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The triglycerides-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) is a predictor of metabolic syndrome and cardiovascular disease onset. However, the relationship between TG/HDL-C and stroke has not been established. This study examined whether TG/HDL-C helps in predicting stroke onset; this was compared between the whole population and healthy body mass index (BMI) population.The Jichi Medical School Cohort Study is a prospective cohort study involving baseline data collected in 12 Japanese districts between April 1992 and July 1995. We used data from 11,699 participants; participants with a healthy BMI (20.0-24.9 kg/mIncreased TG/HDL-C correlated with a significant increase in stroke risk only in the healthy BMI population and not the whole population. Furthermore, it was primarily associated with increased intracerebral hemorrhage and cerebral infarction risk.

Objective Coffee consumption can be expected to reduce mortality due to cardiovascular diseases and cancer. This study tested the hypothesis of an inverse association between coffee intake and all-cause mortality and mortality due to cancer, coronary heart disease, or stroke. Study design Prospective cohort study. Methods We analyzed data from the Jichi Medical School Cohort Study, Japan, enrolling 9946 subjects (men/women: 3870/6,076, age: 19–93 years) from 12 communities. A food frequency questionnaire assessing the subjects’ daily coffee consumption was used. Results During an average follow-up of 18.4 years, the total number of deaths was 2024, including 677 for cancer, 238 for coronary heart disease, and 244 for stroke. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality and cause-specific mortality due to cancer, coronary heart disease, and stroke. Overall, no significant association was shown between coffee consumption and all-cause mortality. In the cause-specific mortality analyses, stroke mortality was significantly lower in those who consumed 1–2 cups of coffee daily (HR [95% CI]: 0.63 [0.42–0.95]) than in those who do not consume coffee, and this association occurred only in men. Conclusion This study showed no significant association between coffee consumption and all-cause mortality. A U-shaped association between coffee consumption and stroke mortality with a 37% lower stroke mortality, only significant in men who consume 1–2 cups of coffee daily was observed. It is necessary to examine the possibility of intervention studies to reduce stroke mortality through coffee consumption

The long-term prognosis of those with a history of Kawasaki disease (KD) is still unknown.Using a permanent registry system in Japan (koseki), 6,576 persons with a history of KD were followed up. The average follow-up period was 30 years. The endpoint was death.With a 99.5% follow-up rate, 68 deaths (48 males and 20 females) were observed. The overall standardized mortality ratio, of which reference was vital statistics in Japan, was not elevated. However, the observation according to the presence or absence of cardiac sequelae showed that the standardized mortality ratio for those with cardiac sequelae significantly elevated. Nine persons, all of whom were males, died of KD (including those cases where KD was suspected), but all deaths occurred in individuals who were under 30 years of age.This study revealed the long-term prognosis for KD, but almost all participants were younger than 40 years. Continuing follow up of this cohort is required to clarify whether a history of KD relates to the development of atherosclerosis when participants become middle aged or older.

Background Lifetime risk is an informative estimate for driving lifestyle and behavioral changes especially for young adults. The impact of composite risk factors for cardiovascular disease on lifetime risk stratified by sex has not been investigated in the Japanese population, which has a much lower mortality of coronary heart disease compared with the Western population. We aimed to estimate lifetime risk of death from cardiovascular disease attributable to traditional risk factors. Methods and Results We analyzed pooled individual data from the Evidence for Cardiovascular Prevention from Observational Cohorts in a Japanese cohort study. A modified Kaplan–Meier approach was used to estimate the remaining lifetime risk of cardiovascular death. In total, 41 002 Japanese men and women with 537 126 person‐years of follow‐up were included. The lifetime risk at the index‐age of 45 years for those with optimal risk factors (total cholesterol Conclusions The magnitude and the number of risk factors were progressively associated with increased lifetime risk even in individuals in early adulthood who tend to have low short‐term risk. The degree of established cardiovascular risk factors can be converted into lifetime risk. Our findings may be useful for risk communication in the early detection of future cardiovascular disease risk.

