Age-Related Platelet Cox-1 Upregulation in Atrial Fibrillation

Aging is associated with enhanced platelet activation that may contribute to the occurrence of cardiovascular events. However, the mechanism linking aging with platelet activation is not fully understood. The objective of this study is to investigate the relationship between aging, platelet Cox-1 expression, and thromboxane (Tx) B2 production in patients with atrial fibrillation. Serum Cox-1 and TxB2 were measured in 134 patients with atrial fibrillation. Correlations were assessed between age, Cox-1, and TxB2. A robust mediation analysis evaluated whether Cox-1 mediates the association between age and TxB2. In vitro experiments were performed in 20 patients to evaluate the effect of aspirin on platelet TxB2 production and to quantify platelet Cox-1 expression across age groups (i.e., < or ≥65 years). Serum Cox-1 and TxB2 progressively increased by decades of age. A positive and significant correlation was found between age and Cox-1 (R = 0.42, p-values < 0.01), age and TxB2 values (R = 0.44, p-value < 0.01), and Cox-1 and TxB2 (R = 0.5, p-value < 0.01). Cox-1 partially and significantly mediated the effect of age on TxB2 (β = 5.23, 95% confidence interval [2.33-8.63]) for the effect of age on TxB2. In vitro analysis showed a reduced inhibitory effect of aspirin on platelet TxB2 production in old compared to young subjects (IC₅₀ 97 μM and 49 μM in ≥ and <65 years, respectively) that was paralleled by Cox-1 overexpression in patients ≥65 years. Platelet Cox-1 expression was inversely related with aspirin inhibitory effects (R = -0.640, p-value < 0.01). Aging is associated with a concomitant increase in Cox-1 concentration and TxB2 production and an impaired ability of aspirin to inhibit Cox-1.