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

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, Ca(10 - x)(HPO4)x(PO4)(6 - x)(OH)(2 - x); with 0<or=x<or=1. Calcification (quintiles) was positively associated with the mean gradient across the aortic valve (44 +/- 14, 52 +/- 17, 54 +/- 16, 60 +/- 15, 68 +/- 19 mm Hg; p<0.001). Males (n=101) had a higher degree of calcification (26.1 +/- 8.9 vs 20.8 +/- 9.2 mass%; p<0.001), despite the same mean gradient across the aortic valve (56 +/- 17 vs 56 +/- 19 mm Hg; p=0.958). 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.