Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-Atrial Fibrillation Trial
JOURNAL OF INTERNAL MEDICINE
Authors: Latini, R.; Masson, S.; Pirelli, S.; Barlera, S.; Pulitano, G.; Carbonieri, E.; Gulizia, M.; Vago, T.; Favero, C.; Zdunek, D.; Struck, J.; Staszewsky, L.; Maggioni, A. P.; Franzosi, M. G.; Disertori, M.
Abstract
Latini R, Masson S, Pirelli S, Barlera S, Pulitano G, Carbonieri E, Gulizia M, Vago T, Favero C, Zdunek D, Struck J, Staszewsky L, Maggioni AP, Franzosi MG, Disertori M on the behalf of the GISSI-AF Investigators (Istituto di Ricerche Farmacologiche "Mario Negri", Milan; Istituti Ospitalieri, Cremona; POL Madonna della Consolazione, Reggio Calabria; Ospedale Nuovo Girolimo Fracastoro, San Bonifacio; Ospedale Garibaldi-Nesima, Catania; Ospedale Luigi Sacco, Milan, Italy; Roche Diagnostics, Rotkreuz, Switzerland; B.R.A.H.M.S. AG, Henningsdorf, Germany; ANMCO Research Center, Florence; and Ospedale Santa Chiara, Trento, Italy). Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-Atrial Fibrillation Trial. J Intern Med 2011; 269: 160-171. Objective. We evaluated the prognostic role of circulating cardiovascular biomarkers in patients with a history of recent atrial fibrillation (AF). Background. Predicting long-term maintenance of sinus rhythm in patients with AF is difficult. Methods. Plasma concentrations of three specific cardiac markers [high-sensitivity troponin T (hsTnT), N-terminal probrain natriuretic peptide (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP)] and three stable fragments of vasoactive peptides [mid-regional proadrenomedullin (MR-proADM), copeptin (CT-proAVP) and CT-proendothelin-1 (CT-proET-1)] were measured at baseline and after 6 and 12 months in 382 patients enrolled in the GISSI-AF study, a prospective randomized trial to determine the effect of valsartan to reduce the recurrence of AF. The association between these markers, clinical characteristics and recurrence of AF was tested by univariate and multivariate Cox models. Results. Mean patient age was 68 +/- 9 years (37.2% females). A total of 84.8% of patients had a history of hypertension. In total, 59.7% qualified for history of AF because of successful cardioversion, 11.8% because of two or more episodes of AF in the 6 months preceding randomization and 28.5% because of both. Patients in AF at 6 or 12 months (203 (53.1%) with first recurrence) had significantly higher concentrations of most biomarkers. Despite low baseline levels, higher concentrations of hsTnT {adjusted hazard ratio (HR) [95% confidence intervals (CIs) for 1 SD increment] (1.15 [1.04-1.28], P = 0.007), MR-proANP (1.15 [1.01-1.30], P = 0.04), NT-proBNP (1.24 [1.11-1.39], P = 0.0001) and CT-proET-1 (1.16 [1.01-1.33], P = 0.03) independently predicted higher risk of a first recurrence of AF. Changes over time of MR-proANP tended to predict subsequent recurrence (adjusted HR [95%CI]) (1.53 [0.98-2.37], P = 0.06). Conclusion. Circulating markers of cardiomyocyte injury/strain and endothelin are related to recurrence of AF in patients in sinus rhythm with a history of recent AF.
Reference intervals and longitudinal changes in copeptin and MR-proADM concentrations during pregnancy
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
Authors: Joosen, Annemiek M. C. P.; van der Linden, Ivon J. M.; Schrauwen, Lianne; Theeuwes, Alisia; de Groot, Monique J. M.; Ermens, Antonius A. M.
Abstract
Background: Vasopressin and adrenomedullin and their stable by-products copeptin and midregional part of proadrenomedullin (MR-proADM) are promising biomarkers for the development of preeclampsia. However, clinical use is hampered by the lack of trimester-specific reference intervals. We therefore estimated reference intervals for copeptin and MR-proADM in disease-free Dutch women throughout pregnancy. Methods: Apparently healthy low risk pregnant women were recruited. Exclusion criteria included current or past history of endocrine disease, multiple pregnancy, use of medication known to influence thyroid function and current pregnancy as a result of hormonal stimulation. Women who miscarried, developed hyperemesis gravidarum, hypertension, pre-eclampsia, hemolysis elevated liver enzymes and low platelets, diabetes or other disease, delivered prematurely or had a small for gestational age neonate were excluded from analyses. Blood samples were collected at 9-13 weeks (n = 98), 27-29 weeks (n = 94) and 36-39 weeks (n = 91) of gestation and at 4-13 weeks post-partum (PP) (n = 89). Sixty-two women had complete data during pregnancy and PP. All analyses were performed on a Kryptor compact plus. Results: Copeptin increases during pregnancy, but 97.5th percentiles remain below the non-pregnant upper reference limit (URL) provided by the manufacturer. MRproADM concentrations increase as well during pregnancy. In trimesters 2 and 3 the 97.5th percentiles are over three times the non-pregnant URL provided by the manufacturer. Conclusions: Trimester-and assay-specific reference intervals for copeptin and MR-proADM should be used. In addition, consecutive measurements and the time frame between measurements should be considered as the differences seen with or in advance of preeclampsia can be expected to be relatively small compared to the reference intervals.