石川 鎮清

Objectives To study the impact of the dosing time of an angiotensin II receptor blocker (ARB) titrated by self-measured home blood pressure (HBP) on cardiorenal damage in hypertensives. Methods We conducted an open-label multicenter trial, the J-TOP study, that enrolled 450 hypertensives with self-measured systolic HBP more than 135 mm Hg. The study patients were stratified into three groups according to the difference between their morning and evening SBPs difference: a morning hypertension group (morning and evening difference at least 15 mm Hg; n=170), a morning and evening hypertension group (0 mm Hg <= morning and evening difference <15 mm Hg; n=198), and an evening hypertension group (morning and evening difference <0 mm Hg; n=82). Individuals were then randomly allocated to receive bedtime dosing or awakening dosing of candesartan (+/-diuretic as needed) titrated to achieve a target systolic HBP less than 135 mm Hg. The 6-month change in the urinary albumin/creatinine ratio (UACR) was assessed. Results In total patients, the UACR was more markedly reduced in the bedtime-dosing group than in the awakening-dosing group (-45.7 vs. -34.5%, P=0.02), whereas there were no differences in the reduction of any of the HBPs including the sleep blood pressures (BPs) between the two groups. Among the three subgroups stratified by the morning and evening difference, the difference in the UACR reduction between the bedtime-dosing and awakening-dosing groups was only significant in the morning hypertension group (-50.6 vs. -31.3%, P=0.02). Conclusion In HBP-guided antihypertensive treatment in hypertensives, bedtime dosing of an ARB may be superior to awakening dosing for reducing microalbuminuria. J Hypertens 28: 1574-1583 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Introduction: An urban-rural gap in stroke incidence or mortality has been reported. However, whether the effect of rurality on stroke is independent of the distribution of conventional individual-level risk factors and other community-level risk factors is inconclusive. Methods: A cohort study was conducted involving 4849 men and 7529 women residing in 12 communities throughout Japan. Baseline data were obtained between April 1992 and July 1995. Follow up was conducted annually to capture first-ever-in-life stroke events. During that period, geographic, demographic and weather information was obtained for each community. Multi-level logistic regression analysis was conducted to evaluate the association between stroke incidence and each geographic/demographic factor adjusted for meteorological parameters (temperature and rainfall), in addition to individual-level risk factors (age, body mass index, smoking, total cholesterol, hypertension, and diabetes). Results: Throughout an average of 10.7 years' follow up, 229 men and 221 women with stroke events were identified. In women, low population (odds ratio [OR] per 1000 persons 0.97; 95% confidence interval 0.94-1.00), low population density (OR per 1/km(2) 0.85; 0.74-0.97) and high altitude (OR per 100 m 1.18; 1.09-1.28) increased the risk of stroke independently of individual-level risk factors; however, significance was absent for all three associations when further adjusted for weather parameters. Conversely, the association between each meteorological parameter and stroke in women was significant, even after adjustment for each of the three geographic/demographic factors. Similar results were obtained for cerebral infarction. Conclusion: The association between living in rural communities and stroke may be caused by the confounding effect of weather conditions in the communities studied.

Objective: Few epidemiological studies have examined the relationship between age at menopause and stroke incidence, and none have done so in Japanese women. Here, we investigated the relationship between age at menopause and stroke incidence in a large group of Japanese women. Methods: The study participants were 4,790 postmenopausal women aged 36 to 89 years enrolled in the Jichi Medical School Cohort Study, a population-based prospective study. Baseline data were obtained by questionnaire and health checkups between April 1992 and July 1995 in 12 rural areas in Japan. The incidence of all strokes and stroke subtypes was monitored. Results: Mean (SD) participant age was 61.0 (6.7) years, and mean (SD) age at menopause was 48.3 (4.8) years. A total of 185 strokes were observed during a mean follow-up of 10.8 years. On adjustment for age, systolic blood pressure, total cholesterol, body mass index, smoking habits, and alcohol drinking habits, hazard ratios (95% CIs) of stroke for women who underwent menopause before age 40 years, at 40 to 44 years, at 45 to 49 years, and at 55 years or after relative to those who underwent menopause at age 50 to 54 years were 1.56 (0.78-3.12), 1.59 (1.00-2.51), 1.28 (0.92-1.78), and 0.83 (0.38-1.81), respectively. However, hazard ratios (95% CI) of cerebral infarction for women who underwent menopause before age 40 years, at 40 to 44 years, at 45 to 49 years, and at 55 years or after relative to those who underwent menopause at age 50 to 54 years were 2.57 (1.20-5.49), 1.49 (0.80-2.78), 1.06 (0.67-1.68), and 1.08 (0.43-2.74), respectively. Conclusions: Our data suggest that Japanese women who undergo menopause before age 40 years are at an increased risk of cerebral infarction. Premature menopause should be considered an indicator of the need for more aggressive medical intervention aimed at the prevention of cerebral infarction.

BACKGROUND The significance of home blood pressure (BP) measurement in type 2 diabetes (T2DM) has not been well investigated. We aimed to test the hypotheses that home BP is more closely associated with target-organ damage than clinic BP, and that the presence of prediabetes/T2DM enhances the impact of home BP measurement. METHODS We studied 551 hypertensives (99 diabetics and 452 nondiabetics) whose self-measured systolic BP (SBP) was >135 mm Hg while on medication. The subjects were followed for 6 months after allocation to either a control group or an active treatment group. The changes in clinic BP and home BP were analyzed in relation to the changes in the spot urine albumin-creatinine ratio (UAR). RESULTS The extent of clinic and home BP reduction was similar between the diabetic and nondiabetic groups. The change in UAR in nondiabetics was significantly associated with the extent of SBP reduction in the clinic (r = 0.19), morning (r = 0.33), and evening (r = 0.22, all P < 0.01). In contrast, in the diabetic group, the change in UAR was significantly associated with the changes in morning SBP (r = 0.23, P = 0.02) and evening SBP (r = 0.39, P < 0.001), but not with clinic BP. The correlation with evening SBP in the diabetic group tended to be stronger than the nondiabetic group. CONCLUSIONS In hypertensives with prediabetes/T2DM, changes in home BP were better than changes in clinic BP to predict changes in UAR. In particular, this suggests the hypothesis that aggressive control of evening home BP might be equally or more important to morning BP in hypertensives with prediabetes/T2DM.

Background: Many studies have reported an association between physical activity and cardiovascular disease (CVD); however, the effect of physical activity remains controversial. Few such studies have been conducted in Japan. Therefore, we examined the relationship between physical activity and death from CVD using prospective data from a Japanese population. Methods: From a prospective cohort study that comprised 12 490 participants, data from 9810 were analyzed. From April 1992 through July 1995, a baseline survey was conducted in 12 communities in Japan. The participants were Followed up until December 2005. Physical activity was assessed using the physical activity index (PAI). PAI scores were grouped in quartiles: Q1 was the lowest PAI quartile and Q4 was the highest. Hazard ratios (HRs) for death from CVD, stroke, and myocardial infarction (MI) were calculated for all PAI quartiles. Results: The mean follow-up period was 11.9 years, during which time 194 participants died of CVD. With Q1 as the reference, the HRs for death from CVD in Q2, Q3, and Q4, were 0.62 (95% confidence interval, 0.40-0.98), 0.53 (0.31-0.88), and 0.40 (0.22-0.73), respectively, in men, and 0.71(0.38-1.32). 0.52 (0.26-1.04), and 0.48 (0.22-1.05), respectively, in women. The HRs for death from CVD subtypes were similar but not statistically significant. Conclusions: Among a Japanese population, physical activity was associated with a decreased risk of death from CVD. However, more evidence is needed to elucidate the relationships between physical activity and CVD subtypes.

