EDITORIAL COMMENT
Are You as Old as Your Arteries or as Old as Your Coronary Artery Calcification Score?*
François Schiele, MD, PhD* and
Nicolas Meneveau, MD, PhD
Department of Cardiology, University Hospital Jean Minjoz, Besançon, France
* Reprint requests and correspondence: Dr. François Schiele, Department of Cardiology, University Hospital Jean Minjoz, University of Franche Comte, EA 3920, Boulevard Fleming, 25000 Besançon, France (Email: francois.schiele{at}univ-fcomte.fr).
Key Words: cardiac CT • coronary calcium • ethnicity • prognosis
Atherosclerosis develops over many years, might be very advanced before any symptoms appear, and the first manifestations are often sudden death or acute coronary syndromes. Among the risk factors that have been identified, age, gender, cholesterol level, blood pressure, diabetes, and tobacco use are the most frequently used in risk prediction algorithms. The Framingham score, the Prospective Cardiovascular Munster score (PROCAM), and the Systemic Coronary Risk Evaluation (SCORE) risk estimators make it possible to calculate 10-year probability for coronary heart disease (CHD) or death. However, these scores have limitations and fail to predict at least 25% of CHD. Conversely, they might lead to unnecessary prevention treatments, because a proportion of patients deemed at high risk will not develop atherosclerosis.
Availability of imaging techniques that can detect and quantify the atherosclerotic process is an important opportunity to increase current risk stratification capacities. Coronary calcium deposit is the result of an active process, specifically related to atherosclerosis, and thus detection of coronary artery calcifications (CAC) corresponds to a definite diagnosis of atherosclerosis. Electron-beam computed tomography (EBCT) or multislice computed tomography (MSCT) are suitable to detect and quantify CAC. Although CAC does not necessarily imply arterial lumen narrowing, it has been shown to be related to atherosclerotic plaque burden and future CHD. In asymptomatic patients, longitudinal cohort studies have shown that the absence of CAC indicates a very low, <1%, risk of CHD, whereas presence of large amounts of CAC is associated with an odds ratio as high as 20 of developing CHD.
A number of cohort studies in asymptomatic patients have shown the incremental prognostic value of CAC, and as a result, an American College of Cardiology/American Heart Association clinical Expert Consensus Panel (1) and the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (2) have recommended coronary artery calcium score (CACS) assessment in patients at intermediate risk (10% to 20% risk prediction at 10 years) to refine the risk assessment and adjust the intensity of treatment accordingly.
 |
Controversy Over Age and Sex Adjustment
|
|---|
Calcium deposit is not only due to aging, although it is extremely rare before the age of 30 years and frequent in elderly subjects. Over the age of 70 years, CAC are detectable in 95% of men and 75% of women (3). Thus, a same CACS can influence risk assessment in both directions according to age and sex, in that it would indicate higher risk in a young woman and a lower risk in an old man. Age and sex percentile ranking have an intuitive interest and a clinical applicability, confirmed by studies reporting that CHD occurs mainly in patients with an age- and sex-adjusted CACS above the 75th percentile (4–6). This served as the rationale for the recommendations of the NCEP Adult Treatment Panel III (2), namely that patients with a CACS above the age- and sex-adjusted 75th percentile should be treated more aggressively for primary prevention. Nevertheless, controversy still exists regarding the need for this age and sex adjustment; the majority of reports have shown a relation between CHD and absolute values of CAC, and so far, only 2 small studies have compared the predictive capability of age- and sex-adjusted CAC percentiles with the absolute CACS (4,7).
The main results of the MESA (Multi Ethnic Study of Atherosclerosis) cohort have recently been published (8). This prospective cohort study showed that, after a follow-up of 46 months, CAC was an independent predictor of death and CHDs and that, when added to a prediction model using conventional risk factors, CACS was able to significantly increase the discriminatory capacity of the model.
In a substudy of the MESA cohort reported in this issue of the Journal, Budoff et al. (9) compare the different uses of the CAC, absolute value versus age and sex adjustment. Their study benefits from the advantages conferred by the design of the MESA cohort, namely prospective data collection, high data quality control, a large population of 6,814 patients, multiethnicity, and long-term follow-up. The results show how absolute CACS better predicts CHD than any age-adjusted percentile.
|
Has the Time Come to Modify the Recommendations for Risk Stratification?
|
|---|
So far, the recommended approach to using the CACS starts by a classical risk estimation (with the Framingham or another risk scoring system) (1). In patients at intermediate risk (10% to 20% at 10 years), CACS assessment is recommended to modify the pre-test prediction into a post-test risk prediction, according to the Bayesian theory (10). The CACS is of less interest in high-risk patients, because they should receive intensive prevention therapy anyway, and assessment of the CACS would not affect the treatment. In low-risk patients, an abnormal CACS would probably increase the risk prediction, but this risk would remain relatively low (10).
