Original article
Increased pulse-wave velocity in patients with anxiety: implications for autonomic dysfunction

https://doi.org/10.1016/j.jpsychores.2005.10.011Get rights and content

Abstract

Decreased vagal function is associated with vascular dysfunction. In this study, we compared vascular indices and correlated heart rate and QT variability measures with vascular indices in patients with anxiety disorders and normal controls. We compared age- and sex-matched controls (n=23) and patients with anxiety (n=25) using the Vascular Profiler (VP-1000; Colin Medical Instruments, Japan), approved by the US Food and Drug Administration. Using this machine, we obtained ankle and brachial blood pressure (BP) in both arms (brachial), both legs (ankle), and carotid artery, and lead I electrocardiogram (ECG) and phonocardiogram. Using these signals, pulse-wave velocity (PWV), and arterial stiffness index % and preejection period can be calculated. We also obtained ECG sampled at 1000 Hz in lead II configuration in supine posture to obtain beat-to-beat interbeat interval (R-R) and QT interval variability for 256 s. Patients with anxiety had significantly higher carotid mean arterial pressure (MAP) %, brachial-ankle PWV (BAPWV), arterial stiffness index %, MAP, and diastolic BP of the extremities compared to controls. We found significant negative correlations (r values from .4 to .65; P<.05 to .007) between R-R interval high-frequency (0.15–0.5 Hz) power (which is an indicator of cardiac vagal function), and increased BAPWV and systolic BP of the extremities only in patients. We were unable to find such correlations in controls. We also found significant positive correlations between QT variability index (a probable indicator of cardiac sympathetic function) and MAP of the extremities and BAPWV only in the patient group. These findings suggest an important association between decreased vagal and increased sympathetic function, and decreased arterial compliance and possible atherosclerotic changes and increased BP in patients with anxiety.

Introduction

Thickening of arterial walls occurs with aging, and risk factors such as smoking, obesity, high fatty-food intake, and several genetic factors influence this process. Atherosclerosis increases blood pressure (BP) and makes the heart a less effective “pump,” eventually leading to ventricular enlargement. This will lead to an increased load on the heart leading to an abnormality of cardiac electrical conduction, which may result in cardiac repolarization lability leading to serious cardiac arrhythmias. Thus, identifying these changes in the vessel walls is of paramount importance.

Pulse-wave velocity (PWV) indicates arterial stiffness and possible atherosclerosis [1], [2]. The noninvasive measurement of PWV can also be used as a prognostic indicator of vascular damage [3], [4], [5], [6]. Hence, this measure may have implications as a screening device for the general population as well [7], [8]. This measure is also valuable in the evaluation of vascular damage in conditions such as diabetes [9], [10]. Similarly, carotid artery patency is an important measure, especially in the earlier stages of stenosis. Vascular Profiler (Colin Medical Instruments, Japan) uses noninvasive techniques to obtain these vascular indices and, hence, is a valuable tool to study any population that is at a higher risk for cardiovascular/cerebrovascular mortality.

Several studies suggest that people with anxiety disorders as well as depression are at a higher risk for cardiovascular mortality and sudden death [11], [12], [13], [14], [15]. All our previous studies mainly focused on cardiac autonomic function in anxiety and depressive disorders compared to normal controls, and our findings suggest an altered sympathovagal balance in patients with panic disorder and depression, which partly contributes to an increased risk for cardiac mortality [16], [17], [18], [19], [20], [21], [22], [23]. Our findings generally show a decrease in heart rate variability (HRV) and an increase in QT variability (QTV) in patients with anxiety and depression [24], [25].

Decreased HRV is an important predictor of sudden cardiac death in patients with cardiac disease as well as normal subjects [26], [27], [28]. Spectral power in the high-frequency (HF; 0.15–0.5 Hz) band reflects respiratory sinus arrhythmia and, thus, cardiac vagal activity. Low-frequency (LF; 0.04–0.15 Hz) power is related to baroreceptor control and is dually mediated by vagal and sympathetic systems. [29], [30]. R-R LF/HF ratios may reflect cardiac sympathovagal interaction, although there is some evidence to the contrary [31], [32].