Objective We tested the reproducibility of ambulatory blood pressure (ABP), BP variability, and BP reduction in hypertensive patients. Methods Forty-two hypertensive patients were enrolled, and ABP monitoring (ABPM) was performed four times in each patient: twice before and twice after the treatment. Morning BP was defined as the average of 2 h after waking, and morning BP surge (MBPS) was defined by four ways: sleep-trough, preawake, morning-evening and morning-after-bed surge. The BP variability was evaluated by standard deviation, weighted standard deviation, coefficient of variation and average real variability. The reproducibility was compared using the repeatability coefficient and the Bland-Altman's method. Results The awake, sleep, 24-h and morning BP were well corresponded in the first and the second ABPM values in each period. The four measures of BP variability also corresponded well between the first and the second ABPM values in each period. MBPS did not correspond well in each period when it was defined by diaries, but the extent of correlation was improved when it was defined by actigraphy. The reproducibility of BP-lowering effect was fair when it was defined by a single parameter, but not very good when it was defined by two parameters (e.g. MBPS). Conclusion The reproducibility of ABP levels and BP variability was fairly good and that of MBPS was moderate when defined by actigraphy. The good reproducibility of BP reduction means that each single ABPM, before and after the treatment, is acceptable for the assessment of drug efficacy. J Hypertens 28:918-924 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Background: Although sleep is one of the most important health-related factors, the relationship between sleep duration and the incidence of cardiovascular events has not been fully described. Methods: The present Study comprised the 11 367 Study Subjects (4413 men and 6954 women) of the Jichi Medical School Cohort Study, a population-based prospective Study. Baseline data were obtained by questionnaire and health examinations between April 1992 and July 1995 in 12 rural areas in Japan, and the main outcome measures were the incidence of cardiovascular diseases (stroke and myocardial infarction [MI]). Cox proportional hazards models were used to analyze the association between sleep duration and the incidence of cardiovascular events. Results: A total of 481 cardiovascular events (255 men and 226 women) were observed during all average follow-Lip period of 10.7 years. After ad Listing for age, systolic blood pressure, serum total cholesterol, body mass index, smoking habits, and alcohol drinking habits, the hazard ratios (95% confidence intervals) for the incidence of cardiovascular diseases for individuals sleeping less than 6 hours and 9 hours or longer were 2.14 (1.11-4.13) and 1.33 (0.93-1.92) in men, and 1.46 (0.70-3.04) and 1.28 (0.88-1.87) in women, respectively, relative to those who reported sleeping 7 to 7.9 hours per day. Conclusions: Our data indicate that men who sleep less than 6 hours a day have a higher risk of cardiovascular events than those sleeping 7 to 7.9 hours.

Background: Although seasonal variation in stroke incidence has been reported, it is not known whether yearlong exposure to particular meteorological conditions affects the risk of stroke independently of conventional cardiovascular risk factors. Methods: We conducted a cohort study involving 4849 men and 7529 women residing in 12 communities dispersed throughout Japan. Baseline data were obtained from April 1992 through July 1995. Follow-Lip was conducted annually to capture first-ever-in-life stroke events. Weather information during the period was also obtained for each community. Multilevel logistic regression analysis was conducted to evaluate the association between stroke incidence and each meteorological parameter adjusted for age, obesity, smoking status, total cholesterol, systolic blood pressure, diabetes, and other meteorological parameters. Results: Over an average of 10.7 years of follow-up, 229 men and 221 women had stroke events. Among women, high annual rainfall (OR per 1000 mm, 1.46; 95% confidence interval, 1.05-2.03). low average ambient temperature (OR per 1 degrees C, 0.79; 0.66-0.94), and number of cold days per year (OR per 10 days, 3.37; 1.43-7.97) were associated with increased risk of stroke incidence, independent of conventional risk factors. Among men, number of cold days (OR per 10 days, 1.07; 1.02-1.12) was associated with all increased risk of stroke incidence, but the association became non-significant after adjustment for other risk factors. Similar results were obtained for cerebral infarction and cerebral hemorrhage. Conclusions: Long-term exposure to some meteorological conditions inlay affect the risk of stroke, particularly in women, independent of conventional risk factors.

Background: Metabolic syndrome increases the morbidity and mortality of cardiovascular diseases. However, few studies have examined the association between the incidence of stroke and metabolic syndrome, as defined by Japanese criteria. The aim of this study was to identify the association between stroke and metabolic syndrome, as defined by criteria used in Japan. Methods: A total of 2205 subjects (920 men and 1285 women) were examined between 1992 and 1995 as part of the Jichi Medical School Cohort Study. Metabolic syndrome was defined using the Japanese criteria. Medical records, computed tomography, and magnetic resonance imaging were used to diagnose stroke. The Cox proportional-hazards model was used to analyze the association between metabolic syndrome and incident stroke. Results: The prevalence of metabolic syndrome at baseline was 9.0% in men and 1.7% in women. There were 96 incident strokes during an 11.2-year follow-up period, 14 of which Occurred in Subjects with metabolic syndrome. Among Subjects with metabolic syndrome, the age-adjusted hazard ratio (95% confidence interval) for stroke was 1.93 (0.94-3.96) in men and 6.85 (2.68-17.47) in women. After adjusting for age, smoking status, and alcohol drinking status, the hazard ratio was 1.89 (0.88-4.08) in men and 7.24 (2.82-18.58) in women. Age-adjusted hazard ratios associated with having 2 or more components of metabolic syndrome, with and without central obesity, were 2.93 (1.21-7.08) and 3.20 (1.23-8.31) in men and 1.75 (0.69-4.44) and 8.64 (2.82-28.03) in women, respectively, Conclusions: The presence of metabolic syndrome, as defined by Japanese criteria, increases the risk of stroke; this effect was highly significant among women.

Background It has been demonstrated that insulin resistance is associated with morning hypertension. We investigated the hypothesis that the lowering of morning blood pressure (BP) can improve insulin resistance in patients with morning hypertension. Methods In the present study, 611 treated hypertensive patients with morning hypertension were randomized into either a doxazosin group, for whom a once-daily bedtime dose of doxazosin was added to the current medication regimen, or a control group, who continued their current medication. The homeostasis model assessment of the insulin resistance index (HOMA-IR) was performed at baseline and the 6th month of treatment. The associations between change in HOMA-IR and changes in systolic BP (SBP) measures were assessed by multiple regression analyses with adjustment for covariates. Results HOMA-IR was significantly decreased in the doxazosin group (2.1 +/- 3.0 to 1.8 +/- 2.6, P = 0.04) but not in the control group. The change in HOMA-IR was significantly associated with the change in morning SBP (r = 0.10, P = 0.02) but not with evening SBP. In multiple regression analysis, the change in HOMA-IR was independently and significantly associated with the change in morning SBP (beta = 0.15, P = 0.016) but not with the change in evening SBP. Conclusion In patients with morning hypertension, specific treatment for morning hypertension with an adrenergic blockade has a beneficial effect on insulin resistance. J Hypertens 27:1252-1257 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Background: Lower mortality has been reported in light-to-moderate alcohol drinkers. We examined the association between the amount and frequency of alcohol consumption and all-cause mortality in a Japanese population. Methods: We conducted a prospective cohort study among 8934 Japanese people (3444 men and 5490 women) who completed a baseline survey between 1992 and 1995. We confirmed the date and cause of death by referring to death certificates. The Cox proportional hazards model was used to evaluate the effect of alcohol consumption on risk for all-cause mortality, after adjustment for potential confounding factors. Results: We identified 637 (397 men and 240 women) deaths during the 12.0 years of mean follow-up. Among men, as compared with non-drinkers, the relative risk was higher in ex-drinkers (hazard ratio [HR], 1.18), lower in light drinkers (HR, 0.95) and moderate drinkers (HR, 0.91), and significantly higher in heavy drinkers (HR, 1.67; 95% confidence interval, 1.10-2.55). Among women, light, moderate, and heavy drinkers were grouped into current drinkers. The relative risk was slightly higher in current drinkers (HR, 1.23), and that in ex-drinkers was near 1.0 (HR, 0.97). In stratified analysis, the harmful effects of heavy drinking were more severe among male smokers and younger men. In terms of frequency, men who drank only on special occasions had the highest mortality (HR, 1.28), regardless of alcohol intake per drinking session. Conclusions: In men, a near J-shaped association was identified between alcohol consumption and all-cause mortality. Both the amount and frequency of alcohol consumption were related to mortality.

