School of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AD, UK.
Ludger Ltd, Culham Science Centre, Abingdon, OX14 3EB, UK.
Glycoconj J. 2023 Dec;40(6):645-654. doi: 10.1007/s10719-023-10138-3. Epub 2023 Nov 22.
Cardiovascular disease (CVD) is a group of health conditions affecting the heart and vascular system with very high prevalence and mortality rates. The presence of CVD is characterised by high levels of inflammation which have previously been associated with increased plasma concentrations of N-acetyl neuraminic acid (Neu5Ac). While Neu5Ac has been studied in the context of CVD, Neu5,9Ac has not, despite being the second most abundant sialic acid in human plasma. A small-scale pilot study of thirty plasma samples from patients with diagnosed CVD, and thirty age and sex-matched healthy controls, was designed to gain insight into sialic acids as biomarkers for CVD and potential future areas of study. Each sample was assayed for Neu5Ac and Neu5,9Ac concentrations. Mean Neu5Ac and Neu5,9Ac concentrations were significantly elevated in patients with CVD compared to healthy controls (Neu5Ac: P < 0.001; Neu5,9Ac: P < 0.04). Receiver operator curve (ROC) analysis indicated that both Neu5Ac and Neu5,9Ac have reasonable predictive power for the presence of CVD (Neu5Ac AUC: 0.86; Neu5,9Ac AUC: 0.71). However, while Neu5Ac had both good sensitivity (0.82) and specificity (0.81), Neu5,9Ac had equivalent specificity (0.81) but very poor sensitivity (0.44). A combination marker of Neu5Ac + Neu5,9Ac showed improvement over Neu5Ac alone in terms of predictive power (AUC: 0.93), sensitivity (0.87), and specificity (0.90). Comparison to a known inflammatory marker, high sensitivity c-reactive protein (hs-CRP: P-value: NS, ROC:0.50) was carried out, showing that both Neu5Ac and Neu5,9Ac outperformed this marker. Further to this, hs-CRP values were combined with the three different sialic acid markers to determine any effect on the AUC values. A slight improvement in AUC was noted for each of the combinations, with Neu5Ac + Neu5,9Ac + hs-CRP giving the best AUC of 0.97 overall. Thus, Neu5Ac would appear to offer good potential as a predictive marker for the presence of CVD, which the addition of Neu5,9Ac predictive power improves, with further improvement seen by the addition of hs-CRP.
心血管疾病 (CVD) 是一组影响心脏和血管系统的健康状况，其患病率和死亡率非常高。CVD 的特征是高水平的炎症，先前已与血浆中 N-乙酰神经氨酸 (Neu5Ac) 浓度升高有关。虽然 Neu5Ac 已在 CVD 背景下进行了研究，但 Neu5,9Ac 尚未进行研究，尽管它是人类血浆中第二丰富的唾液酸。对 30 名患有确诊 CVD 的患者和 30 名年龄和性别匹配的健康对照者的 30 个血浆样本进行了小规模试点研究，旨在深入了解唾液酸作为 CVD 的生物标志物和潜在的未来研究领域。每个样本均测定 Neu5Ac 和 Neu5,9Ac 浓度。与健康对照组相比，CVD 患者的 Neu5Ac 和 Neu5,9Ac 浓度明显升高 (Neu5Ac：P<0.001；Neu5,9Ac：P<0.04)。受试者工作特征曲线 (ROC) 分析表明，Neu5Ac 和 Neu5,9Ac 对 CVD 的存在均具有合理的预测能力 (Neu5Ac AUC：0.86；Neu5,9Ac AUC：0.71)。然而，虽然 Neu5Ac 具有良好的敏感性 (0.82) 和特异性 (0.81)，但 Neu5,9Ac 具有相同的特异性 (0.81)，但敏感性很差 (0.44)。Neu5Ac+Neu5,9Ac 组合标志物在预测能力 (AUC：0.93)、敏感性 (0.87) 和特异性 (0.90) 方面均优于 Neu5Ac 单独标志物。与已知的炎症标志物高敏 C 反应蛋白 (hs-CRP：P 值：NS，ROC：0.50) 进行了比较，结果表明 Neu5Ac 和 Neu5,9Ac 均优于该标志物。在此基础上，将 hs-CRP 值与三种不同的唾液酸标志物相结合，以确定其对 AUC 值的任何影响。每种组合的 AUC 值都略有提高，其中 Neu5Ac+Neu5,9Ac+hs-CRP 的 AUC 值最高，总体为 0.97。因此，Neu5Ac 似乎具有作为 CVD 存在的预测标志物的良好潜力，而 Neu5,9Ac 的添加则提高了其预测能力，hs-CRP 的添加则进一步提高了预测能力。
