Mushroom intake and risk of incident disabling dementia: the Circulatory Risk in Communities Study (CIRCS).

It is uncertain whether dietary intake of mushrooms rich in dietary fibre and several antioxidants is associated with a lower risk of dementia. We sought to examine prospectively the association between mushroom intake and the risk of disabling dementia. We performed a prospective study involving 3750 people aged 40 to 64 years residing in three communities who participated in an annual cardiovascular risk survey from 1985 to 1999. Cases of incident disabling dementia were surveyed from 1999 to 2020. We calculated the hazard ratios (HR) and 95 % CI for incident total dementia according to mushroom intake among participants with or without a history of stroke. During a mean 16·0 years' follow-up in 3739 eligible participants, 670 people developed disabling dementia. For women, mushroom intake was inversely associated with the risk of total dementia and the association was confined to dementia without a history of stroke. The multivariable HR (95 % CI) for total dementia in women were 0·81 (0·62, 1·06) for mushroom intake of 0·1-14·9 g/d and 0·56 (0·42, 0·75) for mushroom intake above 15·0 g/d (Pfor trend = 0·003) compared with no intake. The corresponding HR (95 % CI) for dementia without a history of stroke were 0·66 (0·47, 0·93) and 0·55 (0·38, 0·79) (Pfor trend = 0·01). In men, no associations were observed between mushroom intake and the risk of disabling dementia. Among Japanese women, dietary mushroom intake was associated with a lower risk of disabling dementia.

Serum folate and risk of disabling dementia: a community-based nested case-control study.

PURPOSE: The aim of this study was to examine associations between serum folate levels and risk of disabling dementia that required care under the national insurance (disabling dementia). METHODS: We performed a nested case-control study in a community-based cohort, the Circulatory Risk in Communities Study, involving 13,934 Japanese individuals aged 40-84 years at the baseline period of 1984-2005. Serum folate was measured in 578 cases of incident disabling dementia, and in 1,156 controls whose age (±1 years), sex, area of residence, 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: After a 20.8-year follow-up, serum folate was inversely associated with risk of disabling dementia. The respective multivariable odds ratios (95% CIs) were 0.71 (0.51-0.99), 0.76 (0.54-1.06), 0.70 (0.49-1.00), and 0.62 (0.43-0.90) for persons with the second, third, fourth, and highest quintiles of serum folate as compared with the lowest quintile (P for trend = 0.03). A similar association was observed for dementia with or without stroke. CONCLUSION: In this nested case-control study with a long follow-up, low serum folate levels were associated with an increased risk of disabling dementia among Japanese individuals.

Transitions in sense of coherence among middle-aged women raising adolescents before and during the COVID-19 pandemic.

Objective: A longitudinal study was conducted among Japanese women raising adolescents to determine how the COVID-19 pandemic has affected their sense of coherence (SOC) and to provide suggestions for supporting them. Methods: The SOC scores of 138 pairs of middle-aged women and their children (junior high school students) were compared at two time points: 2019 (before the pandemic, T1) and 2020 (during the pandemic, T2). Results: Overall, the women's SOC did not change, whereas the adolescents' SOC increased. In contrast, 44% of the women's SOC scores decreased during the pandemic; no differences were detected between the SOC maintenance and increase group (G1) and the SOC decrease group (G2) in mental health, subjective physical health, social capital, and job status, and the child variables were not related. Multiple regression analysis of G1 and G2 with SOC at T2 as the dependent variable showed that for G2, at T1, having good mental and physical health conditions, a rich social capital, and having a job were positively associated with SOC during the pandemic. Conclusion: Middle-aged Japanese women, who often work as informal workers, are easily laid off and are involved in care work. Thus, the change in their socioeconomic status due to the pandemic may have been severe. Given the long-term social impact of the pandemic, it is necessary to consider support for women, including economic and social support such as employment and building human connections.

Longitudinal trajectories of smoking status using 25 year annually-updated data and all-cause mortality followed over 30 years: A community-based prospective cohort study.

We aimed to evaluate the long-term risk of smoking for all-cause mortality according to smoking status trajectories using 25-year annually-repeated input, traced by group-based trajectory modeling with an extension to account for non-random participant attrition or truncation due to death. We examined 2682 men and 4317 women aged 40 to 59 years who participated in annual health checks for the community-based prospective cohort study, 1975-1984 enrollment in Japan. The main outcome measure was all-cause mortality (follow-up period: median 30.2 years in men and 32.2 years in women). We traced annual smoking trajectories, stratified by sex and smoking status at baseline. For smokers at baseline, we identified five trajectories in both sexes, with different patterns of smoking cessation (e.g., early quitters and lifelong smokers). We calculated HRs and 95% CI of all-cause mortality using Cox proportional hazards regression modeling adjusted for age, body mass index, alcohol intake, blood pressure category, dyslipidemia and glucose category. Compared with one-time-point-based smokers, trajectory-based lifelong smokers had an increased risk of all-cause mortality; HRs were 1.31 (95% CI, 1.18-1.46) in men and 1.26 (95% CI, 0.91-1.73) in women. Among community residents aged 40 to 59 years, 25-year-trajectory-based lifelong smokers had an approximately 30% increased risk for all-cause mortality compared to one-time-point-based smokers. Risk of all-cause mortality among smokers with earlier cessation varied materially. It is necessary to consider the trajectories of smoking status to clarify the long-term excess risk of smoking.

