Progression of aortic valve stenosis is associated with bone remodelling and secondary hyperparathyroidism in elderly patients--the COFRASA study

Eur Heart J. 2013 Jul;34(25):1915-22. doi: 10.1093/eurheartj/ehs450. Epub 2013 Jan 17.

Abstract

Aims: 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.

Methods and 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).

Conclusion: 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.

Keywords: Aortic stenosis; Bone remodelling; Calcium–phosphorus metabolism.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aortic Valve Stenosis / blood
  • Aortic Valve Stenosis / complications*
  • Biomarkers / metabolism
  • Bone Remodeling / physiology*
  • Calcium / metabolism
  • Collagen Type I / metabolism
  • Creatinine / metabolism
  • Female
  • Humans
  • Hyperparathyroidism, Secondary / blood
  • Hyperparathyroidism, Secondary / etiology*
  • Male
  • Osteocalcin / metabolism
  • Parathyroid Hormone / metabolism
  • Peptides / metabolism
  • Phosphorus / metabolism
  • Prospective Studies
  • Vitamin D / analogs & derivatives
  • Vitamin D / metabolism

Substances

  • Biomarkers
  • Collagen Type I
  • Parathyroid Hormone
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Vitamin D
  • Phosphorus
  • 25-hydroxyvitamin D
  • Creatinine
  • Calcium

Associated data

  • ClinicalTrials.gov/NCT00338676