PTSD: Cause and Consequence of Cancer, Cardiovascular Disease

Nancy A. Melville

January 26, 2017

Increasing evidence shows a bidirectional relationship between psychological stress and physical disease, as underscored in studies linking posttraumatic stress disorder (PTSD) to cancer as well as acute cardiovascular disease and stroke, according to two articles published in the Lancet.

In the first study, researchers outline the evidence supporting the role of PTSD as a potentially causative factor as well as a consequential factor in cardiovascular disease.

"We conclude that post-traumatic stress disorder is a risk factor for incident cardiovascular disease, and a common psychiatric consequence of cardiovascular disease events that might worsen the prognosis of the cardiovascular disease," the authors, led by Donald Edmondson, PhD, MPH, director of the Center for Behavioral Cardiovascular Health at Columbia University Medical Center, New York City, write.

Examples of the evidence include a large systematic review and meta-analysis, conducted by the investigators, involving five studies and more than 400,000 participants with follow-up from 1 to 30 years.

The review showed as much as a 53% increased risk for incident cardiac events or cardiac-specific mortality associated with PTSD, after adjustment for demographic, clinical, and psychosocial factors.

Although adjustment for depression reduced the association to 27%, the increased risk was still significant.

In a separate analysis of 46 cohort studies published in 2016 in the American Journal of Cardiology, researchers found that PTSD was associated with a significant increase in the risk for stroke (relative risk [RR], 2.36). The increased risk for stroke with anxiety in general was lower but was also significant (RR, 1.71).

PTSD and the fight-or-flight response to threat are linked to a "physiologic cascade" full of potential mechanisms related to the risk for cardiovascular events, including those involving hypothalamic-pituitary-adrenal activation and endothelial and inflammatory responses. These can lead to risks for hypercoagulability, as well as variability in heart rate and blood pressure, the authors note.

Dr Edmondson noted that some key symptoms may help clinicians identify those at risk for a PTSD-induced cardiovascular event.

"Increased heart rate and decreased heart rate variability, along with sleep difficulties, are likely the earliest and most easily recognizable indicators," he told Medscape Medical News. "These likely influence endothelial function and inflammation, which in turn contribute to atherosclerosis and cardiovascular risk."

The awareness of PTSD as a potential cause of cardiovascular disease is important in advancing the appreciation for the role of psychosocial factors in cardiovascular disease, Dr Edmondson noted.

"There is growing recognition in both psychiatry and cardiology that the low-hanging fruit for reducing cardiovascular disease mortality is gone and that we now have to turn our attention to more complex psychosocial contributors to cardiovascular disease risk in order to continue the promising trends of the last decades. PTSD may be one of the clearest of those psychosocial targets," he said.

With respect to cardiovascular disease having a causative role in PTSD, the amount of research is less advanced, although meta-analyses suggest that PTSD symptoms are indeed common following cardiovascular disease events.

Dr Edmondson noted that a variety of traumatic environmental factors associated with an acute coronary event can lead to PTSD.

"We have seen that environmental factors during evaluation and treatment for acute coronary syndrome influence risk for PTSD. For example, patients who are evaluated in overcrowded emergency departments, perceive poor clinician-patient communication, or are exposed to other patients who appear close to death in the ED are at increased PTSD risk. Similarly, ICU stay is associated with increased PTSD risk," he said.

Some studies have shown higher rates of PTSD among individuals following cardiac events. The results from three studies in one meta-analysis suggested that PTSD after a cardiac event was associated with a doubling of the risk for recurrence of a cardiovascular event or for mortality.

The findings suggest multiple potential benefits from being able to treat PTSD before and after a cardiac event as early as possible.

"Interventions to reduce the stress of cardiovascular disease evaluation and treatment may be most cost-effective, in that they may reduce both PTSD and secondary cardiovascular disease risk while also improving patient satisfaction in all patients," said Dr Edmondson.

