Serum homocysteine and folate but not vitamin B12 are predictors of CHD mortality in older adults

Eur J Prev Cardiol. 2012 Dec;19(6):1420-9. doi: 10.1177/1741826711424568. Epub 2011 Sep 29.


Aims: The associations of serum levels of homocysteine (tHcy), vitamin B(12), and folate with risk of all-cause and coronary heat disease (CHD) mortality is controversial, and the evidence in older adults is limited. The aim of this study was to examine whether serum folate, vitamin B(12), and tHcy independently predict risk of CHD-related and all-cause mortality in older adults.

Methods and results: Serum concentrations of folate, vitamin B(12), and tHcy were determined from blood samples obtained from 3010 Blue Mountains Eye Study participants (1997-99), aged ≥55 years. CHD and all-cause mortality was confirmed using the Australian National Death Index.

Results: Persons in the highest quartile of serum tHcy had increased risk of CHD mortality compared to those in the lowest quartile (multivariable-adjusted hazard ratio, HR, 2.45, 95% CI 1.30-4.62). A significant continuous association was observed between serum tHcy and CHD mortality (HR per SD ( = 4.8 µmol/l) increase in serum tHcy 1.25, 95% CI 1.08-1.45), after multivariable-adjustment. A significant association between folate deficiency and CHD-mortality was found (multivariable-adjusted HR 1.53, 95% CI 1.01-2.29). Hyperhomocysteinaemia (>15 µmol/l) was a significant predictor of all-cause mortality (multivariable-adjusted HR 1.47, 95% CI 1.18-1.83). A significant interaction was observed between hyperhomocysteinaemia and folate deficiency for all-cause and CHD mortality (p for interaction = 0.03 and p for interaction = 0.05, respectively).

Conclusion: Serum tHcy and folate were independent predictors of CHD and all-cause mortality, while vitamin B(12) was not associated. As raised tHcy levels and folate deficiency are associated with poorer lifestyle, changes to a more healthful lifestyle among older adults may minimize the adverse vascular effects of elevated tHcy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Coronary Disease / blood*
  • Coronary Disease / mortality*
  • Down-Regulation
  • Female
  • Folic Acid / blood*
  • Folic Acid Deficiency / blood*
  • Folic Acid Deficiency / mortality*
  • Homocysteine / blood*
  • Humans
  • Hyperhomocysteinemia / blood*
  • Hyperhomocysteinemia / mortality*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • New South Wales / epidemiology
  • Prognosis
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Up-Regulation
  • Vitamin B 12 / blood*


  • Biomarkers
  • Homocysteine
  • Folic Acid
  • Vitamin B 12