Galecin-3 (Gal-3) is a novel beta-galactoside-binding lectin implicated in pro-fibrotic pathways that are upregulated during cardiac remodeling. Gal-3 has been associated with poor prognosis among patients with heart failure and with development of heart failure after acute coronary syndrome. In this study we sought to ascertain: 1) the cross-sectional demographic, behavioral and clinical correlates of serum levels of Gal-3, and 2) its independent predictive value for incident heart failure among 1,312 participants in The Atherosclerotic Disease, VAscular FunctioN and GenetiC Epidemiology (ADVANCE) Study whose initial presentation of coronary artery disease (CAD) between 10/2001 and 12/2003 was acute myocardial infarction (n=871; mean ± SD age; 62 ± 8 years; 23% female) or stable angina (n=441; mean ± SD age; 61 ± 8 years ; 34% female). Gal-3 was measured in frozen serum collected at the baseline examination (2002 to 2004) with the ARCHITECT assay (Abbott Diagnostics, Abbott Park, IL). Follow-up for incident heart failure using ICD-9 hospital principal discharge diagnostic codes 428, 402, 404 and 398 through 12/31/2012 resulted in 74 events (63 among AMI patients, 11 among stable angina patients). The mean ± SD Gal-3 concentration was 16.9 ± 5.3 ng/mL among AMI patients and 16.1 ± 4.4 ng/mL among stable angina patients. The significant independent correlates of Gal-3 were CAD presentation, age, gender, physical activity and estimated glomerular filtration rate (eGFR). In Cox regression with adjustment for age, gender, race and CAD presentation, each 1 SD increment of Gal-3 was associated with 1.64-fold increased hazard of heart failure (95% CI, 1.40 to 1.93; p<0.0001). After further adjustment for smoking status, activity level, alcohol intake, body mass index, LDL-C, HDL-C, triglycerides, diabetes, hypertension, hs-CRP and e-GFR, Gal-3 remained associated with incident heart failure (HR=1.44; 95% CI, 1.18 to 1.75; p=0.0003). Also in fully-adjusted analysis, and relative to quartile 1, the HRs were 1.10 (95% CI, 0.45 to 2.86) for quartile 2, 1.29 (95% CI, 0.53 to 3.11) for quartile 3 and 2.39 (95% CI, 1.06 to 5.37) for quartile 4 of Gal-3. Our results support the value of Gal-3 as a biomarker of heart failure development among patients with pre-existing CAD.
Coronary artery disease as the cause of incident heart failure in the population