"For those who develop PTSD after a cardiovascular disease event, standard psychotherapy treatments that have been shown effective in non-cardiovascular-disease populations, such as cognitive processing therapy or prolonged exposure, are currently our best options."

PTSD and Cancer

In the second article, a qualitative review of PTSD and cancer, the authors report that studies involving various cancer types, including lung and breast cancer, show rates of traumatization and stress symptoms in approximately 37% to 60% of cancer survivors.

"Thus, evidence suggests that cancer might be experienced as traumatic by some – though not all – people who face cancer," the authors write.

In response to various studies providing evidence of the association, the DSM-IV-TR was expanded to include the diagnosis and treatment of a life-threatening illness as a stressor that could lead to the disorder.

With cancer, the elongated sequence of traumatic events potentially leading to PTSD can begin even before a diagnosis, during the "cancer scare" stage of detection of an abnormality, with anxiety heightening through the progression of diagnosis, staging, and histology procedures, the investigators note.

The experience can only get more traumatizing with treatment, chemotherapy, side effects, and particularly life-threatening invasive procedures.

Cancer survivors who make it through the ordeal can face ongoing anxiety over recurrence.

"While the existential threat of a cancer diagnosis is real, some patients' seemingly excessive reaction to diagnosis and treatment may be related to a PTSD-like response involving intrusive rumination, avoidance of the diagnosis and treatment, excessively negative thoughts about its implications, and excessive arousal," first author David Spiegel, MD, associate chair of psychiatry in the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, California, told Medscape Medical News.

"Patients can be helped to put this situation into perspective, but recognition of trauma-related reactions and means of help with them is available and important."

Dr Spiegel noted that such awareness of the risk for PTSD is often lacking in oncology.

"Most doctors expect a 'rational' response that is in keeping with actual risks," he said.

Studies have highlighted correlates associated with PTSD and cancer. They include having a precancer diagnosis of trauma or PTSD, a lifetime history of trauma or PTSD, low socioeconomic status, young age, limited or negative social support, advanced disease, or invasive treatment.

Clinicians should also watch for certain warning signs of potential PTSD, which can include "excessive preoccupation with cancer-related risks or, conversely, unusual avoidance of dealing with the disease or its treatments," Dr Spiegel said.

Other clues can include "irritability, hopelessness – an undermodulated or apparently exaggerated reaction to the disease and its treatment."

Need for Trauma Screening

The evidence underscores the need for psychosocial assessment in the oncology setting during treatment as well as afterward, the authors note.

"Many patients with cancer undergoing treatment do not have the time or energy to seek care in a separate mental health setting; embedding psycho-oncology specialists in medical settings is crucial to patient-centred care," they add.

An assessment of patients' psychiatric and trauma histories should be a standard part of taking a history and performing a physical examination, and the clinician should determine whether a patient's current distress is associated with a preexisting condition or is a new response to the cancer diagnosis.

Ongoing screening, as outlined in the National Comprehensive Cancer Network's clinical practice guidelines, should include management of stress. Evidence-based PTSD treatments, such as prolonged exposure or cognitive processing therapy, should be considered.

In a previous study, Dr Spiegel and colleagues found important improvements in patient distress among women with advanced breast cancer who received group supportive therapy. Several studies since then have shown similar improvements.

The authors urge caution regarding the use of conventional PTSD medications for patients with cancer-related PTSD, owing to a lack of evidence on the appropriate pharmacology.

Although selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, as well as other psychiatric medications, have been used for cancer-related anxiety, clinicians should be aware of potential interactions with existing medications or comorbidities.

The authors note, for example, that some antidepressants, such as fluoxetine, fluvoxamine, and paroxetine, can lower serum concentrations of endoxifen, which is the active tamoxifen metabolite, possibly reducing the drug's effectiveness.

"Thoughtful and careful assessment and development of appropriate treatment pathways can optimise detection and management of distress and traumatic stress in the oncology setting," they concluded.

The authors report no relevant financial relationships..

Lancet Psychiatry. Published online January 18, 2017. Article 1 abstract, Article 2 abstract

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