Circulating biomarkers linking heart failure and chronic obstructive pulmonary disease: Toward an integrated biological framework - A systematic review

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently coexist and are associated with substantial morbidity, mortality, and healthcare utilization. Accumulating evidence suggests that these conditions also share biological mechanisms that contribute to disease progression. However, although numerous circulating biomarkers have been investigated in both conditions, their interpretation has largely remained disease-specific, limiting a broader understanding of the biological processes underlying HF-COPD coexistence. We conducted a systematic review following PRISMA 2020 recommendations to identify and critically evaluate circulating biomarkers shared by HF and COPD according to their diagnostic, prognostic, and pathophysiological significance. A systematic search of PubMed, Scopus, and Web of Science, supplemented by Google Scholar and backward citation searching, identified 23 eligible studies published between 2015 and 2026. Natriuretic peptides, particularly N-terminal pro-B-type natriuretic peptide, were the most extensively investigated biomarkers for identifying cardiac dysfunction and predicting adverse outcomes. Cardiac troponins, inflammatory mediators, fibrosis- and remodelling-related biomarkers, endothelial markers, and metabolic biomarkers provided complementary insights into distinct biological pathways involved in disease progression. Overall, the available evidence indicates that circulating biomarkers reflect complementary pathophysiological processes, providing a rationale for future evaluation of multimarker approaches. By integrating these findings within a common biological context, this review highlights the potential of multimarker approaches for future investigation in cardiopulmonary risk stratification and translational research.