Anxiety Reduces Baroreflex Cardiac Control in Older Adults With Major Depression LANA L. WATKINS,PHD, PAUL GROSSMAN,PHD, RANGA KRISHNAN, MD, AND JAMES A. BLUMENTHAL,PHD Objective: Although depression and anxiety predict risk of cardiac mortality, the contributions of depression and anxiety to vagal cardiac control have not been systematically evaluated. The goal of this study was to examine the relationship between state anxiety and vagal control of heart rate in older adults with major depressive disorder (MDD). Older adults (50 –70 years old) were selected for this study because of the greater cardiac risk associated with low vagal cardiac control across this age range. Methods: Fifty-six men and women with MDD were evaluated. MDD was diagnosed using the Diagnostic Interview Schedule, and severity of depression was measured using the Beck Depression Inventory and the Hamilton Rating Scale for depression. State anxiety was measured using the Spielberger State Anxiety Inventory. Power spectral analysis was used to measure two indices of vagal control: baroreflex control of heart rate (BRC SPEC ) and respiratory sinus arrhythmia (RSA). Results: State anxiety was negatively correlated with levels of BRC SPEC (r =-0.32, p  .05), whereas depression severity was not related to either RSA or BRC SPEC . Furthermore, BRC SPEC was reduced by approximately 33% in MDD patients with state anxiety scores (ST-ANX) in the highest quartile (ST-ANX  41, N = 13), compared with patients with ST-ANX scores in the lowest quartile (ST-ANX  25, N = 14; p  .05). Conclusions: Anxiety, but not depression severity, is associated with reduced BRC SPEC in older men and women. Future studies are needed to determine whether comorbid anxiety contributes to the increased cardiovascular risk associated with MDD. Key words: baroreflex control of heart rate, respiratory sinus arrhythmia, spectral analysis, Spielberger State Anxiety Inventory, Beck Depression Inventory, Hamilton Rating Scale for Depression. HR = heart rate; HRV = heart rate variability; CAD = coronary artery disease; MDD = major depressive dis- order; RSA = respiratory sinus arrhythmia; BRC SPEC = baroreflex control of heart rate; BDI = Beck Depression Inventory; HRSD = Hamilton Rating Scale for Depres- sion; ST-ANX = state anxiety score; SBP = systolic blood pressure; DBP = diastolic blood pressure; BMI = body mass index; bpm = beats per minute; BRC PHEN = baroreflex sensitivity assessed with phenylephrine in- jection. INTRODUCTION It is well established that impaired autonomic ner- vous system control of HR, defined by low HRV, pre- dicts cardiac mortality (1– 4). Although the role of sympathetic hyperactivity in the genesis of malignant arrhythmias is well documented (5, 6), recent studies have demonstrated that low levels of protective vagal reflexes are a powerful marker of risk of arrhythmias (7–9). In particular, reduced baroreceptor-mediated vagal reflex control of HR has been associated with life-threatening arrhythmias (10, 11) and fatal cardiac events in patients (12–14) and in experimental animal models of myocardial ischemia (7, 8, 15). Loss of the protective effects of vagal activation has been postu- lated to increase the vulnerability to sympathetically driven ischemia and malignant arrhythmias. Recently, it was demonstrated that patients with CAD who have MDD have reduced HRV compared with nondepressed CAD patients (16, 17). These find- ings have been interpreted to suggest that impaired vagal cardiac control may contribute to the excess cardiac mortality associated with depression (18 –20). However, in healthy volunteers, the presence of de- pression has not been found to be related to reduced HRV (21–23). One possible explanation for the inconsistent effects of depression on cardiac autonomic control is that the presence of anxiety confounds the relationship be- tween depression and HRV. High levels of anxiety are common in patients with depression (24), with esti- mates of comorbid anxiety as high as 67% in patients with depressive disorder (25). In addition, several studies have demonstrated a relationship between symptoms of anxiety and reduced HRV. For example, anxiety symptoms are associated with lower HRV mea- sured by the standard deviation of resting HR (26 –28), as well as that measured by more selective measures of vagal cardiac control (28 –32). Interestingly, abnor- mally low vagal control was observed recently in de- pressed patients with high anxiety but not in de- pressed patients with low anxiety (22), suggesting that anxiety may moderate the relationship between de- pression and reduced HRV. The lack of consistent effects of depression on HRV may also be related to the failure to consider the severity of depression when From the Duke University Medical Center, Department of Psychi- atry and Behavioral Sciences, Durham, North Carolina (L.L.W., R.K., J.A.B.); and Hebrew Rehabilitative Center for the Aged, Boston, Massachusetts (P.G.). Address reprint requests to: Dr. Lana Watkins, Department of Psychiatry and Behavioral Sciences, Box 3119, Duke Medical Cen- ter, Durham, NC 27710. Email: watkins1@mail-wa.acpub.duke.edu Received for publication June 12, 1998; revision received Decem- ber 29, 1998. 334 Psychosomatic Medicine 61:334 –340 (1999) 0033-3174/99/6103-0334 Copyright © 1999 by the American Psychosomatic Society