{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:05:39Z","timestamp":1791993939457,"version":"4.4.0"},"reference-count":74,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,11,6]]},"abstract":"\n Background<\/jats:title>\n \n Because systemic inflammation and endothelial dysfunction lead to heart failure with preserved ejection fraction, we characterized plasma levels of inflammatory and cardiac remodeling biomarkers in patients with Fabry disease (\n FD<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Plasma biomarkers were studied in multicenter cohorts of patients with\n FD<\/jats:styled-content>\n (n=68) and healthy controls (n=40). Plasma levels of the following markers of inflammation and cardiac remodeling were determined: tumor necrosis factor (\n TNF<\/jats:styled-content>\n ),\n TNF<\/jats:styled-content>\n receptor 1 (\n TNFR<\/jats:styled-content>\n 1) and 2 (\n TNFR<\/jats:styled-content>\n 2), interleukin\u20106, matrix metalloprotease\u20102 (\n MMP<\/jats:styled-content>\n \u20102),\n MMP<\/jats:styled-content>\n \u20108,\n MMP<\/jats:styled-content>\n \u20109, galectin\u20101, galectin\u20103, B\u2010type natriuretic peptide (\n BNP<\/jats:styled-content>\n ), midregional pro\u2013atrial natriuretic peptide (\n MR<\/jats:styled-content>\n \u2010pro\n ANP<\/jats:styled-content>\n ), and globotriaosylsphingosine. Clinical profile, cardiac magnetic resonance imaging, and echocardiogram were reviewed and correlated with biomarkers. Patients with\n FD<\/jats:styled-content>\n had elevated plasma levels of\n BNP<\/jats:styled-content>\n ,\n MR<\/jats:styled-content>\n \u2010pro\n ANP<\/jats:styled-content>\n ,\n MMP<\/jats:styled-content>\n \u20102,\n MMP<\/jats:styled-content>\n \u20109,\n TNF<\/jats:styled-content>\n ,\n TNFR<\/jats:styled-content>\n 1,\n TNFR<\/jats:styled-content>\n 2, interleukin\u20106, galectin\u20101, globotriaosylsphingosine, and analogues. Plasma\n TNFR<\/jats:styled-content>\n 2,\n TNF<\/jats:styled-content>\n , interleukin\u20106,\n MMP<\/jats:styled-content>\n \u20102, and globotriaosylsphingosine were elevated in\n FD<\/jats:styled-content>\n patients with left ventricular hypertrophy, whereas diastolic dysfunction correlated with higher\n BNP<\/jats:styled-content>\n ,\n MR<\/jats:styled-content>\n \u2010pro\n ANP<\/jats:styled-content>\n , and\n MMP<\/jats:styled-content>\n \u20102 levels. Patients with late gadolinium enhancement on cardiac magnetic resonance imaging had greater levels of\n BNP<\/jats:styled-content>\n ,\n MR<\/jats:styled-content>\n \u2010pro\n ANP<\/jats:styled-content>\n ,\n TNFR<\/jats:styled-content>\n 1,\n TNFR<\/jats:styled-content>\n 2, and\n MMP<\/jats:styled-content>\n \u20102. Plasma\n BNP<\/jats:styled-content>\n ,\n MR<\/jats:styled-content>\n \u2010pro\n ANP<\/jats:styled-content>\n ,\n MMP<\/jats:styled-content>\n \u20102,\n MMP<\/jats:styled-content>\n \u20108,\n TNF<\/jats:styled-content>\n ,\n TNFR<\/jats:styled-content>\n 1,\n TNFR<\/jats:styled-content>\n 2, galectin\u20101, and galectin\u20103 were elevated in patients with renal dysfunction. Patients undergoing enzyme replacement therapy who have more severe disease had higher\n MMP<\/jats:styled-content>\n \u20102,\n TNF<\/jats:styled-content>\n ,\n TNFR<\/jats:styled-content>\n 1,\n TNFR<\/jats:styled-content>\n 2, and globotriaosylsphingosine analogue levels.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Inflammatory and cardiac remodeling biomarkers are elevated in\n FD<\/jats:styled-content>\n patients and correlate with disease progression. These features are consistent with a phenotype dominated by heart failure with preserved ejection fraction and suggest a key pathogenic role of systemic inflammation in\n FD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.009098","type":"journal-article","created":{"date-parts":[[2018,12,16]],"date-time":"2018-12-16T15:51:35Z","timestamp":1544975495000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":88,"title":["Elevated Inflammatory Plasma Biomarkers in Patients With Fabry Disease: A Critical Link to Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1161","volume":"7","author":[{"given":"Haran","family":"Yogasundaram","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Medicine University of Alberta Edmonton Canada"},{"name":"Mazankowski Alberta Heart Institute University of Alberta Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anish","family":"Nikhanj","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine University of Alberta Edmonton Canada"},{"name":"Mazankowski Alberta Heart Institute University of Alberta Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan N.","family":"Putko","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine University of Alberta Edmonton Canada"},{"name":"Mazankowski Alberta Heart Institute University of Alberta Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Boutin","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Universit\u00e9 de Sherbrooke Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailly","family":"Jain\u2010Ghai","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Alberta Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneal","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Pediatrics University of Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Auray\u2010Blais","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Universit\u00e9 de Sherbrooke Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"West","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine Dalhousie University Halifax Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin Y.","family":"Oudit","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine University of Alberta Edmonton Canada"},{"name":"Mazankowski Alberta Heart Institute University of Alberta Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","first-page":"1186","article-title":"Nature and frequency of mutations in the alpha\u2010galactosidase A gene that cause Fabry disease","volume":"53","author":"Eng CM","year":"1993","unstructured":"Eng CM, Resnick\u2010Silverman LA, Niehaus DJ, Astrin KH, Desnick RJ. 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