Aspirin therapy and thromboxane biosynthesis in systemic lupus erythematosus.
Incomplete suppression of thromboxane biosynthesis during aspirin therapy is associated with increased cardiovascular risk. Since systemic lupus erythematosus (SLE) is associated with platelet activation and increased cardiovascular mortality, we compared thromboxane and prostacyclin biosynthesis in patients with SLE and control subjects, and measured inhibition of thromboxane excretion in aspirin-treated subjects. We measured the urinary excretion of 11-dehydro thromboxane B( 2) (TXB(2)) and 2,3-dinor 6-ketoPGF(1alpha) (PGI-M), the stable metabolites of thromboxane A(2) and prostacyclin, respectively, in 74 patients with SLE and 70 controls. In subjects who were not receiving aspirin, TXB(2) excretion was higher in patients with SLE [0.40 ng/mg creatinine (0.26-0.64), median (interquartile range)] than controls [0.31 ng/mg creatinine (0.23-0.44)] (P = 0.04), and in these patients, TXB(2) excretion correlated with disease activity (rho = 0.28, P = 0.03) and tumor necrosis factor alpha (rho = 0.48, P < 0.001). Aspirin therapy resulted in significantly lower TXB(2) excretion in controls (P = 0.01), but not in patients with SLE (P = 0.10), compared with subjects not receiving aspirin. Prostacyclin biosynthesis did not differ among patients and controls, and was not affected by aspirin (P all >0.35). Thromboxane biosynthesis is increased in SLE and is associated with disease activity. Additionally, response to aspirin may be attenuated in some patients with SLE.
Avalos
Ingrid
I
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2681, USA. ingrid.avalos@vanderbilt.edu
Chung
Cecilia P
CP
Oeser
Annette
A
Milne
Ginger L
GL
Borntrager
Holly
H
Morrow
Jason D
JD
Raggi
Paolo
P
Solus
Joseph
J
Stein
C Michael
CM
D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004351:Drug Resistance; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013928:Thromboxane A2 / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D013928:Thromboxane A2; D011464:Epoprostenol; D001241:Aspirin