Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Abstract

BackgroundUrinary 11‐dehydro‐thromboxane (TX)B2 has been described as a potential predictive biomarker of major adverse cardiovascular events (MACEs) in high cardiac risk patients. This part of LTIMI (Leukotrienes and Thromboxane In Myocardial Infarction) study aimed to evaluate the relationship between 11‐dehydro‐TXB 2 and MACEs in patients with acute myocardial infarction (AMI).Methods and Results LTIMI was an observational, prospective study in 180 consecutive patients with AMI type 1 referred for primary percutaneous coronary intervention. On admission and at follow‐up visits (1 month, 1 year), 11‐dehydro‐TXB 2 was measured in urinary samples by using high‐performance liquid chromatography–tandem mass spectrometry. The primary outcome was occurrence of composite MACEs during 1‐year after AMI. Left ventricular ejection fraction was assessed in echocardiography on admission and at 1‐year follow‐up. Analyses of 11‐dehydro‐TXB 2 (pg/mg creatinine) were performed on log‐transformed data and expressed as median with IQR (Q1–Q3). 11‐Dehydro‐TXB 2 level on admission was 7.39 (6.85–8.01) and decreased at 1 month (6.73, 6.27–7.12; P<0.001) and 1‐year follow‐up (6.37, 5.91–6.94; P<0.001). In univariate analysis, baseline 11‐dehydro‐TXB 2 was higher in patients with MACEs (n=60; 7.73, 7.07–8.60) compared with those without MACEs (n=119; 7.28, 6.68–7.79; P=0.002). In multivariate regression model, 11‐dehydro‐TXB 2 and 3 other variables (diabetes, multivessel disease, and left ventricular ejection fraction) were found to be best 1‐year cumulative MACE predictors with odds ratio for 11‐dehydro‐TXB 2 of 1.58 (95% CI 1.095–2.33; P=0.017) and area under the curve (in receiver operating characteristic analysis of 0.8). Baseline 11‐dehydro‐TXB 2 negatively correlated with both left ventricular ejection fraction on admission (R=−0.21; P=0.006) and after 1 year (R=−0.346; P<0.001).Conclusions11‐Dehydro‐TXB 2 predicts 1‐year cumulative MACEs in AMI patients and provides prognostic information on the left ventricular performance.

Reduced Antiplatelet Effect of Aspirin Does Not Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease

“…Finally, serum TXB 2 measurement reflects the pharmacodynamics of low‐dose aspirin, and in CAD patients treated with aspirin, increased serum TXB 2 levels were related to adverse cardiovascular outcomes . Similar results were reported with urinary 11‐dehydro‐TXB 2 …”

“…6 Similar results were reported with urinary 11-dehydro-TXB 2 . 40,41 Some limitations of the present study must be acknowledged. Platelet-aggregation levels over time were not explored because platelet function was measured only once.…”

Differential Impact of Serial Measurement of Nonplatelet Thromboxane Generation on Long‐Term Outcome After Cardiac Surgery

“…Studies have emerged in recent years demonstrating that persistent TXA 2 generation in patients with cardiovascular disease undergoing aspirin therapy predicts an increased risk of atherothrombosis and death . Although initially assumed to be attributable to the failure of aspirin to inhibit platelet COX‐1–mediated thromboxane generation and consequent platelet activation, it is now recognized that aspirin is efficient at inhibiting platelet COX‐1 and that much of the residual TXA 2 generation in patients taking aspirin originates from nonplatelet sources .…”

“…Studies have emerged in recent years demonstrating that persistent TXA 2 generation in patients with cardiovascular disease undergoing aspirin therapy predicts an increased risk of atherothrombosis and death. 4,7,8 Although initially assumed to be attributable to the failure of aspirin to inhibit platelet COX-1-mediated thromboxane generation and consequent platelet activation, it is now recognized that aspirin is efficient at inhibiting platelet COX-1 and that much of the residual TXA 2 generation in patients taking aspirin originates from nonplatelet sources. [26][27][28] A unique feature of our analysis was that it only included subjects in whom inhibition of platelet thromboxane generation was verified, conclusively demonstrating that TXA 2 originating from nonplatelet tissue adversely affects clinical outcome and survival.…”

“…3 A substantial percentage of patients with cardiovascular disease continue to generate significant amounts of TXA 2 despite aspirin therapy, which places them at risk for adverse cardiovascular events. [4][5][6][7][8] Although initially thought to represent a failure of aspirin to inhibit platelet TXA 2 generation, emerging evidence suggests that residual TXA 2 generation derives principally from nonplatelet sources not suppressible by once-daily dosing regimens. 6,[9][10][11][12][13] In the RIGOR (Reduction in Graft Occlusion Rates) study, nonplatelet TXA 2 generation was identified as a novel risk factor for saphenous vein graft thrombotic occlusion after first-time coronary artery bypass graft (CABG) surgery.…”