The main finding of this study was that in DM patients with non-obstructive CAD, higher atherosclerotic extent on CCTA provides incremental prognostic information and was associated with long term cardiovascular outcome, even after adjustment for traditional risk factors including age, gender, hyperlipidemia and High-risk plaque profiles. Our results reinforced the notion that greater efforts are needed to promote risk stratification with non-obstructive CAD, especially in the presence of DM. Segment involvement score, as well as Leidon risk score, represented an effective and reliable tool for calculating atherosclerotic extent, which have a substantial impact on clinical outcome in diabetic patients.
Our findings concurs with previous cohort study[4], which demonstrated that it is possible to identify high-risk diabetic patients based on assessment of CAD revealed by CCTA. However, several disparities must be noted. A higher ratio of non-obstructive/obstructive CAD was observed in the present cohort, approximately half of them non-obstructive, presenting a comparative low-risk population, which was in contrast to the previous study[15]. This may be ascribed to a direct referral to the invasive examination or revascularization driven by CCTA within 3 months, which has met the exclusion criteria, in high-risk population. Nonetheless, a slight higher MACEs rate was present,compared with an annual events rate ranged from 1.5–16.9% as a meta-analysis shown[15], in which diabetes examined by CCTA were investigated. One possibility is that we broadened enrollment to MACEs with stroke and extended follow-up to a median of 31 months, which was a sufficient duration to capture more events. Moreover, up to 4/5 patients received hypoglycemic therapy in baseline, indicating a potential long duration of diabetes and higher vascular risk. Another important observation from our study is that in risk-adjusted hazard analysis, the presence of HRP was found an independent predictor with a high HR of 3.15 (95%CI:1.97–5.04). This corresponds the result from ICONIC study[16] that stressed the importance of HRP + lesions in non-obstructive CAD, which exhibited comparable risk of becoming a culprit lesion to obstructive HRP- lesions. In view of this, we bring it into analysis, which has been done by little research before. However, after adjustment for HRP, extensive non-obstructive CAD was still found a significant indicator. This finding may inform future trials to determine the potential role of non-obstructive CAD in the setting of diabetes.
In the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial, most cardiovascular deaths or myocardial infarction (67%) occurred in patients with a normal stress test at baseline, most of which were found to have non-obstructive atherosclerotic disease by cardiac CT[17]. This suggests that we miss the opportunity to implement comprehensive preventive measure in most patients, especially diabetic patients, by relying on stress test results. The SCOT-HEART (Scottish Computed Tomography of the Heart) trial revealed a reduction of 41% in hazard of CAD-related death or non-fatal myocardial infarction for patients who were assigned to an anatomic versus functional strategy (2.4% vs. 3.9%)[18]. This was attributed to detection of non-obstructive coronary atherosclerosis and the initiation of directed preventive treatment. Our study was partly in line with the results above, and further stress the importance of medical management in diabetic patient with extensive non-obstructive coronary artery disease. The ability of non-invasively detect non-obstructive atherosclerotic disease by CT, thus, should be rendered as a necessary opportunity to initiate prevention earlier or intensive treatment in the process of disease, a strategy proven effective in reducing MACE[19].
Prior studies evaluated the extent and distribution of atherosclerosis with semiquantitative CCTA risk score in diabetes, mainly the SIS and the segment stenosis score (SSS)[20]. However, only the segments involved was quantified in SIS, representing the extent of CAD. Contrast with that, Leidon comprehensive risk score, being reported more strongly predictive than the SIS, integrates stenosis severity with the number and location of stenosis. A recent research from van den Hoogen IJ et al.[21] evaluated the per-segment and per-patient weight scores to determine the contribution of the stenosis, composition and location of CAD to the total score. As a result, all the per-patient weight scores were significantly higher in the setting of DM, while the per-segment location weight score was lower, which might be explainable by the multi-segment disease in DM patients. Based on this premise, we used Leidon score for sensitivity analysis to stress the extent of CAD as a supplement of the SIS. As a double confirm, consistent result was produced that futher supports our hypothesis.
Study Limitation
First, as a retrospective single center study, referral decision for CCTA was made by physicians independently and 894 patients were excluded finally due to various reasons, which may introduce selection bias. Secondly, diabetes is a dynamic risk factor, lack of the diabetes duration and treatment information on baseline may cause the misinterpret of the subsequent data analysis. Thirdly, although downstream treatment and management were recorded, relative treatments were not included in the final multivariate analysis, which may result in potential confounders and impact the effect size of target variables.