日本高血圧学会の高血圧診療ガイドライン(JSH2004）では，高齢者高血圧に対して，前期高齢者(65歳以上75歳未満）と後期高齢者(75歳以上）の降圧目標をいずれも140/90mmHg未満とした．しかし，ガイドラインの中でも示されているように，私たち老年科医が日々遭遇している，80歳前半以降の高齢者高血圧に対してのエビデンスは未だに少ない．海外のEWPHE(European Working Party on High Blood Pressure in the Elderly Trial）では，80歳以上では降圧治療の効果がほとんど消失するとしたのに対し，HYVET(Hypertension in the Very Elderly Trial）パイロット試験では，降圧療法によって脳卒中だけが，降圧療法のベネフィットがあった．さらに，STOP-Hypertension, MRC-old, STONEと同様に，NIPPON DATA90の解析でも，降圧薬を服用していて，正常血圧レベルに達していない群のリスクがもっとも高く，降圧薬を服用し正常血圧にコントロールされている群では，降圧薬を服用せず正常血圧である健康群とほとんどリスクが変わらなかった．我々のフィールドでも高齢者の降圧コントロールが十分でなく，高血圧コントロール不十分例で要介護になりやすいことを考えると，欧米に比し脳卒中が多い日本人では，降圧療法により脳卒中の発症がある程度抑制できるならば，「介護予防の観点」からも高齢者に対する降圧療法は可能な範囲で勧められるべきと考えられる．

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Background Cardiovascular events are known to occur more frequently in patients with a surge in blood pressure (BP), but the correlation between a morning BP surge and corrected QT dispersion (QTc) has not been confirmed to date. Methods and Results The correlation between the morning BP surge and QTc was studied in 82 patients recently diagnosed with high BP (47 males, 35 females). Twenty-four-hours BP monitoring was conducted to classify patients into dipper (n=45) or nondipper (n=37) groups according to the degree of nocturnal BP reduction. QTc was found to be significantly longer in the nondippers compared with the dippers (36.1±17.2 vs 47.6±20.7, p<0.001). In addition, there was a significant increase in the end-diastolic interventricular septum thickness (IVSd), left ventricular posterior wall thickness in diastole (PWT) and left ventricular mass index (LVMI) in the nondippers vs the dippers (respectively, 0.93±0.09 vs 1.03±0.05, p<0.001, 0.94±0.09 vs 1.01±0.04, p<0.01, 109.7±12.8 vs 129.1±20.9, p<0.001). QTc had a significant positive correlation with nighttime BP, IVSd, PWT, and LVMI, but negatively correlated with the nocturnal BP reduction rate. These results were maintained even after adjusting for age and gender. However, a significant correlation between the morning BP surge and QTc was not confirmed. Conclusion In the present nondipper hypertensive patients, QTc, nighttime BP, LVMI, and wall thickness were significantly greater than in the dipper patients. However, there was no significant correlation between the morning BP surge and QTc. (Circ J 2007; 71: 1288 - 1292)

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To assess the relationship between home blood pressure and left ventricular mass, we evaluated cardiac echocardiography in 297 hypertensive subjects (188 men and 109 women; mean age, 62.8±10.3 years) who were treated with amlodipine monotherapy over 1 year (mean dose, 5.5±2.3 mg/day). The morning hypertension group (n =57; 19.2%), who had a morning home systolic blood pressure (HSBP) ≥135 mmHg and an evening HSBP <135 mmHg, had a significantly greater left ventricular mass index (LVMI) concomitant with an increase in the homeostasis model assessment insulin resistance index (HOMA-IR) compared to the good control group (n =174; 58.6%), whose morning and evening HSBP were both <135 mmHg, and had a LVMI roughly equivalent to that of the poor control group (n =63; 21.2%), whose morning and evening HSBP were both ≥135 mmHg. By grouping of subjects according to the difference between morning and evening HSBP (ΔHSBP), subjects with a ΔHSBP≥10 mmHg had a significantly greater LVMI than subjects with a ΔHSBP <10 mmHg. Increases in LVMI in these patients were still significant after adjustment for age, gender, dose of amlodipine, alcohol consumption, body mass index, office systolic blood pressure, and morning and evening HSBP. In a stepwise multivariate regression analysis, ΔHSBP (r² =36.2%, p <0.001), morning HSBP (r² =5.5%, p <0.001), HOMA-IR (r² =1.4%, p =0.016) and age (r² =1.0%, p =0.026) were determined to be significant contributing factors for LVMI. This regression model could explain 44.1% of LVMI variability. These results suggest that morning rise in blood pressure is a dominant predictor of left ventricular hypertrophy. (Hypertens Res 2004; 27: 939-946)

