The DOI matches its Crossref record; 147 of the 148 references it cites were found in a registry or an index.
Anticytokine Agents: Targeting Interleukin Signaling Pathways for the Treatment of Atherothrombosis
Open accessAbstract
The recognition that atherosclerosis is a complex chronic inflammatory disorder mediated through both adaptive and innate immunity has led to the hypothesis that anticytokine therapies targeting specific IL (interleukin) signaling pathways could serve as powerful adjuncts to lipid lowering in the prevention and treatment of cardiovascular disease. Cytokines involved in human atherosclerosis can be broadly classified as proinflammatory and proatherogenic (such as IL-1, IL-6, and TNF [tumor necrosis factor]) or as anti-inflammatory and antiatherogenic (such as IL-10 and IL-1rA). The recent CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) has shown that specific targeting of IL-1β can significantly reduce cardiovascular event rates without lipid or blood pressure lowering. In CANTOS, the magnitude of benefit of this cytokine-targeted approach to atherosclerosis treatment was associated to the magnitude of reduction of the central signaling cytokine IL-6 and the downstream clinical biomarker high-sensitivity CRP (C-reactive protein). By contrast, in the recent CIRT (Cardiovascular Inflammation Reduction Trial), low-dose methotrexate neither reduced IL-1β, IL-6, or high-sensitivity CRP nor lowered cardiovascular event rates. Taken together, these 2 contemporary trials provide proof of principle that focused cytokine inhibition, not broad-spectrum anti-inflammatory therapy, is likely to be crucial for atheroprotection. This review provides an overview of cytokines in atherosclerosis, the potential benefits and risks associated with targeted anticytokine therapies, and a look to the future of clinical practices addressing residual inflammatory risk.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“particularly inhibition of the central interleukin-1β to interleukin-6 to C-reactive protein pathway of innate immunity that is important for atherosclerosis development 4,5”
From Effects of Randomized Treatment With Icosapent Ethyl and a Mineral Oil Comparator on Interleukin-1β, Interleukin-6, C-Reactive Protein, Oxidized Low-Density Lipoprotein Cholesterol, Homocysteine, Lipoprotein(a), and Lipoprotein-Associated Phospholipase A2: A REDUCE-IT Biomarker Substudy (2022) · cites this paper as [5]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Immunity, Inflammation, and Cancer
Grivennikov, S. I., Greten, F. R., & Karin, M. (2010) · Cell · doi:10.1016/j.cell.2010.01.025 · Cited by 10,755
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., Fonseca, F., Nicolau, J., Koenig, W., Anker, S. D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1707914 · Cited by 9,482 · cited 8×
“subcutaneous canakinumab given every 3 months (50, 150, or 300 mg).(4) Virtually, all participants were on statin ther-”
BackgroundMethodResultInfluentialSelf-citationInflammation, Atherosclerosis, and Coronary Artery Disease
Hansson, G. K. (2005) · New England Journal of Medicine · doi:10.1056/nejmra043430 · Cited by 8,773
Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein
Ridker, P. M., Danielson, E., Fonseca, F. A. H., Genest, J., Gotto, A. M., Kastelein, J. J. P., Koenig, W., Libby, P., Lorenzatti, A. J., MacFadyen, J. G., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0807646 · Cited by 6,674 · cited 6×
“This insight eventually led to the JUPITER trial that demonstrated considerable efficacy of high-intensity statin therapy among individuals with low levels of LDL-C but elevated levels of hsCRP.(50)”
BackgroundInfluentialSelf-citationEvolocumab and Clinical Outcomes in Patients with Cardiovascular Disease
Sabatine, M. S., Giugliano, R. P., Keech, A. C., Honarpour, N., Wiviott, S. D., Murphy, S. A., Kuder, J. F., Wang, H., Liu, T., Wasserman, S. M., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1615664 · Cited by 6,138
Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066 · cited 1×
“Beyond IL-1: the NLRP3 Inflammasome, IL-18, IL-6, CD40-CD40L, and TREM-1 as Alternative Cytokine Targets As critical components of the innate immune system, inflammasomes comprise macromolecular protein complexes capable of recognizing a variety of immune stimuli, including microbial and nonmicrobial pathogens, exogen…”
BackgroundRidker, P. M., Hennekens, C. H., Buring, J. E., & Rifai, N. (2000) · New England Journal of Medicine · doi:10.1056/nejm200003233421202 · Cited by 5,850
Self-citationInflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men
Ridker, P. M., Cushman, M., Stampfer, M. J., Tracy, R. P., & Hennekens, C. H. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704033361401 · Cited by 5,504
Self-citationAge-related clonal hematopoiesis associated with adverse outcomes
Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408617 · Cited by 4,841 · cited 1×
“Several recent cohort studies indicate that carriers of CHIP are at increased cardiovascular risk, independent of traditional risk markers.(105,106) Approximately 10% of”
BackgroundC-Reactive Protein, Interleukin 6, and Risk of Developing Type 2 Diabetes Mellitus
Pradhan, A. D. (2001) · JAMA · doi:10.1001/jama.286.3.327 · Cited by 4,433
Research works printed but not linked: 1
- Svennson, EC, Madar, A, Campbell, CD, He, Y, Sultan, M, Healey, ML, D’Aco, K, Fernandez, A, Wache-Mainier, C, Ridker, PM, Beste, MT, Basson, CT. TET-2-driven clonal hematopoiesis predicts response to canakinumab in the CANTOS trials: an exploratory analysis. Abstract presented at American Heart Association Scientific Session, November 12, 2018.