The results from the MESA cohort, presented by Budoff et al. (9), carry another message between the lines: regardless of the risk category estimated by traditional risk scores, a patient with a high CACS, above a 400 Agatston score, is at high risk, whereas the absence of coronary calcification indicates a low risk. All in all, this study shows that the atherosclerotic burden most influences the prognosis, irrespective of age, sex, and ethnicity.
Thus, assessment of the CACS could be justified in all patients (and not only those at intermediate risk), and treatment intensity could be adapted directly in line with this measure. Some published studies have already concluded in this direction, suggesting that large amounts of calcium identify a risk (and require management) equivalent to secondary prevention (11,12). In asymptomatic patients suspected of coronary disease, risk assessment and clinical management based only on the demonstration of atherosclerosis by an imaging technique is clearly not recommended. And yet, a similar approach is already recommended for management of patients with peripheral artery disease: guidelines recommend use of the ankle-brachial index as a screening technique in asymptomatic patients older than age 50 years with diabetes or smoking (13). However, it is too early as yet to draw such a definite conclusion in the setting of CHD, but it is likely that future recommendations will need to consider the role of the CACS, taking into account not only the MESA cohort results but also cost-effectiveness analyses and the potential consequences of patient radiation exposure.
|
Footnotes
|
|---|
* Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. 
|
References
|
|---|
1. Greenland P, Bonow RO, Brundage BH, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography): developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography J Am Coll Cardiol 2007;49:378-402.[Free Full Text]2. 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) final report Circulation 2002;106:3143-3421.[Free Full Text] 3. Hoff JA, Chomka EV, Krainik AJ, Daviglus M, Rich S, Kondos GT. Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35,246 adults Am J Cardiol 2001;87:1335-1339.[CrossRef][Web of Science][Medline] 4. Raggi P, Callister TQ, Cooil B, et al. Identification of patients at increased risk of first unheralded acute myocardial infarction by electron-beam computed tomography Circulation 2000;101:850-855.[Abstract/Free Full Text] 5. Kondos GT, Hoff JA, Sevrukov A, et al. Electron-beam tomography coronary artery calcium and cardiac events: a 37-month follow-up of 5635 initially asymptomatic low- to intermediate-risk adults Circulation 2003;107:2571-2576.[Abstract/Free Full Text] 6. Raggi P, Cooil B, Callister TQ. Use of electron beam tomography data to develop models for prediction of hard coronary events Am Heart J 2001;141:375-382.[CrossRef][Web of Science][Medline] 7. Wong ND, Budoff MJ, Pio J, Detrano RC. Coronary calcium and cardiovascular event risk: evaluation by age- and sex-specific quartiles Am Heart J 2002;143:456-459.[CrossRef][Web of Science][Medline] 8. Detrano RC, Wong ND, Doherty TM, et al. Coronary calcium does not accurately predict near-term future coronary events in high-risk adults Circulation 1999;99:2633-2638.[Abstract/Free Full Text] 9. Budoff MJ, Nasir K, McClelland RL, et al. Coronary calcium predicts events better with absolute calcium scores than age-sex-race/ethnicity percentiles: MESA (Multi-Ethnic Study of Atherosclerosis) J Am Coll Cardiol 2009;53:345-352.[Abstract/Free Full Text] 10. Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals JAMA 2004;291:210-215.[Abstract/Free Full Text] 11. Wayhs R, Zelinger A, Raggi P. High coronary artery calcium scores pose an extremely elevated risk for hard events J Am Coll Cardiol 2002;39:225-230.[Abstract/Free Full Text] 12. 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;167:2437-2442.[Abstract/Free Full Text] 13. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Associations for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) J Am Coll Cardiol 2006;47:1239-1312.[Free Full Text]
Related Articles
-
Coronary Calcium Predicts Events Better With Absolute Calcium Scores Than Age-Sex-Race/Ethnicity Percentiles: MESA (Multi-Ethnic Study of Atherosclerosis)
- Matthew J. Budoff, Khurram Nasir, Robyn L. McClelland, Robert Detrano, Nathan Wong, Roger S. Blumenthal, George Kondos, and Richard A. Kronmal
J. Am. Coll. Cardiol. 2009 53: 345-352.
[Abstract]
[Full Text]
[PDF]
-
Inside This Issue of JACC
J. Am. Coll. Cardiol. 2009 53: A20.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, G. K. Feld, B. H. Greenberg, J. Hall, M. Hlatky, W. Y.W. Lew, J. A.C. Lima, A. S. Maisel, et al.
Highlights of the Year in JACC 2009
J. Am. Coll. Cardiol.,
January 26, 2010;
55(4):
380 - 407.
[Full Text]
[PDF]
|
|
|
|
Top
Controversy Over Age and...
Has the Time Come...