Discussion
Our prospective outcome study clearly supports the use of CTA for screening of asymptomatic patients with high ‘a priori’ risk of CAD after conventional cardiological baseline assessment, due to the following findings: First, the prevalence of CAD in our high-risk study cohort was high with 71%, which is markedly higher than in asymptomatic healthy South Koreans9 ,10 with no-risk or low-risk of CAD (22% rate for coronary stenosis of any severity by CTA9 and 11.4% atherosclerosis prevalence by CTA). Beyond ethnic and genetic differences between Asian and Caucasians,24 a higher CAD rate in our study is explained by the higher ‘a priori’ likelihood of CAD in our ‘high-risk’ population, which is characterised by a higher mean age, a higher rate of male gender, higher risk profile, inclusion of patients with diabetes and abnormal previous ECG-treadmill stress test. An underestimation of occult CAD using national cholesterol education programme (NCEP) guidelines as compared to CTA was suggested by Kim et al.10
In our cohort, the majority of patients had mild or intermediate stenosis. All those patients benefit from medical treatment and restrictive coronary risk control management in order to reduce progression of total atherosclerotic plaque burden.25 However, high-grade stenoses were found in one-quarter, and those patients require further diagnostic work-up, potentially including an invasive coronary angiography.
Studies investigating CTA in asymptomatic patients are rare.9–12 Beyond the two South Korean reports, only two other pivotal studies11 ,12 in small cohorts showed, for example, an excellent outcome in 100 patients with normal CTA scans (0% event rate), but a low event rate (8%) in those with non-obstructive CAD.12
Second, our study revealed that zero CCS does not exclude CAD. CCS zero is known for a high NPV for exclusion of CAD and recommended for screening of asymptomatic patients.26 ,27 This finding is in line with Cheng et al28 in which CCS zero failed to rule out CAD and even high-grade stenosis in selected patients due to non-calcifying plaques. Similarly, well over one-third of all plaques were non-calcified in another study.10
Our study supports the use of CTA instead of CCS for screening of asymptomatic patients for CAD by CTA, particularly in those having a high ‘a priori’ risk of CAD, who have a markedly higher prevalence of CAD, in contrast to no-risk or low-risk patients (eg, CCS zero rate was 93% in asymptomatic healthy Koreans).10
The advantage of CTA over CCS was highlighted in a recent data release from the CONFIRM registry, in which symptomatic patients were enrolled, which showed the incremental value of CCTA using plaque burden and stenosis severity score over CCS for discrimination of individuals at risk of death or myocardial infarct.29 Most recently, incremental value data of CTA over CCS were also released from the CONFIRM registry for 27 125 asymptomatic individuals with diabetes,30 with results similar to those found in our population. Beyond age, gender and CCS (C-index 0.64), CCTA improved discrimination by maximal stenosis, number of obstructive vessels and the coronary segment stenosis score (C-index 0.77–78, respectively) in this study.30
Moreover, our data are in line with other studies emphasising no absolute linearity of increasing CCS and total coronary plaque burden. Particularly low CCS was significantly less reliable in predicting total plaque burden due to their association with higher overall prevalence of non-calcified plaques. This has been shown in other studies with a significant stenosis rate of nearly 10%27 and high prevalence of non-calcifying plaques (83.3%) in those with low CCS (≤100).10
Overall, the total rate of non-calcifying plaques and Calcium Score zero in our study cohort was 7.6%, similar to patients with atypical chest pain and an intermediate Framingham risk profile.6 Non-calcifying plaques may cause chest pain, for example, due to endothelial dysfunction, which occurs at early stages of atherosclerosis, due to lack of regular flow-mediated vasodilation or even vasoconstriction at a lesion with mild stenosis.31
Third, our study revealed that the total and non-calcified plaque burdens (SIS and ncSIS) predict adverse outcome in terms of MACE and revascularisation procedures such as PCI or CABG, respectively, which is in line with results from the CONFIRM trial.32 In contrast, the CONFIRM trial mainly enrolled symptomatic patients.
As a study novelty, we calculated a dedicated non-calcifying plaque score (the ‘ncSIS’), which showed an increased risk of adverse outcome for secondary end point, even if only one (or more) segment was involved.
An increasing total coronary plaque burden by CTA was associated with a significantly increased risk of MACE and revascularisation rate, going in line with results from multicentre-registry CONFIRM, in which were identified as risk factors. The total plaque burden, stenosis severity32 or number of proximal segments with mixed or calcified plaques by CTA.33
Finally, our study provides strong evidence that CTA is a highly reliable and accurate tool to exclude significant CAD and MACE events over a midterm follow-up period of mean 2.65 years (up to 8 years). No cardiac events occurred in patients with negative CTA findings.
In summary, our data support screening of asymptomatic high-risk patients with CTA. Compared to CT Calcium Score, most recently introduced low-dose CT techniques such as prospective ECG-gating allow for almost equal or just slightly higher radiation exposure of ≥1 mSv, however, while adding iodine CA.
Compared to CCS, CTA provides the advantage of detecting non-calcifying plaque (representing early stages of atherosclerosis), coronary plaque load assessment and stenosis quantification for risk stratification. Patients with stenosis >50% by CTA yielded a markedly higher risk of adverse outcome than increasing CCS values.
Whether follow-up of high-risk patients by CCTA should be performed is currently an open item for discussion. There are no scientific data on CTA for monitoring of CAD progression. Follow-up intervals of a minimum of 5–7 years may be reasonable for evaluation of CAD progression. In those with intermediate stenosis (50–70%), a myocardial perfusion stress test (eg, SPECT) should be appended in order to define the haemodynamic significance of a coronary lesion.