Cited by
Sorted by citations
Ridker, P. M., Devalaraja, M., Baeres, F. M. M., Engelmann, M. D. M., Hovingh, G. K., Ivkovic, M., Lo, L., Kling, D. F., Pérgola, P. E., Raj, D. S., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00520-1 · Cited by 802
Self-citationInterleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease
Ridker, P. M., & Rane, M. A. (2021) · Circulation Research · doi:10.1161/circresaha.121.319077 · Cited by 743
Self-citationTargeting cardiovascular inflammation: next steps in clinical translation
Lawler, P. R., Bhatt, D. L., Godoy, L. C., Lüscher, T. F., Bonow, R. O., Verma, S., & Ridker, P. M. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa099 · Cited by 463
Self-citationTherapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed?
Engelen, S. E., Robinson, A., Zurke, Y.-X., & Monaco, C. G. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00668-4 · Cited by 455
Dziedzic, E. A., Gąsior, J. S., Tuzimek, A., Paleczny, J., Junka, A., Dąbrowski, M., & Jankowski, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179553 · Cited by 345
Neuroinflammation across neurological diseases
Shi, F., & Yong, V. W. (2025) · Science · doi:10.1126/science.adx0043 · Cited by 325
Ridker, P. M., MacFadyen, J. G., Thuren, T. Y., & Libby, P. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz542 · Cited by 241
Self-citationLivshits, G., & Kalinkovich, A. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100980 · Cited by 245
Zaki, N., Alashwal, H., & Ibrahim, S. (2020) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2020.07.005 · Cited by 248
Lipoprotein‐associated phospholipase A2: The story continues
Huang, F., Wang, K., & Shen, J. (2020) · Medicinal Research Reviews · doi:10.1002/med.21597 · Cited by 212
“Furthermore, the possibility that Lp‐PLA2 might not be a suitable target to address the residual inflammatory risk could not be excluded, based on the observation that broad‐spectrum anti‐inflammatory therapy by methotrexate failed to reduce cardiovascular events while specific cytokine inhibition by canakinumab could…”
BackgroundWhite Blood Cells and Blood Pressure
Siedliński, M., Józefczuk, E., Xu, X., Teumer, A., Εvangelou, Ε., Schnabel, R. B., Welsh, P. I., Maffia, P., Erdmann, J., Tomaszewski, M., et al. (2020) · Circulation · doi:10.1161/circulationaha.119.045102 · Cited by 206
The Baffling Case of Ischemic Stroke Disappearance from the Casualty Department in the COVID-19 Era
Morelli, N., Rota, E., Terracciano, C., Immovilli, P., Spallazzi, M., Colombi, D., Zaino, D., Michieletti, E., & Guidetti, D. (2020) · European Neurology · doi:10.1159/000507666 · Cited by 191
“Indeed, although high IL-6 levels have been reported to have a negative effect on brain infarct volume and long-term outcome [10] , conversely, in ischemic stroke, there is also experimental evidence that IL-6 has a protective effect and helps in the improvement of poststroke angiogenesis [11] .”
