Author + information
- François Schiele, MD, PhD⁎ ( and )
- Nicolas Meneveau, MD, PhD
- ↵⁎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
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.
↵⁎ 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.
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