Japan Public Health Center-based Prospective Research Articles

Risk and Population Attributable Fraction of Stroke Subtypes in Japan.

Associations of major risk factors for stroke with total and each type of stroke, as well as subtypes of ischemic stroke, and their population attributable fractions had not been examined comprehensively. Participants of the Japan Public Health Center-based prospective (JPHC) Study Cohort II without histories of cardiovascular disease and cancer (n = 14,797) were followed from 1993 through 2012. Associations of current smoking, hypertension, diabetes, overweight (body mass index ≥25 kg/m2), non-high-density lipoprotein cholesterol (non-HDLC) categories, low HDLC (<40 mg/dL), urine protein, and history of arrhythmia were examined in a mutually-adjusted Cox regression model that included age and sex. Population attributable fractions (PAFs) were estimated using the hazard ratios and the prevalence of risk factors among cases. Subjects with hypertension were 1.63 to 1.84 times more likely to develop any type of stroke. Diabetes, low HDLC, current smoking, overweight, urine protein, and arrhythmia were associated with risk of overall and ischemic stroke. Hypertension and urine protein were associated with risk of intracerebral hemorrhage, while current smoking, hypertension, and low non-HDLC were associated with subarachnoid hemorrhage. Hypertension alone accounted for more than a quarter of stroke incidence, followed by current smoking and diabetes. High non-HDLC, current smoking, low HDLC, and overweight contributed mostly to large-artery occlusive stroke. Arrhythmia explained 13.2% of embolic stroke. Combined PAFs of all the modifiable risk factors for total, ischemic, and large-artery occlusive strokes were 36.7%, 44.5%, and 61.5%, respectively. Although there are differences according to subtypes, hypertension could be regarded as the most crucial target for preventing strokes in Japan.

Development and Validation of Prediction Models for the 5-year Risk of Type 2 Diabetes in a Japanese Population: Japan Public Health Center-based Prospective (JPHC) Diabetes Study.

This study aimed to develop models to predict the 5-year incidence of type 2 diabetes mellitus (T2DM) in a Japanese population and validate them externally in an independent Japanese population. Data from 10,986 participants (aged 46-75 years) in the development cohort of the Japan Public Health Center-based Prospective Diabetes Study and 11,345 participants (aged 46-75 years) in the validation cohort of the Japan Epidemiology Collaboration on Occupational Health Study were used to develop and validate the risk scores in logistic regression models. We considered non-invasive (sex, body mass index, family history of diabetes mellitus, and diastolic blood pressure) and invasive (glycated hemoglobin [HbA1c] and fasting plasma glucose [FPG]) predictors to predict the 5-year probability of incident diabetes. The area under the receiver operating characteristic curve was 0.643 for the non-invasive risk model, 0.786 for the invasive risk model with HbA1c but not FPG, and 0.845 for the invasive risk model with HbA1c and FPG. The optimism for the performance of all models was small by internal validation. In the internal-external cross-validation, these models tended to show similar discriminative ability across different areas. The discriminative ability of each model was confirmed using external validation datasets. The invasive risk model with only HbA1c was well-calibrated in the validation cohort. Our invasive risk models are expected to discriminate between high- and low-risk individuals with T2DM in a Japanese population.

Dietary Consumption of Antioxidant Vitamins in Relation to Prostate Cancer Risk in Japanese Men: The Japan Public Health Center-based Prospective Study.

Many epidemiological studies have investigated dietary intake of antioxidant vitamins in relation to prostate cancer risk in Western countries, but the results are inconsistent. However, few studies have reported this relationship in Asian countries. We investigated the association between intake of vitamins, including lycopene, α-carotene, β-carotene, vitamin C, vitamin E, with prostate cancer risk in the Japan Public Health Center-based Prospective (JPHC) study. 40,720 men without history of cancer finished the food frequency questionnaire (FFQ) and were included in the study. Hazard ratios (HRs) and 95% confidence intervals (CIs) of prostate cancer risk were calculated according to the quintiles of energy-adjusted intake of vitamins using Cox models. After an average of 15.2 years (617,599 person-years in total) of follow-up, 1,386 cases of prostate cancer were identified, including 944 localized cases and 340 advanced cases. No associations were observed in consumption of antioxidant vitamins, including α-carotene, β-carotene, vitamin C, and vitamin E, and prostate cancer risk. Although higher lycopene intake was associated with increased risk of prostate cancer (highest vs lowest quintile, HR 1.24; 95% CI, 1.04-1.47; P for trend = 0.01), there was a null association of lycopene intake with risk of prostate cancer detected by subjective symptoms (HR 1.12; 95% CI, 0.79-1.58; P for trend = 0.11). Our study suggested no association between antioxidant intake of vitamins and prostate cancer risk.