BackgroundTargeting the CCL2–CCR2 axis for atheroprotection
Georgakis, M. K., Bernhagen, J., Heitman, L. H., Weber, C., & Dichgans, M. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac094 · Cited by 182
Ridker, P. M., MacFadyen, J. G., Glynn, R. J., Bradwin, G., Hasan, A., & Rifai, N. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa160 · Cited by 169
Self-citationRidker, P. M. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab231 · Cited by 156
“Yet, cardiologists and vascular biologists now have hard evidence that inhibition of the NLRP3 to IL-1b to IL-6 to C-reactive protein (CRP) pathway of innate immunity is also a potent target for atheroprotection.(1) This proof-of-principle derives from the 10 000 participant multi-national CANTOS trial presented in 20…”
BackgroundSelf-citationChallenges and advances in the management of inflammation in atherosclerosis
Xing, Y., & Lin, X. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.06.016 · Cited by 147
“Notably, IL-10 is known for its atheroprotective effects, adding complexity to the role of Th17 cells in atherogenesis [54,55].”
Endothelial shear stress signal transduction and atherogenesis: From mechanisms to therapeutics
He, L., Zhang, C., Chen, Q., Wang, L., & Huang, Y. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108152 · Cited by 141
Ridker, P. M., Rifai, N., MacFadyen, J., Glynn, R. J., Jiao, L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Tardif, J.-C., et al. (2022) · Circulation · doi:10.1161/circulationaha.122.059410 · Cited by 131
Self-citationPCSK9 inhibition and inflammation: A narrative review
Ruscica, M., Tokgözoğlu, L. S., Corsini, A., & Sirtori, C. R. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.07.015 · Cited by 133
“with a 2X2 factorial design, with aggressive LDL-C-lowering and anti-inflammatory therapies are eagerly awaited [140].”
MethodRossi, J., Lu, Z. Y., Massart, C., & Levón, K. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.595722 · Cited by 140
“Dynamic analysis of the inflammatory biomarkers may contribute to a more personalized immune medicine, monitoring both the risks associated to vaccine and the therapies needed, aiming to reduce inflammation by using anti-cytokine targeting IL-1, TNFa, or IL-6, or to amplify an immune response by using immune adjuvants…”
BackgroundInflammation drives residual risk in chronic kidney disease: a CANTOS substudy
Ridker, P. M., Tuttle, K. R., Perkovic, V., Libby, P., & MacFadyen, J. G. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac444 · Cited by 117
Self-citationRidker, P. M. (2020) · Circulation · doi:10.1161/circulationaha.119.045256 · Cited by 111
Self-citationCirculating Monocyte Chemoattractant Protein-1 and Risk of Stroke
Georgakis, M. K., Malik, R., Björkbacka, H., Pana, T. A., Demissie, S., Ayers, C. R., Elhadad, M. A., Fornage, M., Beiser, A., Benjamin, E. J., et al. (2019) · Circulation Research · doi:10.1161/circresaha.119.315380 · Cited by 110
Georgakis, M. K., van der Laan, S. W., Asare, Y., Mekke, J. M., Haitjema, S., Schoneveld, A. H., de Jager, S. C. A., Nurmohamed, N. S., Kroon, J., Stroes, E. S. G., et al. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.121.316091 · Cited by 107
Wang, H., Liu, Z., Shao, J., Lin, L., Jiang, M., Wang, L., Lu, X.-C., Zhang, H. S., Chen, Y., & Zhang, R. (2020) · Journal of Immunology Research · doi:10.1155/2020/4904217 · Cited by 114
“…showed a reduced level of troponin and in fl am-matory markers in the ASSessing the E ff ect of Anti-IL-6 Treatment in MI (ASSAIL-MI) trial [16, 69, 70], which was designed to assess the e ff ects of tocilizumab on ischemia reperfusion injury in patients with ST-elevation myocardial…”
InfluentialHasselbalch, H. C., Elvers, M., & Schafer, A. I. (2021) · Blood · doi:10.1182/blood.2020008109 · Cited by 103
Poizeau, F., Nowak, E., Kerbrat, S., Nautout, B. L., Droitcourt, C., Drici, M., Sbidian, É., Guillot, B., Bachelez, H., Ait‐Oufella, H., et al. (2020) · JAMA Dermatology · doi:10.1001/jamadermatol.2020.2977 · Cited by 102
Roles and Mechanisms of Hawthorn and Its Extracts on Atherosclerosis: A Review
Wu, M., Liu, L., Xing, Y., Yang, S., Li, H., & Cao, Y. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00118 · Cited by 106
“The hyper-activated inflammatory response can lead to Frontiers in Pharmacology | www.frontiersin.org 6 acute coronary syndromes (Gimbrone and García-Cardeña, 2016; Ferrucci and Fabbri, 2018; Ridker, 2019).”