Experience and Resilience of Japanese Public Health Nurses during the COVID-19 Pandemic and Their Impact on Burnout.

Japanese public health nurses (PHNs) at public health centers (PHCs) have played critical roles in infection prevention and control during the COVID-19 pandemic. This study aimed to examine the actual pandemic-related experiences of PHNs and the relation between their experiences, individual resilience, two components of organizational resilience (system and human resilience), and burnout. An analysis of the responses of 351 PHNs revealed that mid-level PHNs scored higher in experience and lower in organizational resilience compared with those in other positions. More than 80% of respondents experienced inappropriate staff allocation. Multiple regression revealed that burnout was positively associated with the components of the experience of PHNs and negatively with individual and human resilience. In hierarchical multiple regression with depersonalization as the dependent variable, the sign of system resilience reversed from negative to positive when human resilience was added. The results highlight the need to prepare for future health crises including establishing a system with enough personnel, promoting human resilience such as collaboration among staff members, and burnout prevention measures, especially among mid-level PHNs. The study also described alternative approaches to comprehend system resilience-namely, a suppression variable of human resilience, promotion of depersonalization, and multicollinearity-and the need for further research on organizational resilience.

Risk Factors for Hyperuricemia or Gout in Men and Women: The Circulatory Risk in Communities Study (CIRCS).

AIM: We aimed to examine sex-specific risk factors for hyperuricemia or gout in Japanese cohorts. METHODS: We followed up 3,188 men (mean age, 55.6 years) and 6,346 women (mean age, 54.1 years) without hyperuricemia, gout, or elevated liver enzymes at baseline from 1986 to 1990 for a median of 14.6 years. The participants were considered as having hyperuricemia or gout if their serum uric acid levels were ≥ 7.0 mg/dL or they were receiving treatment for hyperuricemia or gout during annual health checkups. The sex-specific multivariable hazard ratios (HRs) of hyperuricemia or gout incidence were calculated after adjustment for smoking and drinking status, body mass index, hypertension, diabetes, hypercholesterolemia, and hypertriglyceridemia using the Cox proportional-hazard model. RESULTS: During follow-up, 733 men and 355 women had hyperuricemia or gout. Among men, the multivariable HRs (95% confidence intervals) of hyperuricemia or gout were 1.23 (1.00-1.52) and 1.41 (1.13-1.75) for drinkers of ＜46 and ≥ 46 g ethanol/day, respectively, compared with non-drinkers; 1.00 (0.81-1.24) and 1.18 (0.93-1.50) for smokers of 1-19 and ≥ 20 cigarettes/day, respectively, compared with never smokers; and 1.41 (1.20-1.65) for hypertensive compared with non-hypertensive participants. The HRs for women were 1.02 (0.70-1.48), 1.66 (1.05-2.63), and 1.12 (0.88-1.42) for current drinkers, current smokers, and hypertensive participants, respectively. For both men and women, body mass index, diabetes, hypercholesterolemia, and hypertriglyceridemia were not associated with hyperuricemia or gout incidence. CONCLUSIONS: Hypertension and alcohol drinking are risk factors for hyperuricemia or gout among men and smoking among women.

Trends in stroke, cardiovascular disease, and medical expenditure under a community-based long-term stroke prevention program.

BACKGROUND: Evidence on the effects of preventive measures for noncommunicable disease is urgently needed for low-income and middle-income countries suffering from stroke epidemics along with population aging. OBJECTIVES: We sought to examine the impact of a community-based stroke prevention program on incidences of stroke and ischemic heart disease, mortality from cardiovascular disease, and medical expenditure. METHODS: Trends in the incidences of stroke and ischemic heart disease were documented in a Japanese rural community, Kyowa, from 1981 through 2015. Trends in mortality from cardiovascular disease and in medical expenditures were compared between Kyowa and its surrounding municipalities from 1981 through 2004. RESULTS: In Kyowa, the age-and-sex-adjusted incidences of stroke and of ischemic heart disease decreased by half (from 4.1 to 1.9 and from 1.5 to 0.7 per year/1000 persons, respectively) over the past 35 years. A similar decreasing trend was observed for the age-and-sex-adjusted mortality from cardiovascular disease, and this decreasing trend occurred earlier than that in the surrounding municipalities. The medical expenditures for cardiovascular disease became lower in Kyowa than in the surrounding municipalities over time. CONCLUSION: Our study's findings suggest that a community-based stroke prevention program augmented the decline in the incidences of stroke and ischemic heart disease, mortality from cardiovascular disease, and attenuated the increase in medical expenditures for cardiovascular disease.

