{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:48:16Z","timestamp":1789649296499,"version":"4.0.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011019","name":"National Research Development and Innovation Office of Hungary","doi-asserted-by":"publisher","award":["K146732"],"award-info":[{"award-number":["K146732"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"National Research Development and Innovation Office of Hungary","doi-asserted-by":"publisher","award":["RRF-2.3.1-21-2022-00003"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00003"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"National Research Development and Innovation Office of Hungary","doi-asserted-by":"publisher","award":["K146929"],"award-info":[{"award-number":["K146929"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"National Research Development and Innovation Office of Hungary","doi-asserted-by":"publisher","award":["K132695"],"award-info":[{"award-number":["K132695"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"National Research Development and Innovation Office of Hungary","doi-asserted-by":"publisher","award":["FK131946"],"award-info":[{"award-number":["FK131946"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"National Research Development and Innovation Office of Hungary","doi-asserted-by":"publisher","award":["K150493"],"award-info":[{"award-number":["K150493"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"name":"J\u00e1nos Bolyai Research Scholarship of the Hungarian Academy of Sciences","award":["\u00daNKP-23-5"],"award-info":[{"award-number":["\u00daNKP-23-5"]}]},{"name":"Ministry of Culture and Innovation"},{"name":"FWO Junior Fundamental Research Project","award":["G061521N"],"award-info":[{"award-number":["G061521N"]}]},{"name":"FWO Research Foundation Flanders, Belgium"},{"name":"J\u00e1nos Bolyai Research Scholarship","award":["BO\/00730\/19\/8"],"award-info":[{"award-number":["BO\/00730\/19\/8"]}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["\u00daNKP-22-5-SE-2"],"award-info":[{"award-number":["\u00daNKP-22-5-SE-2"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Culture and Innovation"},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2023-02652"],"award-info":[{"award-number":["2023-02652"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"International Network on Ectopic Calcification"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Inorganic pyrophosphate (PPi) is an endogenous inhibitor of soft tissue calcification. A disturbed equilibrium between pro- and anti-mineralization agents, like extracellular phosphate (Pi) and PPi, has been implicated in the mechanism of aortic valve calcification (AVC). We aimed to investigate the association of the plasma PPi concentration and Pi\/PPi ratio with the degree AVC in cardiovascular patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>One hundred and fifty-four patients referred for cardiac computed tomography (CT), including 43 individuals with severe aortic stenosis, were prospectively enrolled. The aortic valve calcium score (AVCS) was measured on non-contrast CT images. Plasma PPi level was determined enzymatically. Of the entire population (age: 67 \u00b1 12 years, 42.5% female), 42% had some degree of AVC (range 9\u20136641\u2005AU). Plasma PPi showed a significant positive association with plasma Pi and LDL cholesterol (LDL-C) concentration and was inversely related to alkaline phosphatase activity. When controlled for age, female patients had higher PPi levels. In univariate analysis, plasma PPi level did not show an association with AVCS; however, the Pi\/PPi ratio was significantly positively associated with the degree of AVC [estimate: 1508.1; standard error (SE) 616.0, P = 0.015], along with age, hypertension, plasma lipoprotein(a) concentration, and statin treatment, whereas estimated glomerular filtration rate and LDL-C level showed significant negative associations. In multivariate analysis, only age and Pi\/PPi ratio remained significant determinant of the AVCS (estimate: 1128.6; SE 562.5, P = 0.047).