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.

Total protein intake and subsequent risk of chronic kidney disease: the Circulatory Risk in Communities Study.

BACKGROUND: Whether dietary protein intake worsens renal function in the general population has been discussed but not yet determined. We aimed to examine the longitudinal association between dietary protein intake and risk of incident chronic kidney disease (CKD). METHODS: We conducted a 12-year follow-up study with 3,277 Japanese adults (1,150 men and 2,127 women) aged 40-74 years, initially free from CKD, who participated in cardiovascular risk surveys from two Japanese communities under the Circulatory Risk in Communities Study. The development of CKD was defined by the estimated glomerular filtration rate (eGFR) during the follow-up period. Protein intake was measured at baseline by using the brief-type self-administered diet history questionnaire. We estimated sex-, age-, community- and multivariate-adjusted hazard ratios (HR) for incident CKD were calculated using the Cox proportional hazards regression models according to quartiles of percentage of energy (%energy) from protein intake. RESULTS: During 26,422 person-years of follow-up, 300 participants developed CKD (137 men and 163 women). The sex-, age-, and community-adjusted HR (95% confidence interval, CI) for the highest (≥16.9%energy) versus lowest (≤13.4%energy) quartiles of total protein intake was 0.66 (0.48-0.90), p for trend = 0.007. The multivariable HR (95%CI) was 0.72 (0.52-0.99), p for trend = 0.016 after further adjustment for body mass index, smoking status, alcohol drinking status, diastolic blood pressure, antihypertensive medication use, diabetes mellitus, serum total cholesterol levels, cholesterol-lowering medication use, total energy intake, and baseline eGFR. The association did not vary by sex, age, and baseline eGFR. When examining animal and vegetable protein intake separately, the respective multivariable HRs (95%CIs) were 0.77 (0.56-1.08), p for trend = 0.036, and 1.24 (0.89-1.75), p for trend = 0.270. CONCLUSIONS: Higher protein intake, more specifically animal protein intake was associated with a lower risk of CKD.

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.

Dietary behaviours and related lifestyles according to the presence or absence of skipping breakfast in Japanese adults: the JPHC-NEXT study.

OBJECTIVE: To assess dietary behaviours and related lifestyles according to the presence or absence of skipping breakfast. DESIGN: We analysed the cross-sectional data from a baseline survey of a large-scale population-based cohort study in Japan conducted in 2011-2016. Participants provided information on dietary behaviours and lifestyles through a self-administered questionnaire. Skipping breakfast was defined as not eating breakfast at least once a week and was classified according to the frequency of skipping breakfast as 1-2, 3-4 or ≥5 times/week. SETTING: Sixteen municipalities in seven prefectural areas across Japan under the Japan Public Health Centre-based prospective study for the Next Generation. PARTICIPANTS: 112 785 residents (51 952 males and 60 833 females) aged 40-74 years. RESULTS: After adjustment for age, socio-demographic status, drinking status and smoking status, individuals who skipped breakfast at least once a week, compared with those who ate breakfast every day, were more likely to have adverse dietary behaviours such as frequent eating out (multivariable OR = 2·08, 95 % CI (1·96, 2·21) in males and 2·15, 95 % CI (1·99, 2·33) in females), frequent eating instant foods (1·89, 95 % CI (1·77, 2·01) in males and 1·72, 95 % CI (1·56, 1·89) in females). They had late bedtime (1·85, 95 % CI (1·75, 1·95) in males and 1·98, 95 % CI (1·86, 2·11) in females) and living alone (2·37, 95 % CI (2·17, 2·58) in males and 2·02, 95 % CI (1·83, 2·21) in females), using the logistic regression model. CONCLUSIONS: Both adult males and females who skipped breakfast were likely to eat out, to have a dietary habit of eating instant foods and have lifestyles such as late bedtime and living alone than those who ate breakfast.

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 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.

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.

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.

Association between high systolic blood pressure and objective hearing impairment among Japanese adults: a facility-based retrospective cohort study.

