Copeptin in heart failure: Associations with clinical characteristics and prognosis D. Berliner, N. Deubner, W. Fenske, S. Brenner, G. Güder, B. Allolio, R. Jahns, G. Ertl, CE. Angermann, S. Störk for the INH Study Group of the Competence Network Heart Failure Comprehensive Heart Failure Center, Würzburg, Germany Hannover Medical School, Dept. of Cardiology and Angiology, Hannover, Germany University of Würzburg, Department of Internal Medicine I, Würzburg, Germany
Disclosure of interest ThermoFisher Scientific - performed the CT-proAVP (Copeptin) measurements in a blinded fashion - was neither involved in the analysis nor the interpretation of the data
Background: Vasopressin (AVP) & Copeptin (CT-proAVP) Vasopressin (AVP) plays a pivotal role in the regulation of sodium, water homeostasis, and renal function. Synthesis of pro- AVP Hypothalamus Triggers - drop in blood pressure - change in osmotic pressure - acute stress (e.g. AMI) Cleavage Effects - stimulation of ACTH release - water retention in the kidney - vasoconstriction Transport via portal vessels Mediates ACTH release Ant. pituitary Post. pituitary Measurement - AVP: not feasible in clinical routine - CT-proAVP: stable NG Morgenthaler, Congest Heart Fail. 2010
Background: Vasopressin (AVP) & Copeptin (CT-proAVP) Diagnostic utility Copeptin has recently been shown to improve diagnosis in the setting of myocardial infarction. Prognostic utility Reichlin et al. J Am Coll Cardiol 2009;54:60-8 Keller et al. J Am Coll Cardiol 2010;55:2096-2106. Elevated Copeptin levels correlated with worse outcome in patients with heart failure (HF). Stoiser et al. Eur J Clin Invest. 2006;36:771 778. Gegenhuber et al. J Card Fail. 2007;13:42 49.
Aim of the study Investigation of associations of Copeptin with Clinical characteristics Laboratory parameters Comorbidities Outcome in the setting of HF.
Methods 926 patients of the Interdisciplinary Network Heart Failure Study (INH study) were included left ventricular ejection fraction (LVEF) 40% enrolled after best possible recompensation prior to discharge after hospitalisation for cardiac decompensation Besides comprehensive clinical assessment including ECG and echocardiography, an extensive blood testing profile was obtained. Patients underwent serial follow-up at six month intervals in our outpatients clinic or via a structured telephone interview. Follow-up time was 18 months.
Patients characteristics Age (years) 70 (61; 77) Male sex 659 (71.9%) Systolic BP (mmhg) 120 (110; 130) Diastolic BP (mmhg) 70 (60; 80) Sinus rhythm 578 (67.5%) Heart rate (bpm) 78 (66; 92) NYHA class III/IV 408 (44.5%) NT-proBNP (pg/ml) 3035 (1075; 7653) Ischemic cause of HF 460 (50.2%) LA(ES) (mm) 46 (42; 51) LVD(ED) (mm) 61 (55; 67) LVEF (%) 31 (25; 36) Copeptin (pmol/l) 20.35 (10.1; 40.6) Copeptin 12 pmol/l 279 (30.1%) Renal insufficiency (GFR < 60 ml/min) 378 (41.3%) Diabetes mellitus 319 (34.8%) Anemia 284 (31%) ACE inhibitor or AT1-Blocker 808 (88.9%) Mineralocorticoid receptor antagonist 388 (42.6%) Betablocker 765 (83.5%) Digitalis glycosides 332 (36.4%) Diuretics 791 (86.4%) Mortality at 6 months 91 (9.8%) 12 months 143 (15.4%) 18 months 185 (20.0%)
