Exaggerated Differences in Pulse Wave Velocity Between Left and Right Sides Among Patients With Anxiety Disorders and Cardiovascular Disease VIKRAM KUMAR YERAGANI, MBBS, FRCP(C), RAHUL KUMAR, MD, KARL JUERGEN BAR, MD, PRATAP CHOKKA, MD, AND MANUEL TANCER, MD Objective: To compare the left-right differences in pulse wave velocity (PWV) measures in normal controls and patients with anxiety disorders and cardiac disease. Pulses from the right and left sides of normal subjects are highly correlated at each segmental level. However, some evidence suggests that the right hemisphere has a greater effect on parasympathetic activity, as there may be a right hemisphere disadvantage in patients with low cardiac vagal function. Decreased vagal function is associated with vascular dysfunction and hypertension. Methods: We compared normal controls (n = 22), patients with anxiety (n = 26), and patients with cardiovascular disease (n = 72) using the Vascular Profiler (VP-1000), which enables the measurement of ankle and brachial blood pressure (BP) in both arms (brachial), both legs (ankle) and carotid artery, and lead I electrocardiogram and phonocardiogram. Using these signals, PWV, and arterial stiffness index % were calculated for the comparison of these measures on the right and left sides of the body. Results: Patients with anxiety and cardiovascular disease had significantly higher left-right differences in heart-ankle pulse wave velocity, brachial-ankle pulse wave velocity, and arterial stiffness index percentage compared with that of normal controls. Our data also showed significant differences between left-right vascular indices in patients with anxiety and cardiovascular disease (p  .00001); there was no such significant difference in normal controls. Conclusions: These results may implicate an exaggerated vagal withdrawal in the left extremities resulting in higher PWV in patients with anxiety and cardiovascular illness. Key words: pulse wave velocity, autonomic function, atherosclerosis, arterial stiffness index, cardiovascular mortality, anxiety. HR = heart rate; BP = blood pressure; PWV = pulse wave velocity; HF = high frequency (0.15– 0.5 Hz); PTT = pulse transit time; HA = heart-ankle; BA = brachial-ankle; ECG = electrocardiogram; PCG = phonocardiogram; VP = vascular profiler; BMDP = bio- medical data package; ANOVA = analysis of variance; MAP = mean arterial pressure; PEP = pre-ejection period; GAD = gener- alized anxiety disorder. INTRODUCTION P hotoplethysmography pulse signals are body site specific and show differences in pulse transit time, strength and shape, and variation of each over time. A recent study showed a high degree of correlation between the right and the left side signals (1). However, Erciyas et al. (2) reported a more sig- nificant suppression of vagal parasympathetic activity in stroke patients with right hemispheric lesions, which led them to conclude that the right hemisphere seemed to have a greater effect on parasympathetic activity. Malaspina et al. (3) also suggested a connection between right hemisphere disadvan- tage and low vagal cardiac function. On the other hand, Wittling et al. (4) reported that control of autonomic cardiac activity at the level of the cerebral cortex seemed to be characterized by a division of responsibility between the two hemispheres, sympathetic activity being mainly controlled by the right hemisphere and parasympathetic activity, by the left hemisphere. Bar et al. (5) examined the laterality of pupillary light reflexes and found differences between both eyes, sug- gesting cortical localization of central autonomic function. In another recent study, Foster and Harrison (6) found evidence for cerebral asymmetry in the regulation of heart rate (HR) and blood pressure (BP). However, we were unable to find any studies that compared the left-right differences in normal controls and patients with either psychiatric or cardiovascular disease without any apparent cerebral lesions. Some studies suggest a decrease in cardiac vagal function in conditions such as anxiety disorders, hypertension, and several cardiac diseases including coronary artery disease (7–12). This is important in light of the association between anxiety and an increase in cardiovascular mortality and sud- den death (13–16). In a recent study, we found significant correlations between pulse wave velocity (PWV) and R-R interval (interbeat interval) high frequency (HF) (0.15– 0.5 Hz) variability in patients with anxiety, which suggest de- creased cardiac vagal function in these patients (17). PWV is an important noninvasive marker of atherosclerosis (18 –21). PWV indicates the speed at which the pulse is transmitted from the heart to the end artery when blood is expelled during cardiac contraction. PWV is the most widely used measure of arterial stiffness in different clinical fields (22). The stiffer the arterial wall, the faster the arterial wave travels through the arterial wall. Carotid-femoral PWV reflects the stiffness of the large elastic arteries and is the most widely used measure of arterial stiffness. This is due to the fact that the atherosclerotic changes of the arterial wall begin at the aorta and stiffness of the aorta is related to cardiac afterload (23). Carotid-femoral PWV is useful in identifying patients with atherosclerosis as well as patients with a poor prognosis in cardiac disease (21,24 –26). Brachial-ankle PWV (BAPWV), which is derived from the heart-brachial and heart-ankle PWV (HBPWV and HAPWV) is a measure of arterial stiffness (27) and its phys- iological characteristics are closer to carotid-femoral PWV than to femoral ankle PWV (28). The reproducibility of this measure is good (27) and recent data suggest that higher values of BAPWV are associated with more advanced From the Department of Psychiatry and Behavioral Neurosciences (V.K.Y., M.T.), Wayne State University School of Medicine, Detroit, Michigan; Insti- tute of Cardiology (V.K.Y., R.K.), M.S. Ramaiah Institute of Cardiology, Bangalore, India; Department of Psychiatry (V.K.Y., P.C.), University of Alberta (V.K.Y., P.C.), Edmonton, Alberta, Canada; and Department of Psychiatry (K.J.B.), Friedrich Schiller University, Jena, Germany. Address correspondence and reprint requests to V. K. Yeragani, #411, 11135-83 Avenue, Edmonton, Alberta, Canada T6G 2C6. E-mail: Vikramyershr@yahoo.com Received for publication September 18, 2006; revision received June 9, 2007. DOI: 10.1097/PSY.0b013e3181574272 717 Psychosomatic Medicine 69:717–722 (2007) 0033-3174/07/6907-0717 Copyright © 2007 by the American Psychosomatic Society