CERT2 is a ceramide based diagnostic test that identifies patients who are at risk of heart attack or cardiovascular death.

CERT2 helps to find high-risk patients even if traditional clinical parameters such as LDL-C might suggest that they are not at an elevated risk.

Ceramide lipids are central agents of this test.


Publications on CERT and Ceramides:

Introduction to Ceramides in CVD

Leslie M. Straight from the heart. Science vol 379; issue 6637, March 2023: 10980-1083.

Tippetts TS, Holland WL, Summers SA. Cholesterol – the devil you know; ceramide – the devil you don’t. Trends Pharmacol Sci. 2021 Dec;42(12):1082-1095.

Summers SA. Could Ceramides Become the New Cholesterol? Cell Metab. 2018 Feb 6;27(2):276-280.

CERT in Primary Prevention

Hilvo et al. 2021 Absolute and relative risk prediction in cardiovascular primary prevention with a modified SCORE chart incorporating ceramide-phospholipid risk score and diabetes mellitus, Eur Heart J. Open, Vol 1. Issue 3, Nov 2021

Vasile & Jaffe 2021 An enhanced ceramide-based approach for primary prevention of atherosclerotic events. European Heart J. Open, Volume 1, Issue 3, November 2021.

Vasile VC, et al. Ceramide Scores Predict Cardiovascular Risk in the Community. Arterioscler Thromb Vasc Biol. 2021 Apr;41(4):1558-1569.  Epub 2021 Feb 18. PMID: 33596665

Havulinna et al. 2016 Circulating Ceramides Predict Cardiovascular Outcomes in the Population-Based FINRISK 2002 Cohort, Arterioscler Thromb Vasc Biol. 2016; 36

Peterson et al. 2018 Ceramide Remodeling and Risk of Cardiovascular Events and Mortality.  J Am Heart Assoc. 2018 May 3;7(10):e007931

CERT in Secondary Prevention

Leiherer et al. 2024 Ceramides Improve cardiovascular risk prediction beyond low-density lipoprotein cholesterol. Eur Heart J. Open, 2024 (4), 1-9.

Hilvo et al. 2021 Prior myocardial infarction, coronary artery disease extent, diabetes mellitus, and CERT2 score for risk stratification in stable coronary artery disease, Eur J Prev Cardiology, Published 28 August 2021

Leiherer et al. 2021 Comparison of recent ceramide-based coronary risk prediction scores in cardiovascular disease patients, Eur J Prev Cardiology, Published 21 August 2021

Hilvo et al. 2020 Development and validation of a ceramide- and phospholipid-based cardiovascular risk estimation score for coronary artery disease patients. Eur Heart J. 2020; 41:371-380.

Gencer et al. 2020 Plasma ceramide and phospholipid-based risk score and the risk of cardiovascular death in patients after acute coronary syndrome. Eur. J. Prev. Cardiol. Published online Dec 2020

Meeusen et al. 2020 Ceramides improve atherosclerotic cardiovascular disease risk assessment beyond standard risk factors. Clinica Chimica Acta 2020. 511: 138–142

Hilvo et al. 2020 Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification. Front. Endocrinol., 29 September 2020

Hilvo et al. 2020 Prediction of Residual Risk by Ceramide‐Phospholipid Score in Patients With Stable Coronary Heart Disease on Optimal Medical Therapy JAHA published online May 7, 2020.

Mantovani et al. 2020 Associations between specific plasma ceramides and severity of coronary-artery stenosis assessed by coronary angiography. Diabetes & Metabolism, 46(2): 150-157.

Poss et al. 2020 Risky lipids: Refining the ceramide score that measures cardiovascular health. Eur. Heart Journal, 41(3): 381–382.

Meeusen et al. 2018 Plasma Ceramides – A Novel Predictor of Major Adverse Cardiovascular Events After Coronary Angiography.  Arterioscler Thromb Vasc Biol. 2018 Aug;38(8):1933-1939.

Laaksonen et al. 2016 Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol, Eur Heart J., 28 April 2016

Anroedh et al. 2018 Plasma concentrations of molecular lipid species predict long-term clinical outcome in coronary artery disease patients. J. Lipid Research June 2018, 59(6).

