石川 鎮清

The authors aimed to investigate the blood pressure (BP)-lowering ability of eplerenone in drug-resistant hypertensive patients. A total of 57 drug-resistant hypertensive patients whose home BP was 135/85 mm Hg were investigated. The patients were randomized to either an eplerenone group or a control group and followed for 12 weeks. The efficacy was evaluated by clinic, home, and ambulatory BP monitoring. Urinary albumin, pulse wave velocity, and flow-mediated vasodilation (FMD) were also evaluated. Home morning systolic BP (148 +/- 15 vs 140 +/- 15 mm Hg) and evening systolic BP (137 +/- 16 vs 130 +/- 16 mm Hg) were significantly lowered in the eplerenone group (n=35) compared with baseline (both P<.05), while unchanged in the control group (n=22). BP reductions in the eplerenone group were most pronounced for ambulatory awake systolic BP (P=.04), awake diastolic BP (P=.004), and 24-hour diastolic BP (P=.02). FMD was significantly improved in the eplerenone group. In patients with drug-resistant hypertension, add-on use of eplerenone was effective in lowering BP, especially home and ambulatory awake BP.

BackgroundDue to ethic differences in its serum levels, clinical applicability of high-sensitivity C-reactive protein (hsCRP) to the primary prevention of atherosclerotic events has not completely been established in Japanese people whose hsCRP levels are lower than in Western people. This study investigated the relationship between hsCRP and myocardial infarction (MI) in general Japanese people. MethodsIn relation to hsCRP, the incidence of MI was determined in a multiregional population-based prospective cohort study (n = 6,637; mean age 54.9 years; 2,513 men/4,124 women). ResultsFifty-six cases of MI were confirmed during a follow-up period of 10.7 years. The cut-off levels of hsCRP between the highest quartile (fourth quartile) and the other quartiles combined were 0.368 mg/l in men and 0.279 mg/l in women. The hazard ratio (HR) of the highest quartile for MI was significantly greater than that of the other quartiles combined (multivariate-adjusted HR: 2.07, 95% confidence interval: 1.03-4.15) in men, but not in women (1.03, 0.35-2.21). ConclusionsIn this population, serum hsCRP measurement predicted MI in men, but not in women. Under the low hsCRP level, a method of applicability of hsCRP to a risk assessment for preventing MI among Japanese people should be further explored.

Background: Progress testing (PT) is used in Western countries to evaluate students' level of functional knowledge, and to enhance meaning-oriented and self-directed learning. However, the use of PT has not been investigated in East Asia, where reproduction-oriented and teacher-centered learning styles prevail. Here, we explored the applicability of PT by focusing on student perceptions. Methods: Twenty-four students from Years 2, 3, and 5 at Jichi Medical University in Japan attended a pilot PT session preceded by a brief introduction of its concept and procedures. Variations in obtained test scores were analyzed by year, and student perceptions of PT were explored using focus groups. Results: Formula scores (mean +/- standard deviation) in Years 2, 3, and 5 were 12.63 +/- 3.53, 35.88 +/- 14.53, and 71.00 +/- 18.31, respectively. Qualitative descriptive analysis of focus group data showed that students disfavored testing of medical knowledge without tangible goals, but instead favored repetitive assessment of knowledge that had been learned and was tested on a unit basis in the past in order to achieve deep learning. Further, students of all school years considered that post-test explanatory lectures by teachers were necessary. Conclusions: East Asian students' perceptions indicated that, in addition to their intensive memorization within narrow test domains compartmentalized by end-of-unit tests, the concept of PT was suitable for repetitive memorization, as it helped them to integrate their knowledge and to increase their understanding. Post-test explanatory lectures might lessen their dislike of the intangible goals of PT, but at the expense of delaying the development of self-directed learning. Key issues for the optimization of PT in East Asia may include administration of PT after completed end-of-unit tests and a gradual change in feedback methodology over school years from test-oriented post-test lectures to the provision of literature references only, as a means of enhancing test self-review and self-directed learning.

Background: Cause of death (COD) information taken from death certificates is often inaccurate and incomplete. However, the accuracy of Underlying CODs (UCODs) recorded on death certificates has not been comprehensively described when multiple diseases are present. Methods: A total of 450 consecutive autopsies performed at a geriatric hospital in Japan between February 2000 and August 2002 were studied. We evaluated the concordance rate, sensitivity, and specificity of major UCODs (cancer, heart disease, and pneumonia) reported on death certificates compared with a reference standard of pathologist assessment based on autopsy data and clinical records. Logistic regression analysis was performed to assess the effect of sex, age, comorbidity, and UCODs on misclassification. Results: The concordance rate was relatively high for cancer (81%) but low for heart disease (55%) and pneumonia (9%). The overall concordance rate was 48%. Sex and comorbidity did not affect UCOD misclassification rates, which tended to increase with patient age, although the association with age was also not significant. The strongest factor for misclassification was UCODs (P < 0.0001). Sensitivity and specificity for cancer were very high (80% and 96%, respectively), but sensitivity for heart disease and pneumonia was 60% and 46%, respectively. Specificity for each UCOD was more than 85%. Conclusions: Researchers should be aware of the accuracy of COD data from death certificates used as research resources, especially for cases of elderly patients with pneumonia.

Aim: In Japan Atherosclerosis Society guidelines for the prevention of atherosclerotic cardiovascular diseases 2012 (JAS2012), NIPPON DATA80 risk assessment chart (ND80RAC) was adopted to estimate the 10-year probability of coronary artery disease (CAD) mortality. However, there was no comparison between the estimated mortality calculated by ND80RAC and actual mortality in external populations. Accordingly, we used the large pooled database of cohorts in Japan, EPOCH-JAPAN, as an external population.Methods:The participants of EPOCH-JAPAN without a history of cardiovascular disease (15,091 men and 18,589 women aged 40–74 years) were analyzed based on sex. The probability of a 10-year risk of CAD/stroke mortality was estimated by ND80RAC. The participants were divided into both decile of their estimated mortality and three categories according to JAS2012. The calibration between the mean estimated mortality and the actual mortality was performed by the Hosmer and Lemeshow (H-L) test.Results: In both sexes, the estimated CAD mortality was higher than the actual mortality, particularly in higher deciles of estimated mortality, and the estimated stroke mortality was almost concordant with the actual mortality in low/moderate deciles of estimated mortality. As for the categories according to JAS2012, the estimated CAD mortality was higher than the actual mortality in both sexes actual mortality in Category III was lower than that in Category II in women. However, it increased in the ascending order of category when we excluded the presence of diabetes from Category III.Conclusions: The estimated CAD mortality by ND80RAC tended to be higher than the actual mortality in the population in which the baseline survey was more recently performed.

Background: Previous studies on the association between coffee consumption and subarachnoid hemorrhage (SAH) have provided inconsistent results. We examine the risk of SAH from coffee consumption in a Japanese population. Methods: Our analyses were based on the Jichi Medical School Cohort Study, a large-scale population-based prospective cohort study. A total of 9941 participants (3868 men and 6073 women; mean age 55 years) with no history of cardiovascular disease or carcinoma were examined. Participants were asked to choose one of five options to indicate their daily coffee consumption: none, less than 1 cup a day, 1-2 cups a day, 3-4 cups a day, or 5 or more cups a day. The incidence of SAH was assessed independently by a diagnostic committee. Cox proportional hazards models were used to calculate hazard ratios (HRs) and their 95% confidence intervals (CI) after adjustment for age and sex (HR1) and for additional potential confounders (HR2). Results: During 10.7 years of follow-up, SAH occurred in 47 participants. When compared with the participants who consumed less than 1 cup of coffee a day, the HR of SAH was significantly higher in the group who consumed 5 or more cups a day in both models (HR1 4.49; 95% CI, 1.44-14.00; HR2 3.79; 95% CI, 1.19-12.05). Conclusions: The present community-based cohort study showed that heavy coffee consumption was associated with an increased incidence of SAH after adjusting for age, sex, and multiple potential cardiovascular confounders.

