Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification

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.

Dysregulated Metabolites Serve as Novel Biomarkers for Metabolic Diseases Caused by E-Cigarette Vaping and Cigarette Smoking

“…Significant upregulation of sphingolipid metabolites in cigarette smokers was identified in this study, and a recent clinical report described serum sphingolipids as biomarkers of cardiovascular disease [51]. In our cohort, we found increased serum ceramide (d18:1/24:0) levels in cigarette smokers, and ceramide (d18:1/24:0) has been reported as a predictor for the risk of myocardial infarcts and stroke [52]. Our results emphasize that elevated sphingolipids in cigarette smokers could serve as biomarkers for cardiovascular diseases.…”

Plasma Sphingolipid Profile Associated With Subclinical Atherosclerosis and Clinical Disease Markers of Systemic Lupus Erythematosus: Potential Predictive Value

“…Serum ceramide concentrations have been shown to have independent predictive value for CVD, including CAD, stroke, heart failure and atrial fibrillation (reviewed in 42 ), despite the fact that a direct cause-effect relationship between CVD and serum ceramide has not been established yet. A ceramide risk score (CERT1) which was based on C16:0, C18:0, and C24:1 ceramide concentrations and their ratios to C24:0 ceramide was developed for clinical use and was found to identify high-risk coronary heart disease patients beyond LDL-C concentration ( 43 , 44 ).…”

“…Based on CERT1, patients are stratified into four risk categories, where a linear CVD risk increase is associated with the increasing score both in patients with a stable coronary heart disease and ACS. The CERT1 ceramide score has been implemented in clinical use both in Finland and at Mayo Clinic in the USA ( 42 ). In our study, among the three CERT1 ceramide ratios, only C16:0 ceramide/C24:0 ceramide ratio was negatively correlated with TPA (% of control) but positively correlated with change in TPA ( p < 0.01) ( Table 3 ) .…”

Circulating Ceramides- Are Origins Important for Sphingolipid Biomarkers and Treatments?

“…Increased circulating ceramide levels is associated with a variety of metabolic and cardiac pathologies, including obesity, T2DM, insulin resistance and even more convincingly, ceramides could play a role in the onset and pathogenesis of CVD (3,4,14,(32)(33)(34)(35). There is convincing evidence that specific circulating ceramides can be used as biological predictors and markers of CVD (4,34,36), atherosclerosis (4) and T2DM (3,14,(32)(33)(34).…”