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Statin Therapy, Inflammation, and Outcomes in Patients Hospitalized for COVID-19: A Prospective Multicenter Cohort Study - 22/11/24

Doi : 10.1016/j.amjmed.2024.08.011 
Anis Ismail, MD, MSc a, #, Husam R. Shadid, MD b, #, Yiyuan Huang c, Christina G. Hutten, PhD d, Alexi Vasbinder, PhD e, Ian Pizzo d, Tonimarie Claire Catalan d, Kristen Machado Diaz d, Pennelope Kunkle a, Mousumi Banerjee, PhD c, Melvyn Rubenfire, MD f, Eric J. Brandt, MD f, Geoffery Williams, MD f, Rodica Pop-Busui, MD g, Salim S. Hayek, MD a, d, h,
a Division of Cardiology, Department of Internal Medicine, University of Texas Medical Branch, Galveston 
b Department of Cardiology, University of Texas Health Houston, Houston 
c Department of Biostatistics, University of Michigan, Ann Arbor 
d Department of Internal Medicine, University of Michigan, Ann Arbor 
e Department of Biobehavioral Nursing and Health Informatics, School of Nursing, University of Washington, Seattle 
f Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor 
g Division of Endocrinology, Department of Medicine, University of Michigan, Ann Arbor 
h On behalf of the International Study of Inflammation In COVID-19 (ISIC) Investigators 

Requests for reprints should be addressed to Salim Hayek MD, Division of Cardiology, Department of Internal Medicine, University of Texas Medical Branch, UTMB Health, 301 University Blvd, Suite 2.216B, Galveston, Texas, 77555-0895.Division of CardiologyDepartment of Internal MedicineUniversity of Texas Medical BranchUTMB Health, 301 University Blvd, Suite 2.216BGalvestonTexas77555-0895

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Abstract

Background

Statins are lipid-lowering agents with anti-inflammatory effects. Data surrounding the benefits of statins in patients with coronavirus disease 2019 (COVID-19) are conflicting. We sought to better understand the impact of statins in the context of COVID-19-related inflammation.

Methods

We leveraged the International Study of Inflammation in COVID-19, a prospective multicenter cohort of patients hospitalized for COVID-19 between February 2020 and October 2022. Participants underwent systematic assessment of biomarkers of inflammation. We used logistic regression modeling and inverse probability-of-treatment weighting (IPTW) to examine the association between prior statin use and the composite outcome of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy.

Results

A total of 4464 patients were included in the study, of whom 1364 (27.5%) were taking a statin prior to admission. There were 1061 primary outcome events, including 540 deaths, 854 mechanical ventilation and 313 renal replacement therapy. Amongst biomarkers of inflammation, statin use was associated solely with lower levels of soluble urokinase plasminogen activator receptor (suPAR) after adjusting for known confounders. In multivariable logistic regression analysis, statin use was associated with lower odds of the composite outcome (adjusted odds ratio (aOR) 0.63, 95% CI [0.53-0.76]) compared to patients not on statins. Findings were consistent with IPTW (aOR 0.92, 95% CI [0.89- 0.95]). The proportion of the effect of statin on the primary outcome mediated by suPAR was estimated at 31.5%.

Conclusion

Prior-statin use is associated with improved outcomes and lower inflammation as measured by suPAR levels in patients hospitalized for COVID-19.

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Keywords : COVID-19, CRP, Death, Dialysis, IL-6, Inflammation, LDH, Mechanical ventilation, MYD88, Renal replacement therapy, SARS-CoV-2, Statin, SuPAR


Plan


 Funding: Dr. Hayek is funded by NHLBI 1R01HL153384-01, and the Frankel Cardiovascular Center COVID-19: Impact Research Ignitor (U-M G024231) award. Kits and equipment were provided by Ortho Clinical Diagnostics to support this study. The funders had no role in design or conduct of the study; collection, management, analysis, or interpretation of the data; and preparation, review, or decision to publish the manuscript.
 Conflict of Interest: Dr. Salim S Hayek is member of the scientific advisory board of Walden Biosciences.
All other authors have no other disclosures.
 Authorship: AI made significant revisions to the draft. All co-authors had full access to the data and take responsibility for accuracy of the data analysis. All authors approved the final version of the manuscript. AI: Writing – review & editing, Writing – original draft, Visualization, Methodology, Investigation, Data curation; HRS: Writing – original draft, Visualization, Data curation; YH: Writing – review & editing, Visualization, Methodology; Formal analysis; CGH: Writing – review & editing, Visualization; AV: Writing – review & editing, Data curation; IP: Data curation, TCC: Data curation, KMD: Data curation; PK: Writing – review & editing, Project administration, Data curation; MB: Writing – review & editing, Methodology, Conceptualization; MR: Writing – review & editing; EJB: Writing – review & editing, GW: Writing – review & editing; RP-B: Writing – review & editing, Supervision, Methodology, Conceptualization; SSH: Writing – review & editing, Visualization, Validation, Supervision, Software, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization.


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Vol 137 - N° 12

P. 1264 - décembre 2024 Retour au numéro
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