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.


METHODS
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-PGF1alpha), 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- PGF1alpha 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.
Serebruany
Victor L
VL
HeartDrug Research Laboratories, Johns Hopkins University, 7600 Osler Dr., Suite 307, Towson, MD 21204, USA. Heartdrug@aol.com
Suckow
Raymond F
RF
Cooper
Thomas B
TB
O'Connor
Christopher M
CM
Malinin
Alex I
AI
Krishnan
K Ranga R
KR
van Zyl
Louis T
LT
Lekht
Vladimir
V
Glassman
Alexander H
AH
D015415:Biomarkers / Q000097:blood* / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003327:Coronary Disease / Q000097:blood* / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use*; D020280:Sertraline / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use*
D015415:Biomarkers; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C065162:desmethylsertraline