Stroke in Fabry Disease: Identification of Risk Factors for Stroke in a Large Single-Centre Cohort

Abstract

Fabry disease; Lysosomal storage disorders; Stroke

Malaltia de Fabry; Trastorns d'emmagatzematge lisosomal; Ictus

Enfermedad de Fabry; Trastornos de almacenamiento lisosomal; Ictus

Objectives Risk factors for stroke in Fabry disease (FD) are not precisely known. This study presents a retrospective cohort analysis from one reference centre in the United Kingdom to determine risk factors for stroke and to develop a predictive model. Methods Patients > 18 years old were included in the study and were followed from their first visit until March 2019. The main outcome of the survival analysis was time to stroke. The independent risk factors were evaluated using a multivariate Cox regression. Results Of 414 patients, 368 were included in the survival analysis. 227 (61.7%) were female, with a median baseline age of 42.7 (IQR 27.8–54.8) for males and 39.9 (26.6–51.2) years for females. 56 (39.7%) males and 64 (28.2%) females had the N215S genotype. 41 patients had a stroke at baseline (11.2%), rising to 69 (18.8%) at the end—66.7% lacunar, 18.9% anterior circulation, 13% posterior circulation and 1.4% venous thrombosis. Median follow-up was 10.4 years. Median time to stroke in males and females was 43 (43–43) and 58 (58–59) years, respectively. In the multivariate analysis, a concomitant autoimmune disease was associated with an increased risk of stroke, while glomerular filtration rate > 90 and N215S genotype were associated with a decreased risk. Interpretation Sex was not associated with stroke, despite males being more severe. These results might help stratify patients and are of interest not only to metabolic physicians, but to general stroke physicians too.

This work was supported by “La Caixa” Foundation (ID 100010434) with fellowship code LCF/BQ/EU20/11810050, and the MPS Society UK, via the grant Causes, prevention and treatment of stroke in Fabry Disease.