Vascular and inflammatory biomarkers of cardiovascular events in non-steroidal anti-inflammatory drug users.

Autor:	Vaja R; The National Heart and Lung Institute, Imperial College London SW7 2AZ, UK.; The Royal Brompton Hospital, London SW3 6NP, UK., Ferreira P; The National Heart and Lung Institute, Imperial College London SW7 2AZ, UK., Portas L; The National Heart and Lung Institute, Imperial College London SW7 2AZ, UK., Ahmetaj-Shala B; The National Heart and Lung Institute, Imperial College London SW7 2AZ, UK., Cypaite N; The National Heart and Lung Institute, Imperial College London SW7 2AZ, UK., Gashaw H; The National Heart and Lung Institute, Imperial College London SW7 2AZ, UK., Quint J; The National Heart and Lung Institute, Imperial College London SW7 2AZ, UK., Khamis R; The National Heart and Lung Institute, Imperial College London SW7 2AZ, UK., Hartley A; The National Heart and Lung Institute, Imperial College London SW7 2AZ, UK., MacDonald TM; Ninewells Hospital and Medical School, University of Dundee, Dundee DD2 1SG, UK., Mackenzie IS; Ninewells Hospital and Medical School, University of Dundee, Dundee DD2 1SG, UK., Kirkby NS; The National Heart and Lung Institute, Imperial College London SW7 2AZ, UK., Mitchell JA; The National Heart and Lung Institute, Imperial College London SW7 2AZ, UK.
Jazyk:	angličtina
Zdroj:	European heart journal open [Eur Heart J Open] 2024 Nov 02; Vol. 4 (6), pp. oeae088. Date of Electronic Publication: 2024 Nov 02 (Print Publication: 2024).
DOI:	10.1093/ehjopen/oeae088
Abstrakt:	Aims: The Standard care vs. Celecoxib Outcome Trial (SCOT) found similar risk of cardiovascular events with traditional non-steroidal anti-inflammatory drugs (NSAIDs) and the cyclooxygenase-2-selective drug celecoxib. While pre-clinical work has suggested roles for vascular and renal dysfunction in NSAID cardiovascular toxicity, our understanding of these mechanisms remains incomplete. A post hoc analysis of the SCOT cohort was performed to identify clinical risk factors and circulating biomarkers of cardiovascular events in NSAID users. Methods and Results: Within SCOT (7295 NSAID users with osteoarthritis or rheumatoid arthritis), clinical risk factors associated with cardiovascular events were identified using least absolute shrinkage and selection operator regression. A nested case-control study of serum biomarkers including targeted proteomics was performed in individuals who experienced a cardiovascular event within 1 year ( n = 49), matched 2:1 with controls who did not ( n = 97). Risk factors significantly associated with cardiovascular events included increasing age, male sex, smoking, total cholesterol:HDL ratio ≥5, and aspirin use. Statin use was cardioprotective [odds ratio (OR) 0.68; 95% confidence interval (CI) 0.46-0.98]. There was significantly higher immunoglobulin (Ig)G anti-malondialdehyde-modified LDL (MDA-LDL), asymmetric dimethylarginine (ADMA), and lower arginine/ADMA. Targeted proteomic analysis identified serum growth differentiation factor 15 (GDF-15) as a candidate biomarker [area under the curve of 0.715 (95% CI 0.63-0.81)]. Conclusion: Growth differentiation factor 15 has been identified as a candidate biomarker and should be explored for its mechanistic contribution to NSAID cardiovascular toxicity, particularly given the remarkable providence that GDF-15 was originally described as NSAID-activated gene-1 . Competing Interests: Conflict of interest: Pfizer funded the SCOT study from which the samples for this study were obtained. They had no role in this study. T.M.M. has received consulting fees from Novartis and AstraZeneca and was the Chief investigator for the SCOT study. I.S.M. has received consultancy fees from Astrazeneca and payment from Novartis and NovoNordisk and was a co-investigator for the SCOT study. J.A.M. is a member of the scientific advisory board of Antibe Therapeutics, which develops cyclooxygenase inhibitor anti-inflammatory drugs. J.A.M. and N.S.K. hold active research grant funding in the area of cyclooxygenase biology. R.V. previously held grant funding in this area. (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
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