苅尾 七臣

There are reports that indicate that diurnal blood pressure (BP) variation, in addition to high BP per se, is related to target organ damage and the incidence of cardiovascular events. However, the determinants of diurnal BP variation are not adequately understood. We used actigraphy and ambulatory BP monitoring td study the diurnal variation of BP and physical activity in 160 adults. Within individuals, activity was more strongly related to pulse rate than to BP. The correlation between BP and activity was stronger during sleep than when awake, but the correlation between activity and pulse rate was higher during the awake period than during sleep. Between individuals, the sleep/awake ratio of systolic BP (SBP) was correlated with mean sleep activity (r=.17, P<0.05), mean awake activity (r= -0.16, P<0.05), and, especially, the ratio of sleep/awake activity (r=.24, P<0.01). Awake BP variability (SD of awake SEP) was positively: correlated with awake activity (r=.16, P<0.05), In regard to the effect of position, the standing-supine SBP difference was negatively correlated with the sleep/awake SBP ratio:(r= -0.39, P<0.01) and positively correlated with awake SBP variability (r=.33, P<0.01). When we divided the subjects into 3 groups, 19 extreme dippers (with a sleep SBP decrease of greater than or equal to 20% of awake SBP), 102 dippers (with decreases of greater than or equal to 10% to <20%), and 39 nondippers (with decreases of <10%), no significant differences existed in awake activity. among the groups. However, the nondippers exhibited greater sleep activity than extreme dippers (P<0.05) and an increased sleep/awake activity ratio compared with extreme dippers and dippers (P<0.01). Extreme dipping may also be associated with increased BP variability (P=0.08). Individual SBP responses to activity (the within-persen slope of awake SBP regressed on activity) did not differ significantly among the 3 subgroups. In conclusion, physical activity is one of the determinants of ambulatory BP and its diurnal variation. We hypothesize that the association of sleep activity to sleep BP and dipping reflects differences in sleep quality.

An abnormal circadian rhythm of blood pressure [i.e. a lesser or 'reverse' nocturnal fall of blood pressure (nondippers)] is associated with cerebrovascular damage including intracranial hemorrhaging, thrombosis, and vascular dementia. Silent cerebrovascular damage such as lacunae and periventricular hyperintensity lesions is not infrequently detected in apparently healthy hypertensive elderly subjects by brain magnetic resonance imaging and also is more common among nondippers than it is among dippers. Although no exact cause-effect relationship is known, a decrease in nocturnal fall of blood pressure might be secondary to a site-specific injury to the brain resulting in an impairment of central autonomic nervous system functioning. Besides nondipping, evidence suggests that the extreme dipping (a marked nocturnal fall of blood pressure) should be considered a type of abnormal diurnal blood pressure variation in elderly patients with hypertension who are likely to have advanced silent cerebrovascular damage. The pathogenic significance of 'extreme dipping' might be an 'artificial' excess reduction in blood pressure at night beyond the lower limit of blood pressure in the autoregulation of cerebral blood flow that is probably induced by antihypertensive agents. It is also possible that a greater blood pressure variability in extreme dippers itself accelerates the hypertensive target-organ damage. Prospective follow-up of subjects with these distinct subtypes of abnormal circadian blood pressure variation as well as trials comparing a group of treated patients with various degrees of dipping with a group of untreated counterparts may establish the validity of assessing these distinct circadian rhythms of blood pressure as a useful clinical parameter in the management of hypertension.

Background The ACE insertion/deletion (I/D) polymorphism is reported to be associated with myocardial infarction in both whites and Japanese. However, there have been no reports on the association of this polymorphism with stroke in each race. Furthermore, there are some racial differences in the demographics of cardiovascular diseases. In Japanese, stroke (especially that which occurs in preexisting hypertension) is more common and coronary artery disease much less common than in whites. We propose that the ACE I/D polymorphism might be associated with hypertensive cerebrovascular disease in Japanese. Methods and Results To study the association between the ACE IID polymorphism and hypertensive cerebrovascular disease, we identified the ACE I/D genotype in 228 hypertensive and 104 normotensive Japanese subjects. Compared with its detected by magnetic resonance imaging, the ACE*D allele frequency was significantly higher (0.47; P<.001) in the 138 hypertensives with silent or clinically overt ischemic stroke, whereas there was no significant difference between its frequency in hypertensives without lacunae and in 104 normotensive control subjects (0.34). The positive association between the ACE I/D genotype and ischemic stroke in hypertensive patients was independent of other risk factors. Conclusions We found a positive association between the ACE*D allele and ischemic stroke in Japanese hypertensives in our study. The ACE*D allele may be an independent risk factor for the development of cerebrovascular disease in hypertensive patients.

