Chronic obstructive pulmonary disease and CA125 levels in ambulatory chronic heart failure: The COPA-HF study

Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in chronic heart failure (CHF) and is associated with greater symptom burden and worse prognosis. Carbohydrate antigen 125 (CA125) has emerged as a biomarker of congestion and mesothelial/inflammatory activation in heart failure; however, its relationship with COPD in ambulatory CHF populations has not been systematically evaluated. We aimed to (1) determine the prevalence of COPD in a CHF outpatient cohort, (2) compare CA125 levels according to COPD status, and (3) evaluate whether COPD independently predicts CA125 levels.

COPA-HF was a multicenter prospective observational study conducted in five outpatient HF units in Madrid, Spain (May-June 2025). Consecutive adults with HF were enrolled during routine follow-up visits after providing written informed consent. COPD was defined by spirometry according to GOLD criteria in patients with tobacco exposure or respiratory symptoms, using a post-bronchodilator. CA125 and NT-proBNP were measured at inclusion. Multivariable linear regression was used to identify variables independently associated with CA125.

A total of 171 patients were included. Median age was 87.4 years (IQR 82.9-90.9), 55.6% were women, and HFpEF predominated (83%). COPD was present in 61 patients (35.7%). Compared to non-COPD patients, those with COPD were younger, predominantly male, more symptomatic (NYHA class III: 32.8% vs 13.6%; p = 0.011), and showed higher pulmonary artery systolic pressure (40 vs 30 mmHg; p = 0.010) and more frequent B-lines on lung ultrasound. CA125 levels were higher in patients with COPD (23.0 vs 18.0 U/mL; p = 0.034), whereas NT-proBNP did not differ between groups. On multivariable analysis, COPD (β = 16.38; 95% CI 3.59-29.17; p = 0.013) and pleural effusion (β = 20.42; 95% CI 0.58-40.26; p = 0.044) were independently associated with higher CA125.

COPD was highly prevalent in this cohort of ambulatory HF patients and was independently associated with elevated CA125 levels, together with pleural effusion. COPD should therefore be considered when interpreting CA125 during outpatient heart failure follow-up.