Galectin-3 binding protein, coronary artery disease and cardiovascular mortality: Insights from the LURIC study. (May 2017)

• Record Type: Journal Article
• Authors: Gleissner, Christian A.; Erbel, Christian; Linden, Fabian; Domschke, Gabriele; Akhavanpoor, Mohammadreza; Helmes, Christian M.; Doesch, Andreas O.; Kleber, Marcus E.; Katus, Hugo A.; Maerz, Winfried
• Is Part Of: Atherosclerosis. Volume 260(2017)
• Page Start: 121
• Page End: 129
• Publication Date: 2017-05
• Subjects: Atherosclerosis -- Coronary artery disease -- Inflammation -- Biomarker; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2017.03.031
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: 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. Methods: 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 . Results: 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 (HRQ5 1.292 (1.030–1.620), p = 0.027); cardiovascular mortality remained increased in Gal-3BP quintiles two to five (HRQ5 1.433 (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). Conclusions: 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. Highlights: In 2922 LURIC patients, Gal-3BP levels were independently associated with mortality. Gal-3BP levels were not associated with diagnosis or extent of cardiovascular disease. Gal-3BP levels were associated with markers of inflammatory and metabolic distress. Gal-3BP induced a pro-inflammatory phenotype in human macrophage in vitro. Gal-3BP levels improved risk assessment in patients with ESC SCORE-based risk >5%.