Resistant hypertension is an important cardiovascular risk factor. This analysis of the JAMP study (Japan Ambulatory Blood Pressure Monitoring Prospective) data investigated the effects of uncontrolled resistant hypertension diagnosed using ambulatory blood pressure (BP) monitoring on the risk of heart failure (HF) and overall cardiovascular events. The JAMP study patients with hypertension and no HF history were included. They had true resistant hypertension (24-hour BP ≥130/80 mm Hg), pseudoresistant hypertension (24-hour BP P =0.012 and 2.24 [95% CI, 1.17–4.30]; P =0.015, respectively) and versus uncontrolled nonresistant hypertension (1.51 [1.03–2.20]; P =0.034 and 3.03 [1.58–5.83]; P Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000020377.

ObjectivesSmall dense low-density lipoprotein cholesterol (sdLDL-C) might be a better cardiovascular disease (CVD) indicator than low-density lipoprotein cholesterol (LDL-C); however, details regarding its epidemiology remain elusive. The present study aimed at evaluating the association between the demographic factors, such as age, gender and menopausal status, and sdLDL-C levels and sdLDL-C/LDL-C ratio in the Japanese population.DesignThis was a cross-sectional study.Setting13 rural districts in Japan, 2010–2017.ParticipantsThis study included 5208 participants (2397 men and 2811 women), who underwent the health mass screening that was conducted in accordance with the medical care system for the elderly and obtained informed consent for this study.ResultsIn total, 517 premenopausal women (mean age ±SD, 45.1±4.2 years), 2294 postmenopausal women (66.5±8.8 years) and 2397 men (64.1±11.2 years) were analysed. In men, the sdLDL-C levels and sdLDL-C/LDL-C ratio increased during younger adulthood, peaked (36.4 mg/dL, 0.35) at 50–54 years, and then decreased. In women, relatively regular increasing trends of sdLDL-C level and sdLDL-C/LDL-C ratio until approximately 65 years (32.7 mg/dL, 0.28), followed by a downward or pleated trend. Given the beta value of age, body mass index, fasting glucose and smoking and drinking status by multiple linear regression analysis, standardised sdLDL-C levels and sdLDL-C/LDL-C ratio in 50-year-old men, premenopausal women and postmenopausal women were 26.6, 22.7 and 27.4 mg/dL and 0.24, 0.15 and 0.23, respectively. The differences between premenopausal and postmenopausal women were significant (pConclusionsSdLDL-C and sdLDL-C/LDL-C ratios showed different distributions by age, gender and menopausal status. A subgroup-specific approach would be necessary to implement sdLDL-C for CVD prevention strategies, fully considering age-related trends, gender differences and menopausal status.

AIM: Lifetime risk (LTR) indicates the absolute risk of disease during the remainder of an individual's lifetime. We aimed to assess the LTRs for coronary heart disease (CHD) mortality associated with blood pressure (BP) and total cholesterol levels in an Asian population using a meta-analysis of individual participant data because no previous studies have assessed this risk. METHODS: We analyzed data from 105,432 Japanese participants in 13 cohorts. Apart from grade 1 and 2-3 hypertension groups, we defined "normal BP" as systolic/diastolic BP ＜130/＜80 mmHg and "high BP" as 130-139/80-89 mmHg. The sex-specific LTR was estimated while considering the competing risk of death. RESULTS: During the mean follow-up period of 15 years (1,553,735 person-years), 889 CHD deaths were recorded. The 10-year risk of CHD mortality at index age 35 years was ≤ 0.11%, but the corresponding LTR was ≥ 1.84%. The LTR of CHD at index age 35 years steeply increased with an increase in BP of participants with high total cholesterol levels [≥ 5.7 mmol/L (220 mg/dL)]. This risk was 7.73%/5.77% (95% confidence interval: 3.53%-10.28%/3.83%-7.25%) in men/women with grade 2-3 hypertension and high total cholesterol levels. In normal and high BP groups, the absolute differences in LTRs between the low and high total cholesterol groups were ≤ 0.25% in men and ≤ 0.40% in women. CONCLUSIONS: High total cholesterol levels contributed to an elevated LTR of CHD mortality in hypertensive individuals. These findings could help guide high-risk young individuals toward initiating lifestyle changes or treatments. ispartof: JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS vol:28 issue:1 pages:6-24 ispartof: location:Japan status: published

