Screening Low-Risk Individuals for Coronary Artery Disease

  • Chintan S. Desai
  • Roger S. Blumenthal
  • Philip GreenlandEmail author
Coronary Heart Disease (JA Farmer, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Coronary Heart Disease


A large proportion of cardiovascular events occur in individuals classified by traditional risk factors as “low-risk.” Efforts to improve early detection of coronary artery disease among low-risk individuals, or to improve risk assessment, might be justified by this large population burden. The most promising tests for improving risk assessment, or early detection, include the coronary artery calcium (CAC) score, the ankle-brachial index (ABI), and the high-sensitivity C-reactive protein (hsCRP). Data regarding the role of additional testing in low-risk populations to improve early detection or to enhance risk assessment are sparse but suggest that CAC and ABI may be helpful for improving risk classification and detecting the higher-risk people from among those at lower risk. However, in the absence of clinical trials in this patient population, such as has recently been proposed, we do not recommend routine use of any additional testing or screening in low-risk individuals at this time.


Screening Low-risk Asymptomatic Early detection 


Compliance with Ethics Guidelines

Conflict of Interest

Chintan S. Desai, Roger S. Blumenthal, and Philip Greenland declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Ford ES, Ajani UA, Croft JB, et al. Explaining the decrease in U.S. deaths from coronary disease, 1980–2000. N Engl J Med. 2007;356(23):2388–98.PubMedCrossRefGoogle Scholar
  2. 2.
    Ford ES, Capewell S. Coronary heart disease mortality among young adults in the U.S. from 1980 through 2002: concealed leveling of mortality rates. J Am Coll Cardiol. 2007;50(22):2128–32.PubMedCrossRefGoogle Scholar
  3. 3.
    Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095–128.PubMedCrossRefGoogle Scholar
  4. 4.
    Force USPS. Using nontraditional risk factors in coronary heart disease risk assessment: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151(7):474–82.CrossRefGoogle Scholar
  5. 5.
    Shah PK. Screening asymptomatic subjects for subclinical atherosclerosis: can we, does it matter, and should we? J Am Coll Cardiol. 2010;56(2):98–105.PubMedCrossRefGoogle Scholar
  6. 6.
    Lauer MS. Screening asymptomatic subjects for subclinical atherosclerosis: not so obvious. J Am Coll Cardiol. 2010;56(2):106–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA J Am Med Assoc. 2001;285(19):2486–97.CrossRefGoogle Scholar
  8. 8.
    Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97(18):1837–47.PubMedCrossRefGoogle Scholar
  9. 9.
    Califf RM, Armstrong PW, Carver JR, D’Agostino RB, Strauss WE. 27th Bethesda Conference: matching the intensity of risk factor management with the hazard for coronary disease events. Task Force 5. Stratification of patients into high, medium and low risk subgroups for purposes of risk factor management. J Am Coll Cardiol. 1996;27(5):1007–19.PubMedCrossRefGoogle Scholar
  10. 10.
    Rose G. Sick individuals and sick populations. Int J Epidemiol. 2001;30(3):427–32. discussion 433–424.PubMedCrossRefGoogle Scholar
  11. 11.
    Conroy RM, Pyorala K, Fitzgerald AP, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24(11):987–1003.PubMedCrossRefGoogle Scholar
  12. 12.
    Cooney MT, Dudina A, Whincup P, et al. Re-evaluating the Rose approach: comparative benefits of the population and high-risk preventive strategies. Eur J Cardiovasc Prev Rehabil Off J Eur Soc Cardiol Work Group Epidemiol Prev Card Rehabil Exerc Physiol. 2009;16(5):541–9.Google Scholar
  13. 13.
    Rose G. Sick individuals and sick populations. Int J Epidemiol. 1985;14(1):32–8.PubMedCrossRefGoogle Scholar
  14. 14.••
    Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2010;122(25):e584-636. This is an important review of all potential approaches to risk assessment in asymptomatic patients. It is a good source of detailed background on this subject. Google Scholar
  15. 15.••
    Anderson TJ, Gregoire J, Hegele RA, et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2013;29(2):151–67. This update to previous Canadian Guidelines is an important reference source on the topics of prevention and risk assessment. Google Scholar
  16. 16.
    Libby P, Ridker PM, Hansson GK, Leducq Transatlantic Network on A. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009;54(23):2129–38.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Ridker PM, Rifai N, Clearfield M, et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001;344(26):1959–65.PubMedCrossRefGoogle Scholar
  18. 18.
