Skip to main content
SpringerLink
Log in

Comparative Effectiveness of Risk Markers for Cardiovascular Risk Assessment in Intermediate-Risk Individuals: Coronary Artery Calcium vs “The Rest”?

  • Cardiac Computed Tomography (TC Villines and S Achenbach, Section Editors)
  • Published:
Current Cardiovascular Imaging Reports Aims and scope Submit manuscript

Abstract

The last decade has seen the emergence of a multitude of novel risk markers for coronary heart disease (CHD), ranging from genetic markers to serum biomarkers and imaging studies. Comparison between different risk markers has been historically difficult because of the paucity of high quality prospective studies evaluating these candidate risk markers side by side in the same population. In the last 2 years, several population based cohorts like MESA, Rotterdam, EISNER, and the Heinz Nixdorf Recall study have provided new data enabling assessment of comparative effectiveness for several of these risk markers. In this review, we evaluate evidence from these 4 large cohort studies regarding the relative improvement in the net reclassification index (NRI) among intermediate-risk patients. We conclude that CAC is the strongest marker for clinical risk prediction and is the most likely to positively influence downstream clinical outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

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

  1. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125:e2–220.

    Article  Google Scholar 

  2. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837–47.

    Article  CAS  Google Scholar 

  3. Rosjo H, Omland T. New statistical methods for the evaluation of cardiovascular risk markers: what the clinician should know. Clin Sci. 2009;117:13–5.

    Article  Google Scholar 

  4. Pencina MJ, D’Agostino Sr RB, D’Agostino Jr RB, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:157–72.

    Article  Google Scholar 

  5. •• Kavousi M, Elias-Smale S, Rutten JH, Leening MJ, Vliegenthart R, Verwoert GC, et al. Evaluation of newer risk markers for coronary heart disease risk classification: a cohort study. Ann Intern Med. 2012;156:438–44. In the Rotterdam study of 5933 individuals, improvements in FRS predictions were most significant with the addition of CAC scores compared with 12 CHD risk markers.

    Article  Google Scholar 

  6. •• Yeboah J, McClelland RL, Polonsky TS, Burke GL, Sibley CT, O'Leary D, et al. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA. 2012;308:788–95. Coronary artery calcium provided superior discrimination and risk reclassification compared with other risk markers in the Multi-Ethnic Study of Atherosclerosis (MESA) study.

    Article  CAS  Google Scholar 

  7. •• Rana JS, Gransar H, Wong ND, Shaw L, Pencina M, Nasir K, et al. Comparative value of coronary artery calcium and multiple blood biomarkers for prognostication of cardiovascular events. Am J Cardiol. 109:1449–53. In the EISNER study of asymptomatic individuals, addition of CAC but not biomarkers substantially improved risk reclassification for future CVD events beyond traditional risk factors.

  8. Erbel R, Mohlenkamp S, Moebus S, Schmermund A, Lehmann N, Stang A, et al. Coronary risk stratification, discrimination, and reclassification improvement based on quantification of subclinical coronary atherosclerosis: the Heinz Nixdorf Recall study. J Am Coll Cardiol. 2010;56:1397–406.

    Article  Google Scholar 

  9. Rozanski A, Gransar H, Shaw LJ, Kim J, Miranda-Peats L, Wong ND, et al. Impact of coronary artery calcium scanning on coronary risk factors and downstream testing: the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) prospective randomized trial. J Am Coll Cardiol. 2011;57:1622–32.

    Article  CAS  Google Scholar 

  10. Taylor AJ, Bots ML, Kastelein JJ. Vascular disease: meta-regression of CIMT trials-data in, garbage out. Nat Rev Cardiol. 2011;8:128–30.

    Article  Google Scholar 

  11. Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA, et al. ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2010;122:2748–64.

    Article  Google Scholar 

  12. Den Ruijter HM, Peters SA, Anderson TJ, Britton AR, Dekker JM, Eijkemans MJ, et al. Common carotid intima-media thickness measurements in cardiovascular risk prediction: a meta-analysis. JAMA. 2012;308:796–803.

