Plasma Ceramide Levels Are Elevated in Patients With Early Coronary Atherosclerosis and Endothelial Dysfunction

BACKGROUND: Elevated plasma ceramides are independent predictors of cardiovascular disease and mortality in patients with advanced epicardial coronary artery disease. Our understanding of plasma ceramides in early epicardial coronary artery disease, however, remains limited. We examined the role of plasma ceramides in early coronary atherosclerosis characterized by coronary endothelial dysfunction. METHODS AND RESULTS: Participants presenting with chest pain and nonobstructive epicardial coronary artery disease underwent coronary endothelial function. Patients (n=90) demonstrated abnormal coronary endothelial function with acetylcholine (≥20% decrease in coronary artery diameter or ≤50% increase in coronary blood flow). A total of 30 controls had normal coronary endothelial function. Concentrations of plasma ceramide 18:0 (P=0.038), 16:0 (P=0.021), and 24:0 (P=0.019) differed between participants with normal and abnormal coronary endothelial function. Ceramide 24:0 (odds ratio [OR], 2.23 [95% CI, 1.07–4.66]; P=0.033) and 16:0 (OR, 1.91×10(6) [95% CI, 11.93–3.07×10(11)]; P=0.018) were independently associated with coronary endothelial dysfunction. Among participants with endothelium‐dependent coronary dysfunction (n=78), ceramides 16:0 (OR, 5.17×10(5) [95% CI, 2.83–9.44×10(10)]; P=0.033), 24:0 (OR, 2.98 [95% CI, 1.27–7.00]; P=0.012), and 24:1/24:0 (OR, 4.39×10(−4) [95% CI, 4×10(−7)–0.48]; P=0.030) were more likely to be elevated. CONCLUSIONS: The current study demonstrated an association between increased circulating ceramide levels and coronary endothelial dysfunction in the absence of epicardial coronary artery disease. This study supports the role of plasma ceramides as a potential biomarker or a therapeutic target for early coronary atherosclerosis in humans.