Non-traditional lipid biomarkers in atherosclerotic cardiovascular disease: pathophysiological mechanisms and strategies to address residual risk

Atherosclerotic cardiovascular disease (ASCVD) pathogenesis is fundamentally driven by dyslipidemia, characterized by lipid metabolism disorders that facilitate cholesterol deposition within damaged vascular endothelia. This process culminates in atherosclerotic plaque formation and coronary stenosi...

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Main Authors: Cong Wang, Haifeng Fu, Hao Xu, Handong Yang, Xinwen Min, Wenwen Wu, Zhixin Liu, Dongfeng Li, Yun Dong, Jun Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1576602/full
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author Cong Wang
Haifeng Fu
Hao Xu
Handong Yang
Xinwen Min
Wenwen Wu
Wenwen Wu
Zhixin Liu
Dongfeng Li
Yun Dong
Jun Chen
Jun Chen
author_facet Cong Wang
Haifeng Fu
Hao Xu
Handong Yang
Xinwen Min
Wenwen Wu
Wenwen Wu
Zhixin Liu
Dongfeng Li
Yun Dong
Jun Chen
Jun Chen
author_sort Cong Wang
collection DOAJ
description Atherosclerotic cardiovascular disease (ASCVD) pathogenesis is fundamentally driven by dyslipidemia, characterized by lipid metabolism disorders that facilitate cholesterol deposition within damaged vascular endothelia. This process culminates in atherosclerotic plaque formation and coronary stenosis, ultimately inducing myocardial ischemia. While low-density lipoprotein cholesterol (LDL-C) remains the principal lipid determinant of ASCVD progression, emerging evidence indicates persistent residual cardiovascular risk despite optimal statin-mediated LDL-C control. This review aims to systematically evaluate the contributory role of non-traditional lipid biomarkers in ASCVD pathophysiology and clinical outcomes. Through comprehensive analysis of current research, we examine the biological properties and atherogenic mechanisms of non-conventional lipid particles, epidemiological evidence linking these biomarkers with residual cardiovascular risk, and therapeutic implications of targeting alternative lipid pathways. Particular emphasis is placed on elucidating the pathophysiological interplay between triglyceride-rich lipoproteins, lipoprotein(a), and oxidized phospholipids with vascular inflammation and plaque instability. Furthermore, we critically appraise recent clinical trial data regarding novel lipid-modifying agents and propose future research directions to address current knowledge gaps in residual risk management. This synthesis underscores the necessity of expanding therapeutic strategies beyond LDL-C reduction to achieve comprehensive cardiovascular risk mitigation.
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spelling doaj-art-bd236d422e354e7dbed5ef1c2324a8452025-08-20T03:50:12ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-07-011610.3389/fendo.2025.15766021576602Non-traditional lipid biomarkers in atherosclerotic cardiovascular disease: pathophysiological mechanisms and strategies to address residual riskCong Wang0Haifeng Fu1Hao Xu2Handong Yang3Xinwen Min4Wenwen Wu5Wenwen Wu6Zhixin Liu7Dongfeng Li8Yun Dong9Jun Chen10Jun Chen11Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, ChinaSinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, ChinaSinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, ChinaSinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, ChinaSinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, ChinaShiyan Key Laboratory of Virology, Hubei University of Medicine, Shiyan, ChinaSchool of Public Health, Hubei University of Medicine, Shiyan, Hubei, ChinaShiyan Key Laboratory of Virology, Hubei University of Medicine, Shiyan, ChinaSinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, ChinaSinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, ChinaSinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, ChinaShiyan Key Laboratory of Virology, Hubei University of Medicine, Shiyan, ChinaAtherosclerotic cardiovascular disease (ASCVD) pathogenesis is fundamentally driven by dyslipidemia, characterized by lipid metabolism disorders that facilitate cholesterol deposition within damaged vascular endothelia. This process culminates in atherosclerotic plaque formation and coronary stenosis, ultimately inducing myocardial ischemia. While low-density lipoprotein cholesterol (LDL-C) remains the principal lipid determinant of ASCVD progression, emerging evidence indicates persistent residual cardiovascular risk despite optimal statin-mediated LDL-C control. This review aims to systematically evaluate the contributory role of non-traditional lipid biomarkers in ASCVD pathophysiology and clinical outcomes. Through comprehensive analysis of current research, we examine the biological properties and atherogenic mechanisms of non-conventional lipid particles, epidemiological evidence linking these biomarkers with residual cardiovascular risk, and therapeutic implications of targeting alternative lipid pathways. Particular emphasis is placed on elucidating the pathophysiological interplay between triglyceride-rich lipoproteins, lipoprotein(a), and oxidized phospholipids with vascular inflammation and plaque instability. Furthermore, we critically appraise recent clinical trial data regarding novel lipid-modifying agents and propose future research directions to address current knowledge gaps in residual risk management. This synthesis underscores the necessity of expanding therapeutic strategies beyond LDL-C reduction to achieve comprehensive cardiovascular risk mitigation.https://www.frontiersin.org/articles/10.3389/fendo.2025.1576602/fullatherosclerosiscardiovascular diseaseresidual riskblood lipidsbiomarkers
spellingShingle Cong Wang
Haifeng Fu
Hao Xu
Handong Yang
Xinwen Min
Wenwen Wu
Wenwen Wu
Zhixin Liu
Dongfeng Li
Yun Dong
Jun Chen
Jun Chen
Non-traditional lipid biomarkers in atherosclerotic cardiovascular disease: pathophysiological mechanisms and strategies to address residual risk
Frontiers in Endocrinology
atherosclerosis
cardiovascular disease
residual risk
blood lipids
biomarkers
title Non-traditional lipid biomarkers in atherosclerotic cardiovascular disease: pathophysiological mechanisms and strategies to address residual risk
title_full Non-traditional lipid biomarkers in atherosclerotic cardiovascular disease: pathophysiological mechanisms and strategies to address residual risk
title_fullStr Non-traditional lipid biomarkers in atherosclerotic cardiovascular disease: pathophysiological mechanisms and strategies to address residual risk
title_full_unstemmed Non-traditional lipid biomarkers in atherosclerotic cardiovascular disease: pathophysiological mechanisms and strategies to address residual risk
title_short Non-traditional lipid biomarkers in atherosclerotic cardiovascular disease: pathophysiological mechanisms and strategies to address residual risk
title_sort non traditional lipid biomarkers in atherosclerotic cardiovascular disease pathophysiological mechanisms and strategies to address residual risk
topic atherosclerosis
cardiovascular disease
residual risk
blood lipids
biomarkers
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1576602/full
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