Atherosclerotic cardiovascular disease (ASCVD) risk assessment can identify high-risk patients who are likely to benefit from pharmacologic therapy for primary prevention of cardiovascular disease (CVD). Additionally, it can prevent overtreatment of low-risk patients. Clinical risk scores based on traditional cardiovascular risk factors, such as the Pooled Cohort Equations, may overestimate or underestimate ASCVD risk.¹ Optimal management is often uncertain in those at intermediate risk (5% to 20%).^2,3

Coronary artery calcium (CAC) is a marker of overall coronary atherosclerotic burden. It is detected by noncontrast computed tomography (CT) and quantified by the Agatston score, which is the sum of the products of attenuation (Hounsfield units) and area (mm²) of all lesions in the coronary arteries at each slice.^2,3 Because CAC is a marker of atherosclerotic disease, it may provide superior risk estimation over traditional risk factors.

Accuracy

PREDICTIVE VALUE FOR CARDIOVASCULAR EVENTS AND MORTALITY

CAC score is a strong predictor of coronary heart disease (CHD) and ASCVD. The presence of CAC indicates a 2.6- to 4.3-fold increased risk of CHD and a 2.1- to 2.6-fold increased risk of ASCVD, compared with a CAC score of 0.^4–7

In a 12.3-year study of 7,042 participants, the risk of major CHD events was 1.9-fold higher with a CAC score of 1 to 99 and 4.2-fold higher with a score of 100 or greater.⁶ In a cohort study of 3,745 participants, the 10-year rate of major CHD events was 0.6 to 2.7 per 1,000 person-years with a CAC score of 0 vs. 6.5 to 9.9 per 1,000 person-years with a score of 100 or greater.⁸ In another study of 6,749 participants, the 10-year rate of ASCVD events was 3.6% with a CAC score of 0 vs. 17.5% with a score greater than 0.⁷ In a 12.3-year study of 7,042 participants, the relative risk for ASCVD events was 1.6 with a CAC score of 1 to 99 and 2.3 to 3.4 with a score of 100 or greater.⁶

CAC score is also a predictor of all-cause mortality. In a 6.8-year study, patients with a CAC score of 101 to 400 or a score greater than 400 had a 5.6- or 9.7-fold greater risk of all-cause mortality, respectively, compared with a score of 0.⁹ In a 15-year study, the survival rate was 95.1% in patients with a score of 0 vs. 83.7% in those with a score greater than 0.¹⁰

“WARRANTY PERIOD” FOR A CAC SCORE OF 0

Patients with a CAC score of 0 have very low rates of CHD, ASCVD, and all-cause mortality, even those with traditional CVD risk factors.¹⁰ A score of 0 has been associated with event rates of 0.6 to 5.0 per 1,000 person-years for CHD, 0.2 to 5.4 for ASCVD, and 0.87 to 1.0 for all-cause mortality.^{4,7–9,11,12}

Studies have investigated how long patients with a baseline CAC score of 0 remain in the low-risk category. The mean time of progression from absence to presence of CAC is 4.1 years, but the all-cause mortality rate remains low (less than 3%) for 15 years.^10,13,14

Benefit

No studies have shown that using CAC scoring to help guide preventive therapies reduces ASCVD events or mortality.³

CAC SCORE IMPROVES RISK DISCRIMINATION AND CLASSIFICATION

For CHD and ASCVD events and all-cause mortality, CAC scoring improves discrimination provided by traditional risk factors. It is superior to other markers, including C-reactive protein, carotid intima-media thickness, ankle-brachial index, brachial flow-mediated dilation, and family history of premature CHD.^5,15 Discrimination, quantified by the C statistic, is the ability to distinguish between individuals who will or will not experience an event.¹⁶ The Framingham CHD Risk Score and the Pooled Cohort Equations have C statistics of 0.65 to 0.75.¹⁶ Adding CAC to traditional risk factor models improves the C statistic by 0.035 to 0.161 for CHD risk, 0.021 to 0.040 for CVD risk, and 0.04 to 0.08 for all-cause mortality.^{5,6,10,12,15–20}