Protective effects of metformin on myocardial injury in patients with COVID-19 combined with coronary heart diseases and diabetes_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

HUANG Zhenhua ¹ , LIU Qingyun ¹ , LIU Yakun ¹ , TANG Feifei ¹ , LIU Zhelong ² ,  GAO Sihai ¹

1. Department of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P.R.China;
2. Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P.R.China;

Corresponding author：

GAO Sihai, Email: sihaigao73@163.com

Keywords：

Coronavirus disease 2019 (COVID-19); metformin; heart injuries; diabetes; coronary heart diseases

DOI：

10.7507/1007-4848.202012077

Video：

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Objective To investigate whether metformin has protective effect on myocardial injury in patients with coronavirus disease 2019 (COVID-19) combined with coronary heart diseases and diabetes.Methods COVID-19 patients with coronary heart disease and diabetes who were admitted to Tongji Hospital from January 18 to April 25 in 2020 were enrolled. They were divided into a metformin group and a none-metformin group according to whether the metformin was used. The demographic characteristics, clinical symptoms, laboratory parameters, treatment and clinical outcomes of the two groups were analyzed retrospectively.Results There were 29 patients in the metformin group, 3 patients (12.0%, 3/25) suffered myocardial injury and 1 (3.4%) died of acute respiratory failure complicated by septic shock; 67 patients were in the non-metformin group and 24 (37.5%, 24/64) had myocardial injury but 15 died in hospital among whom 1 died of septic shock complicated by disseminated intravascular coagulation, 1 acute respiratory failure complicated by possible cerebral hemorrhage, 2 acute respiratory failure, 1 fulminant myocarditis, 3 acute myocardial infarction and 7 cardiac arrest. The incidence of myocardial injury (12.0% vs. 37.5%, P=0.019), hospital mortality (3.4% vs. 22.4%, P=0.034) and mortality of cardiovascular events (0.0% vs. 16.4%, P=0.049) in the metformin group were significantly lower than those in the non-metformin group. Multivariate analysis showed that the use of insulins (OR=11.235, P=0.003) was an influencing factor for in-hospital mortality of patients. The use of metformin (OR=0.154, P=0.013) was positively correlated with the myocardial injury.Conclusion When patients with coronary heart disease and diabetes are infected with COVID-19, metformin can effectively reduce myocardial damage and has a certain effect on reducing hospital mortality. Combined with clinical considerations, it is worthy of popularization.

Citation： HUANG Zhenhua, LIU Qingyun, LIU Yakun, TANG Feifei, LIU Zhelong, GAO Sihai. Protective effects of metformin on myocardial injury in patients with COVID-19 combined with coronary heart diseases and diabetes. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2021, 28(4): 396-403. doi: 10.7507/1007-4848.202012077 Copy

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1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA, 2020, 323(13): 1239-1242.
2. Fauci AS, Lane HC, Redfield RR. Covid-19 — navigating the uncharted. N Engl J Med, 2020, 382(13): 1268-1269.
3. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA, 2020, 323(11): 1061-1069.
4. Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med, 2008, 359(15): 1577-1589.
5. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet, 1998, 352(9131): 854-865.
6. Luo P, Qiu L, Liu Y, et al. Metformin treatment was associated with decreased mortality in COVID-19 patients with diabetes in a retrospective analysis. Am J Trop Med Hyg, 2020, 103(1): 69-72.
7. 国家卫生健康委办公厅, 国家中医药管理局办公室. 关于印发新型冠状病毒肺炎诊疗方案(试行第七版)的通知. (2020-03-03) [2020-03-03]. http://www.gov.cn/zhengce/zhengceku/2020-03/04/content_5486705.htm.
8. 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2017年版). 中华糖尿病杂志, 2018, 10(1): 4-67.
9. Chen Y, Yang D, Cheng B, et al. Clinical characteristics and outcomes of patients with diabetes and COVID-19 in association with glucose-lowering medication. Diabetes Care, 2020, 43(7): 1399-1407.
10. Cheng X, Liu YM, Li H, et al. Metformin is associated with higher incidence of acidosis, but not mortality, in individuals with COVID-19 and pre-existing type 2 diabetes. Cell Metab, 2020, 32(4): 537-547.
11. Bramante C, Ingraham N, Murray T et al. Observational study of metformin and risk of mortality in patients hospitalized with Covid-19. medRxiv, 2020.
12. Crouse A, Grimes T, Li P et al. Metformin use is associated with reduced mortality in a diverse population with COVID-19 and diabetes. medRxiv, 2020.
13. Kow CS, Hasan SS. Mortality risk with preadmission metformin use in patients with COVID-19 and diabetes: A meta-analysis. J Med Virol, 2021, 93(2): 695-697.
14. Lukito AA, Pranata R, Henrina J, et al. The effect of metformin consumption on mortality in hospitalized COVID-19 patients: a systematic review and meta-analysis. Diabetes Metab Syndr, 2020, 14(6): 2177-2183.
15. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol, 2019, 17(3): 181-192.
16. Wan Y, Shang J, Graham R, et al. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol, 2020, 94(7): e00127-120.
17. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579(7798): 270-273.
18. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020, 181(2): 271-280.
19. Chen L, Li X, Chen M, et al. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res, 2020, 116(6): 1097-1100.
20. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol, 2020, 5(7): 811-818.
21. Malhotra A, Hepokoski M, McCowen KC et al. ACE2, metformin, and COVID-19. iScience, 2020, 23(9): 101425.
22. Sharma S, Ray A, Sadasivam B. Metformin in COVID-19: A possible role beyond diabetes. Diabetes Res Clin Pract, 2020, 164: 108183.
23. Zhang J, Dong J, Martin M, et al. AMP-activated protein kinase phosphorylation of angiotensin-converting enzyme 2 in endothelium mitigates pulmonary hypertension. Am J Respir Crit Care Med, 2018, 198(4): 509-520.
24. Dziubak A, Wójcicka G, Wojtak A et al. Metabolic effects of metformin in the failing heart. Int J Mol Sci, 2018, 19(10): 2869.
25. Douros A, Dell Aniello S, Yu OHY et al. Sulfonylureas as second line drugs in type 2 diabetes and the risk of cardiovascular and hypoglycaemic events: population based cohort study. BMJ, 2018, 362: k2693.
26. Ursini F, Russo E, Pellino G et al. Metformin and autoimmunity: A "new deal" of an old drug. Front Immunol, 2018, 9: 1236.
27. Tzanavari T, Varela A, Theocharis S, et al. Metformin protects against infection-induced myocardial dysfunction. Metabolism, 2016, 65(10): 1447-1458.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Protective effects of metformin on myocardial injury in patients with COVID-19 combined with coronary heart diseases and diabetes

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