title: Galectin-3 binding protein, coronary artery disease and cardiovascular mortality: Insights from the LURIC study.
abstract: Galectin-3 binding protein (Gal-3BP) has been associated with inflammation and cancer, however, its role in coronary artery disease (CAD) and cardiovascular outcome remains unclear.
  
  
  
  Gal-3BP plasma levels were measured by ELISA in 2922 individuals from the LURIC study (62.7 ± 10.6 years, 62.7% male). All-cause and cardiovascular mortality was assessed by Kaplan-Meier analysis and Cox proportional hazards regression. Causal involvement of Gal-3BP was tested for by Mendelian randomization. Gal-3BP effects on human monocyte-derived macrophages were assessed in vitro.
  
  
  
  During 8.8 ± 3.0 years, 866 individuals died, 654 of cardiovascular causes. There was a significant increase in all-cause and cardiovascular mortality with increasing Gal-3BP quintiles. After thorough adjustment, all-cause mortality remained significantly increased in the fifth Gal-3BP quintile (HRQ51.292 (1.030-1.620), p = 0.027); cardiovascular mortality remained increased in Gal-3BP quintiles two to five (HRQ51.433 (1.061-1.935, p = 0.019). Gal-3BP levels were not associated with diagnosis and extent of coronary artery disease. In addition, Mendelian randomization did not show a direct causal relationship between Gal-3BP levels and mortality. Gal-3BP levels were, however, independently associated with markers of metabolic and inflammatory distress. In vitro, Gal-3BP induced a pro-inflammatory response in human monocyte-derived macrophages. Adding Gal-3BP levels to the ESC score improved risk assessment in patients with ESC SCORE-based risk >5% (p = 0.010).
  
  
  
  In a large clinical cohort of CAD patients, Gal-3BP levels are independently associated with all-cause and cardiovascular mortality. The underlying mechanisms may likely involve metabolic and inflammatory distress. To further evaluate the potential clinical value of Gal-3BP, prospective studies are needed.
authors.affiliation: Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg, Germany. Electronic address: christian.gleissner@med.uni-heidelberg.de.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Gleissner
authors.affiliation: Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Erbel
authors.affiliation: Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Linden
authors.affiliation: Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Domschke
authors.affiliation: Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Akhavanpoor
authors.affiliation: Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg, Germany.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Helmes
authors.affiliation: Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Doesch
authors.affiliation: Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany; Medical University of Graz, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz, Austria; Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Maerz
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000401:mortality; D002423:Cause of Death / Q000639:trends; D002478:Cells, Cultured; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005695:Galactosephosphates / Q000097:blood* / Q000235:genetics; D005786:Gene Expression Regulation; D005858:Germany / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends
chemical_list: D015415:Biomarkers; D005695:Galactosephosphates; D012333:RNA, Messenger; C097493:galactitol 3-phosphate
keywords: Atherosclerosis; Biomarker; Coronary artery disease; Inflammation