin did not show a statistically significant prognostic value in predicting stroke severity and mortality in stroke patients who presented within seven days of symptomonset with an area under curve (AUC) of 0.51 (95% CI: 0.36-0.65; p= 0.982). In this study, copeptin was higher among the stroke cases compared with the stroke-free controls which suggests a significant prognostic value in risk stratification in the acute phase of stroke; however, this did not significantly correlate with stroke severity and thus warrants further study in this field to elucidate it's fascinating potential as a prognostic biomarker (especially in the acute period) as this may enable allocation of a better-focused therapy for stroke patients.

Association of serum copeptin and urinary uromodulin with kidney function, blood pressure and albuminuria at 6 weeks post-partum in pre-eclampsia.

Preeclampsia (PE) is associated with subsequent higher risk of cardiovascular and kidney disease. Serum copeptin, as a proxy for vasopressin, and urinary uromodulin, were associated with PE physiopathology and kidney functional mass respectively. We describe concentrations of these proteins in the post-partum period and characterize their association with persistent hypertension (HTN) or albuminuria. Patients with PE and healthy controls with uncomplicated pregnancy were prospectively included at two teaching hospitals in Switzerland. Clinical parameters along with serum copeptin and urinary uromodulin were measured at 6 weeks post-partum. PE patients were further characterized based on presence of HTN (defined as either systolic BP (SBP) ≥140 mmHg or diastolic (BP) ≥90 mmHg) or albuminuria [defined as urinary albumin to creatinine ratio (ACR) ≥3 mg/mmol]. We included 226 patients with 35 controls, 120 (62.8%) PE with persistent HTN/albuminuria and 71 (37.1%) PE without persistent HTN/albuminuria. Median serum copeptin concentration was 4.27 (2.9-6.2) pmol/L without differences between study groups (p > 0.05). Higher copeptin levels were associated with higher SBP in controls (p = 0.039), but not in PE (p > 0.05). Median urinary uromodulin concentration was 17.5 (7.8-28.7) mg/g with lower levels in PE patients as compared to healthy controls (p < 0.001), but comparable levels between PE patients with or without HTN/albuminuria (p > 0.05). Higher uromodulin levels were associated with lower albuminuria in PE as well as control patients (p = 0.040). Serum copeptin levels at 6 weeks post-partum are similar between PE patients and healthy controls and cannot distinguish between PE with or without residual kidney damage. This would argue against a significant pathophysiological role of the vasopressin pathway in mediating organ damage in the post-partum period. On the opposite, post-partum urinary uromodulin levels are markedly lower in PE patients as compared to healthy controls, potentially reflecting an increased susceptibility to vascular and kidney damage that could associate with adverse long-term cardiovascular and kidney outcomes.

Serum Copeptin Level as a Predictor of One-Year Mortality after Acute Decompensated Heart Failure Hospitalization

Background: Acutely decompensated heart failure patients have variable clinical outcomes. Some predictors of mortality in acute heart failure as resting heart rate, blood pressure, Pro-BNP level, and others have been identified. This study addresses the question whether copeptin may add value in the one-year prognosis in this category of high-risk patients. Results: To assess the relationship of serum copeptin level with one year mortality, we evaluated serum copeptin at admission and after 72 hours in 106 consecutive patients hospitalized for acute decompensated heart failure between May 2021 and November 2021 in a tertiary care hospital. Twenty-four patients (23.3%) died during the one-year follow-up period. The mortality was significantly higher in patients with advancing age, male sex, smokers, NYHA class IV heart failure, lower ejection fractions, higher heart rate, higher burden of arrhythmic events, lower creatinine clearance, and higher levels of copeptin at baseline and at day 3. Copeptin level at day 1 with cutoff value of ˃25.4 pmol/l predicted mortality with sensitivity 87.5% and specificity 70.73% [hazard ratio (95% confidence interval): (0.725 - 0.898), P&lt;0.001], while copeptin level at day 3 with cutoff value ˃ 26.1 pmol/l predicted mortality with sensitivity 100% and specificity 73.17% [hazard ratio (95% confidence interval): (0.876 - 0.981), P&lt;0.001]. Finally, increase in copeptin level from bassline was independently associated with increased mortality. (p˂0.001). Conclusions: Elevated copeptin level at baseline and 72 hours post-admission is suggested to be a strong predictor of one year mortality in patients with acute decompensated heart failure.

