Galectin-3 binding protein, coronary artery disease and cardiovascular mortality: Insights from the LURIC study

被引:32
作者
Gleissner, Christian A. [1 ,2 ]
Erbel, Christian [1 ,2 ]
Linden, Fabian [1 ]
Domschke, Gabriele [1 ]
Akhavanpoor, Mohammadreza [1 ]
Helmes, Christian M. [1 ,2 ]
Doesch, Andreas O. [1 ]
Kleber, Marcus E. [3 ]
Katus, Hugo A. [1 ,2 ]
Maerz, Winfried [3 ,4 ,5 ]
机构
[1] Univ Heidelberg Hosp, Dept Cardiol Angiol & Pneumol, Heidelberg, Germany
[2] DZHK German Ctr Cardiovasc Res, Partner Site, Heidelberg, Germany
[3] Heidelberg Univ, Med Fac Mannheim, Med Clin Nephrol Hypertensiol Rheumatol Endocrino, Mannheim, Germany
[4] Med Univ Graz, Clin Inst, Med & Chem Lab Diagnost, Graz, Austria
[5] Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany
关键词
Atherosclerosis; Coronary artery disease; Inflammation; Biomarker; 90K MAC-2 BP; HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERM MORTALITY; BREAST-CANCER CELLS; MAC-2-BINDING PROTEIN; DENDRITIC CELL; POOR SURVIVAL; GROWTH-FACTOR; RISK; EXPRESSION;
D O I
10.1016/j.atherosclerosis.2017.03.031
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (HR(Q5)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. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:121 / 129
页数:9
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