Obesity and laboratory aspirin resistance in high-risk pregnant women treated with low-dose aspirin

BACKGROUND: Low-dose aspirin is used for preeclampsia prevention in high-risk women, but the precise mechanism and optimal dose are unknown. Evidence suggests that an imbalance in prostacyclin and thromboxane A(2) (TXA(2)) plays a key role in the pathogenesis of preeclampsia. Aspirin has a dose-dependent effect blocking production of TXA(2), a potent stimulator of platelet aggregation and promoter of vasoconstriction. Incomplete inhibition of platelet aggregation, designated aspirin resistance, can be reduced by increasing the aspirin dose. Evidence in the nonobstetric literature suggests that aspirin resistance may be more common among patients with a high body mass index. OBJECTIVE: To investigate the association of obesity on platelet-derived thromboxane inhibition in high-risk women treated with low-dose aspirin. MATERIALS AND METHODS: This was a secondary analysis of a prospective multi-centered study investigating the effect of low-dose aspirin (60-mg) administration in women at high risk for preeclampsia. Maternal serum TXB2 (an indirect measure of TxA(2)) levels were drawn at 3 time points: randomization (13-26 weeks' gestation), second trimester (at least 2 weeks after randomization and 24-28 weeks' gestation), and third trimester (34-38 weeks' gestation). Patients were included in the analysis if a TXB2 level was recorded at randomization and at least 1 time point thereafter. Patients were stratified by body mass index category and treatment arm. Median TXB2 levels were calculated at each time point, as well as rates of complete TXB2 inhibition (<0.01 ng/mL). A multivariate logistic regression analysis was performed to generate odds ratios (OR) for complete TXB2 inhibition by body mass index category, adjusting for maternal age, race, high-risk group at randomization, nulliparity, and rate of randomization less than 16 weeks' gestation. RESULTS: A total of 1002 patients were included in the analysis, 496 (49.5%) and 506 (50.5%) in the low-dose aspirin and placebo groups respectively. There were substantial decreases in TXB2 levels among low-dose aspirin-treated women in all body mass index categories. In contrast, women assigned to placebo did not show a marked decrease in TXB2 levels after randomization, and obese women had higher median TXB2 levels in both the second (16.5, interquartile range [IQR] 8.0-31.8 vs 14.0, IQR 6.9-26.7, ng/mL; P = .032) and third (15.7, IQR 7.6-28.5 vs 11.9, IQR 4.6-25.9, ng/mL; P = .043) trimesters. When comparing among stratified body mass index low-dose aspirin groups, women with class III obesity had the lowest odds of undetectable TXB2 levels in the second trimester (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.15-0.72) and third trimester (aOR, 0.30; 95% CI, 0.11-0.78) as well as at both time points (aOR, 0.09; 95% CI, 0.02-0.41). CONCLUSION: High-risk obese women receiving low-dose aspirin for the prevention of preeclampsia have lower rates of complete inhibition of TXB2. These data suggest that an increase in aspirin dosing or frequency may be necessary in this population.