Copeptin is associated with microalbuminuria and renal function in the general Japanese population.

An association between copeptin (precursor molecule of arginine vasopressin) and markers for renal function has been reported, but data on the Japanese population has been limited. In this study, we investigated whether elevated copeptin levels are associated with microalbuminuria and renal dysfunction in the general Japanese population. A total of 1,262 participants (842 female and 420 male) were enrolled. Multiple regression analysis was performed to assess the association of copeptin levels (logarithm) with estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR) after adjusting for age, BMI, and lifestyle variables. Odds ratios (ORs) and 95% confidence intervals were calculated using logistic regression methods in which chronic kidney disease (CKD) was the dependent variable. The copeptin levels differed significantly with sex, but were not found to be related to age or the span of time from preceding meal to blood sampling. In female participants, copeptin level was negatively correlated with eGFR (beta = -0.100, p-value = 0.006) and positively correlated with UACR (beta = 0.099, p-value = 0.003). In male participants, a negative correlation (beta = -0.140, p-value = 0.008) was observed for eGFR. In both females and males, those with high copeptin levels had more than double the ORs of CKD (OR = 2.1-2.9) adjusted for CKD-related factors. The present study found elevated copeptin levels to be associated with renal function loss in the Japanese population and microalbuminuria in female. Moreover, it was evident that high copeptin levels are associated with CKD. These results suggest that copeptin could be considered a marker of renal function.

Association between Copeptin and Metabolic Syndrome: A Systematic Review.

Background Copeptin, a reliable marker for vasopressin release, has been associated with cardiometabolic diseases including metabolic syndrome (MetS). This systematic review aims to evaluate the association between copeptin and MetS. Methods We searched in Pubmed, Scopus, EMBASE, and Web of Science databases until March 2021 and included observational studies (cohort studies, cross-sectional, and case-control) reporting the risk or prevalence of having MetS in patients with elevated copeptin levels compared to patients without elevated copeptin levels. The risk of bias was evaluated with the Newcastle-Ottawa Scale. Meta-analysis was not performed because of the heterogeneity of the copeptin cut-off values. Results A total of 7 studies (5 cross-sectional, 1 case-control, and 1 cohort) were included comprising 11,699 participants. Most of them were performed in the adult general population. Two cross-sectional and one case-control studies found a positive significant association between higher levels of copeptin and MetS. While three cross-sectional and one cohort studies found no association. The case-control study had several methodological limitations, most cross-sectional studies were methodologically adequate and the cohort study had no methodological issues. Conclusions The association between copeptin and MetS is inconsistent. However, the arginine-vasopressin system impairment contributes to metabolic disorders, expressing plasma copeptin changes. Thus, more longitudinal studies are required to corroborate the association of copeptin and MetS.

Association of Serum Albumin and Copeptin with Early Clinical Deterioration and Instability in Community-Acquired Pneumonia.

Background: There is a paucity of data on biomarkers for the early deterioration and clinical instability of patients in community-acquired pneumonia (CAP), as treatment failure occurs in the first seven days in 90% of patients. Aim: To evaluate serum albumin and copeptin with CURB-65, PSI scoring and ATS/IDSA minor criteria for the prediction of early mortality or ICU-admission (7 days) and clinical instability after 72 h. Methods: In 100 consecutive hospitalized adult CAP patients, PSI-scores, CURB-65 scores, ATS/IDSA 2007 minor criteria, copeptin and albumin on admission were evaluated. Univariate and multivariate Cox regression analysis was performed to assess independent risk factors for early combined mortality or ICU admission. Predictive powers of albumin and copeptin were tested with ROC curves and ICU-free survival probability was tested using Kaplan−Meier analysis. Results: Albumin was lower and copeptin higher in patients with short-term adverse outcomes (p < 0.05). Cox regression analysis showed that albumin [HR (95% CI): 0.41 (0.18−0.94, p = 0.034)] and copeptin [HR (95% CI): 1.94 (1.03−3.67, p = 0.042)] were independent risk factors for early combined mortality or ICU admission (7 days). The Kaplan−Meier analysis observed that high copeptin (>27.12 ng/mL) and low albumin levels (<2.85 g/dL) had a lower (p < 0.001) survival probability. The diagnostic accuracy of albumin was better than copeptin. The inclusion of albumin and copeptin into ATS/IDSA minor criteria significantly improved their predictive power. Conclusions: Both biomarkers serum albumin and copeptin can predict early deterioration and clinical instability in hospitalized CAP patients and increase the prognostic power of the traditional clinical scoring systems.

