Original articleIncreased pulse-wave velocity in patients with anxiety: implications for autonomic dysfunction
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)
- et al.
Decreased heart rate variability in panic disorder patients. A study of power spectral analysis of heart rate
Psychiatry Res
(1993) - et al.
Effects of isoproterenol on heart rate variability in patients with panic disorder
Psychiatry Res
(1995) - et al.
Decreased heart period variability in patients with panic disorder: a study of Holter ECG records
Psychiatry Res
(1998) - et al.
Increased QT variability in patients with panic disorder and depression
Psychiatry Res
(2000) - et al.
Decreased heart rate variability and its association with increased mortality after acute myocardial infarction
Am J Cardiol
(1987) - et al.
Beat-to-beat QT interval variability in coronary patients
J Electrocardiol
(2000) - et al.
Effect of fluoxetine, pemoline and placebo on heart period and QT variability in normal humans
J Psychosom Res
(2003) - et al.
Adrenergic status in anxiety disorders: platelet alpha-2 adrenergic binding, blood pressure, pulse and plasma catecholamines in panic and generalized anxiety disorder patients and in normal subjects
Biol Psychiatry
(1990) - et al.
Noradrenergic function in generalized anxiety disorder: effects of yohimbine in healthy subjects and patients with generalized anxiety disorder
Psychiatry Res
(1989) - et al.
Reduced vagal activity in salt-sensitive subjects during mental challenge
Am J Hypertens
(2003)
Clinical value of aortic pulse-wave velocity measurement
Lancet
Assessment of arterial distensibility by autonomic pulse-wave velocity measurement: validation and clinical application studies
Hypertension
Vascular wall function as a risk marker for cardiovascular disease
J Hypertens
Association between arterial stiffness and atherosclerosis: the Rotterdam study
Stroke
Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients
Hypertension
Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure
Circulation
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
Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse-wave velocity measurement
Hypertens Res
Asymptomatic hyperglycemia is associated with intimal plus medial thickness of the carotid artery
Diabetologia
Preferential stiffening of central over peripheral arteries in type 2 diabetes
Diabetes
Mortality among outpatients with anxiety disorders
Am J Psychiatry
Panic disorder and cardiovascular/cerebrovascular problems
Am J Psychiatry
Prospective study of phobic anxiety and risk of coronary heart disease in men
Circulation
Symptoms of anxiety and risk of coronary heart disease: the normative aging study
Circulation
Depression and coronary heart disease: a review for cardiologists
Clin Cardiol
Decreased chaos and increased nonlinearity of heart rate time series in patients with panic disorder
Auton Neurosci
Decreased R-R variance in panic disorder patients
Acta Psychiatr Scand
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
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2012, Journal of Psychosomatic ResearchCitation 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.
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