    Sever PS, Poulter NR, Chang CL, et al. Evaluation of C-reactive protein before and on-treatment as a predictor of benefit of atorvastatin: a cohort analysis from the anglo-scandinavian cardiac outcomes trial lipid-lowering arm. J Am Coll Cardiol. 2013;62(8):717–29.PubMedCrossRefGoogle Scholar
  19. 19.
    Ridker PM. High-sensitivity C-reactive protein and cardiovascular risk: rationale for screening and primary prevention. Am J Cardiol. 2003;92(4B):17K–22K.PubMedCrossRefGoogle Scholar
  20. 20.••
    Yousuf O, Mohanty BD, Martin SS, et al. High-sensitivity C-reactive protein and cardiovascular disease: a resolute belief or an elusive link? J Am Coll Cardiol. 2013;62(5):397–408. This is a comprehensive review of the utility of C-reactive protein for cardiovascular risk. It supports a limited role for hsCRP in risk assessment. Google Scholar
  21. 21.
    Emerging Risk Factors C, Kaptoge S, Di Angelantonio E, et al. C-reactive protein, fibrinogen, and cardiovascular disease prediction. N Engl J Med. 2012;367(14):1310–20.PubMedCrossRefGoogle Scholar
  22. 22.
    Koenig W, Lowel H, Baumert J, Meisinger C. C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment: results from a large cohort study in southern Germany. Circulation. 2004;109(11):1349–53.PubMedCrossRefGoogle Scholar
  23. 23.
    Ankle Brachial Index C, Fowkes FG, Murray GD, et al. Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis. JAMA J Am Med Assoc. 2008;300(2):197–208.CrossRefGoogle Scholar
  24. 24.
    Mohlenkamp S, Lehmann N, Moebus S, et al. Quantification of coronary atherosclerosis and inflammation to predict coronary events and all-cause mortality. J Am Coll Cardiol. 2011;57(13):1455–64.PubMedCrossRefGoogle Scholar
  25. 25.••
    Yeboah J, McClelland RL, Polonsky TS, et al. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA J Am Med Assoc. 2012;308(8):788–95. This is one of a small number of analyses from a large cohort comparing risk assessment approaches using different tests. It supports a conclusion that CAC is the leading contender for improving risk assessment in intermediate risk populations. Google Scholar
  26. 26.
    Pencina MJ, D’Agostino Sr RB, Steyerberg EW. Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med. 2011;30(1):11–21.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.••
    Kavousi M, Elias-Smale S, Rutten JH, et al. Evaluation of newer risk markers for coronary heart disease risk classification: a cohort study. Ann Intern Med. 2012;156(6):438–44. This paper is similar to reference 26 but applies across the entire Rotterdam cohort of mostly elderly men and women. Google Scholar
  28. 28.
    Lakoski SG, Greenland P, Wong ND, et al. Coronary artery calcium scores and risk for cardiovascular events in women classified as “low risk” based on Framingham risk score: the multi-ethnic study of atherosclerosis (MESA). Arch Intern Med. 2007;167(22):2437–42.PubMedCrossRefGoogle Scholar
  29. 29.
    Mohlenkamp S, Lehmann N, Greenland P, et al. Coronary artery calcium score improves cardiovascular risk prediction in persons without indication for statin therapy. Atherosclerosis. 2011;215(1):229–36.PubMedCrossRefGoogle Scholar
  30. 30.
    Desai CS, Ayers CR, Budoff M, et al. Improved coronary heart disease risk prediction with coronary artery calcium in low-risk women: a meta-analysis of four cohorts. J Am Coll Cardiol. 2013;61(10):E995–5.Google Scholar
  31. 31.
    Wilson JM. The evaluation of the worth of early disease detection. J R Coll Gen Pract. 1968;16 Suppl 2:48–57.PubMedCentralPubMedGoogle Scholar
  32. 32.
    Bhatti SK, Dinicolantonio JJ, Captain BK, Lavie CJ, Tomek A, O’Keefe JH. Neutralizing the adverse prognosis of coronary artery calcium. Mayo Clin Proc Mayo Clin. 2013;88(8):806–12.CrossRefGoogle Scholar
  33. 33.
    Cholesterol Treatment Trialists C, Mihaylova B, Emberson J, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380(9841):581–90.PubMedCrossRefGoogle Scholar
  34. 34.•
    Ambrosius WT, Polonsky TS, Greenland P, et al. Design of the value of imaging in enhancing the wellness of your heart (VIEW) trial and the impact of uncertainty on power. Clin Trials. 2012;9(2):232–46. This is a provocative proposal for a large-scale trial of coronary artery calcium testing (screening) in asymptomatic low-risk individuals. It is an important “thought-piece” on this topic. Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Chintan S. Desai
    • 1
    • 3
  • Roger S. Blumenthal
    • 1
    • 4
  • Philip Greenland
    • 2
    Email author
  1. 1.Johns Hopkins Hospital, Ciccarone Center for the Prevention of Heart DiseaseBaltimoreUSA
  2. 2.Department of Preventive MedicineNorthwestern University Feinberg School of MedicineChicagoUSA
  3. 3.Johns Hopkins Ciccarone CenterBaltimoreUSA
  4. 4.Johns Hopkins Ciccarone CenterBaltimoreUSA

Personalised recommendations