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first study to investigate the association between PPi homeostasis and AVC in humans. The plasma Pi\/PPi ratio was significantly positively associated with the AVC load even after adjustment for traditional risk factors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjci\/jeaf247","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T11:22:19Z","timestamp":1756120939000},"page":"12-22","source":"Crossref","is-referenced-by-count":6,"title":["Association between plasma phosphate\/pyrophosphate ratio and computed tomography\u2013derived aortic valve calcification score in an unselected cohort of cardiovascular patients"],"prefix":"10.1093","volume":"27","author":[{"given":"D\u00e9nes","family":"Juh\u00e1sz","sequence":"first","affiliation":[{"name":"Heart and Vascular Centre, Semmelweis University , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"V\u00e1rhegyi","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences , Budapest ,","place":["Hungary"]},{"name":"Doctoral College, Semmelweis University \u00a0 Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rton","family":"Rakovics","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University , Budapest ,","place":["Hungary"]},{"name":"Faculty of Social Sciences, Department of Statistics, ELTE E\u00f6tv\u00f6s Lor\u00e1nd University , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1lint","family":"Szilveszter","sequence":"additional","affiliation":[{"name":"Heart and Vascular Centre, Semmelweis University , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1d\u00e1m Levente","family":"Jermendy","sequence":"additional","affiliation":[{"name":"Heart and Vascular Centre, Semmelweis University , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edit","family":"D\u00f3sa","sequence":"additional","affiliation":[{"name":"Heart and Vascular Centre, Semmelweis University , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9va","family":"Straub","sequence":"additional","affiliation":[{"name":"Heart and Vascular Centre, Semmelweis University , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9la","family":"Merkely","sequence":"additional","affiliation":[{"name":"Heart and Vascular Centre, Semmelweis University , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Ar\u00e1nyi","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences , Budapest ,","place":["Hungary"]},{"name":"Department of Molecular Biology, Semmelweis University , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Apor","sequence":"additional","affiliation":[{"name":"Heart and Vascular Centre, Semmelweis University , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1vid","family":"Sz\u00fcts","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristomenis","family":"Manouras","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart and Vascular Center, Karolinska University Hospital , Stockholm ,","place":["Sweden"]},{"name":"Department of Medicine Solna, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0853-5141","authenticated-orcid":false,"given":"Magnus","family":"B\u00e4ck","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart and Vascular Center, Karolinska University Hospital , Stockholm ,","place":["Sweden"]},{"name":"Department of Medicine Solna, Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"Acute and Chronic Cardiovascular Failure Department, Universit\u00e9 de Lorraine, Inserm, DCAC Nancy F-54000 ,","place":["France"]},{"name":"Department of Research and Innovation, Centre Hospitalier R\u00e9gional Universitaire de Nancy, Vandoeuvre-l\u00e8s-Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00f3ra","family":"Szeri","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0519-5172","authenticated-orcid":false,"given":"Anik\u00f3 Ilona","family":"Nagy","sequence":"additional","affiliation":[{"name":"Heart and Vascular Centre, Semmelweis University , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,30]]},"reference":[{"key":"2026013009123139900_jeaf247-B1","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S0140-6736(06)69208-8","article-title":"Burden of valvular heart diseases: a population-based study","volume":"368","author":"Nkomo","year":"2006","journal-title":"Lancet"},{"key":"2026013009123139900_jeaf247-B2","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.jacc.2013.05.015","article-title":"Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study","volume":"62","author":"Osnabrugge","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"2026013009123139900_jeaf247-B3","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.amjcard.2021.09.046","article-title":"Epidemiology of aortic stenosis\/aortic valve replacement (from the Nationwide Swedish Renal Registry)","volume":"163","author":"Vavilis","year":"2022","journal-title":"Am J Cardiol"},{"key":"2026013009123139900_jeaf247-B4","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1016\/j.jacc.2012.02.093","article-title":"Calcific aortic stenosis: a disease of the valve and the myocardium","volume":"60","author":"Dweck","year":"2012","journal-title":"J Am Coll