BackgroundTocchetti, C. G., Farmakis, D. T., Koop, Y., Andrés, M. S., Couch, L. S., Formisano, L., Ciardiello, F., Pane, F., Au, L., Emmerich, M., et al. (2024) · European Journal of Heart Failure · doi:10.1002/ejhf.3340 · Cited by 102
D’Alessandro, E., Becker, C., Bergmeier, W., Bode, C., Bourne, J. H., Brown, H. C., Buller, H. R., ten Cate‐Hoek, A. J., ten Cate, V., van Cauteren, Y. J. M., et al. (2020) · Thrombosis and Haemostasis · doi:10.1055/s-0040-1708035 · Cited by 91
Inflammation and Cardiovascular Disease: The Future
Arnold, N., Lechner, K., Waldeyer, C., Shapiro, M. D., & Köenig, W. (2021) · European Cardiology Review · doi:10.15420/ecr.2020.50 · Cited by 93
Sex Differences in Proatherogenic Cytokine Levels
Bernardi, S., Toffoli, B., Tonon, F., Francica, M., Campagnolo, E., Ferretti, T., Comar, S., Giudici, F., Stenner, E., & Fabris, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21113861 · Cited by 88
“IL-1β, IL-6, and TNF-α are soluble low-molecular-weight-proteins that mediate crosstalk between immune and nonimmune cells and have been implicated in atherosclerosis development and progression [26].”
BackgroundCupido, A. J., Asselbergs, F. W., Natarajan, P., CHARGE Inflammation Working Group, Ridker, P. M., Hovingh, G. K., & Schmidt, A. F. (2021) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15191 · Cited by 81
Self-citationAnticytokine Immune Therapy and Atherothrombotic Cardiovascular Risk
Ait‐Oufella, H., Libby, P., & Tedgui, A. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.311998 · Cited by 84
The ABCA1-efferocytosis axis: A new strategy to protect against atherosclerosis
Chen, W., Li, L., Wang, J., Zhang, R., Zhang, T., Wu, Y., Wang, S., & Xing, D. (2021) · Clinica Chimica Acta · doi:10.1016/j.cca.2021.02.025 · Cited by 84
Novel Therapeutics and Upcoming Clinical Trials Targeting Inflammation in Cardiovascular Diseases
Potere, N., Bonaventura, A., & Abbate, A. (2024) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.124.319980 · Cited by 85
Modified Lipoproteins Induce Arterial Wall Inflammation During Atherogenesis
Lorey, M. B., Öörni, K., & Kovanen, P. T. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.841545 · Cited by 82
Wada, Y., Jensen, C., Meyer, A., Zonoozi, A. A. M., & Honda, H. (2023) · Journal of Cardiology · doi:10.1016/j.jjcc.2023.05.006 · Cited by 77
Georgakis, M. K., Malik, R., Björkbacka, H., Pana, T. A., Demissie, S., Ayers, C. R., Elhadad, M. A., Fornage, M., Beiser, A., Benjamin, E. J., et al. (2019) · PubMed · doi:10.17863/cam.43602 · Cited by 74
Identification of HMOX1 as a Critical Ferroptosis-Related Gene in Atherosclerosis
Wu, D., Hu, Q., Wang, Y., Jin, M., Tao, Z., & Wan, J. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.833642 · Cited by 75
Cytokines as key players in obesity low grade inflammation and related complications
Uti, D. E., Atangwho, I. J., Omang, W. A., Alum, E. U., Obeten, U. N., Udeozor, P. A., Agada, S. A., Bawa, I., & Ogbu, C. O. (2025) · Obesity Medicine · doi:10.1016/j.obmed.2025.100585 · Cited by 116
Differences in Biomarkers of Inflammation Between Novel Subgroups of Recent-Onset Diabetes
Herder, C., Maalmi, H., Straßburger, K., Zaharia, O., Ratter, J. M., Karusheva, Y., Elhadad, M. A., Bódis, K. B., Bongaerts, B. W. C., Rathmann, W., et al. (2021) · Diabetes · doi:10.2337/db20-1054 · Cited by 78
Li, J., Lin, J., Pan, Y., Wang, M., Meng, X., Li, H., Wang, Y., Zhao, X., 秦海强, Liu, L., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02467-1 · Cited by 77
Atherosclerosis: Insights into Vascular Pathobiology and Outlook to Novel Treatments
Wolf, M., & Hunziker, P. (2020) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-020-09961-y · Cited by 74
“Cytokine blockade therapy has become an important option in the treatment of autoimmune and auto-inflammatory diseases and is considered for treatment of atherosclerosis [151].”