Background: Risk charts are used to estimate the risk of cardiovascular diseases; however, most have been developed in Western Countries. In Japan, currently available risk charts are based on mortality data. Using data on cardiovascular disease incidence from the JMS Cohort Study, we developed charts that illustrated the risk of stroke.Methods and Results: The JMS Cohort Study is a community-based cohort study of cardiovascular disease. Baseline data were obtained between 1992 and 1995, In the present analysis, the participants were 12 276 subjects without a history of stroke; the follow-up period was 10.7 years. Color-coded risk charts were created by using Cox's proportional hazards models to calculate 10-year absolute risks associated with sex, age, smoking status, diabetes status, and systolic blood pressure. The risks of stroke and cerebral infarction rose as age and systolic blood pressure increased. Although the risk of cerebral hemorrhage were generally lower than that of cerebral infarction, the patterns of association with risk factors were similar.Conclusion: These risk charts should prove useful for clinicians and other health professionals who are required to estimate an individual's risk for stroke.

Background: Risk charts that depict the absolute risk of myocardial infarction (MI) for each combination of risk factors in individuals are convenient and beneficial tools for primary prevention of ischemic heart disease. Although risk charts have been developed using data from North American and European cardiovascular cohort studies, there is no such chart derived from cardiovascular incidence data obtained from the Japanese population.Methods and Results: We calculated and constructed risk charts that estimate the 10-year absolute risk of MI by using data from the Jichi Medical School (JMS) Cohort Study-a prospective cohort study which followed 12490 participants in 12 Japanese rural communities for an average of 10.9 years. We identified 92 cases of a clinically-certified MI event. Color-coded risk charts were created by calculating the absolute risk associated with the following conventional cardiovascular risk factors: age, sex, smoking status, diabetes status, systolic blood pressure, and serum total cholesterol.Conclusions: In health education and clinical practice, particularly in rural communities, these charts should prove useful in understanding the risks of MI, without the need for cumbersome calculations. In addition, they can be expected to provide benefits by improving existing risk factors in individuals.

Background: Adiponectin is associated with many cardiovascular risk factors. Thus, a relation between adiponectin and subsequent coronary heart disease has been hypothesized. However, the results of prospective studies have been conflicting. Methods: In this nested case-control study, blood samples were collected from 5243 of 12 490 community residents enrolled in the Jichi Medical School Cohort Study. The samples were taken between 1992 and 1995 and stored until 2007, at which point the plasma adiponectin level was measured. Results: During an average of 9.4 years of follow-up, 38 patients with myocardial infarction and 89 controls matched for age, sex, and community were identified. Plasma adiponectin concentration did not significantly differ between cases and controls (geometric mean 7.6 [interquartile range, 5.0-12.2] versus 7.4 [5.4-11.0] mg/L, respectively, P = 0.57). The odds of myocardial infarction in the lowest tertile of adiponectin concentration was not significantly different from that in the highest tertile, after adjustment for age and sex (OR 1.33; 95% CI, 0.50-3.55) or after further adjustment for other cardiovascular risk factors (OR 1.69; 95% CI, 0.45-6.25). Similarly, there was no significant difference in odds of myocardial infarction between the lowest and highest quartiles of adiponectin concentration. Conclusion: The results do not support an association between hypoadiponectinemia and myocardial infarction.

BACKGROUND The negative white-coat effect (WCE), a phenomenon in which out-of-office blood pressure (BP) is higher than clinic BP, has not been well examined, unlike the WCE. METHODS As part of the Jichi Morning Hypertension Research study, in which clinic and home BP were measured in 969 hypertensive outpatients, 405 patients with normal clinic BP were separately analyzed, Clinic BP was measured on two different occasions, and home BP was measured twice in the morning and twice in the evening for three consecutive days. Clinic and home BP were each averaged from all readings, and negative WCE was defined as clinic systolic BP (SBP) lower than home SBP. RESULTS Negative WCE was observed in 324 (33%) of the patients overall and in 173 (42%) of the patients with controlled BP (clinic BP < 140/90 mm Hg). In multiple logistic regression analysis adjusting for covariates including home SBP and pulse rate, negative WCE was correlated with older age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.06) and male gender (OR 1.08, 95% CI 1.01-1.14) in overall subjects. Among patients with well-controlled clinic BP, negative WCE was significantly correlated with the presence of ischemic heart disease (OR 1.17, 95% CI 1.04-1.31). The association of negative WCE with age and male gender remained significant under stringent criteria (negative WCE < -10.2 mm Hg (the mean -1 s.d.)). CONCLUSIONS Negative WCE remaining even after clinic BP is controlled may be related to cardiovascular risk factors such as older age, male gender, and a history of ischemic heart disease.

Left ventricular hypertrophy (LVH), assessed by ECG, is associated with an increased risk for cardiovascular events among hypertensive subjects. We evaluated the risks of LVH in a Japanese general population including normotensive and prehypertensive subjects. We measured ECG and blood pressure in 10 755 subjects at baseline. The Cornell product (CP) and Sokolow-Lyon (SL) voltage were calculated as markers of LVH (CP >= 2440 mm x ms and SL voltage >= 38 mm). Follow-up was performed for 10 years, and the incidence of stroke and myocardial infarction was evaluated. The prevalence of CP-LVH was 2.7% for normotensives, 5.2% for prehypertensives, and 11.0% for hypertensives, and the prevalence of SL-LVH was 5.0%, 8.2%, and 15.2%, respectively. In all of the subjects, CP-LVH and SL-LVH were both predictors of stroke (CP-LVH: hazard risk: 1.62, 95% CI: 1.19 to 2.20, P = 0.002; SL-LVH: hazard risk: 1.29, 95% CI: 0.98 to 1.71, P = 0.07) after adjustment for confounding factors but were not predictors of myocardial infarction. The adjusted hazard ratio of CP-LVH predicting stroke was especially high in the normotensives (hazard risk: 7.53; 95% CI: 3.39 to 16.77). In the normotensives, diabetes mellitus and hyperlipidemia were significant determinants of CP-LVH but not of SL-LVH. In all of the hypertensive subgroups (normotensives, prehypertensives, and hypertensives), the c-statistic for the equation predicting stroke increased when CP-LVH was added to the model but not when SL-LVH was added. In conclusion, both CP-LVH and SL-LVH are risk factors for stroke in the Japanese general population. CP-LVH is related to glucose abnormality, and its predictive value for stroke is seen even in normotensives and prehypertensives. (Hypertension. 2009; 53: 28-34.)

Background: No prospective studies have examined the association between occupational stress according to the job demand-control model and the risk of stroke in Asian populations.Methods: We conducted a multicenter community-based prospective study of 6553 Japanese male and female workers. Occupational stress was evaluated using a Japanese version of the job demand-control model questionnaire. We used the Cox proportional hazards model to evaluate the association between occupational stress and stroke.Results: During a mean follow-up of 11 years, we identified 147 incident strokes. Multivariable analysis revealed a more than 2-fold increase in the risk of total stroke among men with job strain (combination of high job demand and low job control) (hazard ratio, 2.73; 95% confidence interval, 1.17-6.38) compared with counterpart men with low strain (combination of low job demand and high job control) after adjustment for age, educational attainment, occupation, smoking status, alcohol consumption, physical activity, and study area. Additional adjustments for biologic risk factors attenuated the hazard ratio, but there continued to be statistical significance (hazard ratio, 2.53; 95% confidence interval, 1.08-5.94). In women, no statistically significant differences were found for any stroke incidence among the job characteristic categories.Conclusion: Occupational stress related to job strain was associated with incident strokes among Japanese men.

