Associations Between Occupational Status, Support at Work, and Salivary Cortisol Levels.

OBJECTIVE: The present study investigated associations between occupation, job stress, and salivary cortisol levels after psychological tasks. METHODS: We examined 766 (273 men and 493 women) healthy employed Japanese participants aged 21 to 68 years (mean age = 46.4 years, standard deviation = 8.5) with three types of occupation: manager, teacher, and general worker. The Brief Job Stress Questionnaire was used to evaluate participants' job stress levels, including job demand, job control, support from supervisors, and support from coworkers. Salivary cortisol levels were measured at pre-session, post-stressful tasks, and post-relaxation. All samples were assayed using an enzyme-linked immunosorbent assay test. Natural log transformation was applied before statistical analyses. A multiple regression analysis and a repeated measures analysis of covariance were conducted to test associations between occupation and salivary cortisol levels, adjusting for confounding factors. Statistical analyses were conducted separately for men and women. RESULTS: Among both men and women, general workers had higher cortisol levels than managers throughout the experimental session (men 0.6 µg/dL and 0.4 µg/dL, respectively; women 0.5 µg/dL and 0.4 µg/dL, respectively). Job control was positively associated with cortisol levels measured in all sessions, after adjusting for confounding factors (standardized beta 0.15, 0.21, and 0.18 for pre-session, post-stressful-tasks, and post-relaxation, respectively, all p < 0.05). Men with low support from coworkers had higher cortisol levels than those with high support through the sessions (0.6 µg/dL and 0.4 µg/dL, respectively). CONCLUSION: Socioeconomic disparity according to occupational status was related to cortisol levels in Japanese workers. Support from coworkers may be effective for reducing cortisol secretion in men.

Autonomic nervous system function in adolescent migraineurs.

BACKGROUND: Migraine is a common and disabling neurological disorder. Studies on the relationship between migraine and the autonomic nervous system (ANS) have been inconclusive. Moreover, pediatric studies are extremely limited. Therefore, the present study investigated interictal ANS function in adolescent migraineurs. METHODS: We studied 21 patients with migraine and 26 healthy controls. Beat-to-beat blood pressure (BP) and heart rate (HR) were non-invasively and continuously measured in the supine and standing positions. ANS function was evaluated on power spectral analysis of HR variability and diastolic BP (DBP) variability. RESULTS: Heart rate and systolic BP were not different between the two groups in either the supine or standing position. DBP did not differ between groups in the standing position, but was significantly higher in migraineurs in the supine position. The vasoconstrictor index was significantly higher in migraineurs. High-frequency (HF) RR interval variability (RR-HF) and the ratio of the low-frequency (LF) to HF component of RR interval variability (RR-LF/HF) were not different between the two groups in both positions. The LF component of DBP variability (DBP-LF) in the supine position was significantly lower in migraineurs, while DBP-LF during standing in migraineurs was significantly higher than in controls. CONCLUSION: Migraineurs have significantly lower sympathetic vasomotor activity in the supine position, while sympathetic vasomotor activity was hyperresponsive during standing.

Menopausal status in relation to cardiovascular stress reactivity in healthy Japanese participants.

OBJECTIVE: To investigate the hypothesis that postmenopausal women demonstrate greater cardiovascular stress reactivity during mental stress tasks than do both premenopausal women and men. METHODS: The study included 979 Japanese participants (338 men and 641 women [238 postmenopausal]) aged 16 to 82 years. Blood pressure, heart rate, heart rate variability, and peripheral blood flow were measured at rest and during a mirror drawing stress task and a maze task. Differences between measured variables during tasks and at rest were calculated and considered to represent reactivity to stress. Analyses were adjusted for age and other potential confounding factors. RESULTS: After adjusting for multiple factors, significant group effects were found for systolic blood pressure (SBP), diastolic blood pressure, heart rate, low-frequency (LF), LF/high-frequency, and peripheral blood flow (effect size: partial η = 0.015, 0.011, 0.013, 0.013, 0.008, and 0.009, respectively). Postmenopausal women were more reactive than men to stress for SBP (15.4 ± 0.8 versus 11.7 ± 0.6 mm Hg), diastolic blood pressure (10.4 ± 0.6 versus 8.0 ± 0.5 mm Hg), heart rate (2.7 ± 0.5 versus 0.7 ± 0.4 beats/min), LF (23.0 ± 5.2 versus 3.2 ± 3.8 ms/Hz), and peripheral blood flow (-39.0 ± 3.8 versus -25.9 ± 2.8 Laser Doppler Perfusion Units) and more reactive than premenopausal women (p < .050) for SBP (15.4 ± 0.8 versus. 12.4 ± 0.5 mm Hg) and LF/high-frequency (1.7 ± 0.1 versus 1.3 ± 0.1). CONCLUSIONS: Postmenopausal Japanese women evidenced greater cardiovascular stress reactivity during mental stress tasks than did Japanese men or premenopausal women. Cardiovascular hyperreactivity could play a role in the higher risks of cardiovascular diseases in postmenopausal women.