The effect of age on the relationship between body mass index and risks of incident stroke subtypes: The JPHC study

ObjectiveThe associations between body mass index (BMI) and stroke subtypes, particularly intracerebral hemorrhage, have not been consistent. Such inconsistencies may be due to differences in the age at which BMI was obtained. We examined the possible age modifications in the association between BMI and stroke risk. Materials and MethodsWe followed 88,754 participants, aged 40–69 years at baseline (1990-1994), of the Japan Public Health Center-based prospective (JPHC) study for stroke incidence. BMI was obtained using self-reported body weight and height, which were categorized using the following cut-off points: 18.5, 21, 23, 25, 27.5, and 30 kg/m2. Time-dependent Cox proportional hazards models that updated BMI and covariates using 5- and 10-year questionnaire responses were used to estimate hazard ratios and 95 % confidence intervals. The analyses were stratified by age group (40–59 and ≥60 years) and the age of the individuals was updated. ResultsDuring the median follow-up period of 19 years, we documented 4,690 strokes, including 2,781 ischemic strokes and 1,358 intracerebral hemorrhages. After adjusting for sex, age, smoking, alcohol consumption, leisure-time physical activity, history of hypertension, dyslipidemia, and diabetes mellitus, we observed a positive linear association between BMI and ischemic stroke (linear trend, p < 0.001) in both age groups (interaction p>0.05). In contrast, a curvilinear association between BMI and intracerebral hemorrhage was observed in both the middle (curvilinear trend, p=0.017) and the older group (curvilinear trend, p=0.098) (interaction p>0.05). ConclusionBMI and stroke associations did not vary significantly with age, although the association may differ according to subtype.

P140: Midlife diet and risk of dementia/mild cognitive impairment

The Japan Public Health Center-based prospective (JPHC) Study is a large population-based cohort. Midlife dietary intake was assessed on two occasions: in the years 1995 and 2000 (aged 45-64 in 1995). In 2014-2015, approximately 1300 participants from Saku district in Nagano prefecture completed a mental health screening including later life depression and cognitive decline (i.e., mild cognitive impairment (MCI) and dementia). We used logistic regression analyses to calculate odds ratios (ORs) for MCI and dementia. Based on this survey, we found the following characteristics of midlife diet, which may be useful information to prevent cognitive decline/dementia.1.High-density lipoprotein cholesterol (HDL-C) and later cognitive decline (Svensson et al. Transl Psychiatry, 2019): Midlife high-density lipoprotein cholesterol (HDL-C) is a measure which could help identify individuals at reduced risk of developing age-related cognitive decline. Compared to the lowest HDL-C quartile, the highest HDL-C quartile was significantly inversely associated with MCI. High HDL-C (quartiles 2-4) was inversely associated with dementia compared to low HDL-C (quartile 1).2.Dietary fish and n-3 polyunsaturated fatty acid (PUFA) and later cognitive decline (Nozaki et al. J Alzheimers Dis, 2021): Higher intake of fish, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in midlife significantly reduced risks of dementia.3.Intake of soy and the isoflavone and later cognitive decline (Svensson et al. J Alzheimers Dis, 2021): Compared to the lowest dietary quartile of energy-adjusted isoflavone genistein intake, the highest quartile was significantly associated with late-life cognitive impairment.4.Cancer/diabetes and later cognitive decline (Sadahiro et al. Psychiatry Clin Neurosci, 2019): Comorbid cancer and diabetes from midlife may increase the risk of MCI or dementia in later life. In addition to the increased dementia risk associated with diabetes on the basis of insulin resistance, cancer and cancer therapies may also interfere with cognitive function via insulin resistance.

Midlife intake of the isoflavone genistein and soy, and the risk of late-life cognitive impairment: the JPHC Saku Mental Health Study.

