October 2010
Reviewer: Jeff C. Huffman, MD
Scared to death? Generalized anxiety disorder and cardiovascular events in patients with stable coronary artery disease
Martens EJ, de Jonge P, Na B, Cohen BE, Lett H, Whooley MA
Arch Gen Psychiatry 2010; 67(7):750-758
Background: Depression in cardiac patients has been well established as a risk factor for cardiac events and mortality. Anxiety—and particularly anxiety disorders—have gone relatively understudied in this important population, despite the fact that anxiety is highly prevalent in this cohort. Specifically, there has been relatively limited information on whether generalized anxiety disorder (GAD) is associated with adverse cardiovascular events.
Methods: These results come from the Heart and Soul Study, a large prospective observational study of 1015 patients with stable coronary artery disease (such as CHF, prior MI, 50%+ stenosis, etc). Enrolling subjects underwent DSM-IV-based diagnostic interviews for GAD and for major depression at the outset of their participation. Substantial additional information on cardiac disease severity, cardiac risk factors, health behavior (e.g., smoking, alcohol, exercise), and potential biological mediators of links between anxiety and cardiovascular physiology (e.g, heart rate variability, C-reactive protein) was obtained at study outset. Subjects were monitored for cardiovascular events via yearly phone interviews for hospitalizations for ‘heart trouble’ followed by confirmatory investigation using medical records and other data sources. Associations between GAD and cardiovascular events were examined, first by bivariate analysis, and then via analysis that accounted for multiple potential confounding variables.
Results: Overall, 106 (10.4%) of subjects met criteria for GAD in the year preceding enrollment. Patients with GAD were more likely to have had ‘a cardiovascular event’ (MI, CVA, CHF, or all-cause mortality) than those with no GAD (9.6% vs. 6.6%; p=0.03). GAD continued to be associated with cardiac events after accounting for MDD diagnosis. When the 767 subjects with all available data were considered in a regression analysis, GAD remained an independent risk factor for cardiovascular events (hazard ratio= 1.74 (1.13-2.67); p=0.01).
Commentary: The relationship between anxiety and cardiac events has been of increasing recent interest, and this report emphasizes the potential great importance of this connection. These findings are similar to those found by Frasure-Smith and colleagues (Arch Gen Psychiatry 2008 Jan; 65(1):62-71) in a 2-year follow up study finding both MDD and GAD to be independently associated with cardiac events, and are consistent with a recently published meta-analysis by these authors linking post-MI anxiety with subsequent cardiac events (Psychosom Med 2010 Jul; 72(6):563-9).
Interestingly, this study found that patients with GAD did not have abnormal heart rate variability, catecholamines, or C-reactive protein, and these findings were independent of health behaviors (e.g., smoking, physical activity). Recent work in depression (e.g., Kop et al, Psychosom Med 2010; 72:626-635), has found some links between depression, ANS activity, inflammation, and cardiac outcomes, but most of the of the predictive value of depression on cardiac outcomes appears to remain unexplained by these biological factors. Likely the story is similar in GAD, and these findings leave open questions regarding the mechanism by which GAD may influence cardiac outcomes.
Clinically, a major implication of this work is that evaluation for GAD in cardiac patients, especially those at high risk for having GAD (e.g., those with a known mood disorder or another anxiety disorder), makes good sense, given that safe and effective treatments for GAD exist and given the increasingly established links between GAD and medical outcome.