[Usefulness of copeptin in discarding non-ST elevation acute myocardial infarction in patients with acute chest pain and negative first troponin I]. / Valor de la copeptina para la exclusión del infarto agudo de miocardio sin elevación del segmento ST en pacientes con dolor torácico y primera troponina negativa.

AIM: To evaluate the usefulness of copeptin as a rapid and reliable marker for discarding non-ST elevation acute myocardial infarction (NSTEMI) in patients attended in an Emergency Care Department due to acute chest pain with a normal or non-diagnostic electrocardiogram and a negative first troponin I result. DESIGN: A prospective observational study was carried out. SETTING: The Emergency Care Department of a university hospital. PATIENTS: The study comprised a total of 97 patients attended in the Emergency Care Department due to chest pain suggestive of acute coronary syndrome with an evolution of under 12h, a non-diagnostic electrocardiogram and a negative first troponin I result. INTERVENTIONS: None. VARIABLES OF INTEREST: Patient demographic data and baseline characteristics, copeptin upon admission, troponin I upon admission and after 6h, and final diagnosis. RESULTS: The final diagnosis was NSTEMI in 14 patients (14.4%) -no significant differences in copeptin concentration being observed between the 2 groups, though a tendency towards higher values was recorded in the NSTEMI group (median: 24.6pmol/l [interquartile range: 42.0] vs. 12.0pmol/l [16.1]; P=.06). The AUC ROC for copeptin upon admission was 0.657 (95%CI: 0.504-0.810), with a negative predictive value of 92% for a cutoff point of 14pmol/l. CONCLUSIONS: Copeptin determination upon admission to the Emergency Care Department in patients with chest pain for ≤12h, suggestive of acute coronary syndrome, with a non-diagnostic electrocardiogram and a negative first troponin I determination does not allow rapid and reliable exclusion of the presence of NSTEMI. Serial troponin I measurements are needed in this respect.

[Implications of arginine-vasopressin and copeptin in normal gestation and in pre-eclampsia]. / Implicaciones de la arginina-vasopresina y de la copeptina en la gestación normal y en la preeclampsia.

Preeclampsia represents a specific complication of pregnancy hypertension, which appears de novo after the 20th week of gestation, accompanied by proteinuria and/or maternal or utero-placental organ dysfunction. Despite an uncertain etiopathogenesis, impaired vascular remodeling of the spiral artery and placental ischemia is the most widespread hypothesis. The finding of elevated levels of copeptin in women with preeclampsia compared to normal pregnant women has valued the involvement of arginine vasopressin in the etiopathogenesis of this complication. In this paper, its usefulness as a marker of preeclampsia is considered through the review of the main studies carried out with this molecule.

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

OBJECTIVE: The aim of this study was to investigate the predictive value of copeptin levels in the development of contrast-induced nephropathy (CIN). METHODS: A 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. RESULTS: Copeptin 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. CONCLUSION: Copeptin 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.

[Combined high-sensitivity copeptin and troponin T evaluation for the diagnosis of non-ST elevation acute coronary syndrome in the emergency department]. / Evaluación de una estrategia diagnóstica combinada con copeptina y troponina T ultrasensibles en el infarto de miocardio sin elevación del segmento ST en los servicios de urgencias.

OBJECTIVES: To assess the diagnostic yield of a high-sensitivity copeptin (hs-copep) assay alone or in combination with a high-sensitivity cardiac troponin T (hs-cTnt) assay for the diagnosis of non-ST segment elevation acute coronary syndrome (NSTEMI) in patients with chest pain in the emergency department (ED). The secondary aim was to assess the 1-year prognostic utility of these biomarkers in this clinical context. MATERIAL AND METHODS: Retrospective observational study of a series of patients attended for chest pain suggesting myocardial ischemia in 5 Spanish ED. The first blood drawn in the ED was used for hs-copep and hs-cTnt assays, which were processed in a single laboratory serving all centers. Diagnostic utility was assessed by sensitivity, specificity, positive and negative predictive values and likelihood ratios, and the area under the receiver operating characteristic curve (ROC). We also performed a separate analysis with data for the subgroup of patients with early detection of symptoms (3 h of onset of symptoms). We recorded complications, mortality or reinfarction occurring within a year of the index event. RESULTS: We included 297 patients; 63 (21.2%) with NSTEMI. The median age was 69 years (interquartile range, 70-76 years), and 199 (67%) were men. The ROC was 0.89 (95% CI, 0.85-0.94) for the hs-cTnt assay, 0.58 (95% CI, 0.51-0.66) for the hscopep assay, and 0.90 (95% CI, 0.86-0.94) for the 2 assays combined. The ROC for the 2 assays combined was not significantly better than the ROC for the hs-cTnt by itself (P=.89). We saw the same pattern of results when we analyzed the subgroup of patients who presented early. Sixty percent of the complications occurred in patients with elevated findings on both assays. Elevated hs-copep findings did not provide prognostic information that was not already provided by hs-cTnt findings (P=.56). CONCLUSION: The hs-copep assay does not increase the diagnostic or prognostic yield already provided by the hs-cTnt assay in patients suspected of myocardial infarction in the ED.