BackgroundBallerini, P., Contursi, A., Bruno, A., Mucci, M., Tacconelli, S., & Patrignani, P. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.838079 · Cited by 71
“Chronic inflammation promotes many pathological conditions, including atherothrombosis (Libby et al., 2009; Ridker 2019), tissue fibrosis (Wynn and Ramalingam 2012), aberrant angiogenesis (Jackson et al., 1997), and neoplasia (Coussens and Werb, 2002; Grivennikov et al., 2010; Hanahan and Weinberg…”
BackgroundRidker, P. M., Baeres, F. M. M., Hvelplund, A., Engelmann, M. D. M., Hovingh, G. K., Lincoff, A. M., Marx, N., Návar, A. M., Sattar, N. A., Tuttle, K. R., et al. (2025) · JAMA Cardiology · doi:10.1001/jamacardio.2025.4491 · Cited by 71
Self-citationEffects of Interleukin-1β Inhibition on Incident Anemia
Vallurupalli, M., MacFadyen, J. G., Glynn, R. J., Thuren, T. Y., Libby, P., Berliner, N., & Ridker, P. M. (2020) · Annals of Internal Medicine · doi:10.7326/m19-2945 · Cited by 68
“Earlier analyses from CANTOS revealed that canakinumab treatment modifies several disease processes involving inflammasome signaling (22).”
BackgroundSelf-citationAdvances in biological therapies for dyslipidemias and atherosclerosis
Valanti, E.-K., Dalakoura-Karagkouni, K., Siasos, G., Kardassis, D., Eliopoulos, A. G., & Sanoudou, D. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154461 · Cited by 68
Functional role of skeletal muscle-derived interleukin-6 and its effects on lipid metabolism
Lin, W., Song, H., Shen, J., Wang, J., Yang, Y., Yang, Y., Cao, J., Xue, L., Zhao, F., Xiao, T., et al. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1110926 · Cited by 74
“Among thousands of cytokines, NOD-, LRR-, and pyrin domaincontaining protein 3 (NLRP3), C-reactive protein (CRP), IL-1, and IL-6 were involved in atherosclerosis pathogenesis (Ridker, 2016; Lutgens et al., 2019; Ridker, 2019).”
BackgroundNLRP3 inflammasome in cardiovascular diseases: an update
Mo, B., Ding, Y., & Ji, Q. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1550226 · Cited by 74
“Numerous studies have been conducted to investigate potential treatment approaches that target the in fl ammatory response since the function of the NLRP3 in fl ammasome in cardiovascular diseases has been increasingly validated (195).”
Immunomodulation Strategies for the Successful Regeneration of a Tissue‐Engineered Vascular Graft
Zhang, F., & King, M. W. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202200045 · Cited by 69
Molecular and cellular mechanisms of inflammation in atherosclerosis
Popa‐Fotea, N., Ferdoschi, C., & Micheu, M.-M. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1200341 · Cited by 63
Wei, X., Zhang, Z., Wei, J., & Luo, C. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1248655 · Cited by 64
Decoding inflammation, its causes, genomic responses, and emerging countermeasures
Hawiger, J., & Zienkiewicz, J. (2019) · Scandinavian Journal of Immunology · doi:10.1111/sji.12812 · Cited by 62
Koshino, A., Schechter, M., Sen, T., Vart, P., Neuen, B. L., Neal, B. C., Arnott, C. G., Perkovic, V., Ridker, P. M., Tuttle, K. R., et al. (2022) · Diabetes Care · doi:10.2337/dc22-0866 · Cited by 65
Self-citationTargeting Inflammation After Acute Myocardial Infarction
Imbesi, A., Greco, A., Spagnolo, M., Laudani, C., Raffo, C., Finocchiaro, S., Mazzone, P. M., Landolina, D., Mauro, M. S., Cutore, L., et al. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.07.064 · Cited by 74
Growth Factors as Immunotherapeutic Targets in Cardiovascular Disease
Mindur, J. E., & Świrski, F. K. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.311994 · Cited by 58
Koller, G. M., Schafer, C. M., Kemp, S. S., Aguera, K. N., Lin, P. K., Forgy, J. C., Griffin, C. T., & Davis, G. E. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.313536 · Cited by 57
