The DOI matches its Crossref record; 116 of the 117 references it cites were found in a registry or an index.
Residual Cardiovascular Risk Despite Optimal LDL Cholesterol Reduction with Statins: The Evidence, Etiology, and Therapeutic Challenges
Open accessAbstract
This review captures the existence, cause, and treatment challenges of residual cardiovascular risk (CVR) after aggressive low-density lipoprotein cholesterol (LDL-C) reduction. Scientific evidence implicates low high-density lipoprotein cholesterol (HDL-C) and high triglycerides (TG) in the CVR observed after LDL-C lowering. However, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial with fenofibrate, the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) study with torcetrapib, and the recently terminated Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) study with niacin, do not clearly attribute risk reduction value to HDL-C/TG modulation. The optimum approach to long-term lipid-modifying therapies for CVR reduction remains uncertain. Consequently, absolute risk modulation via lifestyle changes remains the centerpiece of a strategy addressing the physiologic drivers of CVR associated with HDL-C/TG, especially in the context of diabetes/metabolic syndrome.
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“Residual risk persists in many individuals, especially those with features of metabolic syndrome (MetS) or diabetes mellitus (DM), suggesting the need to address additional lipoprotein abnormalities such as elevated triglycerides (TGs) and TG-rich lipoproteins (TRLs) [6, 7].”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [7]
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1 retracted
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Items 401–438 of 438
Kornelius, E., Hu, T., Chiao, C., Hwang, J., & Chan, T. (2025) · International Journal of Cardiology Cardiovascular Risk and Prevention · doi:10.1016/j.ijcrp.2025.200537
“However, despite the established benefits of statin therapy and subsequent LDL-C reduction, a significant residual risk of cardiovascular events persists [5,6].”
Additional file 2 of DNA methylation and gene expression integration in cardiovascular disease
Palou-Márquez, G., Subirana, I., Nonell, L., Fernández‐Sanlés, A., & Elosúa, R. (2021) · Figshare · doi:10.6084/m9.figshare.14396856
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Wang, Y., Wang, S., Sun, S., Li, F., Zhao, W., Yang, H., & Wu, X. (2023) · Figshare · doi:10.6084/m9.figshare.23583477
Huang, Q., Liu, Z., Wei, M., Huang, Q., Feng, J., Liu, Z., & Xia, J. (2023) · Figshare · doi:10.6084/m9.figshare.23250735
Additional file 3 of DNA methylation and gene expression integration in cardiovascular disease
Palou-Márquez, G., Subirana, I., Nonell, L., Fernández‐Sanlés, A., & Elosúa, R. (2021) · Figshare · doi:10.6084/m9.figshare.14396859
Hu, Y., Wang, X., Luo, C., Zheng, T., & Tian, G. (2024) · Figshare · doi:10.6084/m9.figshare.26563141
Guan, B., Wang, A., & Xu, H. (2023) · Figshare · doi:10.6084/m9.figshare.23930429
Huang, Q., Liu, Z., Wei, M., Huang, Q., Feng, J., Liu, Z., & Xia, J. (2023) · Figshare · doi:10.6084/m9.figshare.23250738
Additional file 1 of DNA methylation and gene expression integration in cardiovascular disease
Palou-Márquez, G., Subirana, I., Nonell, L., Fernández‐Sanlés, A., & Elosúa, R. (2021) · Figshare · doi:10.6084/m9.figshare.14396853
Huang, Q., Liu, Z., Wei, M., Huang, Q., Feng, J., Liu, Z., & Xia, J. (2023) · Figshare · doi:10.6084/m9.figshare.23250741
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“Nonetheless, accumulating evidence suggests that residual cardiovascular risk persists even in patients who achieve guideline-recommended LDL-C targets [21, 22].”
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“Statins remain the cornerstone of lipid-lowering treatment in ASCVD, yet they do not fully address all lipid abnormalities, particularly those related to triglyceride-rich lipoproteins and non-HDL-C [4,8].”
Chen, C., Chen, F., Tian, Y., Chen, W., Li, G., & Zhou, L. (2026) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2026.104773
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“18 The model identified 15 key features for predicting short-to long-term prognosis of patients with AMI.”
Lipid-lowering therapy: Evidence and future perspective
Komiyama, M., Wada, H., Dan, G. A., & Hasegawa, K. (2026) · JRSM Cardiovascular Disease · doi:10.1177/20480040261435032
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“…even with effective blood pressure and lipid-lowering interventions, considerable “residual risk” remains, thus motivating the identification of adjunct strategies that directly protect the endothelium (Sampson et al., 2012; Reith and Armitage, 2016; Dhindsa et al., 2020; Manta et al., 2024).”
