Open AccessUric Acid as a Marker of Mortality and Morbidity in Fabry Disease
Author(s) -
Daniel Rob,
Josef Marek,
Gabriela Dostálová,
Lubor Goláň,
Aleš Linhart
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0166290
Subject(s) - medicine , hazard ratio , proportional hazards model , clinical endpoint , confidence interval , fabry disease , renal function , left ventricular hypertrophy , stroke (engine) , cardiology , uric acid , univariate analysis , gastroenterology , disease , multivariate analysis , clinical trial , blood pressure , mechanical engineering , engineering
Background Serum uric acid (UA) elevation is common in patients with cardiovascular, renal and metabolic diseases. However, no study to date has analysed the role of UA in Fabry disease (FD). Objectives To evaluate the association between serum UA levels and mortality and morbidity in FD. Materials and Methods We conducted a post-hoc analysis of a prospectively followed-up cohort of 124 patients with genetically proven FD. Serum UA levels were acquired at baseline; clinical events and mortality were assessed during regular visits every 6 to 12 months. The primary endpoint was a composite of multiple secondary outcomes: all-cause mortality, adverse cardiovascular events, progression of renal dysfunction and stroke or transient ischaemic attack (TIA). Predictive value was assessed using the Cox proportional hazards model and the Kaplan Meyer estimator. Results During follow-up of 7.4 ± 3.7 years, 64 (52%) patients reached the primary combined endpoint. Overall, UA levels were significantly associated with combined outcome (p < 0.001) and remained independently associated after correcting for age, sex and estimated glomerular filtration rate (hazard ratio [HR] per 20 μmol/l increase 1.09, 95% confidence interval [95%CI] (1.00–1.19), p = 0.04). UA was associated with overall mortality in univariate analysis (p = 0.021); however, the association did not reach statistical significance after multivariate correction (HR per 20 μmol/l increase 1.07 95%CI 0.93–1.25, p = 0.32). Higher UA levels were also associated with cardiac adverse outcomes, progression of left ventricular hypertrophy and progression of renal dysfunction (ps < 0.001). No association was observed between UA levels and stroke or TIA (p = 0.323). Conclusion and Implications Increased serum UA levels may represent an independent risk factor for adverse clinical outcomes in Fabry patients and are associated with all-cause mortality. UA is a widely available and cheap biomarker that may improve risk stratification of Fabry patients in clinical practice.