Background: In April 2008, a new health check-up and health guidance system was introduced by the Japanese Government to promote increased physical activity. However, few studies have documented the health benefits of physical activity in Asian populations. We examined the association between all-cause mortality and level of physical activity in a Japanese multicommunity population-based study. Methods: The Jichi Medical School Cohort Study is a multicommunity, population-based study based in 12 districts in Japan. Baseline data from 4222 men and 6609 women (mean age, 54.8 and 55.0 years, respectively) were collected between April 1992 and July 1995. The participants were followed for a mean duration of 11.9 years. To determine the association between all-cause mortality and level of physical activity, crude mortality rates per 1000 person-years and hazard ratios (HRs) with 95% confidence intervals (CI) were determined using the Cox proportional hazards model. Physical activity was categorized by using physical activity index (PAI) quartiles. The lowest (first) PAI quartile was defined as the HR reference. Results: In men, the lowest mortality rate was observed in the third quartile, with 95 deaths and a crude mortality rate of 7.6; the age- and area-adjusted HR was 0.59 (95% CI, 0.45-0.76), and the mortality curve had a reverse J shape. In women, the lowest mortality rate was observed in the highest PAI quartile, with 69 deaths and a crude mortality rate of 3.5; the HR was 0.81 (95% CI, 0.58-1.12). Conclusion: Our results suggest that increased physical activity lowers the risk for all-cause death in Japanese.

Background: It is not known whether short duration of sleep is a predictor of future cardiovascular events in patients with hypertension. Methods: To test the hypothesis that short duration of sleep is independently associated with incident cardiovascular diseases (CVD), we performed ambulatory blood pressure (BP) monitoring in 1255 subjects with hypertension (mean [SD] age, 70.4 [9.9] years) and followed them for a mean period of 50 (23) months. Short sleep duration was defined as less than 7.5 hours (20th percentile). Multivariable Cox hazard models predicting CVD events were used to estimate the adjusted hazard ratio and 95% confidence interval (CI) for short sleep duration. A riser pattern was defined when mean nighttime systolic BP exceeded daytime systolic BP. The end point was a cardiovascular event: stroke, fatal or nonfatal myocardial infarction (MI), and sudden cardiac death. Results: In multivariable analyses, short duration of sleep (<7.5 hours) was associated with incident CVD (hazard ratio [HR], 1.68; 95% CI, 1.06-2.66; P = .03). A synergistic interaction was observed between short sleep duration and the riser pattern (P = .09). When subjects were classified according to their sleep time and a riser vs non-riser pattern, the group with shorter sleep duration-plus the riser pattern had a substantially and significantly higher incidence of CVD than the group with predominant normal sleep duration plus the nonriser pattern (HR, 4.43; 95% CI, 2.09-9.39; P < .001), independent of covariates. Conclusions: Short duration of sleep is associated with incident CVD risk and the combination of the riser pattern and short duration of sleep that is most strongly predictive of future CVD, independent of ambulatory BP levels. Physicians should inquire about sleep duration in the risk assessment of patients with hypertension.

Non-dipping (nocturnal blood pressure [BP] decrease<10%) is related to accelerated urinary salt excretion (u-NaCl), and increased risk of left ventricular hypertrophy (LVH) and cardiovascular events. We evaluated whether non-dippers exhibit an advanced extracellular matrix fibrosis, in relation to increased u-NaCl, among normotensive subjects. We measured plasma tissue inhibitor of matrix metal loproteinase-1 (TIMP-), a marker of collagen fibrosis in extracellular matrix, to evaluate the relationship between non-dipping and u-NaCl In 73 normotensive subjects (no anti hypertensive medications, clinic BP<140/90 mmHg and/or 24-h ambulatory BP <125/80 mmHg). Non-dippers had a significantly higher percentage of subjects with Impaired fasting glucose (IFG) or diabetes mellitus (DM), and had a greater left ventricular mass index (LVMI), plasma TIMP-1 level and u-NaCl than dippers (IFG or DM: 24.0 vs. 6.3%, p=0.029; LVMI: 118 +/- 31 vs. 103 +/- 26 g/m(2), p=0.039; TIMP-1: 168 +/- 35 vs. 151 +/- 30 pg/mL, p=0.035; u-NaCl: 5.1 +/- 1.7 vs. 3.9 +/- 1.7 g/12 h, p=0.005). In logistic regression analysis, non-dipping was independently associated with u-NaCl and TIMP-1. u-NaCl was correlated with non-dipping (r=0.35, p=0.003) and serum glucose level (r=0.26, p=0.027). On the other hand, TIMP-1 level was significantly correlated with the presence of IFG or DM (r=0.23, p=0.046), but not with uNaCl. In conclusion, plasma TIMP-1 level, a measure of cardiovascular fibrosis in extracellular matrix, Is greater in normotensive non-dippers than in dippers; however, the Increased TIMP-1 level may be related to impaired glucose metabolism, and non-dipping may be related to increased u-NaCl associated with high serum glucose levels in normotensive subjects. (Hypertens Res 2008; 31: 2045-2051)

Orthostatic blood pressure (BP) dysregulation is a risk factor for both falls and cardiovascular events. Self-measured BP, carried out at home, is both highly reproducible and useful for evaluating anti hypertensive treatment. However, there have been a few reports on the clinical implications of orthostatic BP changes in home BP monitoring (HBPM). In the baseline examination for the Japan Morning Surge-1 Study, a multi-center randomized control trial, we evaluated 605 hypertensive outpatients who had a morning systolic BP above 135 mmHg. The plasma brain natriuretic peptide (BNP) level and urinary albumin excretion were measured. When the patients were divided into 10 groups, according to orthostatic BP change evaluated by HBPM, after adjusting for age, gender, body mass index and sitting home BP level, those in the top decile (n=60, orthostatic BP increase >7.8 mmHg) had a higher urinary albumin/creatinine ratio (UAR) than the lowest decile group (geometric mean [SEM range]: 209.1 [134.7-318.7] vs. 34.1 [20.1-56.2] mg/g creatinine [Cr], p=0.003) and the pooled second to ninth decile groups (n=485, 209.1 [134.7-318.7] vs. 39.7 [33.2-47.3] mg/g Cr, p<0.02). Additionally, patients in the top decile had a higher BNP level than the second to ninth decile groups (75.7 [55.0-103.1] vs. 23.6 [20.8-26.6] pg/mL, p=0.003). Evaluation of orthostatic hypertension at home might be a high-risk factor for cardiovascular events in hypertensive subjects with increased levels of BNP and a higher UAR, independent of the home sitting BP level. (Hypertens Res 2008; 31: 1509-1516)

Background: Previous reports indicated that the incidence rate of stroke was higher in Japan than in Western countries, but the converse was true in the case of myocardial infarction (MI). However, few population-based studies on the incidence rates of stroke and MI have been conducted in Japan.Methods: The Jichi Medical School (JMS) Cohort Study is a multicenter population-based cohort study that was conducted in 12 districts in Japan. Baseline data were collected between April 1992 and July 1995. We examined samples from 4,869 men and 7,519 women, whose mean ages were 55.2 and 55.3 years, respectively. The incidence of stroke, stroke subtypes, and MI were monitored.Results: The mean follow-up duration was 10.7 years. A total of 229 strokes and 64 MIs occurred in men, and 221 strokes and 28 MIs occurred in women. The age-adjusted incidence rates (per 100,000 person-years) of stroke were 332 and 221 and those of MI were 84 and 31 in men and women, respectively. In the case of both sexes, the incidence rates of stroke and MI were the highest in the group of subjects aged > 70 years.Conclusion: We reported current data on the incidence rates of stroke and MI in Japan. usionThe incidence rate of stroke remains high, considerably higher than that of MI, in both men and women. The incidence rates of both stroke and MI were higher in men than in women.