Copeptin: age and gender Age Gender p=0.535
Copeptin and severity of HF NYHA class Left ventricular ejection fraction
Copeptin and other biomarkers NT-proBNP Troponine-I High sensitivity C-reactive Protein Interleukin-6
Copeptin and renal function Glomerular filtration rate Renal insufficiency* *GFR < 60 ml/min
Copeptin and comorbidities Diabetes mellitus HbA1c
Copeptin and comorbidities No diabetes mellitus Diabetes mellitus p=0.756
Copeptin and comorbidities Anemia Depression
Associations with Copeptin Copeptin (pmol/l) 10.10 10.11 20.35 20.36 40.60 40.61 p Ischaemic cause of HF 111 (48%) 106 (46%) 117 (51%) 126 (56%) 0.002 Sodium (mmol/l) 139 (137; 142) 140 (138; 142) 139 (137; 142) 140 (138; 142) 0.42 Cortisol (µg/dl) 12.95 (9.8; 16.5) 13.75 (10.1; 17.15) 14.9 (11.8; 18.4) 17.85 (13.6; 22.2) <0.001 HbA1c (%) 5.8 (5.4; 6.4) 6.1 (5.6; 6.8) 6.2 (5.8; 6.9) 6.25 (5.8; 7.2) <0.001 Hemoglobin (g/dl) 13.8 (12.8; 14.9) 14.2 (12.6; 15.4) 13.65 (12.2; 14.85) 12.8 (11.1; 14.4) <0.001 Erythropoietin (miu/ml) 12.85 (8.2; 20.5) 12.7 (8.5; 18.2) 14.2 (8.9; 25.9) 21.2 (10.6; 38.7) <0.001 Sinus rhythm (ECG) 186 (85%) 149 (68%) 133 (64%) 110 (53%) <0.001 QRS duration (ms) 110 (94; 140) 101 (95.5; 127.5) 115 (100; 140) 110 (100; 140) 0.54 Heart rate (1/min) 75 (63; 85) 77 (67; 95) 81 (67; 95) 80 (67; 93) 0.002 LA(ES) (mm) 44 (39; 48) 46 (41; 50) 48 (43; 52) 47 (43; 53) <0.001 LVD(ED) (mm) 60 (55; 66) 60 (54; 67) 62 (55; 68) 62 (56; 67) 0.67 LVEF (%) 31 (27; 38) 33 (26; 37) 30 (23; 35) 30 (25; 35) 0.001
Prognosis Mortality (%) Copeptin <= 10.10 10.11 20.35 20.36 40.60 > 40.60 p Mortality at 180 days 9 (3.9%) 15 (6.5%) 22 (9.5%) 45 (19.5%) <0.001 360 days 16 (6.9%) 23 (10%) 35 (15.1%) 69 (29.9%) <0.001 540 days 23 (9.9%) 28 (12.2%) 45 (19.4%) 89 (38.5%) <0.001 50 40 30 20 10 0 10.10 10.11-20.35 20.36-40.60 > 40.60 Quartiles of CT-proAVP 540 days 360 days 180 days
Prognosis Copeptin measured at baseline Copeptin measured after 6 months HR 2.20 (95%CI 1.29-3.76) p=0.003 adjusted for age, sex, NYHA class, and renal function HR 3.59 (95%CI 1.11-11.62) p=0.033 adjusted for age, sex, NYHA class, and renal function
Summary Elevation of copeptin is frequent in HF patients (~70%). associated with factors and comorbidities known to adversely affect prognosis. Copeptin (pmol/l) 10,10 10,11-20,35 20,36-40,60 > 40,60 P for trend Age (years) 63 69 71 76 <0.01 NYHA class III/IV 28% 41% 49% 61% <0.01 Renal insufficiency 12% 28% 48% 78% <0.01 Diabetes mellitus 25% 34% 37% 43% <0.01 Anaemia 20% 25% 32% 48% <0.01 NT-proBNP (pg/ml) 1401 2166 4187 7864 <0.01 hs-crp (mg/l) 7.2 7.8 10.2 15.8 <0.01
Summary Elevation of copeptin is frequent in HF patients (~70%). associated with factors and comorbidities known to adversely affect prognosis. Higher levels of copeptin independently predict an increased mortality risk. The potential clinical utility of such information needs to be tested in further studies.
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