Is There a Role for Coronary Artery Calcium Scoring for Management of Asymptomatic Patients at Risk for Coronary Artery Disease?

Adequate screening for identifying individuals at risk of developing cardiovascular disease (CVD) is important because vascular disorders are a preventable cause of morbidity and mortality worldwide. Furthermore, the lifetime risk of developing CVD is high (an estimated 66% for men and >50% for women) and often the first symptom of disease is a sudden death, thereby occurring without an opportunity for intervention.1–3 Conventional risk factors aggregated as risk scores (such as the National Heart, Lung, and Blood Institute report on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III, based on the Framingham risk score]) have shown to predict the 10-year risk of developing coronary heart disease (CHD) in most individuals,4, 5 and the predictive capability of these risk factors extends over a 30–year time horizon.6 However, established risk scores may underestimate CVD risk in some individuals.7 In addition, it is also recognized now that even among those with an optimal risk factor profile at age 55 years, the residual lifetime risk of CVD remains substantial (40% in men and 30% in women).3 These observations have motivated the search for additional risk factors (including imaging tests that detect subclinical atherosclerosis) that can enhance the predictive utility of conventional risk factors. The underestimation of CVD risk may be especially evident in people with a family history of premature CVD.8–10 Independent of established risk factors, a positive family history has been associated with a greater prevalence of subclinical atherosclerosis (such as an increased coronary artery calcium [CAC] score, obtained by coronary computerized tomography [CCT]).11, 12 Estimation of the CAC score is, therefore, currently considered a valuable supplement to the Framingham Risk Score for the assessment of CVD risk in individuals with a familial history of premature vascular disease11, 12 and among patients classified as having an intermediate 10-year risk of coronary heart disease (CHD) based on Framingham Risk Score.13, 14 Undoubtedly, biomarkers (including imaging tests such as CCT) may aid the risk-stratification of asymptomatic people at risk of developing CVD. Yet, several criteria must be satisfied before any such biomarker can be incorporated into clinical practice at primary care settings. Table 1 summarizes the American Heart Association guidelines for the evaluation of biomarkers for screening for CVD risk.15 A comprehensive evaluation of which criteria are met by a putative screening biomarker assumes specific importance when a candidate test is expensive or not easily obtained (as it is in the case of imaging tests). The present article focuses on the clinical utility of CAC scores derived by CCT (as the prototype imaging test) because it is the most commonly used and best studied imaging modality that is used for screening asymptomatic individuals in the community. To put the discussion into a clinical context, we present 2 clinical cases in Table 2, which should serve as an appetizer for reflection. The 2 examples reflect relevant scenarios where CCT testing is appropriate according to guidelines, but where the interpretation of CAC scores may be challenging. Table 1 Principles for evaluation of a new biomarker, as suggested by Hlatky et al.15 in 2009 AHA guidelines of evaluation of a new biomarker. Table 2 Two illustrative cases. CAC score as an independent risk factor in asymptomatic individuals: Some Challenges Data on Long-Term Outcomes Several population-based cohort studies with a typical follow-up time of 3–5 years have consistently demonstrated that elevated CAC scores are associated with increased risk of new-onset CVD independent of standard risk factors and the Framingham Risk Score.16–23 However, there are very limited data available on CVD risk over a longer time horizon (such as 10-, 20- or 30-year risk of CVD).24 It seems likely that a high CAC score will continue to maintain a strong adverse prognostic value, but it is less clear if a CAC score of 0 will continue to maintain a strong favorable prognostic value over a longer time period. A CAC score of 0 is associated with a low risk of CVD during the subsequent 3–5 years and event rates may be as low as the event rates for those with a low Framingham Risk Score ( 0 during the study period, but that such a conversion was very uncommon before year 4 and escalated at the end of the study period.26 Additional studies are, therefore, clearly needed to establish the longer-term prognosis associated with a CAC score of 0. Although not recommended in guidelines (for several reasons), one theoretical possibility to overcome the issue of limited follow-up time for currently available data could be to re-screen individuals at select time intervals, e.g., every 5 years to define management strategies. Longitudinal data indicate that individuals who have rapid increases in CAC scores over time are at markedly greater risk of CVD.24, 27 For example, 1 study showing that an increase of the CAC score >15% per year translated into a 17-fold increased risk of CHD, compared to those who did not have a progression in CAC scores.27 Recent data from the Multi-Ethnic Study of Atherosclerosis (MESA) confirm the prognostic significance of change in CAC.28 However, another recent study noted that progression of CAC score by >50 over a 5-year period was noted in only 2% of individuals.29 Thus, the use of changes in CAC scores is challenged by the limited variability over shorter periods of follow-up, relative to levels of other CVD risk factors.