The number of people with cognitive impairment, including dementia, in the world is steadily increasing. Although the consumption of isoflavones and soy is associated with a reduced risk of cardiovascular disease, it might also be associated with cognitive impairment. The low number of studies investigating the association between soy/isoflavone intake and cognitive function warrant additional research. The Japan Public Health Center-based prospective (JPHC) Study is a large population-based cohort. Midlife dietary intake of soy and the isoflavone genistein was assessed on two occasions: in the years 1995 and 2000. In 2014-2015, 1299 participants from Nagano prefecture completed a mental health screening. Of these, a total of 1036 participants were included in analyses. Logistic regression was used to determine Odds Ratios (OR) and 95% Confidence Intervals (CI) for the association between midlife energy-adjusted genistein and soy food intake and cognitive impairment. There were 392 cases of cognitive impairment (346 cases of MCI and 46 cases of dementia). Compared to the lowest dietary quartile of energy-adjusted genistein intake, the highest quartile was significantly associated with cognitive impairment (OR=1.51; 95% CI, 1.02-2.24; p for trend=0.03) in the final multivariable analysis. High midlife intake of the isoflavone genistein is associated with late-life cognitive impairment.

Associations between dairy intake and mortality due to all-cause and cardiovascular disease: the Japan Public Health Center-based prospective study

BackgroundSome studies have investigated the relation between dairy products and mortality, but with inconsistent results.ObjectiveWe examined the association between the consumption of dairy products and the risk of all-cause, cancer-related, and cardiovascular disease (CVD)-related mortality.MethodsFrom the Japan Public Health Center-based Prospective (JPHC) study, 43,117 males and 50,193 females with no history of cancer or CVD finished the food frequency questionnaire (FFQ) and were included in the study. Intake of dairy products was assessed using the FFQ and adjusted for total energy by using the residual method. We used multivariate Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for mortality risk in males and females.Results14,211 deaths in males and 9547 deaths in females from all causes were identified during an average follow-up of 19.3 years. For males, total dairy consumption was nonlinearly and significantly associated with lower risk of mortality from all causes [the third quartile, HR = 0.87 (0.83, 0.91), the fourth quartile, HR = 0.89 (0.85, 0.94), P for nonlinearity < 0.001] and CVD [the third quartile, HR = 0.77 (0.70, 0.85), the fourth quartile, HR = 0.78 (0.70, 0.86), P for nonlinearity < 0.001]. Milk and fermented milk intake were inversely associated with all-cause and CVD-related mortality in males. Cheese consumption was inversely associated with CVD-related mortality among males. There was no association between total dairy intake and mortality risk among females.ConclusionFor Japanese people, consumption of dairy products was associated with a decreased risk of mortality from all-cause and cardiovascular diseases among males.

Association Between Physical Activity and Risk of Disabling Dementia in Japan

The associations of daily total physical activity and total moderate to vigorous physical activity (MVPA) with dementia are still unclear. To investigate the association between daily total physical activity and subsequent risk of disabling dementia in large-scale, extended follow-up prospective study. This prospective cohort study used data from questionnaires collected between 2000 and 2003 from 8 areas from the Japan Public Health Center-based Prospective Disabling Dementia Study. Participants included adults aged 50 to 79 years in with available follow-up data on disabling dementia. Data analysis was performed from February 1, 2019, to July 31, 2021. Daily total physical activity, total MVPA, and leisure-time MVPA. The main outcome was incidence of disabling dementia during the dementia ascertainment period between 2006 and 2016, based on the national long-term care insurance system. Risks of dementia in association with daily total physical activity, total MVPA, and leisure time MVPA were calculated using multivariable adjusted hazard ratios (aHRs). Among 43 896 participants (mean [SD] age, 61.0 [7.5] years; 23 659 [53.9%] women), 5010 participants were newly diagnosed with disabling dementia during a mean (SD) of 9.5 (2.8) years in the dementia ascertainment period. In the highest daily total physical activity group, compared with the lowest activity group, risk of dementia was lower in men (aHR, 0.75 [95% CI, 0.66-0.85]; P for trend < .001) and women (aHR, 0.75 [95% CI, 0.67-0.84]; P for trend < .001). Similar inverse associations were observed in men and women for total MVPA (men: aHR, 0.74 [95% CI, 0.65-0.84]; P for trend < .001; women: aHR, 0.74 [95% CI, 0.66-0.83]; P for trend < .001) and leisure-time MVPA (men: aHR, 0.59 [95% CI, 0.53-0.67]; P for trend < .001; women: aHR, 0.70 [95% CI, 0.63-0.78]; P for trend < .001). However, these inverse associations disappeared when participants diagnosed with disabling dementia within 7 years of the starting point were excluded in men (aHR, 0.93 [95%CI, 0.77-1.12]) and within 8 years were excluded in women (aHR, 0.86 [95%CI, 0.71-1.04]). The association remained significant among men in the highest vs lowest group of leisure-time MVPA, after excluding participants diagnosed within the first 9 years (aHR, 0.72 [95% CI, 0.56-0.92]; P for trend = .004). This cohort study examined associations of daily total physical activity and total MVPA with risk of disabling dementia. The findings suggest that a high level of leisure-time MVPA was associated with decreased risk of disabling dementia in men.

