Inflammatory biomarkers in the prediction of residual cardiovascular risk in patients with metabolic syndrome: An integrative literature review
DOI:
https://doi.org/10.33448/rsd-v14i10.49582Keywords:
Metabolic Syndrome, Cardiovascular Risk, Interleukin-6, Tumor Necrosis Factor Alpha, C-Reactive Protein.Abstract
Metabolic syndrome represents a set of interrelated metabolic alterations that significantly increase the risk of cardiovascular events. Even with control of traditional risk factors, many patients continue to experience adverse outcomes, characterizing what is known as residual cardiovascular risk. Recent studies have shown that chronic low-grade inflammation plays a fundamental role in this process, particularly biomarkers such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP). The objective of this article is to conduct an integrative literature review on the clinical applicability of the inflammatory biomarkers IL-6, TNF-α, and hs-CRP in the stratification of residual cardiovascular risk in patients with metabolic syndrome, highlighting the main findings, challenges, and future perspectives in the management of this population. Available evidence on the association between serum levels of these markers and the occurrence of cardiovascular events was analyzed, as well as their potential use in risk stratification beyond traditional parameters. The results suggest that these biomarkers have promising prognostic value and may contribute to a more personalized and effective approach in the secondary prevention of cardiovascular events. Despite advances in understanding this relationship, further research is still needed to consolidate their routine use in clinical practice and establish inflammation-based therapeutic protocols.
References
Alberti, K. G., Eckel, R. H., Grundy, S. M., Zimmet, P. Z., Cleeman, J. I., Donato, K. A., … Smith, S. C. (2009). Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. Circulation, 120(16), 1640–1645. https://doi.org/10.1161/CIRCULATIONAHA.109.192644
Barbaresko, J., Koch, M., Schulze, M. B., & Nöthlings, U. (2013). Dietary pattern analysis and biomarkers of low-grade inflammation: A systematic literature review. Nutrition Reviews, 71(8), 511–527. https://doi.org/10.1111/nure.12035
Bonaccio, M., Di Castelnuovo, A., Pounis, G., Costanzo, S., Persichillo, M., Cerletti, C., … Iacoviello, L. (2016). A score of low-grade inflammation and risk of mortality: Prospective findings from the Moli-sani study. Haematologica, 101(11), 1434–1441. https://doi.org/10.3324/haematol.2016.144543
Cannon, C. P., Blazing, M. A., Giugliano, R. P., McCagg, A., White, J. A., Theroux, P., … Califf, R. M. (2015). Ezetimibe added to statin therapy after acute coronary syndromes. New England Journal of Medicine, 372(25), 2387–2397. https://doi.org/10.1056/NEJMoa1410489
Casarin, S. T., Figueiredo, A. B., & Ribeiro, C. (2020). Revisão narrativa: Aspectos conceituais e metodológicos. Revista Científica da UEM, 25(2), 45–58.
Cesari, M., Penninx, B. W., Newman, A. B., Kritchevsky, S. B., Nicklas, B. J., Sutton-Tyrrell, K., … Pahor, M. (2003). Inflammatory markers and cardiovascular disease (The Health, Aging and Body Composition [Health ABC] Study). American Journal of Cardiology, 92(5), 522–528. https://doi.org/10.1016/S0002-9149(03)00718-5
Emerging Risk Factors Collaboration. (2010). C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: An individual participant meta-analysis. The Lancet, 375(9709), 132–140. https://doi.org/10.1016/S0140-6736(09)61717-7
Fernandez, D. M., Rahman, A. H., & Fernandez, N. F. (2019). Single-cell immune landscape of human atherosclerotic plaques. Nature Medicine, 25(10), 1576–1588. https://doi.org/10.1038/s41591-019-0590-4
