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Is posttraumatic stress disorder related to development of heart disease? An update*

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ABSTRACT

It has long been hypothesized that posttraumatic stress disorder (PTSD) increases coronary heart disease (CHD) risk; however, empirical evidence is limited. In the first prospective study to date, individuals with higher PTSD symptom levels had a significantly increased risk for CHD, after controlling for known coronary risk factors. PTSD indicates a chronic stress reaction and is hypothesized to influence CHD either by causing biological alterations that lead to cardiovascular damage, or by leading to adverse health behaviors that increase CHD risk. A key issue is whether PTSD contributes to the development of CHD, if PTSD and CHD share common pathways, or if CHD causes PTSD. Research combined across different disciplines suggests that prolonged or chronic stress does influence the development of CHD. A better understanding of the relationship will increase prevention and intervention efforts. Cardiologists may be most effective when they can recognize and manage emotional distress in practice.


 

References

We recently published the first prospective test of the hypothesis that individuals with higher levels of posttraumatic stress disorder (PTSD) symptoms are at higher risk of developing coronary heart disease (CHD). With colleagues from the Normative Aging Study, we used a questionnaire-based measure to assess PTSD in a sample of men who had served in the military and did not have CHD at the start of the study. All CHD end points were confirmed by a board-certified cardiologist. Over an average of 10 years of followup, for each standard deviation increase in symptom level, men had age-adjusted relative risks of 1.26 (95% confidence interval [CI], 1.05–1.51) for nonfatal myocardial infarction (MI) and fatal CHD combined. Results were maintained after controlling for all known coronary risk factors and replicated when considering an alternative measure of PTSD.1

Several aspects of the findings were particularly interesting. Cardiotoxic effects of PTSD symptoms were evident even though PTSD symptom levels were low to moderate in this group. In fact, few of the men would have met criteria for a PTSD diagnosis. There was also a dose-response relation between levels of symptoms and CHD risk, suggesting individuals with significantly higher levels of distress would be at considerably greater risk. Moreover, effects of PTSD symptoms on angina were significantly weaker than effects on MI and fatal CHD, each an objectively verified outcome. These results suggest that individuals with PTSD do not merely appear to be ill because they report more pain. Effects were also maintained even after accounting for potentially damaging health behaviors that have often been linked with PTSD. Finally, because PTSD and depression often occur together and since depression has been identified as a risk factor for CHD, an ongoing debate has considered whether PTSD per se may have cardiotoxic effects, or if effects can be explained by its association with depression. Findings from this study indicated that PTSD symptoms were associated with CHD, independent of depression.

NATURE OF PTSD

PTSD has been identified as a marker of extreme distress in response to a potentially traumatic event and may also be indicative of a chronic stress reaction. Diagnosis of PTSD is often difficult because PTSD symptoms overlap with those of anxiety and affective disorders, both of which are generally more recognized. However, unlike depressive and anxiety disorders, PTSD is defined by the combination of exposure to a potentially traumatic event (eg, combat, sexual assault, or serious natural disaster) and the occurrence of three types of symptoms: reexperiencing the traumatic event, avoidance of traumatic reminders and emotional numbing, and hyperarousal.2 The time course of PTS can follow one of several patterns, where high levels of symptoms after traumatic exposure are followed by recovery, chronic symptoms persist over time, or symptoms relapse and remit.3 Since the disorder reflects dysregulation of the stress-response system, which is associated with potentially atherogenic processes, a link between PTSD and CHD has long been speculated.4

PATHWAYS BETWEEN PTSD AND CHD

Numerous studies have found that cardiovascular disease and its risk factors are more prevalent among individuals with PTSD.5–7 PTSD is hypothesized to contribute to the development of CHD, but because these studies have examined concurrent PTSD and cardiovascular disease or risk, they cannot determine the direction of causality. The causal relationship between PTSD and CHD has been hypothesized based on a model of prolonged stress reaction that posits that stress leads to impaired adaptation and increased wear and tear on the body. These processes may ultimately lead to atherosclerosis and cardiovascular system damage.8 Adults with PTSD exhibit neuroendocrinologic alterations characterized by enhanced negative feedback sensitivity of glucocorticoid receptors in the stress-response system and lower than normal urinary and plasma cortisol levels. Exaggerated catecholamine responses to trauma-related stimuli have also been found in adults diagnosed with PTSD.4 Higher concentrations of circulating catecholamines and increased total body sympathetic activity may eventually lead to autonomic nervous system dysfunction, including diminished heart rate variability, baroreflex dysfunction, and increased QT variability.9 Chronic stress and emotional arousal may also lead to or exacerbate endothelial damage and promote the development of atherosclerosis.

Another hypothesized pathway by which PTSD may influence CHD is through behavior. Studies have consistently demonstrated that individuals with PTSD are more likely to engage in adverse behaviors, which are themselves risk factors for CHD. For example, individuals with PTSD are more likely to smoke and to abuse alcohol.10,11 Interestingly, although these behaviors are generally believed to be on the causal pathway between PTSD and CHD, epidemiologic studies generally control for them. As a result, the magnitude of the association between PTSD and CHD may well be underestimated.

COULD THE ASSOCIATION BETWEEN PTSD AND CHD BE SPURIOUS?

At the heart of the endeavor to understand the relationship between PTSD and CHD is the question of whether PTSD actually leads to CHD through behavioral or biological alterations or if PTSD and CHD simply share common pathways. Another possibility is that the development of CHD (which itself can be a traumatic event) may cause PTSD.7 Biomedicine has generally been somewhat skeptical of the notion that feelings or psychological stress may lead to physical health outcomes, with three primary objections typically identified:

  • A third underlying factor (eg, one or more genes or toxic environmental exposures) may cause both PTSD and CHD
  • Most studies to date have been cross-sectional, leaving the question of causality unresolved

  • Even with prospective studies, findings may be explained by either unmeasured potential confounds (ie, physical activity) or residual confounding by inadequately measured factors.

Moreover, since PTSD can develop in response to physical trauma, it may be difficult to distinguish whether effects on CHD are due to physical harm or psychological stress reactions.

CONCLUSION

Support for the theory that PTSD is causally related to CHD is provided by the recent prospective findings and the fact that they are highly consistent with findings from work in related areas. Several studies have reported that exposure to trauma and adverse events increases the risk of CHD.12,13 Other research has suggested that trauma increases the risk of adverse health outcomes only when PTSD develops in response to the trauma.14,15 Moreover, there is a growing body of evidence that chronic stress in various forms (eg, work stress), as well as high levels of emotional distress, may increase risk of CHD.9 Findings from this body of work are less susceptible to the concern that physical trauma rather than psychological stress reaction is driving the effects. Other work has also linked PTSD with reduced vagal tone16 and hypercoagulability. 17 Taken together, research to date suggests that prolonged or chronic stress does play a role in the development of CHD.

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