ORIGINAL ARTICLEHomocysteine Level and Coronary Heart Disease Incidence: A Systematic Review and Meta-analysis
Section snippets
METHODS
We reviewed the MEDLINE and Cochrane Controlled Trials Register Database (1966 through March 2006) using the following keywords: cohort studies, cardiovascular diseases, homocysteine, hyperhomocysteinemia, and cystathionine beta-synthase. To ensure complete ascertainment, we reviewed the bibliographies of reviews, editorials, book chapters, and letters that discussed the association between homocysteine and CHD outcomes. We sought primary prevention trials and studies that evaluated the risk
RESULTS
A total of 603 abstracts were identified from our literature searches, and 163 articles were reviewed for inclusion. Of the 31 studies (articles) from 24 cohorts representing populations from North America and Europe that were included (Table 2), 23 were nested case-control studies,27, 28, 30, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 58 and 8 were cohort studies.29, 51, 52, 53, 54, 55, 56, 57 Of the 23 nested case-control studies, 12 studies were rated good
DISCUSSION
Our review shows an association between elevated homocysteine levels and CHD that is independent of Framingham risk factors. In the overall analysis, the risk of any CHD event increased approximately 20% for each increase of 5 μmol/L of homocysteine. Because some studies reported only CVD events and because statistically these events are dominated by CHD events, we think that the overall estimate of 1.18 for all good and fair studies combined gives an accurate measure of the risk of CHD.
To our
CONCLUSION
Elevated homocysteine levels independently and moderately increase the risk of developing CHD either in a causal manner or as a risk marker by approximately 20%. The prevalence of above-normal homocysteine levels in the United States has been shown to be higher than 5% to 10% in several population-based cohorts, even after widespread fortification of food with folic acid. Thus, if primary prevention treatment studies were to show benefit among persons with elevated homocysteine levels, many CHD
Acknowledgments
We thank Miranda Walker, BA, David Buckley, MD, and Craig Fleming, MD, for their contributions on this project and Andrew Hamilton, MLS, MS, for conducting the literature searches.
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This research was funded by the Agency for Healthcare Research and Quality to support the work of the US Preventive Services Task Force under contract 290-02-0024, task order 2, Rockville, MD.