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.

中文翻译：

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基于神经酰胺和磷脂的冠状动脉疾病患者心血管风险评估评分的开发和验证

目的 不同的神经酰胺脂质已被证明可以预测心血管疾病 (CVD) 事件的风险，尤其是心血管死亡。由于磷脂也与 CVD 风险有关，我们在三项独立的队列研究中研究了神经酰胺与磷脂酰胆碱 (PC) 的组合是否能协同预测动脉粥样硬化性冠心病患者的 CVD 事件。方法和结果 在以下三项研究中使用液相色谱-质谱法 (LC-MS) 分析神经酰胺和 PC：WECAC（挪威西部冠状动脉造影队列）（N = 3789）、LIPID（在缺血性疾病中使用普伐他汀长期干预）试验 (N = 5991) 和 KAROLA (Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung) (N = 1023)。一个简单的风险评分，基于神经酰胺和 PCs 显示出最好的预后特征，是在 WECAC 研究中开发的，并在其他两个队列中得到验证。该评分在预测 CVD 死亡率方面非常显着 [每标准差的多重调整风险比（HR；95% 置信区间）在 WECAC 中为 1.44 (1.28-1.63)，在 LIPID 试验中为 1.47 (1.34-1.61)，在2.17) 在卡罗拉]。此外，风险评分与高敏肌钙蛋白 T 的组合使 WECAC 和 KAROLA 队列的 HR 分别增加至 1.63 (1.44-1.85) 和 2.04 (1.57-2.64)。WECAC 中风险评分与性别和年龄相结合的 C 统计数据是 0.76 的心血管死亡。神经酰胺-磷脂风险评分显示出与先前公布的二级预防 CVD 风险模型具有可比性和协同性的预测性能。