Cardiol"},{"key":"2026013009123139900_jeaf247-B5","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1161\/ATVBAHA.119.313067","article-title":"Aortic valve stenosis: from basic mechanisms to novel therapeutic targets","volume":"40","author":"Goody","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026013009123139900_jeaf247-B6","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jjcc.2017.11.007","article-title":"Mechanisms of aortic stenosis","volume":"71","author":"Akahori","year":"2018","journal-title":"J Cardiol"},{"key":"2026013009123139900_jeaf247-B7","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1161\/CIRCULATIONAHA.105.598086","article-title":"Features of the metabolic syndrome and diabetes mellitus as predictors of aortic valve calcification in the Multi-Ethnic Study of Atherosclerosis","volume":"113","author":"Katz","year":"2006","journal-title":"Circulation"},{"key":"2026013009123139900_jeaf247-B8","doi-asserted-by":"crossref","first-page":"3960","DOI":"10.1093\/eurheartj\/ehac377","article-title":"Lipoprotein(a) is associated with the onset but not the progression of aortic valve calcification","volume":"43","author":"Kaiser","year":"2022","journal-title":"Eur Heart J"},{"key":"2026013009123139900_jeaf247-B9","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1136\/heartjnl-2021-319023","article-title":"Cross-sectional study of aortic valve calcification and cardiovascular risk factors in older Danish men","volume":"107","author":"Khurrami","year":"2021","journal-title":"Heart"},{"key":"2026013009123139900_jeaf247-B10","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1016\/j.jacc.2017.01.025","article-title":"Association between cardiovascular risk factors and aortic stenosis: the CANHEART aortic stenosis study","volume":"69","author":"Yan","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"2026013009123139900_jeaf247-B11","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.jacc.2018.10.068","article-title":"Kidney dysfunction and the risk of developing aortic stenosis","volume":"73","author":"Vavilis","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"2026013009123139900_jeaf247-B12","first-page":"3329","article-title":"Inorganic phosphate-osteogenic induction medium promotes osteogenic differentiation of valvular interstitial cells via the BMP-2\/Smad1\/5\/9 and RhoA\/ROCK-1 signaling pathways","volume":"12","author":"Lu","year":"2020","journal-title":"Am J Transl Res"},{"key":"2026013009123139900_jeaf247-B13","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.atherosclerosis.2013.12.051","article-title":"Serum phosphate is associated with aortic valve calcification in the Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"233","author":"Linefsky","year":"2014","journal-title":"Atherosclerosis"},{"key":"2026013009123139900_jeaf247-B14","doi-asserted-by":"crossref","first-page":"101096","DOI":"10.1016\/j.jacadv.2024.101096","article-title":"Association between serum phosphate levels and progression of aortic stenosis","volume":"3","author":"Candellier","year":"2024","journal-title":"JACC Adv"},{"key":"2026013009123139900_jeaf247-B15","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jacc.2011.01.047","article-title":"Serum phosphate concentrations: a novel pre-clinical biomarker for cardiovascular calcification","volume":"58","author":"Rajamannan","year":"2011","journal-title":"J Am Coll Cardiol"},{"key":"2026013009123139900_jeaf247-B16","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.yjmcc.2012.02.003","article-title":"ATP acts as a survival signal and prevents the mineralization of aortic valve","volume":"52","author":"C\u00f4t\u00e9","year":"2012","journal-title":"J Mol Cell Cardiol"},{"key":"2026013009123139900_jeaf247-B17","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ejphar.2012.05.016","article-title":"Inhibition of ectonucleotidase with ARL67156 prevents the development of calcific aortic valve disease in warfarin-treated rats","volume":"689","author":"C\u00f4t\u00e9","year":"2012","journal-title":"Eur J Pharmacol"},{"key":"2026013009123139900_jeaf247-B18","doi-asserted-by":"crossref","first-page":"4555","DOI":"10.3390\/ijms22094555","article-title":"ABCC6, pyrophosphate and ectopic calcification: therapeutic solutions","volume":"22","author":"Shimada","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2026013009123139900_jeaf247-B19","doi-asserted-by":"crossref","first-page":"5192","DOI":"10.1073\/pnas.88.12.5192","article-title":"Identification of nucleotide pyrophosphatase\/alkaline phosphodiesterase I activity associated with the mouse plasma cell differentiation antigen