title: Progression of aortic valve stenosis is associated with bone remodelling and secondary hyperparathyroidism in elderly patients--the COFRASA study.
abstract: OBJECTIVE
  There is currently no medical therapy that can prevent the progression of aortic valve stenosis (AS). Recent data highlight a possible relationship between bone metabolism and AS progression but prospective data are lacking.
  
  
  RESULTS
  Serum levels of calcium, phosphorus, creatinine, 25-OH vitamin D, intact parathyroid hormon (iPTH), C-terminal-telopeptide of type-1-collagen (CTX) and osteocalcin were assessed at baseline in 110 elderly patients (age ≥70 years) with at least mild AS. CTX/osteocalcin ratio was calculated as a marker of bone remodelling balance. AS severity was assessed at baseline and 1-year based on the mean gradient. Two-thirds of patients had low 25-OH vitamin D and 20% had secondary hyperparathyroidism. AS progression was not associated with age, glomerular filtration rate (GFR), calcium and phosphorus levels, calcium-phosphorus product, but significantly with iPTH, CTX/osteocalcin and vitamin D status (all P < 0.01). There was no correlation between iPTH and CTX/osteocalcin (R = 0.04, P = 0.70) and AS progression was associated with CTX/osteocalcin (R = 0.42, P = 0.009), but not with iPTH (R = 0.10, P = 0.55) in patients with normal vitamin D levels, whereas it was associated with iPTH (R = 0.47, P < 0.001) and not with CTX/osteocalcin (R = 0.04, P = 0.73) in those with low vitamin D levels, especially if mild renal insufficiency was present (R = 0.61, P < 0.001).
  
  
  CONCLUSIONS
  In elderly patients with AS, we observed an association between AS progression and vitamin D, iPTH and CTX/osteocalcin ratio and their respective influence varied according to the vitamin D status. In patients with normal vitamin D levels, AS progression was associated with a bone resorptive balance, whereas in patients with low vitamin D levels, AS progression was associated with iPTH and secondary hyperparathyroidism, especially if mild renal insufficiency was present. These findings may have important prognostic and therapeutic implications. Trial registration information: Clinicaltrials.gov identifier number: NCT00338676, funded by AP-HP, the COFRASA study.
authors: Cardiovascular Division, Department of Cardiology, AP-HP, Bichat Hospital, Paris, France.
authors: Guillaume
authors: G
authors: Hekimian
authors: Anne
authors: A
authors: Boutten
authors: Martin
authors: M
authors: Flamant
authors: Xavier
authors: X
authors: Duval
authors: Monique
authors: M
authors: Dehoux
authors: Joelle
authors: J
authors: Benessiano
authors: Virginie
authors: V
authors: Huart
authors: Thierry
authors: T
authors: Dupré
authors: Nadia
authors: N
authors: Berjeb
authors: Florence
authors: F
authors: Tubach
authors: Bernard
authors: B
authors: Iung
authors: Alec
authors: A
authors: Vahanian
authors: David
authors: D
authors: Messika-Zeitoun
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000097:blood / Q000150:complications*; D015415:Biomarkers / Q000378:metabolism; D016723:Bone Remodeling / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000209:etiology*; D008297:Male; D015675:Osteocalcin / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D011446:Prospective Studies; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D014807:Vitamin D; D010758:Phosphorus; C104450:25-hydroxyvitamin D; D003404:Creatinine; D002118:Calcium
keywords: Aortic stenosis; Bone remodelling; Calcium–phosphorus metabolism