目的 : 当学には, 卒後9年間就業を継続するという前提がある. 今回, 当学女子医学生に求められている卒前教育プログラムを調査するため, ワークライフバランスに関するニーズ分析を行った.方法 : 全女子在校生187人に自記式調査を依頼した.結果 : 回答者104人のうち, 義務年限内に結婚・出産を希望した者はそれぞれ71％, 68.6％であった. 80.0％が「出産」に対して, 78.1％が「家庭との両立」に対して不安が高いと回答した. 回答者の8割以上が希望したプログラムは「卒業生女性医師の経験談」「卒業生女性医師との懇談会」「女性医師支援制度についての情報提供」「キャリアアップについての情報提供」であった.結論 : 当学女子医学生の不安は大きいが, 地域医療に貢献する卒業生女性医師との交流を生かしたプログラムを受けられるメリットがある. 当学の卒前教育において, ロールモデルの存在を明確にすることが求められていると考えられた.

Dietary salt intake has been reported to be associated with cardiovascular disease (CVD). However, there were few studies that assessed the relationship of salt preference with CVD. We examined the association between salt preference and the incidence of CVD and its subtypes in a Japanese general population. Based on the prospective Jichi Medical School Cohort Study, data were analyzed from 11,394 eligible participants. A baseline survey of the preference for salt was obtained by questionnaire and health examinations from April 1992 through July 1995 in 12 communities in Japan. The participants were followed up until December 2005 (mean follow-up period, 10.7 ± 2.4 years). Subjects were divided into three categories according to their preference for salt: favor, so-so, and disfavor. A Cox proportional hazards model was used to calculate hazard ratios (HRs) of the incidence of CVD according to the preference categories. We observed 485 cardiovascular events (258 in men and 227 in women). Among the men, the multivariable adjusted HRs for incidence of myocardial infarction and subarachnoid hemorrhage for favor versus so-so salt preference were 0.34 (95% confidence interval, 0.17 - 0.71) and 7.10 (0.88 - 56.84), respectively. Among the women, age-adjusted HRs for the incidence of CVD, total stroke, cerebral hemorrhage, and cerebral infarction for the favor preference were 1.41 (1.02 - 1.95), 1.36 (0.97 - 1.91), 1.79 (0.87 - 3.71), and 1.40 (0.89 - 2.19), respectively. The data indicated that preference for salt may be associated with an increase in the incidence of CVD in women.

Aim: Whether the association between serum γ-glutamyltransferase (γ-GTP) levels and total cardiovascular disease (CVD) mortality is independent of alcohol drinking in East Asian populations is not well known. We conducted a pooled analysis of Japanese men and women that enabled an analysis restricted to never-drinkers. Methods: A total of 15,987 men and 25,053 women aged 40-79 years, pooled from seven cohort studies throughout Japan, were followed-up to examine sex-specific relationship between serum γ -GTP levels and total CVD mortality. Cox regression model was used that was adjusted for age, smoking status, body mass index, and systolic blood pressure and serum triglyceride, total cholesterol, aspartate aminotransferase, and alanine aminotransferase levels. Results: During an average follow-up of 8.7 years, we documented 361 and 340 deaths from total CVD, 146 and 168 from stroke, and 101 and 53 from coronary heart disease (CHD) for men and women, respectively. Among the never-drinkers, hazard ratios (HRs) for mortality for one standard deviation of log-γ-GTP for men were 1.89 (1.00-3.58) for stroke, 1.04 (0.57-1.90) for CHD, and 1.43 (1.04-1.96) for total CVD. For women, HRs were 1.28 (1.06-1.54), 1.81 (1.34-2.44), and 1.30 (1.14-1.49), respectively. Conclusion: γ-GTP may be a risk factor for total CVD mortality independent of alcohol drinking status in Japanese men and women.

Aim: To investigate the relationship between serum uric acid levels and cardiovascular disease in Asians. Methods: We examined the above relationship using the data of Evidence for Cardiovascular Prevention from Observational Cohorts in Japan (EPOCH-JAPAN Study). The data of 36,313 subjects (15,628 men and 20,685 women aged 35 –89 years without histories of stroke, coronary heart disease, or cancer at baseline) were used for the analyses. Sex-specific hazard ratios (HRs) of mortality from cardiovascular disease were estimated according to the quintiles of serum uric acid using Cox hazard models stratified by cohorts. Results: During 441,771 person-years of follow-up, we documented 1,288 cardiovascular deaths. A J-or U-shaped relationship between serum uric acid level and cardiovascular disease mortality was observed. Compared with the lowest quintile of serum uric acid levels, the highest quintile was associated with an increased cardiovascular disease mortality in men [HR: 1.28 95% confidence interval (CI): 1.01– 1.63] and women (HR: 1.51 95% CI: 1.14–1.99). However, there was no significant association with mortality from stroke, coronary heart disease or heart failure in both men and women. Conclusion: This large pooled analysis in Japan suggested a J-or U-shaped relationship between serum uric acid levels and cardiovascular mortality. The highest quintile of serum uric acid levels was associated with increased cardiovascular disease mortality in both Japanese men and women.

Purpose: General practitioners have an important role in diagnosing a variety of patients, including psychiatric patients with complicated symptoms. We evaluated the relationship between physical symptoms and psychiatric disorders in general internal medicine (GIM) outpatients in a Japanese university hospital. Materials and methods: We coded the symptoms and diagnoses of outpatients from medical documents using the International Classification of Primary Care, second edition (ICPC-2). The participants were new outpatients who consulted the GIM outpatient division at Jichi Medical University Hospital in Tochigi, Japan from January–June, 2012. We reviewed all medical documents and noted symptoms and diagnoses. These were coded using ICPC-2. Results: A total of 1,194 participants were evaluated, 148 (12.4%) of whom were diagnosed as having psychiatric disorders. The prevalence of depression, anxiety disorder, and somatization was 19.6% (number [n] =29), 14.9% (n=22), and 14.2% (n=21), respectively, among the participants with psychiatric disorders. The presence of several particular symptoms was associated with having a psychiatric disorder as compared with the absence of these symptoms after adjusting for sex, age, and the presence of multiple symptoms (odds ratio [OR] =4.98 [95% confidence interval {CI}: 1.66–14.89] for palpitation OR =4.36 [95% CI: 2.05–9.39] for dyspnea OR =3.46 [95% CI: 1.43–8.36] for tiredness and OR =2.99 [95% CI: 1.75–5.13] for headache). Conclusion: Not only the psychiatric symptoms, but also some physical symptoms, were associated with psychiatric disorders in GIM outpatients at our university hospital. These results may be of help to general practitioners in appropriately approaching and managing patients with psychiatric disorders.