It has been reported that subjects with prehypertension (pre-HT) (systolic blood pressure [SBP] 120-139 mmHg and/or diastolic blood pressure [DBP] 80-89 mmHg) have an increased risk of cardiovascular disease (CVD). We evaluated the prevalence and determinants of pre-HT in a Japanese general population. We enrolled 4,706 males and 7,342 females aged 18 to 90 years whose BPs were measured at baseline. The subjects' BPs were classified as follows: normotension (NT: SPB/DBP<120/80 mmHg), pre-HT (120/80-139/89 mmHg), and hypertension (HT: >= 140/90 mmHg or treated hypertension). The prevalence of pre-HT was 34.8% (males), and 31.8% (females). Body mass index (BMI) of more than 23.0 kg/m(2) was the strongest determinant of pre-HT (Males-BMI: 23.0-24.9 kg/m(2), odds ratio [OR]=1.47, 95% confidence interval [Cl]=1.21-1.79; BMI: 25.0-26.9 kg/m(2), OR=2.20,95% CI=1.68-2.87; BMI: 27.0-29.9 kg/m(2), OR=2.75, 95% CI=1.80-4.19; BMI: >= 30.0 kg/m(2), OR=3.39, 95% CI=1.21-9.46. Females-BMI: 23.0-24.9 kg/m(2), OR=1.67, 95% CI=1.421.95; BMI: 25.0-26.9 kg/m(2), OR=1.79,95% CI=1.46-2.19; BMI: 27.0-29.9 kg/m(2), OR=3.65, 95% CI=2.73-4.89; BMI: >= 30.0 kg/m(2), OR=4.23, 95% CI=2.33-7.70). The other determinants of pre-HT were hyperlipidemia (Males: OR=1.25; Females: OR=1.43), and aging (by 10 years; Males: OR=1.12; Females: OR=1.48). Determinants of pre-HT in females were impaired glucose tolerance (OR=1.41, 95% CI=1.03-1.94), diabetes (OR=2.01, 95% CI=1.16-3.47) and a family history of HT in both parents (OR=1.90, 95% CI=1.38-2.62), whereas in males the only other predictor was alcohol drinking (OR = 1.45, 95% CI = 1.23-1.70). In conclusion, even subjects with a mild increase of BMI (23.0-24.9 kg/m2) had an increased risk of pre-HT in a Japanese population, and the level of BMI associated with pre-HT was lower than that in Western countries. Additionally, there were gender differences in the determinants of pre-HT. (Hypertens Res 2008; 31: 1323-1330)

Objective Patients with sleep apnea syndrome have an increased risk of cardiovascular events and frequently show a nondipper pattern (blunted nocturnal decline < 10%) of systolic blood pressure. We investigated neurohumoral activation and risk factors in relation to nocturnal blood pressure dipping pattern and sleep apnea syndrome. Methods We conducted sleep polysomnography and ambulatory blood pressure monitoring and measured high-sensitivity C-reactive protein, tissue-type plasminogen activator inhibitor-1, and neurohumoral factors in 121 outpatients with suspected sleep apnea syndrome who were classified into four groups on the basis of the presence or the absence of dipping/nondipping and sleep apnea syndrome. Results Nondippers with sleep apnea syndrome had higher high-sensitivity C-reactive protein (overall P < 0.001), plasminogen activator inhibitor-1 (overall P=0.004), and aldosterone levels (overall P=0.010) than any of the other three groups. After adjustment for significant covariates such as age, sex, body mass index, waist circumference, smoking, alcohol drinking, aspirin use, presence of diabetes, and insulin, nondippers with sleep apnea syndrome still had a higher high-sensitivity C-reactive protein level than nondippers without sleep apnea syndrome (geometric mean: 1.47 vs. 0.37 mg/l, P=0.001). In multiple linear regression analysis controlling for confounding factors related with sleep apnea syndrome, high-sensitivity C-reactive protein was significantly correlated with 3% oxygen desaturation index (P=0.047). Plasminogen activator inhibitor-1 level was also highest in the nondippers with sleep apnea syndrome but not independent of obesity. Plasminogen activator inhibitor-1 level correlated with insulin (r=0.32, P=0.002) and high-sensitivity C-reactive protein levels (r=0.26, P=0.005). Conclusion Nondipper status was associated with an increased high-sensitivity C-reactive protein level in patients who also had sleep apnea syndrome but not in those who did not. High-sensitivity C-reactive protein level was closely affected by the desaturation level. Plasminogen activator inhibitor-1 level is also increased in nondippers with sleep apnea syndrome and is related to insulin and high-sensitivity C-reactive protein levels.

Background The impact on microalbuminuria of strict treatment aimed at lowering of self-measured morning blood pressure using an adrenergic blockade is unclear. Methods We conducted an open-label multicenter trial, the Japan Morning Surge-1 Study, that enrolled 611 hypertensive patients, whose self-measured morning systolic blood pressure levels were more than 135 mmHg while taking antihypertensive drugs. These were randomly allocated to an experimental group, whose members received bedtime administration of 1-4 mg doxazosin (doxazosin group) or a control group whose members continued without any add-on medication (control group). The urinary albumin/creatinine ratio was investigated at the baseline and 6 months after the randomization. Results Both the morning and evening blood pressures and urinary albumin/creatinine ratio (-3.4 vs. 0.0 mg/gCr for urinary albumin/creatinine ratio; P<0.001) were more markedly reduced in the doxazosin group than in the control group. This difference in the urinary albumin/creatinine ratio between the two groups was more marked in the patients with microalbuminuria (n=238, -27.9 vs. -8.1 mg/gCr, P<0.001). The reduction of urinary albumin/creatinine ratio was significantly associated with the use of doxazosin, and the change in all self-measured blood pressures (morning, evening, the average morning-evening), and these associations were independent of each other (P<0.001). Conclusion Adding a bedtime dose of an a-adrenergic blocker titrated by self-measured morning blood pressure in treated hypertensive patients with uncontrolled morning hypertension significantly reduced blood pressure and urinary albumin excretion rate, particularly in those with microalbuminuria.

This study is to evaluate the associations between adiponectin level and non cardiovascular death and to test a hypothesis that adiponectin level reflects the degree of systemic wasting that precedes death. A nested case-control study was conducted involving 5243 subjects, drawn from 12490 subjects of the Jichi Medical School Cohort Study, whose blood samples had been drawn between 1992 and 1995. Over an average of 10.8 years of follow-up, 103 cases with noncardiovascular death and 565 controls without history/event/death of any cardiovascular disease were identified. Odds ratios (ORs) were estimated relative to the lowest quintile of adiponectin level. The risks for noncardiovascular death of the second lowest quintile and the highest quintile of adiponectin level were significantly higher than that of the lowest quintile when adjusted for age and sex (model 1) (OR, 2.38 [95% confidence interval (CI), 1.12-5.06] and 2.16 [1.01-4.80]). All the statistical significances disappeared when adjusted further for body mass index and C-reactive protein level (model 2). When excluding cases with cancer death, the odds for death in the highest 2 quintiles were significantly higher than those in the lowest quintile in model 1 (OR, 2.80 [95% CI, 1.04-7.59] and 3.74 [1.38-10.18]). The significant difference between the highest vs the lowest quintile remained significant in model 2 and even after adjusting further for smoking, diabetes, and total cholesterol level (model 3) (OR, 3.28 [95% CI, 1.02-10.51] and 3.98 [1.21-13.13]). Adiponectin levels had linear associations with the risks of noncardiovascular noncancer death in models 1, 2, and 3 (OR per 1 SD increase in log-adiponectin, 1.72 [95% CI, 1.23-2.40], 1.89 [1.23-2.91], and 2.01 [1.29-3.15]). Adiponectin is an independent indicator of noncardiovascular mortality that may relate with systemic wasting. (C) 2008 Elsevier Inc. All rights reserved.