Changes in Serum Copeptin and Sphingosine 1-Phosphate in Patients with Restenosis after Stent Implantation of Symptomatic Intracranial Artery Stenosis.

To determine the changes of serum copeptin and sphingosine 1-phosphate (S1P) in patients with restenosis after stent implantation of symptomatic intracranial artery stenosis. An observational study. Changyi people's Hospital, China, from February 2016 to November 2019. A total of 76 patients with symptomatic intracranial artery stenosis and stent implantation were divided into the restenosis group (n = 16) and the non-restenosis group (n=60) according to the intracranial artery restenosis occurred after the follow-up of 1 year. Levels of serum copeptin and S1P were compared between the groups. There were significant differences in diabetes mellitus and hypertension between the two groups (p<0.001 and p = 0.017, respectively). There were no significant differences in serum copeptin and S1P levels between the two groups before and 3 days after the operation (p = 0.927, 0.792, 0.776, and 0.906, respectively). Postoperative follow-up of one year, levels of serum copeptin in the restenosis group were higher than those in the non-restenosis group (p<0.001), and levels of serum S1P in the restenosis group were lower than those in the non-restenosis group (p = 0.003). High serum copeptin level, low serum S1P level, hypertension, and diabetes mellitus are independent risk factors promoting restenosis after stent implantation in patients with symptomatic intracranial artery stenosis. Copeptin, Sphingosine 1-phosphate (S1P), Symptomatic intracranial artery stenosis, Stent implantation, Restenosis.

Value of Copeptin Measurement as A Novel Biomarker for Prognosis in Acute Heart Failure

Abstract Background Copeptin, C-terminal segment of pro-arginine vasopressin, is expected to be a strong novel biomarker for prognosis in acute heart failure (AHF). Aim Evaluate the prognostic role of copeptin in AHF either de novo or on top of chronic heart failure and its correlation with adverse cardiac events. Methods The study included 45 patients with acute decompensated heart failure (ADHF) to assess the relationship of serum copeptin level on admission and 72 hours after admission with adverse cardiac events (death, re-hospitalization and arrhythmias) in patients hospitalized with ADHF between May 2019 and November 2019 with median follow up period 6 months. Results In this study, 15 patients died, re-admission for heart failure occurred in 22 patients and arrhythmias were documented in 14 patients with atrial fibrillation (n = 9) and ventricular arrhythmias (n = 5). Mortality rate was higher among the elderly, smokers and patients with higher heart rate, lower left ventricular ejection fraction, more frequent arrhythmias, impaired kidney function and higher copeptin level. Furthermore, copeptin level at day 1 with cutoff value of &amp;gt; 2.54 pmol/l predicted mortality with sensitivity of 86.67% and specificity of 53.33% while at day 3 copeptin level with cutoff value &amp;gt; 2.74 pmol/l predicted mortality with sensitivity of 93.33% and specificity of 83.33%. Finally, change in copeptin level between day 1 and day 3 was associated with increased mortality. (p&amp;lt;0.001) Conclusion Serum copeptin is suggested to be a strong biomarker to predict adverse clinical outcomes in patients with acute decompensated heart failure.

Peripheral Insulin Resistance Is Associated with Copeptin in Patients with Chronic Kidney Disease.

