Oral Presentation ESA-SRB Conference 2015

Proportion of undercarboxylated osteocalcin and serum P1NP predict incidence of myocardial infarction in older men. (#45)

Bu B Yeap 1 2 , Helman Alfonso 3 , Paul Chubb 4 , Elizabeth Byrnes 5 , John P Beilby 5 , Peter R Ebeling 6 , Carolyn A Allan 7 , Carl Schultz 1 , Graeme J Hankey 1 , Jonathan Golledge 8 , Leon Flicker 9 , Paul E Norman 10
  1. School of Medicine, University of Western Australia, Perth, WA, Australia
  2. Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA
  3. School of Public Health, Curtin University, Perth, Western Australia
  4. PathWest Laboratory Medicine, Fiona Stanley Hospital, Perth, Western Australia
  5. PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, WA
  6. Department of Medicine, School for Clinical Sciences, Monash University, Melbourne, Victoria, Australia
  7. Hudson Institute of Medical Research, Monash University, Melbourne, Victoria, Australia
  8. Vascular Biology Unit, James Cook University, Townsville, QLD, Australia
  9. School of Medicine, University of Western Australia, Perth, WA, Australia
  10. School of Surgery, University of Western Australia, Perth, WA, Australia

Introduction and aims

Undercarboxylated osteocalcin (ucOC) modulates insulin secretion and sensitivity in mice, and higher ucOC is associated with lower diabetes risk in men (1). Diabetes is associated with cardiovascular risk, but the influence of ucOC on incidence of cardiovascular events is unclear. We examined associations of ucOC and other bone turnover markers with incidence of myocardial infarction (MI) and stroke in older men.

Participants and methods

This was a longitudinal study of community-dwelling men aged 70-89 years resident in Perth, Western Australia. Serum total osteocalcin (TOC), N-terminal propeptide of type I collagen (P1NP) and collagen type I C-terminal cross-linked telopeptide (CTX) were measured by immunoassay, and ucOC by hydroxyapatite binding. The ratio ucOC/TOC was calculated. Hospital admissions and deaths from myocardial infarction (MI) and stroke were ascertained.

Results

There were 3,384 men followed for 7.0 years during which 293 experienced an MI, 251 stroke and 2,840 neither. In multivariate analyses, higher ratio of ucOC/TOC (expressed as %) was associated with lower incidence of MI (quartiles Q2-4, ≥49% vs Q1,<49%, hazard ratio [HR]=0.70, 95% confidence interval [CI]=0.54-0.91), but not of stroke (0.99, 0.73-1.34). Higher P1NP was associated with higher incidence of MI (Q2-4, ≥28.2 µg/L vs Q1, <28.2 µg/L, HR=1.45, 95% CI=1.06-1.97), but not of stroke (0.94, 0.70-1.26). CTX was not associated with incident MI or stroke. These results were unchanged following exclusion of men experiencing MI within the first year of follow-up.

Conclusions

A reduced proportion of ucOC relative to TOC, or higher P1NP, is associated with increased incidence of MI. UcOC/TOC ratio and P1NP predict risk of MI but not stroke, in a manner distinct from CTX. Further studies are needed to investigate potential mechanisms by which bone turnover markers related to metabolic risk and to collagen formation could modulate cardiovascular risk.

  1. Yeap BB, Alfonso H, Chubb SAP, Gauci R, Byrnes E, Beilby JP, Ebeling PR, Handelsman DJ, Allan CA, Grossmann M, Flicker L, Norman PE. Higher serum undercarboxylated osteocalcin and other bone turnover markers are associated with reduced diabetes risk and lower estradiol concentrations in older men. J Clin Endocrinol Metab 2015; 100: 63-71.