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Background Anger has been suggested as a risk factor for stroke. Perceived social support (PSS) may relieve anger, thus reducing the risk of stroke; however, evidence supporting this is limited. We aimed to examine whether PSS modifies the risk of stroke associated with anger expression. Methods A cohort study was conducted among 1,806 community residents aged 40-74 years who received a cardiovascular risk survey including anger expression in 1997. A Cox proportional hazards model was applied to the participants with low and high PSS to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the risks of total stroke and its subtypes based on total anger expression after adjusting for known stroke risk factors. Results The median follow-up duration was 18.8 years, with 51 incident strokes. Among the participants with low PSS, anger expression had a positive association with the total stroke risk: The multivariable HR per SD increment of total anger expression was 1.43 (95% CI, 1.13-1.82). In contrast, no association was identified among those with high PSS. The corresponding HR was 0.83 (95% CI, 0.49-1.40), with a significant interaction between low and high PSS (p = 0.037). Similar associations regarding the risk of ischemic stroke were found. Conclusions We found an increased risk of stroke associated with anger expression among the participants with low PSS, but not among those with high PSS. Our results suggest that PSS might mitigate the risk of stroke associated with anger.

We aimed to longitudinally clarify the changes in cardiovascular disease risk factors associated with menopause in Japanese women in the 2000s.Of the 4,596 women who underwent health examinations between 2007 and 2012 in three communities of the Circulatory Risk in Communities Study, 263 women who reported going through menopause during that period were included in the study. We randomly selected 1,665 men as control subjects who participated in a health examination at least once between 2001 and 2009 and at least once between 2010 and 2018 by 1:1 pair-matching for age, community, and examination year. The health examination data from 3 to 6 years before (2001-2009) and after menopause age (2010-2018) were compared in terms of body mass index, systolic and diastolic blood pressure levels, serum total cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, triglycerides, uric acid, hemoglobin A1c, hemoglobin, aspartate aminotransferase, alanine aminotransferase, and current smoker status.Compared with the men, the women showed a greater increase in serum total cholesterol (+16.7 vs -3.1 mg/dL, P0.001), non-high-density lipoprotein cholesterol (+15.9 vs -6.3 mg/dL, P0.001), fasting triglycerides (+1.2 vs +1.0 mg/dL, P = 0.027), triglycerides regardless of fasting status (+1.2 vs -0.9 mg/dL, P0.001), uric acid (+0.5 vs +0.2 mg/dL, P = 0.008), hemoglobin (+0.9 vs -0.3 g/dL, P0.001), aspartate aminotransferase (+2.9 vs -2.7 IU/L, P0.001), and alanine aminotransferase (+2.9 vs -2.6 IU/L, P0.001). No differences were found in the changes in body mass index, systolic and diastolic blood pressures, and hemoglobin A1c between the women and the matched men.Menopause may be a crucial factor related to changes in serum total cholesterol, non-high-density lipoprotein cholesterol, triglycerides, uric acid, hemoglobin, and liver enzymes.

To examine whether bean intake (including soybeans) among Japanese adults is associated with risk of disabling dementia severe enough to require care under the national insurance system.This cohort study involved 3739 individuals aged 40 to 64 years. The participants were categorized into five groups based on their dietary bean intake estimated by a 24h dietary recall. Hazard ratios and 95% confidence intervals of disabling dementia were estimated using Cox proportional hazard models adjusted for potential confounding factors (smoking, drinking, and intakes of energy and fish).During the 59,681 person-year follow-up, 670 cases of disabling dementia were observed. A weak inverse association between bean intake and risk of disabling dementia was found; the multivariable hazard ratios (95% CIs) were 0.79 (0.62-1.00), 0.80 (0.63-1.01), 0.84 (0.67-1.06), and 0.78 (0.62-0.99) for the four groups with higher bean intake, respectively, compared with the lowest group (P for trend = 0.21). A significant inverse association was observed for dementia without a history of stroke; for the four groups with higher bean intake the multivariable hazard ratios were 0.81 (0.61-1.08), 0.70 (0.52-0.95), 0.71 (0.52-0.95), and 0.69 (0.51-0.92), respectively, (P for trend = 0.03). No such association was observed for dementia with history of stroke. The group with increased natto intake were inversely associated with risk of disabling dementia (P for trend = 0.003), but tofu intake was not (P for trend = 0.19).Bean intake was inversely associated with risk of disabling dementia in those without a history of stroke.

Aim We aimed to examine the impact of high-risk levels of cardiovascular risk factors on the incidence of cardiovascular disease (CVD) in overweight and non-overweight individuals without treatment for the risk factors. Methods A total of 8,051 individuals aged 40-74 years without a history of CVD and/or without treatment for hypertension, diabetes, hyperlipidemia, and kidney disease at baseline in 1995-2000 were followed up for a median of 14.1 years. We classified the participants into three risk categories (low-, intermediate-, and high-risk groups) on the basis of individual risk factors (blood pressure, serum glucose, low-density lipoprotein cholesterol [LDL-C], and urinary protein) according to the guidelines of Japanese clinical societies. The high-risk group (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg, fasting serum glucose ≥ 130 mg/dL or non-fasting serum glucose ≥ 180 mg/dL, LDL-C ≥ 180 mg/dL, proteinuria ≥ 2+) needed to refer to physicians or start treatment immediately. Overweight was defined as a body mass index of ≥ 25 kg/m2. Results Compared with those in the non-overweight low-risk group, the hazard ratios (HRs) (95% confidence intervals, population-attributable fractions [PAFs]) of CVD in the high-risk categories of blood pressure were 2.0 (1.4-2.9, 7.0%) in the non-overweight high-risk group and 2.9 (1.9-4.3, 6.8%) in the overweight high-risk group. The corresponding HRs (95% confidence intervals, PAFs) of serum glucose were 2.0 (1.2-3.4, 2.5%) and 2.2 (1.1-4.3, 1.5%) in the non-overweight and overweight high-risk groups, respectively. Such associations were not observed for the high-risk group of LDL-C and proteinuria. Conclusions The present long-term observational study implies that targeting persons with non-treated severe hypertension and diabetes is prioritized to prevent CVD regardless of overweight status.

