Tan SH, Wu JL, Zhuo SX, Zhang Y, Wang M. Residual risk in atherosclerotic cardiovascular disease after statin therapy: Clinical mechanisms and management strategies. World J Cardiol 2026; 18(2): 114960 [DOI: 10.4330/wjc.v18.i2.114960]
Corresponding Author of This Article
Miao Wang, MD, PhD, Chief Physician, Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, No. 725 South Wanping Road, Xuhui District, Shanghai 200032, China. wangmiao_126@126.com
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Cardiac & Cardiovascular Systems
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Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Feb 26, 2026 (publication date) through Feb 9, 2026
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World Journal of Cardiology
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1949-8462
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Tan SH, Wu JL, Zhuo SX, Zhang Y, Wang M. Residual risk in atherosclerotic cardiovascular disease after statin therapy: Clinical mechanisms and management strategies. World J Cardiol 2026; 18(2): 114960 [DOI: 10.4330/wjc.v18.i2.114960]
World J Cardiol. Feb 26, 2026; 18(2): 114960 Published online Feb 26, 2026. doi: 10.4330/wjc.v18.i2.114960
Residual risk in atherosclerotic cardiovascular disease after statin therapy: Clinical mechanisms and management strategies
Sze-Hua Tan, Jia-Lin Wu, Shu-Xiong Zhuo, Yi Zhang, Miao Wang
Sze-Hua Tan, International Education College, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Jia-Lin Wu, Shu-Xiong Zhuo, Department of Medical Rehabilitation, Nanmatou Community Health Service Center, Shanghai 200125, China
Yi Zhang, Miao Wang, Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Co-first authors: Sze-Hua Tan and Jia-Lin Wu.
Co-corresponding authors: Yi Zhang and Miao Wang.
Author contributions: Tan SH and Wu JL were responsible for study conceptualization, literature review, data acquisition, and drafting of the manuscript, they contributed equally to this article, they are the co-first authors of this manuscript; Zhuo SX participated in data analysis, provided clinical interpretation, and contributed to manuscript revision; Zhang Y and Wang M supervised the study design, provided critical intellectual input, and revised the manuscript for important academic content, they contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors thoroughly reviewed and endorsed the final manuscript.
Supported by the Shanghai Pudong New Area Health System Excellent Young Medical Talent Training Program, No. PWRq2025-39.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Miao Wang, MD, PhD, Chief Physician, Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, No. 725 South Wanping Road, Xuhui District, Shanghai 200032, China. wangmiao_126@126.com
Received: October 10, 2025 Revised: November 5, 2025 Accepted: December 18, 2025 Published online: February 26, 2026 Processing time: 128 Days and 18.5 Hours
Abstract
Atherosclerotic is one of the leading causes of death worldwide. Although lowering low-density lipoprotein cholesterol (LDL-C) levels reduces cardiovascular risk, studies have shown that even when LDL-C is well controlled, patients may still develop atherosclerotic cardiovascular disease, a phenomenon known as residual risk. This review synthesizes current research on the definition, pathogenesis, and therapeutic strategies of residual risk, aiming to provide a theoretical basis for future advances in its diagnosis and management. Evidence derived exclusively from human clinical trials, cohort studies, and meta-analyses is summarized, excluding data from animal or in vitro experiments to maintain clinical relevance. We focus on lipid and inflammatory biomarkers beyond LDL-C, including non-high-density lipoprotein (HDL) cholesterol, apolipoprotein B, lipoprotein(a), triglycerides, triglyceride-rich lipoproteins, HDL dysfunction, and systemic inflammatory markers. Therapeutic interventions encompassing lifestyle modification, lipid-lowering agents, anti-inflammatory therapies, and novel gene-silencing approaches are reviewed. Evidence indicates that in patients receiving statin therapy, non-HDL-cholesterol and apolipoprotein B provide superior assessment of residual risk compared with LDL-C. Lipoprotein(a) remains predictive of cardiovascular events even when LDL-C levels are well controlled, while elevated triglycerides and triglyceride-rich lipoproteins consistently associate with higher cardiovascular risk. Inflammatory biomarkers such as high-sensitivity C-reactive protein and interleukin-6 serve as indicators of residual inflammatory risk. Persistent residual risk despite LDL-C control underscores the need for integrated, multi-target strategies to achieve comprehensive cardiovascular protection.
