Long-term changes in arterial structure and function and left ventricular geometry after enzyme replacement therapy in patients affected with Fabry disease.

Abstract

AIMS:

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.

METHODS AND 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).

CONCLUSION:

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: Cédric Collin, Marie Briet, Thi-Chien Tran, Hélène Beaussier, Karelle Benistan, Mourad Bensalah, Elie Mousseaux, Marc Froissart, Erwan Bozec, Stéphane Laurent, Pierre Boutouyrie, Dominique P Germain
• Journal: European journal of preventive cardiology (Eur J Prev Cardiol) Vol. 19 Issue 1 Pg. 43-54 (Feb 2012) ISSN: 2047-4881 [Electronic] England
• PMID: 21450622 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• alpha-Galactosidase
• agalsidase beta

Topics

• Adult
• Aorta (pathology, physiopathology)
• Blood Pressure
• Carotid Arteries (pathology, physiopathology)
• Carotid Intima-Media Thickness
• Case-Control Studies
• Compliance
• Enzyme Replacement Therapy
• Fabry Disease (complications, drug therapy, enzymology, genetics)
• Female
• France
• Humans
• Hypertrophy, Left Ventricular (diagnosis, etiology, pathology, physiopathology)
• Isoenzymes (therapeutic use)
• Linear Models
• Longitudinal Studies
• Magnetic Resonance Imaging, Cine
• Male
• Manometry
• Middle Aged
• Multivariate Analysis
• Prospective Studies
• Pulsatile Flow
• Radial Artery (pathology, physiopathology)
• Stroke Volume
• Time Factors
• Treatment Outcome
• Vascular Diseases (diagnosis, etiology, pathology, physiopathology)
• Ventricular Function, Left
• Young Adult
• alpha-Galactosidase (genetics, therapeutic use)