Non invasive evaluation of endothelial function in patients with Anderson-Fabry disease

Fabry's disease is an X-linked recessive abnormality of glycosphingolipid metabolism. Increased levels of endothelial prothrombotic factors have recently been demonstrated in Fabry's disease, whereas endothelial function has not been studied using high resolution ultrasound.

We enrolled 6 patients (4 male, 2 female; mean age, 37 years) and 12 sex matched control subjects (mean age, 37 years). Patients' exclusion criteria included a prior history of cardiac disease, diabetes and treated or untreated hypertension. Patients underwent: anamnesis, physical examination, EKG, 2-dimensional echocardiography with tissue Doppler, measurement of body weight and height, blood pressure. Biochemistry variables were also considered: fasting blood sugar, total cholesterol, HDL-C, LDL-C, triglycerides, fibrinogen, C reactive protein and homocysteine. Using high resolution ultrasound, we assessed the brachial vasodilator response to reactive hyperemia (endothelium-dependent) and sublingual nitroglycerin (NTG) (endothelium-independent). Flow-mediated dilatation (FMD) was expressed as percentage change in post-stimulus diameter in comparison with the baseline.

In baseline condition, there was no significant difference between patients and controls in the brachial artery diameter (3.5+/-0.55 vs 3.1+/-0.4). After reactive hyperemia, the FMD change was significantly higher in controls than in patients (16.5+/-6.3% vs 9.3+/-6.2%, P<0.05). After NTG, endothelium-independent vasodilation did not show a significant difference between cases and controls (15+/-7.7% vs 13.8+/-7.1%).

Our study demonstrated the presence of endothelial dysfunction in patients with Fabry's disease in comparison to controls. We hypothesized that endothelial dysfunction may contribute to the pathogenesis of ischemic events in patients with Fabry's disease.