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.