Uric Acid as a Marker of Mortality and Morbidity in Fabry Disease.
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).


OBJECTIVE
To evaluate the association between serum UA levels and mortality and morbidity in FD.


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).


CONCLUSIONS
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.
2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Daniel
D
Rob
2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Josef
J
Marek
2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Gabriela
G
Dostálová
2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Lubor
L
Goláň
2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Aleš
A
Linhart
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D000795:Fabry Disease / Q000097:blood* / Q000453:epidemiology / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002546:Ischemic Attack, Transient / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D017063:Outcome Assessment, Health Care / Q000379:methods* / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D011446:Prospective Studies; D020521:Stroke / Q000453:epidemiology; D015996:Survival Rate; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
D015415:Biomarkers; D014527:Uric Acid