This study aimed to investigate the association between retinal microvascular abnormalities and the risk of incident stroke and its subtypes in the general Japanese population.A total of 12 965 residents aged 40-74 years without a history of stroke and/or coronary heart disease underwent retinal photography during the annual health checkups of four Japanese communities between 1990 and 1999. Retinal microvascular abnormalities, such as the presence or absence of generalized arteriolar narrowing, focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar light reflex, and retinal hemorrhages were graded using standard protocols.During a median follow-up of 20 years, 817 patients were diagnosed with incident stroke. Retinal microvascular abnormalities were positively associated with the risk of total stroke; after adjustment for age, sex, community, SBP, antihypertensive medication use, and other cardiovascular risk factors, the multivariable hazard ratio [95% confidence interval (CI)] was 1.68 (1.42-1.98), 1.67 (1.34-2.07), 1.41 (1.17-1.72), 1.54 (1.26-1.87), and 1.57 (1.19-2.07) for generalized arteriolar narrowing, focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar light reflex, and retinal hemorrhages, respectively. Similar positive associations were observed for the risk of stroke subtypes, except for subarachnoid hemorrhage, for which no association was observed. Furthermore, the positive associations were similar in participants with and without hypertension.Retinal microvascular abnormalities were positively associated with the risk of incident stroke in the general Japanese population. Routine retinal photography could provide positive clinical insights into stroke risk stratification independent of blood pressure, antihypertensive medication use, and other risk factors.

Aim Seaweed contains soluble dietary fibers, potassium, and flavonoids and was recently reported to be inversely associated with the risk of coronary heart disease and mortality from stroke. However, epidemiological evidence on this issue has remained scarce. Methods At the baseline survey of four Japanese communities between 1984 and 2000, we enrolled 6,169 men and women aged 40-79 years who had no history of cardiovascular disease. We assessed their seaweed intake using the data from a 24 h dietary recall survey and categorized the intake into four groups (0, 1-5.5, 5.5-15, and ≥ 15 g/day). We used sex-specific Cox proportional hazards models to examine the association between seaweed intake and risk of cardiovascular disease (stroke, stroke subtypes, and coronary heart disease). Results During the 130,248 person-year follow-up, 523 cases of cardiovascular disease occurred: 369 cases of stroke and 154 cases of coronary heart disease. Seaweed intake levels were inversely associated with the risk of total stroke and cerebral infarction among men but not among women. Adjustment for cardiovascular risk factors did not change the associations: the hazard ratios (95% confidence intervals; P for trend) for the highest versus lowest categories of seaweed intake were 0.63 (0.42-0.94; 0.01) for total stroke and 0.59 (0.36-0.97; 0.03) for cerebral infarction. No associations were observed between seaweed intake and risks of intraparenchymal hemorrhage, subarachnoid hemorrhage, or coronary heart disease among men or women. Conclusions We found an inverse association between seaweed intake and risk of total stroke, especially that from cerebral infarction, among Japanese men.

Background: The association between overweight and chronic musculoskeletal pain may vary by anatomical site and be modified by hypertension status. This study examined the associations between overweight and low back and knee pains and their effect modification by hypertension status. Methods: We conducted a community-based cross-sectional study involving 2,845 adults (1,080 men and 1,765 women) aged 40–89 years. Chronic knee pain (CKP) and low back pain (CLBP) lasting more than 3 months were categorized into more or less severe pain. Odds ratios (ORs) and 95% confidence intervals (CIs) of the association between overweight and more or less severe CKP and CLBP were determined using logistic regression and stratified by hypertension status. Adjustment variables were age, sex, area, hypertension, smoking and drinking status, inactivity, job category, mental stress, depression, and overall CKP or CLBP. Results: Overall, 288 (10.1%) and 631 (22.2%) adults had more and less severe CKP, respectively, and 284 (10.0%) and 830 (29.2%) had more and less severe CLBP, respectively. Overweight was associated with overall CKP and more or less severe CKP, regardless of hypertension status. Overweight was not associated with overall CLBP; its association was more pronounced for more severe CLBP. The association between overweight and more severe CLBP was evident among non-hypertensives (multivariable OR 1.72; 95% CI, 1.09–2.71); however, that between overweight and less severe CLBP was not evident (multivariable OR 1.07; 95% CI, 0.73–1.56). Conclusions: As hypertension may attenuate the association between overweight and CLBP, we should consider hypertension status for proper management of CLBP among overweight individuals.