Although it is confirmed that anti hypertensive treatment for hypertension (HT) reduces stroke, it is uncertain whether the risk of stroke in controlled hypertensives is as low as that in normotensives. To address this question, we examined the risk of stroke in hypertensives with or without anti hypertensive treatment in the general population. A total of 11,103 men and women were enrolled in for this multi-center, population-based cohort study. Subjects were divided into three categories: normotensives (blood pressure < 140/90 mmHg), treated hypertensives, and non-treated hypertensives (blood pressure >= 140/90 mmHg without antihypertensive treatment). The treated hypertensives were divided into controlled and uncontrolled HT groups. The non-treated hypertensives were also divided into two groups: mild HT, and moderate or severe HT. The mean follow-up duration was 10.7 years. Risk of all stroke was significantly higher in the hypertensives than in the normotensives (treated HT: hazard ratio=3.00 in men and 3.34 in women, 95% confidence interval =2.00-4.51 in men and 2.29-4.87 in women; non-treated HT: 2.56, 1.83-3.57 in men and 1.93, 1.35-2.76 in women). Risk of stroke in controlled treated hypertensives was about three times as high as that in normotensives (2.96, 1.66-5.26 in men and 3.69, 2.20-6.17 in women). Risk of stroke was about 2.5 times higher in individuals with hyperglycemia than in those with normoglycemia among both treated hypertensive men and women. In conclusion, compared with normotensives, hypertensives of all categories had a significantly higher risk of stroke. Residual confounding might have affected the result that risk of stroke was higher in controlled treated HT than in non-treated mild HT. Moreover, it is important to control blood pressure and blood glucose in hypertensives in order to reduce the risk of stroke.

Strong adherence to antihypertensive therapy has been shown to reduce the frequency of cardiovascular events by strictly controlling blood pressure. Although calcium channel blockers (CCBs) are among the most popular antihypertensive drugs in Japan, few trials have been conducted using high CCB doses in Japanese patients. In this study, we administered amlodipine 5 mg or 10 mg to patients with hypertension in order to compare the efficacy and tolerability of low and high doses, and measured two surrogate markers of hypertensive target organ damage, i.e., brain natriuretic peptide (BNP) as a risk marker of cardiac overload and microalbuminuria as a measure of renal damage. Seventy-two patients were randomly assigned to either amlodipine 5 mg (n = 35) or 10 mg (n = 37) dose groups. The latter group achieved greater reductions in clinic as well as both morning and evening home BP levels without an increase in pulse rate (the differences between the two groups in clinic/morning/evening systolic BP were 4.7/4.7/5.4 mmHg, and for diastolic BP they were 4.2/3.6/3.8 mmHg). Reductions in BNP and urinary albumin/creatinine ratio (UAR) levels were significantly correlated with the reductions in systolic BP levels (BNP, clinic/morning BP: r = 0.256, p = 0.030/r = 0.330, p = 0.005; UAR, clinic BP: r = 0.316, p = 0.007). In conclusion, the higher dose (10 mg) of amlodipine induced greater reductions in all BP levels than did the lower dose, without increasing the pulse rate. These additional reductions were significantly correlated with reductions in hypertensive cardiac overload, as evaluated by BNP levels, and a reduction in renal damage, as evaluated by microalbuminuria levels. Moreover, a reduction in the microalbuminuria may have occurred concomitant with a reduction in clinic systolic BP level.

BACKGROUND The prognostic significance of ambulatory blood pressure (ABP) has not been established in patients with type 2 diabetes (T2DM). METHODS In order to clarify the impact of ABP on cardiovascular prognosis in patients with or without T2DM, we performed ABP monitoring (ABPM) in 1,268 subjects recruited from nine sites in Japan, who were being evaluated for hypertension. The mean age of the patients was 70.4 +/- 9.9 years, and 301 of them had diabetes. The patients were followed up for 50 23 months. We investigated the relation between incidence of cardiovascular diseases (CVDs) and different measures of ABP, including three categories of awake systolic blood pressure (SBP < 135,135-150, and > 150 mm Hg), sleep SBP (< 120,120-135, and > 135 mm Hg), and dipping trends in nocturnal blood pressure (BP) (dippers, nondippers, and risers). Cox regression models were used in order to control for classic risk factors. RESULTS Higher awake and sleep SBPs predicted higher incidence of CVD in patients with and without diabetes. In multivariable analyses, elevated SBPs while awake and asleep predicted increased risk of CVD more accurately than clinic 1313 did, in both groups of patients. The relationships between ABP level and CVD were similar in both groups. In Kaplan-Meier analyses, the incidence of CVD in nondippers was similar to that in dippers, but risers experienced the highest risk of CVD in both groups (P < 0.01). The riser pattern was associated with a similar to 150% increase in risk of CVD, in both groups. CONCLUSIONS These findings suggest that ABPM is a better predictor of cardiovascular risk than clinic BP, and that this holds true for patients with or without T2DM.

Background: Associations between dietary patterns and cardiovascular disease risk factors remain unclear. The objective of this study was to evaluate the association between dietary patterns derived from factor analysis and the levels of blood pressure and serum lipids in a Japanese population.Methods: We conducted a cross-sectional analysis among 6886 (in the analysis on blood pressure) and 7641 (in the analysis on serum lipids) Japanese subjects aged 40-69 years. Dietary patterns were identified from a food frequency questionnaire by factor analysis. Associations between dietary patterns and blood pressure and serum lipids were examined after taking potential confounders into account.Results: Three dietary patterns were identified: vegetable, meat, and Western. In men, the meat pattern was associated with higher total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol. The Western pattern was associated with higher total and LDL cholesterol. In women, the vegetable pattern was associated with lower systolic and diastolic blood pressure and pulse pressure, and higher HDL cholesterol. The meat pattern was associated with higher total and HDL cholesterol. The Western pattern was associated with higher total, HDL, and LDL cholesterol, and the least intake pattern of Western diet was associated with higher systolic and diastolic blood pressures.Conclusions: Dietary patterns of a Japanese population were related to cardiovascular disease risk factors, especially in women.

BACKGROUND AND PURPOSE - Even though adiponectin is associated with many traditional cardiovascular risk factors, studies assessing the association between adiponectin and cerebrovascular disease (CVD) are scarce. We assessed the odds of CVD at different plasma levels of adiponectin. METHODS - A nested case-control study was conducted involving 5243 subjects, drawn from 12 490 subjects of the Jichi Medical School Cohort Study, whose blood samples had been drawn between 1992 and 1995. Over an average of 9.7 years of follow-up, through 2005, 179 patients with cerebrovascular events were identified, in addition to 630 controls matched for age, sex, and community (total n=809). Odds ratios were estimated relative to the highest quartile of adiponectin level. RESULTS - There was neither a significant difference in the odds of stroke between the lowest and highest adiponectin quartiles, nor a significant linear trend toward a reduced risk of stroke at higher adiponectin levels. These results did not change after excluding participants with diabetes, impaired glucose metabolism, or metabolic syndrome. The odds of ischemic stroke in the lowest quartile were significantly higher than in the highest quartile, when adjusted for age and sex (OR 2.04 [95% CI, 1.09 to 3.80]). However, the odds failed to achieve statistical significance when adjusted further for other cardiovascular risk factors. Again exclusion of subjects with diabetes, impaired glucose metabolism, or metabolic syndrome did not alter results. CONCLUSIONS - Adiponectin levels are not independently associated with stroke or brain infarction. The use of adiponectin as a cerebrovascular disease predictor may be premature. © 2008 American Heart Association, Inc.

Objective Cardiovascular prognosis in diabetic white-coat hypertension (WCH) has not yet been described. We designed this study to investigate the impact of WCH on cardiovascular events in patients with type 2 diabetes, compared with those having type 2 diabetes along with sustained hypertension (SH), and with nondiabetic hypertensive individuals. Methods We performed ambulatory blood pressure (BP) monitoring in 1207 consecutive hypertensive patients at baseline, and they were followed up for 49 +/- 22 months. The mean age was 70.7 +/- 9.8 years; 262 had type 2 diabetes; and 945 did not. They were classified as having SH with diabetes (n = 210); diabetic WCH (n = 52); SH alone (n = 719); or WCH alone (n = 226), using awake BP of 135/85 mmHg as the cutoff value. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals of the risk for cardiovascular events, after controlling for age, sex, body mass index, current smoking, serum creatinine, and clinical systolic BP. Results During the follow-up period, 97 cardiovascular events occurred. The incidence of cardiovascular events in the diabetic SH group was significantly higher than in the diabetic WCH, nondiabetic SH, and nondiabetic WCH (P<0.05; log-rank test) groups. In Cox regression analysis, the diabetic SH group had significantly higher risk of cardiovascular events compared with the diabetic WCH group (HR: 8.2; 95% confidence intervals: 1.09-61.8; P = 0.04). Although nonsignificant, the HRs in the SH and WCH groups, relative to diabetic WCH, exceeded 3.0. Conclusions The cardiovascular prognosis for diabetic WCH was better than that for diabetic SH during 4 years of follow-up.