García-Hernández, A., Aráuz-Pacheco, C., Rojas, R., & Aguilar-Salinas, C. A. (2018). High-sensitivity C-reactive protein as a marker of cardiovascular risk in metabolic syndrome. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 12(3), 469–475. https://doi.org/10.1016/j.dsx.2018.02.004
Golia, E., Limongelli, G., Natale, F., Fimiani, F., Maddaloni, V., Pariggiano, I., … Calabrò, R. (2014). Inflammation and cardiovascular disease: From pathogenesis to therapeutic target. Current Atherosclerosis Reports, 16(9), 435. https://doi.org/10.1007/s11883-014-0435-z
Gottlieb, M. G. V., Ávila, P. R., da Silva, N. R., & Mota, R. P. (2015). Síndrome metabólica e doenças cardiovasculares: Relação entre interleucina-6 e exercício físico. FIEP Bulletin, 85(1), 20–23. https://www.fiepbulletin.net/index.php/fiepbulletin/article/download/85.a1.20/10431
Greenland, P., Blaha, M. J., Budoff, M. J., Erbel, R., & Watson, K. E. (2018). Coronary calcium score and cardiovascular risk. Journal of the American College of Cardiology, 72(4), 434–447. https://doi.org/10.1016/j.jacc.2018.05.027
Hansel, B., Giral, P., Nobecourt, E., Chantepie, S., Bruckert, E., Chapman, M. J., & Kontush, A. (2004). Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity. Journal of Clinical Endocrinology & Metabolism, 89(10), 4963–4971. https://doi.org/10.1210/jc.2004-0305
Hotamisligil, G. S. (2017). Inflammation, metaflammation and immunometabolic disorders. Nature, 542(7640), 177–185. https://doi.org/10.1038/nature21363
Huoya, M. O., Monteiro, A. S. M. J., Lima, T. F., & Costa, P. R. (2009). Comparação de biomarcadores inflamatórios entre pacientes diabéticos e não-diabéticos com angina instável. Arquivos Brasileiros de Cardiologia, 93(4), 360–366. https://www.scielo.br/j/abc/a/9NMCbqgqyh7WH5gr9YDFjSq/
Jialal, I., & Devaraj, S. (2020). Inflammation and atherothrombosis: The role of biomarkers in risk assessment and therapy. Cardiology Clinics, 38(1), 1–12. https://doi.org/10.1016/j.ccl.2019.09.001
Junqueira, A. S. M., Romêo Filho, L. J. M., & Junqueira, C. L. C. (2009). Avaliação do grau de inflamação vascular em pacientes com síndrome metabólica. Arquivos Brasileiros de Cardiologia, 93(4), 360–366. https://www.scielo.br/j/abc/a/nNx8GkkCKGdmXvyTZcPrM9R/
Kivimäki, M., Lawlor, D. A., Davey Smith, G., Keltikangas-Järvinen, L., Elovainio, M., Vahtera, J., & Ferrie, J. E. (2008). Avaliação da proteína C-reativa como preditor para doenças cardiovasculares. 1Library. https://1library.org/document/q0g6knlz-avaliacao-proteina-reativa-como-preditor-para-doencas-cardiovasculares.html
Libby, P., & Ridker, P. M. (2018). Inflammation and atherosclerosis: Role of C-reactive protein in risk prediction and treatment. Circulation, 138(2), 115–125. https://doi.org/10.1161/CIRCULATIONAHA.118.033391
Libby, P., Buring, J. E., Badimon, L., Hansson, G. K., Deanfield, J., Bittencourt, M. S., … Ridker, P. M. (2019). Atherosclerosis. Nature Reviews Disease Primers, 5(1), 56. https://doi.org/10.1038/s41572-019-0106-z
Mora, S., & Ridker, P. M. (2006). C-reactive protein and cardiovascular disease: A review of risk prediction and intervention trials. Journal of Clinical Endocrinology & Metabolism, 91(8), 2453–2463. https://doi.org/10.1210/jc.2006-0693
Mottillo, S., Filion, K. B., Genest, J., Joseph, L., Pilote, L., Poirier, P., … Eisenberg, M. J. (2010). The metabolic syndrome and cardiovascular risk: A systematic review and meta-analysis. Journal of the American College of Cardiology, 56(14), 1113–1132. https://doi.org/10.1016/j.jacc.2010.05.034
Neves, C. V. B., Oliveira, C. C., Santos, J. L. F., & Duarte, Y. A. O. (2019). Associação entre síndrome metabólica e marcadores inflamatórios em idosos residentes na comunidade. Cadernos de Saúde Pública, 35(3), e00129918. https://doi.org/10.1590/0102-311X00129918
Pereira, A. S., et al. (2018). Metodologia da pesquisa científica. [e-book]. Ed. UAB/NTE/UFSM.
