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Suboptimal Inhibition of Platelet Cyclooxygenase 1 by Aspirin in Systemic Lupus Erythematosus: Association With Metabolic Syndrome
Author(s) -
Kawai Vivian K.,
Avalos Ingrid,
Oeser Annette,
Oates John A.,
Milne Ginger L.,
Solus Joseph F.,
Chung Cecilia P.,
Stein C. Michael
Publication year - 2014
Publication title -
arthritis care and research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.032
H-Index - 163
eISSN - 2151-4658
pISSN - 2151-464X
DOI - 10.1002/acr.22169
Subject(s) - aspirin , medicine , platelet , thromboxane b2 , interquartile range , cyclooxygenase , thromboxane a2 , thromboxane , gastroenterology , metabolite , biochemistry , chemistry , enzyme
Objective Low‐dose aspirin prevents platelet aggregation by suppressing thromboxane A 2 (TXA 2 ) synthesis. However, in some individuals TXA 2 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 TXA 2 , serum thromboxane B 2 (sTXB 2 ), 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 sTXB 2 synthesis to <10 ng/ml represents suboptimal inhibition of platelet COX‐1 by aspirin. Results Aspirin almost completely suppressed sTXB 2 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.