{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:16:06Z","timestamp":1784715366269,"version":"3.55.0"},"reference-count":117,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Calcific aortic valve disease (CAVD) is the predominant valvular pathology in older adults, advancing from aortic sclerosis to life\u2010threatening stenosis. Without effective medical therapies, intervention mainly relies on timely valve replacement, although silent myocardial and valvular damage may progress before symptoms arise. Early, non\u2010invasive detection of disease activity is a crucial unmet need.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To review circulating and mechanistic biomarkers reflecting the core pathogenic pathways of CAVD and asses their potential for early detection and patient\u2010specific risk stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Narrative review of literature focusing on traditional protein biomarkers, emerging non\u2010coding RNAs, and extracellular vesicles (EVs) associated with lipid oxidation and inflammation, bone and mineral metabolism, extracellular matrix (ECM) remodelling, endothelial dysfunction and non\u2010coding RNA regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Traditional protein biomarkers\u2014such as lipoprotein(a), osteopontin, fetuin\u2010A, galectin\u20103 and matrix metalloproteinases\u2014offer insights into the disease and correlate with disease burden but lack sensitivity for detecting early\u2010stage CAVD. Emerging non\u2010coding RNA markers, including long non\u2010coding RNAs (lncRNAs) and microRNAs (like miR\u201030b and miR\u2010125b), show promise as predictive and diagnostic tools by mediating key molecular pathways involved in calcification and inflammation. EVs, which carry proteins, lipids and nucleic acids across all pathogenic pathways, provide stable and comprehensive signatures that enhance risk stratification compared to conventional markers. Notably, no single biomarker has demonstrated sufficient sensitivity or specificity across all stages of the disease. Combining proteins, RNAs and EV cargo into integrative, multimodal panels\u2014supported by proteomics and transcriptomics\u2014provides the greatest potential for early detection and patient\u2010specific management. However, further validation in prospective cohorts and standardization of assays are necessary before clinical implementation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Biomarker\u2010guided approaches could revolutionize CAVD management by enabling early detection and patient stratification before irreversible valvular damage occurs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.70147","type":"journal-article","created":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T08:35:27Z","timestamp":1763195727000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrated biomarker landscape for the early detection and management of calcific aortic valve 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