title: Long-term changes in arterial structure and function and left ventricular geometry after enzyme replacement therapy in patients affected with Fabry disease.
abstract: OBJECTIVE
  Fabry disease is a lysosomal storage disorder due to deficient alpha-galactosidase A activity, characterised by glycosphingolipids deposition in tissues. Patients have a common arterial involvement and contract progressive renal and cardiac disease. Although short-term effects of enzyme replacement therapy (ERT) on target organs have been established, no data are available on the long-term outcome.
  
  
  RESULTS
  We studied the effects of ERT (agalsidase beta, 1 mg/kg/14 days) on arterial and cardiac structure and function during a longitudinal study beginning in 1999, with 4.5 ± 0.4 years follow-up (four visits) in 30 patients (age: 33 ± 12 years). In addition, we studied 16 untreated Fabry patients during 2.6 ± 1.6 years (two visits). Aortic stiffness was determined by carotid-femoral pulse wave velocity, central pulse pressure by aplanation tonometry, and carotid and radial intima-media thickness and diameter by high definition echotracking device. Left ventricular mass was determined by MRI. A significant decrease in aortic stiffness (-0.56 ± 0.13 m/s/yr, p = 0.0002) was observed after ERT whereas central pulse pressure did not change. Carotid intima-media thickness (IMT) increased (+18 ± 6 µm/yr; p < 0.005) whereas radial IMT remained stable. Radial artery diameter decreased (-50 ± 20 µm/years, p < 0.05) whereas carotid diameter did not change. Carotid circumferential wall stress was reduced (-1.7 ± 0.6 kPa/yrs, p < 0.01). Left ventricular mass index significantly decreased (-7.8 ± 2.3 g/m(2)/yr, p < 0.005).
  
  
  CONCLUSIONS
  A sustained reduction in aortic stiffness and left ventricular hypertrophy, and a limited radial artery wall thickening were observed after long-term enzyme replacement therapy. There was no significant benefit of treatment on carotid hypertrophy.
authors: University of Versailles-Saint Quentin en Yvelines, Division of Medical Genetics, Hôpital Raymond Poincaré (AP-HP), Garches, France.
authors: Cédric
authors: C
authors: Collin
authors: Marie
authors: M
authors: Briet
authors: Thi-Chien
authors: TC
authors: Tran
authors: Hélène
authors: H
authors: Beaussier
authors: Karelle
authors: K
authors: Benistan
authors: Mourad
authors: M
authors: Bensalah
authors: Elie
authors: E
authors: Mousseaux
authors: Marc
authors: M
authors: Froissart
authors: Erwan
authors: E
authors: Bozec
authors: Stéphane
authors: S
authors: Laurent
authors: Pierre
authors: P
authors: Boutouyrie
authors: Dominique P
authors: DP
authors: Germain
mesh_terms: D000328:Adult; D001011:Aorta / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure; D002339:Carotid Arteries / Q000473:pathology / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D003187:Compliance; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005260:Female; D005602:France; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007527:Isoenzymes / Q000627:therapeutic use*; D016014:Linear Models; D008137:Longitudinal Studies; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008365:Manometry; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D011673:Pulsatile Flow; D017534:Radial Artery / Q000473:pathology / Q000503:physiopathology; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D000519:alpha-Galactosidase; C459420:agalsidase beta