BACKGROUND Several studies have described an association between hemoglobin concentration and stroke; however, the influence of hemoglobin on stroke incidence has not been fully revealed. Our objective was to elucidate the association between hemoglobin concentration and stroke incidence in Japanese community residents. METHODS In the present study, we collected the data of 12,490 subjects who were enrolled between April 1992 and July 1995 in the Jichi Medical School (JMS) Cohort Study. We excluded the subjects with a history of stroke. Hemoglobin concentrations were grouped in quartiles, and quartile 2 (Q2) was used as the reference category. A Cox proportional-hazards model was used to examine hazard ratios (HRs) and the stroke incidence rates with 95% confidence intervals (CIs). RESULTS During 10.8 years of follow-up, 409 participants (212 men and 197 women) experienced a new stroke, including 97 intracerebral hemorrhages, 259 cerebral infarctions, and 52 subarachnoid hemorrhages (SAH). In sex-specific hemoglobin quartiles, the multivariate-adjusted HR was statistically significantly higher in Q1 than in Q2, and a relationship similar to a J shape was observed between all strokes (HR in Q2 vs. Q1, 1.36; 95% CI, 1.02-1.83; Q3, 1.20; 95% CI, 0.87-1.64; and Q4, 1.16; 95% CI, 0.84-1.60). Furthermore, the analysis of stroke subtypes showed a statistically significantly higher multivariate-adjusted HR in Q1 than in Q2 for SAH (HR, 2.61; 95% CI, 1.08-6.27). CONCLUSIONS A low hemoglobin concentration was associated with an increased risk of stroke, which was strongly influenced by the incidence of SAH.

ObjectiveTo examine the association between polarity of atrial premature complexes (APCs) and stroke.DesignA prospective study.Setting and participantsA total of 11 092 participants in the Jichi Medical School cohort study were included after excluding patients with atrial fibrillation. We analysed stroke events in patients with (n=136) and without (n=10 956) APCs. With regard to polarity of APCs, patients were subcategorised into having (1) negative (n=39) or non-negative (n=97) P waves in augmented vector right (aVR), and (2) positive (n=28) or non-positive (n=108) P waves in augmented vector left (aVL).Outcome measuresThe primary endpoint was stroke.ResultsPatients with APCs were significantly older than those without APCs (64.1±9.2 vs 55.1±11.6 years, pConclusionsThe presence of APCs with non-negative P wave in aVR or non-positive P wave in aVL on 12-lead ECG was associated with a higher risk of incident stroke.

We aimed to investigate the relationship between high-density lipoprotein cholesterol (HDL-C) concentration and the incident stroke subtypes. We enrolled 11 027 participants between the ages of 18 and 90 years without a history of stroke in 12 Japanese communities. Cox’s regression models were used for stroke subtypes, adjusted for traditional risk factors, according to the categories based on HDL-C concentrations: 1.04 to 1.55 mmol/L, ≥1.56 mmol/L, and

Smoking is a risk factor for stroke. The relationship between smoking and the risk of different subtypes of stroke has not been fully elucidated. We investigated the relationship between smoking and the incidence of stroke in the Japanese population.This prospective, population-based cohort study included 11,324 participants (4447 men; 6877 women) from 12 districts in Japan, between April 1992 and July 1995. Participants were stratified according to smoking status (non-smoker [never smoked]/ex-smoker/current smoker). Male current smokers were further stratified according to the number of cigarettes smoked per day (1-14, 15-29, or ≥ 30). The non-smoking group was used as a reference. Cox proportional hazards analysis was used to determine the risk of stroke due to smoking.Four hundred and seventeen new stroke events (212 men; 205 women) were recorded during a mean follow-up of 10.7 years, including 95 intracerebral hemorrhages (48 men; 47 women), 267 cerebral infarctions (152 men; 115 women), and 54 subarachnoid hemorrhages (12 men; 42 women). In multivariable analysis, the hazard ratios (95% confidence intervals) for male current smokers (≥ 30 cigarettes/day) were 1.89 (1.08-3.31) and 3.41 (1.22-9.57) for all strokes and intracerebral hemorrhages, respectively; those for female current smokers were 2.78 (1.62-4.74), 3.14 (1.51-6.54), and 4.03 (1.64-9.93) for all strokes, cerebral infarctions, and subarachnoid hemorrhages, respectively.Smoking ≥ 30 cigarettes/day is a risk factor for stroke, especially intracerebral hemorrhage in men. Furthermore, smoking increases the risk of cerebral infarction and subarachnoid hemorrhage in women.

