Specific plasma ceramides, particularly Cer(18:1/16:0), are independently associated with coronary artery calcification severity in CAD patients, with stronger associations in those with chronic kidney disease.
Key Findings
Results
Patients with moderate-to-severe CAC had higher levels of Cer(18:1/16:0) and Cer(18:1/24:1) and differed on several clinical features compared with those with no or mild CAC.
Cross-sectional analysis of 851 CAD patients from the CRUISE-MET trial (NCT06383208).
Six plasma ceramide species were quantified by UHPLC-MS/MS, and CAC severity was classified angiographically as absent, mild, moderate, or severe.
Patients with moderate-to-severe CAC were also older, had higher SYNTAX scores, and had lower eGFR (all p<0.05).
Results
Higher Cer(18:1/16:0) was independently associated with greater odds of moderate-to-severe CAC.
Each SD increase was associated with 59% higher odds (OR = 1.59, 95% CI: 1.33-1.88, p<0.001).
The highest tertile was associated with 151% higher odds (OR = 2.51, 95% CI: 1.68-3.75, p<0.001).
Analyses used logistic regression, ROC analysis, and restricted cubic splines.
Results
CKD modified the association between Cer(18:1/16:0) and moderate-to-severe CAC, with coexisting CKD and high ceramide exposure conferring nearly fourfold higher odds.
The p for interaction was 0.032.
Joint analysis of CKD and high ceramide exposure gave OR = 3.94 (95% CI: 2.47-6.28, p<0.001).
Results
Cer(18:1/16:0) statistically mediated part of the association between CKD and CAC.
Mediation analysis indicated Cer(18:1/16:0) accounted for 15.6% of the CKD-CAC association.
Results
Ceramide-CAC associations were directionally consistent across sensitivity analyses, including subgroups.
Sensitivity analyses evaluated consistency across subgroups.
Associations remained directionally consistent.
Results
In a subgroup with non-ECG-gated chest CT-derived CAC scores, selected ceramide species showed modest associations with quantitative CACS.
This imaging validation used a cohort with non-ECG-gated chest CT scores.
The associations were described as modest.
What This Means
This study looked at 851 people with coronary artery disease to see whether certain fats in the blood, called ceramides, were linked to calcium buildup in the heart's arteries. Calcium buildup stiffens the arteries and is especially common in people with chronic kidney disease. Researchers measured six ceramide types in blood and graded calcification on angiograms as none, mild, moderate, or severe.
One ceramide, Cer(18:1/16:0), stood out. People with higher levels had substantially greater odds of moderate-to-severe calcification, with those in the highest third having about 2.5 times the odds of those in the lowest third. The link was stronger in people with kidney disease: those with both kidney disease and high ceramide levels had nearly four times the odds. Statistical analysis suggested this ceramide may account for about 16% of the connection between kidney disease and calcification. In a smaller group with chest CT scans, associations with calcium scores were weaker but present.
This research suggests ceramides, especially Cer(18:1/16:0), may be markers of coronary calcification risk and could help explain how kidney problems contribute to it. Because the study is cross-sectional, it cannot show that ceramides cause calcification, and the findings would need confirmation in longer-term studies.
Chen Q, Guo S, Li X, Li Y, Xie Y, Fu S, et al.. (2026). Sphingolipid-renal interplay in coronary artery calcification: ceramide profiling and imaging validation from the CRUISE-MET study.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1974775