Carbohydrate antigen 125 concentrations across the ejection fraction spectrum in chronic heart failure: The EMPEROR
João Pedro Ferreira1,2,3, Milton Packer4,5, Naveed Sattar6
1Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Cardiovascular Research and Development Center (UnIC@RISE), Porto, Portugal.
Insights
Carbohydrate antigen 125 (CA-125) is not a reliable biomarker for congestion in chronic heart failure (HF). However, elevated CA-125 levels may predict adverse outcomes in patients with heart failure with reduced ejection fraction (HFrEF).
Area of Science:
- Cardiology
- Biomarkers
- Heart Failure
Background:
- Vascular congestion is a known factor that can elevate carbohydrate antigen 125 (CA-125) levels.
- The prognostic value of CA-125 in chronic heart failure (HF) across the ejection fraction (EF) spectrum is not well-established.
Purpose of the Study:
- To investigate the association between CA-125 and congestion in patients with chronic heart failure (HF).
- To evaluate CA-125 as a prognostic biomarker for cardiovascular outcomes in HF patients with varying ejection fractions (EF).
Main Methods:
- Serum CA-125 levels were analyzed in 1111 participants from the EMPEROR-Reduced and EMPEROR-Preserved trials.
- Cox regression models assessed the relationship between CA-125 tertiles and the composite outcome of HF hospitalization or cardiovascular death.
- Congestive signs and symptoms were evaluated across CA-125 tertiles.
Main Results:
- No significant association was found between baseline CA-125 levels and congestive signs or symptoms.
- Higher CA-125 levels were associated with an increased risk of the primary outcome in heart failure with reduced ejection fraction (HFrEF) but not in heart failure with preserved ejection fraction (HFpEF).
- Elevated CA-125 levels correlated with a faster decline in estimated glomerular filtration rate.
Conclusions:
- CA-125 is not a significant biomarker for congestion in the majority of chronic HF patients studied.
- CA-125 may serve as a prognostic indicator for HF hospitalization or cardiovascular death in HFrEF patients, but not in HFpEF patients.
Aim:
Vascular congestion may lead to an increase of carbohydrate antigen 125 (CA-125). The role of CA-125 as a biomarker of congestion or for prognosis across the full ejection fraction (EF) spectrum of chronic heart failure (HF) remains unknown.
Methods And Results:
Serum CA-125 was measured in 1111 study participants from the EMPEROR-Reduced and EMPEROR-Preserved trials. Congestive signs and symptoms were evaluated across CA-125 tertiles. Cox regression was used to study the association with outcomes. The primary outcome was a composite of first HF hospitalization or cardiovascular (CV) death. No significant association was present between baseline CA-125 levels and congestive signs or symptoms. In the overall population, higher CA-125 levels were not associated with an increased risk of primary outcome (tertile 3 vs. tertile 1: hazard ratio [HR] 1.34; 95% confidence interval [CI] 0.91-1.96; p-trend = 0.11). However, higher CA-125 levels were associated with an increased risk of primary outcome in patients with HF and reduced EF (HFrEF; tertile 3 vs. tertile 1: HR 2.25 [95% CI 1.30-3.89]), but not among patients with preserved EF (HFpEF; tertile 3 vs. tertile 1: HR 0.68 [95% CI 0.38-1.21]); interaction-p = 0.02). Patients in the upper CA-125 tertile also showed the steepest estimated glomerular filtration rate decline over time (p-trend = 0.03). The effect of empagliflozin to reduce the risk of CV death or HF hospitalization appeared to be attenuated in those with lower baseline CA-125 levels (interaction-p-trend = 0.09).
Conclusion:
Across the range of EF in patients with chronic HF enrolled in the EMPEROR trials, the majority of whom did not have clinical evidence of congestion, CA-125 concentrations were not significantly associated with congestive signs or symptoms. CA-125 concentrations may predict HF hospitalization/CV death in patients with HFrEF, but not those with HFpEF.
Clinical Trial Registration:
EMPEROR-Reduced (NCT03057977), EMPEROR-Preserved (NCT03057951).
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