PC-1","volume":"88","author":"Rebbe","year":"1991","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026013009123139900_jeaf247-B20","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.3390\/ijms18091941","article-title":"The ABCC6 transporter: a new player in biomineralization","volume":"18","author":"Favre","year":"2017","journal-title":"Int J Mol Sci"},{"key":"2026013009123139900_jeaf247-B21","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1093\/cvr\/cvab038","article-title":"From organic and inorganic phosphates to valvular and vascular calcifications","volume":"117","author":"B\u00e4ck","year":"2021","journal-title":"Cardiovasc Res"},{"key":"2026013009123139900_jeaf247-B22","doi-asserted-by":"crossref","first-page":"6001","DOI":"10.1073\/pnas.100041297","article-title":"Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter","volume":"97","author":"Ringpfeil","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026013009123139900_jeaf247-B23","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/76109","article-title":"Mutations in ABCC6 cause pseudoxanthoma elasticum","volume":"25","author":"Bergen","year":"2000","journal-title":"Nat Genet"},{"key":"2026013009123139900_jeaf247-B24","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/ng1221","article-title":"Mutations in ENPP1 are associated with \u2018idiopathic\u2019 infantile arterial calcification","volume":"34","author":"Rutsch","year":"2003","journal-title":"Nat Genet"},{"key":"2026013009123139900_jeaf247-B25","first-page":"ehv605","article-title":"Phosphate, pyrophosphate, and vascular calcification: a question of balance","volume":"38","author":"Villa-Bellosta","year":"2017","journal-title":"Eur Heart J"},{"key":"2026013009123139900_jeaf247-B26","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.15252\/emmm.201707532","article-title":"Oral administration of pyrophosphate inhibits connective tissue calcification","volume":"9","author":"Dedinszki","year":"2017","journal-title":"EMBO Mol Med"},{"key":"2026013009123139900_jeaf247-B27","first-page":"387","article-title":"The role of inorganic pyrophosphate in aortic valve calcification","volume":"23","author":"Rathan","year":"2014","journal-title":"J Heart Valve Dis"},{"key":"2026013009123139900_jeaf247-B28","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.atherosclerosis.2014.10.027","article-title":"Extracellular pyrophosphate is reduced in aortic interstitial valve cells acquiring a calcifying profile: implications for aortic valve calcification","volume":"237","author":"Rattazzi","year":"2014","journal-title":"Atherosclerosis"},{"key":"2026013009123139900_jeaf247-B29","doi-asserted-by":"crossref","first-page":"6502","DOI":"10.3390\/ijms25126502","article-title":"A plasma pyrophosphate cutoff value for diagnosing pseudoxanthoma elasticum","volume":"25","author":"Rubera","year":"2024","journal-title":"Int J Mol Sci"},{"key":"2026013009123139900_jeaf247-B30","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s00216-022-04430-8","article-title":"A new enzymatic assay to quantify inorganic pyrophosphate in plasma","volume":"415","author":"Lundkvist","year":"2023","journal-title":"Anal Bioanal Chem"},{"key":"2026013009123139900_jeaf247-B31","doi-asserted-by":"crossref","first-page":"573727","DOI":"10.3389\/fcell.2020.573727","article-title":"Plasma inorganic pyrophosphate deficiency links multiparity to cardiovascular disease risk","volume":"8","author":"Veiga-Lopez","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"2026013009123139900_jeaf247-B32","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/ndt\/gfp362","article-title":"Plasma pyrophosphate and vascular calcification in chronic kidney disease","volume":"25","author":"O'Neill","year":"2010","journal-title":"Nephrol Dial Transplant"},{"key":"2026013009123139900_jeaf247-B33","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.kint.2017.11.035","article-title":"Pyrophosphate deficiency in vascular calcification","volume":"93","author":"Villa-Bellosta","year":"2018","journal-title":"Kidney Int"},{"key":"2026013009123139900_jeaf247-B34","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.3390\/ijms20092142","article-title":"The role of vitamin K and its related compounds in Mendelian and acquired ectopic mineralization disorders","volume":"20","author":"Nollet","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2026013009123139900_jeaf247-B35","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.4065\/83.9.1032","article-title":"Bisphosphonates: mechanism of action and role in clinical practice","volume":"83","author":"Drake","year":"2008","journal-title":"Mayo