Abstract
Current therapies have not shown benefit in organ damage reversal in Fabry disease (FD), but biomarkers could help risk stratification and prognosis. We investigated if several biomarkers of cardiac fibrosis, cardiac wall stress, myocardial injury, renal function and inflammation, are associated with early cardiac affectation in FD patients. We included FD patients from four cardiology outpatient clinics of southeastern Spain. At inclusion, Galectin-3 (Gal-3), N-terminal proB-type natriuretic peptide, high sensitivity troponin T (hsTnT), β-trace protein (BTP) and interleukin-6 concentrations were measured. The relation of biomarkers concentrations with clinical features, cardiac involvement and organ affectation according to the Mainz Severity Score Index (MSSI) was investigated. 44 FD patients (n = 21 affected and n = 23 unaffected) were compared to age and sex-respectively matched healthy controls. Significant differences in biomarkers’ concentration between FD groups were observed. Importantly, Gal-3 and BTP levels were higher in unaffected patients when compared with age and sex-matched healthy controls (both p < 0.05). All the biomarkers correlated with clinical features. When cut-off values for clinical affectation (measured as MSSI ≥ 20) were established, only hsTnT (OR 30.69, 95% CI 2.70–348.42) and male sex (OR 8.17, 95% CI 1.16–57.75) were independently associated with cardiac damage by multivariate regression analysis. Gal-3 and BTP levels are increased in unaffected FD patients compared to healthy controls. This suggests that these biomarkers could be useful for the early detection of cardiac affectation in FD patients. On the other hand, hsTnT and male sex are independent risk factors for established clinical cardiac damage in FD.
Highlights
Fabry disease (FD) is a rare inherited lysosomal storage disorder linked to the X chromosome
We have measured selected biomarkers of different molecular pathophysiological pathways, including cardiac fibrosis, cardiac wall stress, myocardial injury, renal function and inflammation, in order to investigate if any is associated with early cardiac affectation in FD patients
Differences in enzyme replacement therapy (ERT), New York Heart Association (NYHA) functional class, Glomerular Filtration Rate (GFR), history of atrial fibrillation, left ventricular hypertrophy (LVH) and left ventricular maximum wall thickness (LVMT), α-Galactosidase activity and Lyso-Gb3 levels or Mainz Severity Score Index (MSSI) were present between the two cohorts
Summary
Fabry disease (FD) is a rare inherited lysosomal storage disorder linked to the X chromosome. Due to the heterogeneity in clinical manifestations of patients with FD, the Mainz Severity Score Index (MSSI) was proposed as an attempt to develop a disease-specific scoring system[8] This scheme covers different areas including cardiac signs and symptoms. Despite that the available evidence suggests that specific treatment using enzyme replacement therapy (ERT) with recombinant αGAL-A (agalsidase), is able to slow down the progression of FD, further reversal of organ involvement seems to remain out of reach[12]. This fact supports the importance of future research on the identification of early cardiac damage. We have measured selected biomarkers of different molecular pathophysiological pathways, including cardiac fibrosis, cardiac wall stress, myocardial injury, renal function and inflammation, in order to investigate if any is associated with early cardiac affectation in FD patients
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