Cardiac repolarization lability plays an important role in causing sudden death. An increase in sympathetic activity and a decrease in cardiac vagal activity make the myocardium vulnerable to fatal arrhythmias [33], [34]. A recent measure, beat-to-beat QT interval variability appears to be an important and independent measure of cardiac mortality and severity of illness in patients with heart disease and also in coronary patients with effort angina pectoris [35], [36], [37]. We have found that beat-to-beat QT interval variability significantly increases during challenges associated with an increase in cardiac sympathetic activity including a change from supine to standing posture and administration of intravenous isoproterenol [24], [38], [39], [40], suggesting an influence of sympathetic system on QT interval variability. There is also other evidence linking QTV to cardiac sympathetic function [41], [42]. Several previous reports have shown abnormal sympathetic function in patients with anxiety disorders [43], [44], [45], [46], [47].

Our previous studies mainly dealt with cardiac autonomic function in anxiety and depressive disorders compared to normal controls, suggesting an altered sympathovagal balance in patients with panic disorder and depression, which probably contributes to an increased risk for cardiac mortality [16], [17], [18], [19], [20], [21], [22].

In this study, we compared several vascular indices including brachial-ankle PWV (BAPWV), arterial stiffness index, and BP between normal controls and age-matched patients with anxiety disorders. In addition, we also compared HRV and QT variability index (QTvi) and examined the relationship between these variables and the vascular indices.

Section snippets

Subjects

There were 23 normal controls (19 males and 4 females; age, 45±14 years) and 25 patients (20 males and 5 females; age, 45±13 years) with anxiety disorders. Both groups were matched for age and gender. All patients were of East Asian origin. The patients were consecutive outpatients whose complaint was mainly anxiety. Eight patients had generalized anxiety disorder, seven had panic disorder, and 10 had symptoms of both disorders. Eight of the 17 patients with a diagnosis of panic disorder had

Results

Table 1 shows the mean±S.D. of demographic data, HR and QTvi data, and vascular indices for normal controls and patients. The patients had significantly higher SAI scores, mean HR and QTvi (Table 1). Two-way ANOVA showed significant group differences for BAPWV (F=5.9; df=1,46; P=.02) and arterial stiffness index % (F=10.9; df=1,46; P=.002). Three-way ANOVA showed significant group differences for ankle-brachial MAP (F=4.9; df=1,46; P=.03) and DBP (F=9.6; df=1,46; P=.003). Patients with anxiety

Discussion

This report compares vascular indices in patients with anxiety compared to normal controls. As expected, the patients had significantly higher SAI scores. However, there were no significant differences in these scores among different groups of patients. We found a significantly higher carotid MAP %, BAPWV, arterial stiffness index %, and average MAP and DBP of the extremities in patients with anxiety disorder. These findings are important in the context of excess cerebrovascular/cardiovascular

References (57)

  • ED Lehman

    Clinical value of aortic pulse-wave velocity measurement

    Lancet

    (1999)
  • R Asmar et al.

    Assessment of arterial distensibility by autonomic pulse-wave velocity measurement: validation and clinical application studies

    Hypertension

    (1995)
  • JN Cohn

    Vascular wall function as a risk marker for cardiovascular disease

    J Hypertens

    (1999)
  • NM van Popele et al.

    Association between arterial stiffness and atherosclerosis: the Rotterdam study

    Stroke

    (2001)
  • S Laurent et al.

    Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients

    Hypertension

    (2001)
  • AP Guerin et al.

    Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure

    Circulation

    (2001)
  • R Asmar et al.

    Pulse-wave velocity as end point in large-scale intervention trial: the complior study: scientific quality control, coordination and investigation committees of the complior study

    J Hypertens

    (2001)
  • A Yamashina et al.

    Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse-wave velocity measurement

    Hypertens Res

    (2002)
  • Y Yamasaki et al.

    Asymptomatic hyperglycemia is associated with intimal plus medial thickness of the carotid artery

    Diabetologia

    (1995)
  • E Kimoto et al.

    Preferential stiffening of central over peripheral arteries in type 2 diabetes

    Diabetes

    (2003)
  • W Coryell et al.

