Alessandro Mantovani1, Stefano Bonapace2, Gianluigi Lunardi3, Matteo Salgarello4, Clementina Dugo2, Guido Canali2, Christopher D Byrne5, Stefania Gori3, Enrico Barbieri2, Giovanni Targher6. 1. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. 2. Division of Cardiology, "Sacro Cuore-Don Calabria" Hospital, Negrar, VR, Italy. 3. Division of Medical Oncology, "Sacro Cuore-Don Calabria" Hospital, Negrar, VR, Italy. 4. Division of Nuclear Medicine, "Sacro Cuore-Don Calabria" Hospital, Negrar, VR, Italy. 5. Nutrition and Metabolism, Faculty of Medicine, University of Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton SO16 6YD, UK. 6. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. Electronic address: giovanni.targher@univr.it.
Abstract
BACKGROUND: Recent studies have suggested that specific plasma ceramides are independently associated with major adverse cardiovascular events in patients with coronary artery disease (CAD), but it is currently unknown whether plasma ceramide levels are associated with stress-induced reversible myocardial ischemia. METHODS: We measured six previously identified high-risk plasma ceramide molecules [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1)] in 167 consecutive patients with established or suspected CAD who underwent either exercise or dypiridamole myocardial perfusion scintigraphy (MPS) for various clinical indications. Plasma ceramide levels were measured by a targeted liquid chromatography-tandem mass spectrometry assay both at baseline and after MPS. RESULTS: Seventy-eight patients had inducible myocardial ischemia on stress MPS. Women had significantly higher circulating levels of basal and post-stress Cer(d18:1/16:0) and Cer(d18:1/18:0) compared to men, whereas all other plasma ceramides did not differ between the sexes. Of the six measured plasma ceramides, basal Cer(d18:1/24:1) showed the strongest association with the presence of stress-induced myocardial perfusion defects in univariate analysis (unadjusted-odds ratio 1.48 per 1-SD increment, 95% confidence interval 1.08-2.04). Notably, after adjustment for age, sex, smoking, dyslipidemia, hypertension, diabetes, prior history of CAD, left ventricular ejection fraction, and type of stress testing (exercise vs. dypiridamole), all measured ceramides, except for plasma Cer(d18:1/24:0), were independently associated with the presence of inducible myocardial ischemia. CONCLUSIONS: Distinct plasma ceramides are positive and independent predictors of stress-induced myocardial perfusion defects in patients with established or suspected CAD referred for clinically indicated MPS. Further research is needed to examine whether distinct plasma ceramides could be a useful therapeutic target for treatment and management of CAD.
BACKGROUND: Recent studies have suggested that specific plasma ceramides are independently associated with major adverse cardiovascular events in patients with coronary artery disease (CAD), but it is currently unknown whether plasma ceramide levels are associated with stress-induced reversible myocardial ischemia. METHODS: We measured six previously identified high-risk plasma ceramide molecules [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1)] in 167 consecutive patients with established or suspected CAD who underwent either exercise or dypiridamole myocardial perfusion scintigraphy (MPS) for various clinical indications. Plasma ceramide levels were measured by a targeted liquid chromatography-tandem mass spectrometry assay both at baseline and after MPS. RESULTS: Seventy-eight patients had inducible myocardial ischemia on stress MPS. Women had significantly higher circulating levels of basal and post-stress Cer(d18:1/16:0) and Cer(d18:1/18:0) compared to men, whereas all other plasma ceramides did not differ between the sexes. Of the six measured plasma ceramides, basal Cer(d18:1/24:1) showed the strongest association with the presence of stress-induced myocardial perfusion defects in univariate analysis (unadjusted-odds ratio 1.48 per 1-SD increment, 95% confidence interval 1.08-2.04). Notably, after adjustment for age, sex, smoking, dyslipidemia, hypertension, diabetes, prior history of CAD, left ventricular ejection fraction, and type of stress testing (exercise vs. dypiridamole), all measured ceramides, except for plasma Cer(d18:1/24:0), were independently associated with the presence of inducible myocardial ischemia. CONCLUSIONS: Distinct plasma ceramides are positive and independent predictors of stress-induced myocardial perfusion defects in patients with established or suspected CAD referred for clinically indicated MPS. Further research is needed to examine whether distinct plasma ceramides could be a useful therapeutic target for treatment and management of CAD.
Authors: Débora L M Junqueira; Alline Stach; Adriano Caixeta; Juliana Sallum; Erika Yasaki; Jeane Tsutsui; Edgar Rizatti; Carlos E Rochitte; Jean-Paul Kovalik; José E Krieger; A Mark Richards; Mark Y Chan; Leonardo P de Carvalho Journal: Arq Bras Cardiol Date: 2022-04 Impact factor: 2.000