Age-Related Enhancement of COX-1–Mediated Thromboxane Production in Patients with Atrial Fibrillation
Selected Abstract – Spring Meeting 2026
Copyright (c) 2026 Emanuele Valeriani, Vittoria Cammisotto, Danilo Menichelli, Valentina Castellani, Simona Bartimoccia, Giovanni Cucchiara, Arianna Pannunzio, Ilaria Maria Palumbo, Roberto Carnevale, Francesco Violi, Pasquale Pignatelli
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Published: April 30, 2026
Abstract
Background: Enhanced platelet activation contributes to the increased cardiovascular risk of elderly patients with atrial fibrillation. The biological mechanisms underlying this phenomenon are not fully clarified. This study investigated whether age-related increases in serum thromboxane B₂ (TxB₂) are associated with platelet cyclooxygenase-1 (Cox-1) upregulation in older individuals.
Methods: Serum levels of Cox-1 and TxB₂ were assessed in patients with atrial fibrillation enrolled between 2022 and 2023. A subset of participants underwent in vitro analyses to evaluate the inhibitory effect of aspirin on platelet TxB₂ generation and to quantify platelet Cox-1 expression across different age groups (<65 vs. ≥65 years). The relationship between Cox-1 expression and aspirin-mediated inhibition of TxB₂ was also explored. Associations were analyzed using Spearman correlation, and mediation analysis was performed to assess indirect effects.
Results: The study included 134 patients. Age showed a positive correlation with both Cox-1 expression (R = 0.42, p <0.01) and TxB₂ levels (R = 0.44, p <0.01). Additionally, Cox-1 expression was positively associated with TxB₂ concentrations (R = 0.50, p <0.01). Mediation analysis demonstrated that Cox-1 partially mediated the relationship between age and TxB₂ levels (β = 5.23, 95% CI: 2.33–8.63). In vitro experiments revealed a reduced sensitivity to aspirin in older patients, as reflected by higher IC₅₀ values for inhibition of platelet TxB₂ production (96.78 μM in ≥65 years vs. 48.92 μM in <65 years). This reduced response was accompanied by increased platelet Cox-1 expression in the elderly group. Moreover, higher Cox-1 levels were inversely correlated with aspirin-induced inhibition of platelet TxB₂ (R = −0.64, p <0.01).
Conclusions: Advancing age is associated with increased thromboxane production, driven in part by platelet Cox-1 upregulation. This alteration is accompanied by a reduced capacity of aspirin to suppress Cox-1 activity, potentially contributing to the heightened thrombotic risk observed in elderly patients.