    Article  Google Scholar 

  13. Polak JF, Pencina MJ, Pencina KM, O’Donnell CJ, Wolf PA, D’Agostino Sr RB. Carotid-wall intima-media thickness and cardiovascular events. N Engl J Med. 2012;365:213–21.

    Article  Google Scholar 

  14. Tison GH, Blaha MJ, Nasir K. Atherosclerosis imaging in multiple vascular beds—enough heterogeneity to improve risk prediction? Atherosclerosis. 2011;214:261–3.

    Article  CAS  Google Scholar 

  15. Folsom AR, Kronmal RA, Detrano RC, O'Leary DH, Bild DE, Bluemke DA, et al. Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA). Arch Intern Med. 2008;168:1333–9.

    Article  Google Scholar 

  16. Roman MJ, Naqvi TZ, Gardin JM, Gerhard-Herman M, Jaff M, Mohler E. Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society of Vascular Medicine and Biology. J Am Soc Echocardiogr. 2006;19:943–54.

    Article  Google Scholar 

  17. Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr. 2008;21:93–111.

    Article  Google Scholar 

  18. Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. Circulation. 1995;92:2157–62.

    Article  CAS  Google Scholar 

  19. • Nasir K, Rubin J, Blaha MJ, Shaw LJ, Blankstein R, Rivera JJ, et al. Interplay of coronary artery calcification and traditional risk factors for the prediction of all-cause mortality in asymptomatic individuals. Circ Cardiovasc Imaging. 2012;5:467–73. This study followed more than 44, 000 individuals over nearly 6 years and suggested that the majority of the risk predictive power is held by CAC and not traditional risk factors, setting the stage for a paradigm shift towards earlier use of subclinical atherosclerosis in primary prevention risk assessment.

    Article  Google Scholar 

  20. Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, et al. Coronary calcium as a predictor of coronary events in 4 racial or ethnic groups. N Engl J Med. 2008;358:1336–45.

    Article  CAS  Google Scholar 

  21. • Tota-Maharaj R, Blaha MJ, McEvoy JW, Blumenthal RS, Muse ED, Budoff MJ, et al. Coronary artery calcium for the prediction of mortality in young adults <45 years old and elderly adults >75 years old. Eur Heart J. 2012;33:2955–62. This study shows that elderly persons >75 years old with no CAC have a lower mortality rate than younger persons <45 years old with very high CAC.

    Article  CAS  Google Scholar 

  22. Blaha M, Budoff MJ, Shaw LJ, Khosa F, Rumberger JA, Berman D, et al. Absence of coronary artery calcification and all-cause mortality. JACC Cardiovasc Imaging. 2009;2:692–700.

    Article  Google Scholar 

  23. Budoff MJ, McClelland RL, Nasir K, Greenland P, Kronmal RA, Kondos GT, et al. Cardiovascular events with absent or minimal coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA). Am Heart J. 2009;158:554–61.

    Article  Google Scholar 

  24. Sarwar A, Shaw LJ, Shapiro MD, Blankstein R, Hoffmann U, Cury RC, et al. Diagnostic and prognostic value of absence of coronary artery calcification. JACC Cardiovasc Imaging. 2009;2:675–88.

    Article  Google Scholar 

  25. •• Nasir K, Clouse M. Role of nonenhanced multidetector CT coronary artery calcium testing in asymptomatic and symptomatic individuals. Radiology. 2012;264:637–49. This is the latest and best state-of-the-art review on the implications of coronary artery calcium scoring.

    Article  Google Scholar 

  26. Blaha MJ, Blumenthal RS, Budoff MJ, Nasir K. Understanding the utility of zero coronary calcium as a prognostic test a bayesian approach. Circ: Cardiovasc Qual Outcomes. 2011;4:253–6.

    Article  Google Scholar 

  27. Blaha MJ, Budoff MJ, DeFilippis AP, Blankstein R, Rivera JJ, Agatston A, et al. Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study. Lancet. 2011;378:684–92.

