Suboptimal inhibition of platelet cyclooxygenase 1 by aspirin in systemic lupus erythematosus: association with metabolic syndrome.

Abstract

OBJECTIVE:

Low-dose aspirin prevents platelet aggregation by suppressing thromboxane A2 (TXA2 ) synthesis. However, in some individuals TXA2 suppression by aspirin is impaired, indicating suboptimal inhibition of platelet cyclooxygenase 1 (COX-1) by aspirin. Because patients with systemic lupus erythematosus (SLE) have increased risk of thrombotic events, many receive aspirin; however, the efficacy of aspirin in SLE has not been determined. We examined the hypothesis that aspirin response is impaired in SLE.

METHODS:

We assessed the effect of aspirin by measuring concentrations of the stable metabolite of TXA2 , serum thromboxane B2 (sTXB2 ), before and after treatment with daily aspirin (81 mg) for 7 days in 34 patients with SLE and 36 control subjects. The inability to suppress sTXB2 synthesis to <10 ng/ml represents suboptimal inhibition of platelet COX-1 by aspirin.

RESULTS:

Aspirin almost completely suppressed sTXB2 in control subjects to median 1.5 ng/ml (interquartile range [IQR] 0.8-2.7) but had less effect in patients with SLE (median 3.1 ng/ml [IQR 2.2-5.3]) (P = 0.002). A suboptimal effect of aspirin was present in 15% (5 of 34) of the patients with SLE but not in control subjects (0 of 36) (P = 0.023). Incomplete responders were more likely to have metabolic syndrome (P = 0.048), obesity (P = 0.048), and higher concentrations of C-reactive protein (CRP) (P = 0.018).

CONCLUSION:

The pharmacologic effect of aspirin is suboptimal in 15% of patients with SLE but in none of the control subjects, and the suboptimal response was associated with metabolic syndrome, obesity, and higher CRP concentrations.

• Authors: Vivian K Kawai, Ingrid Avalos, Annette Oeser, John A Oates, Ginger L Milne, Joseph F Solus, Cecilia P Chung, C Michael Stein
• Journal: Arthritis care & research (Arthritis Care Res (Hoboken)) Vol. 66 Issue 2 Pg. 285-92 (Feb 2014) ISSN: 2151-4658 [Electronic] United States
• PMID: 24022862 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 by the American College of Rheumatology.

Chemical References

• Biomarkers
• Cyclooxygenase Inhibitors
• Thromboxane B2
• C-Reactive Protein
• Cyclooxygenase 1
• PTGS1 protein, human
• Aspirin

Topics

• Adult
• Aspirin (therapeutic use)
• Biomarkers (blood)
• Blood Platelets (drug effects, enzymology)
• C-Reactive Protein (metabolism)
• Chi-Square Distribution
• Cyclooxygenase 1 (blood)
• Cyclooxygenase Inhibitors (therapeutic use)
• Female
• Humans
• Lupus Erythematosus, Systemic (blood, complications, diagnosis, drug therapy, enzymology)
• Male
• Metabolic Syndrome (blood, complications)
• Middle Aged
• Obesity (complications)
• Prospective Studies
• Thromboxane B2 (blood)
• Time Factors
• Treatment Outcome