Abstract P3102: Urinary thromboxane metabolites, circulating omega-3 and omega-6 fatty acids, and incident cardiovascular disease: results from the Framingham Heart Study

Background: Urinary thromboxane B2 metabolites (TXB 2 ) are biomarkers of systemic thromboxane A2 (TXA 2 ) activity, an eicosanoid synthesized from arachidonic acid (AA) that is recognized to contribute to cardiovascular disease (CVD) independent of its platelet effects. The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), produce downstream molecules that can suppress TXA 2 . Whether circulating EPA+DHA or AA may influence TXB 2 levels or modify its association with incident CVD is unknown. Aims: To investigate the relations of circulating EPA, DHA, and AA to urinary TXB 2 and to assess whether these fatty acids may modify the association between TXB 2 and incident CVD. Methods: We studied 2,524 participants in the Framingham Heart Study Offspring/Omni cohorts, who were free of CVD at baseline, with measurements of urinary TXB 2 and circulating EPA, DHA, and AA. Incident CVD included a composite of coronary heart disease, stroke, peripheral artery disease, heart failure, and cardiovascular mortality. Hazard ratio (HR) and 95% confidence interval (CI) of the association between urinary TXB 2 (comparing high vs low using pre-determined cut-offs) and CVD, were calculated using multivariable-adjusted Cox models. We analyzed the cross-sectional relationship between circulating EPA, DHA, and AA with TXB 2 and assessed the relation between a per-1 standard deviation increment in TXB 2 and CVD stratified by tertiles of EPA+DHA or AA. Results: Among non-aspirin users, median TXB 2 decreased across tertiles of EPA (T3 vs T1: 3696 vs 4486 pg/mg creatinine) and DHA (T3 vs T1: 3670 vs 4497) ( P trend <0.0005 for each) ( Table 1 ). On the other hand, TXB 2 increased with higher AA (T3 vs T1: 4378 vs 3857 ( P trend =0.009). Similar trends were seen among aspirin users. After a median 12.9 years of follow-up, 428 incident CVD events occurred. Higher urinary TXB 2 was associated with incident CVD, with HR (95% CI) of 1.61 (1.19, 2.18) for aspirin non-users and 1.36 (1.02, 1.81) for users. Higher EPA+DHA or AA did not appear to modify the association between TXB 2 and incident CVD ( P interaction >0.05 for each). Conclusion: Urinary TXB 2 is associated with incident CVD after accounting for standard CVD risk factors. While circulating EPA and DHA are inversely related to TXB 2 , the association of TXB 2 with incident CVD is consistent across levels of EPA+DHA, suggesting likely separate biological pathways linking TXB 2 and omega-3 fatty acids with CVD development.