摘要
亚临床动脉粥样硬化和代谢紊乱是心血管健康的重要风险因素,应用免疫球蛋白G(IgG)N-聚糖模式作为炎症指标表征其发病风险已有研究报道。然而,对于IgG N-糖基谱在心血管疾病(CVD)风险分层中的能力仍然未知。本研究旨在利用IgG N-糖基标志物开发追踪心血管疾病风险的年龄指数。本研究基于横断面调查,从Busselton健康和老龄研究中共招募1465名40~70岁之间的个体。使用机器学习递归特征消除和惩罚回归算法逐步筛选特征糖基,并开发IgG N-糖基化心血管年龄(GlyCage)指数,以反映归因于心血管风险的与真实年龄间的偏差。结果显示,对GlyCage指数贡献最大的是具有双分叉N-乙酰葡萄糖胺(GlcNAc)的岩藻糖基化N-聚糖(GP6,FA2B)和具有双分叉GlcNAc的双半乳糖基化N-聚糖(GP13,A2BG2)。GlyCage独立于真实年龄,与较高的Framingham十年心血管风险[优势比(OR)为1.09;95%CI:1.05~1.13]和患心血管疾病概率(OR,1.07;95%CI:1.01~1.13)显著相关。GlyCage大于真实年龄三年及以上的个体,其心血管风险和心血管疾病患病概率增加,调整后的OR值分别为2.22(95%CI:1.41~3.53)和2.71(95%CI:1.25~6.41)。GlyCage指数区分十年心血管风险和事件的ROC曲线下面积(AUC)值分别为0.73和0.65,而真实年龄为0.65和0.63。因此,本研究开发的GlyCage指数利用IgG N-糖基谱追踪心血管健康水平。GlyCage和真实年龄之间的差距能够独立地表征心血管风险,提示IgG N-糖基化在心血管疾病的发病机制中起作用。GlyCage指数对心血管风险的预测能力需要在其他人群中进行外部和纵向验证。
The use of an altered immunoglobulin G(IgG)N-glycan pattern as an inflammation metric has been reported in subclinical atherosclerosis and metabolic disorders,both of which are important risk factors in cardiovascular health.However,the usable capacity of IgG N-glycosylation profiles for the risk stratification of cardiovascular diseases(CVDs)remains unknown.This study aimed to develop a cardiovascular aging index for tracking cardiovascular risk using IgG N-glycans.This cross-sectional investigation enrolled 1465 individuals aged 40-70 years from the Busselton Healthy and Ageing Study.We stepwise selected the intersection of altered N-glycans using feature-selection methods in machine learning(recursive feature elimination and penalized regression algorithms)and developed an IgG N-glycosylation cardiovascular age(GlyCage)index to reflect the deviation from calendar age attributable to cardiovascular risk.The strongest contributors to GlyCage index were fucosylated N-glycans with bisecting N-acetylglucosamine(GlcNAc)(glycan peak 6(GP6),FA2B,)and digalactosylated N-glycans with bisecting GlcNAc(GP13,A2BG2).A one-unit increase of GlyCage was significantly associated with a higher Framingham ten-year cardiovascular risk(odds ratio(OR),1.09;95%confidence interval(95%CI):1.05-1.13)and probability of CVDs(OR,1.07;95%CI:1.01-1.13)independent of calendar age.Individuals with excessive GlyCage(exceeding a calendar age>3 years)had an increased cardiovascular risk and probability of CVDs,with adjusted ORs of 2.22(95%CI:1.41-3.53)and 2.71(95%CI:1.25-6.41),respectively.The area under curve(AUC)values of discriminating high cardiovascular risk and events were 0.73 and 0.65 for GlyCage index,and 0.65 and 0.63 for calendar age.The GlyCage index developed in this study can thus be used to track cardiovascular health using IgG N-glycosylation profiles.The distance between GlyCage and calendar age independently indicates the cardiovascular risk,suggesting that IgG N-glycosylation plays a role in the pathogenesis of CVDs.The generalization of the observed associations and the predictive capability of GlyCage index require external and longitudinal validation in other populations.
作者
武志远
郭政
郑雨露
王玉涛
张海平
潘慧颖
李志伟
Lois Balmer
李霞
陶丽新
郭秀花
王嵬
Zhiyuan Wu;Zheng Guo;Yulu Zheng;Yutao Wang;Haiping Zhang;Huiying Pan;Zhiwei Li;Lois Balmer;Xia Li;Lixin Tao;Xiuhua Guo;Wei Wang(Centre for Precision Health,Edith Cowan University,Joondalup,WA 6027,Australia;Beijing Municipal Key Laboratory of Clinical Epidemiology,School of Public Health,Capital Medical University,Beijing 100069,China;Shanghai Fufan Information Technology Co.,Ltd.,Shanghai 200433,China;Department of Mathematics and Statistics,La Trobe University,Melbourne,VIC 3086,Australia)
出处
《Engineering》
SCIE
EI
CAS
CSCD
2023年第7期99-107,I0004,I0005,共11页
工程（英文）
基金
funded by National Natural Science Foundation of China(8177120753)
China-Australia International Collaborative Grant(NHMRC APP1112767,NSFC 81561128020)to Wei Wang
Zhiyuan Wu was supported by the China Scholarship Council(201908110447)
Yulu Zheng and Zheng Guo were supported by the Edith Cowan University Higher Degree by Research Scholarship(ECU-HDR ST10469322 and ST10468211).
