Mantovani Alessandro, Lunardi Gianluigi, Bonapace Stefano, Molinero Agustin E, Morandin Riccardo, Fiorio Veronica, Molon Giulio, Byrne Christopher D, Targher Giovanni
Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
Clinical Analysis Laboratory and Transfusional Medicine, Clinical Pharmacology, "IRCCS Sacro Cuore - Don Calabria" Hospital, Negrar di Valpolicella, Italy.
Diabetes Obes Metab. 2025 Mar;27(3):1488-1497. doi: 10.1111/dom.16156. Epub 2024 Dec 26.
Whether the plasma-based ceramide-based risk score CERT1 improves risk prediction for cardiovascular disease (CVD) is uncertain.
Baseline and follow-up data were combined from two cohorts, 334 patients with established/suspected CVD and 196 patients with type 2 diabetes followed for a median of 74 months (interquartile range 54-79 months). For the calculation of CERT1 risk score, we measured four specific plasma ceramides [Cer(d18:1/16:0), Cer(d18:1/18:0) and Cer(d18:1/24:1)] and their ratios to Cer(d18:1/24:0). Based on the CERT1 risk score, patients were split into four risk categories (low, moderate, increased or high risk). The primary outcome was a composite of overall mortality and incident nonfatal CVD outcomes (including myocardial infarction, ischaemic stroke or permanent atrial fibrillation).
One hundred and thirty-nine patients developed the primary composite outcome (72 nonfatal CVD outcomes and 67 total deaths) during follow-up. Baseline CERT1 risk categories were significantly associated with the risk of developing the primary composite outcome (adjusted HR for high vs. low-risk category 2.43, 95% CI 1.39-4.22, p = 0.002, and adjusted HR for increased vs. low-risk category 2.16, 95% CI 1.28-3.63, p = 0.004). Receiver operator characteristic curve analysis showed that adding CERT1 risk score to traditional CVD risk factors and pre-existing CVD, improved the discriminatory capability of the regression model for predicting the primary composite outcome (AUROC 0.691 [95% CI 0.674-0.769] vs. 0.722 [95% CI 0.642-0.742], p = 0.0275).
The ceramide-based risk score CERT1 risk score improves risk prediction for long-term risk of overall mortality and adverse cardiovascular outcomes in patients with and without CVD.
基于血浆神经酰胺的风险评分CERT1是否能改善心血管疾病（CVD）的风险预测尚不确定。
合并了两个队列的基线和随访数据，334例确诊/疑似CVD患者和196例2型糖尿病患者，随访时间中位数为74个月（四分位间距54 - 79个月）。为计算CERT1风险评分，我们测量了四种特定的血浆神经酰胺[Cer(d18:1/16:0)、Cer(d18:1/18:0)和Cer(d18:1/24:1)]及其与Cer(d18:1/24:0)的比值。根据CERT1风险评分，将患者分为四个风险类别（低、中、高或极高风险）。主要结局是全因死亡率和非致死性CVD事件（包括心肌梗死、缺血性中风或永久性心房颤动）的复合结局。
139例患者在随访期间发生了主要复合结局（72例非致死性CVD事件和67例全因死亡）。基线CERT1风险类别与发生主要复合结局的风险显著相关（高风险类别与低风险类别相比，调整后HR为2.43，95%CI为1.39 - 4.22，p = 0.002；高风险类别与低风险类别相比，调整后HR为2.16，95%CI为1.28 - 3.63，p = 0.004）。受试者工作特征曲线分析表明，将CERT1风险评分添加到传统CVD风险因素和已有的CVD中，可提高回归模型预测主要复合结局的辨别能力（曲线下面积0.691[95%CI 0.674 - 0.769]对比0.722[95%CI 0.642 - 0.742]，p = 0.0275）。
基于神经酰胺的风险评分CERT1可改善有或无CVD患者的全因死亡率和不良心血管结局的长期风险预测。
