Scared to Death? Generalized Anxiety Disorder and Cardiovascular Events in Patients With Stable Coronary Heart Disease: The Heart and Soul Study | Cardiology | JAMA Psychiatry | JAMA Network
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    1 Comment for this article
    Exercise Training, Cardiorespiratory Fitness, and Anxiety
    Carl J. Lavie, MD | The John Ochsner Heart & Vascular Institute,
    To the Editor:
    We read with considerable interest the excellent paper by Martens and colleagues1 from The Heart and Soul Study in the last issue of the Journal demonstrating a strong association between anxiety and major cardiovascular (CV) events in patients with established coronary heart disease (CHD). Unlike 2 original investigations in the last issue of our leading clinical CV journal that were analyzed by Dimsdale,2 the paper by Martens et al1 accounted for self-reported physical activity( PA), as well as baseline exercise capacity. Nevertheless, we still feel that the true value of exercise training (ET) and cardiorespiratory fitness
    (CF) on psychological stress, including anxiety, is underappreciated.3
    Although our work has focused on the role of ET to improve symptoms of depression and depression-related increased mortality,4 there is substantial evidence that ET also improves anxiety symptoms.5,6 We previously demonstrated that patients with CHD have a high prevalence of anxiety (27%) that was successfully reduced to 12% after formal cardiac rehabilitation and ET.5 Moreover, young CHD patients (< 55 years) had a much higher prevalence (28% vs 14%; p<0.01) of anxiety than older patients (> 70 years), and both groups had marked reductions in the prevalence of anxiety symptoms (-69% and -32%, respectively) following formal ET programs.6 Most recently, we demonstrated that a global psychosocial stress (PSS) score (which combines scores for depression, hostility, as well as anxiety), strongly predicted 3-year mortality in 522 CHD patients following major CHD events.7 In fact, almost all of the excess mortality occurred in patients with high levels of PSS who did not improve CF (defined as = 10% increase in peak oxygen consumption) following a formal ET program. Very low mortality during follow-up was noted in those patients with low PSS as well as those with high PSS who significantly improved their CF. Additionally, a recent meta-analysis also demonstrates that ET significantly reduces anxiety symptoms.8
    Although the present paper by Martens et al1 suggests that anxiety predicts CV events in CHD patients independent of PA and estimated exercise capacity, we believe that our data suggests that ET is an effective modality for treating anxiety and other components of PSS, thus leading to a better prognosis. These data have been emphasized to the lay public,9 but we are concerned that the benefits of ET on psychological risk factors, including anxiety, have not been emphasized by general physicians, CV disease specialists or by the psychiatric community.
    Finally, we are also intrigued that patients with high anxiety in the current study had lower blood levels of omega-3 fatty acids. Certainly, we have emphasized the marked benefits of omega-3 in many aspects of preventive cardiology.10 It is appealing to speculate that omega-3 supplementation, combined with ET, could lead to additive benefits on psychological stress, anxiety, and major CV events, which should be assessed in prospective studies.
    Carl J. Lavie, M.D., FACC, FACP, FCCP Richard V. Milani, M.D., FACC, FAHA The John Ochsner Heart & Vascular Institute New Orleans, LA 70121
    Thomas J. Lavie, M.D. Department of Clinical Psychiatry Vanderbilt University School of Medicine Nashville, TN
    1. Martens EJ, de Jonge P, Na B, Cohen BE, Lett H, Whooley MA. Scared to death? Generalized anxiety disorder and cardiovascular events in patients with stable coronary heart disease. Arch Gen Psychiatry. 2010;67(7):750- 758.
    2. Dimsdale J. What does heart disease have to do with anxiety? J Am Coll Cardiol. 2010;56(1):47-48.
    3. Lavie CJ, Milani RV, Lavie TJ. Impact of cardiac rehabilitation, exercise training, and fitness on psychological distress. In: Psychological Factors and Cardiovascular Disorders: The Role of Stress and Psychosocial Influences. Leo Sher, ed. Nova Science Publishers, Inc. Hauppauge, NY. 2009, Chapter 14, pp. 313-329.
    4. Milani RV, Lavie CJ. Impact of cardiac rehabilitation on depression and its associated mortality. Am J Med. 2007;120(9):799-806.
    5. Lavie CJ, Milani RV. Prevalence of anxiety in coronary patients with improvement following cardiac rehabilitation and exercise training. Am J Cardiol. 2004;93(3):336-339.
    6. Lavie CJ, Milani RV. Adverse psychological and coronary risk profiles in young patients with coronary artery disease and benefits of formal cardiac rehabilitation. Arch Intern Med. 2006;166(17):1878-1883.
    7. Milani RV, Lavie CJ. Reducing psychosocial stress: a novel mechanism of improving survival from exercise training. Am J Med. 2009;122(10):931- 938.
    8. Herring MP, O'Connor PJ, Dishman RK. The effect of exercise training on anxiety symptoms among patients. Arch Intern Med. 2010;170(4):321-331.
    9. Ratey JJ, Hagerman E. SPARK: The revolutionary new science of exercise and the brain. New York: Little, Brown and Company. Hachette Book Group. January 2008; pp 101-102.
    10. Lavie CJ, Milani RV, Mehra MR, Ventura HO. Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J AM Coll Cardiol. 2009;54(7):585 -594.

