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Screening for Intermediate Risk Factors for Coronary Heart Disease

Evidence Syntheses, No. 73

Investigators: , MD, MPH, , MD, , MD, , PhD, , MPH, , MD, MPH, , MD, and , MA.

Author Information and Affiliations
Rockville (MD): Agency for Healthcare Research and Quality (US); .
Report No.: 10-05141-EF-1

Structured Abstract


In the United States, coronary heart disease and cardiovascular disease account for nearly 40% of deaths each year. An individual’s estimated risk for coronary heart disease events, often based on factors incorporated into the Framingham risk score, guides the intensity of risk reduction interventions. We conducted a systematic review of epidemiologic studies to help the U.S. Preventive Services Task Force determine which, if any, of 9 additional risk factors should be considered for incorporation into guidelines for coronary and cardiovascular risk assessment in primary care.

Data Sources:

We conducted multiple searches of MEDLINE (1966 to March 2006) for epidemiologic studies relevant to the independent predictive ability of the risk factor when used in intermediate-risk individuals. We obtained additional articles from recent systematic reviews, reference lists of pertinent studies, reviews, editorials, websites, and by consulting experts.

Review Methods:

We rated the validity and applicability of each included study and characterized several dimensions of the body of evidence for each risk factor. For applicability, we assessed whether the study was drawn from the general population or a demographic subset of asymptomatic adults; whether it included or focused on intermediate-risk individuals (those who have a 10% – 20% 10-year risk of coronary heart disease events); and the measurement of the Framingham and emerging risk factors and of endpoints. We conducted several meta-analyses of the ability of each of the risk factors to predict major coronary heart disease events independently of Framingham risk factors in intermediate-risk subjects.


Results of the literature review are summarized in the Tables. There are no definitive data from randomized trials on how use of any of these factors in risk assessment would affect cardiac morbidity and mortality. We used a mathematical model to assess the potential impact of using a test for C-reactive protein in intermediate-risk individuals. Under the assumption that those reclassified as high risk (>20% 10-year risk) would have a 30% reduction in the 10-year risk of coronary heart disease events, the main finding was that, use of C-reactive protein could reclassify enough intermediate-risk men to have a major impact.


Several emerging risk factors provided independent information about coronary heart disease risk, but for most there were limitations in the evidence base. Across all of the criteria listed in the table, C-reactive and electron beam computed tomography scan had the strongest evidence for an independent effect in intermediate-risk individuals, and both reclassify some individuals as high-risk. However, data on electron beam computed tomography are relatively sparse, the technique is more expensive, and its potential harms require more investigation. Periodontal disease, carotid intima media thickness, homocysteine, and lipoprotein(a) probably provide independent information about coronary heart disease risk, but data about their prevalence and impact when added to Framingham risk score in intermediate-risk individuals are limited.


This Systematic Evidence Review has been updated in the following publications:

Helfand M, Buckley DI, Freeman M, Fu R, Rogers K, Fleming C, Humphrey L. Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151:496–508.

Buckley DI, Fu R, Freeman M, Rogers K, Helfand M. C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151:483–495.

Humphrey LL, Fu R, Rogers K, Freeman M, Helfand M. Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis. Mayo Clin Proc. 2008;83:1203–1212.

Humphrey LL, Fu R, Buckley DI, Freeman M, Helfand M. Periodontal disease and coronary heart disease incidence: a systematic review and mets-analysis. J Gen Intern Med. 2008;23:2079–2086.

This report is based on research conducted by the Oregon Evidence-based Practice Center (EPC)1 under contract to the Agency for Healthcare Research and Quality (AHRQ)2 (Contract No. 290-02-0024).

Suggested citation:

Helfand M, Buckley D, Fleming C, Fu R, Freeman M, Humphrey L, Rogers K, Walker M. Screening for Intermediate Risk Factors for Coronary Heart Disease: Systematic Evidence Synthesis. Evidence Synthesis No. 73. AHRQ Publication No. 10-05141-EF-1. Rockville, Maryland: Agency for Healthcare Research and Quality, October 2009.

The investigators involved have declared no conflicts of interest with objectively conducting this research. The findings and conclusions in this document are those of the authors, who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the US Department of Health and Human Services.

The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.

This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or US Department of Health and Human Services endorsement of such derivative products may not be stated or implied.


Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, Oregon 97239


540 Gaither Road, Rockville, MD 20850. www​.ahrq.gov

Bookshelf ID: NBK35208PMID: 20722172


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