Previous studies have found the prevention paradox in the association between stroke events and a single specific risk factor, indicating that a population-based strategy may be more effective than a high-risk-based strategy for prevention. We tested the hypothesis that the prevention paradox does not apply when focusing on multiple potential risk factors simultaneously. The study cohort included 9051 individuals from Japan aged 40–89 years. The time-dependent Cox proportional-hazards models were used to identify the primary risk factor associated with stroke onset. We classified participants based on risk factors in two distinct ways: 1) classifying the high-risk group participants according to a single specific risk factor that had a large association with stroke in both sexes and all ages and 2) classifying the high-risk group participants according to 1–3 risk factor(s) including hypertension, hyperglycemia, and/or dyslipidemia. Then, we compared the proportions of the total number of participants who developed stroke in both groups to assess the prevention paradox. We found that hypertension was a primary risk factor for stroke incidence, regardless of sex and age. The percentage of patients with a single specific risk of and developed stroke was 46%–63%, while the percentage of patients with 1–3 risk factor(s) was 71–83%. This finding leads to the conclusion that the prevention paradox does not hold when multiple stroke risk factors were associated, suggesting that a high-risk-based strategy that focuses on patients with multiple risk factors may be more effective in preventing strokes.

Background Whereas high body mass index (BMI) is reportedly a risk factor for cardiovascular events in Western countries, low BMI has been reported as a risk factor for cardiovascular death in Asia, including Japan. Although subarachnoid hemorrhage (SAH) is a highly fatal disease and common cause of disability, few cohort studies have examined the associations between BMI and SAH in Japan. This study investigated the associations between BMI and incidence of SAH using prospective data from Japanese community residents. Methods Data were analyzed from 12,490 participants in the Jichi Medical School Cohort Study. Participants were categorized into 5 BMI groups: ≤18.5, 18.6-21.9, 22.0-24.9, 25.0-29.9, and ≥30.0 kg/m 2 . Multivariate-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard model with BMI of 22.0-24.9 kg/m 2 as the reference category. Results During the mean follow-up period of 10.8 years, 55 participants (13 men, 42 women) experienced SAH. BMI ≥30.0 kg/m 2 was associated with significantly higher risk for SAH (HR, 5.98; 95% CI, 2.25-15.87). BMI ≤18.5 kg/m 2 showed a nonsignificant tendency toward high risk of SAH (HR, 2.51; 95% CI, .81-7.79). Conclusions High BMI was a significant risk factor for SAH. Lower BMI showed a nonsignificant tendency toward higher risk of SAH. Our results suggest a J-shaped association between BMI and risk of SAH incidence.

Background High body mass index (BMI) has been reported as a risk factor for cardiovascular events in Western countries, while low BMI has been reported as a risk factor for cardiovascular death in Asian countries, including Japan. Although stroke is a major cause of death and disability in Japan, few cohort studies have examined the association between BMI and stroke incidence in Japan. This study aimed to examine the association between BMI and stroke incidence using prospective data from Japanese community residents. Methods Data were analyzed from 12,490 participants in the Jichi Medical School Cohort Study. Participants were categorized into five BMI groups: ≤18.5, 18.6–21.9, 22.0–24.9, 25.0–29.9, and ≥30.0 kg/m2. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model. The group with a BMI of 22.0–24.9 kg/m2 was used as the reference category. Results During mean follow-up of 10.8 years, 395 participants (207 men and 188 women) experienced stroke, including 249 cerebral infarctions and 92 cerebral hemorrhages. Men with a BMI ≤18.5 kg/m2 (HR 2.11; 95% CI, 1.17–3.82) and women with a BMI ≥30.0 kg/m2 (HR 2.25; 95% CI, 1.28–5.08) were at significantly higher risk for all-stroke. Men with a BMI ≤18.5 kg/m2 were at significantly higher risk for cerebral infarction (HR 2.15; 95% CI, 1.07–4.33). Conclusions The association between BMI and stroke incidence observed in this population was different than those previously reported: low BMI was a risk factor for all-stroke and cerebral infarction in men, while high BMI was a risk factor for all-stroke in women., Highlights • The association of body mass index (BMI) with stroke remains controversial in Japan. • Our large cohort study examined the association of interest in a Japanese population. • Low BMI increased the risk of all-stroke and cerebral infarction incidence in men. • In contrast, high BMI increased the risk of all-stroke incidence in women.

Prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Tsuda et al. show that Crhr2 activation causes cardiac dysfunction and suggest Crhr2 blockade is a promising therapeutic strategy for chronic heart failure., Heart failure occurs when the heart is unable to effectively pump blood and maintain tissue perfusion. Despite numerous therapeutic advancements over previous decades, the prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Here, we show that corticotropin releasing hormone receptor 2 (Crhr2) is a G protein–coupled receptor highly expressed in cardiomyocytes and continuous infusion of the Crhr2 agonist, urocortin 2 (Ucn2), reduced left ventricular ejection fraction in mice. Moreover, plasma Ucn2 levels were 7.5-fold higher in patients with heart failure compared to those in healthy controls. Additionally, cardiomyocyte-specific deletion of Crhr2 protected mice from pressure overload-induced cardiac dysfunction. Mice treated with a Crhr2 antagonist lost maladaptive 3′-5′-cyclic adenosine monophosphate (cAMP)–dependent signaling and did not develop heart failure in response to overload. Collectively, our results indicate that constitutive Crhr2 activation causes cardiac dysfunction and suggests that Crhr2 blockade is a promising therapeutic strategy for patients with chronic heart failure.

Background The cardiovascular relevance of isolated low levels of high‐density lipoprotein cholesterol (HDL‐C) is yet to be determined. Stroke often leads to long‐term disability, and thus, not only stroke mortality but also stroke incidence is a topic of research. Although isolated low HDL‐C level has been found to be a predictor for stroke mortality previously, whether it can predict stroke incidence is unknown. Methods In the Jichi Medical School cohort study, 11 025 community‐living residents without a history of stroke were examined. Hazard ratios (HRs) for isolated and non‐isolated low HDL‐C levels were calculated relative to those for normal HDL‐C levels in stroke patients using Cox's regression models. Results During the mean follow‐up period of 10.7 years, 412 residents had their first‐ever stroke. The multivariable‐adjusted HRs for the levels of isolated and non‐isolated low HDL‐C were 1.11 (95% confidence interval, 0.85‐1.44) and 1.35 (1.01‐1.81), respectively, when compared to that for normal HDL‐C. Conclusion Low HDL‐C levels with other dyslipidemias may contribute to the incidence of stroke, not isolated low HDL‐C.

Lifetime risk (LTR) provides an absolute risk assessment during the remainder of one’s life. Few studies have focused on the LTRs of stroke and coronary heart disease (CHD), categorized by fine blood pressure in Asian populations. We aimed to assess it using a large database of a meta-analysis with the individual participant data. The present meta-analysis included 107 737 Japanese (42.4% men; mean age, 55.1 years) from 13 cohorts. During the mean follow-up of 15.2±5.3 years (1 559 136 person-years), 1922 died from stroke and 913 from CHD. We estimated risks after adjusting for competing risk of death other than the outcome of interest. The 10-year risk of stroke and CHD deaths at index age of 35 years was ≤1.9% and ≤0.3%, respectively. The LTRs of stroke death at the index age of 35 years (men/women) were 6.1%/4.8% for optimal, 5.7%/6.3% for normal, and 6.6%/6.0% for high-normal blood pressure groups, and 9.1%/7.9% for grade 1, 14.5%/10.3% for grade 2, and 14.6%/14.3% for grade 3 hypertension groups. The LTRs of CHD death similarly elevated with an increase in blood pressure but were lower (≤7.2%) than those of stroke death. In conclusion, blood pressure was clearly associated with an elevated LTR of stroke or CHD death, although the LTR of CHD death was one-half of that of stroke death in an Asian population. These results would help young people with hypertension to adopt a healthy lifestyle or start antihypertensive therapy early.

Japan is an aging society, and the incidence of diseases related to aging, such as pneumonia, heart failure, vertebral compression fracture (VCF), is increasing. Prolonged hospital stays are becoming a serious social problem, leading to elevated medical expenses. Thus, shortening the period of hospitalization is important. This study aimed to reveal determinants associated with prolonged hospital stays for patients with VCF. Our institution is the primary hospital in a rural area in the Kanto region of Japan. Altogether, 110 patients with a VCF, aged 65 years or older, including 79 women, were divided into two groups according to the average hospital stay period of 28 days: the long-stay group (mean stay 40.0 ± 11.6 days, n = 39) and the short-stay group (mean stay 20.6 ± 4.4 days, n = 71). Notably, the short-stay group included 55 women. Multivariate logistic regression analyses in male showed no variates significantly associated with prolonged hospitalization. By contrast, multivariate logistic regression analyses in female showed requiring emergency transportation to hospital was significantly associated with prolonged hospitalization [odds ratio 7.69, 95% confidence interval 1.13-52.29, P = 0.04]. In conclusion, this study implies that patients with better levels of activities of daily living are able to walk alone sooner and are easily discharged. Furthermore, the patient requiring emergency transportation might be in a poor social living environment, such as living alone. These results may give us a good opportunity to re-consider fundamental problems surrounding the elderly.