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Background: Few studies have provided observational data on long-term trends in the incidence of stroke and its subtypes, and shown the urban–rural disparities of stroke incidence in Japan. Methods: A multiple-source, community-based stroke surveillance was performed since 1963/1964 to determine all first-ever stroke cases among Japanese residents aged ⩾40 years living in the Minami-Takayasu district in Yao city, an urban community, and Ikawa town, a rural community. Sex-specific, age-standardized incidence per 1000/year with 95% confidence intervals was calculated during seven periods of 1963/1964–1971 (urban population (% men): 3242 (47.3%); rural population (% men): 2311 (46.0%)), 1972–1979, 1980–1987, 1988–1995, 1996–2003, 2004–2011, and 2012–2018 (13,307 (46.7%); 3586 (44.8%)). Results: The age-standardized incidence of all strokes in the Japanese urban community decreased from 6.60 to 1.15 per 1000/year for men and 3.28 to 0.59 for women. In the rural community, the corresponding incidence decreased from 11.51 to 1.98 for men and 6.46 to 1.31 for women. Similar reductions were observed in the incidence of intracerebral hemorrhage, subarachnoid hemorrhage, ischemic stroke, and lacunar stroke. In the period of 2012–2018, the incidence ratios (95% confidence intervals) of all strokes for the rural compared to the urban community were 1.72 (1.08–2.75) for men and 2.23 (1.23–4.03) for women. Conclusion: The stroke incidence continued to decline in both urban and rural Japanese communities with the regional disparities over the past half century, whereas it remained higher than that in many Western countries.

Evidence on the risk factors for incident heart failure in Asia has been limited. We sought to identify the risk factors for pre-heart failure or symptomatic heart failure, based on N-terminal pro-B-type natriuretic peptide (NT-proBNP), in the Japanese general population.We performed a retrospective cohort study based on the Circulatory Risk in Communities Study involving 5335 Japanese individuals whose NT-proBNP levels were measured between 2010 and 2015. Of these, 2768 people aged between 30 and 69 years who undertook annual cardiovascular risk surveys at least once between 1990 and 2000 were retrospectively eligible to be participants in this study. We performed multivariable logistic regression analyses to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pre-heart failure or symptomatic heart failure defined as NT-proBNP400 pg/mL or as having a diagnosis of heart failure and taking medication for heart failure for several cardiovascular risk factors (body mass index, blood pressure, diabetes mellitus, total cholesterol, triglyceride, smoking status, drinking status).We identified 85 cases of heart failure. The multivariable ORs (95% CIs) were 5.70 (2.70-12.0) for body mass index of 27-29.9 kg/mThe accumulation of these risk factors was associated with a graded higher risk of pre-heart failure or symptomatic heart failure.

This study aimed to investigate whether the impact of body mass index (BMI) on the risk of cardiovascular disease (CVD) has changed among the 1960s, 1970s, 1980s, 1990s, and early 2000s in Japan.The study population consisted of residents in Japan aged 40-69 years who had no history of CVD. The baseline surveys have been conducted every year since 1963. We defined the first, second, third, fourth, and fifth cohorts as 1963-1969 (n=4,248), 1970-1979 (n=6,742), 1980-1989 (n=12,789), 1990-1999 (n=12,537), and 2000-2005 (n=9,140) respectively. The participants were followed up for a median of 15 years for each cohort to determine the incidence of CVD. We classified them into four categories (BMI ＜21.0, 21.0-＜23.0, 23.0-＜25.0, and ≥ 25.0 kg/mFrom 1963-1969 to 2000-2005, the prevalence of BMI ≥ 25.0 increased over time. Compared with BMI 23.0-＜25.0, the age-, sex- and community-adjusted hazard ratios (95% confidence interval [CIs]) of CVD for BMI ≥ 25.0 were 1.10 (0.77-1.57), 0.89 (0.68-1.18), 1.03 (0.85-1.26), 1.28 (1.04-1.58), and 1.36 (1.04-1.78)in the first, second, third, fourth, and fifth cohorts, respectively. The corresponding population attributable fractions were 2.0% (nonsignificant), -2.6% (nonsignificant), 0.9% (nonsignificant), 7.6%, and 10.9%. Further adjustment for systolic blood pressure and antihypertensive medication use in the fourth and fifth cohorts attenuated the associations, which may reflect that blood pressure may mediate the BMI-CVD association.The proportion of CVD attributable to overweight/obesity has increased during the periods between 1963-1969 and 2000-2005. The significant associations between overweight/obesity and risk of CVD after the 1990s were mediated by blood pressure levels.

Aim N-terminal pro-B-type natriuretic peptide (NT-proBNP), frequently used as a biochemical marker for detecting and monitoring heart failure, is also a risk marker for development of coronary heart disease and total stroke. However, studies that explore subtypes of ischemic stroke with regard to NT-proBNP are scarce. Here, we examined NT-proBNP and its impact upon subtypes of ischemic stroke (lacunar stroke, large-artery occlusive stroke and embolic stroke) among Japanese. Methods We measured NT-proBNP and categorized 4,393 participants of the Circulatory Risk in Communities Study into four groups (＜55, 55-124, 125-399, and ≥ 400 pg/ml). We used a multivariable Cox proportional hazards model to examine association with risks of stroke and subtypes. Results During 4.7 years of follow-up, we identified 50 strokes, including 35 ischemic (15 lacunar, 6 largeartery occlusive, 10 embolic strokes) and 14 hemorrhagic strokes. NT-proBNP was associated with stroke risk: the multivariable hazard ratio of total strokes was 7.29 (2.82-18.9) for the highest and 2.78 (1.25-6.16) for the second highest NT-proBNP groups compared with the lowest group. The respective hazard ratios for the highest NT-proBNP group were 9.37 (3.14-28.0) for ischemic stroke and 6.81 (1.11-41.7) for lacunar stroke. Further adjustment for atrial fibrillation did not attenuate these associations. The associations were similarly observed for large-artery occlusive and embolic strokes. Conclusion We found that even moderate serum levels of NT-proBNP were associated with the risk of total and ischemic strokes among Japanese whose NT-proBNP levels were relatively low compared with Westerners.