Advances in the treatment of atherosclerosis with ligand‐modified nanocarriers
Deng, X., Wang, J., Yu, S., Tan, S., Yu, T., Xu, Q., Chen, N., Zhang, S., Zhang, M., Hu, K., et al. (2023) · Exploration · doi:10.1002/exp.20230090 · Cited by 56
Advances in Atherosclerosis Theranostics Harnessing Iron Oxide‐Based Nanoparticles
Wang, S., He, H., Mao, Y., Zhang, Y., & Gu, N. (2024) · Advanced Science · doi:10.1002/advs.202308298 · Cited by 59
Hoffmann, J., Mas‐Peiró, S., Berkowitsch, A., Boeckling, F., Rasper, T., Pieszko, K., Rosa, R. D., Hiczkiewicz, J., Burchardt, P., Fichtlscherer, S., et al. (2020) · ESC Heart Failure · doi:10.1002/ehf2.12837 · Cited by 59
“The era of anti-inflammatory therapies in cardiovascular disease and heart failure has just begun.(41) A recent subgroup”
BackgroundMonomeric C-Reactive Protein in Atherosclerotic Cardiovascular Disease: Advances and Perspectives
Melnikov, I., Kozlov, S. G., Saburova, O., Avtaeva, Y., Guria, K. G., & Ахнафович, Г. З. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032079 · Cited by 56
“Moreover, the mechanism of the anti-inflammatory action of methotrexate does not affect the NLRP3 inflammasome and IL-1β/IL-6/CRP axis [36].”
BackgroundInfluentialQuagliariello, V., Passariello, M., Mauro, A. D., Cipullo, C., Paccone, A., Barbieri, A., Palma, G., Luciano, A., Buccolo, S., Bisceglia, I., et al. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.930797 · Cited by 51
“Moreover, the results of this study warrant further preclinical cardioprotective trials with anti-cytokine (52, 53), anti-NLRP3 (54–56) or anti-MyD88 (57, 58) therapies in primary or secondary prevention of ICIs-related cardiotoxicity.”
ResultImmunomodulatory hybrid micro-nanofiber scaffolds enhance vascular regeneration
Liu, S. M., Yao, L., Wang, Y., Li, Y., Jia, Y., Yang, Y., Li, N., Hu, Y., Kong, D., Dong, X., et al. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.08.018 · Cited by 49
“IL-1β triggered the secretion of various pro-inflammatory cytokines related to the level of stenosis and athetosis [50,51].”
BackgroundDziedzic, E. A., Gąsior, J. S., Tuzimek, A., Dąbrowski, M., & Jankowski, P. (2022) · Nutrients · doi:10.3390/nu14194212 · Cited by 53
Alisma orientalis Beverage Treats Atherosclerosis by Regulating Gut Microbiota in ApoE-/- Mice
Zhu, B., Zhai, Y., Ji, M., Wei, Y., Wu, J., Xue, W., Tao, W. W., & Wu, H. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.570555 · Cited by 48
“Under constant stimulation of chronic systemic inflammation and high blood lipid levels, the arteries will suffer corresponding damage and produce atherosclerotic lesions (Fatkhullina et al., 2018; Komaroff, 2018; Ridker, 2019).”
BackgroundGeorgakis, M. K., Malik, R., Burgess, S., & Dichgans, M. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.121.023277 · Cited by 45
“10 Here, we use large-scale data to test whether there is genetic support for this hypothesis before investing in a clinical trial.”
Reflections on Atherosclerosis: Lesson from the Past and Future Research Directions
Minelli, S., Minelli, P., & Montinari, M. R. (2020) · Journal of Multidisciplinary Healthcare · doi:10.2147/jmdh.s254016 · Cited by 54
Gu, H., Yang, K., Lin, J., Jing, J., Zhao, X., Wang, Y., Liu, L., Meng, X., Jiang, Y., Li, H., et al. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104054 · Cited by 47
Li, X., Yang, Y., Wang, Z., Jiang, S., Meng, Y., Song, X., Zhao, L., Zou, L., Li, M., & Yu, T. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.62506 · Cited by 49
“In patients with AS, activated NLRP3 inflammasomes produce IL-1β and IL-18 [77, 78], which up-regulate VCAM to induce T-cell differentiation and promote a downstream inflammatory response, thus leading to plaque progression [79, 80].”