Nocturnal Intermittent Hypoxia and the Risk of Cardiovascular Disease among Japanese Populations: The Circulatory Risk in Communities Study (CIRCS).

AIMS: Information is limited about the influence of obstructive sleep apnea (OSA) on developing cardiovascular disease (CVD) among Asian community-dwelling populations. We examined the association between nocturnal intermittent hypoxia as a surrogate marker of OSA and the risk of CVD in a Japanese community-based cohort study. METHODS: We used baseline surveys from 2000 to 2008 to study the cohort data of 5,313 residents from three Japanese communities who were between the ages of 40 and 74 years and initially free from ischemic heart disease and stroke. We assessed the number of 3% oxygen desaturation index (ODI) as the indicator of nocturnal intermittent hypoxia. We divided individuals into two groups depending on 3% ODI (3% ODI ≥ 5 or 3% ODI ＜5). Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD according to 3% ODI. Age, sex, body mass index, alcohol, and smoking were adjusted in the multivariable models. RESULTS: During 12.8 years of the median follow-up with 66,796 person-years, 185 cases with CVD (115 stroke and 70 coronary heart disease [CHD]) were recorded. The multivariable HRs (95% CIs) were 1.49 (1.09-2.03), 2.13 (1.08-4.22), and 1.93 (1.16-3.19) for the 3% ODI ≥ 5 group versus the 3% ODI ＜5 group of developing CVD, lacunar infarction, and CHD, respectively. CONCLUSIONS: Nocturnal intermittent hypoxia may increase the risk of developing lacunar infarction and CHD among community-dwelling Japanese populations. However, we could not find a significant risk of developing total stroke or stroke subtypes such as intraparenchymal hemorrhage, subarachnoid hemorrhage, and total ischemic stroke.

Dietary fiber intake and risk of incident disabling dementia: the Circulatory Risk in Communities Study.

OBJECTIVES: 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). METHODS: 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. RESULTS: 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 (P for trend = 0.03). The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke. As for fiber-containing foods, potatoes, but not vegetables or fruits, showed a similar association. CONCLUSIONS: Dietary fiber intake, especially soluble fiber, was inversely associated with risk of disabling dementia in a general Japanese population.

Trends for the Association between Body Mass Index and Risk of Cardiovascular Disease among the Japanese Population: The Circulatory Risk in Communities Study (CIRCS).

AIM: 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. METHODS: 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/m2). RESULTS: From 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. CONCLUSION: 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.

Serum High-Sensitivity Cardiac Troponin T as an Independent Predictor for Incident Coronary Heart Disease in the Japanese General Population: The Circulatory Risk in Communities Study (CIRCS).

AIMS: Epidemiological evidence is extremely limited about high-sensitivity cardiac troponin T (hs-cTnT) and future coronary heart disease (CHD) events for the general population in countries with low mortality from CHD. Therefore, we investigated the association between hs-cTnT levels and the risk of incident CHD using a nested case-control study in a large Japanese cohort study. METHODS: The participants were residents of four Japanese communities in the Circulatory Risk in Communities Study (CIRCS). We obtained 120 cases (81 men and 39 women, aged 38-86 years at baseline) of first incident CHD and 240 controls matched by age, sex, communities, and blood sampling term. Serum hs-cTnT levels were measured using an electrochemiluminescence immunoassay with stored sera collected between 2001 and 2011. The median period between sampling at survey and CHD incidence was 2.0 (interquartile range, 0.9-3.7) years. After adjusting for conventional risk factors, the multivariable odds ratios (ORs) of CHD were calculated using conditional logistic regression analyses. RESULTS: hs-cTnT ranged from ≤ 3 (assay detection limit) to 155 ng/L. Compared with the lowest quartile of hs-cTnT, multivariable ORs (95% confidence intervals) of CHD for the second, third, and highest quartiles were 1.30 (0.57-2.95), 2.48 (1.09-5.64), and 3.01 (1.27-7.12), respectively. Similar associations were observed after adjusting for estimated glomerular filtration, or after excluding matched groups, including people with chronic kidney disease. CONCLUSION: Serum hs-cTnT could predict CHD in the Japanese general population. These findings implicate a benefit from monitoring hs-cTnT to predict CHD even among populations in countries with low mortality from CHD.

Risk factors for pre-heart failure or symptomatic heart failure based on NT-proBNP.