Pereira, A. S., Shitsuka, D. M., Parreira, F. J., & Shitsuka, R. (2018). Metodologia da pesquisa científica. UFSM.
Pradhan, A. D., Aday, A. W., Rose, L. M., & Ridker, P. M. (2018). Residual inflammatory risk on treatment with PCSK9 inhibition and statin therapy. Circulation, 138(2), 141–149. https://doi.org/10.1161/CIRCULATIONAHA.118.034645
Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., … Glynn, R. J. (2017). Antiinflammatory therapy with canakinumab for atherosclerotic disease. New England Journal of Medicine, 377(12), 1119–1131. https://doi.org/10.1056/NEJMoa1707914
Ridker, P. M., MacFadyen, J. G., Everett, B. M., Libby, P., & Glynn, R. J. (2018). Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: A secondary analysis from the CANTOS randomized controlled trial. The Lancet, 391(10118), 319–328. https://doi.org/10.1016/S0140-6736(17)32814-3
Rother, E. T. (2007). Revisão sistemática X revisão narrativa. Acta Paulista de Enfermagem, 20(2), 5–6. https://doi.org/10.1590/S0103-21002007000200001
Ross, R. (1999). Atherosclerosis—An inflammatory disease. New England Journal of Medicine, 340(2), 115–126. https://doi.org/10.1056/NEJM199901143400207
Sabatine, M. S., Giugliano, R. P., Keech, A. C., Honarpour, N., Wiviott, S. D., Murphy, S. A., … FOURIER Steering Committee and Investigators. (2017). Evolocumab and clinical outcomes in patients with cardiovascular disease. New England Journal of Medicine, 376(18), 1713–1722. https://doi.org/10.1056/NEJMoa1615664
Schmidt, F. M., Weschenfelder, J., Sander, C., Minkwitz, J., Thormann, J., Chittka, T., … Himmerich, H. (2015). Inflammatory cytokines in general and central obesity and modulating effects of physical activity. PLOS ONE, 10(3), e0121971. https://doi.org/10.1371/journal.pone.0121971
Silva, D., & Lacerda, A. P. (2012). Proteína C reativa de alta sensibilidade como biomarcador de risco na doença coronária. Revista Portuguesa de Cardiologia, 31(11), 733–745. https://doi.org/10.1016/j.repc.2012.02.018
Tabas, I., & Glass, C. K. (2013). Anti-inflammatory therapy in chronic disease: Challenges and opportunities. Science, 339(6116), 166–172. https://doi.org/10.1126/science.1230720
Thomasi, D. I., Batistella, F., & de Bem, A. F. (2008). Proteína C reativa-ultra sensível (PCR-US) e aterosclerose: O papel inflamatório das doenças cardíacas. Saúde (Santa Maria), 33(2), 14–20. https://doi.org/10.5902/223658346466
Toth, P. P., Grabner, M., Ramey, N., Brilakis, E. S., & Foody, J. M. (2017). Cardiovascular risk in patients achieving low-density lipoprotein cholesterol and hs-CRP goals. Atherosclerosis, 267, 1–8. https://doi.org/10.1016/j.atherosclerosis.2017.10.010
Tousoulis, D., Oikonomou, E., Economou, E. K., Crea, F., & Kaski, J. C. (2016). Inflammatory cytokines in atherosclerosis: Current therapeutic approaches. European Heart Journal, 37(22), 1723–1732. https://doi.org/10.1093/eurheartj/ehv759
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Copyright (c) 2025 Ingrid Gonçalves Siqueira Brown, Anna Clara Angelo de Sousa, Marcelle Sant Anna Rosa Pinheiro Luna, Alice Lima Macedo, João Victor de Souza Maciel, Rafael Guerra dos Santos, Arthur Mota dos Santos, Daniela Rosa Lourenço, Jefferson da Silva Sousa, Lívia Thurler de Mendonça

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