Risk of death in heart disease is associated with elevated urinary globotriaosylceramide.

[fabry disease]

Elevated urinary globotriaosylceramide (Gb 3 ) has been considered a hallmark of Fabry disease , an X-linked lysosomal disorder that is a risk factor for most types of heart disease .We screened 1421 consecutive patients with common forms of heart disease for Fabry disease by measuring urinary Gb 3 in whole urine using tandem mass spectrometry , α-galactosidase A activity in dried blood spots , and we looked for GLA mutations by parallel sequencing of the whole gene (exons and introns ) in pooled genomic DNA samples followed by Sanger sequencing verification . GLA variants were found in 13 patients . In the 1408 patients without GLA mutations , urinary Gb 3 levels were significantly higher in heart disease patients compared to 116 apparently healthy controls (median difference =10 .0 ng /mL and P <0 .001 ). Urinary lipid profiling showed that levels of 5 other lipids significantly distinguished between urine of patients with Fabry disease (n =7 ) and heart disease patients with elevated urinary Gb 3 (n =6 ). Sphingomyelin and Gb 3 levels were abnormal in the left ventricular wall of patients with ischemic heart failure . Elevated levels of urinary Gb 3 were independently associated with increased risk of death in the average follow-up of 17 months (hazard ratio =1 .59 for increase in Gb 3 of 200 , 95 % CI =1 .36 and 1 .87 , and P <0 .0001 ).In heart disease patients who do not have Fabry disease or GLA gene mutations , a higher level of urinary Gb 3 is positively associated with near-term mortality . The elevation of urinary Gb 3 and that of other lipids suggests that heart disease is associated with multiorgan lipid abnormalities .clinicaltrials .gov . Unique Identifier : NCT 01019629 .