Variant cardiovascular regulation in children with postural tachycardia syndrome.

BACKGROUND: Postural tachycardia syndrome (POTS) manifests as marked tachycardia while standing. We noticed two forms of circulatory response to orthostatic stress in POTS. We investigated cardiovascular and autonomic nervous response to orthostatic stress in the two forms. METHODS: We studied 79 patients with POTS and 38 healthy control subjects (Ct). Beat-to-beat blood pressure (BP) and heart rate (HR) were non-invasively and continuously measured in the supine and standing positions. Autonomic nervous function was evaluated on power spectral analysis of HR variability and diastolic BP variability. We divided the subjects into two groups: standing-induced tachycardia (SI group; increase in HR ≥35 beats/min) and supine tachycardia (Su group; standing HR ≥115 beats/min with standing-induced HR increase <35 beats/min). RESULTS: The Su group had higher supine BP and HR compared with the other groups, indicating dominant sympathetic control of the heart in the supine position. While rising, the SI group had a higher increase in HR than the Ct group, indicating excessive withdrawal of vagal tone. The Su group had a smaller increase in HR and a greater decrease of systolic BP and cardiac index by standing compared with the SI group. These results suggest that compensatory mechanisms of sympathetic function during standing failed in the Su group, probably because of exhaustion by the nearly maximum effort to generate sympathetic drive even in the supine position with low central blood volume. CONCLUSION: There is a difference between the two types of POTS, in the balance of resting autonomic function and hemodynamic response to standing.

GNB3 C825T polymorphism is associated with postural tachycardia syndrome in children.

AIM: Postural tachycardia syndrome (POTS) is one of the most frequent forms of chronic orthostatic intolerance in children and adolescents. The aim of the present study was to examine the influence of a genetic background on POTS. METHODS: A total of 96 children and adolescents with orthostatic dysregulation were studied. The polymorphism of the G protein ß3 subunit (GNB3) C825T and G protein α subunit (GNAS1) T131C of genes encoding components of the autonomic nervous system were determined and compared with circulatory responses to active standing. RESULTS: In the GNB3 gene C825T polymorphism, the CT and TT genotype had a significant lower supine heart rate and a larger increase of heart rate by standing than the CC, associated with evaluated power of the high-frequency component of heart rate variability. According to the criteria of the Japanese clinical guidelines, 48 children were diagnosed as POTS and 30 were as normal responder with somatoform disorder (SD). In GNB3 C825T polymorphism, the TT genotype was more frequently found in the POTS group (45.8%) than in the SD group (20.0%; P = 0.036) [corrected]. In the GNAS1 T393C, the genotype frequencies for the T393C polymorphisms of GNA1 did not differ significantly between the groups. CONCLUSION: The gene polymorphisms GNB3 C825T might be a risk factor for POTS through the enhanced vagal withdrawal of the heart in children and adolescents.

Clinicopathological features of acute autonomic and sensory neuropathy.