    Mortality among outpatients with anxiety disorders

    Am J Psychiatry

    (1986)
  • MW Weissmann et al.

    Panic disorder and cardiovascular/cerebrovascular problems

    Am J Psychiatry

    (1990)
  • I Kawachi et al.

    Prospective study of phobic anxiety and risk of coronary heart disease in men

    Circulation

    (1994)
  • I Kawachi et al.

    Symptoms of anxiety and risk of coronary heart disease: the normative aging study

    Circulation

    (1994)
  • RM Carney et al.

    Depression and coronary heart disease: a review for cardiologists

    Clin Cardiol

    (1997)
  • RKA Radhakrishna et al.

    Decreased chaos and increased nonlinearity of heart rate time series in patients with panic disorder

    Auton Neurosci

    (2001)
  • VK Yeragani et al.

    Decreased R-R variance in panic disorder patients

    Acta Psychiatr Scand

    (1990)
  • VK Yeragani et al.

    Effects of yohimbine on heart rate variability in panic disorder patients and normal controls: a study of power spectral analysis of heart rate

    J Cardiovasc Pharmacol

    (1992)
  • Cited by (38)

    • One-day acceptance and commitment therapy (ACT) workshop improves anxiety but not vascular function or inflammation in adults with moderate to high anxiety levels in a randomized controlled trial

      2021, General Hospital Psychiatry
      Citation Excerpt :

      One possible mechanism that may contribute to increased CVD risk in anxiety is the development of arterial stiffness and microvascular endothelial dysfunction. Yeragani et al. (2006) found that persons with high anxiety, compared to controls, had significantly higher brachial-ankle pulse wave velocity (PWV), a composite measure of peripheral muscular and central elastic artery stiffness [7]. Similarly, Seldenrijk et al. (2011) compared persons with Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) lifetime diagnoses of depressive and/or anxiety disorders to normal controls and found that those with current depression or anxiety had a higher aortic augmentation index (AIx), a readout of timing and amplitude of augmented central pressure wave reflection partly related to arterial stiffness [8].

    • Acute psychological stress, autonomic function, and arterial stiffness among women

      2020, International Journal of Psychophysiology
      Citation Excerpt :

      The clinical importance of elastic central arteries in buffering high ejection pressure is well documented in epidemiological studies, showing that cfPWV (rather than other measures of arterial stiffness in peripheral arteries) has the most significant prognostic value of cardiovascular morbidity and mortality. Although a few studies have reported the association between SNS activity and central arterial stiffness in healthy humans (Nakao et al., 2004; Swierblewska et al., 2010), more studies have demonstrated nonsignificant associations (Ahn and Kong, 2011; Yeragani et al., 2006). For example, one study reported that plasma levels of catecholamines had no significant correlation with aortic compliance measured by PWV (Potocka-Plazak et al., 1998).

    • Psychological stress and arterial stiffness in Korean Americans

      2012, Journal of Psychosomatic Research
      Citation Excerpt :

      This relationship remained significant after controlling for age, blood pressure (BP), and plasma noradrenalin levels, suggesting that arterial stiffness is related to increased sympathetic activity [52]. In another study with 23 healthy participants (mean age 45 years) and 25 patients with anxiety disorder (mean age 45 years), baPWV did not have any relationship to LF/HF ratio, but was negatively related to HF only in patients with anxiety disorder [49], suggesting increased arterial stiffness and reduced vagal tone in people with anxiety disorders. Another notable finding of this study is the levels of psychological stress in Korean Americans.

    • Depression, anxiety, and arterial stiffness

      2011, Biological Psychiatry
      Citation Excerpt :

      The autonomic nervous system balance may be perturbed in stressful situations. Evidence in support of the hypothesis that stress connected to depressive or anxiety disorders is associated with parasympathetic withdrawal (16,17,43,44) or sympathetic activation (45,46) has been published. More specifically, increasing levels of the vasoconstrictive hormone norepinephrine is one of the sympathetic changes potentially responsible for stiffness (47).

    View all citing articles on Scopus
    View full text