{"title":"血浆神经酰胺和肾功能与冠状动脉病变严重程度的联合关系：CRUISE-MET研究。","authors":"Qiang Chen, Yike Li, Haoming He, Yingying Xie, Dongliang Fu, Ruilong Gao, Nan Li, Sunjin Fu, Yakun Mu, Yuxuan Sun, Zixuan Yang, Jiahui Zhou, Xu Li, Yanxiang Gao, Jingang Zheng","doi":"10.1016/j.jacl.2025.09.002","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ceramides and chronic kidney disease (CKD) independently promote atherosclerosis, yet their synergistic effect remains underexplored. This study systematically investigates their combined impact on coronary lesion severity.</p><p><strong>Method: </strong>This cross-sectional analysis included coronary artery disease (CAD) patients from the CRUISE-MET trial (NCT06383208). Six ceramide species: Cer (18:1/16:0), Cer (18:1/18:0), Cer (18:1/20:0), Cer (18:1/22:0), Cer (18:1/24:0), and Cer (18:1/24:1), were quantified via ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry. Baseline SYNTAX score (bSS) > 22 defined complex CAD. CKD was classified based on both estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). The combined and mediating effects of ceramides and renal dysfunction on coronary lesion complexity were further evaluated.</p><p><strong>Result: </strong>Among 691 CAD patients, those with complex lesions exhibited elevated UACR, Cer (18:1/16:0), Cer (18:1/18:0), Cer (18:1/24:1), and decreased eGFR (all P < .05). Cer (18:1/16:0) demonstrated the strongest correlation with bSS (r = 0.186, P < .001) and highest predictive accuracy (area under the curve = 0.616). Multivariable-adjusted logistic regression revealed that per-SD increase in Cer (18:1/16:0) conferred 31% higher odds of complex CAD (odds ratio [OR] = 1.31, 95% CI: 1.08-1.59; P = .006), with the highest tertile showing 88% elevated risk (OR = 1.88, 95% CI: 1.18-3.01; P = .008). Synergistic effects were observed between CKD and elevated Cer (18:1/16:0) (> median), with combined exposure increasing complex CAD risk 4.4-fold (OR = 4.40, 95% CI: 2.74-7.07; P < .001). Mediation analysis implicated renal impairment in 28.1% (UACR) and 13.9% (eGFR) of ceramide's atherogenic effects. Sensitivity analyses confirmed robustness in diabetic and hypertensive subgroups.</p><p><strong>Conclusion: </strong>The study highlights ceramide-renal synergy in exacerbating coronary atherosclerosis, advocating integrated biomarker profiling for risk stratification and dual-targeted therapies.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Joint association of plasma ceramide and renal function with coronary artery lesion severity: The CRUISE-MET study.\",\"authors\":\"Qiang Chen, Yike Li, Haoming He, Yingying Xie, Dongliang Fu, Ruilong Gao, Nan Li, Sunjin Fu, Yakun Mu, Yuxuan Sun, Zixuan Yang, Jiahui Zhou, Xu Li, Yanxiang Gao, Jingang Zheng\",\"doi\":\"10.1016/j.jacl.2025.09.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Ceramides and chronic kidney disease (CKD) independently promote atherosclerosis, yet their synergistic effect remains underexplored. This study systematically investigates their combined impact on coronary lesion severity.</p><p><strong>Method: </strong>This cross-sectional analysis included coronary artery disease (CAD) patients from the CRUISE-MET trial (NCT06383208). Six ceramide species: Cer (18:1/16:0), Cer (18:1/18:0), Cer (18:1/20:0), Cer (18:1/22:0), Cer (18:1/24:0), and Cer (18:1/24:1), were quantified via ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry. Baseline SYNTAX score (bSS) > 22 defined complex CAD. CKD was classified based on both estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). The combined and mediating effects of ceramides and renal dysfunction on coronary lesion complexity were further evaluated.