Effects of colchicine adjuvant therapy on disease control, serum NALP3, sICAM-1, MMP-9 and MMP-13 in patients with coronary heart disease and acute gout attack

Colchicine Effects on Coronary Disease and Acute Gout Markers

  • Bingxun Wang
  • Yongqing Liu
  • Wenya Han
  • Bing Li
  • Jie Pang
  • Wenwen Yang
  • Zengcai Ma
  • Zesheng Xu Department of Cardiology, Cangzhou Central Hospital
DOI: https://doi.org/10.5937/jomb0-51326
Keywords: Colchicine, Coronary heart disease, Acute gout attack, Nucleotide binding oligomerization domain-like receptor protein 3, Soluble intercellular adhesion molecule-1, Matrix metalloproteinase-9, Matrix metalloproteinase-13, Cardiac function

Abstract


Background: To investigate the impact of colchicine adjuvant therapy on disease control and serum levels of nucleotide-binding oligomerization domain-like receptor (NALP) 3, soluble intercellular adhesion molecule (sICAM)-1, matrix metalloproteinase (MMP)-9, and MMP-13 in patients with coronary heart disease (CHD) complicated by acute gout attacks.

Methods: Ninety-two patients with CHD and acute gout attacks admitted to our hospital from October 2021 to January 2023 were randomly divided into an observation group and a control group, with 46 patients in each group. The control group received conventional treatment, while the observation group received colchicine adjuvant therapy on top of the control group's treatment for 7 days. Clinical efficacy in both groups was assessed. Before and after treatment, cardiac function indicators (left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular posterior wall thickness (LVPWT)), vascular endothelial function indicators (sICAM-1, endothelin-1 (ET-1), and vascular endothelial growth factor (VEGF)), inflammatory factors (NALP3, MMP-9, MMP-13) levels, changes in immune cell populations (CD3+ lymphocytes, CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes ratio, and CD3+CD4+/CD3+CD8+ ratio) were compared, and the incidence of adverse reactions was recorded. Three months after treatment, the occurrence of major adverse cardiovascular events was also recorded.

Results: The total effective rate in the observation group was significantly higher than that in the control group (93.48% vs 79.07%) (P<0.05). After treatment, the levels of NALP3, MMP-9, and MMP-13 in both groups decreased, with the observation group being lower than the control group (P<0.05). After treatment, LVPWT and LVEDD levels in the observation group were lower than those in the control group, and LVEF was higher (P<0.05). After treatment, the levels of ET-1 and sICAM-1 in the observation group were lower than those in the control group, and VEGF levels were higher (P<0.05). After treatment, the proportions of CD3+ lymphocytes, CD3+CD4+ lymphocytes, and CD3+CD4+/CD3+CD8+ ratio were significantly higher in the observation group than in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). The occurrence of major adverse cardiovascular events in the observation group was lower than that in the control group (2.17% vs 13.04%).

Conclusion: Colchicine adjuvant therapy improves the efficacy of CHD patients with acute gout attacks, helps improve cardiac function and vascular endothelial function, reduces serum levels of NALP3, sICAM-1, MMP-9, and MMP-13, enhances patient immunity, and controls disease progression.

