Anxiety and Depression as Predictors of Cardiovascular Outcomes After Cardiac Surgery We read the article by Williams et al, 1 who curiously suggest that the relation between pre-existing anxiety and cardiac surgery outcomes has not been clearly defined, in fact referring to a past “failure to consider depression and anxiety simultaneously.” Putting the alleged “past failure” in appropriate context, several studies published during the past 6 years have elucidated the simultaneous role of anxiety and depression with respect to various cardiac surgery out- comes. 2e10 Overlooking previous studies would not be so conspicuous had Williams et al 1 used a questionnaire other than the Hospital Anxiety and Depres- sion Scale (HADS). A recent factor analysis has shown that the HADS does not clearly distinguish depression from anxiety, 11 questioning the extent to which anxiety and depression were independently measured. 1 A final limi- tation of previous research highlighted by Williams et al 1 was the sample size and, presumably, insufficient statistical power. Most of these cited studies 2e10 had sample sizes approximate to, or larger than, that in the study by Williams et al. 1 In fact, the study by Williams et al 1 provides a suitable exemplar of insuffi- cient statistical power in relation to the morbidity event rate that is reflected in the extraordinarily large confidence intervals spanning a 1- to 20-fold morbidity risk of HADS anxiety scores >11 (odds ratio 5.1, 95% confidence interval 1.27 to 20.2). In conclusion, the limitations of the HADS construct val- idity, the width of the confidence interval for anxiety, and the lack of any clear hypothesis suggests that the study by Williams et al 1 will not overcome previous limitations or markedly add to understanding of the role of anxiety on cardiac surgery outcomes as was claimed. Phillip J. Tully, PhD Adelaide, Australia Andrea Székely, MD, PhD Budapest, Hungary 21 December 2012 1. Williams JB, Alexander KP, Morin J-F, Langlois Y, Noiseux N, Perrault LP, Smolderen K, Arnold SV, Eisenberg MJ, Pilote L, Monette J, Bergman H, Smith PK, Afilalo J. Preoperative anxiety as a predictor of mortality and major morbidity in patients aged >70 years undergoing cardiac surgery. Am J Cardiol 2013;111:137e142. 2. Szekely A, Balog P, Benko E, Breuer T, Szekely J, Kertai MD, Horkay F, Kopp MS, Thayer JF. Anxiety predicts mortality and morbidity after coronary artery and valve surgery—a 4-year follow-up study. Psychosom Med 2007;69:625e631. 3. Oxlad M, Stubberfield J, Stuklis R, Edwards J, Wade TD. Psychological risk factors for cardiac-related hospital readmission within 6 months of coronary artery bypass graft surgery. J Psychosom Res 2006;61:775e781. 4. Tully PJ, Pedersen SS, Winefield HR, Baker RA, Turnbull DA, Denollet J. Cardiac morbidity risk and depression and anxiety: a disorder, symptom and trait analysis among cardiac surgery patients. Psychol Health Med 2011;16:333e345. 5. Tully PJ, Bennetts JS, Baker RA, McGavigan AD, Turnbull DA, Winefield HR. Anxiety, depression, and stress as risk factors for atrial fibrillation after cardiac surgery. Heart Lung 2011;40:4e11. 6. Tully PJ, Baker RA, Winefield HR, Turnbull DA. Depression, anxiety disorders and type D personality as risk factors for delirium after cardiac surgery. ANZ J Psychiatry 2010;44: 1005e1011. 7. Tully PJ, Baker RA, Turnbull D, Winefield H. The role of depression and anxiety symptoms and hospital readmissions after cardiac surgery. J Behav Med 2008;31:281e290. 8. Cserep Z, Losoncz E, Balog P, Szili-Torok T, Husz A, Juhasz B, Kertai MD, Gal J, Szekely A. The impact of preoperative anxiety and education level on long-term mortality after cardiac surgery. J Cardiothorac Surg 2012;7:86. 9. Tully PJ, Baker RA, Knight JL, Turnbull DA, Winefield HR. Neuropsychological function five years after cardiac surgery and the effect of psychological distress. Arch Clin Neuropsychol 2009;24:741e751. 10. Cserep Z, Balog P, Szekely J, Treszl A, Kopp MS, Thayer JF, Szekely A. Psychosocial factors and major adverse cardiac and cerebrovascular events after cardiac surgery. Interact Car- diovasc Thorac Surg 2010;11:567e572. 11. Cosco TD, Doyle F, Ward M, McGee H. Latent structure of the Hospital Anxiety And Depression Scale: a 10-year systematic review. J Psychosom Res 2012;72:180e184. http://dx.doi.org/10.1016/j.amjcard.2013.01.001 Reply We would like to thank Dr. Tully for bringing attention to a number of pertinent publications from the psychiatry literature, which, we believe reinforce our findings. Regardless of the instrument used to measure anxiety, the totality of the evidence points in a consistent direc- tion—demonstrating that anxiety is a key predictor of outcomes for patients under- going cardiac surgery. Whereas many of the publications cited by Dr. Tully concentrated on anxiety as a driver of long-term mortality and hospital read- missions, our study focused on anxiety as a predictor of short-term postoperative complications (an effect that persisted after adjusting for the Society of Thoracic Surgeons predicted risk). We selected the HADS instrument because of its desirable balance of prac- ticality and validity. The instruments used by Dr. Tully and the cited investi- gators were lengthy, including 40 anxiety-related questions (instead of 7 in the HADS-Anxiety module) and/or specialized neuropsychiatric interviews, which are not feasible for the average cardiovascular practitioner. The HADS has a long track record in clinical practice and has been repeatedly shown to be valid in differentiating anxiety from depression in various settings and in multiple languages. 1e4 Finally, despite the limited sample size in all these studies, the aggregated data have been concordant, highlighting the negative effects of anxiety before cardiac surgery. We look forward to ongoing prognostic data and, ultimately, to therapeutic studies aimed at reducing the morbidity caused by anxiety in our vulnerable cardiac surgery patients. Jonathan Afilalo, MD, MSc Montreal, Quebec, Canada Judson B. Williams, MD, MHS Karen P. Alexander, MD Durham, North Carolina 4 January 2013 1. Hunt-Shanks T, Blanchard C, Reid R, Fortier M, Cappelli M. A psychometric evaluation of the Hospital Anxiety and Depression Scale in cardiac patients: addressing factor structure and gender invariance. Brit J Health Psychol 2010;15:97e114. 2. Martin CR, Thompson DR, Barth J. Factor structure of the Hospital Anxiety and Depression Scale in coronary heart disease patients in three countries. J Eval Clin Pract 2008;14:281e287. 3. Helvik A-S, Engedal K, Skancke RH, Selbaek G. A psychometric evaluation of the Hospital Anxiety and Depression Scale for the medi- cally hospitalized elderly. Nord J Psychiatry 2011;65:338e344. 4. Wang W, Chair SY, Thompson DR, Twinn SF. A psychometric evaluation of the Chinese version of the Hospital Anxiety and Depression Scale in patients with coronary heart disease. J Clin Nurs 2009;18:1908e1915. http://dx.doi.org/10.1016/j.amjcard.2013.01.002 Prognostic Usefulness of C-Reactive Protein: Importance of the Diurnal Variation We read the report by Makrygiannis et al 1 regarding the prognostic usefulness of serial C-reactive protein (CRP) mea- surements in patients with ST-segment Readers’ Comments 1079