Acute autonomic and sensory neuropathy is a rare disorder that has been only anecdotally reported. We characterized the clinical, electrophysiological, pathological and prognostic features of 21 patients with acute autonomic and sensory neuropathy. An antecedent event, mostly an upper respiratory tract or gastrointestinal tract infection, was reported in two-thirds of patients. Profound autonomic failure with various degrees of sensory impairment characterized the neuropathic features in all patients. The initial symptoms were those related to autonomic disturbance or superficial sensory impairment in all patients, while deep sensory impairment accompanied by sensory ataxia subsequently appeared in 12 patients. The severity of sensory ataxia tended to become worse as the duration from the onset to the peak phase of neuropathy became longer (P<0.001). The distribution of sensory manifestations included the proximal regions of the limbs, face, scalp and trunk in most patients. It tended to be asymmetrical and segmental, rather than presenting as a symmetric polyneuropathy. Pain of the involved region was a common and serious symptom. In addition to autonomic and sensory symptoms, coughing episodes, psychiatric symptoms, sleep apnoea and aspiration, pneumonia made it difficult to manage the clinical condition. Nerve conduction studies revealed the reduction of sensory nerve action potentials in patients with sensory ataxia, while it was relatively preserved in patients without sensory ataxia. Magnetic resonance imaging of the spinal cord revealed a high-intensity area in the posterior column on T(2)*-weighted gradient echo image in patients with sensory ataxia but not in those without it. Sural nerve biopsy revealed small-fibre predominant axonal loss without evidence of nerve regeneration. In an autopsy case with impairment of both superficial and deep sensations, we observed severe neuronal cell loss in the thoracic sympathetic and dorsal root ganglia, and Auerbach's plexus with well preserved anterior hone cells. Myelinated fibres in the anterior spinal root were preserved, while those in the posterior spinal root and the posterior column of the spinal cord were depleted. Although recovery of sensory impairment was poor, autonomic dysfunction was ameliorated to some degree within several months in most patients. In conclusion, an immune-mediated mechanism may be associated with acute autonomic and sensory neuropathy. Small neuronal cells in the autonomic and sensory ganglia may be affected in the initial phase, and subsequently, large neuronal cells in the sensory ganglia are damaged.

Job stress factors measured by Brief Job Stress Questionnaire and sickness absence among Japanese workers: A longitudinal study.

This study aimed to investigate associations between Brief Job Stress Questionnaire (BJSQ)-measured job stress factors and sickness absence in Japanese workers. Among 551 healthy, employed Japanese men and women (age range: 21-73 years) who underwent mental health examinations at the Osaka Medical Center for Health Science and Promotion between 2006 and 2009, 197 (67 men, 130 women) consented to participate in this study. Their sickness absences until the end of March 2010 were then followed-up via postal mail survey, with 112 participants effectively responding to the question on sickness absence (56.9%). The hazard ratio (HR) and 95% confidence interval (CI) were calculated using the Cox proportional hazards model, adjusting for age, sex, and lifestyle factors. Among the 112 respondents, 12 took sickness absence after their study entry, as found during the mean 2.3 years of follow-up (258.8 person-years). Among all sickness absences, those of eight participants were because of mental illness. Physical demands were positively associated with increased risks of all sickness absence (adjusted HR: 2.78, 95% CI: 1.01-7.64). Physical demands were predictive for all sickness absence, and should be alleviated at workplaces to prevent such absence.

Cardiovascular reactivity to acute stress associated with sickness absence among Japanese men and women: A prospective study.

OBJECTIVE: We aimed to investigate associations between cardiovascular reactivity to acute stress and sickness absence among Japanese male and female workers, in a prospective study. METHODS: Among healthy employed Japanese workers who underwent mental health checks between 2006 and 2009, data of 111 participants were analyzed. Changes in blood pressure, pulse rate, peripheral blood flow (PBF), and heart rate variability (HRV) (high frequency [HF] and low frequency [LF]) were calculated using differences between the two tasks, mirror drawing stress [MDS] and a maze task, and the postperiod value. Sickness absence through March 2010 was followed up by mail survey (average follow-up 2.3 years). Logistic regression analysis was used, adjusting for lifestyle factors. RESULTS: Among 12 participants who took sickness absences, eight were owing to mental problems. Changes in the LF during the MDS and maze tasks and LF-to-HF ratio during the MDS task were positively associated with all sickness absences (odds ratio [OR], 95% confidence interval [CI]: 2.09, 1.03-4.22; 2.04, 1.09-3.82; and 3.10, 1.46-6.58, respectively). Changes in PBF during the MDS task were also associated with increased risk of sickness absence (OR, 95% CI: 2.53, 1.10-5.81). CONCLUSION: Cardiovascular reactivity to acute stress should be considered at workers' health checks.

Quantitative study on cerebral blood volume determined by a near-infrared spectroscopy during postural change in children.