The role of serum uric acid as a predictor of stroke among the general Japanese population remains controversial. We conducted a prospective cohort study of 5235 men and 8185 women aged 40-79 years at baseline between 1985 and 1994 in four Japanese communities, who were initially free from stroke, coronary heart disease, and medication for hyperuricemia or gout. Cox proportional hazards models were used to estimate sex-specific hazard ratios of stroke and its types in relation to serum uric acid level. During a median follow-up of 23.1 years, we recorded 1018 (488 men and 530 women) incident strokes, including 222 (99 and 123) intraparenchymal hemorrhages, 113 (33 and 80) subarachnoid hemorrhages and 667 (347 and 320) ischemic strokes. After adjustment for age, community and known cardiovascular risk factors, the multivariable hazard ratios (95% CIs) in the highest vs. lowest quintile of serum uric acid were 1.45 (1.07-1.96) for total stroke, 1.20 (0.65-2.20) for intraparenchymal hemorrhage, 1.46 (0.69-3.09) for subarachnoid hemorrhage and 1.61 (1.07-2.41) for ischemic stroke in women. The corresponding multivariable hazard ratios (95% CIs) in men were 1.02 (0.74-1.35), 0.83 (0.40-1.72), 1.19 (0.38-3.75) and 1.00 (0.70-1.41). Furthermore, those positive associations with risks of total and ischemic strokes in women were more evident in nonusers of antihypertensive medication than the users. In conclusion, elevated serum uric acid level is an independent predictor of total stroke in women but not in men. The positive association in women was mostly attributable to ischemic stroke and was more pronounced among nonusers of antihypertensive medication.

It has been hypothesized that dietary fiber intake has a beneficial impact on prevention of dementia, but the epidemiological evidence is scant. We sought to examine whether dietary fiber intake is inversely associated with risk of dementia requiring care under the national insurance (disabling dementia).The study setting was the Circulatory Risk in Communities Study, involving 3739 Japanese individuals aged 40-64 years at the dietary surveys (1985-99). Dietary fiber intake was estimated using the 24-hour dietary recall method. Incident disabling dementia was followed up from 1999 through 2020. Disabling dementia was further classified into that with or without a history of stroke. Hazard ratios of disabling dementia according to quartiles of total, soluble, and insoluble fiber intake were calculated using the Cox proportional hazards model.During a median 19.7-year follow-up, a total of 670 cases of disabling dementia developed. Dietary fiber intake was inversely associated with risk of dementia: the multivariate hazards ratios (95% confidence intervals) were 0.83 (0.67-1.04), 0.81 (0.65-1.02), and 0.74 (0.57-0.96) for individuals with the second, third, and highest quartiles of dietary fiber intake, respectively, as compared with the lowest quartile (Dietary fiber intake, especially soluble fiber, was inversely associated with risk of disabling dementia in a general Japanese population.

Background Folate regulates homocysteine metabolism and high blood homocysteine level has been associated with risk of dementia. Accordingly, serum folate is hypothesized to decrease the risk of dementia but epidemiological evidence, especially for Japanese, is scant. The aim of this study was to examine associations between serum folate and risk of disabling dementia within a Japanese cohort over 20 years of follow-up. Methods We performed an intracohort case-control study nested in a community-based cohort, the Circulatory Risk in Communities Study (CIRCS), involving 13934 Japanese individuals aged 40-84 years at the baseline period of 1984-2005. Serum folate was measured in 511 cases of incident disabling dementia, and in 1022 controls whose age (±1 years), sex, area, and baseline year were matched with the cases. The diagnosis of disabling dementia was performed by attending physicians under the National Long-Term Care Insurance System in Japan. Conditional odds ratios of disabling dementia according to quintiles of serum folate were calculated using conditional logistic regression models. Results Serum folate was inversely associated with risk of disabling dementia. The multivariate odds ratios (95% confidence intervals) were 0.62(0.43-0.88), 0.71(0.49-1.00), 0.63(0.43-0.91), and 0.51(0.34-0.76) for persons with the second, third, fourth, and highest quintiles of serum folate, respectively, compared with the lowest quintiles (P for trend = 0.19). Conclusions Low serum folate level was associated with increased risk of disabling dementia among Japanese. Key messages e Low folate intake may have an adverse effect on developing dementia.

Introduction: Chronic low back pain (CLBP), defined as low back pain persisting for at least 3 months, leads to limitations in the activities of daily living and decreased quality of life. Individualized self-exercise education could be a preferable treatment option, especially in community-dwelling people with CLBP. Previous studies, however, did not directly compare the effects of therapist-led self-exercise education and material-only education, and there are only a few studies investigating the effects of low-dose (comprising a few sessions) self-exercise education on CLBP. We present a protocol of community-based, randomized study to evaluate the effects of low-dose (comprising a few sessions), therapist-led self-exercise education on CLBP. Methods: Forty-eight participants with CLBP (men and women, aged 40-74 years) will be allocated to therapeutic self-exercise education programs, either a therapist-led group (2-week therapist's consultation and material use) or material-only group (material use only), in a randomized controlled trial. Pain intensity (NRS, numeric rating scale), pain disability (RDQ, Roland-Morris disability questionnaire), pain self-efficacy (PSEQ, pain self-efficacy questionnaire), and quality of life score (EQ-5D, European quality of life-5 dimensions) will be measured at baseline and at 4, 12, and 24 weeks. We will apply a repeated-measures design with mixed-effect models to estimate group differences from the baseline. Ethics/Trial registration number: The protocol was approved by the Ethics Committees of the Osaka Center for Cancer and Cardiovascular Disease Prevention and Osaka University. The trial registration number is registered on the University Hospital Medical Information Network (UMIN000024537).