Jia-mei, F., Sun, X.-Z., Guo, Z.-Y., Zhao, Q., Ya-Xiong, S., Li, H.-X., & Yu, X. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1806765
НОВІТНЯ ЛІПІДОЗНИЖУЮЧА ТЕРАПІЯ: ЗА МЕЖАМИ СТАТИНІВ
Руснак-Каушанська, О. В., Колодніцька, Н., Курелюк, А., & Велієва, Н. (2026) · ГРААЛЬ НАУКИ · doi:10.36074/grail-of-science.29.05.2026.158
“Саме тут реалізується дія бемпедоєвої кислоти - інноваційного інгібітора АТФ - цитратліази [12].”
MLK3 promotes atherosclerosis by regulating ferroptosis in macrophages
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“However, despite effectively lowering LDL cholesterol to guideline-recommended levels, these therapies reduce major adverse cardiovascular events by less than 50% [49, 56].”
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“Although statin-based lipid-lowering therapy has substantially improved outcomes in patients with ASCVD, a considerable residual cardiovascular risk persists [3].”
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“Large clinical trials and contemporary meta-analyses consistently demonstrate substantial residual cardiovascular risk even when traditional risk factors are controlled [ 9, 10 ].”
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“Extensive clinical observations indicate that many patients with well-controlled LDL-C levels still experience cardiovascular events, suggesting a signi fi cant residual risk (12).”
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Development of a Prognostic Model for MACE in Atherosclerosis Based on MTHFR and Serum Markers
Dou, X., Zhang, X., Zeng, L., 虎晓燕, Zeng, L., Wan, Y., Jiang, X., Ge, M., & Huang, X. (2026) · Clinical and Applied Thrombosis/Hemostasis · doi:10.1177/10760296261476828
“4 Among various non-traditional cardiovascular risk factors, systematic disturbances in the homocysteine (Hcy) metabolic pathway have increasingly been recognized as an independent and potent mechanism of vascular endothelial injury.”
Assemie, M. A., Miller, K., Gall, S., Cleland, V. J., & Tian, J. (2026) · Heart Lung and Circulation · doi:10.1016/j.hlc.2026.04.008
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“Pooled analyses similarly suggest that annual residual risk may approach 9% in patients with established coronary artery disease despite intensive statin therapy [ 12 ].”
Kovyanova, T. I., Карагодин, В. П., Borodko, D. D., Rozhkova, U. V., Antonov, S. A., Utkina, A. S., & Vaganova, A. N. (2026) · Biomolecules · doi:10.3390/biom16091319
“Additionally, statin treatment is associated with adverse effects, including myopathy, hepatotoxicity, or new cases of diabetes mellitus [25].”
CORONARY PLAQUE BURDEN AND ATHEROGENIC LIPID INDICES IN NON-DIABETIC PATIENTS
Kozluca, V., Özbeyaz, N. B., Atan, Ş., Cunetoglu, M. E., & Özdöl, Ç. (2026) · Bozok Tıp Dergisi · doi:10.16919/bozoktip.1927745
Metadata
- Authors
- Sampson, U. K., Fazio, S., & Linton, M. F.
- Affiliations
- Vanderbilt University Medical Center (US)
- Corresponding author
- Linton, MacRae F.
- Venue
- Current Atherosclerosis Reports
- Published
- 2011-11-19
- Volume
- 14
- Issue
- 1
- Pages
- 1-10
- ISSN
- 1523-3804 (ISSN-L)
- 1534-6242
- PMC
- PMC3697085
- OpenAlex
- W2079979713
- Cited by
- 439
- References
- 117
- Citations by year
- 2026: 37 · 2025: 36 · 2024: 38 · 2023: 50 · 2022: 43 · 2021: 36 · 2020: 34 · 2019: 36 · 2018: 33 · 2017: 25 · 2016: 19 · 2015: 18 · 2014: 15 · 2013: 11 · 2012: 7
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Current Atherosclerosis Reports (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL065709, R01HL086988, HL086988, HL105375, HL65709, R01HL105375)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- residual cardiovascular risk, LDL cholesterol lowering, statins, HDL cholesterol, triglycerides, fenofibrate, torcetrapib, nicotinic acid, AIM-HIGH trial, ILLUMINATE trial, diabetes mellitus, metabolic syndrome, lifestyle modification, lipid therapy
- MeSH terms
- Cardiovascular Diseases, Humans, Life Style, Cholesterol, LDL, Morbidity, Risk Factors, Risk Assessment, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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