PTSD Linked to Endothelial Dysfunction

Posttraumatic stress disorder (PTSD) is associated with impaired coronary distensibility and an increased risk for major adverse cardiac events (MACE), a new study shows.

Researchers report that PTSD was independently associated with impaired coronary distensibility, as reflected in the coronary distensibility index (CDI), as well as atherosclerosis and that it predicted MACE independent of age, sex, or other conventional coronary risk factors. Impaired coronary distensibility was also independently associated with the severity of PTSD symptoms.

These results clearly point to the important role of impaired CDI as a first step in the continuum of the actual manifestations of coronary atherosclerosis on PTSD and its related poor cardiovascular outcome,” Naser Ahmadi, MD, PhD, concluded. “This highlights incremental value of CDI in the identification and management of individuals with PTSD.”

Our conclusion was basically that there’s a significant linkage between these two that can be used as a prognostication tool, coronary distensibility, to screen patients who are at risk for future problems,” Dr Ahmadi told Medscape Medical News. It also supports a case for monitoring, he said, “because it’s related to the severity of symptoms, and that’s the direction that we’re heading next.”

Dr Ahmadi presented the results here at the American Psychiatric Association (APA) 2015 Annual Meeting.

What is post-traumatic stress disorder (PTSD)?

Post-traumatic stress disorder (PTSD) can develop following a traumatic event that threatens your safety or makes you feel helpless.

Most people associate PTSD with battle-scarred soldiers - and military combat is the most common cause in men - but any overwhelming life experience can trigger PTSD, especially if the event feels unpredictable and uncontrollable.

Post-traumatic stress disorder (PTSD) can affect those who personally experience the catastrophe, those who witness it, and those who pick up the pieces afterwards, including emergency workers and law enforcement officers. It can even occur in the friends or family members of those who went through the actual trauma.

PTSD develops differently from person to person. While the symptoms of PTSD most commonly develop in the hours or days following the traumatic event, it can sometimes take weeks, months, or even years before they appear.

Endothelial Dysfunction

Previous studies have linked PTSD to cardiovascular disease, including myocardial infarction, but “a conclusive link between PTSD and atherosclerosis has not been made,” he said.

PTSD Linked to Endothelial Dysfunction A recent article, for example, showed that PTSD was linked to increasing levels of coronary artery calcium. In comparison with those participants who did have have PTSD, the presence of PTSD was associated with increased risk for death at the same levels of coronary artery calcium.

Coronary endothelial-dependent microvascular dysfunction is an early reversible process in coronary artery disease (CAD) and is associated with poor clinical outcome, he noted.

PTSD can occur at any age, including childhood. The disorder can be accompanied by depression, substance abuse, or anxiety. Symptoms may be mild or severe - people may become easily irritated or have violent outbursts. In severe cases, they may have trouble working or socializing. In general, the symptoms seem to be worse if the event that triggered them was initiated by a person - such as a murder, as opposed to a flood.

Ordinary events can serve as reminders of the trauma and trigger flashbacks or intrusive images. A flashback may make the person lose touch with reality and reenact the event for a period of seconds or hours, or very rarely, days. A person having a flashback, which can come in the form of images, sounds, smells, or feelings, usually believes that the traumatic event is happening all over again.

Posttraumatic stress disorder can be treated, usually with a combination of psychotherapy and medications (for specific symptom relief, such as for the common accompanying depressive feelings). People with PTSD should seek out a therapist or psychologists with specific experience and background in treatment posttraumatic stress disorder.

Impaired CDI is an endothelial-dependent process and is associated with vulnerable plaque composition and cardiovascular mortality. “We recently reported that PTSD is independently associated with impaired CDI,” Dr Ahmadi said.

In this study, they investigated the relationship of impaired CDI, as measured by CT angiography, with PTSD, as well as the combination of impaired CDI and PTSD with MACE, using data from the Veterans Health Administration, the largest healthcare system in the United States, which provides comprehensive physical and psychological care for veterans.

The study included 246 participants (mean age, 63 years; 12% women) with PTSD (n = 50) and without PTSD (n = 196). All underwent clinically indicated CT angiography (CTA) and CDI assessment, as well as assessment of psychological status to distinguish patients with PTSD from those without PTSD. CDI in the left anterior descending artery (LAD) was defined as follows: [(Early diastole - mid diastole lumen cross-section area (CSA) ÷ (lumen CSA in mid diastole × central pulse pressure) x 1000].


The PTSD Checklist–Military (PCL-M), and the Clinician Administered PTSD Scale (CAPS) were used to diagnose PTSD.

Electronic medical record review was used to determine diagnoses and outcomes; patients were followed for a mean of 50 months. MACE was defined as myocardial infarction or cardiovascular death. The investigators used survival regression to assess the relation of impaired CDI and PTSD with MACE.

The primary endpoint was the occurrence of myocardial infarction or cardiovascular death, verified by the Social Security Death Index obtained from electronic medical records, telephone interview follow-up, and primary physician verification.

They found that CDI was significantly lower in patients with PTSD than in patients without PTSD (3.4 ± 1.4 vs 4.8 ± 1.5; P = .01). This effect was more prominent in women than men (P = .0001).

CDI was inversely associated with severity of CAD and was more prominent in patients with PTSD than in patients without PTSD.

After adjustment for risk factors, the relative risk for MACE was 56% higher in those with PTSD than in those without PTSD (P = .001). Similarly, the relative risk for MACE was 95% higher with each unit decrease in CDI (P = .001).

However, regression analyses showed significant linkage between PTSD and impaired CDI with increased risk for MACE, Dr Ahmadi said. After adjustment for age, sex, conventional risk factors, and CTA-diagnosed CAD, the relative risk for MACE was 234% higher with each unit decrease in CDI and presence of PTSD as compared with those without PTSD (P = .001).

Receiving operating characteristic (ROC) curves showed that the area under the curve for PTSD alone in predicting MACE was .69 but increased to .94 for the combination of PTSD, impaired CDI plus confirmed CAD.

After adjustment for risk factors, event-free survival was 98% among those without PTSD whose CDI values were normal; it was 86.2% for those without PTSD but whose CDI values indicated impairment; it was 89.5% for those with PTSD but with normal CDI; and it was 67.5% for those with both PTSD and impaired CDI (P = .001).

Further studies are warranted to investigate early diagnosis of PTSD and its related coronary atherosclerosis, and management can prevent MACE,” Dr Ahmadi concluded.

Their group is already investigating further, Dr Ahmadi told Medscape Medical News. In one study, they are investigating whether treatment of PTSD can positively affect coronary distensibility. They hope to then conduct a longer-term study to see whether successful PTSD intervention at an early stage might prevent long-term MACE.

The authors report no relevant financial relationships.


American Psychiatric Association (APA) 2015 Annual Meeting. Psychosomatic and consultative psychiatry presentation 1. Presented May 18, 2015.

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