Relationship between release of platelet/endothelial biomarkers and plasma levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression

Objective: In a platelet/endothelial biomarker substudy of the Sertraline Anti-Depressant Heart Attack Randomized Trial (SADHART), the authors sought to determine whether plasma levels of sertraline and its primary metabolite N-desmethylsertraline affect the release of platelet/endothelial biomarkers. Method: Fifty-five acute coronary syndrome patients with depression were randomly assigned to receive sertraline (N = 23) or placebo (N = 32). Twenty-six serial plasma samples collected at week 6 (N = 12) and week 16 (N = 14) were analyzed. Platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), platelet/endothelial cell adhesion molecule 1 (PECAM-1), P-selectin, thromboxane B-2 (TxB(2)), prostacyclin (6-keto-PGF1 alpha), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin were measured by enzyme-linked immunosorbent assay. Concentrations of sertraline and N-desmethylsertraline were determined by liquid chromatography with fluorescence detection in autologous samples. Results: Strong, mostly time-dependent negative correlations were found for the plasma levels of sertraline and N-desmethylsertraline with PF4 (week 6: r = -0.69 and -0.33, respectively; week 16: r = -0.63 for both), beta-TG (week 6: r = -0.43 and -0.29; week 16: r = -0.66 and -0.57), PECAM-1 (week 6: r = -0.82 and -0.49; week 16: r = -0.60 for both), P-selectin (week 6: r = -0.82 and -0.49; week 16: r = -0.73 and -0.43), and TxB(2) (week 6: r = -0.66 and -0.59; and week 16: r = -0.64 and -0.41). Regression analysis revealed some borderline correlations for endothelial markers such as 6-keto-PGF1 alpha and E-selectin and a positive correlation for VCAM-1. Conclusions: This is the first documented evidence that plasma release of platelet/endothelial biomarkers is directly related to the levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. The clinical significance of these findings should be assessed in the setting of a randomized clinical trial.