Qiang Chen, Xuexi Li, Yingying Xie, Yike Li, Zhaoxue Sheng, Wuqiang Che, Shuoyan An, Sunjing Fu, Lining He, Cui Fang, Wenjun Dong, Jingang Zheng, Yanxiang Gao
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引用次数: 0
Abstract
Background: Ceramides and chronic kidney disease (CKD) independently associate with coronary microvascular dysfunction (CMD), but their combined association remains unestablished, warranting investigation.
Method: This cross-sectional analysis included coronary artery disease (CAD) patients from the CRUISE-MET trial (NCT06383208) who underwent coronary angiography and ceramide profiling measurement. The microvascular resistance was assessed in all patients using the angiography-derived microcirculatory resistance (AMR). CKD was classified based on both estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). The combined associations and statistical mediation of ceramides and renal dysfunction on CMD was examined, with sensitivity analyses to ensure the robustness.
Result: In this analysis of 794 CAD patients, CKD patients demonstrated significantly higher AMR values [2.56 ± 0.51 vs 2.46 ± 0.48, p = 0.003] and CMD prevalence (57.1% vs 41.7%, p<0.001). Three ceramide species - Cer(18:1/16:0), Cer(18:1/18:0), and Cer(18:1/24:1) - showed strong positive correlations with AMR (all p < 0.05). LASSO regression identified 14 factors associated with CMD, with E/e', CKD, and Cer(18:1/16:0) emerging as top correlates. Cer(18:1/16:0) demonstrated superior predictive performance (AUC=0.609, 95%CI: 0.570-0.648, p<0.001), with its addition to baseline models significantly improving reclassification (δAUC=0.03, p=0.010; cNRI＞0=0.23, p<0.001; IDI=0.03, p<0.001). Notably, patients with concurrent CKD and elevated Cer(18:1/16:0) exhibited significantly higher odds of CMD (OR=3.74, 95%CI: 2.39-5.84). Statistical mediation analysis suggested that Cer(18:1/16:0) mediated 13.8% of the association between CKD and CMD.
Conclusion: Ceramides, particularly Cer(18:1/16:0), partially mediated the statistical association between CKD and CMD. These findings highlight the potential role of sphingolipid metabolism in cardiorenal pathophysiology.
背景：神经酰胺和慢性肾脏疾病（CKD）单独与冠状动脉微血管功能障碍（CMD）相关，但它们之间的联合关系尚未确定，值得进一步研究。方法：本横断面分析包括CRUISE-MET试验（NCT06383208）中接受冠状动脉造影和神经酰胺谱测量的冠状动脉疾病（CAD）患者。使用血管造影衍生的微循环阻力（AMR）评估所有患者的微血管阻力。CKD的分类基于肾小球滤过率（eGFR）和尿白蛋白与肌酐比值（UACR）。神经酰胺和肾功能障碍对CMD的联合关联和统计中介进行了检查，并进行了敏感性分析以确保稳健性。结果：在794例CAD患者中，CKD患者的AMR值（2.56±0.51 vs 2.46±0.48,p = 0.003）和CMD患病率（57.1% vs 41.7%）显著高于CKD患者（p = 0.003）。结论：神经酰胺，尤其是Cer（18:1/16:0）在CKD与CMD之间的统计学关联中起部分介导作用。这些发现强调了鞘脂代谢在心肾病理生理中的潜在作用。
期刊介绍：
The journal ''Cardiorenal Medicine'' explores the mechanisms by which obesity and other metabolic abnormalities promote the pathogenesis and progression of heart and kidney disease (cardiorenal metabolic syndrome). It provides an interdisciplinary platform for the advancement of research and clinical practice, focussing on translational issues.
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