Insulin resistance is associated with cardiovascular disease risk and worsened kidney function. Patients with CKD have higher levels of insulin resistance. Elevated levels of copeptin (a surrogate for vasopressin levels) have been associated with an increased incidence and progression of CKD, and with incident diabetes mellitus. The purpose of our study was to examine the relationship between insulin resistance, copeptin, and CKD. We performed a cross-sectional study to investigate if insulin resistance was associated with higher copeptin levels in nondiabetic patients with stage 3-4 CKD versus controls. We measured plasma copeptin levels and used data from 52 patients with stage 3-4 CKD and 85 controls (eGFR ≥60 ml/min per 1.73 m2) enrolled in the Insulin Resistance in Chronic Kidney Disease (IRCKD) study. We then used a multivariable linear-regression model to assess the independent relationship between peripheral or hepatic insulin resistance and copeptin across levels of eGFR. We found that in patients with CKD (eGFR of 30-60 ml/min per 1.73 m2), but not in controls, peripheral insulin resistance was significantly correlated with higher levels of log copeptin (r=-0.21, P=0.04). In patients with CKD, when adjusted for age, sex, BMI, serum osmolality, log IL6, and log leptin/adiponectin ratio, each 1 SD decrease in insulin sensitivity was associated with a 39% increase in serum copeptin levels. The relationship between hepatic insulin resistance, copeptin, and eGFR is similar between controls and patients with reduced eGFR. Peripheral insulin resistance is associated with elevated copeptin levels in nondiabetic patients with stage 3-4 CKD. Further research into how the interaction between peripheral insulin resistance and elevated vasopressin affects CKD progression could be of interest.

Higher Copeptin Levels are Associated with the Risk of Atrial Fibrillation in Patients with Rheumatic Mitral Stenosis.

Correlations between increased copeptin levels and various cardiovascular diseases have been described. In this study, we aimed to investigate the correlation between increased copeptin levels and paroxysmal atrial fibrillation (PAF) in rheumatic mitral stenosis (MS). Patients with mild/moderate rheumatic MS and sinus rhythm were consecutively recruited from an echocardiography laboratory. Patients with a history of PAF and those with PAF on 24-48-hour ambulatory electrocardiography (ECG) monitoring constituted the study group, and those without PAF on ambulatory ECG monitoring constituted the control group. Clinical characteristics, echocardiographic parameters and levels of copeptin, plasma N-terminal proBNP (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) were evaluated. Twenty-nine patients with PAF and 124 control MS patients were studied. Patients in the PAF group were older, but the mitral valve areas and transmitral gradients were not different between the groups. In the PAF group, hs-CRP (1.2 vs. 0.8 mg/L, p < 0.001), NT-proBNP (335 vs. 115 pg/mL, p < 0.001) and copeptin (6.9 vs. 4.0 pmol/L, p < 0.001) levels were significantly higher than in the control group. Multivariable logistic regression analysis revealed that age [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.04-1.38; p = 0.024], left atrial volume index (OR 1.23, 95% CI 1.06-1.41; p = 0.032), copeptin levels (OR 2.81, 95% CI 1.30-5.29; p < 0.001) and hs-CRP levels (OR 15.5, 95% CI 1.41-71.5; p = 0.012) were independent predictors of PAF. In patients with mild/moderate rheumatic MS, higher copeptin and hs-CRP levels predicted a higher risk of developing atrial fibrillation.

Serum Copeptin Level and High-Sensitivity C-Reactive Protein in Centrally Obese Middle-Aged Male Subjects

Background and Aim: Copeptin, a surrogate marker of Arginine Vasopressin, has been recently used as stress related neuroendocrine marker. In addition, chronic psychosocial stress had an association with increased inflammatory cytokines. Moreover, obesity has been recognized as high inflammatory status. Thus, it has been generated an interest whether centrally obese with high copeptin level have higher inflammatory status comparing to those with low copeptin level or not. Methods: Eighty-seven centrally obese male subjects between 40-60 years were recruited for this study. Anthropometric measurements such as height, weight, BMI and waist circumference were measured. Blood sample was collected to measure copeptin and hsCRP. Results: 29 subjects (33.33%) had low copeptin level (&lt;5 pmol/L) and 58 subjects (66.67%) had high copeptin level (≥5 pmol/L). Median hs-CRP levels were 2.86 mg/L (IQR: 1.63-6.7) and 3.42 mg/L (IQR: 2.44-5.46) in obese with low copeptin level and obese with high copeptin level respectively. There was no significant difference in hs-CRP levels between these two study groups (p=0.7). Conclusion: In the study population of the present study, there was no correlation found between copeptin and inflammatory status.

