TY - JOUR
T1 - Effect of Galectin 3 on Aldosterone-Associated Risk of Cardiovascular Mortality in Patients Undergoing Coronary Angiography
AU - Grübler, Martin Robert
AU - Delgado, Graciela
AU - Kleber, Marcus
AU - Hartaigh, Bríain
AU - de Boer, Rudolf Allert
AU - Verheyen, Nicolas
AU - Keppel, Martin
AU - Schmid, Johannes
AU - Siontis, George CM
AU - Räber, Lorenz
AU - Pieske, Burkert
AU - Pilz, Stefan
AU - Tomaschitz, Andreas
AU - März, Winfried
N1 - Funding Information:
Dr. Martin Grübler reports travel support from Amgen Inc. and Synlab Holding GmbH. Dr. März reports grants from Abbott Diagnostics, during the conduct of the study; other from Synlab Services GmbH, other from Synlab Holding GmbH, grants and personal fees from Numares GmbH, grants and personal fees from Aegerion Pharmaceuticals, grants and personal fees from AMGEN, grants and personal fees from Astrazeneca, grants and personal fees from Danone Research, grants and personal fees from Sanofi/Genzyme, personal fees from Hoffmann LaRoche, personal fees from MSD, grants and personal fees from Pfizer, personal fees from Sanofi, personal fees from Synageva, grants and personal fees from BASF, outside the submitted work. Dr. Pieske reports other from BG Medicine, outside the submitted work. Dr. de Boer reports personal fees from BG Medicine, during the conduct of the study; personal fees from Novartis, personal fees from Medcon International, grants from AstraZeneca, outside the submitted work. Dr. Andreas Tomaschitz is partially supported by the project EU-SYSVASC ([HEALTH.2013.2.4.2-1] [“Systems Biology To Identify Molecular Targets For Vascular Disease Treatment”]; Grant agreement no: 603288). All other authors have nothing to disclose. Dr. Lorenz Räber reports research contracts to the institution from St. Jude Medical/Abbott, Sanofi, and Regeneron.
Funding Information:
Funding: We are indebted to Abbott (Wiesbaden, Germany) for providing the assays for Gal-3. LURIC has received funding from the 7th Framework Program (Atheroremo, grant agreement number 201668 and RiskyCAD, grant agreement number 305739) of the European Union from the INTERREG IV Oberrhein Program (Project A28, Genetic mechanisms of cardiovascular diseases) with support from the European Regional Development Fund (ERDF) and the Wissenschaftsoffensive TMO, and from the German Ministry of Education and Research (Project e:AtheroSysMed).
Publisher Copyright:
© 2020 The Author(s)
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7/15
Y1 - 2020/7/15
N2 - Recent experimental studies have suggested that galectin-3 has an interaction with aldosterone, and modifies its adverse effects. We therefore aimed to elucidate whether the relationship between plasma aldosterone concentrations (PACs) and long-term fatal cardiovascular (CV) events would depend on plasma galectin-3 levels. A total of 2,457 patients (median age: 63.5 [interquartile range (IQR) = 56.3 to 70.6] years, 30.1% women) from the LUdwigshafen RIsk and Cardiovascular Health study, with a median follow-up of 9.9 (IQR = 8.5 to 10.7) years, were included. We tested the interaction between aldosterone and galectin-3 for CV-mortality using a multivariate Cox proportional hazard model, reporting hazard ratios (HRs) with 95% confidence intervals (95%CIs). Adjustments for multiple CV risk factors as well as medication use were included. Mean PAC was 79.0 (IQR = 48.0 to 124.0) pg/ml and there were 558 (16.8%) CV deaths. There was a significant interaction between PAC and galectin-3 (p = 0.021). When stratifying patients by the median galectin-3, there was a significant association between aldosterone and CV-mortality for those above (HR per 1 standard deviation = 1.14; 95%CI [1.01 to 1.30], p = 0.023), but not below the cut-off value (HR per 1 standard deviation = 1.00; 95%CI [0.87 to 1.15], p = 0.185). In conclusion, the current study demonstrates for the first time a modifying effect of galectin-3 on the association between aldosterone and CV-mortality risk in humans. These findings indicate that galectin-3 is an intermediate between aldosterone and adverse outcomes.
AB - Recent experimental studies have suggested that galectin-3 has an interaction with aldosterone, and modifies its adverse effects. We therefore aimed to elucidate whether the relationship between plasma aldosterone concentrations (PACs) and long-term fatal cardiovascular (CV) events would depend on plasma galectin-3 levels. A total of 2,457 patients (median age: 63.5 [interquartile range (IQR) = 56.3 to 70.6] years, 30.1% women) from the LUdwigshafen RIsk and Cardiovascular Health study, with a median follow-up of 9.9 (IQR = 8.5 to 10.7) years, were included. We tested the interaction between aldosterone and galectin-3 for CV-mortality using a multivariate Cox proportional hazard model, reporting hazard ratios (HRs) with 95% confidence intervals (95%CIs). Adjustments for multiple CV risk factors as well as medication use were included. Mean PAC was 79.0 (IQR = 48.0 to 124.0) pg/ml and there were 558 (16.8%) CV deaths. There was a significant interaction between PAC and galectin-3 (p = 0.021). When stratifying patients by the median galectin-3, there was a significant association between aldosterone and CV-mortality for those above (HR per 1 standard deviation = 1.14; 95%CI [1.01 to 1.30], p = 0.023), but not below the cut-off value (HR per 1 standard deviation = 1.00; 95%CI [0.87 to 1.15], p = 0.185). In conclusion, the current study demonstrates for the first time a modifying effect of galectin-3 on the association between aldosterone and CV-mortality risk in humans. These findings indicate that galectin-3 is an intermediate between aldosterone and adverse outcomes.
UR - http://www.scopus.com/inward/record.url?scp=85084526641&partnerID=8YFLogxK
U2 - 10.1016/j.amjcard.2020.04.017
DO - 10.1016/j.amjcard.2020.04.017
M3 - Article
C2 - 32418719
AN - SCOPUS:85084526641
VL - 127
SP - 9
EP - 15
JO - American Journal of Cardiology
JF - American Journal of Cardiology
SN - 0002-9149
ER -