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Review
. 2024 Sep;13(3):465-491.
doi: 10.1007/s40119-024-00376-3. Epub 2024 Jul 20.

Recent Advances in Targeted Management of Inflammation In Atherosclerosis: A Narrative Review

Rafael Zubirán  1 , Edward B Neufeld  1 , Amaury Dasseux  1 , Alan T Remaley  1 , Alexander V Sorokin  2   3   4
Affiliations
Review

Recent Advances in Targeted Management of Inflammation In Atherosclerosis: A Narrative Review

Rafael Zubirán et al. Cardiol Ther. 2024 Sep.

Abstract

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite effective low-density lipoprotein cholesterol-targeted therapies. This review explores the crucial role of inflammation in the residual risk of ASCVD, emphasizing its impact on atherosclerosis progression and plaque stability. Evidence suggests that high-sensitivity C-reactive protein (hsCRP), and potentially other inflammatory biomarkers, can be used to identify the inflammatory residual ASCVD risk phenotype and may serve as future targets for the development of more efficacious therapeutic approaches. We review the biological basis for the association of inflammation with ASCVD, propose new therapeutic strategies for the use of inflammation-targeted treatments, and discuss current challenges in the implementation of this new treatment paradigm for ASCVD.

Keywords: Atherosclerosis; Atherosclerotic cardiovascular disease; Canakinumab; Colchicine; Inflammation; Interleukins; LDL-C; NLRP3 inflammasome; Triglyceride-rich lipoproteins; Ziltivekimab.

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Conflict of interest statement

Alan T. Remaley, Edward B Neufeld and Rafael Zubirán are full-time US Government employees. Amaury Dasseux has declared that no potential conflict of interest exists. Alexander V. Sorokin is a full-time employee of Regeneron Pharmaceuticals Inc.

Figures

Fig. 1
Fig. 1
Inflammatory signaling pathways and targeted therapeutic interventions. LDL low-density lipoprotein, TRL triglyceride-rich lipoprotein, hsCRP high-sensitivity C-reactive protein, PCSK9i proprotein convertase subtilisin/kexin type 9 inhibitor, BA bempedoic acid, IL-6 interleukin 6, IL-1β interleukin 1 beta, IL-18 interleukin-18, TNF-α tumor necrosis factor alpha, NLRP3 nucleotide-binding oligomerization domain-like receptor 3, Lp-PLA2 lipoprotein phospholipase A2. This original figure was created using BioRender
Fig. 2
Fig. 2
Percentage reduction in hsCRP with different therapies. hsCRP high-sensitivity C-reactive protein, PCSK9i proprotein convertase subtilisin/kexin type 9 inhibitor. This original figure was created using GraphPad Prism
Fig. 3
Fig. 3
Relative risk reduction for major cardiovascular events in trials in a population who achieved high-sensitivity C-reactive protein (hsCRP) < 2 mg/L. This original figure was created using GraphPad Prism
Fig. 4
Fig. 4
Potential assessment of secondary prevention phenotype. Dotted lines indicate unanswered questions. LDL-C low-density lipoprotein cholesterol, hsCRP high-sensitivity C-reactive protein, PCSK9i proprotein convertase subtilisin/kexin type 9 inhibitor, BA bempedoic acid, IL-6 interleukin 6. This original figure was created using BioRender
See this image and copyright information in PMC

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