This study aimed to investigate the associations of body mass index (BMI) and metabolically unhealthy weight with all-cause mortality, cardiovascular disease (CVD) mortality, and cancer mortality as well as the effect of age on the associations. This prospective study enrolled Japanese individuals in the general population. Participants were divided into eight phenotypes according to the BMI classification and metabolic status. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox regression hazard model. In total, 10,824 individuals with a mean age of 55.3 years were evaluated. During a mean follow-up of 18.4 years (198,776 person-years), 2,274 participants died. Among the metabolically unhealthy, the association between BMI and mortality was J-shaped after adjustment for various confounders (multivariable HR [95% CI] for all-cause mortality: underweight, 2.0 [1.5–2.7]; obesity 2.8 [2.1–3.6]). The association remained the same in metabolically unhealthy participants aged

Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40-89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.

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.

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.

Rationale & Objective Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. Study Design Cross-sectional individual participant-level analyses in a global consortium. Setting & Study Populations 17 CKD and 38 general population and high-risk cohorts. Selection Criteria for Studies Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. Data Extraction Data were obtained and analyzed between July 2015 and January 2018. Analytical Approach We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. Results The CKD cohorts (n = 254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n = 1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59 mL/min/1.73 m 2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30 mg/g). Limitations Variations in study era, health care delivery system, typical diet, and laboratory assays. Conclusions Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD. © 2018. This is the authors’ accepted and refereed manuscript to the article. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ "

Background Minor ST-T changes are frequently observed on the electrocardiogram (ECG), but the risk of stroke associated with such changes is unclear.Methods and Results:In 10,642 subjects from the Japanese general population, we evaluated minor and major ST-T changes (major ST depression ≥0.1 mV) on ECGs obtained at annual health examinations. At baseline, minor ST-T changes were found in 10.7% of the subjects and 0.5% had major ST-T changes. Minor ST-T changes were associated with older age, female gender, higher systolic blood pressure, presence of hyperlipidemia, and use of antihypertensive medication. There were 375 stroke events during the follow-up period (128.7±28.1 months). In all subjects, minor ST-T changes (HR, 2.10; 95% CI: 1.57-2.81) and major ST-T changes (HR, 8.64; 95% CI: 4.44-16.82) were associated with an increased risk of stroke, but the stroke risk associated with minor ST-T changes had borderline significance after adjustment for conventional risk factors (P=0.055). In subgroup analysis, the risk of stroke was significantly associated with minor ST-T changes in subjects who had hyperlipidemia (HR, 1.75; 95% CI: 1.15-2.67) compared to those without hyperlipidemia (HR, 1.01; 95% CI: 0.64-1.59; P for interaction=0.016), even after adjustment for ECG-diagnosed left ventricular hypertrophy. Conclusions Minor ST-T changes were particularly associated with a higher risk of stroke in subjects with hyperlipidemia and this association was independent of electrocardiographic left ventricular hypertrophy.

Objectives To reveal the features of death and subsequent funeral services, we analyzed self-reported obituaries in The Shimotsuke, a local daily newspaper in Tochigi, Japan. In addition, the usefulness and disadvantages of such a database of deaths based on the obituaries were discussed.Method For a 5-year period, from January 2011 through December 2015, all the obituary columns in The Shimotsuke were computerized as a database and analyzed. Some results were compared with the vital statistics data in the corresponding period of time. Data analyzed were: dead persons' address (municipalities), name, sex, cause of death, age at death, date of death and funeral services, the chief mourner (Moshu), and so on.Results During the observed 5-year period, 69,793 deaths appeared in the columns, which were 67.6% of the all deaths in the vital statistics. No difference was observed in the proportions between the sexes in the published deaths in comparison with the vital statistics. In both sexes, the proportion was low in 0-9 years old, then high among 10-19 years, decreasing in 20s, and after then the proportion increased according to the age. The proportion was low in city areas, such as Utsunomiya and Oyama, and high in some cities and towns in the northern or eastern parts of Tochigi prefecture. The highest was in Motegi Town (88.0%), and the lowest was Nogi Town (38.0%), which is located in the southern-most part of the prefecture and is closest to the Tokyo metropolitan area. Almost all the funeral services were conducted within a week of the death, and no delays were observed to have been caused by the short supply of cremation services, which exists in large cities in Japan. In case where the chief mourner was a child, a parent, or a spouse of a child, the male sex was dominant. Analyses of death from senile decay, suicide, and homicide indicated that the accuracy of the published cause of death was low. The date of the funeral services was strongly influenced by superstitions in this country.Conclusions Observations of the self-reported obituaries in a local daily newspaper over five years revealed the situations of the deaths in the area that could not be observed using vital statistics. Despite limitations, the information was partially useful as a database.