Clin Proc"},{"key":"2026013009123139900_jeaf247-B36","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.bbrc.2011.10.095","article-title":"ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: relevance to pathomechanisms of pseudoxanthoma elasticum","volume":"415","author":"F\u00fcl\u00f6p","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"2026013009123139900_jeaf247-B37","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1161\/ATVBAHA.114.304017","article-title":"ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report","volume":"34","author":"Jansen","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026013009123139900_jeaf247-B38","article-title":"Risk factors for aortic stenosis","volume":"18","author":"B\u00e4ck","year":"2020","journal-title":"e-Journal of Cardiology Practice: European Society of Cardiology"},{"key":"2026013009123139900_jeaf247-B39","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.amjcard.2009.10.071","article-title":"Incidence and progression of aortic valve calcium in the Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"105","author":"Owens","year":"2010","journal-title":"Am J Cardiol"},{"key":"2026013009123139900_jeaf247-B40","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.3390\/jcm11092588","article-title":"Relationships between plasma pyrophosphate, vascular calcification and clinical severity in patients affected by pseudoxanthoma Elasticum","volume":"11","author":"Leftheriotis","year":"2022","journal-title":"J Clin Med"},{"key":"2026013009123139900_jeaf247-B41","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.3390\/jcm12051893","article-title":"Inorganic pyrophosphate plasma levels are decreased in pseudoxanthoma elasticum patients and heterozygous carriers but do not correlate with the genotype or phenotype","volume":"12","author":"Van Gils","year":"2023","journal-title":"J Clin Med"},{"key":"2026013009123139900_jeaf247-B42","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1210\/clinem\/dgab615","article-title":"A reference range for plasma levels of inorganic pyrophosphate in children using the ATP sulfurylase method","volume":"107","author":"Bernhard","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"2026013009123139900_jeaf247-B43","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.3390\/jcm12031047","article-title":"Plasma level of pyrophosphate is low in pseudoxanthoma elasticum owing to mutations in the ABCC6 gene, but it does not correlate with ABCC6 genotype","volume":"12","author":"Koz\u00e1k","year":"2023","journal-title":"J Clin Med"},{"key":"2026013009123139900_jeaf247-B44","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1161\/01.CIR.90.2.844","article-title":"Characterization of the early lesion of \u2018degenerative\u2019 valvular aortic stenosis. Histological and immunohistochemical studies","volume":"90","author":"Otto","year":"1994","journal-title":"Circulation"},{"key":"2026013009123139900_jeaf247-B45","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1016\/S0140-6736(16)31357-5","article-title":"Interpretation of the evidence for the efficacy and safety of statin therapy","volume":"388","author":"Collins","year":"2016","journal-title":"Lancet"},{"key":"2026013009123139900_jeaf247-B46","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1161\/CIRCULATIONAHA.104.512681","article-title":"Aggressive versus moderate lipid-lowering therapy in hypercholesterolemic postmenopausal women: Beyond Endorsed Lipid Lowering with EBT Scanning (BELLES)","volume":"112","author":"Raggi","year":"2005","journal-title":"Circulation"},{"key":"2026013009123139900_jeaf247-B47","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1161\/CIRCULATIONAHA.105.568147","article-title":"Effect of intensive versus standard lipid-lowering treatment with atorvastatin on the progression of calcified coronary atherosclerosis over 12 months: a multicenter, randomized, double-blind trial","volume":"113","author":"Schmermund","year":"2006","journal-title":"Circulation"},{"key":"2026013009123139900_jeaf247-B48","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1161\/01.ATV.0000154278.01871.64","article-title":"Paradoxical effects of statins on aortic valve myofibroblasts and osteoblasts: implications for end-stage valvular heart disease","volume":"25","author":"Wu","year":"2005","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026013009123139900_jeaf247-B49","doi-asserted-by":"crossref","first-page":"e006339","DOI":"10.1161\/JAHA.117.006339","article-title":"Valve interstitial cells: the key to understanding the pathophysiology of heart valve