Systemic inflammation is a minor contributor to remnant cholesterol atherogenicity

Jordan M Kraaijenhof, Marije Kerkvliet, Nick S. Nurmohamed, Aldo Grefhorst, Jeffrey Kroon, Nicholas J. Wareham, G. Kees Hovingh, Erik SG Stroes, S. Matthijs Boekholdt, Laurens F. Reeskamp
{"title":"Systemic inflammation is a minor contributor to remnant cholesterol atherogenicity","authors":"Jordan M Kraaijenhof, Marije Kerkvliet, Nick S. Nurmohamed, Aldo Grefhorst, Jeffrey Kroon, Nicholas J. Wareham, G. Kees Hovingh, Erik SG Stroes, S. Matthijs Boekholdt, Laurens F. Reeskamp","doi":"10.1101/2024.07.18.604203","DOIUrl":null,"url":null,"abstract":"Background:\nBoth plasma levels of remnant cholesterol and low-density lipoprotein cholesterol (LDL-C) levels are independent risk factors for atherosclerotic cardiovascular disease. However, only remnant cholesterol has consistently been associated with systemic inflammation. The extent to which inflammation mediates the effect of remnant cholesterol on major adverse cardiovascular events (MACE) remains unclear.\nMethods and Results:\nThis study included 16,445 participants without prior atherosclerotic cardiovascular disease from the EPIC-Norfolk cohort, with a mean age of 58.8 +/- 9.1 years, of which 9,357 (56.9%) were women. Every 1 mmol/L higher remnant cholesterol was associated with 29.5% higher hsCRP levels (95% Confidence Interval (CI): 22.1, 37.4, p<0.001), whereas LDL-C was not significantly associated with hsCRP levels in the fully adjusted model. Additionally, each 1 mmol/L higher remnant cholesterol was associated with a hazard ratio (HR) of 1.31 (95% CI: 1.14, 1.50, p<0.001) for MACE, compared to a HR of 1.21 (95% CI: 1.13, 1.31, p<0.001) for LDL-C. Mediation analysis showed that hsCRP mediated 5.9% (95% CI: 1.2, 10.6%, p<0.001) of the effect of remnant cholesterol on MACE, whereas hsCRP did not mediate the effect of LDL-C.\nConclusions:\nPlasma remnant cholesterol levels are independently associated with systemic inflammation and cardiovascular events. Inflammation, as measured with hsCRP, contributed minorly to the association between remnant cholesterol and MACE. This underscores the need to address both remnant cholesterol and systemic inflammation separately in the clinical management of cardiovascular disease.","PeriodicalId":501213,"journal":{"name":"bioRxiv - Systems Biology","volume":"70 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv - Systems Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.07.18.604203","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Both plasma levels of remnant cholesterol and low-density lipoprotein cholesterol (LDL-C) levels are independent risk factors for atherosclerotic cardiovascular disease. However, only remnant cholesterol has consistently been associated with systemic inflammation. The extent to which inflammation mediates the effect of remnant cholesterol on major adverse cardiovascular events (MACE) remains unclear. Methods and Results: This study included 16,445 participants without prior atherosclerotic cardiovascular disease from the EPIC-Norfolk cohort, with a mean age of 58.8 +/- 9.1 years, of which 9,357 (56.9%) were women. Every 1 mmol/L higher remnant cholesterol was associated with 29.5% higher hsCRP levels (95% Confidence Interval (CI): 22.1, 37.4, p<0.001), whereas LDL-C was not significantly associated with hsCRP levels in the fully adjusted model. Additionally, each 1 mmol/L higher remnant cholesterol was associated with a hazard ratio (HR) of 1.31 (95% CI: 1.14, 1.50, p<0.001) for MACE, compared to a HR of 1.21 (95% CI: 1.13, 1.31, p<0.001) for LDL-C. Mediation analysis showed that hsCRP mediated 5.9% (95% CI: 1.2, 10.6%, p<0.001) of the effect of remnant cholesterol on MACE, whereas hsCRP did not mediate the effect of LDL-C. Conclusions: Plasma remnant cholesterol levels are independently associated with systemic inflammation and cardiovascular events. Inflammation, as measured with hsCRP, contributed minorly to the association between remnant cholesterol and MACE. This underscores the need to address both remnant cholesterol and systemic inflammation separately in the clinical management of cardiovascular disease.
全身炎症是残余胆固醇致动脉粥样硬化的一个次要因素
背景:血浆中的残余胆固醇水平和低密度脂蛋白胆固醇(LDL-C)水平都是动脉粥样硬化性心血管疾病的独立危险因素。然而,只有残余胆固醇一直与全身炎症相关。方法与结果:该研究纳入了 EPIC-Norfolk 队列中 16,445 名既往未患动脉粥样硬化性心血管疾病的参与者,平均年龄为 58.8 +/- 9.1 岁,其中 9,357 人(56.9%)为女性。残余胆固醇每升高 1 毫摩尔/升,hsCRP 水平就会升高 29.5%(95% 置信区间 (CI):22.1, 37.4,p<0.001),而在完全调整模型中,低密度脂蛋白胆固醇与 hsCRP 水平无显著相关性。此外,残余胆固醇每升高 1 毫摩尔/升,MACE 的危险比 (HR) 为 1.31(95% CI:1.14, 1.50,p<0.001),而 LDL-C 的危险比为 1.21(95% CI:1.13, 1.31,p<0.001)。中介分析显示,hsCRP介导了残余胆固醇对MACE影响的5.9%(95% CI:1.2, 10.6%,p<0.001),而hsCRP并不介导低密度脂蛋白胆固醇的影响。用 hsCRP 测定的炎症对残余胆固醇与心血管事件之间的关系影响较小。这突出表明,在心血管疾病的临床治疗中,需要分别处理残余胆固醇和全身炎症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信