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.

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.

ObjectiveWe investigated whether serum high-sensitivity C reactive protein (hs-CRP) levels measured in an emergency department (ED) are associated with inhospital mortality in patients with cardiovascular disease (CVD).DesignA retrospective cohort study.SettingED of a teaching hospital in Japan.Participants12 211 patients with CVD aged ≥18 years who presented to the ED by an ambulance between 1 February 2006 and 30 September 2014 were evaluated.Main outcome measuresInhospital mortality.Results1156 patients had died. The inhospital mortality increased significantly with the hs-CRP levels (ConclusionOur findings suggest that increased hs-CRP is a significant risk factor for inhospital mortality among patients with CVD in an ED. Particular attention should be given to our finding that non-CVD death is a major cause of death among patients with CVD with higher hs-CRP levels.

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.

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/m2), but not obesity (BMI ≥25 kg/m2), 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 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.

Prostate cancer is a common disease in modern, developed societies and has a high incidence and mortality. High-density 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.

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

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.

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 12334 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 (4.14–5.17mmol/L), the age-adjusted hazard ratio (HR) of low cholesterol (

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 10623 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.

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.

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

Summary Background and purpose Premature ventricular complexes (PVCs) are frequently encountered in healthy people. But the association between PVCs and cardiac events is not well established in Japan. We investigated the association of PVCs and cardiac deaths in people without cardiovascular disease in the Jichi Medical School (JMS) Cohort study. Methods and subjects We conducted a prospective cohort study in 12 districts in Japan as part of the JMS cohort study. Baseline data were obtained between April 1992 and July 1995. We excluded subjects who had myocardial infarction and stroke and those who had not received 12-lead electrocardiograms. Cox's proportional hazard model was used to calculate the hazard ratios (HRs) of cardiovascular mortality of subjects with PVCs, using subjects without PVCs as reference. Results A total of 11,158 participants (4333 males and 6825 females) were analyzed. Participants were followed for an average of 11.9 years. PVCs were present in 1.4% of men and 1.1% of women. There were 92 cardiac deaths (47 males and 45 females) during the follow-up period. In crude cardiovascular mortality, HRs (95% confidence interval [CI]) were 5.29 (1.64–17.0) in males and 2.14 (0.29–15.5) in females. Age-adjusted HRs were 3.73 (1.16–12.0) and 0.98 (0.13–7.21), respectively. After further adjustment for body mass index, systolic blood pressure, total cholesterol level, high-density lipoprotein-cholesterol, and blood glucose, HRs were 3.98 (1.21–13.0) and 0.95 (0.13–7.11), respectively. Conclusions We conclude that PVCs are a predictive factor for cardiac death in men without structural heart disease.

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.

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.

We tested the reproducibility of ambulatory blood pressure (ABP), BP variability, and BP reduction in hypertensive patients.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.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).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.

Background: Although seasonal variation in stroke incidence has been reported, it is not known whether year-long 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-up 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 °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 an increased risk of stroke incidence, but the association became nonsignificant after adjustment for other risk factors. Similar results were obtained for cerebral infarction and cerebral hemorrhage.Conclusions: Long-term exposure to some meteorological conditions may affect the risk of stroke, particularly in women, independent of conventional risk factors.

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 clinicallycertified 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: 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.

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×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.

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 1.68; 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: 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.

Non-dipping (nocturnal blood pressure [BP] decrease

This study is to evaluate the associations between adiponectin level and noncardiovascular 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.