Aims: The frequency of breakfast intake has been reported to be inversely associated with the risk of cardiovascular events; however, it is uncertain what the impact of the energy and nutrient intakes from breakfast are. We assessed the association between these intakes from breakfast and the risk of stroke prospectively. Methods: In a baseline survey of four Japanese communities between 1981 and 1990, we enrolled 3 248 residents (1 662 men and 1 586 women) aged 40–59 years who were free from stroke and heart disease and who responded to the 24-hour dietary recall survey. We assessed the dietary intake at breakfast, lunch, dinner, and other times separately. Results: During the median 25-year follow-up, 230 individuals (147 men and 83 women) developed stroke. After adjustment for age, community, other dietary intakes, and lifestyle and physiological factors, the multivariable-adjusted hazard ratios (95% confidence intervals) of intracerebral hemorrhage for the highest versus lowest quartiles of energy intake from breakfast were 0.38 (0.15–0.99) in men and 1.36 (0.36–5.10) in women. For the major nutrients, a higher saturated or monounsaturated fat intake at breakfast was associated with a reduced risk of intracerebral hemorrhage in men, and remained statistically significant after further adjustment for intake of other major nutrients from breakfast. Conclusions: A higher intake of energy from breakfast, primarily saturated or monounsaturated fat, was associated with a reduced risk of intracerebral hemorrhage in Japanese men.

Aim This study aimed to investigate the associations of leukocyte count with the risks of stroke and coronary heart disease among the general Japanese population. Methods A total of 5,242 residents aged 40-69 years living in two Japanese communities underwent leukocyte count measurements between 1991 and 2000, and the data were updated using 5- or 10-year follow-ups or both. Participants who had histories of stroke, coronary heart disease, or high values of leukocyte count (＞130×102 cells/mm3) were excluded. Hazard ratios with 95% confidence intervals (CIs) were calculated according to quartiles of cumulative average leukocyte count. Results During follow-up of 21 years, 327 stroke and 130 coronary heart disease cases were determined. After adjustments for age, sex, community, and updated cardiovascular risk factors, the multivariable hazard ratio (95% CI) for the highest versus lowest quartile of leukocyte count was 1.50 (1.08-2.08) for ischemic stroke, 1.59 (1.00-2.51) for lacunar infarction, 1.42 (0.90-2.26) for non-lacunar infarction, 2.17 (1.33-3.55) for coronary heart disease, and 1.40 (1.11-1.76) for total cardiovascular disease. In smoking status-stratified analyses, the corresponding multivariable hazard ratio (95% CI) was 2.45 (1.11-5.38) for ischemic stroke, 2.73 (1.37-5.44) for coronary heart disease in current smokers, 2.42 (1.07-5.46), 1.55 (0.58-4.15) in former smokers, and 1.17 (0.75-1.82), 1.78 (0.83-3.82) in never smokers. Conclusion Leukocyte count was positively associated with the risks of ischemic stroke and coronary heart disease among the general Japanese population, especially in current smokers.

Background Evidence on the associations of carotid intima‐media thickness and carotid plaque characteristics with stroke subtypes and coronary artery disease risks in Asians is limited. This study investigated these associations in the Japanese general population. Methods and Results Maximum intima‐media thicknesses of both the common carotid artery and internal carotid artery and carotid plaque characteristics were evaluated in 2943 Japanese subjects aged 40 to 75 years without history of cardiovascular disease. Subjects were followed up for a median of 15.1 years. Using a multivariate Cox proportional hazard model, we found that hazard ratios (HRs) and 95% CIs for the highest (≥1.07 mm) versus lowest (≤0.77 mm) quartiles of maximum intima‐media thicknesses of the common carotid artery were 1.97 (1.26–3.06) for total stroke, 1.52 (0.67–3.41) for hemorrhagic stroke, 2.45 (1.41–4.27) for ischemic stroke, 3.60 (1.64–7.91) for lacunar infarction, 1.53 (0.69–3.41) for nonlacunar cerebral infarction, 2.68 (1.24–5.76) for coronary artery disease, and 2.11 (1.44–3.12) for cardiovascular disease (similar results were found for maximum intima‐media thicknesses of the internal carotid artery). HRs(95% CIs) for heterogeneous plaque versus no plaque were 1.58 (1.09–2.30) for total stroke, 1.25 (0.58–2.70) for hemorrhagic stroke, 1.74 (1.13–2.67) for ischemic stroke, 1.84 (1.03–3.19) for lacunar infarction, 1.58 (0.80–3.11) for nonlacunar cerebral infarction, 2.11 (1.20–3.70) for coronary artery disease, and 1.71 (1.25–2.35) for cardiovascular disease. Conclusions Maximum intima‐media thicknesses of the common carotid artery, maximum intima‐media thicknesses of the internal carotid artery, and heterogeneous plaque were associated with the risks of stroke, lacunar infarction, coronary artery disease, and cardiovascular disease in Asians.

