Abstract

Ceramides are bioactive lipids that have an important role in many cellular functions such as apoptosis and inflammation. During the past decade emerging clinical data have shown that ceramides are not only of great biochemical interest but may also have diagnostic utility. Ceramides have shown independent predictive value for negative cardiovascular outcomes as well as for the onset of type 2 diabetes. Based on abundant published data, risk score using the concentrations of circulating ceramides have been developed and adapted for routine clinical practice. Currently serum ceramides are used clinically as efficient risk stratifiers for primary and secondary prevention of atherosclerotic cardiovascular disease (CVD). A direct cause-effect relationship between CVD and ceramide has not been established to date. As ceramide-specific medications are being developed, conventional strategies such as lipid lowering agents and lifestyle interventions can be used to reduce overall risk. Ceramides can identify a very high-risk coronary heart disease category of patients in need for more intense medical attention, specifically those patients at higher risk as highlighted in the 2019 European Society of Cardiology guidelines for stable chronic coronary syndrome patients. In addition, the ceramide risk score may be used as a decision-making tool in primary prevention patients with moderate CVD risk. Finally, the ceramide risk score may have a unique utility as a motivational tool to increase patient's adherence to medical therapy and lifestyle changes.

Highlights

  • Ceramides are bioactive lipids that play important roles in many central processes of human cells, such as apoptosis and inflammation [for additional information see e.g., the following reviews [1,2,3,4,5]]

  • The purpose of this review is to provide a summary of cardiovascular disease (CVD)- and diabetes-related ceramide data published as of spring 2020 and to depict how the results have been translated into clinical practice

  • Jenssen et al evaluated whether the length of the saturated fatty acid carried by ceramide or their sphingomyelin precursors were associated with incident atrial fibrillation (AF) risk among 4,206 Cardiovascular Health Study participants

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Summary

INTRODUCTION

Ceramides are bioactive lipids that play important roles in many central processes of human cells, such as apoptosis and inflammation [for additional information see e.g., the following reviews [1,2,3,4,5]]. Serum ceramide concentrations have been shown to predict cardiovascular atherosclerotic disease (CVD) such as coronary artery disease (CAD), stroke, as well as heart failure and atrial fibrillation [12,13,14,15,16,17,18]. These associations were initially observed in small case-control studies or in investigations. Several studies revealed that ceramides may provide important clinical value, yet the significance of individual ceramides and their mechanistic contribution to the disease pathogenesis has remained uncertain This has hindered the development of clinical tests of single ceramides. The purpose of this review is to provide a summary of CVD- and diabetes-related ceramide data published as of spring 2020 and to depict how the results have been translated into clinical practice

CERAMIDES IN CARDIOVASCULAR
FACTORS AFFECTING CIRCULATING CERAMIDE CONCENTRATIONS
CERAMIDE SCORE AS THE CLINICAL
Stable CAD
Unbiased Machine Learning Based SIC Score
CLINICAL USE OF SCORES
CONCLUSIONS
Findings
Improved insulin sensitivity after exercise training is linked to reduced plasma

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