BackgroundDongoran, R. A., Lin, T., Byekyet, A., Tang, S., Yang, J., & Liu, C. (2020) · Biomolecules · doi:10.3390/biom10121689 · Cited by 46
Yin, T., Li, Y., Ren, Y., Fuad, A. R. M., Hu, F., Du, R., Wang, Y., Wang, Y., & Wang, Y. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-00863-y · Cited by 40
Role of the adaptive immune system in atherosclerosis
Ley, K. F. (2020) · Biochemical Society Transactions · doi:10.1042/bst20200602 · Cited by 46
Hafiane, A., & Daskalopoulou, S. S. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106157 · Cited by 41
Sánchez-Azofra, A., Gu, W., Masso-Silva, J. A., Sánz-Rubio, D., Marín‐Oto, M., Cubero, P., Gil, A. V., Moya, E. A., Barnes, L. A., Mesarwi, O. A., et al. (2023) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.10600 · Cited by 39
Yang, L., Yue, Q., Fang, F., Zhang, Y., Liu, P., Zhang, Z., Wang, G., Chen, S., Wu, S., & Yang, X. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01826-3 · Cited by 39
“OxLDL-C can also increase the expression of hs-CRP [31], which can activate the complement system to form atherosclerotic plaque [32, 33].”
BackgroundStrategies to Overcome Residual Risk During Statins Era
Cho, K. I., Yu, J., Hayashi, T., Han, S. H., & Koh, K. K. (2019) · Circulation Journal · doi:10.1253/circj.cj-19-0624 · Cited by 39
Effects of Bilberry Supplementation on Metabolic and Cardiovascular Disease Risk
Chan, S. W., & Tomlinson, B. (2020) · Molecules · doi:10.3390/molecules25071653 · Cited by 42
“Furthermore, data from the recent Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) and Cardiovascular Inflammation Reduction Trial (CIRT) provide clinical support of the benefit of anti-cytokine therapies, but not weaker broad-spectrum antiinflammatory therapy, in atherosclerosis treatment [65,66].”
ResultNon-stenotic Carotid Plaques in Embolic Stroke of Unknown Source
Tatuene, J. K., Nomani, A. Z., Falcione, S. R., Munsterman, D., Sykes, G. P., Joy, T., Spronk, E., Vargas, M. I., & Jickling, G. C. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.719329 · Cited by 40
Mullis, C. E., & Swartz, T. H. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00095 · Cited by 41
New evidence on the role of inflammation in CVD risk
Lorenzatti, A. J., & Servato, L. (2019) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000625 · Cited by 39
Atherothrombosis and the NLRP3 inflammasome – endogenous mechanisms of inhibition
Satish, M., & Agrawal, D. K. (2019) · Translational research · doi:10.1016/j.trsl.2019.08.003 · Cited by 39
Sun, L., Yuan, J., Chen, Q.-C., Xiao, W.-K., Ma, G., Liang, J., Chen, X., Wang, S., Zhou, X., Wu, H. M., et al. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.996467 · Cited by 39
Georgakis, M. K., Malik, R., Gill, D., Franceschini, N., Sudlow, C. L. M., & Dichgans, M. (2019) · medRxiv · doi:10.1101/19007682 · Cited by 36
Gallucci, G., Turazza, F. M., Inno, A., Canale, M. L., Silvestris, N., Farì, R., Navazio, A., Pinto, C., & Tarantini, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084232 · Cited by 37
“The remarkable inflammatory features of atherosclerosis explain the beneficial effect of drugs that target the inflammasome pathway, but a “focused” cytokine inhibition is necessary, as Ridker states, to yield an effective atheroprotective effect [87,88].”
BackgroundDing, E., Deng, F., Fang, J., Liu, J., Yan, W., Yao, Q., Miao, K., Wang, Y., Sun, P., Li, C., et al. (2024) · Environmental Health Perspectives · doi:10.1289/ehp13864 · Cited by 32
“88 Epidemiological studies have also supported the fi ndings of our pathway analysis.”
