A total of 45 patients were enrolled in patient-level analysis. The study flow chart is shown in Supplementary Figure S1. As shown in Table 1, the mean age of the patients was 60 years, 75% were male, and 67% had one-vessel disease. The mean time between coronary CTA and invasive angiography and FFR was 11 days. In all, 68 lesions had a diameter stenosed ≥30%. Among them, FFR was performed on 65 (96%) lesions. Three lesions with diameters stenosed >90% were not measured by FFR. After screening, 55 lesions were enrolled in lesion-level analysis (Supplementary Figure S1). As shown in Table 2, most of lesions were in the left anterior descending (LAD) coronary artery (71%) or its middle segments (66%). Nearly half of the lesions had intermediate stenosis (49%), and 62% had calcified plaque. The mean preoperative FFR value was 0.82. Ischemic lesions accounted for 47%, and eventually 29% of patients (22% of lesions) underwent percutaneous coronary intervention (PCI).
EAT volume and myocardial ischemia in patient-level analysis
Patients were divided into non-ischemia and ischemia groups based on the presence of at least one hemodynamically relevant lesion (44% and 56%, respectively). The ischemic patients were slightly older than the non-ischemic patients, had more extensive and more severe CAD, and half underwent PCI (Table 1). As shown in Figure 2A, the total EAT volume was non-significantly greater in ischemic patients than non-ischemic patients (102.0 vs 84.0 ml, P=0.077), whereas this pattern became statistically significant regarding the indexed total EAT volume (ischemia vs non-ischemia, 53.4 vs 47.6 ml/m2, P=0.032). Patients were also divided into non-significant and significant stenosis groups according to the presence of at least one significantly stenotic lesion (58% and 42%, respectively). Similarly, as shown in Figure 2B, compared with non-significant stenosis patients, significant stenosis patients had a slightly higher total EAT volume (102.0 vs 85.9 ml, P=0.061) and a markedly higher indexed total EAT volume (53.4 vs 47.6 ml/m2, P=0.046). The relation of EAT volume and myocardial ischemia in a dose-dependent manner was not further investigated because most of the patients had at least one ischemic or significant stenosis (91% and 95%, respectively).
In addition, we found that the total EAT volume positively correlated with the body mass index (r=0.381, P=0.010), fasting blood glucose level (r=0.341, P=0.022), and glycatedserum protein level (r=0.434, P=0.003). Moreover, the indexed total EAT volume was still positively correlated with the fasting blood glucose (r=0.330, P=0.027) and glycated serum protein (r=0.466, P=0.001) (Figure2C). Glycated serum protein was also positively correlated with the total veEAT volume (r=0.308, P=0.040) and its index value (r=0.293, P=0.051) (Figure2D).
EAT volume or density and myocardial ischemia in lesion-level analysis
All study lesions were divided into non-ischemic and ischemic lesions, the baseline characteristics of which are shown in Table 2. Compared with non-ischemia lesions, ischemic lesions had more severe diameter stenosis and greater plaque length. Pre-procedural FFR values for ischemic lesions were significantly lower than those of the non-ischemic lesions: 0.74±0.08 vs 0.89±0.05 (P<0.001). Ischemic lesions accounted for 46% of all lesions that underwent PCI. None of the non-ischemic lesions were treated. As shown in Table 2, compared with non-ischemic lesions, ischemic lesions had higher leEAT volumes (0.64 vs 0.50 ml, P=0.051) and a significantly higher leEAT volume index (0.34 vs 0.27 ml/m2, P=0.045). This pattern, however, was not apparent for the veEAT volume (6.89 vs 7.20 ml, P=0.607) or veEAT volume index (3.83 vs 3.80 ml/m2, P=0.508). Subgroup analysis showed that, except for the ischemic lesions (P=0.045), the leEAT volume index was not significantly different with respect to proximal lesions, LAD, calcified plaque, or diameter stenosed ≥75% (all P>0.05) (Figure3A). Furthermore, as shown in Supplementary Table S1, the independent lesion-level predictors for ischemia were diameter stenosis of ≥75% [hazard ratio (HR) 14.56, 95% CI 2.93–72.24, P=0.001] and the leEAT volume index (per 0.1 ml/m2 increase) (HR 1.56, 95% CI 1.04–2.33, P=0.032), after adjusting for LAD, proximal segment, plaque length, plaque calcification, and reference vessel diameter.
We also evaluated EAT density between non-ischemic and ischemic lesions, which showed no significant differences with regard to leEAT density (−76.54±12.71 vs −78.23±10.44 HU, P=0.600), veEAT density of the proximal reference vessel (−71.94±9.60 vs −74.00±11.63 HU, P=0.475)], or the distal reference vessel (-90.40±9.65 vs -91.38±14.04 HU, P=0.763) (Figure3B). Additionally, we found that baseline FFR values negatively correlated with the leEAT volume (r=-0.282, P=0.043) (Figure3C) or the leEAT volume index (r=−0.281, P=0.044) (Figure3D).