</p><p><strong>Result: </strong>Among 691 CAD patients, those with complex lesions exhibited elevated UACR, Cer (18:1/16:0), Cer (18:1/18:0), Cer (18:1/24:1), and decreased eGFR (all P < .05). Cer (18:1/16:0) demonstrated the strongest correlation with bSS (r = 0.186, P < .001) and highest predictive accuracy (area under the curve = 0.616). Multivariable-adjusted logistic regression revealed that per-SD increase in Cer (18:1/16:0) conferred 31% higher odds of complex CAD (odds ratio [OR] = 1.31, 95% CI: 1.08-1.59; P = .006), with the highest tertile showing 88% elevated risk (OR = 1.88, 95% CI: 1.18-3.01; P = .008). Synergistic effects were observed between CKD and elevated Cer (18:1/16:0) (> median), with combined exposure increasing complex CAD risk 4.4-fold (OR = 4.40, 95% CI: 2.74-7.07; P < .001). Mediation analysis implicated renal impairment in 28.1% (UACR) and 13.9% (eGFR) of ceramide's atherogenic effects. 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引用次数: 0
摘要
背景：神经酰胺和慢性肾脏疾病（CKD）单独促进动脉粥样硬化，但它们的协同作用仍未被充分研究。本研究系统地调查了它们对冠状动脉病变严重程度的综合影响。方法：该横断面分析纳入了CRUISE-MET试验（NCT06383208）中的冠状动脉疾病（CAD）患者。采用超高效液相色谱-质谱/质谱法对Cer（18:1/16:0）、Cer（18:1/18:0）、Cer（18:1/20:0）、Cer（18:1/22:0）、Cer（18:1/24:0）、Cer(18:1/24:1) 6种神经酰胺进行定量分析。基线SYNTAX评分（bSS） bbb22定义复杂CAD。CKD的分类基于肾小球滤过率（eGFR）和尿白蛋白与肌酐比值（UACR）。进一步评价神经酰胺与肾功能对冠状动脉病变复杂性的联合及介导作用。结果：691例CAD患者中，病变复杂者UACR、Cer（18:1/16:0）、Cer（18:1/18:0）、Cer（18:1/24:1）升高，eGFR降低（均P < 0.05）。Cer（18:1/16:0）与bSS相关性最强（r = 0.186, P < .001），预测准确率最高（曲线下面积= 0.616）。多变量调整logistic回归显示，每sd增加的Cer（18:1/16:0）使复杂CAD的风险增加31%（比值比[OR] = 1.31, 95% CI: 1.08-1.59; P = 0.006），最高的单位数显示风险增加88% （OR = 1.88, 95% CI: 1.18-3.01; P = 0.008）。在CKD和Cer升高之间观察到协同效应（18:1/16:0）（中位数>），联合暴露使复杂CAD风险增加4.4倍（OR = 4.40, 95% CI: 2.74-7.07; P < .001）。中介分析涉及28.1% （UACR）和13.9% （eGFR）的神经酰胺的动脉粥样硬化作用的肾脏损害。敏感性分析证实了糖尿病和高血压亚组的稳健性。结论：该研究强调神经酰胺-肾脏协同作用可加重冠状动脉粥样硬化，提倡综合生物标志物分析进行风险分层和双靶向治疗。
Joint association of plasma ceramide and renal function with coronary artery lesion severity: The CRUISE-MET study.
Background: Ceramides and chronic kidney disease (CKD) independently promote atherosclerosis, yet their synergistic effect remains underexplored. This study systematically investigates their combined impact on coronary lesion severity.
Method: This cross-sectional analysis included coronary artery disease (CAD) patients from the CRUISE-MET trial (NCT06383208). Six ceramide species: Cer (18:1/16:0), Cer (18:1/18:0), Cer (18:1/20:0), Cer (18:1/22:0), Cer (18:1/24:0), and Cer (18:1/24:1), were quantified via ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry. Baseline SYNTAX score (bSS) > 22 defined complex CAD. CKD was classified based on both estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). The combined and mediating effects of ceramides and renal dysfunction on coronary lesion complexity were further evaluated.
Result: Among 691 CAD patients, those with complex lesions exhibited elevated UACR, Cer (18:1/16:0), Cer (18:1/18:0), Cer (18:1/24:1), and decreased eGFR (all P < .05). Cer (18:1/16:0) demonstrated the strongest correlation with bSS (r = 0.186, P < .001) and highest predictive accuracy (area under the curve = 0.616). Multivariable-adjusted logistic regression revealed that per-SD increase in Cer (18:1/16:0) conferred 31% higher odds of complex CAD (odds ratio [OR] = 1.31, 95% CI: 1.08-1.59; P = .006), with the highest tertile showing 88% elevated risk (OR = 1.88, 95% CI: 1.18-3.01; P = .008). Synergistic effects were observed between CKD and elevated Cer (18:1/16:0) (> median), with combined exposure increasing complex CAD risk 4.4-fold (OR = 4.40, 95% CI: 2.74-7.07; P < .001). Mediation analysis implicated renal impairment in 28.1% (UACR) and 13.9% (eGFR) of ceramide's atherogenic effects. Sensitivity analyses confirmed robustness in diabetic and hypertensive subgroups.
Conclusion: The study highlights ceramide-renal synergy in exacerbating coronary atherosclerosis, advocating integrated biomarker profiling for risk stratification and dual-targeted therapies.
期刊介绍：
Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner.
Sections of Journal of clinical lipidology will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.
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