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C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S.
David I Buckley1, Rongwei Fu, Michele Freeman
1Oregon Evidence-based Practice Center, Oregon Health & Science University, Portland, Oregon 97239, USA.
Insights
C-reactive protein (CRP) improves coronary heart disease (CHD) risk assessment for intermediate-risk individuals. While CRP levels predict CHD events, evidence for preventing them by lowering CRP is insufficient.
Area of Science:
- Cardiology
- Preventive Medicine
- Biomarkers
Background:
- C-reactive protein (CRP) is a potential biomarker for refining coronary heart disease (CHD) risk assessment.
- Its utility is particularly noted for individuals at intermediate risk based on traditional factors alone.
Purpose of the Study:
- To evaluate the evidence for incorporating CRP into CHD risk assessment guidelines.
- To assist the U.S. Preventive Services Task Force (USPSTF) in this decision-making process.
Main Methods:
- A comprehensive literature search of MEDLINE and other sources (1966-2007) was conducted.
- Included were prospective cohort, case-cohort, and nested case-control studies assessing CRP's predictive ability in intermediate-risk populations.
- Study quality and data were systematically reviewed and synthesized, including meta-analysis.
Main Results:
- Strong evidence shows CRP is associated with incident CHD events (RR 1.58 for high vs. low CRP).
- Adding CRP to risk models consistently improves risk stratification in intermediate-risk persons.
- CRP has desirable test characteristics, with good data on prevalence in this group.
Conclusions:
- While CRP improves risk stratification for CHD, study methods and population representation (ethnic/racial minorities) present limitations.
- Moderate evidence supports using CRP for risk prediction in intermediate-risk individuals.
- Insufficient evidence currently exists to confirm that reducing CRP levels prevents CHD events.
Background:
C-reactive protein (CRP) may help to refine global risk assessment for coronary heart disease (CHD), particularly among persons who are at intermediate risk on the basis of traditional risk factors alone.
Purpose:
To assist the U.S. Preventive Services Task Force (USPSTF) in determining whether CRP should be incorporated into guidelines for CHD risk assessment.
Data Sources:
MEDLINE search of English-language articles (1966 to November 2007), supplemented by reference lists of reviews, pertinent studies, editorials, and Web sites and by expert suggestions.
Study Selection:
Prospective cohort, case-cohort, and nested case-control studies relevant to the independent predictive ability of CRP when used in intermediate-risk persons.
Data Extraction:
Included studies were reviewed according to predefined criteria, and the quality of each study was rated.
Data Synthesis:
The validity of the body of evidence and the net benefit or harm of using CRP for CHD risk assessment were evaluated. The combined magnitude of effect was determined by meta-analysis. The body of evidence is of good quality, consistency, and applicability. For good studies that adjusted for all Framingham risk variables, the summary estimate of relative risk for incident CHD was 1.58 (95% CI, 1.37 to 1.83) for CRP levels greater than 3.0 mg/L compared with levels less than 1.0 mg/L. Analyses from 4 large cohorts were consistent in finding evidence that including CRP improves risk stratification among initially intermediate-risk persons. C-reactive protein has desirable test characteristics, and good data exist on the prevalence of elevated CRP levels in intermediate-risk persons. Limited evidence links changes in CRP level to primary prevention of CHD events.
Limitations:
Study methods for measuring Framingham risk variables and other covariates varied. Ethnic and racial minority populations were poorly represented in most studies, limiting generalizability. Few studies directly assessed the effect of CRP on risk reclassification in intermediate-risk persons.
Conclusion:
Strong evidence indicates that CRP is associated with CHD events. Moderate, consistent evidence suggests that adding CRP to risk prediction models among initially intermediate-risk persons improves risk stratification. However, sufficient evidence that reducing CRP levels prevents CHD events is lacking.
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