Physicians

CERT – Coronary Event Risk Test (brand name Hertta) is a new test to assess the patient’s risk for adverse cardiovascular events. Also Hertta-test measures the risk of type 2 diabetes onset.

CERT is a blood sample based diagnostic method to measure the risk of severe infarction or cardiac death, and risk of type 2 diabetes. The test is based on quantification of certain ceramide lipid molecules.

The test gives as a result two risk scores:

  1. Cardiovascular Risk Score (S -CVrisk) and a risk-based statement.
  2. Diabetes Risk Score (S -DMrisk) and a risk-based statement.

Cardiovascular Risk

Cardiovascular Risk (S -CVrisk) is divided into four risk categories:

    Risk of cardiac death (%)
CV Risk Score Risk Category Population Stable coronary artery disease patients Acute coronary syndrome patients
0-2 Low risk 0,5% / 10y 2,3% / 5y 1,6% / 1y
3-6 Medium risk 1,1% / 10y 3,3% / 5y 2,6% / 1y
7-9 Elevated risk 2,2% / 10y 5,3% / 5y 3,3% / 1y
10-12 High risk 2,9% / 10y 10,1% / 5y 9,4% / 1y

 

Cardiovascular Risk Score is determined based on the ceramide levels and their ratios. Depending on the ceramide and ratio levels, the measurement receives either 0, 1 or 2 points. The sum of the points indicates the person’s risk score.

CERT predicts cardiovascular events such as myocardial infarction, and cardiac death more accurately than traditional cholesterol tests. The test also measures the residual risk in patients on cholesterol medication, and predicts myocardial infarction in people who have not yet been diagnosed with coronary artery disease.

Diabetes risk

Diabetes Risk Score reflects a person’s probability to develop a type II diabetes over the next ten years. It is calculated from a specific ceramide ratio and taking into account the person’s body mass index, age and sex.

Diabetes Risk Score (S -DMrisk) is divided into three risk categories:

Diabetes Risk Score Risk Category
0-4 Low risk
5-14 Medium risk
> 15 High risk

Indications

CERT can be used to predict the risk of myocardial infarction and cardiovascular death, and risk of developing type II diabetes, especially in the following patient groups:

  1. CV Risk: People who are not known to have coronary artery disease or elevated cholesterol levels but who, for example have family history of cardiovascular disease or have other risk factors.
  2. CV Risk: Coronary artery disease patients. Identification of high risk of heart attack and cardiac death can lead to changes in medication, intensification of monitoring, or consideration for an invasive procedure.
  3. Diabetes Risk: People who are not diagnosed with diabetes. The test is especially recommended for people having family history of type II diabetes or having other risk factors.

Background of ceramide measurements

Ceramides are cell membrane lipids whose levels rise in inflammatory reactions, excessive calorie intake associated with lipid accumulation, or tissue deficiency. Ceramides are associated with several mechanisms of coronary heart disease, for example by accumulating in the arterial plaques and increasing thrombotic risk by activating platelets. Ceramides are also associated to insulin resistance.

By determining ceramides in stable or non-diagnosed patients with coronary artery disease, the assessment of heart attack risk can be refined.

Interpretation of CERT results

For patients with a high CERT score, it is recommended to intensify the coronary artery disease treatment. Motivation for treatment and lifestyle changes can be provided by using CERT to flag a more concrete and specific risk for a heart attack or cardiovascular death. In addition, a high-risk score can support decisions to intensify cholesterol lowering medication. In addition, using CERT to monitor the changes in risk will improve patient motivation and commitment to the treatment over a longer period of time.

Patients with a high risk of diabetes are recommended to motivate for lifestyle changes. For example, 5% weight loss or moderate physical activity may reduce the risk. Commitment to life-style change can be supported by raising the more specific risk of type II diabetes. The Diabetes Risk Score measurement can be used to follow-up the effects of lifestyle changes.

How to treat a patient with a high CERT risk score?

 

CERT Cardiovascular Risk Test was developed by Finnish Zora Biosciences Oy.

References:

By Zora:

CERT in Secondary Prevention:

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

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.

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.

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

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

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 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, Published 13 July 2021

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

 

CERT and Diabetes risk:

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

 

CERT Analytical Validation:

Kauhanen et al. 2016 Development and validation of a high-throughput LC-MS/MS assay for routine measurement of molecular ceramides, Anal Bioanal Chem. 2016 May;408(13):3475-83

 

Ceramides and Cardiovascular Disease Publications by Others:

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.

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

Field et al. 2020 The Role of Ceramides in Diabetes and Cardiovascular Disease Regulation of Ceramides by Adipokines. Front. Endocrinol., 02 October 2020

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

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

Meeusen et al. 2018 Plasma Ceramides – A Novel Predictor of Major Adverse Cardiovascular Events After Coronary Angiography. ATVB DOI:10.1161/ATVBAHA.118.311199

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

Mantovani et al. 2018 Association between plasma ceramides and inducible myocardial ischemia in patients with established or suspected coronary artery disease undergoing myocardial perfusion scintigraphy. Metabolism 2018. doi:10.1016/j.metabol.2018.05.006

Peterson et al. 2018 Ceramide Remodeling and Risk of Cardiovascular Events and Mortality. JAHA 2018 May 3;7(10).

Summers 2018 Could Ceramides Become the New Cholesterol, Cell Metabolism 27 (2), 276-280.

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.

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

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.

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.

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.