Soy and soy products are popular ingredients in the Japanese diet. This study aimed to determine whether soy or soy products intake was associated with all-cause mortality in a community-based cohort in Japan. A total of 11 066 participants were obtained from an annual community-based health examination program. A self-administered questionnaire was used to collect information concerning soy and soy products intake and potential confounding factors. Associations between soy and soy products intake and all-cause mortality were assessed using hazard ratios (HRs). After adjusting for all factors, morality was significantly higher in men with infrequent soy intake (HR = 1.53; 95% confidence interval [CI] = 1.13-2.07) and with almost daily intake (HR = 1.55; 95% CI = 1.19-2.03) compared with intake 1 to 2 times per week. Cancer mortality was higher among men who reported rarely eating soy (HR = 1.74; 95% CI = 1.08-2.79). Soy products intake was not statistically significantly associated with all-cause mortality in both sexes.

To study whether sleep blood pressure (BP) self-measured at home is associated with organ damage, the authors analyzed the data of 2562 participants in the J-HOP study who self-measured sleep BP using a home BP monitoring (HBPM) device, three times during sleep (2am, 3am, 4am), as well as the home morning and evening BPs. The mean sleep home systolic BPs (SBPs) were all correlated with urinary albumin/creatinine ratio (UACR), left ventricular mass index (LVMI), brachial-ankle pulse wave velocity (baPWV), maximum carotid intima-media thickness, and plasma N-terminal pro-hormone pro-brain-type natriuretic peptide (NTproBNP) (all P<.001). After controlling for clinic SBP and home morning and evening SBPs, associations of home sleep SBP with UACR, LVMI, and baPWV remained significant (all P<.008). Even in patients with home morning BP <135/85mmHg, 27% exhibited masked nocturnal hypertension with home sleep SBP 120mmHg and had higher UACR and NTproBNP. Masked nocturnal hypertension, which is associated with advanced organ damage, remains unrecognized by conventional HBPM.

The predictive value of serum non-high-density lipoprotein cholesterol (non-HDL-C) levels for the incidence of ischemic stroke and its subtypes has not yet been established. The present cohort study investigated their relationships in a Japanese population. The first incidence of ischemic stroke and its subtypes was documented as the primary outcome. A total of 249 ischemic stroke patients (men/women = 145/104) were identified during a follow-up period of 10.7 years among 10 760 community-dwelling subjects (men/women = 4212/6548). Cox proportional hazard model analyses revealed that when compared with the lowest tertile of non-HDL-C, multivariate-adjusted hazard ratios for the highest tertile were 0.55 (95% confidence interval = 0.32-0.95, P =.03) on ischemic stroke and 0.29 (95% confidence interval = 0.08-1.05, P =.06) on cardioembolic infarction in women. Men did not show such significant relationships. Low serum non-HDL-C levels may be a predictive marker associated with an increase in the incidence of ischemic stroke and possibly of cardioembolic infarction in Japanese women.

The aim of the study was to investigate the relation between insulin resistance and risk of cerebral infarction in a Japanese general population. The subjects were 2610 men and women without past history of stroke or myocardial infarction and who were under treatment for diabetes. Subjects were divided into quartiles by the homeostasis model assessment of insulin resistance (HOMA-IR), and Cox's proportional hazard model was used to calculate hazard ratios (HRs) for cerebral infarction. In men, the multivariate-adjusted HRs were 2.51 (95% confidence interval [CI] = 0.98-6.42) in quartile 1 (Q1), 1.43 (95% CI = 0.54-3.82) in Q2, and 2.13 (95% CI = 0.82-5.51) in Q4, using Q3 as the reference. In women, the multivariate-adjusted HRs were 2.12 (95% CI = 0.72-6.31) in Q1, 2.96 (95% CI = 1.06-8.26) in Q3, and 2.31 (95% CI = 0.80-6.69) in Q4, using Q2 as the reference. The association between risk of cerebral infarction and HOMA-IR was not dose dependent.

Background: We attempted to evaluate whether the relationship between the QTc interval and mortality (including sudden cardiac death) is linear or J-shaped in the general Japanese population, who tend to be at greater risk of strokes than cardiac events. Methods: we classified 10,804 subjects according to their Bazett QTc interval quartiles (determined by electrocardiography) at the baseline and followed them up for a mean period of 141.9 +/- 28.3 months (127,712 person-years). Results: In total, 878 subjects died during the study period. including 104 from cardiovascular events, 100 from stroke, and 46 from sudden cardiac death. In a Cox proportional hazards regression model adjusted for conventional cardiovascular risk factors, the risk of cardiovascular mortality increased progressively with the QTc interval quartile [Q2, hazard ratio (HR) = 0.94 (0.43-2.03); Q3, HR = 1.11 (0.53-2.34); Q4, HR = 2.21 (1.12-4.36); HR are vs. Q1]. A parallel analysis found that the risk of stroke mortality was marginally increased in the highest Bazett QTc interval quartile [HR = 1.93 (0.97-3.85)]. On the other hand, the risk of sudden cardiac death exhibited a J-shaped relationship with the Bazett QTc interval quartile [Q1, HR = 8.58(1.07-69.05); Q3, HR = 7.17(0.88-58.73); Q4, HR 13.18(1.72-101.03); HR are vs. Q2]. Conclusion: In the general Japanese population, cardiovascular and stroke mortality increase progressively with the Bazett QTc interval quartile, while the risk of sudden cardiac death exhibits a j-shaped relationship with the latter variable. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

We attempted to evaluate whether subjects who exhibit prolonged corrected QT (QTc) interval (>= 440 ms in men and >= 460 ms in women) on ECG, with and without ECG-diagnosed left ventricular hypertrophy (ECG-LVH; Cornell product, >= 244 mVxms), are at increased risk of stroke. Among the 10 643 subjects, there were a total of 375 stroke events during the follow-up period (128.7 +/- 28.1 months; 114 142 person-years). The subjects with prolonged QTc interval (hazard ratio, 2.13; 95% confidence interval, 1.22-3.73) had an increased risk of stroke even after adjustment for ECG-LVH (hazard ratio, 1.71; 95% confidence interval, 1.22-2.40). When we stratified the subjects into those with neither a prolonged QTc interval nor ECG-LVH, those with a prolonged QTc interval but without ECG-LVH, and those with ECG-LVH, multivariate-adjusted Cox proportional hazards analysis demonstrated that the subjects with prolonged QTc intervals but not ECG-LVH (1.2% of all subjects; incidence, 10.7%; hazard ratio, 2.70, 95% confidence interval, 1.48-4.94) and those with ECG-LVH (incidence, 7.9%; hazard ratio, 1.83; 95% confidence interval, 1.31-2.57) had an increased risk of stroke events, compared with those with neither a prolonged QTc interval nor ECG-LVH. In conclusion, prolonged QTc interval was associated with stroke risk even among patients without ECG-LVH in the general population.