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As a disease management program, comprehensive cardiac rehabilitation is needed during hospital stay, and should also be continued after patients are discharged from the hospital and return to society. Cardiac rehabilitation is composed of not only exercise therapy but also patient education and counseling. Nurses’ skills of supporting self-management in cardiac rehabilitation are to assess the individual risks of the patients and to use the assessment for the management of safe rehabilitation; for patient education, to assess correctly the status of self-management; and, for counseling, to show interest in patients, consider how they are feeling, and provide them with mental support. Collaborating with different health professionals and providing continuous comprehensive support, as well as playing the role of coordinator for these, are also important parts of nurses’ responsibilities in cardiac rehabilitation.

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Measurements of ambulatory blood pressure (ABP) and of home blood pressure (HBP) as an adjunct to casual/clinic BP (CBP) measurements are currently widely used for the diagnosis and treatment of hypertension. We have monitored a rural cohort of people from the population of Ohasama, Japan, with respect to their prognosis and have previously reported that ABP and HBP are superior to CBP for the prediction of cardiovascular mortality. We examined the prognostic significance of white-coat hypertension for mortality and found that the relative hazard for the overall mortality of patients with white-coat hypertension was significantly lower than that for true hypertension during 5-year observation period but observed that the development of sustained hypertension was more frequent in patients with white-coat hypertension than those with true normotension during 10-year observation period. Our results also confirmed that day-by-day variability as well as short-term blood pressure variability (as measured every 30 min) was independently associated with cardiovascular mortality. In addition, research has recently focused on isolated systolic hypertension and pulse pressure as independent risk factors for poor cardiovascular prognosis. The Ohasama study also clearly demonstrated that isolated systolic hypertension and increased pulse pressure, as assessed by HBP, were associated with an increase in the risk of cardiovascular mortality. Concerning diurnal blood pressure variation, the relative hazard for cardiovascular mortality increased in non-dippers and inverted dippers while that in extreme dipper did not. The Ohasama study also clearly demonstrated that nocturnal BP levels in hypertensive patients with extreme dipper were significantly higher than those in normotensive subjects. The Ohasama study showed that the level and variability of hypertension as assessed by ABP and HBP are independent predictors of cardiovascular morbidity and mortality. It also demonstrated an independent association between the prognosis of hypertension and each component of ABP and HBP, indicating the prognostic significance of these blood pressure measurements.

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Unexplained high serum corticosteroid-binding globulin (CBG) concentrations (mean±SD, 74.1±12.1μg/dl; normal women, 32.5±5.6μg/dl) were found in an unmarried woman who was not pregnant or taking exogenous estrogens. She was also found to suffer from subclinical chronic thyroiditis, pituitary adenoma and empty sella. The increased serum CBG concentrations in this patient were not due to any of the factors known to increase CBG. Consistently high basal serum GH levels and unusual GH responses to GH-releasing factor (GRF) and L -dopa were also noted.

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The exposure of gasoline pump repairers and inspectors to gasoline was studied at service stations and repair shops in Finland in April-June 2004. The average air temperature ranged from 7°C to 16°C and wind speed from 2.5 to 7 m/s. The gasoline blends contained mixtures of methyl tert-butyl ether (MTBE) and tert-amyl methyl ether (TAME), the total content of oxygenates being 11-12%. The content of benzene was <1%. Breathing zone air was collected during the work task using passive monitors. The mean sampling period was 4.5 h. The mean TWA-8 h concentrations for MTBE, TAME, hexane, benzene, toluene, ethylbenzene and xylene were 4.5, 1.3, 0.55, 0.23, 2.2, 0.26 and 1.1 mg/m³, respectively. None of the individual benzene concentrations exceeded the binding limit value for benzene (3.25 mg/m³). The sum concentration of MTBE and TAME in urine was between 8.9 and 530 nmol/l in individual post-shift samples. The individual sum concentrations of the metabolites tert-butyl alcohol and tert-amyl alcohol collected the following morning after the exposure ranged from 81 to 916 nmol/l. All individual results were below corresponding biological action levels. Exposure to aromatic hydrocarbons was estimated from post-shift urine samples, with benzene showing the highest concentration (range 4.4 and 35 nmol/l in non-smokers). The exposure levels were similar to those measured in previous studies during unloading of tanker lorries and railway wagons. The results indicated a slightly higher exposure for inspectors, who calibrated fuel pump gauges at the service stations, than for pump repairers. No significant skin exposure occurred during the study.