This retrospective longitudinal study examined the association between systolic blood pressure and hearing impairment among 13,187 Japanese individuals (men, 46.5%) aged 20-59 years. The systolic blood pressure of participants was categorized as <120, 120-129, 130-139, 140-149, 150-159, and ≥160 mmHg. Using pure-tone audiometry, hearing impairment at 1 and 4 kHz was defined as hearing thresholds in either ear >30 and >40 dB, respectively. We performed multivariable Cox proportional-hazards regression analysis to examine the association using two multiple-imputation methods (fully conditional specification and Markov chain Monte Carlo). There were 695 and 774 hearing-impairment cases at 1 and 4 kHz, respectively, during ~77,000 person-years of follow-up. Compared with the <120 mmHg group, the hazard ratios (95% confidence intervals) of hearing impairment for the 120-129, 130-139, 140-149, 150-159, and ≥160 mmHg groups after adjustment for age, sex, body mass index, high serum glucose, current smoking, and other potential confounders were 1.35 (1.12-1.63), 1.45 (1.13-1.86), 1.07 (0.73-1.58), 1.91 (1.18-3.07), and 1.81 (1.01-3.25), respectively, at 1 kHz using the first imputation method; 1.36 (1.13-1.63), 1.48 (1.17-1.86), 1.09 (0.76-1.58), 1.99 (1.29-3.06), and 1.92 (1.08-3.41), respectively, at 1 kHz using the second imputation method; 1.04 (0.86-1.24), 1.14 (0.91-1.43), 1.13 (0.83-1.54), 1.45 (0.96-2.19), and 1.35 (0.82-2.23), respectively, at 4 kHz using the first imputation method; and 1.03 (0.86-1.24), 1.17 (0.95-1.44), 1.15 (0.87-1.53), 1.54 (1.06-2.24), and 1.44 (0.88-2.35), respectively, at 4 kHz using the second imputation method. In conclusion, higher systolic blood pressure was associated with hearing impairment at 1 kHz. No clear association was observed at 4 kHz.

Serum High-Sensitivity C-Reactive Protein Levels and the Risk of Atrial Fibrillation in Japanese Population: the Circulatory Risk in Communities Study.

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.

Urinary 8-Hydroxy-2'-Deoxyguanosine Levels and Cardiovascular Disease Incidence in Japan.

AIM: The association between urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker, and the incidence of cardiovascular disease (CVD) has not been confirmed because no previous studies evaluated 24-hour 8-OHdG excretion levels in the general population. We aimed to confirm the association between 24-hour urinary 8-OHdG levels and CVD risk among Japanese men and women. METHODS: A nested case-control study was performed based on a 24-hour urine collection in a community-based cohort study performed from 1996 to 2005. Seventy-six cases (55 men and 21 women) who experienced their first CVD incidence during the follow-up period (median: 5.9 years) were recruited. The controls were frequency-matched 1:2, with each case for sex, age, area of residence, and baseline year. The 8-OHdG level was measured by enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression models adjusted for body mass index, ethanol intake, smoking status, and estimated glomerular filtration rate. RESULTS: The geometric mean and geometric standard deviation (SD) of 8-OHdG levels (nmol/day) for cases and controls were 35.5 (1.55) and 35.5 (1.54) for men and 32.1 (1.35) and 25.0 (1.39) for women, respectively. The multivariable OR (95% CI) of CVD incidence according to the 1-SD increment of the log-transformed 8-OHdG level was 2.08 (0.99-4.37) for women. The multivariable ORs (95% CIs) for the 1st (lowest) and 4th versus 2nd quartile according to 8-OHdG for men were 3.29 (1.02-10.61) and 2.77 (0.96-7.96), respectively. CONCLUSION: A high 8-OHdG level tended to be associated with CVD incidence among women.

Incidence of Metabolic Syndrome in Young Japanese Adults in a 6-Year Cohort Study: The Uguisudani Preventive Health Large-Scale Cohort Study (UPHLS).

INTRODUCTION: To clarify the incidences of metabolic syndrome (MS) and risks in young Japanese adults by gender. METHODS: A total of 58,901 adults who had undergone annual health check-ups in 2010 without a diagnosis of MS or missing data were divided into three age groups (20s through 40s) by gender. Participants were followed up for 6 years for new-onset MS according to Japanese criteria. The incidences of MS and risks were analyzed using the Cox proportional hazards model to adjust for confounding factors. RESULTS: The incidences of MS per 1,000 person-years were 2.2, 5.5, and 10.2 for women aged in their 20s, 30s, and 40s, respectively, and 26.3, 40.5, and 57.4 in the respective men groups. Compared with the group aged in their 40s, the hazard ratios of new MS were 0.19 (95% confidence interval [CI], 0.13-0.29) for women in their 20s and 0.50 (95% CI, 0.41-0.61) for women in their 30s, and 0.46 (95% CI, 0.42-0.50) and 0.70 (95% CI, 0.66-0.73) for men in their 20s and 30s, respectively, after adjustment for lifestyle factors. For women, MS was associated with smoking in their 20s and 30s, and eating speed in their 30s, and for men, was associated with physical activity, eating speed, alcohol intake in their 20s and 30s, and smoking in their 30s. CONCLUSION: Our findings suggest that the incidences of MS in the 20s and 30s are lower, but account for about 20-50% of women with MS and 50-70% of men with MS in their 40s. However, the data are not negligible and early lifestyle intervention for MS is necessary in young adults.

