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Homocysteine Level and Coronary Heart Disease Incidence: A Systematic Review and Meta-analysis

  • Linda L. Humphrey
    Correspondence
    Individual reprints of this article are not available. Address correspondence to Linda Humphrey, MD, MPH, Oregon Health & Science University, Mailcode BICC, 3181 SW Sam Jackson Park Rd, Portland, OR 97239-3098
    Affiliations
    Oregon Evidence-based Practice Center, Oregon Health & Science University, Portland

    Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland

    Department of Medicine, Oregon Health & Science University, Portland

    Public Health and Preventive Medicine, Oregon Health & Science University, Portland

    Hospital and Specialty Medicine, Veterans Affairs Medical Center, Portland, Oregon
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  • Rongwei Fu
    Affiliations
    Oregon Evidence-based Practice Center, Oregon Health & Science University, Portland

    Public Health and Preventive Medicine, Oregon Health & Science University, Portland

    Emergency Medicine, Oregon Health & Science University, Portland
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  • Kevin Rogers
    Affiliations
    Oregon Evidence-based Practice Center, Oregon Health & Science University, Portland

    Division of Cardiology, University of Utah Health Sciences Center, Salt Lake City
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  • Michele Freeman
    Affiliations
    Oregon Evidence-based Practice Center, Oregon Health & Science University, Portland
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  • Mark Helfand
    Affiliations
    Oregon Evidence-based Practice Center, Oregon Health & Science University, Portland

    Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland

    Department of Medicine, Oregon Health & Science University, Portland

    Hospital and Specialty Medicine, Veterans Affairs Medical Center, Portland, Oregon
    Search for articles by this author

      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-μmol/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 μmol/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 μmol/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 μmol/L in homocysteine level increases the risk of CHD events by approximately 20%, independently of traditional CHD risk factors.
      CHD (coronary heart disease), CI (confidence interval), CVD (cardiovascular disease), MI (myocardial infarction), RR (risk ratio), USPSTF (US Preventive Services Task Force)
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      Linked Article

      • Homocysteine: The Rubik's Cube of Cardiovascular Risk Factors
        Mayo Clinic ProceedingsVol. 83Issue 11
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          In the 20th century, the United States witnessed a steady and dramatic increase in the prevalence of coronary heart disease (CHD), with CHD ranking as the leading cause of death every year after 1910. After World War II, the National Heart Institute (now known as the National Heart, Lung, and Blood Institute) embarked on an ambitious longitudinal study of healthy men and women to identify potential causes of this growing epidemic and funded the Framingham Heart Study in 1948. A decade later, the study's director, Dr Thomas Dawber, published a series of landmark articles from the Framingham cohort identifying what he coined risk factors for the development of heart disease; these included hypertension, high cholesterol, and smoking.
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