This study was undertaken to evaluate the differences in chronotherapeutic effects of angiotensin-II receptor blockers, valsartan and olmesartan in hypertensive patients with non-dipper blood pressure (BP) pattern during valsartan at morning. Ninety four patients were enrolled, and 40 patients were judged to be non-dippers. In these patients, same dose of valsartan was changed to evening (Val-E, n = 12), or olmesartan (equivalent dose of valsartan) was given at morning (Olm-M, n = 13) or evening (Olm-E, n = 15) for 4 months. BP decreased during sleep and increased during waking hours in Val-E group. In Olm-M and Olm-E groups, BP decreased during sleep and waking hours. Percent reduction in BP at night-time compared to BP at waking hours significantly increased after changing the dose regimen in each group. Serum creatinine decreased and estimated glomerular filtration rate (eGFR) elevated in Olm-M and Olm-E, but not Val-E groups. Positive correlation between systolic BP (SBP) during sleep and serum creatinine, and negative correlation between SBP during sleep and eGFR were detected. These data suggest that dipper BP pattern could be obtained by chronotherapeutic approach using valsartan and olmesartan in non-dipper patients with valsartan at morning. Morning and evening olmesartan, but not evening valsartan improved renal function in these patients. (C) 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V.

Aim: Whether plasma glucose concentrations at the screening level in the public health care setting can predict mortality remains to be determined in Japanese people. The aim of this study was to investigate the relationships between screening plasma glucose concentrations and cause- and all-cause mortality in a general Japanese cohort. Subjects and methods: The current study investigated 11,998 community-dwelling participants from 12 Japanese communities who had been registered in the Jichi Medical School Cohort Study (a population-based prospective cohort study) between 1992 and 1995. Mortality was documented as the primary outcome. The relationships between screening plasma glucose concentrations and outcomes were analyzed using Cox proportional hazard models. Results: In all, 1,050 deaths (men/women = 631/419) were identified during a follow-up period of 10.7 years. Compared with the lowest glucose concentration (&lt 5.22 mmol/L), multivariate-adjusted hazard ratios for the highest glucose concentration (≥6.11 mmol/L) were 1.52 (95 % confidence interval [CI], 1.25–1.85) for all-cause mortality and 1.76 (95 % CI, 1.29–2.41) for cancer-cause mortality in men and 4.65 (95 % CI, 1.69–12.78) for myocardial infarction mortality in women. Conclusions: The current Japanese population-based cohort study suggests that high screening plasma glucose concentrations can predict cancer- and all-cause mortality, particularly in men.

Background: ECG-diagnosed left ventricular hypertrophy (LVH), the Cornell voltage (CV: >= 2.8 mV in males and mV in females) or Cornell product (CP: >= 244.0 mVxms), were selected in Western countries for their ability to diagnose anatomical LVH. Methods and Results: We aimed to elucidate the CV and CF values that were associated with a significantly increased risk of cardiovascular or stroke mortality and morbidity in a Japanese general population (n=10,172). In the receiver-operating curves analysis of CV and CP for predicting the risks, the area under the curve in females was greater than in males. In a quintile-based multivariate analysis that was performed separately for females and males, the mortality and morbidity risks of CV were significantly increased at the highest quintile of CV (>1.71 mV) in females. In males, the mortality risk was significantly increased at the highest quintile of CV (>2.04 mV). Additionally, in the parallel analysis of CP that included both males and females, the morbidity risk was significantly elevated in subjects with CF belonging to the 4th (158.7-193.4 mVxms; hazard ratio=1.387) or 5th quintiles (>= 193.5 mVxms; hazard ratio=1.507), compared with those with CP values within the lowest quintile (<101.9 mVxms). Conclusions: Cardiovascular and stroke risks may be elevated at lower levels of CV and CP in Japanese subjects, especially females.

Objective: We investigated the relation between fasting insulin (FI) and risk of cerebral infarction in a Japanese general population. Methods: The subjects were 2,610 men and women without past history of stroke or myocardial infarction and under treatment for diabetes, examined between 1992 and 1995 as part of the Jichi Medical School Cohort Study. The FI level was measured once at the baseline. Subjects were divided into quintiles by FI levels, and Cox's proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cerebral infarction. Results: During an average of 11.1 years of follow-up, 87 participants developed cerebral infarction. Crude incidence rates of FI quintiles 1-5 were 4.69, 2.35, 1.85, 2.77 and 3.30 per 1,000 person-years, respectively. The multivariate-adjusted HRs for cerebral infarction were 2.33 (95% CI, 1.10 - 4.96) in quintile 1 (Q1), 1.25 (95% CI, 0.55 - 2.84) in Q2, 1.68 (95% CI, 0.76 - 3.70) in Q4 and 2.06 (95% CI, 0.94 - 4.47) in Q5, using Q3 as the reference. Conclusions: The lowest FI level was associated with increased risk of cerebral infarction and the association between FI and risk of cerebral infarction appeared to be a U-shaped relationship.

ObjectiveTo evaluate the efficacy of endoscopic and radiographic screening for gastric cancer. DesignA retrospective cohort study. SettingCommunity in an isolated island. ParticipantsThe study involved 186 patients (131 men, 55 women) diagnosed with gastric cancer between 2000 and 2005. InterventionsEndoscopic and radiographic screening. Main outcome measurementsThe odds ratio of death from gastric cancer in participants versus non-participants of screening, the cumulative survival rate of the gastric cancer patients. ResultsThe odds ratio of death from gastric cancer in the participants versus non-participants of screening was 0.091 (95% confidence interval (CI) 0.027-0.308; P<0.0001). The cumulative survival rate of the gastric cancer patients in the screening group was higher than that in the non-screening group (P<0.0001). In the endoscopic screening district, the odds ratio of death from gastric cancer among the participants versus non-participants of endoscopic screening was 0.117 (95% CI 0.013-1.056; P=0.0525), while in the radiographic screening district, it was 0.086 (95% CI 0.020-0.376; P<0.0001). The cumulative survival rates were higher in both the screening groups as compared with the non-screening group (endoscopy, P=0.0302; radiography, P=0.0012). ConclusionThe results suggest that both radiographic and endoscopic screening may prevent gastric cancer deaths.

OBJECTIVE-To examine the BMI-stratified associations between diabetes and the risks of all-cause death, cardiovascular disease (CVD) death, and cancer death.RESEARCH DESIGN AND METHODS-Using a prospective study with 12 rural Japanese general populations (n = 3,641, mean age, 53.7 years; 33.5% men), we examined the associations between diabetes and the risk of all-cause death, CVD death, and cancer death. We also examined the effects of BMI and age on such associations.RESULTS-During an average duration of 10.2 years (37,278 person-years), 240 deaths occurred (54 deaths from CVD, 101 from cancer, and 85 from other causes). Cox regression analysis showed leanness (defined as the lowest quartile of entire BMI; mean, 19.5 kg/m(2)), but not obesity (BMI >= 25 kg/m(2)), and diabetes were independently associated with an increased risk of all-cause death (hazard ratio [HR] 1.70 and 1.65, respectively; both P < 0.01.). Stratification with cause-specific deaths showed that leanness and obesity were associated with CVD death (HR 3.77 and 2.94, respectively), whereas diabetes was associated with cancer death (HR 1.87; all P < 0.05). The increased risk of all-cause death in diabetes was substantially higher in lean subjects aged <65 years (HR 3.4) or those aged >= 65 years (HR 4.2), whereas the risk in obese diabetes patients was significant only in subjects aged <65 years (HR 2.32; all P < 0.05).CONCLUSIONS-Among the Japanese general population, diabetes confers an increased risk of all-cause death. Particular attention must be paid to the pronounced high mortality in diabetes accompanied with leanness, regardless of age.

