Galectin-3 Is Associated With Risk of Cardiovascular and Kidney Outcomes in Ambulatory Veterans

Abstract

Rationale & Objective

Cardiovascular and kidney disease are highly prevalent comorbid conditions, and each is a risk factor for the other condition. We evaluated whether Galectin-3 (Gal-3), a biomarker of organ fibrosis, is associated with cardiovascular and kidney events in ambulatory Veterans.

Study Design

An observational cohort study.

Setting & Participants

Ambulatory Veterans presenting for an outpatient echocardiogram at the San Diego Veterans Affairs between 2010 and 2013.

Predictor

Blood Gal-3 levels.

Outcomes

The primary cardiovascular outcome was major adverse cardiac events (MACEs: acute coronary syndrome [ACS], stroke, heart failure [HF] hospitalization, or cardiovascular death). The primary kidney outcome was major adverse kidney events (MAKEs: ≥40% estimated glomerular filtration rate decrease or renal replacement therapy). Secondary outcomes were cardiovascular death, incident HF, ACS, and all-cause mortality.

Analytical Approach

Cox proportional hazard models adjusting for cardiovascular and kidney disease risk factors.

Results

A total of 882 Veterans with an average age of 66 ± 12 years, 97% were men, average eGFR of 78 ± 20 mL/min/1.73 m², 40% prevalence of coronary artery disease, and 17% prevalence of HF. Higher Gal-3 was associated with a greater risk of MACEs (hazard ratio [HR], 1.54 per 2-fold higher Gal-3; 95% confidence interval [CI], 1.02-2.32; P = 0.04), cardiovascular death (HR, 3.41; 95% CI, 1.75-6.66; P < 0.001), and all-cause mortality (HR, 1.81; 95% CI, 1.41-2.33; P < 0.001), but not incident HF or ACS. Higher Gal-3 was associated with a greater risk of MAKEs (HR, 1.92; 95% CI, 1.20-3.08; P = 0.004). Higher Gal-3 was associated with >350% greater risk of experiencing both MACEs and MAKEs during follow-up (HR, 3.57; 95% CI, 1.63-7.84; P = 0.002).

Limitations

Select population of Veterans presenting for an echocardiogram who were primarily older men with multiple comorbid conditions.

Conclusions

Gal-3 is associated with risk of cardiovascular and kidney outcomes among ambulatory Veterans.

Plain Language Summary

Galectin-3 is a biomarker of organ fibrosis and has been associated with risk of cardiovascular and kidney outcomes individually, but its association with both outcomes is less well described. We assessed whether Galectin-3 was associated with risk of cardiovascular and kidney events in 882 ambulatory Veterans with 13 years of follow-up. We found that Galectin-3 was associated with risk for major adverse cardiac events (acute coronary syndrome, stroke, cardiovascular death, or heart failure hospitalization) and major kidney events (need for renal replacement therapy or ≥40% decrease in estimated glomerular filtration rate), even when adjusting for cardiovascular and kidney disease risk factors. These findings suggest Galectin-3 may help identify individuals at risk for cardiovascular and kidney events earlier.