    Article  CAS  Google Scholar 

  28. Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation. 2007;115:2390–7.

    Article  Google Scholar 

  29. Dhangana R, Murphy TP, Pencina MJ, Zafar AM. Prevalence of low ankle-brachial index, elevated plasma fibrinogen, and CRP across Framingham risk categories: data from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Atherosclerosis. 2011;216:174–9.

    Article  CAS  Google Scholar 

  30. Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR, McCann TJ, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992;326:381–6.

    Article  CAS  Google Scholar 

  31. Murabito JM, Evans JC, Larson MG, Nieto K, Levy D, Wilson PW. The ankle-brachial index in the elderly and risk of stroke, coronary disease, and death: the Framingham Study. Arch Intern Med. 2003;163:1939–42.

    Article  Google Scholar 

  32. Blankenberg S, Zeller T, Saarela O, Havulinna AS, Kee F, Tunstall-Pedoe H, et al. Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project. Circulation. 2010;121:2388–97.

    Article  Google Scholar 

  33. Melander O, Newton-Cheh C, Almgren P, Hedblad B, Berglund G, Engstrom G, et al. Novel and conventional biomarkers for prediction of incident cardiovascular events in the community. JAMA. 2009;302:49–57.

    Article  CAS  Google Scholar 

  34. Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006;355:2631–9.

    Article  CAS  Google Scholar 

  35. Using nontraditional risk factors in coronary heart disease risk assessment: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151:474–82.

  36. Di Angelantonio E, Chowdhury R, Sarwar N, Ray KK, Gobin R, Saleheen D, et al. B-type natriuretic peptides and cardiovascular risk: systematic review and meta-analysis of 40 prospective studies. Circulation. 2009;120:2177–87.

    Article  Google Scholar 

  37. Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375:132–40.

    Article  Google Scholar 

  38. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto Jr AM, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.

    Article  CAS  Google Scholar 

  39. Wang TJ, Wollert KC, Larson MG, Coglianese E, McCabe EL, Cheng S, et al. Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study. Circulation. 2012;126:1596–604.

    Article  CAS  Google Scholar 

  40. Cavanaugh-Hussey MW, Berry JD, Lloyd-Jones DM. Who exceeds ATP-III risk thresholds? Systematic examination of the effect of varying age and risk factor levels in the ATP-III risk assessment tool. Prev Med. 2008;47:619–23.

    Article  Google Scholar 

  41. Blaha MJ, Nasir K, Blumenthal RS. Statin therapy for healthy men identified as “increased risk”. JAMA. 2012;307:1489–90.

    Article  CAS  Google Scholar 

  42. Whelton SP, Nasir K, Blaha MJ, Gransar H, Metkus TS, Coresh J, et al. Coronary artery calcium and primary prevention risk assessment: what is the evidence? An updated meta-analysis on patient and physician behavior. Circ: Cardiovasc Qual Outcomes. 2012;5:601–7.

    Article  Google Scholar 

Download references

Conflict of Interest

Andreas S. Barth declares no conflict of interest. Thura T. Abd declares no conflict of interest. Roger S. Blumenthal declares no conflict of interest.

Michael J. Blaha declares no conflict of interest.

Author information

Authors and Affiliations

  1. Blalock 565 Division of Cardiology, Johns Hopkins Ciccarone Center, 600 North Wolfe St, Baltimore, MD, 21287, USA

    Andreas S. Barth, Thura T. Abd, Roger S. Blumenthal & Michael J. Blaha

Authors
  1. Andreas S. Barth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thura T. Abd
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roger S. Blumenthal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael J. Blaha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael J. Blaha.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barth, A.S., Abd, T.T., Blumenthal, R.S. et al. Comparative Effectiveness of Risk Markers for Cardiovascular Risk Assessment in Intermediate-Risk Individuals: Coronary Artery Calcium vs “The Rest”?. Curr Cardiovasc Imaging Rep 6, 203–210 (2013). https://doi.org/10.1007/s12410-013-9193-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12410-013-9193-5

Keywords

Search

Navigation