Development and validation of a ceramide- And phospholipid-based cardiovascular risk estimation score for coronary artery disease patients

Mika Hilvo; Peter J. Meikle; Eva Ringdal Pedersen; Grethe S. Tell; Indu Dhar; Hermann Brenner; Ben Schöttker; Mitja Lääperi; Dimple Kauhanen; Kaisa M. Koistinen; Antti Jylhä; Kevin Huynh; Natalie A. Mellett; Andrew M. Tonkin; David R. Sullivan; John Simes; Paul Nestel; Wolfgang Koenig; Dietrich Rothenbacher; Ottar Nygård; Reijo Laaksonen

doi:10.1093/eurheartj/ehz387

Development and validation of a ceramide- And phospholipid-based cardiovascular risk estimation score for coronary artery disease patients

Mika Hilvo^*, Peter J. Meikle, Eva Ringdal Pedersen, Grethe S. Tell, Indu Dhar, Hermann Brenner, Ben Schöttker, Mitja Lääperi, Dimple Kauhanen, Kaisa M. Koistinen, Antti Jylhä, Kevin Huynh, Natalie A. Mellett, Andrew M. Tonkin, David R. Sullivan, John Simes, Paul Nestel, Wolfgang Koenig, Dietrich Rothenbacher, Ottar NygårdReijo Laaksonen^*

^*Corresponding author for this work

Not published at VTT

Research output: Contribution to journal › Article › Scientific › peer-review

211 Citations (Scopus)

Abstract

AIMS: Distinct ceramide lipids have been shown to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular death. As phospholipids have also been linked with CVD risk, we investigated whether the combination of ceramides with phosphatidylcholines (PCs) would be synergistic in the prediction of CVD events in patients with atherosclerotic coronary heart disease in three independent cohort studies.

METHODS AND RESULTS: Ceramides and PCs were analysed using liquid chromatography-mass spectrometry (LC-MS) in three studies: WECAC (The Western Norway Coronary Angiography Cohort) (N = 3789), LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) trial (N = 5991), and KAROLA (Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung) (N = 1023). A simple risk score, based on the ceramides and PCs showing the best prognostic features, was developed in the WECAC study and validated in the two other cohorts. This score was highly significant in predicting CVD mortality [multiadjusted hazard ratios (HRs; 95% confidence interval) per standard deviation were 1.44 (1.28-1.63) in WECAC, 1.47 (1.34-1.61) in the LIPID trial, and 1.69 (1.31-2.17) in KAROLA]. In addition, a combination of the risk score with high-sensitivity troponin T increased the HRs to 1.63 (1.44-1.85) and 2.04 (1.57-2.64) in WECAC and KAROLA cohorts, respectively. The C-statistics in WECAC for the risk score combined with sex and age was 0.76 for CVD death. The ceramide-phospholipid risk score showed comparable and synergistic predictive performance with previously published CVD risk models for secondary prevention.

CONCLUSION: A simple ceramide- and phospholipid-based risk score can efficiently predict residual CVD event risk in patients with coronary artery disease.

Original language	English
Pages (from-to)	371-380
Journal	European Heart Journal
Volume	41
Issue number	3
DOIs	https://doi.org/10.1093/eurheartj/ehz387
Publication status	Published - 14 Jan 2020
MoE publication type	A1 Journal article-refereed

Funding

Funding for the KAROLA study was received from the German Federal Ministry of Education and Research (01GD9820/0 and 01ER0814), the Willy Robert Pitzer Foundation, Bad Nauheim, Germany, and by the Waldburg-Zeil Clinics Isny, Germany. P.J.M. received grants from National Health and Medical Research Council during the conduct of the study.

Keywords

Cardiovascular
Ceramide
Death
Phospholipid
Prevention
Risk
Chromatography, Liquid/methods
Prognosis
Humans
Middle Aged
Risk Factors
Male
Ceramides/blood
Coronary Angiography
Phospholipids/blood
Mass Spectrometry/methods
Biomarkers/blood
Female
Aged
Risk Assessment/methods
Atherosclerosis/blood
Coronary Artery Disease/blood

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/eurheartj/ehz387

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Hilvo, M., Meikle, P. J., Pedersen, E. R., Tell, G. S., Dhar, I., Brenner, H., Schöttker, B., Lääperi, M., Kauhanen, D., Koistinen, K. M., Jylhä, A., Huynh, K., Mellett, N. A., Tonkin, A. M., Sullivan, D. R., Simes, J., Nestel, P., Koenig, W., Rothenbacher, D., ... Laaksonen, R. (2020). Development and validation of a ceramide- And phospholipid-based cardiovascular risk estimation score for coronary artery disease patients. European Heart Journal, 41(3), 371-380. https://doi.org/10.1093/eurheartj/ehz387