Association between hypertension and hearing impairment in health check-ups among Japanese workers: a cross-sectional study.

OBJECTIVES: Prevention of hearing impairment (HI) is important because recovery of hearing is typically difficult. Epidemiological studies have examined the risk factors for HI. However, the association between hypertension and HI remains unclear. We aimed to clarify the association between hypertension and HI. DESIGN: Cross-sectional study. SETTING: Japanese workers in an information and communication technologies company. PARTICIPANTS: Of 24 823 employees of the same company, we recruited 13 475 participants who underwent hearing testing by audiometry in annual health check-ups and did not have missing data regarding body measurement, blood test results and drinking/smoking status (mean age: 49.4 years; males: 86.4%). PRIMARY OUTCOMES: Hearing tests were performed at two frequencies (1 kHz, 4 kHz). We defined the inability of participants to respond to 30 dB at 1 kHz and/or 40 dB at 4 kHz as overall moderate HI. We also defined moderate HI at 1 or 4 kHz as an abnormal finding at 1 or 4 kHz. We defined hypertension as ≥140 mm Hg systolic blood pressure and/or ≥90 mm Hg diastolic blood pressure and/or taking medication for hypertension. We examined the association between hypertension and HI after adjusting for age, sex, body mass index, smoking/drinking status, diabetes mellitus, hyperlipidaemia and proteinuria. RESULTS: Moderate HI was identified in 980 participants (7.3%). Of these, 441 participants (3.3%) exhibited moderate HI at 1 kHz, and 787 participants (5.8%) exhibited moderate HI at 4 kHz. Subjects with hypertension showed a higher prevalence of any HI. The prevalence of overall moderate HI, moderate HI at 1 kHz and moderate HI at 4 kHz among subjects with hypertension was 8.7%, 4.3% and 6.8%, while those among subjects without hypertension was 6.9%, 3.0% and 5.6% (p<0.01, p<0.01 and p=0.01, respectively). CONCLUSIONS: Hypertension was associated with moderate HI in Japanese workers.

Associations of Tobacco Smoking with Impaired Endothelial Function: The Circulatory Risk in Communities Study (CIRCS).

AIMS: Smoking impairs endothelial function as an acute effect. However, few population-based studies have examined the association between smoking status and endothelial function or the dose-response and duration-response association of smoking with endothelial function. We examined whether smoking habits were associated with impaired endothelial function depending on smoking dose and duration. METHODS: We conducted a cross-sectional study of 910 men and women aged 30-79 years from 2013 to 2016. Statistical analyses of the data were conducted between 2016 and 2017. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD) measurement. Low FMD was defined in two ways as the cutoff point based on the lowest quartile of %FMD (＜5.1%) and median of %FMD (＜6.8%), regarding as impaired endothelial function. We investigated the smoking status in terms of cigarettes consumed per day and the duration of smoking. RESULTS: Heavy and chronic smokers were associated with a high prevalence of impaired endothelial function. Those associations did not change substantially after adjustment for other cardiovascular risk factors. Among all participants, the multivariable-adjusted ORs (95% CIs) of low FMD (＜5.1%) with reference to never smokers were 2.23 (1.00-5.14) for current heavy smokers of ≥ 30 cigarettes per day, 1.83 (1.04-3.20) for heavy smokers of ≥ 40 pack-years, and 2.16 (1.15-4.06) for chronic smokers of ≥ 40 years. For low FMD (＜6.8%) those values was 2.17 (1.01-5.05), 1.70 (1.01-2.86), and 1.98 (1.07-3.69), respectively. CONCLUSIONS: Similar associations were observed among only men. Heavy or long-term tobacco smoking may induce impaired endothelial function.

