Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Impaired Responses to Aspirin in Patients with Systemic Lupus Erythematosus: The Role of Inflammation and Oxidative Stress.

Kawai1,  Vivian K., Avalos2,  Ingrid B., Oeser1,  Annette M., Oates1,  John A., Milne1,  Ginger L., Chung3,  Cecilia P., Stein1,  C. Michael

Vanderbilt University, Nashville, TN
Harvard University, Boston, MA
Vanderbilt Medical Center, Nashville, TN

Background/Purpose:

Aspirin is a widely used effective therapy for decreasing the risk of thrombosis. However, in some patients aspirin does not adequately suppress platelet thromboxane formation, a phenomenon termed "aspirin resistance". Many patients with lupus (SLE) have increased risk of thrombosis and thus receive aspirin. We previously reported that 15% of patients with SLE have impaired response to aspirin, and that this was associated with features of the metabolic syndrome (obesity, diabetes, and hypertension). The mechanism is unknown, but oxidative stress, which is associated with obesity and inflammation, has been implicated as contributing to this impaired response. Therefore, we tested the hypothesis that impaired response to aspirin in SLE is associated with increased oxidative stress.

Methods:

We prospectively studied 34 patients with SLE who had stable disease and no contraindication to aspirin therapy. Patients received immediate-release aspirin 81 mg/day for 7 days. NSAIDs were withdrawn for 7 days before and during the study. We collected blood and urine before and after aspirin treatment to measure concentrations of serum TxB2 (in whole blood allowed to clot at 37[cir]C) and urinary 8-iso prostanglandin F2a (F2-isoprostanes) excretion, a robust measure of oxidative stress. We defined an impaired response to aspirin as the inability to suppress serum TxB2 concentrations to <10 ng/ml. We compared urinary F2-isoprostane excretion in patients with and without impaired responses to aspirin. Continuous data are described as median with interquartile ranges [IQR].

Results:

Impaired response to aspirin was present in 15% (5/34) of patients with lupus. Patients with impaired aspirin response (n=5) were 60% female, age 45 [34–46 years], and those who were aspirin sensitive (n=29) were 86% female, age 40 [29–48 years]) (p>0.05). SLE patients with impaired response to aspirin had higher BMI (36.2, [28.9–36.6 kg/m2] vs. 24.5, [22.3–27.7 kg/m2]), p=0.055) and serum CRP concentrations (17.2, [1.8–19.9 mg/L] vs. 0.9,[0.6–4.0 mg/L], p=0.018) (Fig 1), and were more likely to be obese (60% vs. 14%, p=0.018) and have diabetes (40% vs. 7%, p=0.034). However, urinary F2-isoprostane excretion did not differ significantly in aspirin insensitive (1.48, [1.37–2.82 ng/mg of creatinine]) and sensitive patients (1.56, [1.24–2.71 ng/mg of creatinine]) (p=0.933) (Fig 2).

Conclusion:

Oxidative stress, measured by urinary F2-isoprostane excretion, was not associated with variability in sensitivity to aspirin in patients with SLE. However, decreased sensitivity to aspirin was associated with inflammation, as measured by CRP concentrations.

To cite this abstract, please use the following information:
Kawai, Vivian K., Avalos, Ingrid B., Oeser, Annette M., Oates, John A., Milne, Ginger L., Chung, Cecilia P., et al; Impaired Responses to Aspirin in Patients with Systemic Lupus Erythematosus: The Role of Inflammation and Oxidative Stress. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1391
DOI:

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