Heart and Soul: More evidence linking anxiety and coronary heart disease

Deborah Brauser

July 09, 2010

Tilburg, the Netherlands - Patients with stable CHD plus generalized anxiety disorder have a higher risk of experiencing cardiovascular events—such as stroke, MI, and death—than patients with CHD only, according to a new cohort analysis from the Heart and SoulStudy[1].

In fact, after adjustment for a variety of potentially confounding variables, generalized anxiety disorder was associated with a 74% increased risk for adverse cardiovascular outcomes.

"A robust association . . . was found that could not be explained by disease severity, health behaviors, or biological mediators," write lead study author Dr Elisabeth J Martens (Tilburg University, the Netherlands) and colleagues in the July 2010 issue of the Archives of General Psychiatry.

"These findings have implications for clinical practice and research," add the study authors. "General anxiety disorder is common and treatable and could, therefore, be an important modifiable risk factor in patients with CHD."

The study is the latest in a series of analyses published in recent weeks linking cardiovascular disease and anxiety disorders.

Common combination

Although 24% to 31% of patients with CHD also have symptoms of anxiety, relatively few studies have looked at the role that anxiety may play—especially compared with the "extensive literature on depression in patients with CHD," the investigators write.

Plus, "studies examining anxiety as a risk factor for future CHD events have yielded conflicting results," they add.

"We previously found that the association between depressive symptoms and cardiovascular events was largely explained by poor health behaviors, especially physical inactivity, in depressed patients with CHD," Martens said in an interview. "For me, [this] was a great opportunity to be involved in a study that could shed more light onto the relationship between body and mind."

The investigators assessed 1015 San Francisco area outpatients with stable CHD from the Heart and Soul Study, which focused on the association between various psychological disorders and cardiovascular events.

All patients underwent interviews, blood and urine sample testing, exercise treadmill testing, and electrocardiography at their first baseline visit between September 2000 and December 2002. Follow-ups were then conducted until March 18, 2009.

A cardiovascular event was defined as "stroke, heart failure, myocardial infarction, transient ischemic attack, and death."

The presence of generalized anxiety disorder during the past year and of major depressive disorder (MDD) during the past month was determined with the computerized version of the Diagnostic Interview Schedule. A total of 106 patients (10.4%) were found to have generalized anxiety disorder.

Generalized anxiety disorder associated with higher cardiovascular risks

Results showed that 371 cardiovascular events occurred in the patients after an average follow-up time of 5.6 years.

After adjustment for age, the yearly rate of cardiovascular events was 9.6% for the CHD patients with generalized anxiety disorder compared with 6.6% for those without the disorder (hazard ratio [HR] 1.43; 95% CI 1.03-2.00; p=0.03).

"After adjustment for demographic characteristics, comorbid conditions [including MDD], cardiac disease severity, and medication use, general anxiety disorder remained associated with a 62% higher rate of cardiovascular events (HR 1.62; 95% CI 1.11-2.37; p=0.01)," report the study authors.

"Additional adjustment for a variety of potential behavioral and biological mediators had little effect on this association" (HR 1.74; 95% CI 1.13-2.67; p=0.01), they add.

Martens noted that "despite an exhaustive search for potential mediators," the investigators did not identify the exact reason for the increased risk of adverse cardiovascular outcomes associated with generalized anxiety disorder. "This was quite surprising."

The study authors write that possible reasons for the associations include that "anxiety may be associated with surges in catecholamines," that anxious patients with CHD may be less likely to seek preventive medical care due to an "avoidant coping strategy," or that these patients may be more likely to seek care and receive a diagnosis only once they have symptoms.

Another possibility is a common underlying factor that predisposes certain individuals. "The interplay of genetic factors or the programming effects of fetal or postnatal growth patterns may play a role," they add.

"The results of this study indicate the need for future research to identify the underlying processes by which general anxiety disorder contributes to adverse events in patients with CHD and to test interventions to alleviate the risk," they write.

Treatment studies needed

Commenting on the study, Dr Thomas Rutledge (University of California, San Diego) noted that generalized anxiety disorder is one of the most common anxiety disorders, "but there are a lot of others out there." Since many of the participants in this study were recruited among veterans, posttraumatic stress disorder may have been the more relevant anxiety disorder, while others may have suffered from social phobia or other form. "All we can really talk about in this study is general anxiety disorder; we can't really say it's about anxiety overall."

Rutledge also noted that anxiety often overlaps with depression. "Clinically, we need to be paying attention to both. Patients that have one are at much higher risk of having the other."

He noted that he'd like to see some future treatment studies that try to explain these relationships between psychological disorders and adverse cardiovascular outcomes.

"If we can take an identifiable condition like general anxiety disorder, treat patients, and then follow the changes in some of their behavior markers such as smoking, physical-activity level, and specific biomarkers that we think might be relevant, then I think this would all start to make more sense and be more credible medically. And then perhaps clinicians can actually alter the course of future heart disease risk," concluded Rutledge.

The study authors have disclosed no relevant financial relationships.

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