    Conflict of Interest: None declared
    Original Article
    July 2010

    Scared to Death? Generalized Anxiety Disorder and Cardiovascular Events in Patients With Stable Coronary Heart Disease: The Heart and Soul Study

    Author Affiliations

    Author Affiliations: Department of Medical Psychology, Tilburg University, Tilburg (Drs Martens and de Jonge), Department of Psychiatry, University of Groningen, Groningen (Dr de Jonge), the Netherlands; Section of General Internal Medicine, VA Medical Center, San Francisco, California (Ms Na and Drs Cohen and Whooley); Department of Medicine, University of California, San Francisco (Drs Cohen and Whooley); and Department of Psychology, University of California, Irvine (Dr Lett).

    Arch Gen Psychiatry. 2010;67(7):750-758. doi:10.1001/archgenpsychiatry.2010.74

    Context  Anxiety is common in patients with coronary heart disease (CHD), but studies examining the effect of anxiety on cardiovascular prognosis and the role of potential mediators have yielded inconsistent results.

    Objectives  To evaluate the effect of generalized anxiety disorder (GAD) on subsequent cardiovascular events and the extent to which this association is explained by cardiac disease severity and potential behavioral or biological mediators.

    Design  Prospective cohort study (Heart and Soul Study).

    Setting  Participants were recruited between September 11, 2000, and December 20, 2002, from 12 outpatient clinics in the San Francisco Bay Area and were followed up until March 18, 2009.

    Participants  One thousand fifteen outpatients with stable CHD followed up for a mean (SD) of 5.6 (1.8) years.

    Main Outcome Measures  We determined the presence of GAD using the Diagnostic Interview Schedule. Proportional hazards models were used to evaluate the association of GAD with subsequent cardiovascular events and the extent to which this association was explained by potential confounders and mediators.

    Results  A total of 371 cardiovascular events occurred during 5711 person-years of follow-up. The age-adjusted annual rate of cardiovascular events was 9.6% in the 106 participants with GAD and 6.6% in the 909 participants without GAD (P = .03). After adjustment for demographic characteristics, comorbid conditions (including major depressive disorder), cardiac disease severity, and medication use, GAD remained associated with a 62% higher rate of cardiovascular events (hazard ratio, 1.62; 95% confidence interval, 1.11-2.37; P = .01). Additional adjustment for a variety of potential behavioral and biological mediators had little effect on this association (hazard ratio, 1.74; 95% confidence interval, 1.13-2.67; P = .01).

    Conclusions  In outpatients with CHD, a robust association between GAD and cardiovascular events was found that could not be explained by disease severity, health behaviors, or biological mediators. How GAD leads to poor cardiovascular outcomes deserves further study.