Introduction: Although lipoprotein(a) (Lp(a)) is involved in cardiometabolic disease processes, the association between serum Lp(a) and stroke and/or its subtypes has not yet been elucidated among Japanese people. This study investigated the association between Lp(a) and the incidence of stroke and/or its subtypes in the general Japanese population. Materials and Methods: This population-based prospective cohort study included 10,494 community-dwelling participants (4,030 males/6,464 females). The incidence of stroke and its subtypes was the primary outcome. The subjects were divided into tertiles based on their Lp(a) levels, and the risk of all stroke and stroke subtypes was examined using Cox's proportional hazard model. Results: A total of 393 subjects (199 males and 194 females) with stroke were identified during a follow-up duration of 10.7 years. The multivariate-adjusted hazard ratios for all stroke events were 0.55 (95% confidence interval: 0.38-0.81) and 0.69 (0.49-0.99) in the 2nd (9-19 mg/dl) and 3rd tertiles (&gt;= 20 mg/dl) of Lp(a) in reference to the 1st tertile (&lt;9 mg/dl) in males, and 0.85 (0.59-1.24) and 0.76 (0.52-1.11) in 2nd (10-22 mg/dl) and 3rd tertiles (&gt;= 23 mg/dl) of Lp(a) in reference to the 1st tertile (&lt;10 mg/dl) in females. The multivariate-adjusted hazard ratios for cerebral hemorrhage were 0.26 (0.10-0.67) and 0.34 (0.15-0.76) in the 2nd and 3rd tertiles of Lp(a) in reference to the 1st tertile in males, and were 0.48 (0.23-1.04) and 0.44 (0.21-0.96) in the 2nd and 3rd tertiles of Lp(a) in females. Conclusions: Lp(a) was associated with the incidence of cerebral hemorrhage in the general Japanese population, particularly among males, while a similar trend was seen among females. A low Lp(a) level may be a marker of the risk of cerebral hemorrhage in this population. (c) 2012 Elsevier Ltd. All rights reserved.

Context. Advance directives are poorly understood in Japanese nursing homes. In April 2006, additional funding for end-of-life care became available as the first support for terminal care at Japanese nursing homes. Objectives. The objectives of this study were to investigate the adoption of advance directives by Japanese nursing homes, the effect of additional funding for end-of-life care in nursing homes from long-term care insurance on the use of advance directives, and the types of directives used. Methods. A nationwide questionnaire survey of nursing homes was performed in Japan. The participants were 913 nursing homes. We investigated the prevalence of advance directives, details of the directives, and demographic data of the responders. Results. Advance directives were used in 58.4% of nursing homes. The timing of introduction of the directives and the results of multivariate analysis at the facility level suggested a relation between the availability of additional funding for end-of-life care and the adoption of advance directives. Most nursing homes used instructional directives, especially directives providing an explanation and informed consent for end-of-life care in the nursing home. Conclusion. More than half of Japanese nursing homes have introduced advance directives, and additional funding for end-of-life care is related to their introduction. Most nursing homes have adopted instructional directives, especially those providing an explanation and informed consent regarding end-of-life care at the nursing home. J Pain Symptom Manage 2013;45:63-70. (C) 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Prostate cancer is a common disease in modern, developed societies and has a high incidence and mortality. Highdensity lipoprotein cholesterol (HDL-C) has recently received much attention as a possible risk marker of prostate cancer development and prognosis. In the present article, we summarized findings from epidemiologic studies of the association between HDL-C and prostate cancer. Low HDL-C level was found to be a risk and prognostic factor of prostate cancer in several epidemiologic studies, although the overall linkage between HDL and prostate cancer has not been definitively established. The mechanisms for this association remain uncertain however, limited data from experimental studies imply a possible role of HDL in the pathophysiology of prostate cancer. More epidemiologic research, in combination with experimental studies, is needed in this field. © 2013 Kazuhiko Kotani et al.

Background: Helicobacter pylori (H. pylori) infection has been reported to be associated with cardiovascular risk factors by inducing chronic low-grade inflammation and by influencing endocrine and metabolic systems, as well as the immunological response evoked by the host. This study investigated the association between H. pylori infection and high density lipoprotein cholesterol (HDL-C) in Japanese subjects.<br>Methods: The study subjects were 2,632 (1,061 men and 1,571 women) living in rural areas in Japan. We checked H. pylori serum immunoglobulin G (IgG), HDL-C and other cardiovascular risk factors in 1999.<br>Results: The overall prevalence of H. pylori seropositivity was 53.5% and increased with age. The prevalence was higher among men (58.3%) than women (50.3%). H. pylori seropositive women were more associated with decreased HDL-C than seronegative subjects (58.1±13.6 vs. 60.5±14.7, p<0.01). Multiple linear regression analysis with H. pylori seropositivity, age, body mass index (BMI), fibrinogen, blood glucose, and smoking and alcohol habits demonstrated that H. pylori seropositivity was a significant predictor of decreased HDL-C in women. In addition, there was a linear decrease in HDL-C with increments in the value of H. pylori antibody titer as a continuous variable in women. This association remained in H. pylori seropositive women aged ≥50 years. Moreover, H. pylori seropositive women with BMI <22 were associated with decreased HDL-C, whereas the association was not significant in women with BMI ≥22.<br>Conclusions: We show that H. pylori seropositivity is associated with decreased HDL-C, especially in women with a lower BMI in rural areas of Japan.

Aims: We tested the hypothesis that short sleep duration is not only a risk factor for diabetes, but that the two conditions in combination would be associated with the risk of incident cardiovascular disease (CVD). Methods: We analyzed 1255 hypertensive patients (mean age: 70.4 +/- 9.9 years) with (N = 299) and without diabetes (N = 956). Short sleep duration was defined as a sleep time &lt;7.5 h. A Hard CVD event was defined as either myocardial infarction, stroke, or sudden cardiac death; and All CVD events as Hard CVD events plus angina, heart failure and end-stage renal disease. Results: When the patients were divided into 4 categories by diabetes (present or absent) and sleep duration (short or long), the diabetes + short sleep group had a significantly higher incidence of both Hard CVD events (HR = 2.27, 95% CI = 1.17-4.42, P = 0.015) and All CVD events (HR = 2.47, 95% CI = 1.37-4.43, P = 0.003) compared with the non-diabetes + long sleep group, independent of significant covariates. There were significant interactions between sleep duration and glycemic control on CVD events. Conclusions: The combination of both diabetes and short duration of sleep was associated with higher risk of incident CVD compared with those with only one or neither condition. Altered glycemic control and short sleep duration could act synergistically to pose a risk for future CVD. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

In ambulatory blood pressure (BP) monitoring, nighttime BP has a superior ability to predict hypertensive target organ damage than awake BP. We evaluated whether nighttime BP, assessed by a home BP monitor, was associated with hypertensive target organ damage. We measured clinic BP, out-of-clinic BP including nighttime home BP, and the urinary albumin: creatinine ratio (UACR) in 854 patients who had cardiovascular risk factors. Nighttime home BP was measured at 2: 00, 3: 00, and 4: 00 am, in addition to clinic, awake ambulatory, nighttime ambulatory, and awake home BP. Nighttime home systolic BP (SBP) was slightly higher than nighttime ambulatory SBP (difference, 2.6 mm Hg; P&lt;0.001). Clinic (r=0.186), awake ambulatory (r=0.173), nighttime ambulatory (r=0.194), awake home (r=0.298), and nighttime home (r=0.311) SBPs were all associated with log-transformed UACR (all P&lt;0.001). The correlation coefficient for the relationship between nighttime home SBP and log-transformed UACR was significantly greater than that for the relationship between nighttime ambulatory SBP and log-transformed UACR (P&lt;0.001). The goodness of fit of the association between SBP and UACR was improved by adding nighttime home SBP to the other SBPs (P&lt;0.001). Nighttime home diastolic BP also improved the goodness-of-fit of the association between diastolic BP and UACR (P=0.001). Similar findings were observed for the left ventricular mass index in the subgroup (N=594). In conclusion, nighttime home BP is slightly different from (but comparable to) nighttime ambulatory BP. The addition of nighttime home BP to other BP measures improves the association of BP with hypertensive target organ damage. (Hypertension. 2012; 60: 921-928.) center dot Online Data Supplement