AIM: To investigate changes in cerebral blood volume during standing in healthy children with or without abnormal cardiovascular responses. METHODS: We studied 53 children (age, 10-15 years). Cerebral oxygenated haemoglobin (oxy-Hb) and deoxygenated Hb (deoxy-Hb) were non-invasively and continuously measured using near-infrared spectroscopy (NIRS) (NIRO 300, Hamamatsu Photomedics, Shizuoka, Japan) during active standing. Beat-to-beat arterial pressure was monitored by Portapres. RESULTS: Of 49 children with complete data acquisition, 33 had a normal cardiovascular response to the test (Group I) and 16 showed an abnormal response (Group II); nine with instantaneous orthostatic hypotension, three with postural tachycardia syndrome, three with neutrally mediated syncope and one with delayed orthostatic hypotension. At the onset of standing, Group II showed a significantly larger fall of oxy-Hb than Group I did (-2.9 +/- 2.8 micromol/L vs. -6.4 +/- 7.2 micromol/L, respectively, p < 0.05). During min 1 to 7 of standing, with one exception, changes in oxy-Hb were normally distributed over the level of -4 micromol/L in Group I. Group II also showed a significantly marked decrease in oxy-Hb compared to Group I. Decreases in oxy-Hb were not correlated with blood pressure changes. CONCLUSION: This study shows that precise change in cerebral blood volume caused by orthostatic stress can be determined by NIRS in children in a quantitative manner of NIRS. Children with abnormal circulatory responses to standing showed a significant reduction of oxy-Hb compared with normal counterparts, suggesting impairment of cerebral autoregulation in these children.

Japanese clinical guidelines for juvenile orthostatic dysregulation version 1.

This clinical practice guideline provides recommendations for the assessment, diagnosis and treatment of school-aged children and juveniles with orthostatic dysregulation (OD), usually named orthostatic intolerance in USA and Europe. This guideline is intended for use by primary care clinicians working in primary care settings. The guideline contains the following recommendations for diagnosis of OD: (i) initial evaluation composed of including and excluding criteria, the assessment of no evidence of other disease including cardiac disease and so on; (ii) a new orthostatic test to determine four different subsets: instantaneous orthostatic hypotension, postural tachycardia syndrome, neurally mediated syncope and delayed orthostatic hypotension; (iii) evaluation of severity; and (iv) judgment of psychosocial background with the use of rating scales. The guideline also contains the following recommendations for treatment of OD on the basis of the result of an orthostatic test in addition to psychosocial assessment: (i) guidance and education for parents and children; (ii) non-pharmacological treatments; (iii) contact with school personnel; (iv) use of adrenoceptor stimulants and other medications; (v) strategies of psychosocial intervention; and (vi) psychotherapy. This clinical practice guideline is not intended as a sole source of guidance in the evaluation of children with OD. Rather, it is designed to assist primary care clinicians by providing a framework for decision making of diagnosis and treatments.

Variant autonomic regulation during active standing in Swedish and Japanese junior high school children.

The present investigation is about cardiovascular responses and relevant autonomic function in Swedish and Japanese pubertal children on active standing using non-invasive continuous beat-to-beat finger arterial pressure (FAP) monitoring and power spectral analysis. Examined were 54 Swedish and 57 Japanese children (13-15 years). FAP and heart rate (HR) was continuously recorded in the supine position and during standing. Supine FAP was significantly higher in Swedish compared with Japanese children (121/62 versus 103/53 mmHg, P < 0.001). Swedish children showed a higher increase in arterial pressure and HR upon uprising, resulting in a higher vasoconstrictor index (5.04 +/- 0.22 versus 2.31 +/- 0.11 mmHg s(-1), P < 0.001, respectively). There were also higher increases in arterial pressure and HR in the following steady state period (1-7 min) between the two groups. These differences were also found after adjustment of body weight and height. Frequency domain analysis of HR and arterial pressure variability indicated significantly higher low/high frequency power of HR and low frequency power of arterial pressure. These results suggest that Swedish pubertal children have higher basal blood pressure and enhanced cardiovascular sympathetic responses. These differences in the two cohorts might be caused by genetic factors.

Dehydroepiandrosterone-sulfate is associated with cardiovascular reactivity to stress in women.

Cardiovascular stress reactivity is a predictor of atherosclerosis and cardiac events. Dehydroepiandrosterone (DHEA) protects against cardiovascular diseases, but results among previous studies have been inconsistent. We investigated the association between dehydroepiandrosterone-sulfate (DHEA-s) and cardiovascular stress reactivity in Japanese women and men. Among 979 healthy Japanese subjects (641 women and 338 men), serum levels of DHEA-s, systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate, heart rate variability, and peripheral blood flow were measured under rest and two types of task. Mean differences in measured variables during tasks and a post-task period were calculated as changes in stress reactivity. Variables of stress reactivity were adjusted for multiple potential confounding factors. In women, DHEA-s levels showed positive associations with changes in SBP and DBP (standardized beta=0.12, p=0.020; 0.17, 0.002, respectively). Stratification by menopausal status and other lifestyle factors (e.g., smoking status, alcohol consumption) were conducted. Significant positive associations remained in pre-menopausal (standardized beta=0.13, p=0.037; 0.18, 0.005), non-smoking (0.12, 0.010; 0.18, <0.001), and non-drinking women (0.14, 0.021; 0.21, 0.001), and women without a medical history (0.15, 0.020; 0.20, 0.001). In men, there was no significant association between DHEA-s levels and changes in stress reactivity. DHEA-s levels were positively associated with high blood-pressure reactivity to stress in women, and being menopausal, smoking, and alcohol consumption modified this association.