AIMS: 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. METHODS: 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-proBNP >400 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). RESULTS: 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/m2 and 5.91 (2.19-16.0) for ≥30 kg/m2 compared with 21-22.9 kg/m2 ; 2.49(1.01-6.13) for systolic blood pressure of ≥160 mmHg vs. <130 mmHg; 2.87(1.23-6.68) for diastolic blood pressure of ≥100 mmHg vs. <80 mmHg; 5.16(2.14-12.4) for diabetes vs. non-diabetes; and 2.24 (0.92-5.49) for current smokers of ≥20 cigarettes/day vs. never smokers. The multivariable ORs (95% CIs) of the number of risk factors, defined as the sum of four risk factors (obesity, hypertension, diabetes, and current smoker) was 6.80 (3.69-12.5) for ≥2 risk factors vs. no risk factors. CONCLUSIONS: The accumulation of these risk factors was associated with a graded higher risk of pre-heart failure or symptomatic heart failure.

Trends in the incidence of stroke and its subtypes from 1963 to 2018 in Japanese urban and rural communities: The Circulatory Risk in Communities Study (CIRCS).

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.

Changes in cardiovascular disease risk factors during menopausal transition in Japanese women: the Circulatory Risk in Communities Study (CIRCS).

OBJECTIVE: We aimed to longitudinally clarify the changes in cardiovascular disease risk factors associated with menopause in Japanese women in the 2000s. METHODS: 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 A 1c , hemoglobin, aspartate aminotransferase, alanine aminotransferase, and current smoker status. RESULTS: Compared with the men, the women showed a greater increase in serum total cholesterol (+16.7 vs -3.1 mg/dL, P < 0.001), non-high-density lipoprotein cholesterol (+15.9 vs -6.3 mg/dL, P < 0.001), fasting triglycerides (+1.2 vs +1.0 mg/dL, P = 0.027), triglycerides regardless of fasting status (+1.2 vs -0.9 mg/dL, P < 0.001), uric acid (+0.5 vs +0.2 mg/dL, P = 0.008), hemoglobin (+0.9 vs -0.3 g/dL, P < 0.001), aspartate aminotransferase (+2.9 vs -2.7 IU/L, P < 0.001), and alanine aminotransferase (+2.9 vs -2.6 IU/L, P < 0.001). No differences were found in the changes in body mass index, systolic and diastolic blood pressures, and hemoglobin A 1c between the women and the matched men. CONCLUSIONS: 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.

Dietary intake of beans and risk of disabling dementia: The Circulatory Risk in Communities Study (CIRCS).

OBJECTIVE: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: Bean intake was inversely associated with risk of disabling dementia in those without a history of stroke.

Retinal microvascular abnormalities and risks of incident stroke and its subtypes: The Circulatory Risk in Communities Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Impact of Major Cardiovascular Risk Factors on the Incidence of Cardiovascular Disease among Overweight and Non-Overweight Individuals: The Circulatory Risk in Communities Study (CIRCS).

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.

Leukocyte Count and Risks of Stroke and Coronary Heart Disease: The Circulatory Risk in Communities Study (CIRCS).

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.

Dietary intake of tocopherols and risk of incident disabling dementia.

Tocopherols, strong antioxidants, may be useful in preventing dementia, but the epidemiological evidence is insufficient. We performed a community-based follow-up study of Japanese, the Circulatory Risk in Community Study, involving 3739 people aged 40-64 years at baseline (1985-1999). Incident disabling dementia was followed up from 1999 through 2020. For subtype analysis, we classified disabling dementia into that with and that without a history of stroke. Dietary intake of tocopherols (total, α, ß, γ, and δ) were estimated using 24-h recall surveys. During a median follow-up of 19.7 years, 670 cases of disabling dementia developed. Total tocopherol intake was inversely associated with risk of disabling dementia with multivariable hazard ratios (95% confidence intervals) of 0.79 (0.63-1.00) for the highest versus lowest quartiles of total tocopherol intake (P for trend = 0.05). However, the association was strengthened when further adjusted for α-linolenic acid intake (Spearman correlation with total tocopherol intake = 0.93), with multivariable hazard ratios of 0.50 (0.34-0.74) (P for trend = 0.001) but was weakened and nonsignificant when further adjusted for linoleic acid intake (Spearman correlation with total tocopherol intake = 0.92), with multivariable hazard ratios of 0.69 (0.47-1.01) (P for trend = 0.05). Similar but nonsignificant inverse associations were observed for α-, γ-, and δ-tocopherols but not for ß-tocopherol. These results were similar regardless of the presence of a history of stroke. Dietary tocopherol intake was inversely associated with risk of disabling dementia, but its independent effect was uncertain owing to a high intercorrelation of α-linolenic linoleic acids with total tocopherol intake. Even with such confounding, a diet high in tocopherols may help prevent the onset of dementia.

Seaweed Intake and Risk of Cardiovascular Disease: The Circulatory Risk in Communities Study (CIRCS).

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.