We evaluated whether morning minus evening systolic blood pressure (SBP) difference (MEdif) in home blood pressure measurements can be a marker for hypertensive target organ damage. The authors analyzed 611 hypertensive patients who had high morning SBP levels (>= 135 mm Hg) The patients with morning hypertension (MEdif >= 15 mm Hg, average of morning and evening SBP [MEave] >= 135 mm Hg) were older (P<.001) and bad a longer duration of hypertension and antihypertensive medication use, a higher prevalence of left ventricular hypertrophy (LVH) on electrocardiograph),, a lower glomerular filtration rate by the Cockcroft-Gault equation (P=.002), and a higher brain natriuretic peptide (BNP) level (P<.001) than those with well-controlled blood pressure (MEdif <15 mm Hg, Wave <135 mm Hg). The patients with morning hypertension had a higher BNP level than those with well-controlled blood pressure after adjustment for the confounding factors (28.7 pg/mL vs 20.0 pg/mL; P=.033). In conclusion, nlorning hypertension is more likely seen among patients with older age and longer duration of hypertension and anti-hypertensive medication use, and it may be associated with a higher prevalence of LVH and a higher BNP level. (J Clin Hypertens (Greenwich). 2008;10:34-42) (C) 2008 Le Jacq

Background. Recently, it was reported that high pulse rate (PR), which was measured using by self-measured blood pressure (BP) monitoring at home, was associated with cardiovascular risk. However, the predictor of high PR at home in treated hypertensives is unknown. In this study, we studied the predictor of high PR and evaluated pulse rate variability (PRV). Methods. In the JMS-1 study, 611 hypertensive outpatients were recruited. Self-measured BP monitoring was conducted consecutively twice in the morning and evening for three days. PR analysis was conducted using the average of these two measurements for three days (six readings in total). We defined home PR as the mean of these six readings. Home PRV was defined as the standard deviation of these six readings. Results. Multivariate linear regression analysis demonstrated that current smoking (beta = 0.12, p = 0.002), diabetes (beta = 0.16, p < 0.001), lack of angiotensin-converting enzyme (ACE) inhibitor use (beta = 0.10, p = 0.008), decreased brain-type natriuretic peptide (BNP; beta = 0.17, p < 0.001), and elevated home diastolic blood pressure (beta = 0.14, p = 0.009) were determinants of high PR. Determinants of decreased home PRV were female gender (beta = 0.10, p < 0.03) and increased hemoglobin A1c (HbA1c; beta = 0.15, p < 0.001). When we divided the patients into four groups according to home PR and its variability, hypertensives whose home PR was high and variability was low were found to have high HbA1c (ANOVA, p > 0.05). Conclusions. Smoking habit, diabetes, lack of ACE inhibitor use, and low BNP value were determinants of home PR, and female gender and higher HbA1c were significantly associated with its low variability. Home PR and its variability may be useful for detecting high-risk hypertensive patients, particularly with autonomic neuropathy.

Background: Pulse pressure (PP) is an independent marker of cardiovascular risk, even in treated hypertensive subjects, but is often little changed by antihypertensive treatment. We assessed the hypothesis that changes in PP during antihypertensive therapy correlate with changes in surrogate markers of target-organ damage. Methods: We studied 540 treated hypertensive subjects whose home systolic blood pressure (SBP) was >= 135 mm Hg. They were followed for 6 months after allocation to either a control group or an added treatment group (doxazosin, 1 to 4 mg plus beta-blocker when needed). The changes in PP and various blood pressure (BP) measures, including mean BP (MP), SBP, and diastolic BP (DBP) during follow-up, were related to changes in plasma B-type natriuretic peptide (BNP) and the urine albumin-creatinine ratio (UAR). Results: Although self-measured MP was significantly lowered in the added treatment group, PP was not changed overall, although some patients showed a decrease, and others showed an increase. In multivariable analyses, changes in both clinic and home PP were positively associated with changes in log BNP, such that increases in clinic and home PP were paralleled by corresponding increases in BNP. However, no such corresponding relationships were observed when home PP decreased. The change in home PP, but not clinic PP, was positively and linearly associated with the change in UAR. Conclusions: Changes in PP during antihypertensive treatment are important because PP may increase in some patients, in whom there are adverse changes in surrogate markers of target-organ damage. These changes of PP are best evaluated by home monitoring. Am J Hypertens 2007;20:1268-1275 (c) 2007 American Journal of Hypertension, Ltd.

BACKGROUND: Metabolic syndrome is known to increase morbidity and mortality of cardiovascular disease. The National Cholesterol Education Program Adult Treatment Expert Panel III in 2001 (revised in 2005) and the Japanese definition of metabolic syndrome were launched in 2005. No study regarding the association between metabolic syndrome by Japanese definition and mortality has been Performed. The aim of this study was to clarify the prevalence of metabolic syndrome and its effects to mortality in a population-based cohort study. METHODS: A total of 2176 subjects who satisfied the necessary criteria for metabolic syndrome were examined between 1992 and 1995 as a part of Jichi Medical School Cohort Study by Japanese definition. Cox's proportional hazard models were used to analyze the association of metabolic syndrome with mortality. RESULTS: The prevalence of metabolic syndrome was 9.0% in males and 1.7% in females. There were 17 deaths (14 males), including 6 cardiovascular deaths (5 males), during a 12.5-year follow-up period among metabolic syndrome subjects. After adjusting for age, smoking status, and alcohol drinking status, the hazard ratio (95% confidence interval) for all-cause mortality was 1.13 (0.64-1.98) in males and 1.31 (0.41-4.18) in females, and HR for cardiovascular mortality was 1.84 (0.68-4.96) in males, and 1.31 (0.17-9.96) in females. CONCLUSION: No statistical significant relationship between metabolic syndrome by Japanese defini tion and all-cause mortality was observed in a population-based cohort study.

Background Cardiovascular prognostic significance of relative wall thickness (RWT) in patients with diabetes has not been reported although concentric hypertrophy is common in diabetic patients. Purpose This study was conducted to test the hypothesis that the prognostic significance of different measures of left ventricular (LV) geometric change, principally IV mass index (LVMI) and RWT, would be different in diabetic patients compared with nondiabetic individuals among Japanese hypertensive subjects. Methods Ambulatory blood pressure monitoring and echocardiography were performed in 400 uncomplicated hypertensive individuals at baseline, of whom 379 (157 with diabetes and 222 without diabetes, mean age 67.8.8.8 years) were successfully followed up for 63 +/- 26 months to document cardiovascular events. We dichotomized LVMI and RWT to the highest quartile vs other 3 quartiles for further categoric analyses in diabetic and nondiabetic patients. Results Fifty-three cardiovascular events occurred during the follow-up period. With Kaplan-Meier analysis, both diabetic and nondiabetic patients with the highest quartile of LVMI showed a significantly higher incidence of cardiovascular vents. However, the highest quartile of RWT was associated with cardiovascular events only in diabetic subjects. With Cox regression analyses controlling for age, sex, body mass index, serum creatinine, triglycerides, and clinic systolic blood pressure, RWT (per 0.01 change), but not LVMI, was associated with cardiovascular events in diabetic patients (relative risk: 1.06, 95% confidence interval 1.02-1.11; P =.008), whereas LVMI (9/m(2)), but not RWT, was associated with cardiovascular events in nondiabetic patients (relative risk: 1.02, 95% confidence interval 1.01 -1.03; P =.005). Conclusion In hypertensive subjects with type 2 diabetes mellitus, echocardiographic LV RWT is a predictor of cardiovascular events independent of LV mass and other confounders.

