Impact of Nontreatment Duration and Keratopathy on Major Adverse Cardiovascular Events in Fabry Disease: A Nationwide Cohort Study.

Abstract

Fabry disease (FD) is a rare inherited X-linked lysosomal storage disorder that results in the progressive accumulation of glycosphingolipids in multiple organs. Early FD-specific treatments may improve clinical outcomes; however, clinical evidence about early FD treatment is limited. We aimed to determine the cardiovascular outcomes of patients with FD who received enzyme replacement therapy. This nationwide observational study was conducted using the National Health Claims database of the Korean population with FD. The primary outcome was major adverse cardiovascular events (MACEs). MACE risk factors in FD were evaluated using time-dependent Cox regression. Between January 2007 and April 2022, 188 patients with FD were analyzed. Among them, 22 (11.7%) experienced MACE (males: 14/95 [14.7%]; females: 8/93 [8.6%]). The mean age at MACE diagnosis was 53.5 ± 11.0 years in all patients with FD, which was lower in males compared with in females (49.7 ± 9.6 vs. 60.0 ± 10.7 years, p = 0.030). Multivariate analysis (HR, 95% CI) revealed that age (1.042; 1.004-1.082) and duration of FD nontreatment (1.040; 1.003-1.078) were significant MACE risk factors in all patients. In males, age (1.080; 1.032-1.131), FD nontreatment duration (1.099; 1.048-1.152), and keratopathy (18.920; 4.174-85.749) were significant MACE risk factors in multivariate analysis. In females, the only significant MACE risk factor was a high Charlson comorbidity index score (1.795; 1.229-2.622). In conclusion, duration of FD nontreatment and keratopathy are significant MACE risk factors in males with FD. These findings suggest the importance of early initiation of FD-specific treatment and careful evaluation of keratopathy in males with FD.