Occupational status and job stress in relation to cardiovascular stress reactivity in Japanese workers.

This study aimed to investigate the effects of occupational status and job stress factors on cardiovascular stress reactivity in Japanese workers. In this baseline assessment between 2001 and 2009 in Osaka, Japan, we examined 928 healthy Japanese employees (330 men, 598 women) from two occupational statuses: managers/professionals and general workers. A brief job stress questionnaire was used to evaluate job stress levels. Systolic and diastolic blood pressure (SBP, DBP), heart rate, heart rate variability (high-frequency [HF], low-frequency [LF], LF/HF], and peripheral blood flow were measured at rest and during two stressful tasks. Changes in stress reactivity were calculated as the difference between the measured variables during the tasks and the rest period. Men showed inverse associations between quantitative job overload and DBP, heart rate, and LF/HF, between physical demands and blood pressure (SBP, DBP), and between a poor physical environment and HF. Men also had positive associations between qualitative job overload and heart rate, and between physical demands and peripheral blood flow (all p < 0.05). Women showed inverse associations between qualitative job overload and SBP, and showed positive associations between qualitative job overload and peripheral blood flow, and between a poor physical environment and SBP (all p < 0.05). When stratified by occupational status, significant associations between job stress and changes in stress reactivity were observed in male managers/professionals and female general workers (p < 0.05). Job stress levels are associated with changes in cardiovascular stress reactivity in men and women. Occupational status may modify these associations.

Effects of a laughter and exercise program on physiological and psychological health among community-dwelling elderly in Japan: randomized controlled trial.

AIM: To examine the effects of a once-weekly laughter and exercise program on physical and psychological health among elderly people living in the community. As a regular exercise program can be difficult to maintain, we provided a more enjoyable program to enhance adherence to exercise. METHODS: A total of 27 individuals aged 60 years or older, without disabilities, were randomly assigned to either an immediate treatment group (n=14) or a delayed treatment group (n=13). The intervention was a 120-min session consisting of laughter and exercise, carried out once a week for 10 consecutive weeks. Measurements taken at baseline, 3 and 6 months included bodyweight, height, body fat, lean mass, bone mineral density, hemoglobin A1c (HbA(1c)), glucose, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides, as well as self-rated health and psychological factors. RESULTS: All participants completed the 3-month program. Bone mineral density increased significantly in the immediate treatment group compared with the delayed treatment group during the first 3 months (P<0.001). In addition, HbA(1c) decreased significantly (P=0.001), and self-rated health increased significantly (P=0.012). CONCLUSIONS: The combination of a laughter and exercise program might have physiological and psychological health benefits for the elderly. Laughter might be an effective strategy to motivate the elderly to participate in physical activity.

Effect of angiotensin-converting enzyme inhibitor on matrix metalloproteinase-9 activity in patients with Kawasaki disease.

BACKGROUND: Matrix metalloproteinase (MMP)-9 is thought to be involved in coronary artery aneurysms (CAAs) in patients with Kawasaki disease (KD); however, MMP-9 inhibitors are not used clinically. This study investigated whether the angiotensin-converting enzyme (ACE) inhibitor captopril could inhibit serum MMP-9 activity using serum from KD patients in an in vitro experiment. METHODS: In 7 KD patients, serum MMP-9 activity was measured using the MMP-9 assay kit 3 times: before and after intravenous immunoglobulin (IVIG) treatment, and during the convalescent phase. The effect of captopril on MMP-9 activity was also assessed using serum obtained before IVIG treatment. RESULTS: Serum MMP-9 activity was significantly higher during the pre-treatment phase than during the post-treatment and convalescent phases. MMP-9 activity during the pre-treatment phase was dose-dependently inhibited by captopril, and the IC(50) for MMP-9 was 500nM. The potency of captopril for MMP-9 inhibition was comparable to that for ACE inhibition. CONCLUSION: ACE inhibitor may be effective for preventing CAA formation in KD patients, especially IVIG non-responders.