Exaggerated platelet reactivity to physiological agonists in war veterans with posttraumatic stress disorder.

An association between traumatic stress and cardiovascular disease (CVD) is supported by various epidemiological studies. Platelet activation and binding of activated platelets to leukocytes contributes to the pathophysiology of CVD. Evidence of hyperactive sympathetic nervous system, altered expression of platelet α(2)-adrenoreceptors (α(2)AR), and altered platelet adenylate cyclase activity in patients with posttraumatic stress disorder (PTSD) suggest that platelet reactivity in PTSD may be altered as well. We tested whether platelet reactivity to increasing doses of adenosine-diphosphate (ADP), epinephrine (EPI), or their combination differs between war veterans with PTSD (n=15) and healthy controls (n=12). For this purpose, citrated whole blood was incubated with increasing concentrations of ADP (0.1, 1, 10 µM), EPI alone (10 nM, 100 nM, 1000 nM), or EPI (10 nM, 100 nM, 1000 nM) in combination with 0.1 µM ADP. A subset of samples was also incubated with 10 µM yohimbine (YOH), α(2)AR antagonist, to distinguish receptor-specific effects. Platelet CD62P expression and formation of platelet-leukocyte aggregates (PLA) [platelet-monocyte (P-Mo), -lymphocyte (P-Ly), and -neutrophil (P-Ne) aggregates] were measured using three-color flow cytometry. Platelet reactivity was higher in war veterans with PTSD when compared to controls, as determined by greater CD62P expression and formation of PLA in response to ADP alone or in combination with EPI. Platelet reactivity also correlated with the severity of PTSD symptoms. Preliminary experiments with YOH indicate that stress-associated EPI elevations may contribute to platelet activation through a α(2)AR-dependent mechanism. The enhanced platelet reactivity observed in our study may be the underlying mechanism contributing to the development of CVD in PTSD patients.

Homocysteine and serum lipids concentration in male war veterans with posttraumatic stress disorder.

The evidence of increased cardiovascular disease (CVD) risk in posttraumatic stress disorder (PTSD) is accumulating. The present study aimed to determine whether chronic, combat-related PTSD is associated with serum lipid and homocysteine concentrations that could indicate higher CVD risk. The authors tested 66 war veterans with PTSD, 33 war veterans without PTSD, and 42 healthy volunteers for serum concentrations of homocysteine, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides. All the subjects were men and the analyses were adjusted for age, body mass index and smoking. Potential influences of depression, anxiety, and psychotic symptoms on the outcome measures were checked by introducing the scores from the Hamilton Depression Rating Scale (HAM-D-17), the Hamilton Anxiety Scale (HAMA), and the Positive and Negative Syndrome Scale (PANSS) into the overall statistical model. No differences in total cholesterol, LDL-C, HDL-C and triglycerides were found between the groups. Non-smoking PTSD war veterans had higher homocysteine concentrations (mean=10.4 micromol/L, SD=1.7) when compared to non-smoking war veterans without PTSD (mean=8.2 micromol/L, SD=4.0, P=0.014) and both smoking (mean=8.7 micromol/L, SD=2.3, P=0.008) and non-smoking healthy volunteers (mean=8.8 micromol/L, SD=2.2, P=0.021). The results of our cross-sectional study are possibly confounded by many factors, especially behavioral and life-style related which are difficult to control comprehensively and might have influenced serum lipids and homocysteine concentration in a complex manner. An increase in the homocysteine concentration observed in the non-smoking PTSD patients needs further investigation with a carefully designed prospective study to confirm associated, possibly enhanced CVD risk.