Vascular and inflammatory biomarkers of cardiovascular events in non-steroidal anti-inflammatory drug (NSAID) users
European Heart Journal Open, 2024
Vaja R., Ferreira P., Portas L., Ahmetaj-Shala B., Cypaite N., Gashaw H., Quint J., Khamis R., Hartley A., MacDonald T., Mackenzie I., Kirkby N., Mitchell J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases CVD | Pathophysiology | Serum | O Olink Explore 3072/384 |
Abstract
Background
The Standard care vs. Celecoxib Outcome Trial (SCOT) found similar risk of cardiovascular events with traditional non-steroidal anti-inflammatory drugs (NSAIDs) and the COX-2 selective drug celecoxib. Whilst 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
Within SCOT, (7,295 NSAID users with osteo 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).
Results
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 (OR 0.68; 95% CI 0.46 to 0.98). There was significantly higher IgG anti-malondialdehyde-modified low-density lipoprotein (MDA-LDL), ADMA and lower arginine/ADMA. Targeted proteomic analysis identified serum growth differentiation factor 15 (GDF-15) as a candidate biomarker (AUC of 0.715 (95% CI 0.63 to 0.81)).
Conclusions
GDF-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 (NAG-1).