Emerging Risk Factors for Coronary Heart Disease: A Summary of Systematic Reviews Conducted for the U.S. Preventive Services Task Force

  1. Mark Helfand, MD, MPH;
  2. David I. Buckley, MD, MPH;
  3. Michele Freeman, MPH;
  4. Rongwei Fu, PhD;
  5. Kevin Rogers, MD;
  6. Craig Fleming, MD; and
  7. Linda L. Humphrey, MD, MPH
  1. From the Oregon Evidence-based Practice Center, Veterans Affairs Medical Center, and Oregon Health & Science University, Portland, Oregon; University of Utah Health Sciences Center, Salt Lake City, Utah; and Group Health Olympia Medical Center, Olympia, Washington.

    Abstract

    Background: Traditional risk factors do not explain all of the risk for incident coronary heart disease (CHD) events. Various new or emerging risk factors have the potential to improve global risk assessment for CHD.

    Purpose: To summarize the results of 9 systematic reviews of novel risk factors to help the U.S. Preventive Services Task Force (USPSTF) evaluate the factors' clinical usefulness.

    Data Sources: Results from a MEDLINE search for English-language articles published from 1966 to September 2008, using the Medical Subject Heading terms cohort studies and cardiovascular diseases in combination with terms for each risk factor.

    Study Selection: Studies were included if the participants had no baseline cardiovascular disease and the investigators adjusted for at least 6 Framingham risk factors.

    Data Extraction: Study quality was evaluated by using USPSTF criteria and overall quality of evidence for each risk factor by using a modified version of the Grading of Recommendations, Assessment, Development, and Evaluation framework. Each factor's potential clinical value was evaluated by using a set of criteria that emphasized the importance of the effect of that factor on the reclassification of intermediate-risk persons.

    Data Synthesis: 9 systematic reviews were conducted. C-reactive protein (CRP) was the best candidate for use in screening and the most rigorously studied, but evidence that changes in CRP level lead to primary prevention of CHD events is inconclusive. The other evaluated risk factors were coronary artery calcium score as measured by electron-beam computed tomography, lipoprotein(a) level, homocysteine level, leukocyte count, fasting blood glucose, periodontal disease, ankle–brachial index, and carotid intima–media thickness. The availability and validity of the evidence varied considerably across the risk factors in terms of aggregate quality, consistency of findings, and applicability to intermediate-risk persons in the general population. For most risk factors, no studies assessed their usefulness for reclassifying intermediate-risk persons.

    Limitations: Because of lack of access to original data, no firm conclusions could be drawn about differences in risk prediction among racial and ethnic groups. The review did not emphasize within-cohort comparisons of multiple risk factors.

    Conclusion: The current evidence does not support the routine use of any of the 9 risk factors for further risk stratification of intermediate-risk persons.

    Article and Author Information

    • Acknowledgment: The authors thank Agency for Healthcare Research and Quality Medical Officer Janelle Guirguis-Blake, MD, for commenting on draft versions of the Systematic Evidence Synthesis (20) and the USPSTF members who served as leads for this project, including Kimberly D. Gregory, MD, MPH; Russell Harris, MD, MPH; George F. Sawaya, MD; and Barbara Yawn, MD, MSc. They also thank Andrew Hamilton, MLS, MS, for conducting the literature searches and Christina Bougatsos, BS, for assistance with the manuscript.

    • Grant Support: By the Agency for Healthcare Research and Quality (contract no. 290-02-0024, Task Order Number 2).

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Mark Helfand, MD, MPH, Oregon Health & Science University, Mailcode BICC, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239.

    • Current Author Addresses: Drs. Helfand, Buckley, Fu, and Humphrey: Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239.

    • Ms. Freeman: 3710 U.S. Veterans Hospital Road, Building 6, Room 200, Portland, OR 97239.

    • Dr. Rogers: 2150 South Main 511, Salt Lake City, UT 84115.

    • Dr. Fleming: 700 Lilly Road Northeast, Group Health Olympia Medical Center, Olympia, WA 98506.

    • Author Contributions: Conception and design: M. Helfand, D.I. Buckley, L.L. Humphrey.

    • Analysis and interpretation of the data: M. Helfand, D.I. Buckley, M. Freeman, R. Fu, K. Rogers, C. Fleming, L.L. Humphrey.

    • Drafting of the article: M. Helfand, D.I. Buckley, M. Freeman.

    • Critical revision of the article for important intellectual content: M. Helfand, D.I. Buckley, M. Freeman, R. Fu, K. Rogers, L.L. Humphrey.

    • Final approval of the article: M. Helfand, D.I. Buckley, R. Fu, K. Rogers, C. Fleming, L.L. Humphrey.

    • Statistical expertise: M. Helfand, R. Fu.

    • Obtaining of funding: M. Helfand.

    • Administrative, technical, or logistic support: M. Helfand, M. Freeman.

    • Collection and assembly of data: M. Helfand, D.I. Buckley, M. Freeman, R. Fu, K. Rogers, L.L. Humphrey.

    Summary for Patients

    • Summaries for Patients:Using Nontraditional Risk Factors to Estimate Risk for Coronary Heart Disease Ann Intern Med October 6, 2009 151:I-38; doi:10.1059/0003-4819-151-7-200910060-00003
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    This Article

    1. Ann Intern Med October 6, 2009 vol. 151 no. 7 496-507
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