Galectin-3 is independently associated with cardiovascular mortality in community-dwelling older adults without known cardiovascular disease: The Rancho Bernardo Study

Abstract

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. Our aim was to determine the association between galectin-3 levels and all-cause and CVD mortality in community-dwelling older adults without known CVD.

Methods: We measured plasma galectin-3 levels in 1,393 Rancho Bernardo Study participants without CVD with a mean age of 70 years. Participants were followed up for a mean of 11 years for coronary heart disease, CVD mortality, and all-cause 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, 1.01-1.24), but not coronary heart disease (HR 1.09, 0.92-1.30). After further adjusting for N-terminal pro B-type natriuretic peptide, galectin-3 remained an independent predictor (HR 1.24, 1.05-1.47) of CVD mortality. Galectin-3 improved the c statistic (0.847-0.851, P = .003) for prediction of CVD death. Net reclassification improvement (>0) with the addition of galectin-3 was 35% (P < .0001); the integrated discrimination index was also significant (P = .03). Participants with both galectin-3 and N-terminal pro B-type natriuretic peptide above the median had increased risk of CVD death vs those with higher levels of only 1 of these markers (HR 1.74, 1.24-2.43).

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.

Figure 1

Flowchart showing which Rancho Bernardo Study participants were included in the present analyses.

Figure 2

Cumulative incidence of all-cause (A) and cardiovascular (B) mortality by sex-specific quartile of Gal-3. Cut-points for men were as follows: ≤10.6 ng/mL, 10.7 to 13.7 ng/mL, 13.8 to 17.4 ng/mL, and ≥17.5 ng/mL. Cut-points for women were as follows: ≤12.0 ng/ mL, 12.1 to 15.2 ng/mL, 15.3 to 19.8 ng/mL, and ≥19.9 ng/mL.

Figure 3

Forest plot of adjusted HR and 95% CI for the risk of death per 1-SD increase in log₁₀ units of Gal-3. All HRs are adjusted for age, sex (except for the sex subgroup analysis), current smoking, hypertension, systolic blood pressure, total cholesterol, HDL, GFR (except for the GFR subgroup analysis), and BMI.