Abstract
Background: Ceramides, biologically active lipids correlated to oxidative stress and inflammation, have been associated with adverse outcomes in acute myocardial infarction (AMI). The purpose of this study was to assess the association between ceramides/ratios included in the CERT1 score and increased cardiovascular (CV) risk, inflammatory and left ventricular function parameters in AMI. Methods: high performance liquid chromatography-tandem mass spectrometry was used to identify Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) levels and their ratios to Cer(d18:1/24:0), in 123 AMI patients (FTGM coronary unit, Massa, Italy). Results: Cer(d18:1/16:0): higher in female patients (<0.05), in patients with dyslipidemia (<0.05), and it directly and significantly correlated with aging, brain natriuretic peptide-BNP, erythrocyte sedimentation rate-ESR and fibrinogen. Cer(d18:1/18:0): higher in females (<0.01) and patients with dyslipidemia (<0.01), and increased according to the number of CV risk factors (considering hypertension, dyslipidemia and diabetes). Moreover, it significantly correlated with BNP, troponin at admission, ESR, C reactive protein-CRP, and fibrinogen. Cer(d18:1/24:1): significantly correlated with aging, BNP, fibrinogen and neutrophils. Cer(d18:1/16:0)/Cer(d18:1/24:0): higher in female patients (<0.05), and in patients with higher wall motion score index-WMSI (>1.7; ≤0.05), and in those with multivessel disease (<0.05). Moreover, it significantly correlated with aging, BNP, CRP, ESR, neutrophil-to-lymphocyte ratio-NRL, and fibrinogen. Cer(d18:1/18:0)/Cer(d18:1/24:0): higher in female patients (<0.001), and increased according to age. Moreover, it was higher in patients with lower left ventricular ejection fraction (<35%, ≤0.01), higher WMSI (>1.7, <0.05), and in those with multivessel disease (0.13 ± 0.06 vs. 0.10 ± 0.05 µM, <0.05), and correlates with BNP, ESR, CRP, fibrinogen and neutrophils, platelets, NLR, and troponin at admission. Multiple regression analysis showed that Cer(d18:1/16:0)/Cer(d18:1/24:0) and Cer(d18:1/18:0)/Cer(d18:1/24:0) remained as independent determinants for WMSI after multivariate adjustment (Std coeff 0.17, T-value 1.9, ≤0.05; 0.21, 2.6, <0.05, respectively). Conclusion: Distinct ceramide species are associated with CV risk, inflammation and disease severity in AMI. Thus, a detailed analysis of ceramides may help to better understand CV pathobiology and suggest these new biomarkers as possible risk predictors and pharmacological targets in AMI patients.
Highlights
IntroductionA lipidomic profile improves prediction of cardiovascular events upon traditional risk factors, as in the American ADVANCE trial and in the Italian Bruneck study [7,8]
Distinct ceramides resulted progressively higher in patients with stable angina, unstable angina, and acute myocardial infarction (AMI) with respect to healthy controls, and their levels appear related to disease severity [5,6]
It has been postulated that ceramides promote aggregation and absorption of lipoproteins in the arterial wall, which renders the lipid-rich core larger and more prone to rupture, a fact confirmed by two recent imaging studies, which involve ceramides in the plaque rupture [15,16,23]
Summary
A lipidomic profile improves prediction of cardiovascular events upon traditional risk factors, as in the American ADVANCE trial and in the Italian Bruneck study [7,8] These associations with clinical cardiovascular risk are supported by the multiple critical cellular pathways which may link ceramides to atherosclerosis, in particular those related to chronic inflammation and cytokines, oxidative stress, increased uptake of lipoproteins and accumulation of cholesterol within macrophages, and enhanced platelet activation [1,9]. Cer(d18:1/18:0): higher in females (
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