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title = "Development and validation of a ceramide- And phospholipid-based cardiovascular risk estimation score for coronary artery disease patients",

abstract = "AIMS: Distinct ceramide lipids have been shown to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular death. As phospholipids have also been linked with CVD risk, we investigated whether the combination of ceramides with phosphatidylcholines (PCs) would be synergistic in the prediction of CVD events in patients with atherosclerotic coronary heart disease in three independent cohort studies.METHODS AND RESULTS: Ceramides and PCs were analysed using liquid chromatography-mass spectrometry (LC-MS) in three studies: WECAC (The Western Norway Coronary Angiography Cohort) (N = 3789), LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) trial (N = 5991), and KAROLA (Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung) (N = 1023). A simple risk score, based on the ceramides and PCs showing the best prognostic features, was developed in the WECAC study and validated in the two other cohorts. This score was highly significant in predicting CVD mortality [multiadjusted hazard ratios (HRs; 95% confidence interval) per standard deviation were 1.44 (1.28-1.63) in WECAC, 1.47 (1.34-1.61) in the LIPID trial, and 1.69 (1.31-2.17) in KAROLA]. In addition, a combination of the risk score with high-sensitivity troponin T increased the HRs to 1.63 (1.44-1.85) and 2.04 (1.57-2.64) in WECAC and KAROLA cohorts, respectively. The C-statistics in WECAC for the risk score combined with sex and age was 0.76 for CVD death. The ceramide-phospholipid risk score showed comparable and synergistic predictive performance with previously published CVD risk models for secondary prevention.CONCLUSION: A simple ceramide- and phospholipid-based risk score can efficiently predict residual CVD event risk in patients with coronary artery disease.",

keywords = "Cardiovascular, Ceramide, Death, Phospholipid, Prevention, Risk, Chromatography, Liquid/methods, Prognosis, Humans, Middle Aged, Risk Factors, Male, Ceramides/blood, Coronary Angiography, Phospholipids/blood, Mass Spectrometry/methods, Biomarkers/blood, Female, Aged, Risk Assessment/methods, Atherosclerosis/blood, Coronary Artery Disease/blood",

author = "Mika Hilvo and Meikle, {Peter J.} and Pedersen, {Eva Ringdal} and Tell, {Grethe S.} and Indu Dhar and Hermann Brenner and Ben Sch{\"o}ttker and Mitja L{\"a}{\"a}peri and Dimple Kauhanen and Koistinen, {Kaisa M.} and Antti Jylh{\"a} and Kevin Huynh and Mellett, {Natalie A.} and Tonkin, {Andrew M.} and Sullivan, {David R.} and John Simes and Paul Nestel and Wolfgang Koenig and Dietrich Rothenbacher and Ottar Nyg{\aa}rd and Reijo Laaksonen",

note = "{\textcopyright} The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.",

year = "2020",

month = jan,

day = "14",

doi = "10.1093/eurheartj/ehz387",

language = "English",

volume = "41",

pages = "371--380",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "3",

}

Hilvo, M, Meikle, PJ, Pedersen, ER, Tell, GS, Dhar, I, Brenner, H, Schöttker, B, Lääperi, M, Kauhanen, D, Koistinen, KM, Jylhä, A, Huynh, K, Mellett, NA, Tonkin, AM, Sullivan, DR, Simes, J, Nestel, P, Koenig, W, Rothenbacher, D, Nygård, O & Laaksonen, R 2020, 'Development and validation of a ceramide- And phospholipid-based cardiovascular risk estimation score for coronary artery disease patients', European Heart Journal, vol. 41, no. 3, pp. 371-380. https://doi.org/10.1093/eurheartj/ehz387

TY - JOUR

T1 - Development and validation of a ceramide- And phospholipid-based cardiovascular risk estimation score for coronary artery disease patients

AU - Hilvo, Mika

AU - Meikle, Peter J.

AU - Pedersen, Eva Ringdal

AU - Tell, Grethe S.

AU - Dhar, Indu

AU - Brenner, Hermann

AU - Schöttker, Ben

AU - Lääperi, Mitja

AU - Kauhanen, Dimple

AU - Koistinen, Kaisa M.

AU - Jylhä, Antti

AU - Huynh, Kevin

AU - Mellett, Natalie A.

AU - Tonkin, Andrew M.

AU - Sullivan, David R.

