背景:钠-葡萄糖协同转运蛋白-2抑制剂(SGLT2i)是一种用于治疗2型糖尿病(T2DM)的新型口服药物,具有明显的心血管益处。先前在载脂蛋白E敲除小鼠中的研究表明SGLT2i与动脉粥样硬化的进展减弱有关。然而,在现实环境中,这种效应是否会扩展到有冠状动脉粥样硬化的T2DM患者仍不得而知.
方法:在这项使用冠状动脉计算机断层扫描血管造影术(CCTA)的纵向队列研究中,在2019年至2022年间在我们中心接受≥2项CCTA检查的T2DM患者进行筛查。符合条件的患者有多个研究斑块,定义为基线时非梗阻性狭窄,在连续CCTA期间未干预。排除标准包括CCTA时间间隔<12个月,先前的SGLT2i治疗,或在串行CCTA期间启动/停止SGLT2i。使用CCTA斑块分析软件测量每个研究斑块的斑块体积(PV)和动脉粥样硬化体积百分比(PAV)。基于SGLT2i治疗对患者和斑块进行分类,并使用1:1倾向评分匹配(PSM)分析进行比较。
结果:该研究包括236例患者(平均年龄60.5±9.5岁;男性占69.1%),研究斑块435例(直径狭窄≥50%,31.7%)。SGLT2i治疗后的中位持续时间为14.6个月(四分位距:13.0,20.0),总的来说,非钙化,低衰减PV和PAV显著下降,而钙化PV和PAV增加(均p<0.001)。同时,总PV的减少,非钙化PV,总体PAV,与未SGLT2i治疗的斑块相比,SGLT2i治疗的斑块和未钙化的PAV明显更高(均p<0.001)。PSM分析表明,SGLT2i治疗与总PV的更高降低相关(-11.77mm3vs.4.33mm3,p=0.005),非钙化PV(-16.96mm3vs.-1.81mm3,p=0.017),总体PAV(-2.83%与3.36%,p<0.001),和非钙化PAV(-4.60%vs.0.70%,p=0.003)。在评估总体和组成PV和PAV的年度变化时,这些发现保持一致。多变量回归模型表明SGLT2i治疗与总体或非钙化性PV或PAV的进展减弱有关,即使在调整了心血管危险因素后,药物,和基线整体或非钙化PV或PAV,分别(均p<0.05)。SGLT2i对减弱非钙化斑块进展的作用在各个亚组中是一致的(所有p均为相互作用>0.05)。
结论:在2型糖尿病患者的纵向CCTA队列中,SGLT2i治疗显著降低了冠状动脉总体PV和PAV,主要是由于非钙化斑块的显著减少。
BACKGROUND: Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) is a novel oral drug for treating type 2 diabetes mellitus (T2DM) with demonstrated cardiovascular benefits. Previous studies in apolipoprotein E knockout mice have shown that SGLT2i is associated with attenuated progression of atherosclerosis. However, whether this effect extends to T2DM patients with coronary atherosclerosis in real-world settings remains unknown.
METHODS: In this longitudinal cohort study using coronary computed tomography angiography (CCTA), T2DM patients who underwent ≥ 2 CCTA examinations at our center between 2019 and 2022 were screened. Eligible patients had multiple study plaques, defined as non-obstructive stenosis at baseline and not intervened during serial CCTAs. Exclusion criteria included a CCTA time interval < 12 months, prior SGLT2i treatment, or initiation/discontinuation of SGLT2i during serial CCTAs. Plaque volume (PV) and percent atheroma volume (PAV) were measured for each study plaque using CCTA plaque analysis software. Patients and plaques were categorized based on SGLT2i therapy and compared using a 1:1 propensity score matching (PSM) analysis.
RESULTS: The study included 236 patients (mean age 60.5 ± 9.5 years; 69.1% male) with 435 study plaques (diameter stenosis ≥ 50%, 31.7%). Following SGLT2i treatment for a median duration of 14.6 (interquartile range: 13.0, 20.0) months, overall, non-calcified, and low-attenuation PV and PAV were significantly decreased, while calcified PV and PAV were increased (all p < 0.001). Meanwhile, reductions in overall PV, non-calcified PV, overall PAV, and non-calcified PAV were significantly greater in SGLT2i-treated compared to non-SGLT2i-treated plaques (all p < 0.001). PSM analysis showed that SGLT2i treatment was associated with higher reductions in overall PV (- 11.77 mm3 vs. 4.33 mm3, p = 0.005), non-calcified PV (- 16.96 mm3 vs. - 1.81 mm3, p = 0.017), overall PAV (- 2.83% vs. 3.36%, p < 0.001), and non-calcified PAV (- 4.60% vs. 0.70%, p = 0.003). These findings remained consistent when assessing annual changes in overall and compositional PV and PAV. Multivariate regression models demonstrated that SGLT2i therapy was associated with attenuated progression of overall or non-calcified PV or PAV, even after adjusting for cardiovascular risk factors, medications, and baseline overall or non-calcified PV or PAV, respectively (all p < 0.05). The effect of SGLT2i on attenuating non-calcified plaque progression was consistent across subgroups (all p for interaction > 0.05).
CONCLUSIONS: In this longitudinal CCTA cohort of T2DM patients, SGLT2i therapy markedly regressed coronary overall PV and PAV, mainly result from a significant reduction in non-calcified plaque.