Validity of a Risk Prediction Equation for CKD After 10 Years of Follow-up in a Japanese Population: The Ibaraki Prefectural Health Study.

BACKGROUND: Chronic kidney disease (CKD) is an important health problem for which risk equations have been developed for Western populations. This study aimed to develop and validate a risk prediction equation for CKD in a Japanese population. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: The study included 135,007 participants who completed an annual health checkup in 1993 to 1996 in the Ibaraki Prefecture in Japan. Participants were initially free of CKD (defined as stage 3, 4, or 5 CKD or proteinuria [2+ or 3+] by dipstick). Follow-up information was available from health checkups 10 years after the initial evaluation. We used data from 40,963 women and 17,892 men in the northern region of the prefecture for the development of risk prediction equations and 53,042 women and 23,110 men in the southern region for external validation. PREDICTORS: Age, estimated glomerular filtration rate (eGFR), body mass index, proteinuria, hematuria, hypertension, diabetes mellitus, smoking, and drinking. OUTCOME: Occurrence of CKD (defined as eGFR<60mL/min/1.73m2 and/or proteinuria [2+ or 3+] by dipstick). ANALYTICAL APPROACH: Logistic regression analysis to estimate risk for CKD stratified by sex. RESULTS: During follow-up, 7,500 cases of CKD developed in the northern region and 8,964, in the southern region. Older age, proteinuria (1+), higher systolic blood pressure, medication for hypertension, and current smoking were associated with increased risk for CKD in both sexes, whereas higher eGFR and daily alcohol intake were associated with lower risk. C statistics of risk estimation equations for CKD at 10 years were >0.8 for both the development and external validation populations, and discrimination of the risk estimation was fairly good in women and men. LIMITATIONS: Fluctuations in variables were not evaluated because the study used annual health checkups. This study excluded a large number of people for whom a 10-year health checkup was not available. CONCLUSIONS: Estimations of risk for CKD after 10 years of follow-up in a general Japanese population can be achieved with a high level of validity.

Impact of Hypertension and Subclinical Organ Damage on the Incidence of Cardiovascular Disease Among Japanese Residents at the Population and Individual Levels　- The Circulatory Risk in Communities Study (CIRCS).

BACKGROUND: In Japan, a community-based screening program for cardiovascular disease (CVD) has been effective in preventing stroke and coronary artery disease (CAD). The present study aimed to clarify which risk factors assessed at the screening examinations affect the incidence of CVD and the magnitude of the association after the late 1990 s.Methods and Results:We conducted a 12.5-year prospective study of 10,612 Japanese residents aged 40-74 years between 1995 and 2000, initially free of CVD and who underwent the screening examinations. During the follow-up, 364 cases of stroke and 137 cases of CAD were identified. The population attributable fraction of stroke was the largest for hypertension (HT; 46%), while the relative risk of stroke was the highest for atrial fibrillation (multivariable hazard ratio, 4.9; 95% confidence interval, 2.9-8.3). The population attributable fraction of CAD was relatively large for HT, current smoking, and high non-high-density lipoprotein cholesterol (20-29%). A dose-response relationship was found between the incidence of these cardiovascular events and the number of comorbid hypertensive subclinical organ damage markers: funduscopic changes, ST-T changes on ECG at rest, proteinuria and low estimated glomerular filtration rate. CONCLUSIONS: HT and hypertensive subclinical organ damage are significantly associated with incident stroke and CAD at the population level, suggesting that management of HT and assessment of subclinical organ damage in hypertensive subjects at a screening program are still beneficial for community-based CVD prevention.

Relationships among drinking and smoking habits, history of diseases, body mass index and idiopathic sudden sensorineural hearing loss in Japanese patients.

OBJECTIVES: To present the cardiovascular risk factors in idiopathic sudden sensorineural hearing loss (SSNHL) patients enrolled in a nationwide epidemiological survey of hearing disorders in Japan. MATERIALS AND METHODS: We compiled the cardiovascular risk factors in 3073 idiopathic SSNHL subjects (1621 men and 1452 women) and compared their proportions with controls as part of the National Health and Nutrition Survey in Japan, 2014. The cardiovascular risk factors consisted of drinking and smoking habits, a history of five conditions related to cardiovascular disease and body mass index. RESULTS: The proportion of current smokers was significantly higher among men aged 50-59, 60-69 and 70+ and among women aged 30-39, 40-49 and 60-69. The proportion of patients with a history of diabetes mellitus was significantly higher among men aged 50-59, 60-69 and 70+, but not in women. In addition, male and female SSNHL subjects aged 60-69 showed lower proportions of current drinking; and female SSNHL subjects aged 60-69 showed higher proportions of overweight (BMI ≥25 kg/m2). CONCLUSIONS: The present cross-sectional study revealed showed significantly higher proportions of current smokers among both men and women as well as those with a history of diabetes mellitus among men across many age groups in patients with idiopathic SSNHL compared with the controls.

