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 |
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Pages (from-to) | 371-380 |
Journal | European Heart Journal |
Volume | 41 |
Issue number | 3 |
DOIs | |
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