Introduction: Recent studies show that a clinical pathway (CP) optimizes pain management in palliative care; however, studies on CPs in home palliative care, especially in remote locations, are scarce. Physicians performing palliative care in remote areas frequently face characteristic difficulties. The CP is an effective tool to overcome these difficulties. This study evaluates the effectiveness of the CP in home palliative care on a remote island. Methods: This study reviewed 24 patients (17 in a pre-CP group and seven in a post-CP group) who received home palliative care on Kozu Island in south-eastern Japan from April 2006 to December 2011. To evaluate CP effectiveness, the authors compared patients in whom a rescue opioid was set, and nonsteroidal anti-inflammatory drugs (NSAIDs), antiemetics, and laxatives drug were used with opioids in the post-CP group compared with those in the pre-CP group. To assess pain management quality, authors compared Pain Management Index (PMI) scores on day 1 (baseline); day 8 following CP initiation; and within 3 days before death. Results: The proportion of patients in whom a rescue dose was set was 100% in the post-CP group versus 46% in the pre-CP group (p=0.04). The proportion of patients in whom NSAIDs were used with opioids was 100% in the post-CP group versus 18% in the pre-CP group (p=0.002). The proportion of patients in whom antiemetics and laxatives were used with opioids was 100% in the post-CP group versus 27% in the pre-CP group (p=0.009). Baseline PMI scores were not significantly different between groups (-1 in post-CP group versus 0 in pre-CP group, p=0.1); however, PMI scores at day 8 and within 3 days before death were significantly higher in the post-CP group (1.9 and 2.9) than in the pre-CP group (0.2 and -0.4) (p=0.007 and p=0.0005, respectively). Conclusion: Implementation of a CP for pain management in home palliative care in remote locations could improve compliance with the WHO pain management guidelines and the quality of pain management.

Background: Chronic infections, such as Helicobacter pylori (H. pylori) and Chlamydophila pneumoniae (C. pneumoniae), are known to contribute to atherosclerosis. However, the relationship of the infections to cerebral infarction is still controversial. Methods: The Jichi Medical School (JMS) Cohort Study, a prospective population-based study, investigated the risk factors of cardiovascular disease in Japanese community-dwelling populations. In 1999, we measured serum H. pylori IgG, C. pneumoniae IgG and IgA levels in 2,632 subjects. Logistic regressions were used to analyze associations between H. pylori and C. pneumoniae seropositivities and cerebral infarction. Results: A total of 2,243 subjects were followed up and, during 10.7-years, 64 developed cerebral infarctions, whose prevalence of H. pylori IgG, C. pneumoniae IgG and IgA seropositivities were 51.6%, 71.9%, and 67.2%, respectively. Among seropositive subjects, adjusted odds ratios (ORs) for cerebral infarctions were 1.04 (95% confi dence interval (CI), 0.58-1.87, P=0.89), 2.02 (1.03-3.95, P=0.04), and 1.35 (0.73-2.49, P=0.34) respectively, after adjusting for sex, age, body mass index, total cholesterol, high-density lipoprotein cholesterol, fasting blood sugar, smoking, alcohol, and fibrinogen. C. pneumoniae IgG seropositivities in subjects aged &gt;= 65 years were associated with cerebral infarctions, whereas those in subjects aged &lt; 65 years, were not. Conclusions: C. pneumoniae IgG was associated with cerebral infarction, C. pneumoniae IgA and H. pylori IgG were not.

J Clin Hypertens (Greenwich). 2012; 14:422428. (c) 2012 Wiley Periodicals, Inc. The authors tested the hypothesis that an aggressive antihypertensive treatment is beneficial in protecting against target organ damage (TOD) in patients with type 2 diabetes/prediabetes. The authors enrolled 60 patients with uncontrolled hypertension and diabetes/prediabetes and performed clinic, home, and ambulatory blood pressure (BP) monitoring. Irbesartan, amlodipine, and indapamide were used according to a titration schedule from step 1 to 5 for target home BP level =125/75 mm Hg. The flow-mediated vasodilation (FMD), radial augmentation index (AI), pulse wave velocity (PWV), and urinary albumin excretion ratio (UACR), as a surrogate marker of TOD, were measured at baseline and 6 months. Compared with baseline, clinic, home, and ambulatory BP measures were significantly lower in the sixth month. FMD was increased significantly and AI, PWV, and UACR were reduced by the treatment. The extent of the changes in PWV and UACR were associated with the changes in all BP measures, but only the change in home morning BP was associated with the change in FMD. The change in AI was not associated with the change in BP levels, but was associated with the change in PWV. A very aggressive antihypertensive therapy guided by home morning BP was effective for surrogate end points in patients with diabetes/prediabetes.

Background: There have been few reports on the relationship between P-wave characteristics and long-term cardiovascular events. Methods: A nested case-control study was conducted as part of the Jichi Medical School cohort study, which enrolled 12,490 subjects in a community-dwelling population. The mean follow-up period was 10.7 years. The P-wave characteristics of 526 patients who suffered cardiovascular events (fatal/nonfatal stroke, fatal/nonfatal myocardial infarction, and sudden death) within the follow-up period (case group) were compared with those of 1578 matched controls (control group). The P-wave morphology was classified as normal, deflected, and notched type in precordial leads. A broad P wave was defined as a maximum P-wave duration of more than 120 ms in any of the 12 leads. Results: The mean age was 64 +/- 8 years and the percentage of males was 54% in both groups. A notched P wave at baseline was observed in 10.1% of the case group and 6.0% of the control group (P = 0.001). A notched P wave was a significant predictor of cardiovascular events after adjustment for covariates (odds ratio = 1.59; 95% confidence interval = 1.082.33). Among the patients with left ventricular hypertrophy as evaluated by the SokolowLyon criteria or Cornell product criteria, there was no significant difference in cardiovascular events between those with and those without a notched P wave, but in the absence of left ventricular hypertrophy, patients with a notched P wave suffered more cardiovascular events than those without a notched P wave by each criteria. Conclusion: P-wave morphologic characteristics were effective for predicting cardiovascular events.

