In the present study, we investigated the possible role and clinical implication of LECS association with CAD in patients with symptomatic PAD. We demonstrated that PAD patients with multivessel CAD had significantly higher LECS than those with nonsignificant CAD. Furthermore, LECS in LECTA was a significant predictor for the diagnosis of multivessel-CAD.
PAD is a systemic atherosclerotic disease and a high global risk factor for CAD (
1-
3). We therefore investigated the relationships among the extent of PAD, the extent of CAD, LECS, and CCS in patients with PAD. CAI had a strong correlation with LECS compared to LEAI in our study. LECS and CCS were predictors for multivessel-CAD in our study. There has been no report demonstrating a direct relationship between LECS and the extent of CAD in patients with PAD. Previous studies, however, did demonstrate that the presence of peripheral arterial calcification was strongly associated with cardiovascular mortality in Monckeberg’s arteriosclerosis (
25), diabetes (
26), and end-stage renal disease (
27). Calcification does not play a major role in inducing vascular stenosis in the early atherosclerotic stages, but increased arterial stiffness may contribute vascular calcification and subsequently stenosis in the later atherosclerotic stages (
28). That is why we enrolled symptomatic patients with PAD, which indicates advanced PAD. Patients with peripheral arterial calcification were therefore included in our study. Previous studies demonstrated that increased arterial stiffness causes aortic calcification and adverse cardiovascular events in patients with PAD (
29-
31).
We further investigated the difference of LEAI, LECS, and CAD in relation to vascular regions. In our study, LEAI and LECS in the below-knee region were significantly higher in multivessel-CAD rather than in nonsignificant CAD. Our study, however, showed that the diagnostic performance of LEAI and LECS in the below-knee region were relatively lower than in all segments. In other words, LEAI and LECS in the below-knee region were weakly associated with CAD; that is, the diagnostic impact of those variables was weak. PAD is a heterogeneous disease group and the disease location and distribution of PAD is important when predicting mortality. A previous study showed CAD was associated with LEAI in the femoropopliteal and below-knee regions, even though LEAI of the below-knee region was less associated with CAD (
32). This study also showed that older age, being male, having diabetes, and having critical limb ischemia were strongly associated with LEAI in the below-knee region (
32), so those variables could be confounding factors of our study.
We further investigated whether calcification and severity of the lower extremity arteries could predict multivessel-CAD. Until now, there have been no specific clinical trials to investigate the survival benefit in those patients. Coronary revascularization, however, has been known to be superior to medical therapy alone for reducing cardiovascular events in multivessel-CAD (
33,
34). The presence of multivessel-CAD may therefore be useful when determining a further treatment plan in patients with PAD. Our study showed that if calcifications were observed in more than six segments of the lower extremity arteries, there was a high probability of multivessel-CAD. Traditionally, the coronary calcium score has been a widely accepted indicator of significant CAD and cardiovascular outcomes (
14,
16-
18,
20). The previous study notably reported that increased CCS was associated with an increased frequency of multi-vessel CAD (
35). In our study, the diagnostic performance of LECS in all segments for the prediction of multivessel-CAD was relatively higher than that of LEAI and slightly lower than that of CCS. These findings suggest that we could predict multivessel-CAD using LECT alone, without additional radiation exposure, but LECS could not replace CCS in the prediction of multivessel-CAD.
We acknowledge several limitations in our study. First, our study had a retrospective design and included a relatively small number of patients. Additionally, well-known cardiovascular risk factors, such as diabetes, chronic renal disease, and hypertension, were not controlled in this study, so the results may be biased. Second, calcifications in the lower extremity arteries were not measured quantitatively, as with calcium volume or Agatston scores, because there was no pre-enhanced image for LECT in our study. Furthermore, calcified plaques with lower density of calcium could be missed. Automatic quantitative analysis in a pre-enhanced CT scan is a more accurate and reproducible method for measuring the amount of calcification. Third, hemodynamically significant CAD, rather than multivessel-CAD, would be more important for determining a treatment plan and predicting the cardiovascular outcome in patients with CAD. The stress perfusion image might be useful to identify the predictors of cardiovascular outcomes in patients with PAD.
In conclusion, LECS is associated with CCS and CAD. LECS measured by LECTA might be a useful marker for predicting multivessel-CAD in patients with PAD.