Elevated homocysteine levels and risk of cardiovascular and all-cause mortality: a meta-analysis of prospective studies

J Zhejiang Univ Sci B. 2015 Jan;16(1):78-86. doi: 10.1631/jzus.B1400183.


Objective: To investigate whether elevated homocysteine levels were a predictor of subsequent coronary heart disease (CHD) mortality, cardiovascular mortality or all-cause mortality in the general population by a meta-analysis.

Methods: In a systematic search conducted in the databases of PubMed and Embase prior to October 2013, we identified relevant prospective observational studies evaluating the association between baseline homocysteine levels and CHD mortality, cardiovascular or all-cause mortality in the general population. Pooled adjust risk ratio (RR) and corresponding 95% confidence interval (CI) were calculated separately for categorical risk estimates and continuous risk estimates.

Results: Twelve studies with 23623 subjects were included in the meta-analysis. Comparing the highest to lowest homocysteine level categories, CHD mortality increased by 66% (RR 1.66; 95% CI 1.12-2.47; P=0.012), cardiovascular mortality increased by 68% (RR 1.68; 95% CI 1.04-2.70; P=0.033), and all-cause mortality increased by 93% (RR 1.93; 95% CI 1.54-2.43; P<0.001). Moreover, for each 5 μmol/L homocysteine increment, the pooled RR was 1.52 (95% CI 1.26-1.84; P<0.001) for CHD mortality, 1.32 (95% CI 1.08-1.61; P=0.006) for cardiovascular mortality, and 1.27 (95% CI 1.03-1.55; P=0.023) for all-cause mortality.

Conclusions: Elevated homocysteine levels are an independent predictor for subsequent cardiovascular mortality or all-cause mortality, and the risks were more pronounced among elderly persons.

Keywords: All-cause mortality; Cardiovascular mortality; Coronary heart disease; Homocysteine; Meta-analysis.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / mortality*
  • Coronary Disease / blood
  • Coronary Disease / mortality
  • Female
  • Homocysteine / blood*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Observational Studies as Topic
  • Odds Ratio
  • Prospective Studies
  • Young Adult


  • Homocysteine