Background: Asleep blood pressure (BP) has been shown to better reflect cardiovascular risk than awake BP in hypertensive patients. This study investigated the correlation of brain natriuretic peptide (BNP) to asleep BP during antihypertensive treatment. Methods: In the Japan Morning Surge-Target Organ Protection (J-TOP) study, which was an open-label multicenter trial to compare bedtime or awakening dosing of candesartan (+ diuretics as needed) among individuals with home SBP higher than 135 mmHg, we evaluated 254 hypertensive patients who underwent ambulatory BP monitoring, and measured their BNP at baseline and after 6th month of treatment. Results: At follow-up, the decrease in log-transformed BNP was significantly related to the decrease in asleep SBP (r = 0.27, P &lt; 0.001); the relationship remained significant (beta = 0.20, P = 0.002) even after adjusting for the decrease in the awake SBP (beta = 0.001, P = 0.991). When we divided participants by their time of candesartan administration, the relationship between the decrease in log-transformed BNP and asleep SBP was still significant in both the awakening-dosing group (beta = 0.21, P = 0.028) and the bedtime-dosing group (beta = 0.21, P = 0.029). Furthermore, this relationship was strong in the participants who were receiving diuretics. Conclusion: The decrease in BNP is associated with asleep BP reduction by candesartan (R diuretics as needed) over and above the awake BP reduction, regardless of the time of administration.

Background: Experimental studies support the anti-neoplastic effect of apo(a), but several clinical studies have reported contradictory results. The purpose of this study was to determine whether a low lipoprotein(a) [Lp(a)] concentration is related to mortality from major causes of death, especially cancer. Methods: The subjects were 10,413 participants (4,005 men and 6,408 women) from a multi-center population-based cohort study in Japan (The Jichi Medical School cohort study). The average age at registration was 55.0 years, and the median observation period was 4,559 days. As the estimated hazard ratio was high for both the low and very high Lp(a) levels, we defined two Lp(a) groups: a low Lp(a) group [Lp(a)&lt;80 mg/L] and an intermediate-to-high Lp(a) group [Lp(a)&gt;= 80]. Participants who died from malignant neoplasms (n=316), cardiovascular disease (202), or other causes (312) during the observation period were examined. Results: Cumulative incidence plots showed higher cumulative death rates for the low Lp(a) group than for the intermediate-to-high Lp(a) group for all-cause, cancer, and miscellaneous-cause deaths (p&lt;0.001, p=0.03, and p=0.03, respectively). Cox proportional hazards analyses with the sex and age of the participants, body mass index, and smoking and drinking histories as covariates showed that a low Lp(a) level was a significant risk for all-cause, cancer, and miscellaneous-cause deaths (p&lt;0.001, p=0.003, and p=0.01, respectively). The hazard ratio (95% CI) [1.48, 1.15-1.92] of a low Lp(a) level for cancer deaths was almost the same as that for a male sex (1.46, 1.00-2.13). Conclusions: This is the first report to describe the association between a low Lp(a) level and all-cause or cancer death, supporting the anti-neoplastic effect of Lp(a). Further epidemiological studies are needed to confirm the present results.

BACKGROUND Our aim was to assess whether home blood pressure (HBP) and ambulatory BP monitoring measurement (ABPM), in addition to office BP (OBP) predict changes of cardiovascular biomarkers during antihypertensive treatment. METHODS Two hundred and fifty-two hypertensive patients (mean age, 68 years; men: 41%) underwent measurements of OBP, HBP, ABPM, and cardiovascular biomarkers (urinary albumin excretion (UAE) and brain natriuretic peptide (BNP)) before and after 6 months of treatment with candesartan (+/- thiazide-diuretics). RESULTS During the intervention, the OBP, HBP, daytime and night-time BP, and UAE levels were all significantly reduced (all P &lt; 0.01). BNP was reduced only in the patients using diuretics (P = 0.003). For predicting the treatment-induced change in UAE, each of home systolic BP (SBP) and night-time SBP changes, but not daytime SBP change, had independent and significant value beyond OBP measurement (both P &lt; 0.05). In contrast, for predicting the treatment-induced change in BNP, night-time SBP changes, but not home or daytime SBP changes, had significant value beyond OBP measurement (both P &lt; 0.05). Patients who achieved a reduction in all three SBP parameters (office, home, and night-time SBP; n = 122) showed a more significant reduction of UAE compared with those who did not (-52.6 vs. 32.5%; P = 0.001), and patients who achieved a reduction in both office and night-time SBP (n = 134) showed a more significant reductions of BNP than those who did not (-12.9 vs. +12.8%; P &lt; 0.05). CONCLUSIONS HBP and ABPM measurements, particularly night-time SBP values provide additional information for predicting treatment-induced changes of cardiovascular biomarkers when used in conjunction with office SBP measurement during antihypertensive treatment.

Background: Although many population-based studies have reported an association between physical activity and cardiovascular disease (CVD) among healthy populations, the association among CVD survivors has been less reported. We examined the relationship between physical activity and CVD risk among survivors. Methods and Results: This was a prospective cohort study of 12,490 Japanese participants, including 754 individual CVD survivors. Between April 1992 and July 1995, a baseline survey was conducted in 12 communities in Japan. The mean follow-up period was 11.9 years, during which time 74 individuals had non-fatal CVD and 51 cases were fatal CVD. Among CVD survivors, analysis was performed after exclusion of participants with a history of cancer and those who died within the first 2 years of follow-up. Physical activity was analyzed in tertiles (low, moderate and heavy), and the hazard ratios (HRs) were calculated for non-fatal or fatal CVD among CVD survivors. After setting the low group as the reference, the HRs for non-fatal CVD in the moderate and heavy groups were 0.61 (95% confidence interval: 0.30-1.24) and 0.50 (0.20-1.25) (P for trend=0.059), respectively, and the HRs for fatal CVD were 0.75 (0.33-1.69) and 0.18 (0.04-0.83) (P for trend=0.026), respectively. Conclusions: Physical activity reduced the risk of CVD, both fatal and non-fatal events, among CVD survivors. (Circ J 2011; 75: 1368 1372)

Background: It has been reported that fruit intake protects against cardiovascular disease (CVD). However, most of the relevant studies were conducted in Western countries, and only a few investigated Japanese populations. The present cohort study assessed the effect of citrus fruit intake on the incidence of CVD and its subtypes in a Japanese population. Methods: A baseline examination consisting of physical and blood examinations and a self-administered questionnaire was conducted during the period from April 1992 through July 1995. Dietary habits were assessed using a food frequency questionnaire that was divided into 5 categories. Citrus fruit was examined separately due to its frequent consumption by the general Japanese population. Using the Cox proportional hazards model, data from 10 623 participants (4147 men, 6476 women) who had no history of CVD or carcinoma were analyzed to assess the association between frequency of citrus fruit intake and CVD incidence. Results: Frequent intake of citrus fruit was associated with a lower incidence of CVD: the hazard ratio for almost daily intake versus infrequent intake of citrus fruit was 0.57 (95% confidence interval: 0.33-1.01, P for trend = 0.04) in men and 0.51 (0.29-0.88, P for trend = 0.02) in women. Frequent intake of citrus fruit was also associated with lower incidences of both all stroke and cerebral infarction, but not hemorrhagic stroke or myocardial infarction. Conclusions: Frequent intake of citrus fruit may reduce the incidence of CVD, especially cerebral infarction, in men and women.