Carvalho et al. 2018 Plasma Ceramides as Prognostic Biomarkers and Their Arterial and Myocardial Tissue Correlates in Acute Myocardial Infarction  JACC Basic Transl Sci. 2018 May 30;3(2):163-175.

Cheng et al. 2015 Plasma concentrations of molecular lipid species in relation to coronary plaque characteristics and cardiovascular outcome: Results of the ATHEROREMO-IVUS study, Atherosclerosis 2015 Dec;243(2):560-6.

CERT and Diabetes Risk

Hilvo et al. 2018 Ceramide stearic to palmitic acid ratio predicts incident diabetes. Diabetologia 2018; 61: 1424-1434.

Mustaniemi et al. 2023 Serum ceramides in early pregnancy as predictors of gestational diabetes. Sci Rep. 2023 Aug 15;13(1):13274.

Bae et al. 2023 Associations of plasma sphingolipids with measures of insulin sensitivity, β-cell function, and incident diabetes in Japanese Americans. Nutr Metab Cardiovasc Dis. 2023 Oct 29:S0939-4753(23)00434-9.

Chaurasia B, Tippetts TS, Mayoral Monibas R, et al. Targeting a ceramide double bond improves insulin resistance and hepatic steatosis. Science. 2019 Jul 26;365(6451):386-392.

CERT and Hypertension

Shoghli  et al. 2023 The Novel Ceramide- and Phosphatidylcholine-Based Risk Score for the Prediction of New-Onset of Hypertension. J. Clin Med. 2023 Dec 6;12(24):7524.

Rigamonti et al. 2023  Ceramide Risk Score in the Evaluation of Metabolic Syndrome: An Additional or Substitutive Biochemical Marker in the Clinical Practice? Int. J. Mol Sci. 2023 Aug 5;24(15):12452.

Akhiyat et al. 2022  Plasma Ceramide Levels Are Elevated in Patients With Early Coronary Atherosclerosis and Endothelial Dysfunction. J. Am. Heart Assoc. 2022 Apr 5;11(7):e022852.


Leiherer et al.  2023 Coronary Event Risk Test (CERT) as a Risk Predictor for the 10-Year Clinical Outcome of Patients with Peripheral Artery Disease. J. Clin. Med. 2023 Sep 23;12(19):6151.

CERT in Elderly

Katajamäki et al. 2022 Ceramides and Phosphatidylcholines Associate with Cardiovascular Diseases in the Elderly. Clin. Chem. 2022 Dec 6;68(12):1502-1508.

Strandberg et al. 2022 Plasma ceramides independently predict all-cause mortality in men aged 85. Age Ageing. 2022 Jun 1;51(6):afac136.

Ceramides and physical exercise

Carrard et al. 2021 How Ceramides Orchestrate Cardiometabolic Health-An Ode to Physically Active Living. Metabolites. 2021 Sep 30;11(10):675.

Petrocelli et al. 2020 Ceramide Biomarkers Predictive of Cardiovascular Disease Risk Increase in Healthy Older Adults After Bed Rest. J Gerontol A Biol Sci Med Sci. 2020 Sep 16;75(9):1663-1670.

Helge et al. 2004 Exercise and training effects on ceramide metabolism in human skeletal muscle. Exp Physiol. 2004 Jan;89(1):119-27. doi: 10.1113/expphysiol.2003.002605.

Other Relevant Publications on Ceramides

Wang DD et al. 2017 Plasma Ceramides, Mediterranean Diet, and Incident Cardiovascular Disease in the PREDIMED Trial (Prevención con Dieta Mediterránea). Circulation. 2017, 135(21):2028-2040.

Ye Q, et al. 2020 Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Plasma Ceramide Levels. Am J Cardiol. 2020 Aug 1;128:163-167.

Hilvo et al.  2018 PCSK9 inhibition alters the lipidome of plasma and lipoprotein fractions. Atherosclerosis. (2018) 269:159-65.

Petrocelli et al. 2020 Ceramide Biomarkers Predictive of Cardiovascular Disease Risk Increase in Healthy Older Adults After Bed Rest. J Gerontol A Biol Sci Med Sci. 2020 Sep 16;75(9):1663-1670

Kasumov et al. 2015 Improved insulin sensitivity after exercise training is linked to reduced plasma C14:0 ceramide in obesity and type 2 diabetes. Obesity (Silver Spring). 2015 Jul;23(7):1414-21.