Aim This study aimed to investigate the association between the serum high-sensitivity C-reactive protein (hs-CRP) levels and incident atrial fibrillation risk in the general Japanese population, who have lower hs-CRP levels than the Western population, and assess whether the association is modified by sex, overweight, hypertension, and smoking status. Methods We conducted a prospective study in 6517 Japanese men and women aged 40-79 years without atrial fibrillation at baseline and enrolled in the Circulatory Risk in Communities Study (2002-2008). The hs-CRP levels were measured using the latex particle-enhanced immunonephelometric assay. Atrial fibrillation was identified using standard 12-lead electrocardiograms and information on physician-diagnosed atrial fibrillation history from the follow-up surveys. We used a Cox proportional hazard regression stratified by community. Results During a median follow-up of 11 years, 127 new cases of atrial fibrillation (74 and 53 cases among men and women, respectively) were found. Compared to the lowest quintile of hs-CRP levels, the multivariable hazard ratios (95% confidence intervals) were 2.54 (1.17-5.50), 2.28 (1.06-4.93), 2.92 (1.37-6.23), and 2.77 (1.30-5.91) for the second, third, fourth, and fifth (highest) quintiles, respectively. There was no significant effect modification by sex, overweight, hypertension, and smoking status (P for interaction ＞0.05). Conclusions Elevated hs-CRP levels were significantly associated with increased risk of atrial fibrillation in the Japanese population. The association of hs-CRP levels with incident atrial fibrillation did not vary according to sex, overweight, hypertension status, or smoking status.

This study aimed to assess the association of cigarette smoking with radial augmentation index among the Asian general population. We conducted a cross-sectional population-based study including 1593 men and 2671 women aged 40-79 years. Smoking status was ascertained through interviews, and the number of pack-years was calculated. The radial augmentation index was defined as the ratio of central pulse pressure to brachial pulse pressure, as measured using an automated tonometer: the HEM-9000AI (Omron Healthcare co., Kyoto, Japan). There was a higher prevalence of an increased radial augmentation index among current male smokers who smoked ≥ 30 cigarettes/day and all female smokers than among never smokers. After adjusting for known risk factors of atherosclerosis, the multivariable odds ratio (OR) [95% confidence interval (CI)] for a high radial augmentation index for current male smokers who smoked ≥30 cigarettes/day compared with never smokers was 1.9 (1.1-3.4). The multivariable OR (95% CI) for a high radial augmentation index for former female smokers and current female smokers compared with never smokers was 1.8 (1.2-2.7) and 2.5 (1.6-3.9), respectively. Moreover, smoking pack-years was positively associated with a high radial augmentation index in both sexes. There were no relationship between smoking status and high central or brachial pulse pressures among subjects of either sex. In conclusion, cigarette smoking and cumulative smoking exposure were positively associated with an increased radial augmentation index in men who smoked heavily and in women.

Although evidence about skeletal muscle mass loss and type 2 diabetes risk has accumulated, little information is available on the combined effect of skeletal muscle mass and abdominal obesity on type 2 diabetes. We examined whether skeletal muscle mass and abdominal obesity were synergistically associated with the prevalence of type 2 diabetes.Skeletal muscle mass and waist circumference (WC) were measured in 1515 Japanese aged 40 to 69 years. Relative muscle mass was calculated as percentage of total skeletal muscle mass in body weight (SMM%). Type 2 diabetes was identified as fasting serum glucose ≥7.0 mmol/L (126 mg/dL), nonfasting serum glucose ≥11.1 mmol/L (200 mg/dL), glycosylated hemoglobin ≥ 6.5%, and/or diabetes medication use.The multivariable-adjusted odds ratio (OR) of prevalent diabetes from the lowest to the third quartile of SMM% compared to the highest quartile gradually increased in both sexes. The association between a high WC and prevalent diabetes was similar. The multivariable-adjusted OR (95% confidence intervals) for the prevalence of type 2 diabetes in the low skeletal muscle mass/high WC group was 3.19 (1.78-5.71) for men and 4.46 (2.09-9.51) for women compared with the high skeletal muscle mass/low WC group. The relative excess risk due to interaction was 2.2 (0.5-3.9) in men and 2.8 (0.2-5.3) in women for an excess burden of type 2 diabetes for low skeletal muscle mass and high WC.Low skeletal muscle mass and abdominal obesity were synergistically associated with presence of type 2 diabetes.背景: 虽然关于骨骼肌肉质量的下降与2型糖尿病风险的证据已有研究, 但关于骨骼肌质量和腹型肥胖对2型糖尿病的联合作用的信息很少。我们研究了骨骼肌质量和腹型肥胖是否与2型糖尿病的患病率协同相关。 方法: 测量1515名40-69岁日本人的骨骼肌质量和腰围。相对肌量以总骨骼肌质量占体重的百分比(SMM%)计算。2型糖尿病被定义为空腹血糖≥7.0 mmol/L(126 mg/dL), 非空腹血糖≥11.1mmol/L(200mg/dL), 糖化血红蛋白≥6 5%, 且或正在使用糖尿病药物。 结果: 相对肌量最低的四分之一与最高四分之一相比, 男性及女性糖尿病患病率的多变量调整优势比(OR)都有所升高。较高腰围和糖尿病发病率之间的联系也是相似的。与高骨骼肌质量/低腰围组相比, 低骨骼肌质量/高腰围组的2型糖尿病患病率多变量调整OR值于男性为3.19(1.78~5.71), 女性为4.46(2.09~9.51)。低骨骼肌质量与高腰围之间的交互作用导致了额外的糖尿病相对风险, 男性为2.2(0.5-3.9), 女性为2.8(0.2-5.3)。 结论: 低骨骼肌质量和腹型肥胖与2型糖尿病发病存在协同关系。.

