Copyright © 2004 by the European Society of Cardiology.
Clinical research
The amount of calcium-deficient hexagonal hydroxyapatite in aortic valves is influenced by gender and associated with genetic polymorphisms in patients with severe calcific aortic stenosis
a Medical Clinic I, University Hospital of Aachen, Aachen University of Technology, Pauwelsstrasse 30, 52152 Aachen, Germany
b Institute of Inorganic Chemistry, Aachen University of Technology, Aachen, Germany
c Clinic for Cardiac Surgery, University Hospital of Aachen, Aachen University of Technology, Aachen, Germany
d Institute for Human Genetics, University Hospital of Aachen, Aachen University of Technology, Aachen, Germany
e Division of Molecular Cardiovascular Research, Medical Clinic I, Aachen University of Technology, Pauwelsstrasse 30, 52057 Aachen, Germany
Received March 25, 2003;
revised August 9, 2003;
accepted September 4, 2003
* Corresponding author. Tel.: +49-241-8089300/8088660; fax: +49-241-8082414
E-mail address: jrortlepp{at}ukaachen.de
Aims The study evaluated the relationship between cardiovascular risk factors (CRF), gene polymorphism, calcification and fibrosis of stenotic aortic valves.
Methods and results The calcium content of 187 excised stenotic aortic valves was determined using atomic absorption spectroscopy. Hydroxyproline content was quantified. Left-heart catheterization was performed. CRF and genotypes of the interleukin 10, connective tissue growth factor (CTGF) and chemokine receptor 5 (CCR5) polymorphisms were assessed. Calcification consisted of Ca-deficient hexagonal hydroxyapatite, Ca10–x(HPO4)x(PO4)6–x(OH)2–x; with 
. Calcification (quintiles) was positively associated with the mean gradient across the aortic valve (44±14, 52±17, 54±16, 60±15, 68±19 mmHg; 
). Males (
) had a higher degree of calcification (26.1±8.9 vs 20.8±9.2 mass%; ), despite the same mean gradient across the aortic valve (56±17 vs 56±19 mmHg; 
). CRF were not, whereas interleukin 10 polymorphisms –1082, –819, and –592 were significantly associated with the degree of calcification. Furthermore, if certain allele carriers had additionally the rare CCR5 or CTGF allele the degree of calcification was higher.
Conclusion Calcification of stenotic aortic valves consists of Ca-deficient hexagonal hydroxyapatite. Gender and genetic polymorphisms have an impact on the degree of aortic valve calcification.
Key Words: Calcification • Degenerative calcific aortic stenosis • Gene polymorphisms • Cardiovascular risk factors • Mass spectroscopy
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