Background Galectin-3 is a marker of myocardial fibrosis that has been implicated in the pathophysiologic pathway of fibrosis; its association with all-cause and cardiovascular disease (CVD) mortality in a community-based cohort free of baseline CVD has not been reported. mortality. Results During follow-up 436 participants died (169 from CVD). In models adjusted for traditional CVD risk factors and renal function galectin-3 was a significant predictor of CVD mortality (hazard ratio [HR] per SD log increase 1.30 95 CI 1.10-1.53) and all-cause mortality (HR 1.12 1.01 but not coronary heart disease (HR 1.09 0.92 After further adjusting for N-terminal pro B-type Remogliflozin natriuretic peptide galectin-3 remained an independent predictor (HR 1.24 1.05 of CVD mortality. Galectin-3 improved the statistic (0.847-0.851 = .003) for prediction of CVD death. Net reclassification Remogliflozin improvement (>0) with the addition of galectin-3 was 35% (= .03). Participants with both galectin-3 and Remogliflozin N-terminal pro B-type natriuretic peptide above the median had increased risk of CVD death vs those with higher levels of only 1 1 of these markers (HR 1.74 1.24 Conclusion Higher levels of galectin-3 are independently associated with all-cause and CVD mortality among community-dwelling older adults with no known CVD at baseline. (Am Heart J 2014;0:1-9.e1.) Galectin-3 (Gal-3) is a member of the β-galactoside- binding lectin family of proteins and plays an important role in inflammation and fibrosis. Galectin-3 is expressed in fibroblasts endothelial cells and inflammatory cells including macrophages.1-3 In the myocardium Gal-3 is nearly undetectable in cardiomyocytes but is expressed at higher levels in cardiac fibroblasts and appears to exert a Rabbit Polyclonal to SLC9A9. profibrotic effect.1 Galectin-3 induces myocardial collagen deposition and remodeling when Remogliflozin infused into the pericardium in hypertensive rats.1 It plays a role in cardiac dysfunction via cardiac fibroblast proliferation collagen deposition and ventricular dysfunction. 1 Galectin-3 also appears to be a mediator of aldosterone-induced vascular fibrosis.4 In the setting of acute and chronic heart failure higher Gal-3 levels are associated with increased morbidity and mortality.5-9 Elevated Gal-3 levels are also associated with a higher risk of incident heart failure among patients with acute coronary syndromes.10 In contrast to what is known about Gal-3 in patients with underlying cardiovascular disease (CVD) relatively little is known about Gal-3 in the general population. Only 2 previous studies have evaluated Gal-3 in the general population. The Prevention of Renal and Vascular End-Stage Disease (PREVEND) study and the Framingham Offspring Study reported that Gal-3 levels are associated with cardiovascular risk factors as well as with all-cause mortality11 and incident heart failure.12 However neither of these studies excluded individuals with known CVD at baseline. To our knowledge no studies have reported on the association between Gal-3 levels and coronary heart disease (CHD) or mortality outcomes in apparently CVD-free individuals from the community. Because Gal-3 levels have previously been shown to be prognostic for individuals with underlying CVD we sought to evaluate whether Gal-3 levels are independently associated with CVD and mortality among older community-dwelling individuals from the Rancho Bernardo Study who were free of known CVD at baseline. Methods Study population The Rancho Bernardo Study is an ongoing prospective population-based study of the epidemiology of cardiovascular and other chronic diseases. The study began in 1972 when all adults between 30 and 80 years of age who resided in Rancho Bernardo California were invited to participate in a study of heart disease risk factors; 5 52 (82%) enrolled. Nearly all were white and middle to upper-middle class. At a follow-up study visit in 1992 to 1996 which served as the baseline visit Remogliflozin for the present analyses 1 781 of the surviving participants returned. Sufficient blood was available for measurement of Gal-3 in 98% (n = 1 742 of the participants of whom 1 393 (80%) had no history of CVD and are the focus of these analyses. was defined as a history of coronary revascularization physician-diagnosed myocardial infarction transient ischemic attack stroke or peripheral arterial disease. Four participants who were lost to follow-up immediately after their study visit were excluded from outcomes analyses (Figure 1). Medical histories and information about physical activity.