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

TY - JOUR

T1 - Vascular and inflammatory biomarkers of cardiovascular events in non-steroidal anti-inflammatory drug users

AU - Vaja, Ricky

AU - Ferreira, Plinio

AU - Portas, Laura

AU - Ahmetaj-Shala, Blerina

AU - Cypaite, Neringa

AU - Gashaw, Hime

AU - Quint, Jennifer

AU - Khamis, Ramzi

AU - Hartley, Adam

AU - MacDonald, Thomas M.

AU - Mackenzie, Isla S.

AU - Kirkby, Nicholas S.

AU - Mitchell, Jane A.

N1 - © The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.

PY - 2024/11

Y1 - 2024/11

N2 - 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.

AB - 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.

KW - Non-steroidal anti-inflammatory

KW - NSAID

KW - Biomarkers

KW - Cardiovascular

UR - https://www.scopus.com/pages/publications/85212695883

U2 - 10.1093/ehjopen/oeae088

DO - 10.1093/ehjopen/oeae088

M3 - Article

C2 - 39660078

VL - 4

JO - European Heart Journal Open

JF - European Heart Journal Open

IS - 6

M1 - oeae088

ER -