Gender features of changes in clinical and laboratory indicators in patients with acute Q-myocardial infarction complicated by acute heart failure and hyperglycemia on admission

The aim was to determine the gender characteristics of changes in the levels of heart failure markers, neurohumoral stress and blood biochemical parameters in patients with acute Q-myocardial infarction (Q-MI) complicated by acute heart failure (AHF) and hyperglycemia (HG) on admission. Materials and methods. The study involved 84 patients with Q-MI complicated by AHF and HG on admission without a history of diabetes. The average age was 67.00 ± 1.34 years (M ± m). The patients were divided into 2 groups based on gender. Male patients made up the 1 group (n = 52), the mean age was 63.00 ± 1.56 years (M ± m). Group 2 (n = 32) included female patients, the mean age was 78.00 ± 1.81 years. The patients underwent measurements of admission blood glucose level, average glycemia during the first day, glycemic profile (GP) variability, the level of copeptin, NTproBNP, insulin, lipid profile, coagulogram, blood electrolytes, and HOMA index was calculated. On the 12th day, the patients were further examined in order to determine the cause of the HG development. Results. Men had a significantly higher level of standard deviation of HP by 33 %, and average glycemia during the first day by 14 %. There was a tendency towards higher levels of insulin and HOMA-index in male patients compared with women (2.2 times and 1.95 times, respectively). In women, the level of copeptin on day 12 was significantly higher than in men by 2.14 times, and NTproBNP by 2.09 times. In men, there was a tendency towards a decrease in these indicators during the acute period of Q-MI, and the levels of markers increased on the 12th day in women. Troponin I levels in male patients was 2 times higher compared to those in women, but not significantly. No significant differences were found in terms of coagulogram indicators. In women, the level of total cholesterol (TC) on day 1 exceeded that in men by 14 %, on day 12 – by 7 %, the level of low density lipoproteins (LDL) on day 1 – by 18 %, on day 12 – by 17 %. In a dynamic follow-up, the level of TC in men significantly decreased by 10 % (P = 0.002), and in women by 16 % (P &lt; 0.001). The LDL level in men decreased by 17 % (P &lt; 0.001), and in women by 18 % (P &lt; 0.001). Conclusions. The men with acute Q-MI complicated by AHF and HG on admission had significantly higher mean levels of glycemia (by 14 %) and standard deviation of HF during the first day of treatment (by 33 %) as compared to women, and also they showed the tendency to higher levels of troponin I, insulin and HOMA index. Female patients with acute Q-MI complicated by AHF and HG on admission, were found to have significantly higher levels of copeptin (2.14 times) and NTproBNP (2.09 times) on day 12, higher levels of TC and LDL on day 1 (GC by 14 %, LDL by 18 %) and on day 12 (GC by 7 %, LDL by 17 %), but they had better dynamics of the decrease in lipid profile indicators during treatment compared with that in men. Coagulogram indices did not differ significantly depending on the patient gender.

Activation of Vasopressin System During COVID-19 is Associated With Adverse Clinical Outcomes: An Observational Study.

BackgroundActivation of the vasopressin system plays a key role for the maintenance of osmotic, cardiovascular, and stress hormone homeostasis during disease. We investigated levels of copeptin, the C-terminal segment of the vasopressin prohormone, that mirrors the production rate of vasopressin in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsWe measured levels of copeptin on admission and after days 3/4, 5/6, and 7/8 in 74 consecutive hospitalized adult COVID-19 patients and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and acute or chronic bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality.ResultsMedian admission copeptin levels in COVID-19 patients were almost 4-fold higher in nonsurvivors compared with survivors (49.4 pmol/L [iterquartile range (IQR) 24.9–68.9 pmol/L] vs 13.5 pmol/L [IQR 7.0–26.7 pmol/L]), resulting in an age- and gender-adjusted odds ratio of 7.0 (95% confidence interval [CI] 1.2–40.3), p < 0.03 for mortality. Higher copeptin levels in nonsurvivors persisted during the short-term follow-up. Compared with the control group patients with acute/chronic bronchitis and pneumonia, COVID-19 patients did not have higher admission copeptin levels.ConclusionsA pronounced activation of the vasopressin system in COVID-19 patients is associated with an adverse clinical course in COVID-19 patients. This finding, however, is not unique to COVID-19 but similar to other types of respiratory infections.

