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Review
. 2024 Jan 1;20(1):32-44.
doi: 10.4244/EIJ-D-23-00606.

Targeting inflammation in atherosclerosis: overview, strategy and directions

Ron Waksman  1 , Ilan Merdler  1 , Brian C Case  1 , Ori Waksman  1 , Italo Porto  2   3
Affiliations
Review

Targeting inflammation in atherosclerosis: overview, strategy and directions

Ron Waksman et al. EuroIntervention. .

Abstract

Atherosclerosis is a chronic condition characterised by the build-up of plaque in the inner lining of the blood vessels and it is the main underlying cause of cardiovascular disease. The development of atherosclerosis is associated with the accumulation of cholesterol and inflammation. Although effective therapies exist to lower low-density lipoprotein cholesterol (LDL-C) levels, some patients still experience cardiovascular events due to persistent inflammation, known as residual inflammatory risk (RIR). Researchers have conducted laboratory and animal studies to investigate the measurement and targeting of the inflammatory cascade associated with atherosclerosis, which have yielded promising results. In addition to guideline-directed lifestyle modifications and optimal medical therapy focusing on reducing LDL-C levels, pharmacological interventions targeting inflammation may provide further assistance in preventing future cardiac events. This review aims to explain the mechanisms of inflammation in atherosclerosis, identifies potential biomarkers, discusses available therapeutic options and their strengths and limitations, highlights future advancements, and summarises notable clinical studies. Finally, an evaluation and management algorithm for addressing RIR is presented.

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Conflict of interest statement

R. Waksman reports serving on the advisory boards of Abbott, Boston Scientific, Medtronic, Philips IGT, and Pi-Cardia Ltd.; being a consultant for Abbott Vascular, Biotronik, Boston Scientific, Cordis, Medtronic, Philips IGT, Pi-Cardia Ltd., Swiss Interventional Systems/SIS Medical AG, Transmural Systems Inc., and Venus MedTech; receiving institutional grant support from Amgen, Biotronik, Boston Scientific, Chiesi, Medtronic, and Philips IGT; and being an investor in MedAlliance and Transmural Systems Inc. I. Porto reports consultant or speaker fees from SysMedical, Medtronic, Abbott, Edwards Lifesciences, Abiomed, Terumo, Philips, Sanofi, Amgen, Daiichi Sankyo, AstraZeneca, Bayer, and Pfizer; and a department grant (minor) from Chiesi, Bayer, Medtronic, and Abbott. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Mechanism of inflammation in atherosclerosis.
ang II: angiotensin II; CD8: cluster of differentiation 8; ET-1: endothelin-1; ICAM-1: intercellular adhesion molecule-1; IFN: interferon; IL: interleukin; LDL: low-density lipoprotein; NLRP: nod-like receptor family pyrin; NO: nitric oxide; PDGF: platelet-derived growth factor; TNF: tumour necrosis factor; VCAM-1: vascular cell adhesion molecule-1; VEGF: vascular endothelial growth factor
Figure 2
Figure 2. Suggested strategy for treating residual inflammatory risk.
hs-CRP: high sensitivity C-reactive protein; LDL-C: low-density lipoprotein cholesterol
Central illustration
Central illustration. Mechanisms of inflammation in atherosclerosis, biomarkers of inflammation in atherosclerosis, potential treatments, and prominent clinical trials.
hs-CRP: high sensitivity C-reactive protein; IL: interleukin; miRNA: microRNA; MMPs: matrix metalloproteinases; PCSK9: proprotein convertase subtilisin/kexin type 9
See this image and copyright information in PMC

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