Impact and attribute of each obesity-related cardiovascular risk factor in combination with abdominal obesity on total health expenditures in adult Japanese National Health insurance beneficiaries: The Ibaraki Prefectural health study.

BACKGROUND: The aim of this study was to examine the attribution of each cardiovascular risk factor in combination with abdominal obesity (AO) on Japanese health expenditures. METHODS: The health insurance claims of 43,469 National Health Insurance beneficiaries aged 40-75 years in Ibaraki, Japan, from the second cohort of the Ibaraki Prefectural Health Study were followed-up from 2009 through 2013. Multivariable health expenditure ratios (HERs) of diabetes mellitus (DM), high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), and hypertension with and without AO were calculated with reference to no risk factors using a Tweedie regression model. RESULTS: Without AO, HERs were 1.58 for DM, 1.06 for high LDL-C, 1.27 for low HDL-C, and 1.31 for hypertension (all P < 0.05). With AO, HERs were 1.15 for AO, 1.42 for DM, 1.03 for high LDL-C, 1.11 for low HDL-C, and 1.26 for hypertension (all P < 0.05, except high LDL-C). Without AO, population attributable fractions (PAFs) were 2.8% for DM, 0.8% for high LDL-C, 0.7% for low HDL-C, and 6.5% for hypertension. With AO, PAFs were 1.0% for AO, 2.3% for DM, 0.4% for low HDL-C, and 5.0% for hypertension. CONCLUSIONS: Of the obesity-related cardiovascular risk factors, hypertension, independent of AO, appears to impose the greatest burden on Japanese health expenditures.

Personal status of general health checkups and medical expenditure: A large-scale community-based retrospective cohort study.

BACKGROUND: We sought to clarify the association between the personal utilization of general health checkups (GHCs) and medical expenditures (MEs) in a middle-aged Japanese population. METHODS: A retrospective cohort study was conducted. Subjects were 33,417 residents (15,819 males and 17,598 females) aged 48 years or older in 2010 who were invited to undergo GHCs every year. Official records on GHCs from 2002 to 2007 and MEs from 2008 to 2010 were provided by Soka City, Saitama Prefecture, Japan. The utilization of GHCs was divided into zero times (non-utilizers), 1-3 times (low-frequency utilizers), and 4-6 times (high-frequency utilizers). Tweedie distributions in the generalized linear model were used to analyze the association between MEs and the subgroups of GHC utilization after adjustment for age and sex. RESULTS: Of the 33,417 subjects, 20,578 (61.6%) were non-utilizers, 5,777 (17.3%) were low-frequency utilizers, and 7,062 (21.1%) were high-frequency utilizers, based on the attendance to GHCs from 2002 to 2007. Compared with the non-utilizers, the high-frequency utilizers showed significantly higher outpatient MEs (JPY394,700 vs. JPY373,100). The low- and high-frequency utilizers showed significantly lower inpatient MEs (JPY224,000 and JPY181,500 vs. JPY309,300) and total MEs (JPY610,600 and JPY580,700 vs. JPY689,600) than the non-utilizers based on the pooled data from 2008 to 2010. CONCLUSIONS: This study suggests that the outpatient MEs rise when annual GHCs are increasingly attended (not including the GHC cost), but inpatient and total MEs are lower. To reduce MEs, increasing the rates of attendance at GHCs by the general public may be important.

Retinal Vascular Changes and Prospective Risk of Disabling Dementia: the Circulatory Risk in Communities Study (CIRCS).

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 disabling 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 generalized arteriolar narrowing, 7.7 (7.5)% for focal arteriolar narrowing, 15.7 (11.8)% for arteriovenous nicking, 10.5 (9.3)% for increased arteriolar wall reflex, and 11.4 (9.8)% for any other retinopathy. Generalized arteriolar narrowing was associated with an increased 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 useful markers for identifying persons at higher risks of disabling dementia.