References

1. Nematy M, Alinezhad-Namaghi M, Rashed MM, Mozhdehifard M, Sajjadi SS, Akhlaghi S, et al. Effects of Ramadan fasting on cardiovascular risk factors: a prospective observational study. Nutr J 2012; 11: 69.
2. Saito Y, Tanaka A, Node K, Kobayashi Y. Uric acid and cardiovascular disease: A clinical review. J Cardiol 2021; 78(1): 51-7.
3. Tunon J, Badimon L, Bochaton-Piallat ML, Cariou B, Daemen MJ, Egido J, et al. Identifying the anti-inflammatory response to lipid lowering therapy: a position paper from the working group on atherosclerosis and vascular biology of the European Society of Cardiology. Cardiovasc Res 2019; 115(1): 10-9.
4. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. New Engl J Med 2017; 377(12): 1119-31.
5. Deftereos SG, Beerkens FJ, Shah B, Giannopoulos G, Vrachatis DA, Giotaki SG, et al. Colchicine in Cardiovascular Disease: In-Depth Review. Circulation 2022; 145(1): 61-78.
6. Dasgeb B, Kornreich D, McGuinn K, Okon L, Brownell I, Sackett DL. Colchicine: an ancient drug with novel applications. Brit J Dermatol 2018; 178(2): 350-6.
7. Chaldakov GN. Colchicine, a microtubule-disassembling drug, in the therapy of cardiovascular diseases. Cell Biol Int 2018; 42(8): 1079-84.
8. Arber S, McKinlay J, Adams A, Marceau L, Link C, O'Donnell A. Patient characteristics and inequalities in doctors' diagnostic and management strategies relating to CHD: a video-simulation experiment. Soc Sci Med 2006; 62(1): 103-15.
9. Lorenzin M, Ughi N, Ariani A, Raffeiner B, Ceccarelli F, Lucchetti R, et al. Impact of disease duration and gender on the sensitivity and specificity of 2015 ACR/EULAR classification criteria for gout. Cross-sectional results from an Italian multicentric study on the management of crystal-induced arthritis (ATTACk). Clin Exp Rheumatol 2022; 40(7): 1368-77.
10. Zdrojewski T, Gaudron P, Whittaker P, Poelzl S, Schiemann J, Hu K, et al. Ventricular remodeling after myocardial infarction and effects of ACE inhibition on hemodynamics and scar formation in SHR. Cardiovasc Pathol 2002; 11(2): 88-93.
11. Li Y, Yang H, Tian Y, Duan L. Factors Influencing the Serum Uric Acid in Gout with Cerebral Infarction. Mediat Inflamm 2021; 2021(5523490.
12. Gracheva IA, Shchegravina ES, Schmalz HG, Beletskaya IP, Fedorov AY. Colchicine Alkaloids and Synthetic Analogues: Current Progress and Perspectives. J Med Chem 2020; 63(19): 10618-51.
13. Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. New Engl J Med 2019; 381(26): 2497-505.
14. Whayne TJ. Inflammation May be the Future of Cardiovascular Risk Reduction: Does Colchicine have a Current Indication? Am J Cardiovasc Drug 2021; 21(1): 1-10.
15. Fan J, Watanabe T. Atherosclerosis: Known and unknown. Pathol Int 2022; 72(3): 151-60.
16. Liu P, Xu Y, Ye J, Tan J, Hou J, Wang Y, et al. Qingre Huazhuo Jiangsuan Decoction promotes autophagy by inhibiting PI3K/AKT/mTOR signaling pathway to relieve acute gouty arthritis. J Ethnopharmacol 2023; 302(Pt A): 115875.
17. Quesada IM, Lucero A, Amaya C, Meijles DN, Cifuentes ME, Pagano PJ, et al. Selective inactivation of NADPH oxidase 2 causes regression of vascularization and the size and stability of atherosclerotic plaques. Atherosclerosis 2015; 242(2): 469-75.
18. Pavkova GM, Jarkovsky J, Lipkova J, Littnerova S, Poloczek M, Spinar J, et al. Relationship of long-term prognosis to MMP and TIMP polymorphisms in patients after ST elevation myocardial infarction. J Appl Genet 2017; 58(3): 331-41.
19. Tuomainen AM, Kormi I, Havulinna AS, Tervahartiala T, Salomaa V, Sorsa T, et al. Serum tissue-degrading proteinases and incident cardiovascular disease events. Eur J Prev Cardiol 2014; 21(7): 806-12.
20. Nidorf SM, Fiolet A, Mosterd A, Eikelboom JW, Schut A, Opstal T, et al. Colchicine in Patients with Chronic Coronary Disease. New Engl J Med 2020; 383(19): 1838-47.
21. Nidorf SM, Thompson PL. Why Colchicine Should Be Considered for Secondary Prevention of Atherosclerosis: An Overview. Clin Ther 2019; 41(1): 41-8.
22. Puig N, Camps-Renom P, Camacho M, Aguilera-Simon A, Jimenez-Altayo F, Fernandez-Leon A, et al. Plasma sICAM-1 as a Biomarker of Carotid Plaque Inflammation in Patients with a Recent Ischemic Stroke. Transl Stroke Res 2022; 13(5): 745-56.
23. Opstal T, van Broekhoven A, Fiolet A, Mosterd A, Eikelboom JW, Nidorf SM, et al. Long-Term Efficacy of Colchicine in Patients With Chronic Coronary Disease: Insights From LoDoCo2. Circulation 2022; 145(8): 626-8.
24. Fiolet A, Nidorf SM, Cornel JH. Colchicine for secondary prevention in coronary disease. Eur Heart J 2021; 42(11): 1060-1.
Published
2024/08/21
Issue
Vol. 44 No. 1 (2025): Journal of Medical Biochemistry
Section
Original paper

Copyright (c) 2024 Bingxun Wang, Yongqing Liu, Wenya Han, Bing Li, Jie Pang, Wenwen Yang, Zengcai Ma, Zesheng Xu

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