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Associations of total osteocalcin with all-cause and cardiovascular mortality in older men. The Health In Men Study
B B Yeap1, S A P Chubb, L Flicker
1School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia. byeap@cyllene.uwa.edu.au
Insights
Total osteocalcin (TOC) levels in older men show a U-shaped relationship with mortality. Both low and high TOC levels are associated with increased all-cause and cardiovascular mortality risk.
Area of Science:
- Gerontology
- Endocrinology
- Cardiovascular Health
Background:
- Reduced total osteocalcin (TOC) is linked to obesity, insulin resistance, and type 2 diabetes, suggesting a role in cardiovascular risk.
- Limited longitudinal data exist on TOC levels and survival outcomes.
- This study investigates the association between TOC levels and mortality in older men.
Purpose of the Study:
- To examine the relationship between baseline total osteocalcin (TOC) levels and all-cause and cardiovascular mortality in elderly men.
- To determine if TOC levels predict mortality risk in a longitudinal cohort.
Main Methods:
- Prospective cohort study of 3,542 community-dwelling men aged 70-89 years.
- Plasma TOC levels were measured at baseline (2001-2004).
- Mortality data (all-cause and cause-specific) were collected through December 2008 and analyzed using Cox regression, adjusting for cardiovascular risk factors.
Main Results:
- During a median follow-up of 5.2 years, 572 deaths occurred.
- Mortality risk was lowest in the second quintile of TOC levels.
- Men in the lowest and highest TOC quintiles had significantly increased all-cause mortality (HR 1.36 and 1.53, respectively).
- Low TOC levels were associated with similar risks for cardiovascular and non-cardiovascular deaths, while high TOC levels predicted cardiovascular disease mortality (HR 1.69).
Conclusions:
- Total osteocalcin (TOC) is a predictor of all-cause and cardiovascular mortality in older men.
- The association between TOC and mortality is U-shaped, with increased risk at both low and high levels.
- Further research is needed to elucidate the mechanisms, including bone turnover and osteocalcin's biological activity.
Summary:
In older men, both lower and higher total osteocalcin levels predict increased all-cause mortality, with comparable associations for cardiovascular and non-cardiovascular deaths. Differences in osteocalcin levels might influence glucose metabolism and thereby cardiovascular risk, or reflect changes in bone turnover thus representing a marker for poorer health outcomes.
Introduction:
Reduced levels of total osteocalcin (TOC) are associated with adiposity, insulin resistance and type 2 diabetes, implying this bone-derived peptide might modulate cardiovascular risk. However, there are few longitudinal data relating TOC levels to survival. We examined associations of TOC level with all-cause and cardiovascular mortality in older men.
Methods:
We conducted a prospective cohort study of community-dwelling men aged 70-89 years. Aliquots of plasma collected at baseline (2001-2004) were assayed for TOC. Incidence and causes of death to 31 December 2008 were ascertained using data linkage. Cox regression analyses were performed with adjustment for conventional cardiovascular risk factors.
Results:
From 3,542 men followed for median 5.2 years there were 572 deaths (16.1%). Mortality was lowest in men with TOC levels in the second quintile (12.6%). In multivariate analyses, men with TOC in the lowest and highest quintiles of values had increased all-cause mortality (Q1 vs Q2: hazard ratio [HR], 1.36; 95% confidence interval 1.02-1.80 and Q5 vs Q2: HR, 1.53, 95% CI 1.18-1.98). Men with low TOC levels had similar HR for cardiovascular and non-cardiovascular deaths (Q1 vs Q2: HR, 1.35 and 1.30 respectively). Higher TOC levels predicted cardiovascular disease (CVD)-related mortality (Q5 vs Q2, HR, 1.69, 95% CI 1.09-2.64).
Conclusions:
TOC predicts all-cause and CVD-related mortality in community-dwelling older men. However, the relationship is U shaped with men at both ends of the distribution at increased risk. Further investigation is required to clarify whether the underlying mechanisms involve altered bone turnover or relate specifically to the biological activity of osteocalcin.
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