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Anxiety has been shown to be associated with cardiovascular disease. Atherosclerosis is responsible for the vast majority of cardiovascular events. Recent evidence is accumulating to show that insulin resistance (IR) plays a central role in determining the clinical manifestations of established atherosclerotic lesions. The current preliminary study aimed to investigate the associations between trait anxiety, IR, and atherosclerotic progression in healthy elderly subjects with normal fasting glucose and without metabolic syndrome. Thirty-five healthy elderly subjects (19 males and 16 females, mean age 64.5+/-4.7 years) were enrolled in this study. Trait anxiety was measured using a questionnaire corresponding to the trait anxiety scale taken from the State and Trait Anxiety Inventory. The homeostasis model assessment (HOMA-R) and plasma leptin-to-adiponectin ratio (L/A ratio), which are convenient IR indexes calculated from fasting blood sampling, were examined. As measurements of atherosclerotic progression, we performed two ultrasound methods, namely brachial artery flow-mediated dilation (FMD), an endothelial function assessment quantitatively reflecting the endothelium-dependent vasodilation responses following hyperemia, and measurement of carotid intima-media thickness (IMT). The severity of trait anxiety was positively associated with HOMA-R and L/A ratio, and negatively associated with the percent change of brachial artery FMD (%FMD). HOMA-R and L/A ratio were positively associated with carotid IMT, and L/A ratio was negatively associated with %FMD. These data showed the associations between trait anxiety, IR indexes and endothelial dysfunction or atherosclerotic progression. This pilot study, with a cross-sectional design, supports the promising role of IR for clarifying the pathophysiological mechanism by which anxiety contributes to an increasing risk of atherosclerosis.

Objective. A fall in nocturnal blood pressure (BP) is generally observed in normotensive subjects as well as in those with mild to moderate essential hypertension, regardless of the level of daytime BP. Among elderly hypertensive subjects, extreme-dippers with a marked nocturnal fall in BP as well as non-dippers with nocturnal fall absence are at increased risk for cardiovascular and cerebrovascular complications. However, the relationship between these abnormal diurnal BP variation patterns in normotensive elderly subjects has not been investigated. Methods. We classified 45 healthy late middle-aged and older adults into three groups according to the nocturnal systolic BP fall pattern examined by 24-h ambulatory BP monitoring (dipper, non-dipper and extreme-dipper), and compared the parameters of initial atherosclerosis, endothelial function and autonomic function. As a parameter of atherosclerotic factors, the intima-media thickness (IMT) of the carotid artery was examined, and as a parameter of endothelial function, brachial artery endothelium-dependent flow-mediated dilation (FMD) was ultrasonographyically measured. Autonomic function was assessed by power spectral analysis of heart rate variability (HRV). Results. No difference was observed in the severity of IMT between the three groups. The percent change of FMD in subjects in the extreme-dipper group was significantly lower than that of subjects in the dipper group, indicating that extreme-dippers in healthy elderly subjects may be associated with endothelial dysfunction. Also, HRV due to sympathetic modulation of subjects in the extreme-dipper group was significantly higher than that of subjects in the dipper and non-dipper groups, suggesting the activation of sympathetic tone. Conclusion. In healthy elderly subjects, the extreme-dipper type may reflect a decrease in endothelial function, i.e. initial stage atherosclerosis, rather than the dipper type.

Multifractal analysis based on generalized concepts of fractals has been applied to evaluate biological tissues composed of complex structures. This type of analysis can provide a precise quantitative description of a broad range of heterogeneous phenomena. Previously, we applied multifractal analysis to describe heterogeneity in white matter signal fluctuation on T2-weighted MR images as a new method of texture analysis and established Deltaalpha as the most suitable index for evaluating white matter structural complexity (Takahashi et al. J. Neurol. Sci., 2004; 225: 33-37). Considerable evidence suggests that pathophysiological processes occurring in deep white matter regions may be partly responsible for cognitive deterioration and dementia in elderly subjects. We carried out a multifractal analysis in a group of 36 healthy elderly subjects who showed no evidence of atherosclerotic risk factors to examine the microstructural changes of the deep white matter on T2-weighted MR images. We also performed conventional texture analysis, i.e., determined the standard deviation of signal intensity divided by mean signal intensity (SD/MSI) for comparison with multifractal analysis. Next, we examined the association between the findings of these two types of texture analysis and the ultrasonographically measured intima-media thickness (IMT) of the carotid arteries, a reliable indicator of early carotid atherosclerosis. The severity of carotid IMT was positively associated with Deltaalpha in the deep white matter region. In addition, this association remained significant after excluding 12 subjects with visually detectable deep white matter hyperintensities on MR images. However, there was no significant association between the severity of carotid IMT and SD/MSI. These results indicate the potential usefulness of applying multifractal analysis to conventional MR images as a new approach to detect the microstructural changes of apparently normal white matter during the early stages of atherosclerosis.

Abstract: Negative psychological characteristics have been recognized as independent risk factors of cardiovascular disease (CVD). The purpose of this study was to evaluate the influence of depression and anxiety on cardiac autonomic function and endothelial function in healthy elderly subjects. Forty-six healthy elderly volunteers (mean age 60.8 years) were enrolled in this study. Cardiac autonomic function was assessed by spectral analysis of heart rate variability (HRV) with the head-up tilt test. Brachial artery endothelium-dependent flow-mediated dilation (FMD) was measured using high-resolution ultrasound. A significant positive correlation was observed between the State and Trait Anxiety Inventory (STAI)-trait score as a parameter of anxiety and HRV sympathetic modulation in the supine position (baseline), and a significant negative correlation between this score and the head-up-induced HRV sympathetic response from the baseline. The STAI-trait score also showed a significant negative correlation with the percent change of FMD (%FMD). Analysis using structural equation modeling showed that higher trait anxiety reduced %FMD via abnormalities of sympathetic activity. On the other hand, psychometric parameters of depression were not associated with any HRV component or %FMD. These results suggest that there are specific interactions among higher trait anxiety, abnormalities of sympathetic activity, and endothelial dysfunction. This finding may be useful in clarifying the pathophysiological mechanism by which anxiety is associated with increased risks for atherosclerosis and CVD. [Copyright &y& Elsevier]

Objective. The white coat phenomenon (WCP) is a blood pressure (BP) elevation specifically observed in the clinical setting. Though WCP has been suggested to associate with emotional responses such as anxiety or with cardiovascular complications, its pathogenesis and clinical significance are unclear. We studied the possible association between WCP and anxiety or vascular function in normotensive elderly subjects without major cardiovascular risk factors. Methods. As a parameter of anxiety, the State and Trait Anxiety Inventory (STAI) was used. WCP was evaluated by calculating the difference between the clinic BP and mean daytime ambulatory BP. As parameters of vascular function, brachial artery endothelium‐dependent flow‐mediated dilation (FMD) and the endothelium‐independent dilation response to sublingual glyceryl trinitrate (GTN) were measured using high‐resolution ultrasound. Results. Using confounding factors as covariates, no association was observed between WCP and the STAI‐trait or STAI‐state score. There was a significant negative association between WCP and the percent change of FMD but no association between WCP and the percent change of GTN. Conclusion. WCP in the healthy normotensive elderly subjects may reflect a decrease in endothelial function, i.e. initial stage atherosclerosis, rather than anxiety. [ABSTRACT FROM AUTHOR]