Test Catalog

Test Name

Test ID: CERAM    
Ceramides, Plasma

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluation for risk of major adverse events due to cardiovascular disease within the next 1 to 5 years

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Plasma ceramides are predictors of adverse cardiovascular events resulting from unstable atherosclerotic plaque. Ceramides are complex lipids that play a central role in cell membrane integrity, cellular stress response, inflammatory signaling, and apoptosis. Synthesis of ceramides from saturated fats and sphingosine occurs in all tissues. Metabolic dysfunction and dyslipidemia results in accumulation of ceramides in tissues not suited for lipid storage. Elevated concentrations of circulating ceramides are associated with atherosclerotic plaque formation,(1) ischemic heart disease, myocardial infarction,(2,3) hypertension,(4) stroke,(5) type 2 diabetes mellitus, insulin resistance and obesity.(6)

 

Three specific ceramides have been identified as highly linked to cardiovascular disease and insulin resistance: Cer16:0, Cer18:0, and Cer24:1. Individuals with elevated plasma ceramides are at higher risk of major adverse cardiovascular events even after adjusting for age, gender, smoking status, and serum biomarkers such as low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, c-reactive protein (CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2). Direct interventional studies have not yet been reported; however, ceramide concentrations are reduced by current cardiovascular therapies including statins, ezetimibe, and Proprotein convertase subtilisin/kexin type 9 (PCSK9) activity.(3,7)

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Ceramide (16:0): 0.19-0.36 mcmol/L

Ceramide (18:0): 0.05-0.14 mcmol/L

Ceramide (24:1): 0.65-1.65 mcmol/L

Ceramide (16:0)/(24:0): <0.11

Ceramide (18:0)/(24:0): <0.05

Ceramide (24:1)/(24:0): <0.45

Ceramide Risk Score:

0-2 Lower risk

3-6 Moderate risk

7-9 Increased risk

10-12 Higher risk

 

Reference values have not been established for patients who are <18 years of age.

 

Note: Ceramide (24:0) alone has not been independently associated with disease and will not be reported.

Interpretation Provides information to assist in interpretation of the test results

Elevated plasma ceramides are associated with increased risk of myocardial infarction, acute coronary syndromes, and mortality within 1 to 5 years.

Ceramide Score

Relative Risk

Risk Category

0-2

1.0

Lower

3-6

1.8

Moderate

7-9

2.3

Increased

10-12

5.1

Higher

Score is based on trial data including >4,000 subjects.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Samples should not be collected from patients receiving Intralipid, as it may cause false-elevations in measured ceramides.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Cheng JM, Suoniemi M, Kardys I, et al: Plasma concentrations of molecular lipid species in relation to coronary plaque characteristics and cardiovascular outcome: Results of the ATHEROREMO-IVUS study. Atherosclerosis 2015;243:560-566

2. Pan W, Yu J, Shi R, et al: Elevation of ceramide and activation of secretory acid sphingomyelinase in patients with acute coronary syndromes. Coron Artery Dis 2014;25:230-235

3. Tarasov K, Ekroos K, Suoniemi M, et al: Molecular lipids identify cardiovascular risk and are efficiently lowered by simvastatin and PCSK9 deficiency. J Clin Endocrinol Metab 2014;99:E45-52

4. Spijkers LJ, van den Akker RF, Janssen BJ, et al: Hypertension is associated with marked alterations in sphingolipid biology: a potential role for ceramide. PLoS One 2011;6:e21817

5. Yu RK, Tsai YT, Ariga T, Yanagisawa M: Structures, biosynthesis, and functions of gangliosides--an overview. J Oleo Sci 2011;60:537-544

6. Bergman BC, Brozinick JT, Strauss A, et al: Serum sphingolipids: relationships to insulin sensitivity and changes with exercise in humans. Am J Physiol Endocrinol Metab 2015;309:E398-408

7. Ng TW, Ooi EM, Watts GF, et al: Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome. J Clin Endocrinol Metab 2014;99:E2335-2340

8. Laaksonen R, Ekroos K, Sysi-Aho M, et al: Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol. Eur Heart J [epub ahead of print] April 28th, 2016. DOI:10.1093/eurheartj/ehw148