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 AntiDepressant 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), β-thromboglobulin (β-TG), platelet/endothelial cell adhesion molecule 1 (PECAM-1), P-selectin, thromboxane B₂ (TxB₂), prostacyclin (6-keto-PGF1α), 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), β-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 TxB₂ (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- PGF1α 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.