Anxiety May Increase Cardiovascular Events, Death in Heart Disease Patients

Deborah Brauser

July 07, 2010

July 7, 2010 — Patients with stable coronary heart disease (CHD) plus generalized anxiety disorder (GAD) have a higher risk of experiencing cardiovascular events — such as stroke, myocardial infarction, and death — than patients with CHD only, according to a new cohort analysis from the Heart and Soul Study.

In fact, after adjusting for a variety of potentially confounding variables, GAD 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 Elisabeth J. Martens, PhD, from the Department of Medical Psychology at Tilburg University in the Netherlands, and colleagues.

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

The study is published in the July issue of the Archives of General Psychiatry.

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," Dr. Martens told Medscape Medical News. "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 GAD 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 GAD.

GAD 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 adjusting for age, the yearly rate of cardiovascular events was 9.6% for the CHD patients with GAD compared with 6.6% for those without the disorder (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.03 – 2.00; P = .03).

"After adjustment for demographic characteristics, comorbid conditions [including MDD], cardiac disease severity, and medication use, GAD remained associated with a 62% higher rate of cardiovascular events (HR, 1.62; 95% CI, 1.11 – 2.37; P = .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 = .01), they add.

Dr. 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 GAD. "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 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 GAD contributes to adverse events in patients with CHD and to test interventions to alleviate the risk," they write.

Treatment Studies Needed

"There's been a lot lately in the news about anxiety and heart disease, and this study is typical in a lot of ways," said Thomas Rutledge, PhD, associate professor in the Department of Psychiatry at the University of California–San Diego.

"It's a well-designed prospective cohort study that has more evidence suggesting that anxiety might be something our providers should be paying attention to among patients who were at risk for heart disease as well as depression. But it also suffers from a lot of the same kinds of problems we've seen in other studies," added Dr. Rutledge, who was not involved in the research.

"One of the nice things is that it took a diagnostic approach and some very sound, state-of-the art data in terms of talking about [GAD] as opposed to just a questionnaire approach," he noted.

"However, GAD 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, PTSD 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 GAD; we can't really say it's about anxiety overall."

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

He noted that he would 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 GAD, 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 Dr. Rutledge.

This study was funded by the Veterans Affairs (VA) Epidemiology Program and the VA Health Services Research and Development service Career Development Program and by grants from the National Heart, Lung, and Blood Institute; the American Federation for aging Research; the Robert Wood Johnson Foundation; the Ischemia Research and Education Foundation; the Ischemia Research and Education Foundation; and the Nancy Kirwan Heart Research Fund. The study authors have disclosed no relevant financial relationships.

Arch Gen Psychiatry. 2010;67:750-758.

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