OBJETIVO: Estudio fue evaluar la capacidad diagnóstica de la copeptina de elevada sensibilidad (copep-es), de forma aislada o conjuntamente con troponina cardiaca T de elevada sensibilidad (Tnc T-es), en el diagnóstico de infarto agudo de miocardio sin elevación del segmento ST (IAMSEST) en los pacientes atendidos por dolor torácico con sospecha de infarto de miocardio en los servicios de urgencias (SU), y seguidamente la capacidad pronóstica a los 12 meses. METODO: Estudio observacional retrospectivo de una serie de pacientes atendidos por dolor torácico sugestivo de isquemia miocárdica en 5 SU españoles. Se midieron centralizadamente copep-es y Tnc T-es en la primera muestra sanguínea extraída a la llegada al SU. El rendimiento diagnóstico se evaluó mediante la sensibilidad, la especificidad, los valores predictivos, las razones de verosimilitud, y el área bajo la curva (ABC) de la característica operativa del receptor (COR). Se realizó un análisis separado en el subgrupo de pacientes con presentación precoz (< 3 h desde el inicio de los síntomas). Se registraron las complicaciones, mortalidad o reinfarto, ocurridas a los 12 meses desde el evento índice. RESULTADOS: Se incluyeron 297 pacientes. Se diagnosticaron 63 (21,2%) IAMSEST. La mediana de edad fue 69 (RIC 70- 76) y 199 (67%) fueron varones. Las ABC COR fueron 0,89 (IC 95% 0,85-0,94) para Tnc T-es, 0,58 (IC 95% 0,51- 0,66) para copep-es y 0,90 (IC 95% 0,86-0,94) para la determinación conjunta. El ABC COR de la medida conjunta no mejoró a la de Tnc T-es aislada (p = 0,89). El análisis de los pacientes con presentación precoz mostró el mismo patrón de resultados. Un 60% de las complicaciones ocurrió en los pacientes con ambos biomarcadores elevados. Los incrementos aislados de copep-es no aportaron información pronóstica adicional a la proporcionada por Tnc T-es (p = 0,56). CONCLUSIONES: La medida de copep-es no mejora el valor diagnóstico o pronóstico de la Tnc T-es en los pacientes con sospecha de IAMSEST atendidos en los SU.

[Usefulness of copeptin in the diagnosis of acute coronary syndrome in the emergency department of a tertiary hospital]. / Utilidad de copeptina en el diagnóstico de síndrome coronario agudo en el departamento de urgencias de un hospital de tercer nivel.

OBJECTIVES: This 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 METHODS: The 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. RESULTS: Statistically 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. CONCLUSIONS: The 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.

[High levels of atrial natriuretic peptide and copeptin and mortality risk]. / Asociación de valores elevados de péptido natriurético auricular y copeptina con riesgo de mortalidad.

OBJECTIVE: To determine whether high levels of mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin, and procalcitonin (PCT) plasma concentrations are associated with increased mortality risk. METHODS: Prospective observational study including 254 critically ill children. MR-proANP, copeptin and PCT were compared between children with high (Group A; n=33) and low (Group B; n=221) mortality risk, and between patients with failure of more than 1 organ (Group 1; n=71) and less than 2 (Group 2; n=183). RESULTS: Median (range) of MR-proANP, copeptin, and PCT levels in group A vs B were, respectively: 209.4 (30.5-1415.8) vs. 75.0 (14.6-867.2) pmol/L (P<.001); 104.4 (7.4-460.9) vs. 26.6 (0.00-613.1) pmol/L (P<.001), and 7.8 (0.3-552.0) vs. 0.3 (0.02-107.0) ng/mL (P<.001). The area under the curve (AUC) for the differentiation of group A and B was 0.764 (95% CI: 0.674-0.854) for MR-proANP; 0.735 (0.642-0.827) for copeptin, and 0.842 (0.744-0.941) for PCT, with no statistical differences. The AUCs for the differentiation of group 1 and 2 were: 0.837 (0.784-0.891) for MR-proANP, 0.735 (0.666-0.804) for copeptin, and 0.804 (0.715-0.892) for PCT, with statistical differences between MR-proANP and copeptin, P=.01. CONCLUSIONS: High levels of MR-proANP, copeptin and PCT were associated with increased mortality risk scores. MR-proANP showed a higher association than copeptin with number of organs in failure.