Ng et al. 2014 Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome. J. Clin. Endocrinol Metab. (2014) 99:E2335-40.

Han, Kim, Jung et al. Metabolic Alterations Associated with Atorvastatin/Fenofibric Acid Combination in Patients with Atherogenic Dyslipidaemia: A Randomized Trial for Comparison with Escalated-Dose Atorvastatin. Sci Rep. 2018 Oct 2;8(1):14642.

Camacho-Muñoz D et al. Omega-3 carboxylic acids and fenofibrate differentially alter plasma lipid mediators in patients with non-alcoholic fatty liver disease. FASEB J. 2021 Nov;35(11):e21976.

Croyal M et al. Fenofibrate decreases plasma ceramide in type 2 diabetes patients: A novel marker of CVD? Diabetes Metab. 2018 Mar;44(2):143-149. doi: 10.1016/j.diabet.2017.04.003. Epub 2017 May 9. PMID: 28499696.

Marfella R et al. Lipid Accumulation in Hearts Transplanted From Nondiabetic Donors to Diabetic Recipients. J Am Coll Cardiol. 2020 Mar 24;75(11):1249-1262.

Djekic D et al. Effects of a Lacto-Ovo-Vegetarian Diet on the Plasma Lipidome and Its Association with Atherosclerotic Burden in Patients with Coronary Artery Disease-A Randomized, Open-Label, Cross-over Study. Nutrients. 2020 Nov 23;12(11):3586.

Zobel EH et al. Ceramides and phospholipids are downregulated with liraglutide treatment: results from the LiraFlame randomized controlled trial. BMJ Open Diabetes Res Care. 2021 Sep;9(1):e002395.

Vijay A et al. Dietary Interventions Reduce Traditional and Novel Cardiovascular Risk Markers by Altering the Gut Microbiome and Their Metabolites. Front Cardiovasc Med. 2021 Jul 14;8:691564.

Reviews and Commentaries

Meeusen et al. 2020 Ceramides improve atherosclerotic cardiovascular disease risk assessment beyond standard risk factors. Clinica Chimica Acta 2020. 511: 138–142

Hilvo et al. 2020 Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification. Front. Endocrinol. vol 11, 29 September 2020

Kovilakath et al. 2020 Sphingolipids in the Heart: From Cradle to Grave. Front. Endocrinol., 15 September 2020

Choi et al. 2021 Ceramides and other sphingolipids as drivers of cardiovascular disease. Nature Reviews Cardiology. Published 26 March 2021

Öörni et al. 2020 Why and how increased plasma ceramides predict future cardiovascular events? Atherosclerosis. 2020 Dec; 314: P71-73.

Chaurasia B, Summers SA. 2015 Ceramides – Lipotoxic Inducers of Metabolic Disorders. Trends Endocrinol. Metab. 2015, 26(10):538-50.

Holland WL, Summers SA. 2008 Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. Endocr Rev. 2008, 29(4):381-402.

Chavez JA, Summers SA. 2012 A ceramide-centric view of insulin resistance. Cell Metab, 2012, 15(5):585-94.

Bikman BT, Summers SA. 2011 Ceramides as modulators of cellular and whole-body metabolism. J Clin Invest. 2011, 121(11):4222-30.

LDL performance in middle-aged adults  

Hilvo et al. 2021 Primary cardiovascular risk prediction by LDL-cholesterol in Caucasian middle-aged and older adults: a joint analysis of three cohorts. Eur J Prev Cardiol. 2021 Jun 1;zwab075. doi: 10.1093/eurjpc/zwab075

Tsaban G. Low-density lipoprotein cholesterol and cardiovascular risk: a necessary causal agent but an insufficient predictor. Eur J Prev Cardiol. 2021 Jun 15:zwab098. doi: 10.1093/eurjpc/zwab098.

Ridker PM, et al. Inflammation and Cholesterol as Predictors of Cardiovascular Events Among 13 970 Contemporary High-Risk Patients With Statin Intolerance. Circulation. 2024 Jan 2;149(1):28-35.

Ridker PM, et al. PROMINENT, REDUCE-IT, and STRENGTH Investigators. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials. Lancet. 2023 Apr 15;401(10384):1293-1301.