Background: C-reactive protein (CRP) is an acute phase reactant, and has been reported as a predictor of cardiovascular diseases. Measurements of high sensitive CRP in thawed samples are possible and the values are thought to remain stable even after frozen storage. However, the long-term stability of CRP values has not been documented. We measured the values of CRP before and after long-term storage, and examined the difference in determined values. Methods: High sensitive CRP was measured before and after long-term storage of samples from 99 men and women among the JMS Cohort Study subjects. We selected subjects who underwent measurement of high sensitive CRP at the baseline by stratified sampling methods using baseline CRP values. CRP was measured in serum samples at the baseline and in thawed plasma samples after an average storage period of 13.8 years. Results: Geometric means of CRP were 0.25 mg/L and 0.59 mg/L before and after storage, respectively. The CRP values were significantly higher after long-term frozen storage than at the baseline (p<0.0001). The both values of logarithm CRP were significantly correlated using Pearson's correlation (r = 0.920, 95% confidence interval: 0.883-0.945). Conclusion: CRP values increased after long-term frozen storage. The CRP values showed a high correlation between before and after long-term storage.

Few studies have reported on risk factors by blood pressure categories based on antihypertensive treatment in the general population. We examined the associations between blood pressure categories and other risk factors in Japan. Cross-sectional study, multicenter population-based study was designed. A total of 11,302 men and women were eligible. Data were obtained from April 1992 to July 1995 in 12 rural districts in Japan. Subjects were divided into three categories: normotensives (with blood pressure < 140/90 mmHg), treated hypertensives (antihypertensive treatment regardless of current blood pressure), and nontreated hypertensives (blood pressure >= 140/90 mmHg without hypertensive treatment). The proportions of normotensives, treated hypertensives, and nontreated hypertensives were 63%, 10%, and 27% among men, and 67%, 13%, and 20% among women, respectively. Total cholesterol, triglyceride, blood glucose, and body mass index were higher in treated or nontreated hypertensives than in normotensives. Fibrinogen, factor VIIc, and physical activity index were higher in treated hypertensives than in normotensives. High-density lipoprotein (HDL) cholesterol was higher in normotensives than in treated or nontreated hypertensives in women; but no tendency was shown in men. The proportions of dyslipidemia, impaired glucose tolerance, and metabolic syndrome were significantly higher in treated and nontreated hypertensives than in normotensive men and women. In conclusion, cardiovascular risk factors were higher in hypertensives with or without treatment than in normotensives in a general population in Japan.

Background: A dual angiotensin type 1 receptor blocker (ARB)/peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonist telmisartan may be more useful for microalbuminuria reduction than ARBs with no PPAR gamma agonistic action. We investigated whether there is a difference between the effects of telmisartan and valsartan with respect to microalbuminuria reduction, and the association with improvement of metabolic features or suppression of the inflammatory state. Methods: Fifty-three patients who had metabolic syndrome and had been taking valsartan were recruited. All of these patients were randomly assigned to replace valsartan by telmisartan (telmisartan group; n = 30) or to keep taking valsartan (control group; n = 21). Various parameters were measured at baseline and 12 weeks after randomization. Results: There were no significant changes in blood pressure (BP), glucose, and lipid parameters between baseline and 12 weeks after randomization in either group. There was a significant increase in high molecular weight adiponectin in the telmisartan group (4.6 v 5.0 mu g/mL, P =.024), whereas there was no significant change in the control group. The reductions of microalbuminuria and high-sensitivity C-reactive protein (hs-CRP) were significant in the telmisartan group (28.1 v 18.9 mg/g center dot Cr and 0.77 v 0.60 mg/L, respectively, P =.001 and P =.022), whereas there was no significant change in the control group. The reductions of microalbuminuria and hs-CRP were significantly correlated with each other (gamma = 0.413, P =.003). Conclusions: The dual ARB/PPAR gamma agonist telmisartan achieved more microalbuminuria reduction than an ARB with no PPAR gamma agonistic action, possibly through suppression of the inflammatory state in metabolic hypertensive patients.

Background and Purpose - High-sensitivity C-reactive protein (hsCRP), a marker of inflammation, is associated with atherosclerosis, hypertensive target organ damage, and cardiovascular events. In the general Japanese population, the level of hsCRP is reported to be lower than that in Western countries, and the relationships among hsCRP, silent cerebral infarcts (SCIs), and clinical stroke events in older Japanese hypertensives remain unclear. Methods - We conducted brain MRI and measured hsCRP at baseline in 514 older Japanese hypertensives ( clinic blood pressure >= 140/90 mm Hg, age >= 50 years old) who were enrolled in the Jichi Medical School ABPM Study, wave 1. They were followed up for an average of 41 months ( range: 1 to 68 months, 1751 person-years) and the incidence of subsequent clinical stroke events was evaluated. Results - The subjects with SCIs at baseline (n = 257) had a higher hsCRP level than those without SCIs ( geometric mean hsCRP [SD range];0.19 [0.18 to 0.21] versus 0.14 [0.13 to 0.16] mg/L, P = 0.007) after adjustment for confounding factors, and the OR for the presence of SCIs was increased with the quartile of hsCRP levels. In Cox regression analysis, the patients with above median hsCRP level (>= 0.21 mg/L) (hazard ratio [HR]: 2.50, 95% CI: 1.24 to 5.00, P = 0.01) and those with SCIs ( HR: 4.60, 95% CI: 1.91 to 11.03, P = 0.001) at baseline had independently higher risks for clinical stroke events after adjustment for age, smoking status, antihypertensive medication use, and 24-hour systolic blood pressure level. Compared with the patients with below median hsCRP level without SCIs, those with above median hsCRP level and SCIs at baseline had a higher risk for clinical stroke events ( HR: 7.32, 95% CI: 2.17 to 24.76, P = 0.001), although those with below median hsCRP level and SCIs ( HR: 2.46, 95% CI: 0.64 to 9.47, P = 0.19) and those with above median hsCRP level without SCIs ( HR: 1.11, 95% CI: 0.22 to 5.55, P = 0.90) did not have significant risks. Conclusion - High-sensitivity C-reactive protein is a risk factor for clinical stroke events in addition to silent cerebral infarcts in Japanese older hypertensives, indicating that the risk for clinical stroke events increases with preexisting hypertensive target organ damage in the brain and additionally with ongoing low-grade inflammation.

BACKGROUND: Relationships between consumption of dairy products and death from various types of cancer are largely unknown. METHODS: Between April 1992 and July 1995, a baseline survey was conducted for 11,349 residents in 12 communities in Japan, which included collection of demographic data and a self-administered food-frequency questionnaire inquiring about three dairy products: milk, butter and yogurt. The subjects were followed prospectively until 2002. Causes of death were identified using death certificates. Hazard ratios (HRs) and their 95% confidence intervals (Cls) for each dairy product were calculated using Cox's proportional hazard models. RESULTS: Among eight common cancers, only deaths from hernatopoietic neoplasm (n=14) were significantly associated with consumption of butter (HR=5.11, 95% Cl: 1.40-18.62), though they exhibited a nearly-significant association with milk consumption (HR=3.17, 95% Cl: 0.99-10.17), independent of age and sex. Consumption of milk and butter was significantly associated with non-lymphoma deaths 7 (n=9) when adjusted for age and sex (HR=9.86, 95% Cl: 1.23-, 9.19 for milk; and HR=1 0.04, 95% Cl: 2.39-42.18 for butter). CONCLUSION: The frequencies of butter consumption, and probably that of milk, were correlated with death from hematopoietic neoplasm, particularly from non-lymphomas.