We investigated the relationships between hyperinsulinemia (a major indicator of the insulin resistance syndrome), blood pressure, dyslipidemia, and coagulation factors in 2606 community-dwelling Japanese individuals as part of the Jichi Medical School Cohort Study. An age-related decrease of the fasting insulin level was found in men but not in women. Body mass index, systolic and diastolic blood pressure, triglyceride and fasting glucose levels, and factor VII activity all increased in both sexes as the insulin level became higher, while the HDL cholesterol level decreased. In addition, total cholesterol and LDL cholesterol levels increased as the insulin level became higher and lipoprotein(a) levels decreased in the men. Fibrinogen levels were not related to the insulin level in either sex. Multiple logistic regression analysis revealed that fasting insulin levels were positively correlated with body mass index and fasting glucose and factor VII activity levels, whereas they were negatively correlated with HDL cholesterol in both sexes. In addition, fasting insulin levels were positively correlated with LDL cholesterol levels in men and with triglyceride levels in women. Our results indicate that hyperinsulinemia is associated with high factor VII activity in a general Japanese population as well as with high blood pressure and dyslipidemia. The accumulation of these cardiovascular risk factors in hyperinsulinemic subjects appears to contribute to cardiovascular events in the Japanese as well as in westerners.

To study the relation between diurnal blood pressure variations and silent cerebrovascular damage, we performed both 24-hour ambulatory blood pressure monitoring and brain magnetic resonance imaging in 131 elderly asymptomatic hypertensive patients. Silent cerebrovascular damage was identified by the magnetic resonance imaging findings of lacunae (low intensity in T-1-weighted images and high intensity in T-2-weighted images) and advanced periventricular hyperintense lesions (on T-2-weighted images). The frequency of silent cerebrovascular damage in the 100 patients with sustained hypertension was greater than that in the 31 patients with white coat hypertension. We further classified the former group into nondippers (nocturnal reduction of systolic pressure by <10% of awake systolic pressure; n=46), dippers (reduction by greater than or equal to 10% to <20%; n=38), and extreme dippers (reduction by greater than or equal to 20%; n=16). The extent of silent cerebrovascular damage was least severe in the dipper group (P<.05). This J-shaped relation was not found either with the cardiac hypertrophy detected by electrocardiography or with the renal damage assessed by urinary albumin excretion. More than half of the extreme dippers were patients with isolated systolic hypertension, and this prevalence was significantly greater than that in dippers or in nondippers (21% and 30%, respectively). Extreme dippers also had greater variability of pressure (standard deviation of awake systolic pressure) than dippers. Our results indicate that in addition to nondipping, extreme dipping (marked nocturnal fall of blood pressure should be considered a type of abnormal diurnal blood pressure variation in elderly patients with hypertension who are likely to have advanced silent cerebrovascular damage.

Factor VII (FVII) plays an important role in initiation of the tissue factor-induced coagulation pathway. An increase in FVII coagulant activity (FVIIc) has been proposed as an independent risk factor for coronary artery disease. However, it remains uncertain whether high FVIIc levels are due to an increase in the activation of FVII or an increase in the concentration of FVII mass. We developed a new fluorogenic assay for plasma activated FVII (FVIIa) that used soluble tissue factor. The sensitivity of this assay ranged from 0.2 to 1000 ng FVIIa per milliliter of plasma. Plasma FVIIa levels were measured in 110 healthy subjects and 93 patients with hypertension, diabetes mellitus, and/or cardiovascular disease. The mean plasma FVIIa level in healthy Japanese individuals was 2.5 ng/mL, which was lower than that in Western subjects. Gel filtration analysis showed that most of the circulating FVIIa was in a free form, and binding of FVIIa to tissue factor in plasma was not detected. Aging increased both the FVIIa level and FVII mass, whereas menopause increased mainly the FVII mass. Elderly patients with arterial cardiovascular diseases showed increases in plasma FVIIa levels and FVIIa to FVII antigen (FVII:Ag) ratios. Among the elderly, arterial cardiovascular disease was more common in a high-FVIIa than a low-FVIIa group. Plasma FVIIa levels were not correlated with serum levels of total cholesterol or triglycerides. The FVIIa level and the FVIIa-to-FVII:Ag ratio were positively correlated with fibrinogen level and negatively correlated with body mass index and serum albumin level in the elderly. In conclusion, aging, cardiovascular disease, and malnutrition increased plasma FVIIa levels. FVIIa levels were not correlated with lipid levels or hepatic synthesis, suggesting that FVIIa may be an independent risk factor for cardiovascular disease.