Abstract Background Galectin-3 is a multifunctional carbohydrate-binding lectin that is involved in inflammation, tissue remodeling, and fibrosis. High circulating levels of galectin-3 are associated with all-cause mortality, cardiovascular (CV) mortality, and/or major adverse CV events in patients with CV diseases such as heart failure and coronary artery disease (CAD). However, the associations of galectin-3 with non-CV mortality and cancer mortality in patients with suspected or known CAD are unknown. Methods Serum galectin-3 levels were measured in 2,418 patients with suspected or known CAD undergoing elective coronary angiography. The outcomes were all-cause death, CV death, non-CV death, cancer death, and other non-CV death. Patients were followed up over a 6-year period. Results During the follow-up, 536 (22.2%) deaths occurred, including 166 (6.9%) CV deaths, 326 (13.5%) non-CV deaths, 128 (5.3%) cancer deaths, 198 (8.2%) other non-CV deaths, and 44 (1.8%) undetermined deaths. After adjustment for potential clinical confounders (i.e., age, sex, body mass index, hypertension, dyslipidemia, diabetes, current smoker, estimated glomerular filtration rate, the Gensini score, previous myocardial infarction, previous stroke, previous heart failure hospitalization, atrial fibrillation, valvular heart disease, malignancies, anemia, antihypertensive drug use, statin use, and aspirin use) and established CV biomarkers (i.e., N-terminal pro-brain natriuretic peptide, high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein), galectin-3 levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.22; 95% confidence interval [CI], 1.13–1.31), CV death (HR, 1.16; 95% CI, 1.02–1.33), non-CV death (HR, 1.27; 95% CI, 1.15–1.40), cancer death (HR, 1.31; 95% CI, 1.07–1.61), and other non-CV death (HR, 1.30; 95% CI, 1.15–1.46). The addition of galectin-3 levels to the model with potential clinical confounders and established CV biomarkers significantly improved the prediction of all-cause death (P<0.001 for continuous net reclassification improvement [NRI], P<0.001 for integrated discrimination improvement [IDI]) and cancer death (P=0.001 for NRI, P=0.005 for IDI), but not that of CV death (P=0.601 for NRI, P= 0.708 for IDI), non-CV death (P=0.060 for NRI, P=0159 for IDI), or other non-CV death (P=0.266 for NRI, P=0.699 for IDI). Conclusions The galectin-3 level independently predicted all-cause mortality and cancer mortality in patients with suspected or known CAD.
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