Homocyst(e)ine and cardiovascular disease: a systematic review of the evidence with special emphasis on case-control studies and nested case-control studies.
BACKGROUND
Elevated concentrations of homocyst(e)ine are thought to increase the risk of vascular diseases including coronary heart disease and cerebrovascular disease.


METHODS
We searched MEDLINE (1966-1999), EMBASE (1974-1999), SciSearch (1974- 1999), and Dissertation Abstracts (1999) for articles and theses about homocyst(e)ine concentration and coronary heart disease and cerebrovascular disease.


RESULTS
We included 57 publications (3 cohort studies, 12 nested case-control studies, 42 case-control studies) that reported results on 5518 people with coronary heart disease (11,068 control subjects) and 1817 people with cerebrovascular disease (4787 control subjects) in our analysis. For coronary heart disease, the summary odds ratios (OR) for a 5-micromol/l increase in homocyst(e)ine concentration were 1.06 (95% CI : 0.99-1.13) for 2 publications of cohort studies, 1.23 (95% CI : 1.07-1.41) for 10 publications of nested case-control studies, and 1.70 (95% CI : 1.50-1.93) for 26 publications of case-control studies. For cerebrovascular disease, the summary OR for a 5-micromol/l increase in homocyst(e)ine concentration were 1.10 (95% CI : 0.94-1.28) for 2 publications of cohort studies, 1.58 (95% CI : 1.35-1.85) for 5 publications of nested case-control studies, and 2.16 (95% CI : 1.65-2.82) for 17 publications of case-control studies.


CONCLUSIONS
Prospective studies offer weaker support than case-control studies for an association between homocyst(e)ine concentration and cardiovascular disease. Although other lines of evidence support a role for homocyst(e)ine in the pathogenesis of cardiovascular disease, more information from prospective epidemiological studies or clinical trials is needed to clarify this role.
Ford
Earl S
ES
Division of Nutrition and Physical Activity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
Smith
S Jay
SJ
Stroup
Donna F
DF
Steinberg
Karen K
KK
Mueller
Patricia W
PW
Thacker
Stephen B
SB
D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D012307:Risk Factors
D006710:Homocysteine