MORE STUDIES FOCUSING ON POTENTIAL MECHANISMS
As empirical evidence emerges that consistently suggests that PTSD is involved in the etiology of CHD, more studies are focusing on potential mechanisms and biological alterations related to PTSD that may help to explain its association with CHD. It has long been observed that individuals with PTSD often exhibit hypocortisolism and corresponding alterations in hypothalamic-pituitary-adrenal axis regulation that seem to be linked with reduced responsiveness to glucocorticoids.23 Moreover, several studies have suggested an association of PTSD with inflammatory and autoimmune diseases, leading investigators to speculate that PTSD causes chronic low-level inflammation.21,24
As a result, studies focusing directly on the relationship between PTSD and inflammation or consequences of inflammation are beginning to appear. For example, one recent study compared levels of both proinflammatory and anti-inflammatory activity across patients with PTSD and age- and gender-matched controls without PTSD.25 Findings indicated the presence of a low-grade systemic proinflammatory state among patients with PTSD, and levels of proinflammatory activity were associated in a dose-response fashion with PTSD symptom levels. In another study, patients with PTSD were found to have more endothelial dysfunction, as measured by plasma concentrations of soluble tissue factor, compared with age- and gendermatched controls without PTSD.26
Another line of research has considered whether links between PTSD and CHD may be explained in part by alterations in vagal function.27 Various studies in small samples have found reduced heart rate vari ability and increased sympathetic activity at rest,28–30 with parasympathetic activity blunted in response to challenge or trauma reminder among PTSD patients compared with healthy individuals without PTSD.16,29,31 A similar line of work has considered the effect of PTSD on parasympathetic nervous system functioning by examining effects on baroreflex sensitivity. Arterial baroreflex responses contribute to parasympathetic tone and have been linked with psychosocial stress, carotid atherosclerosis, and increased risk of cardiovascular disease.32–34 Two studies have considered whether baroreflex sensitivity is reduced among individuals with PTSD relative to those without PTSD.35,36 One study, conducted among smokers, found reduced baroreceptor sensitivity among women but not men after controlling for demographics, medications, diagnostic characteristics, and smoking variables. 36 A second study, conducted among women only, found baroreceptor sensitivity to again be reduced among women with PTSD after controlling for a range of potential confounders, including comorbid psychiatric disorders.35 These women also appeared to have attenuated parasympathetic withdrawal response during a stressful challenge condition, similar to findings from studies of heart rate variability. Results from this small number of studies are somewhat preliminary, but given the consistency across these initial findings and other work linking related disorders (such as depression and anxiety) with reduced heart rate variability, ongoing work in this area is recommended.27
CAN IT BE SHOWN THAN PTSD PRECEDES CHD DEVELOPMENT?
One of the challenges for studying potential mechanisms and biological alterations that explain how PTSD might influence the development of CHD is establishing that PTSD actually precedes the biological change under study. Much of the research to date compares individuals with PTSD or high levels of PTSD symptoms to individuals without PTSD or its symptoms. As a result, these studies cannot definitively determine whether PTSD caused the biological alteration or if presence of the biological alteration preceded PTSD and in fact increased susceptibility to the disorder.23 Convincing evidence that PTSD is involved in the etiology of CHD will include demonstrating that PTSD precedes the biological changes posited to contribute to the development of CHD.
Suggestive evidence from an animal model
One recent study in animals provides some reassurance that the posited direction of effects for the research reviewed above is plausible. Using an animal model of PTSD, rats were randomly assigned to exposure to a severe stress (a predator) for 10 minutes or to a control group.37 Behavioral reactions were tested 7 days after the stress exposure, and measures of ACTH, prolactin, and heart rate variability were obtained. Rats exposed to extreme stress demonstrated behavioral and biological changes commensurate with disruptions expected with PTSD. For example, stressed rats exhibited increased plasma ACTH, higher heart rate, lower heart rate variability, and many more maladaptive behaviors when compared with control rats. Since the animals were randomly assigned to exposure to severe stress, it is unlikely that these effects could be attributed to biological differences between the groups at baseline. Moreover, clear biological changes were evident as a result of exposure to severe stress. Taken together, these findings provide some reassurance that PTSD may have biological sequelae that in turn influence the risk of CHD, although prospective studies of PTSD and biological alterations in human populations clearly are needed.
AS PTSD PREVALENCE RISES, URGENCY FOR INSIGHTS INCREASES
PTSD occurs commonly in the general population but is of particular concern for individuals working in high-risk service occupations and in the military. With ongoing conflicts we may expect to see significant increases in the population prevalence of PTSD. Giving due consideration to the burden of illness associated with PTSD has added urgency, as recent studies have highlighted problems with access to and quality of mental health care.19,38 Thus, understanding the relationship between PTSD and CHD remains critical. Insights obtained from this work may increase our understanding of how biological susceptibility to heart disease develops and may aid in identifying strategies for disease prevention and intervention.