calcification","volume":"6","author":"Rutkovskiy","year":"2017","journal-title":"J Am Heart Assoc"},{"key":"2026013009123139900_jeaf247-B50","doi-asserted-by":"crossref","first-page":"H903","DOI":"10.1152\/ajpheart.00263.2012","article-title":"A time course investigation of the statin paradox among valvular interstitial cell phenotypes","volume":"303","author":"Monzack","year":"2012","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026013009123139900_jeaf247-B51","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.kint.2021.01.016","article-title":"Hyperphosphatemia in chronic kidney disease exacerbates atherosclerosis via a mannosidases-mediated complex-type conversion of SCAP N-glycans","volume":"99","author":"Zhou","year":"2021","journal-title":"Kidney Int"},{"key":"2026013009123139900_jeaf247-B52","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/j.kint.2021.02.022","article-title":"Phosphate meeting cholesterol-consequences for cardiovascular disease in chronic kidney disease?","volume":"99","author":"H\u00e9naut","year":"2021","journal-title":"Kidney Int"},{"key":"2026013009123139900_jeaf247-B53","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.ajpath.2022.01.012","article-title":"Inorganic pyrophosphate deficiency syndromes and potential treatments for pathologic tissue calcification","volume":"192","author":"Ralph","year":"2022","journal-title":"Am J Pathol"},{"key":"2026013009123139900_jeaf247-B54","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/jbmr.4791","article-title":"Weighing the evidence for the roles of plasma versus local pyrophosphate in ectopic calcification disorders","volume":"38","author":"Ralph","year":"2023","journal-title":"J Bone Miner Res"},{"key":"2026013009123139900_jeaf247-B55","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.jid.2016.11.042","article-title":"Abcc6 knockout rat model highlights the role of liver in PPi homeostasis in pseudoxanthoma Elasticum","volume":"137","author":"Li","year":"2017","journal-title":"J Invest Dermatol"},{"key":"2026013009123139900_jeaf247-B56","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1038\/ki.2013.521","article-title":"Vascular calcification is dependent on plasma levels of pyrophosphate","volume":"85","author":"Lomashvili","year":"2014","journal-title":"Kidney Int"},{"key":"2026013009123139900_jeaf247-B57","doi-asserted-by":"crossref","first-page":"116868","DOI":"10.1016\/j.bone.2023.116868","article-title":"Evidence that pyrophosphate acts as an extracellular signalling molecule to exert direct functional effects in primary cultures of osteoblasts and osteoclasts","volume":"176","author":"Bourne","year":"2023","journal-title":"Bone"},{"key":"2026013009123139900_jeaf247-B58","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13063-024-08666-w","article-title":"The PROPHECI trial: a phase II, double-blind, placebo-controlled, randomized clinical trial for the treatment of pseudoxanthoma elasticum with oral pyrophosphate","volume":"26","author":"Clotaire","year":"2025","journal-title":"Trials"},{"key":"2026013009123139900_jeaf247-B59","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.coph.2016.03.003","article-title":"Pyrophosphate: a key inhibitor of mineralisation","volume":"28","author":"Orriss","year":"2016","journal-title":"Curr Opin Pharmacol"},{"key":"2026013009123139900_jeaf247-B60","doi-asserted-by":"crossref","first-page":"116750","DOI":"10.1016\/j.bone.2023.116750","article-title":"Effects of food, fasting, and exercise on plasma pyrophosphate levels and ENPP1 activity in healthy adults","volume":"171","author":"Khursigara","year":"2023","journal-title":"Bone"}],"container-title":["European Heart Journal - Cardiovascular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ehjcimaging\/advance-article-pdf\/doi\/10.1093\/ehjci\/jeaf247\/64167632\/jeaf247.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjcimaging\/article-pdf\/27\/1\/12\/64167632\/jeaf247.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjcimaging\/article-pdf\/27\/1\/12\/64167632\/jeaf247.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T14:12:46Z","timestamp":1769782366000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ehjcimaging\/article\/27\/1\/12\/8244715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,30]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,8,30]]},"published-print":{"date-parts":[[2026,1,30]]}},"URL":"https:\/\/doi.org\/10.1093\/ehjci\/jeaf247","relation":{},"ISSN":["2047-2404","2047-2412"],"issn-type":[{"value":"2047-2404","type":"print"},{"value":"2047-2412","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,8,30]]}}}