Background:The effect of postprandial glucose on the risk of cardiovascular disease has been emphasized, but it is controversial whether nonfasting glucose is related to incident stroke and its types. Methods and Results:We investigated the associations of nonfasting glucose with incident stroke and its types among 7,198 participants aged 40–74 years from the Circulatory Risk in Communities Study, enrolled in 1995–2000. We estimated multivariable hazard ratios (HR) using Cox proportional hazard models. Over a median follow-up of 14.1 years, 291 cases of total stroke (ischemic strokes: 191 including 109 lacunar infarctions) were identified. Nonfasting glucose concentration was associated with greater risk of incident total stroke, ischemic stroke and lacunar infarction when modeled categorically (for prediabetic type: 7.8–11.0 mmol/L vs. normal type

Background and aims Limited evidence is available on the association between markers of arterial stiffness and the prevalence of atrial fibrillation among Asian populations. Therefore, we examined those associations in the Japanese population. Methods We conducted a cross-sectional population-based study of 4264 men and women aged 40–79 years. The augmentation index (AI), a marker of arterial stiffness, was calculated as the ratio of central pulse pressure/brachial pulse pressure, where the AI and central aortic pressure were measured by an automated tonometer: the HEM-9000AI device (Omron Healthcare co., Kyoto, Japan). Atrial fibrillation was estimated by the Minnesota codes using resting electrocardiograph (ECG). Results The prevalence of atrial fibrillation and total arrhythmia were higher with larger AI values. These associations did not change after adjustment for known cardiovascular risk factors. The multivariable odd ratios (95% confidence intervals) in the highest versus lowest tertiles of AI were 3.4 (1.4–8.6, p for trend = 0.008) for atrial fibrillation and 1.8 (1.2–2.7, p for trend = 0.004) for total arrhythmia. There was no association of central or brachial pulse pressure levels with the prevalence of atrial fibrillation or total arrhythmia. Conclusions AI values, but not brachial or central pulse pressures, were positively associated with the prevalence of atrial fibrillation and total arrhythmia, independent of cardiovascular risk factors.

Aim: To investigate the association of retinal vascular changes with a risk of dementia in longitudinal population-based study., Methods: We performed a nested case-control study of 3,718 persons, aged 40–89 years, enrolled between 1983 and 2004. Retinal vascular changes were observed in 351 cases with disabling dementia (average period before the onset, 11.2 years) and in 702 controls matched for sex, age, and baseline year. Incidence of disabling dementia was defined as individuals who received cares for disabilities including dementia-related symptoms and/or behavioral disturbance. Conditional logistic regression analysis was used to calculate odds ratio (OR) and multivariable adjusted OR (Models 1 and 2) for incidence of dis- abling dementia according to each retinal vascular change. Regarding confounding variables, Model 1 included overweight status, hypertension, hyperglycemia, dyslipidemia, and smoking status, whereas Model 2 also included incidence of stroke prior to disabling dementia for further analysis., Results: The proportion of cases (controls) with retinal vascular changes was 23.1 (15.7)% for general-ized arteriolar narrowing, 7.7 (7.5)% for focal arter iolar narrowing, 15.7 (11.8)% for arteriovenous nick-ing, 10.5 (9.3)% for increased arteriolar wall reflex, and 11.4 (9.8)% for any other retinopathy. General-ized arteriolar narrowing was associated with an in creased risk of disabling dementia: crude OR, 1.66 (95% confidence interval, 1.19 –2.31); Model 1: OR, 1.58 (1.12–2.23); Model 2: OR, 1.48 (1.04–2.10). The number of retinal abnormalities was associated in a dose–response manner with the risk., Conclusion: Generalized arteriolar narrowing and total number of retinal abnormalities may be use-ful markers for identifying persons at higher risks of disabling dementia.

Objective The prognostic importance of changes in ischaemic ECG abnormalities over time (especially ST-T abnormalities) among Asians has not been fully investigated. We examined the associations between changes in ischaemic abnormalities upon serial ECG (improvement, persistence, deterioration) and cardiovascular disease (CVD) risk. Methods A prospective study cohort was conducted with 9374 men and women aged 40–69 years in four communities. Participants had multiple ECGs at study entry and during the next 10 years, and were followed up for a median period of 23.0 years. Total CVD (stroke and coronary heart disease) was ascertained under systematic surveillance. ECG abnormalities were defined by the Minnesota Code, ST depression (Code4), abnormal T wave (Code5) and categorised into nine groups (no–no, no–minor, no–major, minor–no, minor–minor, minor–major, major–no, major–minor, major–major) by comparison with the point of entrance and maximum change. Results We documented 1196 CVD events. Compared with no–no abnormality, no–minor, minor–major and major–major in Code4, HRs (95% CI) adjusted for cardiovascular risk factors were 1.19 (1.00–1.42), 1.57 (1.15–2.12) and 1.87 (1.42–2.47). Similar results were observed in Code5. Conclusions Changes in ischaemic ECG abnormalities from none to minor, and minor to major, as well as persistent major abnormalities, were associated with an increased risk of CVD.