AU - Simes, John

AU - Nestel, Paul

AU - Koenig, Wolfgang

AU - Rothenbacher, Dietrich

AU - Nygård, Ottar

AU - Laaksonen, Reijo

N1 - © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

PY - 2020/1/14

Y1 - 2020/1/14

N2 - AIMS: Distinct ceramide lipids have been shown to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular death. As phospholipids have also been linked with CVD risk, we investigated whether the combination of ceramides with phosphatidylcholines (PCs) would be synergistic in the prediction of CVD events in patients with atherosclerotic coronary heart disease in three independent cohort studies.METHODS AND RESULTS: Ceramides and PCs were analysed using liquid chromatography-mass spectrometry (LC-MS) in three studies: WECAC (The Western Norway Coronary Angiography Cohort) (N = 3789), LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) trial (N = 5991), and KAROLA (Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung) (N = 1023). A simple risk score, based on the ceramides and PCs showing the best prognostic features, was developed in the WECAC study and validated in the two other cohorts. This score was highly significant in predicting CVD mortality [multiadjusted hazard ratios (HRs; 95% confidence interval) per standard deviation were 1.44 (1.28-1.63) in WECAC, 1.47 (1.34-1.61) in the LIPID trial, and 1.69 (1.31-2.17) in KAROLA]. In addition, a combination of the risk score with high-sensitivity troponin T increased the HRs to 1.63 (1.44-1.85) and 2.04 (1.57-2.64) in WECAC and KAROLA cohorts, respectively. The C-statistics in WECAC for the risk score combined with sex and age was 0.76 for CVD death. The ceramide-phospholipid risk score showed comparable and synergistic predictive performance with previously published CVD risk models for secondary prevention.CONCLUSION: A simple ceramide- and phospholipid-based risk score can efficiently predict residual CVD event risk in patients with coronary artery disease.

AB - AIMS: Distinct ceramide lipids have been shown to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular death. As phospholipids have also been linked with CVD risk, we investigated whether the combination of ceramides with phosphatidylcholines (PCs) would be synergistic in the prediction of CVD events in patients with atherosclerotic coronary heart disease in three independent cohort studies.METHODS AND RESULTS: Ceramides and PCs were analysed using liquid chromatography-mass spectrometry (LC-MS) in three studies: WECAC (The Western Norway Coronary Angiography Cohort) (N = 3789), LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) trial (N = 5991), and KAROLA (Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung) (N = 1023). A simple risk score, based on the ceramides and PCs showing the best prognostic features, was developed in the WECAC study and validated in the two other cohorts. This score was highly significant in predicting CVD mortality [multiadjusted hazard ratios (HRs; 95% confidence interval) per standard deviation were 1.44 (1.28-1.63) in WECAC, 1.47 (1.34-1.61) in the LIPID trial, and 1.69 (1.31-2.17) in KAROLA]. In addition, a combination of the risk score with high-sensitivity troponin T increased the HRs to 1.63 (1.44-1.85) and 2.04 (1.57-2.64) in WECAC and KAROLA cohorts, respectively. The C-statistics in WECAC for the risk score combined with sex and age was 0.76 for CVD death. The ceramide-phospholipid risk score showed comparable and synergistic predictive performance with previously published CVD risk models for secondary prevention.CONCLUSION: A simple ceramide- and phospholipid-based risk score can efficiently predict residual CVD event risk in patients with coronary artery disease.

KW - Cardiovascular

KW - Ceramide

KW - Death

KW - Phospholipid

KW - Prevention

KW - Risk

KW - Chromatography, Liquid/methods

KW - Prognosis

KW - Humans

KW - Middle Aged

KW - Risk Factors

KW - Male

KW - Ceramides/blood

KW - Coronary Angiography

KW - Phospholipids/blood

KW - Mass Spectrometry/methods

KW - Biomarkers/blood

KW - Female

KW - Aged

KW - Risk Assessment/methods

KW - Atherosclerosis/blood

KW - Coronary Artery Disease/blood

UR - http://www.scopus.com/inward/record.url?scp=85072877124&partnerID=8YFLogxK

U2 - 10.1093/eurheartj/ehz387

DO - 10.1093/eurheartj/ehz387

M3 - Article

C2 - 31209498

SN - 0195-668X

VL - 41

SP - 371

EP - 380

JO - European Heart Journal

JF - European Heart Journal

IS - 3

ER -

Development and validation of a ceramide- And phospholipid-based cardiovascular risk estimation score for coronary artery disease patients

Abstract

Funding

Keywords

UN SDGs

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