Cardiovascular events in patients with fabry disease natural history data from the fabry registry.

Objectives: These analyses were designed to determine the incidence of major cardiovascular (CV) events and the natural history of CV complications in patients with Fabry disease.

Background: Fabry disease, a genetic disorder caused by deficiency of alpha-galactosidase A activity, is associated with CV dysfunction.

Methods: Major CV events (myocardial infarction, heart failure, or cardiac-related death) were analyzed in 2,869 Fabry Registry patients during the natural history period (i.e., before enzyme replacement therapy or among patients who never received therapy). Multivariate logistic regression analyses were performed to identify significant predictors of CV events.

Results: Eighty-three of 1,424 men (5.8%) and 54 of 1,445 women (3.7%) experienced CV events at mean ages of 45 and 54 years, respectively. Heart failure was the most common first CV event, reported by 50 men (3.5%) and 33 women (2.3%). Hypertension and left ventricular hypertrophy were the risk factors most strongly associated with CV events. When these parameters were used as covariates in logistic regression analyses, the odds ratio (OR) for hypertension in men was 7.8 (95% confidence interval [CI]: 2.1 to 28.6, p = 0.0019), and the OR for hypertension in women was 4.5 (95% CI: 1.6 to 12.3, p = 0.0037). The OR for left ventricular hypertrophy was 4.8 in men (95% CI: 1.03 to 22.2, p = 0.0463) and 8.2 in women (95% CI: 2.6 to 26.0, p = 0.0003).

Conclusions: Major CV events occurred in approximately 5% of Fabry Registry patients during the natural history period. All patients with Fabry disease should be monitored for possible CV risk factors, particularly hypertension and left ventricular hypertrophy.