Copeptin levels predict left ventricular systolic function in STEMI patients: A 2D speckle tracking echocardiography-based prospective observational study.

In the present study, we aimed to investigate whether copeptin values on admission are related to left ventricle (LV) systolic function and its improvement at 6 months in ST-segment elevation myocardial infarction (STEMI) patients.In this single-center, prospective observational study, we included 122 STEMI patients from January 2016 to November 2016. LV systolic functions in the form of global longitudinal strain (GLS) in addition to conventional echocardiography parameters were evaluated on admission and at 6-month. Serum copeptin levels were determined using an ultrasensitive immunofluorescence assay.The study population was divided into 2 groups according to median values of copeptin. GLS was significantly lower in patients with high copeptin levels compared to those with low copeptin levels at early stage and 6-month (−16% (16–16.5) vs −15% (15–15.5), P < .001 and −18% (18–19) vs −16% (16–16.25), P < .001, respectively). Copeptin values were negatively correlated with an early and 6-month GLS (r = –0.459 at early stage and r = –0.662 at 6-month). In addition, we observed that copeptin values were negatively correlated with the improvement of GLS at 6-month follow-up (r = −0.458, P < .001 and r = −0.357, P = .005, respectively).Serum copeptin levels in STEMI patients at the time of admission may predict early and 6-month LV systolic function assessed by two-dimensional GLS. To the best of our knowledge, this study is the first to specifically address the relationship between copeptin values and GLS in STEMI patients.

Sex-based differences of copeptin for early rule-out of non-ST-elevation myocardial infarction

Abstract Objective There is paucity of data on the role of sex in the dual biomarker strategy using copeptin and conventional troponin for the early rule-out of non-ST-elevation myocardial infarction (NSTEMI). We aimed to evaluate sex-based differences on copeptin levels, combined negative predictive value (NPV) and predictors of copeptin elevation at admission. Methods Biomarkers were measured in 852 adult patients presenting to the emergency department with chest pain and suspected NSTEMI. Logistic regression analyses on predictors of copeptin elevation were evaluated by sex. Results Overall, 362 women (42.5%) and 490 men (57.5%) were included. Copeptin levels were higher in men (median 7.36 pmol/L vs. 4.8 pmol/L; P&amp;lt;0.001). Men had a similar NPV (100%) as women (99.6%, CI: 98.8–100) using the dual biomarker rule-out strategy and when compared to troponin alone (men, NPV=98.7%, CI: 97.5–99.8; and women, NPV=98.7%, CI: 97.5–100). Multivariate logistic regression showed positive association of male sex with copeptin elevation (OR=2.37; CI: 1.61–3.49; P&amp;lt;0.001). In men, diastolic blood pressure was a negative predictor of copeptin elevation (OR=0.98, 95% CI: 0.96–0.99), while positive predictors were current MI (OR=2.16, 95% CI: 1.19–3.91), chronic renal insufficiency (OR=3.58, 95% CI: 1.33–9.62), and atrial fibrillation (OR=2.56, 95% CI: 1.23–5.32), respectively (all P&amp;lt;0.05). In women, current MI (OR=2.98, CI: 1.23–7.24), atrial fibrillation (OR=2.90, CI: 1.26–6.70) and syncope (OR=7.56, CI: 2.26–25.30) were significant predictors of copeptin elevation. Conclusions Men with suspected NSTEMI have higher copeptin levels. The dual biomarker rule-out strategy has a similar performance in both male and female patients. Certain predictors of copeptin elevation are sex-specific. Copeptin levels at presentation Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria

Regulation and role of arginine vasopressin in myocardial infarction/reperfusion

Abstract Background Little attention is paid to the coronary microvasculature when treating acute myocardial infarction (MI). Microvascular obstruction contributes to ischaemia-reperfusion (I-R) injury. One proposed mechanism is a persistent vasoconstrictor tone during MI/reperfusion. Arginine vasopressin (AVP) has a vasoactive effect on the coronary microvessels. Moreover, cardiac AVP synthesis was found in an animal model. To exert vasoconstriction, AVP binds to its receptor 1a (AVPR1a). Aims (i) To analyse the AVP levels during MI/reperfusion (ii) To assess cardiac AVP and AVPR1a expressions in MI/reperfusion mouse models. Methods We took arterial blood samples from ST elevation MI (STEMI) patients admitted to our hospital over the course of MI/reperfusion for AVP levels quantification. We also measured AVP through its more stable surrogate biomarker, copeptin. Cardiac MRI was done to evaluate coronary microvasculature, infarct size, and left ventricular ejection fraction (LVEF) 1 week post-admission. Cardiac AVP and AVPR1a expressions were assessed by polymerase chain reaction (PCR) in mouse models. Results STEMI patients displayed bothAVPand copeptinlevels elevation at baseline (130.8±20.5 pmol/l, n=23) until 90 min post-reperfusion (55.7±6.2 pmol/l, n=23). Their concentrations began to approach normal levels at 24h. Patients with poorer reperfusion outcomes had copeptin concentrations that remained above normal level after 24h following reperfusion. Copeptin levels at 24h post-reperfusion were significantly higher in patients who developed larger infarct size (p=0.004) and lower LVEF (p=0.009). Patients with microvascular obstruction tended to have higher copeptin levels from admission until 24h post-reperfusion. Mouse models showed no cardiac AVP expression but significantly high AVPR1a expression at 2h post-reperfusion. Conclusion In STEMI patients, circulating AVP level is elevated over the course of MI/reperfusion. In MI/reperfusion mouse models, cardiac AVP synthesis is absent but cardiac AVPR1a is upregulated. The combination of delayed decline in AVP concentrations and AVPR1a upregulation may increase the possibility for AVP to mediate I-R injury through microvascular disturbance. Increased AVP levels at 24h post-reperfusion are significantly associated with poor reperfusion outcome. These results warrant further studies concerning the use of AVP receptor antagonist in STEMI patients undergoing reperfusion therapy Copeptin levels and reperfusion outcomes Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Newcastle University MRes Programme

The Stress Hormone Copeptin as a Prognostic Biomarker in Acute Illness

Background: Copeptin has been evaluated as biomarker for several illnesses such as cerebrovascular stroke, heart failure, showing a promising role mainly as a prognostic biomarker. Copeptin levels seem to be strongly related to short, mid, and long-term mortality in patients admitted to hospital showing that copeptin could be a valuable prognostic tool in the most frequent disease entities. Objective: The aim of the current study was to study the level of copeptin as a prognostic biomarker in acute illness. Patients and Methods: This study included a total of 64 patients with acute deterioration of their chronic illness as chronic liver diseases (most of them were child C on Child-Pugh score), COPD (admitted with infective exacerbation), cerebrovascular stroke and Decompensate heart failure and 20 controls, attending at emergency room, Ain Shames University Hospital. Results: Serum copeptin levels have positive correlation with longer duration of hospitalization, the higher the copeptin level the more length of hospital stay (r= 0.264* p= 0.035). There was highly statistically significant difference between copeptin level and survival rate, copeptin concentrations were significantly higher in non- survivors than in survivors (p=0.000).The mean of copeptin level among patient who died was 500 ) pmol/L with range of 70 to 750 pmol/L, while the mean of copeptin level among survivors was 60 pmol/L with range of 20-600 pmol/L. Conclusion: It could be concluded that copeptin has a role in prognosis of mortality and morbidity of hospitalized patients and high copeptin level significantly associated with a longer hospital stay and a poor outcome of hospital admission.

Is there an association between sarcoidosis and atherosclerosis?