ResultRole of Periodontal Infection, Inflammation and Immunity in Atherosclerosis
Choi, H., Dey, A. K., Priyamvara, A., Aksentijevich, M., Bandyopadhyay, D., Dey, D. K., Dani, S. S., Guha, A., Nambiar, P. H., Nasir, K., et al. (2020) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2020.100638 · Cited by 36
Ma, J., & Chen, X. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.631398 · Cited by 36
Fang, Q., Li, X., Wang, M., Qiao, X., Huang, F., Hu, C., Xue, Y., Zhao, S., & Lin, Y. (2022) · Food & Function · doi:10.1039/d2fo00012a · Cited by 31
Clemens, D. L., Duryee, M. J., Hall, J. H., Thiele, G. M., Mikuls, T. R., Klassen, L. W., Zimmerman, M. C., & Anderson, D. R. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107413 · Cited by 32
Radionuclide Image-Guided Repair of the Heart
Hess, A., Thackeray, J. T., Wollert, K. C., & Bengel, F. M. (2019) · JACC. Cardiovascular imaging · doi:10.1016/j.jcmg.2019.11.007 · Cited by 30
Bugueno, I. M., Zobairi, F., Batool, F., Itawi, H. E., Anglés‐Cano, E., Benkirane-Jessel, N., Toti, F., & Huck, O. (2020) · Scientific Reports · doi:10.1038/s41598-020-58374-z · Cited by 35
Colchicine – new horizons for an ancient drug. Review based on the highest hierarchy of evidence
Schattner, A. (2021) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2021.10.002 · Cited by 32
Macrophage Dysfunction in Autoimmune Rheumatic Diseases and Atherosclerosis
Герасимова, Е. В., Попкова, Т. В., Gerasimova, D. A., & Kirichenko, T. V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094513 · Cited by 31
“CIRT [96], and COLCOT studies [97], several new anti-inflammatory and anticytokine agents are expected to be developed for the treatment of atherosclerosis [98].”
BackgroundEverett, B. M. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.02.056 · Cited by 30
“Novel therapies directed at the NLRP3 inflammasome and its downstream signaling cascade—including IL-1b and -6—are in development (2).”
BackgroundHigh l -Carnitine Ingestion Impairs Liver Function by Disordering Gut Bacteria Composition in Mice
Wu, Q., Zhang, X., Zhao, Y., & Yang, X. (2020) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b08313 · Cited by 29
Targeting the ACOD1-itaconate axis stabilizes atherosclerotic plaques
Harber, K. J., Neele, A. E., van Roomen, C. P. A. A., Gijbels, M. J., Beckers, L., den Toom, M., Schomakers, B. V., Heister, D., Willemsen, L., Griffith, G. R., et al. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103054 · Cited by 28
Nordeng, J., Schandiz, H., Solheim, S., Åkra, S., Hoffman, P., Roald, B., Bendz, B., Arnesen, H., Helseth, R., & Seljeflot, I. (2021) · Mediators of Inflammation · doi:10.1155/2021/5525917 · Cited by 28
“Further downstream C-Reactive-Protein (CRP), produced in the liver as a response to IL-6, has been demonstrated to be a sustainable clinical marker of cardiovascular disease [19, 20].”
BackgroundFifty years of research on antithrombotic therapy: Achievements and disappointments
Hirsh, J., Eikelboom, J. W., & Chan, N. (2019) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2019.10.023 · Cited by 27
Anti-inflammatory Therapies for Coronary Heart Disease: A Systematic Review and Meta-Analysis
Wang, H., Jiang, M., Li, X., Zhao, Y., Shao, J., Liu, Z., Lin, L., Xu, Q., Wang, L., Lu, X.-C., et al. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.726341 · Cited by 27
“Current Evidence of Anti-inflammatory Therapy for CHD The attainment of cardiovascular benefits is compromised by the limitations of available treatment for CHD (1, 2, 8, 28).”
Background
Metadata
- Authors
- Ridker, P. M.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Ridker, Paul M
- ORCID
- Ridker, Paul M
- Venue
- Circulation Research
- Published
- 2019-02
- Volume
- 124
- Issue
- 3
- Pages
- 437-450
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC6386195
- OpenAlex
- W2914237180
- Cited by
- 260
- References
- 148
- Citations by year
- 2026: 15 · 2025: 30 · 2024: 30 · 2023: 38 · 2022: 42 · 2021: 40 · 2020: 37 · 2019: 28
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (U01HL101422)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- anti-cytokine therapy, atherosclerosis, cytokines, IL-1β, interleukin-6, TNF-α, CANTOS trial, methotrexate, cardiovascular inflammation, high-sensitivity C-reactive protein, residual inflammatory risk, atheroprotection, cardiovascular disease prevention
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Triggering Receptor Expressed on Myeloid Cells-1, Interleukin-6 Inhibitors, Animals, Antibodies, Monoclonal, C-Reactive Protein, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Disease Models, Animal, Hematopoiesis, Humans, Methotrexate, Thrombosis, Signal Transduction, Randomized Controlled Trials as Topic, CD40 Antigens, Interleukin-18, Stroke, CD40 Ligand, Atherosclerosis, Mice, Renal Insufficiency, Chronic, Interleukin-1beta, Inflammasomes, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
