Objective- Ceramides are sphingolipids involved with cellular signaling. Synthesis of ceramides occurs in all tissues. Ceramides accumulate within tissues and the blood plasma during metabolic dysfunction, dyslipidemia, and inflammation. Elevations of ceramides are predictive of cardiovascular mortality. We sought to verify the utility of plasma concentrations of 4 ceramides: N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)], and N-lignoceroyl-sphingosine [Cer(24:0)] in predicting major adverse cardiovascular events in a diverse patient population referred for coronary angiography. Approach and Results- Plasma ceramides were measured in 495 participants before nonurgent coronary angiography. Coronary artery disease, defined as >50% stenosis in ≥1 coronary artery, was identified 265 (54%) cases. Ceramides were not significantly associated with coronary artery disease. Patients were followed for a combined primary end point of myocardial infarction, percutaneous intervention, coronary artery bypass, stroke, or death within 4 years. Ceramides were significantly predictive of outcomes after adjusting for age, sex, body mass index, hypertension, smoking, LDL (low-density lipoprotein) cholesterol, HDL (high-density lipoprotein) cholesterol, triglycerides, serum glucose, and family history of coronary artery disease. The fully adjusted per SD hazard ratios (95% confidence interval) were 1.50 (1.16-1.93) for Cer(16:0), 1.42 (1.11-1.83) for Cer(18:0), 1.43 (1.08-1.89) for Cer(24:1), and 1.58 (1.22-2.04) for the ceramide risk score. Conclusions- Elevated plasma concentrations of ceramides are independently associated with major adverse cardiovascular events in patients with and without coronary artery disease.

Retinoic acid (RA)

IBS-D with increased BA excretion or synthesis is associated with significant pathophysiological changes relative to patients with normal BA profile. BA diarrhea is identified more effectively with total fecal BA than with serum C4.

The anticarcinogenic activities of retinoic acid

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.