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Although reconstruction from the 2011 Great East Japan earthquake and tsunami is proceeding, the environment of children living in the disaster area has not yet recovered. Anxiety among such children may have adverse effects on their future mental and physical health. The purpose of this study was to examine fluctuations in chronic stress and immune conditions in children and adolescents living in the disaster area. The participants were elementary and junior high school students living in the Pacific coastal area of northern Japan. This serial cross-sectional study performed five surveys in September 2011 (6 months, n = 391), March 2012 (1 year, n = 394), March 2013 (2 years, n = 281), March 2014 (3 years, n = 332), and March 2015 (4 years, n = 313). Stimulated whole saliva samples were collected, and saliva flow, secretory immunoglobulin A concentration, secretory immunoglobulin A secretion rate, and cortisol concentration were determined. Cortisol concentration significantly decreased from 6 months to year 2 of the study period, but increased between year 2 and year 4. Secretory immunoglobulin A concentration significantly increased between year 1 and year 4 compared to the first 6 months. Gender differences were observed in saliva flow and secretory immunoglobulin A concentration, and significant differences between elementary and junior high school students were observed in cortisol concentration. Therefore, fluctuation of cortisol concentration as a chronic stress biomarker and an increase in SIgA as an immune biomarker were observed during the 4 years after the disaster, but the changes in the two biomarkers did not correspond.

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It is universally acknowledged that glucocorticoids are hormones that exert a significant effect on hemostasis. The aim of this study was to analyze the activities of coagulation factors VIII, von Willebrand (vW), IX, X, and XI, in patients with overt and subclinical hypercortisolism, as well as to examine possible associations between activities of these factors and the degree of hypercortisolism. Thirty endogenous hypercortisolemic patients were included in the study. Twelve of them were diagnosed with overt Cushing’s syndrome (OCS), and eighteen with subclinical Cushing’s syndrome (SCS). Healthy, age- and sex-matched volunteers comprised the control group. Activities of coagulation factors VIII, IX, X, and XI were examined using a coagulometric method, and von Willebrand factor (vWF) using an immunoturbidimetric method. Mean activities of examined coagulation factors were significantly higher in OCS patients in comparison to healthy controls. SCS patients had significantly higher mean vWF activities versus controls; and a clear trend toward higher mean activities of other factors in SCS patients versus controls was recorded (but no significant differences). Furthermore, statistically significant positive correlations were found between activities of factor IX and: morning serum cortisol concentrations, 24-hour urinary cortisol excretion values, cortisol concentrations in the overnight suppression test with 1 mg of dexamethasone. Activities of factors X and XI positively correlated with cortisol levels in the overnight suppression test. In endogenous hypercortisolemic patients the coagulation pathway is hyperactivated as indicated by increased activities of coagulation factors. These disorders are evident among patients with overt hypercortisolism.

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By using structural equations, we investigated the effect of chronic stress on salivary cortisol rhythm and proposed a causal model of chronic stress by using psychosocial and physiological data. First, 111 healthy workers (48 males, 63 females) completed questionnaires on chronic stress and lifestyle habits. Then, they provided saliva samples and answered questionnaires that were prepared to assess their psychological states 5 times (on waking up and at 10:00, 11:40, 14:00, and 16:00) on workdays. Structural equation modeling (SEM) revealed that chronic stress and longer commuting time resulted in sleep irregularities and this disrupted the cortisol circadian rhythm. This suggests that chronic stress disrupts the cortisol circadian rhythm even in healthy individuals, and sleep regularity mediates the effect of chronic stress on the cortisol rhythm.

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