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Renal function largely influences Galectin-3 prognostic value in heart failure
Elisabet Zamora1, Josep Lupón1, Marta de Antonio1
1Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Department of Medicine, Autonomous University of Barcelona, Spain.
Insights
Galectin-3 (Gal-3) levels strongly correlate with reduced kidney function in heart failure (HF) patients. This association diminishes Gal-3
Area of Science:
- Cardiology
- Nephrology
- Biomarker Research
Background:
- Galectin-3 (Gal-3) is linked to cardiac remodeling and heart failure (HF) prognosis.
- Renal function is a known prognostic indicator in HF.
- The interplay between renal insufficiency, HF, and Gal-3 requires further elucidation.
Purpose of the Study:
- To investigate the association between circulating Galectin-3 (Gal-3) and renal function in ambulatory heart failure (HF) patients.
- To determine if Gal-3 remains a significant prognostic marker for HF outcomes after accounting for renal function.
Main Methods:
- A cohort of 876 ambulatory HF patients was analyzed.
- Circulating Gal-3 levels were measured and correlated with estimated glomerular filtration rate (eGFR) using CKD-EPI and CKD-EPI-cystatin-C equations.
- Patients were stratified by eGFR levels, and Gal-3 associations with mortality were assessed before and after adjusting for renal function.
Main Results:
- Circulating Gal-3 showed a strong inverse correlation with eGFR (r = -0.64 with CKD-EPI) and a positive correlation with Cystatin-C levels (r = 0.70) after adjustments.
- Gal-3 levels significantly increased across decreasing eGFR strata (p < 0.001), independent of NYHA class and LVEF.
- While Gal-3 was associated with mortality in univariate analysis, this association lost significance after adjusting for eGFR.
Conclusions:
- Circulating Gal-3 is highly associated with impaired renal function in outpatients with heart failure.
- The prognostic value of Gal-3 for HF outcomes is significantly reduced when renal function is taken into account.
Background:
Galectin-3 (Gal-3) has been associated with cardiac remodeling and heart failure (HF) prognosis. Renal function is also a well known HF prognostic indicator. The link between renal insufficiency, HF, and Gal-3 is not completely elucidated.
Methods And Results:
We explored the association between Gal-3 and renal function in a cohort of 876 consecutive ambulatory patients with HF (mean age: 68 years; mean left ventricular ejection fraction [LVEF]: 36%), 52.2% had HF etiology of ischemic heart disease. Circulating Gal-3 was highly correlated with estimated glomerular filtration rate (eGFR), calculated with either the chronic kidney disease-epidemiology (CKD-EPI) equation (r = -0.64) or the CKD-EPI-cystatin-C equation (r = -0.59) and with Cystatin-C levels (r = 0.70), after adjusting for age, sex, New York Heart Association (NYHA) functional class, LVEF, and HF etiology (all p<0.001). Patients were stratified by CKD-EPI-eGFR (ml/min/1.73 m(2)), as follows: ≥ 60 (n = 218), 30 to 59 (n = 434), and <30 (n = 224). In these strata, Gal-3 significantly increased (median [IQR]: 12.3 [10.4-15.6]; 16.1 [13-19.8]; and 24.5 [20-33.8] ng/ml, respectively; trend p < 0.001). This was independent of NYHA functional class (I-II and III-IV) and LVEF (<45% and ≥ 45%). Gal-3 was associated with mortality in univariate analyses, but after adjusting for CKD-EPI-eGFR, the hazard ratios were 1.10 (95% CI: 0.89-1.34, p = 0.39) for all cause death, and 0.90 (95% CI: 0.68-1.21, p = 0.50) for cardiovascular death. Similar results were obtained with eGFRs calculated with the CKD-EPI-cystatin-C equation.
Conclusion:
Circulating Gal-3 was highly associated with renal function in outpatients with HF. The value of Gal-3 for HF prognosis declined after adjusting for renal function.
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