The aims of the present study were to analyze the association between incident stroke, occupational class and stress and to examine whether the association is found in both men and women in a prospective study of Japanese male and female workers. A total of 3190 male and 3363 female Japanese community-dwelling workers aged 65 or under with no history of cardiovascular disease were followed. Occupational stress was evaluated using a demand-control questionnaire. The impact on stroke was examined in stratified analyses of occupational classes. We identified 147 incident strokes (91 in men and 56 in women) during the 11-year follow-up period. Men with high strain jobs (combination of high job demand and low job control) were nearly three times more likely to suffer from a stroke than men with low strain jobs (combination of low job demand and high job control). Among male workers in low occupational classes (blue-collar and non-managerial work), job strain was associated with a higher risk of stroke. In contrast, there was no association between job strain and incident stroke among male workers in high occupational classes (white-collar and managerial work). No statistically significant differences were found for stroke incidence among the job characteristic categories in all the female participants. However, significant, over five-fold excess risks were found among white-collar and managerial female workers exposed to high job strain, compared with their counterparts with low strain jobs. Our study of Japanese workers provided supportive evidence for vulnerability to occupational stress among lower occupational class workers in males but not in females. (C) 2011 Elsevier Ltd. All rights reserved.

Background: Only a few population-based cohort studies have investigated the impact of atrial fibrillation (AF) on stroke in Japan. Methods: A total of 10 929 participants (4147 men and 6782 women) were included in this population-based prospective cohort study. Baseline data, including electrocardiograms (ECGs) to ascertain AF status, were obtained from April 1992 through July 1995 in 12 areas in Japan. Cox proportional hazards models were used to analyze the association of AF with stroke. Results: A total of 54 participants had AF (0.49%). The mean follow-up period was 10.7 years, during which 405 strokes were identified; 12 of these occurred in participants with AF. The crude incidence of stroke in participants with and without AF was 14.9 and 4.5 per 1000 person-years in men, respectively, and 39.3 and 2.7 per 1000 person-years in women. After adjusting for geographical area, sex, age, smoking status, drinking status, obesity, hypertension, dyslipidemia, and diabetes mellitus, the hazard ratios (95% confidence interval) of AF in all participants and in male and female participants were 4.11 (2.28-7.41), 2.12 (0.77-5.84), and 10.6 (5.01-22.4), respectively. The population attributable fraction (PAF) of stroke caused by AF was 2.2%; the PAFs were 1.0% and 3.6% in men and women, respectively. Conclusions: The present Japanese population-based prospective cohort study showed that AF is a major risk factor for stroke, especially in women.

Background. The relationship between pulse pressure (PP) and stroke has been described in populations outside Japan. Here, we investigated the relationship between PP and stroke incidence in Japan. Methods. Study subjects were 11,097 people (4315 men and 6782 women) in 12 rural areas of Japan enrolled in the Jichi Medical School Cohort Study, a population-based prospective study. The subjects were divided into quintiles of PP. Baseline data were obtained by questionnaire and health checkups between April 1992 and July 1995, and the incidence of all strokes and stroke subtypes was monitored. Results. A total of 412 strokes were observed during a mean follow-up period of 10.7 years. After adjusting for age, smoking status, drinking status, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, body mass index and diabetes mellitus, hazard ratios [HRs] in the second to fifth quintiles of PP for all strokes were 1.06 (95% confidence interval [CI] 0.69-1.64), 1.53 (CI 1.02-2.28), 2.02 (CI 1.38-2.96) and 2.22 (CI 1.53-3.20) compared with the first quintile using Cox&apos;s proportional hazard model, respectively. Conclusion. Our findings suggest high PP is at an increased risk of stroke.

Background: We investigated the relationship between low cholesterol and mortality and examined whether that relationship differs with respect to cause of death. Methods: A community-based prospective cohort study was conducted in 12 rural areas in Japan. The study subjects were 12 334 healthy adults aged 40 to 69 years who underwent a mass screening examination. Serum total cholesterol was measured by an enzymatic method. The outcome was total mortality, by sex and cause of death. Information regarding cause of death was obtained from death certificates, and the average follow-up period was 11.9 years. Results: As compared with a moderate cholesterol level (4.14-5.17 mmol/L), the age-adjusted hazard ratio (FIR) of low cholesterol (&lt;4.14 mmol/L) for mortality was 1.49 (95% confidence interval [CI]: 1.23-1.79) in men and 1.50 (1.10-2.04) in women. High cholesterol (&gt;= 6.21 mmol/L) was not a risk factor. This association was unchanged in analyses that excluded deaths due to liver disease, which yielded age-adjusted HRs of 1.38 (95% CI, 1.13-1.67) in men and 1.49 (1.09-2.04) in women. The multivariate-adjusted HRs and 95% CIs of the lowest cholesterol group for hemorrhagic stroke, heart failure (excluding myocardial infarction), and cancer mortality significantly higher than those of the moderate cholesterol group, for each cause of death. Conclusions: Low cholesterol was related to high mortality even after excluding deaths due to liver disease from the analysis. High cholesterol was not a risk factor for mortality.

Data relating habitual sleep duration to the risk of silent or overt stroke are sparse. We tested the hypothesis that short duration of sleep is associated with increased risk of silent cerebral infarct (SCI) and stroke events in hypertensive patients. We performed ambulatory BP monitoring in 1268 hypertensives (mean age: 70.4 years) and followed them for 50 months. Brain MRI was performed in 932 of these subjects for the assessment of SCI, and these subjects were analyzed in this study. Cox proportional hazard models were used to calculate the hazard ratios (HR) of sleep-duration-associated risk for cardiovascular events while controlling for significant covariates. In multivariable Cox regression analysis, a sleep duration &lt;7.5 h was independently associated with the risk of stroke (HR = 2.21; P = 0.003). The presence of SCI was also associated with stroke events (HR = 2.60; P = 0.005). When the subjects were divided into an SCI(+) group and SCI(-) group, the short sleep duration was a significant predictor for incident stroke only in the SCI(+) group (HR = 2.52; P = 0.001). Shorter sleep duration was an independent risk for future incidence of stroke events in hypertensive patients, especially those with SCIs. J Am Soc Hypertens 2010;4(5):255-262. (C) 2010 American Society of Hypertension. All rights reserved.

Background Prehypertension is associated with an increased risk of the development of hypertension and subsequent cardiovascular disease. However, it is unclear whether the increased risk of cardiovascular disease associated with prehypertension varies by duration of follow-up (i.e., the first 5 years vs. second 5 years) or varies between nonelderly and elderly individuals. Methods We enrolled 11 000 community dwelling persons (6739 women and 4261 men, aged 18-90 years) from the Japanese general population, followed them for an average of 10.7 +/- 2.4 years (117 517 person-years) and evaluated the incidence of cardiovascular events (including both stroke and myocardial infarction). Results In the full cohort, prehypertension was associated with a 45% higher risk of cardiovascular events than normal blood pressure after adjusting for traditional cardiovascular risk factors (hazard ratio = 1.45, P = 0.03). The risk of cardiovascular events with prehypertension during the second 5-year period was elevated in the nonelderly subgroup (&lt;65 years) (hazard ratio = 2.13, P = 0.01), but not in the elderly subgroup (&gt;= 65 years) (hazard ratio = 0.93, P = 0.82) (P = 0.054 for the difference in hazard ratio). The elevated risk with prehypertension during the first 5-year period was not significant in either the nonelderly (hazard ratio = 1.60, P = 0.36) or elderly (hazard ratio = 1.19, P = 0.63) group. However, the risks with prehypertension were not statistically different between the first and second 5-year period. Conclusion Prehypertension is associated with an increased 10-year risk of cardiovascular disease; the provocative finding that this risk may be especially elevated during the second 5-year period in the nonelderly requires confirmation in a larger cohort. J Hypertens 28: 1630-1637 (c) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.