Sarcoidosis is a multisystemic chronic inflammatory disease that the specific etiology is not known clearly. The aim of this study is, to investigate the presence of subclinical atherosclerosis and endothelial dysfunction by using carotid intima-media thickness and flow-mediated dilatation measurements, measuring the copeptin values, which is a stress marker, and interpreting the association of copeptin values with these two variables in sarcoidosis patients without conventional risk factors for coronary artery disease. Seventy-four patients (50 f, 24m) with histopathological diagnosis of sarcoidosis and 60 healthy volunteers (35 f, 25m) with similar sociodemographic characteristics were included in this study. CIMT, FMD, and serum copeptin levels of all participants were measured. The values of CIMT and Copeptin in sarcoidosis patients were significantly higher (p = 0.001, p < 0.001 respectively), and FMD was significantly lower (p = 0.01) than the control group. In sarcoidosis patients not significant correlation found among CIMT with copeptin (r: 0.16, p = 0.18) and FMD with copeptin (r: 0.01, p = 0.96). With the demonstration of the presence of subclinical atherosclerosis and endothelial dysfunction, we suggest; sarcoidosis patients may be followed more closely in terms of cardiovascular diseases. And new studies are needed to investigate the pathophysiology and the effects of high copeptin levels in sarcoidosis patients.

Gender-based differences of copeptin alone or combined with troponin for early rule-out of non-ST-elevation myocardial infarction.

Little is known about the role of gender in the dual biomarker strategy using copeptin and troponin for the early rule-out of non-ST-elevation myocardial infarction (NSTEMI). We aimed to evaluate gender-based differences on copeptin levels, combined negative predictive value (NPV) and predictors of copeptin elevation at admission. Biomarkers were measured in 852 adult patients presenting to the emergency department with chest pain and suspected NSTEMI. Logistic regression analyses on predictors of copeptin elevation were evaluated by gender. Overall, 362 women (42.5%) and 490 men (57.5%) were included. Copeptin levels were higher in men (median 7.36pmol/L vs. 4.8pmol/L; P<.001). Men had a similar NPV (100%) as women (99.6%, CI: 98.8-100) using the dual biomarker rule-out strategy and when compared to troponin alone (men, NPV=98.7%, CI: 97.5-99.8; and women, NPV=98.7%, CI: 97.5-100). Multivariate logistic regression showed positive association of male gender with copeptin elevation (OR=2.37; CI: 1.61-3.49; P<.001). In men, diastolic blood pressure was a negative predictor of copeptin elevation (OR=0.98, 95% CI: 0.96-0.99), while positive predictors were current MI (OR=2.16, 95% CI: 1.19-3.91), chronic renal insufficiency (OR=3.58, 95% CI: 1.33-9.62), and atrial fibrillation (OR=2.56, 95% CI: 1.23-5.32), respectively (all P<.05). In women, current MI (OR=2.98, CI: 1.23-7.24), atrial fibrillation (OR=2.90, CI: 1.26-6.70) and syncope-like events (OR=7.56, CI: 2.26-25.30) were significant predictors of copeptin elevation. Men with suspected NSTEMI have higher copeptin levels. The dual biomarker rule-out strategy has a similar performance in both male and female patients. Certain predictors of copeptin elevation are gender-specific.

Prognostic performance of copeptin among patients with acute decompensated heart failure

Background In heart failure (HF), various biomarkers have been established for prognosis. However, little is known about the relevance of copeptin measurements to HF. This study aimed to explore the prognostic value of copeptin for predicting cardiovascular (CV) death or HF-related re-hospitalisation in patients with acute decompensated HF. Materials and Methods We prospectively enrolled 155 consecutive patients with acute signs and symptoms of HF. Plasma copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at admission. Patients were monitored for 90 days regarding the composite endpoint of CV death or acute HF-related re-hospitalisation. Results Of the 155 patients enrolled, 40 reached the endpoint, and 115 were in a stable condition during follow-up. Patients who reached an adverse endpoint showed higher NT-proBNP and copeptin levels compared to patients in stable condition. Receiver operating characteristic curve analysis revealed that the area under curve of copeptin 0.844 (95% CI, 0.753–0.935) was superior to that of NT-proBNP 0.809 (95% CI, 0.729–0.890) for the prediction of adverse events within 90 days. Meanwhile, compared to the group with lower copeptin levels (<34 pmol/L), patients with higher copeptin levels (≥34 pmol/L) were at a 10.672-times higher risk of CV death or acute HF-related re-hospitalisation. Multivariate Cox proportional hazards regression analysis revealed that increased copeptin level was a significantly independent predictor of adverse events (risk ratio, 1.051; 95% CI, 1.020–1.083; p < 0.001). Conclusion Copeptin was found to be a strong, novel marker for predicting CV death or HF-related re-hospitalisation in patients with acute decompensated HF.