Implicaciones de la arginina-vasopresina y de la copeptina en la gestación normal y en la preeclampsia / Implications of arginine-vasopressin and copeptin in normal gestation and in pre-eclampsia

La preeclampsia representa una complicación específica de hipertensión del embarazo, que aparece de novo después de la 20 semana de gestación, acompañada de proteinuria y/o disfunción orgánica materna o útero-placentaria. A pesar de una etiopatogenia incierta, la alteración en el remodelado vascular de la arteria espiral e isquemia placentaria es la hipótesis más generalizada. El hallazgo de niveles elevados de copeptina, en mujeres con preeclampsia respecto a gestantes normales, ha puesto en valor la implicación de la arginina-vasopresina en la etiopatogenia de esta complicación. En este trabajo se considera su utilidad como marcador de preeclampsia a través de la revisión de los principales estudios efectuados con esta molécula.(AU)

Preeclampsia represents a specific complication of pregnancy hypertension, which appears de novo after the 20th week of gestation, accompanied by proteinuria and/or maternal or utero-placental organ dysfunction. Despite an uncertain etiopathogenesis, impaired vascular remodeling of the spiral artery and placental ischemia is the most widespread hypothesis. The finding of elevated levels of copeptin in women with preeclampsia compared to normal pregnant women has valued the involvement of arginine vasopressin in the etiopathogenesis of this complication. In this paper, its usefulness as a marker of preeclampsia is considered through the review of the main studies carried out with this molecule.(AU)

Estratificación de riesgo de muerte a 28 días en pacientes con infarto agudo de miocardio con base en sus concentraciones séricas de copeptina / Early death risk stratification in post-myocardial infarction patients based on plasma copeptin levels

Resumen: ANTECEDENTES: la copeptina es un biomarcador reciente que ha demostrado su utilidad en el diagnóstico temprano de pacientes con infarto agudo de miocardio; sin embargo, no se ha establecido su utilidad en el pronóstico de la supervivencia a corto plazo en estos pacientes. OBJETIVO: determinar el valor pronóstico de la copeptina en la predicción de muerte temprana (28 días) en pacientes posinfarto agudo de miocardio. MATERIAL Y MÉTODO: estudio prospectivo, observacional, realizado del 1 de enero de 2014 al 30 de septiembre de 2015 en una cohorte de pacientes con infarto agudo de miocardio, en el que se cuantificó la copeptina sérica inicial y se analizó la mortalidad en 28 días, ajustada con factores de riesgo conocidos. RESULTADOS: se incluyeron 34 pacientes que se clasificaron en riesgo bajo si tenían concentraciones séricas de copeptina iniciales ≤ 12 pmol/L; en riesgo intermedio entre 12.1 y 32.5 pmol/L y en riesgo alto ≥ 32.5 pmol/L, con mortalidad de 0, 15 y 30%, respectivamente. Se encontró una razón de riesgos entre altos y bajos ajustado a factores de confusión de 15.9 (intervalo de confianza a 95% [IC95%] de 1.3 a 190; p = 0.02 por análisis multivariable de regresión de Cox). CONCLUSIONES: la elevación de copeptina está directamente relacionada con el riesgo de muerte temprana en pacientes posinfarto agudo de miocardio y puede usarse como marcador de pronóstico.

Abstract: BACKGROUND: Copeptin is a novel biomarker that has demonstrated good diagnostic performance in the early diagnosis of patients with acute coronary syndrome; however, its prognostic performance in the short-term survival (28 days) has not been established. OBJECTIVE: To determine the prognostic performance of copeptin for 28 day-mortality in patients with acute coronary syndrome. MATERIAL AND METHOD: A prospective, observational cohort of patients with acute coronary syndrome was done from January 1st 2014 to November 30 2015, measuring copeptin at presentation, registering deaths and event-free survivors over 28 days. RESULTS: Thirty-four patients were included, stratified as having low risk of death if copeptin was ≤ 12 pmol/L, intermediate risk between 12.1 and 32.5 pmol/L, and high risk ≥ 32.5 pmol/L, with a mortality of 0%, 15% and 30%, respectively; hazard ratio between high and low adjusted to confuse factors of 15.9 (CI95% 1.3-190; p = 0.02, Cox multivariable regression model). CONCLUSION: Elevated concentrations of copeptin are directly proportional to a higher risk of all-cause mortality, hence it could be used as a prognostic marker.