Chronic Obstructive Pulmonary Disease in Heart Failure: Influence on Circulating Biomarkers and Outcome

Abstract Background Chronic obstructive pulmonary disease (COPD) is common in patients with chronic heart failure (CHF). Purpose We aimed to explore the impact of COPD on HF biomarkers (N-terminal fraction of pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [hs-TnT], and soluble suppression of tumorigenesis-2 [sST2]) and outcome. Methods Individual data from 14 cohorts of patients with stable chronic HF and NT-proBNP and hs-TnT values were analysed. Patients with known COPD status were evaluated. Results Patients (n=13,178) were aged 67 years (58–75), 75% males, and 76%, 11%, 13% with HF with reduced, mid-range, or preserved ejection fraction (HFrEF/HFmrEF/HFpEF), respectively. Patients with COPD were older than those without COPD (age 71 years [64–77] vs. 66 [57–75]; p<0.001), more frequently males (79% vs. 74%; p<0.001), had more often ischaemic HF (54% vs. 52%; p<0.001), and HFpEF (14% vs. 12%; p=0.011), but not HFpEF (12% vs. 11%; p=0.097). COPD patients had also more severe dyspnoea (44% in NYHA class III-IV vs. 31%; p<0.001), and slightly worse renal function (median estimated glomerular filtration rate [eGFR] 58 mL/min/1.73 m2 [44–74] vs. 60 [46–67]; p<0.001). Patients with COPD had higher NT-proBNP (1501 ng/L [642–3333] vs. 1225 ng/L [476–2902]; p<0.001), hs-TnT (22 ng/L [13–38] vs. 17 ng/L [9–30]; p<0.001), and sST2 (30 ng/mL [22–45] vs. 29 [21–43]; p<0.001). Over a median follow-up of 2.1 years (1.5–3.7, range 0–18 years), 3,865/12,489 patients (31%) died; among them, 2,443/12,450 (20%) died for cardiovascular causes; 3,373/12,469 patients (27%) were hospitalized for HF over 35 months (15–63, range 0–216 months). Patients with COPD had a significantly higher all-cause mortality, cardiovascular mortality, and worse survival free from HF hospitalization (all p<0.001; Figure). In a model including age, gender, ischaemic vs. non-ischaemic aetiology, eGFR, HFrEF/HFmrEF/HFpEF, and NYHA class III-IV, COPD retained independent prognostic significance from NT-proBNP for 1-year all-cause (p=0.009) and cardiovascular mortality (p=0.022), 5-year all-cause (p<0.001) and cardiovascular mortality (p=0.011) as well as 3- (p=0.033), 6- (p=0.019) and 12-month HF hospitalization (p=0.033). COPD lost its independent prognostic significance when hs-TnT and sST2 were included in the model. Conclusions COPD in HF is characterized by higher NT-proBNP, hs-TnT and sST2 levels. COPD adds prognostic significance over NT-proBNP alone, but not over the combination of NT-proBNP, hs-TnT, and sST2. Funding Acknowledgement Type of funding source: None