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Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis
Linda L Humphrey1, Rongwei Fu, Kevin Rogers
1Department of Medical Informatics and Clinical Epidemiology, Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR 97239-3098, USA.
Insights
Elevated homocysteine levels significantly increase the risk of coronary heart disease (CHD). A 5 micromol/L rise in homocysteine independently boosts CHD event risk by about 20%.
Area of Science:
- Cardiovascular epidemiology
- Clinical biochemistry
Background:
- Coronary heart disease (CHD) remains a leading cause of mortality worldwide.
- Identifying novel risk factors is crucial for effective prevention strategies.
- Homocysteine has been investigated as a potential contributor to CHD development.
Purpose of the Study:
- To evaluate if elevated homocysteine levels are an independent risk factor for incident coronary heart disease (CHD).
- To provide evidence for the US Preventive Services Task Force's assessment of novel CHD risk factors.
Main Methods:
- A systematic review and meta-analysis of prospective cohort studies were conducted.
- Studies published between 1966 and March 2006 were identified via MEDLINE and reference lists.
- Quality-rated studies measuring homocysteine and CHD incidence in adults without prior CHD were included.
Main Results:
- Twenty-six high-quality articles were analyzed.
- A 5 micromol/L increase in homocysteine was associated with a 20% to 50% elevation in CHD risk across most studies.
- The meta-analysis revealed a combined risk ratio of 1.18 (95% CI, 1.10-1.26) for coronary events per 5 micromol/L homocysteine increase.
Conclusions:
- Elevated homocysteine levels independently increase the risk of coronary heart disease events.
- Each 5 micromol/L increment in homocysteine raises CHD risk by approximately 20%.
Objective:
To determine whether an elevated homocysteine level is an independent risk factor for the development of coronary heart disease (CHD) to aid the US Preventive Services Task Force in its evaluation of novel risk factors for incident CHD.
Methods:
Studies of homocysteine and CHD were identified by searching MEDLINE (1966 through March 2006). We obtained additional articles by reviewing reference lists from prior reviews, original studies, editorials, and Web sites and by consulting experts. We included prospective cohort studies that measured homocysteine and Framingham risk factors and the incidence of CHD in the general adult population without known CHD. Each study was quality rated using criteria developed by the US Preventive Services Task Force. We conducted a meta-analysis using a random-effects model to determine summary estimates of the risk of major CHD associated with each 5-micromol/L increase in homocysteine level. The systematic review and meta-analysis were conducted between January 25, 2005, and September 17, 2007.
Results:
We identified 26 articles of good or fair quality. Most studies found elevations of 20% to 50% in CHD risk for each increase of 5 micromol/L in homocysteine level. Meta-analysis yielded a combined risk ratio for coronary events of 1.18 (95% confidence interval, 1.10-1.26) for each increase of 5 micromol/L in homocysteine level. The association between homocysteine and CHD was similar when analyzed by sex, length of follow-up, outcome, study quality, and study design.
Conclusion:
Each increase of 5 micromol/L in homocysteine level increases the risk of CHD events by approximately 20%, independently of traditional CHD risk factors.
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