{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T11:39:44Z","timestamp":1778931584108,"version":"3.51.4"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,1,27]]},"abstract":"\n Background<\/jats:title>\n \n Elevated urinary globotriaosylceramide (Gb\n 3<\/jats:sub>\n ) has been considered a hallmark of\n F<\/jats:styled-content>\n abry disease, an X\u2010linked lysosomal disorder that is a risk factor for most types of heart disease.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We screened 1421 consecutive patients with common forms of heart disease for\n F<\/jats:styled-content>\n abry disease by measuring urinary Gb\n 3<\/jats:sub>\n in whole urine using tandem mass spectrometry, \u03b1\u2010galactosidase A activity in dried blood spots, and we looked for\n GLA<\/jats:styled-content>\n mutations by parallel sequencing of the whole gene (exons and introns) in pooled genomic\n DNA<\/jats:styled-content>\n samples followed by Sanger sequencing verification.\n \n GLA<\/jats:styled-content>\n <\/jats:styled-content>\n variants were found in 13 patients. In the 1408 patients without\n \n GLA<\/jats:styled-content>\n <\/jats:styled-content>\n mutations, urinary Gb\n 3<\/jats:sub>\n levels were significantly higher in heart disease patients compared to 116 apparently healthy controls (median difference=10.0\u00a0ng\/mL and\n P<\/jats:italic>\n <0.001). Urinary lipid profiling showed that levels of 5 other lipids significantly distinguished between urine of patients with\n F<\/jats:styled-content>\n abry disease (n=7) and heart disease patients with elevated urinary Gb\n 3<\/jats:sub>\n (n=6). Sphingomyelin and Gb\n 3<\/jats:sub>\n levels were abnormal in the left ventricular wall of patients with ischemic heart failure. Elevated levels of urinary Gb\n 3<\/jats:sub>\n were independently associated with increased risk of death in the average follow\u2010up of 17\u00a0months (hazard ratio=1.59 for increase in Gb\n 3<\/jats:sub>\n of 200, 95%\n CI<\/jats:styled-content>\n =1.36 and 1.87, and\n P<\/jats:italic>\n <0.0001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In heart disease patients who do not have\n F<\/jats:styled-content>\n abry disease or\n \n GLA<\/jats:styled-content>\n <\/jats:styled-content>\n gene mutations, a higher level of urinary Gb\n 3<\/jats:sub>\n is positively associated with near\u2010term mortality. The elevation of urinary Gb\n 3<\/jats:sub>\n and that of other lipids suggests that heart disease is associated with multiorgan lipid abnormalities.\n <\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n URL: clinicaltrials.gov. Unique Identifier:\n NCT<\/jats:styled-content>\n 01019629.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.113.000394","type":"journal-article","created":{"date-parts":[[2014,2,5]],"date-time":"2014-02-05T02:16:16Z","timestamp":1391566576000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Risk of Death in Heart Disease is Associated With Elevated Urinary Globotriaosylceramide"],"prefix":"10.1161","volume":"3","author":[{"given":"Raphael","family":"Schiffmann","sequence":"first","affiliation":[{"name":"Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Forni","sequence":"additional","affiliation":[{"name":"Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caren","family":"Swift","sequence":"additional","affiliation":[{"name":"Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nastry","family":"Brignol","sequence":"additional","affiliation":[{"name":"Amicus Therapeutics, Cranbury, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyang","family":"Wu","sequence":"additional","affiliation":[{"name":"Amicus Therapeutics, Cranbury, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Lockhart","sequence":"additional","affiliation":[{"name":"Amicus Therapeutics, Cranbury, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek","family":"Blankenship","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Baylor Institute for Immunology Research, Dallas, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Baylor Institute for Immunology Research, Dallas, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A.","family":"Grayburn","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Baylor University Medical Center, Dallas, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew R. 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