Association of Plasma Ceramides With Myocardial Perfusion in Patients With Coronary Artery Disease Undergoing Stress Myocardial Perfusion Scintigraphy

Abstract

Objective— It is known that specific plasma ceramides are associated with stress-induced reversible myocardial perfusion defects in patients with established or suspected coronary artery disease undergoing myocardial perfusion scintigraphy (MPS). However, it is currently uncertain whether plasma ceramides are also associated with reduced poststress myocardial perfusion in these patients. Approach and Results— We measured 6 previously identified high-risk plasma ceramide species (ceramide [d18:1/16:0], ceramide [d18:1/18:0], ceramide [d18:1/20:0], ceramide [d18:1/22:0], ceramide [d18:1/24:0], and ceramide [d18:1/24:1]) in 167 consecutive patients with established or suspected coronary artery disease undergoing stress MPS for clinical indications. Plasma ceramides were measured by a targeted liquid chromatography–tandem mass spectrometry assay both at baseline and after MPS. Multivariable linear regression analysis was undertaken to examine the associations (standardized B coefficients) between plasma ceramides and the percentage of poststress myocardial perfusion after adjustment for multiple cardiovascular risk factors. Seventy-eight patients had stress-induced myocardial ischemia on MPS (mainly located in the anteroapical wall). Of the 6 measured plasma ceramides, higher levels of basal ceramide (d18:1/18:0; B=−0.182; P =0.019), ceramide (d18:1/20:0; B=−0.224; P =0.004), ceramide (d18:1/22:0; B=−0.163; P =0.035), and ceramide (d18:1/24:1; B=−0.20; P =0.010) were associated with lower poststress anteroapical wall perfusion. Notably, these significant associations persisted even after adjustment for conventional cardiovascular risk factors, previous coronary artery disease, electrocardiographic left bundle branch block, left ventricular ejection fraction and type of stress testing. Similar results were observed for poststress plasma ceramides. Conclusions— Higher circulating levels of specific ceramides, both at baseline and after stress, were independently associated with lower poststress anteroapical wall perfusion in patients with suspected or established coronary artery disease referred for clinically indicated MPS.