The role of serum uric acid as a predictor of stroke among the general Japanese population remains controversial. We conducted a prospective cohort study of 5235 men and 8185 women aged 40-79 years at baseline between 1985 and 1994 in four Japanese communities, who were initially free from stroke, coronary heart disease, and medication for hyperuricemia or gout. Cox proportional hazards models were used to estimate sex-specific hazard ratios of stroke and its types in relation to serum uric acid level. During a median follow-up of 23.1 years, we recorded 1018 (488 men and 530 women) incident strokes, including 222 (99 and 123) intraparenchymal hemorrhages, 113 (33 and 80) subarachnoid hemorrhages and 667 (347 and 320) ischemic strokes. After adjustment for age, community and known cardiovascular risk factors, the multivariable hazard ratios (95% CIs) in the highest vs. lowest quintile of serum uric acid were 1.45 (1.07-1.96) for total stroke, 1.20 (0.65-2.20) for intraparenchymal hemorrhage, 1.46 (0.69-3.09) for subarachnoid hemorrhage and 1.61 (1.07-2.41) for ischemic stroke in women. The corresponding multivariable hazard ratios (95% CIs) in men were 1.02 (0.74-1.35), 0.83 (0.40-1.72), 1.19 (0.38-3.75) and 1.00 (0.70-1.41). Furthermore, those positive associations with risks of total and ischemic strokes in women were more evident in nonusers of antihypertensive medication than the users. In conclusion, elevated serum uric acid level is an independent predictor of total stroke in women but not in men. The positive association in women was mostly attributable to ischemic stroke and was more pronounced among nonusers of antihypertensive medication.

Background: The effect of lowering diastolic blood pressure (DBP) on the risk for ischemic cardiovascular disease (CVD) is usually only assessed with a single timepoint at baseline. This has led to a lack of explanation for the U- or J-shaped association between DBP and the risk for ischemic CVD among hypertensive patients. Methods: We studied a cohort of 7074 hypertensive patients (42.9% men) aged 35-79 years (mean age=56.5 years) at baseline in 1980-1989, with annually repeated blood pressure measurements. Time-dependent DBP trajectories were assessed by group-based trajectory analysis, adjusted by sex, age, and antihypertensive medication use. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) of ischemic CVD, composed of ischemic stroke and myocardial infarction, according to DBP trajectories were estimated by competing risk analysis. For references, we examined the same approaches mentioned above were used for systolic blood pressure. Findings: For 24.1 years, there were 799 incident cases of ischemic CVD. Eight DBP trajectories were identified. We found a U-shaped association between DBP trajectories and a risk for ischemic CVD. The HRs (95%CI) of ischemic CVD with reference to a moderately-stable trajectory were 2.0 (1.8-2.2) for a very-low-stable, 1.4 (1.3-1.6) for low-decreasing, 1.6 (1.3-1.5) for low-stable, 1.4 (1.3-1.5) for moderately-decreasing, 1.5 (1.4-1.7) for high-decreasing, 1.2 (1.1-1.4) for high-stable, and 1.4 (1.2-1.62) for very-high-stable. This U-shaped association was more pronounced in antihypertensive medication users than in non-users. No such association was observed for SBP trajectories. Interpretation: We found a U-shaped association between DBP trajectory and ischemic CVD in hypertensive patients in a time-dependent analysis, which cannot be detected by single timepoint analysis. Changes in DBP among hypertensive patients should be carefully documented for preventing ischemic CVD. Funding Statement: Ministry of Health, Labor and Welfare of Japan. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the ethics committees of Osaka University and Osaka Center for Cancer and Cardiovascular Disease Prevention, and was performed in accordance with the Declaration of Helsinki.

The Circulatory Risk in Communities Study (CIRCS) is an ongoing community-based epidemiological study of lifestyle-related disease involving dynamic prospective cohorts of approximately 12,000 adults from five communities of Japan: Ikawa, Ishizawa and Kita-Utetsu (Akita Prefecture), Minami-Takayasu (Osaka Prefecture), Noichi (Kochi Prefecture), and Kyowa (Ibaraki Prefecture). One of the most notable features of CIRCS is that it is not only an observational cohort study to identify risk factors for cardiovascular diseases (CVD), such as stroke, coronary heart disease, and sudden cardiac death, but it also involves prevention programs for CVD. Using basic, clinical, epidemiological, and statistical techniques, CIRCS has clarified characteristics of CVD and the related risk factors to develop specific methodologies towards CVD prevention in Japanese middle-aged or older adults for more than half a century.

Background The aim of this study was to examine whether the burden of diabetes on cardiovascular disease (CVD) in Japan has increased in recent years.Methods and Results:Three cohorts were established, consisting of Japanese residents aged 40-69 years, in 1992-1995 (n=8,744), 1996-1999 (n=7,996), and 2000-2003 (n=7,273). All participants had follow-up for a median of 10 years. Diabetes was defined according to the following criteria: (1) fasting serum glucose ≥7.0 mmol/L; (2) non-fasting serum glucose ≥11.1 mmol/L; or (3) anti-diabetic treatment at baseline. During follow-up, the number of CVD incidents was 277 in the first, 214 in the second, and 190 in the third cohorts. The prevalence of diabetes increased slightly over time. Adjusting for traditional cardiovascular risk factors, multivariable HR (95% CI) for diabetes as a cardiovascular risk factor were 1.40 (0.91-2.14) in the first, 1.93 (1.25-3.00) in the second, and 2.59 (1.77-3.81) in the third cohorts. The population attributable fraction of CVD due to diabetes was 2.8%, 5.6%, and 12.4%, respectively. Conclusions This is the first study in middle-aged Japanese people to clarify an increased burden of CVD due to diabetes since the early 1990 s. Further efforts are needed to prevent and control diabetes through lifestyle modification and treatment. (Circ J 2016; 80: 2343-2348).