We conducted a retrospective analysis of consecutive patients undergoing CCTA for suspected obstructive CAD at Hospital Santa Cruz (Carnaxide, Portugal) between January 2017 and December 2018 and Hospital da Luz (Lisbon, Portugal) between January 2015 and October 2016. Patients were identified from prospective registries kept by both laboratories, for which all patients gave written informed consent. Patients were excluded if they had diabetes, history of acute coronary syndrome, previous coronary revascularization procedure, previous stroke/transient ischemic attack, symptomatic peripheral arterial disease, renal failure (calculated creatine clearance <60 ml/min/1.73 m2), or familial hypercholesterolemia. Patients were also excluded if they were found to have at least one ≥50% coronary stenosis on CCTA, or if there were missing data on any of the variables composing the MESA risk score (age, gender, ethnicity, smoking, family history of myocardial infarction, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, lipid-lowering medication, and antihypertensive medication).

In both hospitals, CAC scoring and CCTA were performed on dual source 64-slice computed tomography scanners (Siemens SOMATOM Definition®, Siemens Healthineers, Erlangen, Germany) according to the Society of Cardiovascular Computed Tomography guidelines.9 CAC score was determined using the Agatston method.1 All scans were analyzed by a cardiologist and/or radiologist with level III experience, on an Aquarius® workstation (Terarecon® Inc., San Mateo, CA, USA). Coronary atherosclerotic lesions on CCTA were assessed by visual estimation. The Systematic COronary Risk Evaluation (SCORE) risk estimate was calculated for each individual and categorized as low (<1%), moderate (1-<5%), high (5-<10%) or very high (≥10%). The MESA risk score was also calculated for each patient without and with the CAC score value (pre- and post-CAC scoring MESA score, respectively). Patients were categorized as low (<5.0%), borderline (5.0-<7.5%), intermediate (7.5-<20%) or high risk (≥20%), in accordance with the published literature.8 Both risk scores were calculated subsequently (and therefore not included in the clinical reports).

In a subset of 184 patients who were referred from the cardiology clinic at Hospital Santa Cruz, electronic medical records were also used to analyze the prescription of statins and antiplatelet agents before CCTA and after the first post-CCTA appointment. Changes in medication were assessed in patients with a CAC score of zero (for whom pharmacological preventive therapy is less likely to be beneficial) and in those with CAC score >100 (in whom therapy is more likely to be of benefit according to the current evidence).5,6,10

Normally and non-normally distributed variables were expressed as means ± standard deviation and median, respectively. Differences between groups were assessed using the independent samples t test and Fisher's exact test for continuous and categorical variables, respectively. All analyses were performed using IBM SPSS software version 22. Two-tailed p-values <0.05 were considered statistically significant.

The study was approved by the appropriate ethics committee and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Patients provided written informed consent for both the procedure and publication of any relevant data.

The clinical characteristics of the 467 patients included in this study are presented in Table 1. Overall, the SCORE system classified 116 (25%), 249 (53%), 77 (17%), and 25 (5%) in the low, moderate, high and very high risk categories, respectively. Before inputting CAC score data, the MESA score ranked 40% (n=188), 23% (n=105), 34% (n=159) and 3% (n=15) of patients in the low, borderline, intermediate and high-risk categories, respectively. The distribution of CAC score in each of these subgroups is presented in Table 2. Among patients classified by SCORE as being at moderate risk, 12% had CAC score >100 AU, reclassifying them into a higher risk category according to current guidelines. Likewise, in patients classified as intermediate risk by the MESA score, 19% had CAC score >100 AU, making them eligible for preventive statin therapy. The median MESA score was 6% (interquartile range [IQR] 4-9%) before the inclusion of CAC scoring data, and 4% (IQR 2-7%) afterward (p<0.001). Overall, adding CAC score results to the MESA score resulted in the reclassification of 215 (46%) patients. Individual risk reclassification is depicted in Table 3. While the majority of low- and high-risk patients remained in the same risk category, more than half of borderline- and intermediate-risk patients had their risk downgraded. Risk reclassification was highest in borderline-risk patients, where 83% were reclassified, mainly to the low-risk group (65%).

In the 184 patients whose prescriptions were analyzed, CAC score was 0, 1-100 and >100 AU in 83, 74 and 27 patients, respectively. Seventy-five (41%) were taking a statin, and 58 (29%) were taking antiplatelet agents before undergoing CCTA. After CCTA, 13 patients were started on statins and two others stopped, while 11 patients started and 10 stopped antiplatelet prescriptions. In total, the proportions of patients treated with statins and antiplatelet agents after CCTA were 47% and 29%, respectively. The proportions of patients treated with statins and antiplatelet agents were similar in the various CAC score categories and did not change significantly after the results of CCTA were known (Table 4). In the group of patients with CAC score over 100 AU, 41% remained without statins and 52% without an antiplatelet. At the other end of the risk spectrum, 27% of patients maintained antiplatelet therapy despite CAC score 0 AU.

Several limitations of this study should be recognized. It was a retrospective study of patients undergoing CCTA in two Portuguese centers. Our analysis used the MESA score, which, although derived from patients with a diverse ethnic background, was meant for use in US patients and may not be applicable to our European population. Although the American guidelines recommend the use of the pooled cohort equation for risk calculation, we used the MESA risk score since it is the only one that allows the inclusion of CAC scoring directly into the score. It should be acknowledged that not all risk reclassifications prompted by the inclusion of CAC score results are necessarily correct. However, other studies have shown a clear net benefit in risk reclassification if CAC scoring is included (i.e., correct reclassifications outweigh incorrect classifications).3,26 The lack of follow-up data and the relatively small sample size of this study preclude the use of cardiovascular events to confirm those findings. Also, we did not assess the impact of CAC scoring on statin dose titration. Finally, the guideline recommendations for how to use CAC scoring to guide statin therapy were published after this study's inclusion period, suggesting that prescription patterns after CCTA could now be different.