Menstrual and reproductive factors and limitations in activities of daily living: A case–control study within the Japan Public Health Center‐based Prospective Study

Although menstrual/reproductive factors are known to be associated with physical disability, little is known about these associations in relation to activities of daily living (ADL). This study aimed to clarify associations between menstrual/reproductive factors and ADL limitations in peri- and postmenopausal women. A nested case-control study of the Japan Public Health Center-based Prospective (JPHC) Study. The main outcome measure was self-reported ADL levels in the 10-year follow-up questionnaire survey of the JPHC Study conducted between 2000 and 2004 (N=36 460). Women who "live inside almost independently, but go out with assistance" or had a lower level of activity were considered to have ADL limitations ("cases"), and all others served as controls. Candidate menstrual/reproductive predictors were as follows: menarcheal age, menopausal status, menopausal age, regularity of menses, menstrual cycle, number of pregnancies, age at first pregnancy, number of deliveries, age at first delivery, and breast feeding. Multiple logistic regression analyses were conducted, and odds ratios adjusted for age and past lifestyle were calculated. Mean ages of cases (N=592) and controls (N=38 656) were 68.3 (SD=7.6) and 61.1 (SD=7.7) years, respectively. With respect to menopausal age, groups aged <45 and ≥55 years had significantly higher adjusted ORs (1.44, 95% CI: 1.09-1.90 and 1.55, 95%CI: 1.09-2.18, respectively) than the reference group (50-54 years). Multiparous women had significantly lower ORs than nulliparous women. Our findings suggest that menopausal age and parity may predict future ADL limitations in women.

990Seaweed intake and risk of cardiovascular disease: the Japan Public Health Center–based Prospective (JPHC) Study

Abstract Background The minerals, vitamins, soluble dietary fibers, and flavonoids of seaweed are protective for preventing cardiovascular diseases. However, the association between seaweed intake and risk of cardiovascular disease has not been established. We examined the dietary intake of seaweed and its impact upon stroke and ischemic heart disease (IHD) risk among a Japanese study population. Methods We surveyed 40,707 men and 45,406 women from 2 large cohorts (age range: 40–69 y). Seaweed intake in the study subjects was estimated from the food frequency questionnaire at baseline (1990–1994). Stroke and IHD events were identified until the end of 2009 (Cohort I) or 2012 (Cohort II). The hazard ratios (HRs) (95% confidence intervals [CIs]) for incident cardiovascular disease (CVD) and its subtype were estimated using Cox proportional hazard models after stratification by area and adjustment for cardiovascular disease risk and dietary factors by sex. Results During 1,493,232 person-years of follow-up, 4,777 strokes and 1,204 IHD cases were identified. Among men, significant multivariable HRs (95% CIs) for almost daily consumption were seen in IHD (0.76 [0.58-0.99]; P-trend=0.04) compared to almost no seaweed consumption. Among women, such inverse associations were observed in incident IHD (0.56 [0.36-0.85]; P-trend=0.006). No significant associations were observed between seaweed intake and risk of stroke nor stroke subtypes among either men or women. Conclusions Seaweed intake has been shown to contribute to the prevention of IHD in a large Japanese cohort. Key messages Seaweed intake could be beneficial for prevention of IHD.

Non-High-Density Lipoprotein Cholesterol and Risk of Stroke Subtypes and Coronary Heart Disease: The Japan Public Health Center-Based Prospective (JPHC) Study

Aim: A positive association between non-high-density lipoprotein cholesterol (non-HDL-C) and coronary heart disease (CHD) has been established; however, associations between non-HDL-C and stroke subtypes have not been determined.Methods: We conducted a prospective study of 30,554 individuals aged 40–69 yrs with no history of cardiovascular disease (CVD) in Japan. Sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of stroke subtypes and CHD were estimated according to quintiles of non-HDL-C, using Cox proportional hazard models adjusted for other established risk factors.Results: We identified 1,705 stroke and 296 CHD events over a median 15 yrs of follow-up. The fractional polynomials analysis revealed a U-shaped association between non-HDL-C and stroke risk in men. When analyzed for stroke subtypes, the data revealed an inverse relationship between non-HDL-C and intracerebral hemorrhage (ICH), primarily with lobar ICH, and a positive association between non-HDL-C and large-artery occlusive infarction in men [adjusted HR 0.55 (95% CI, 0.35–0.87) and 2.05 (95% CI, 1.07–3.93) for the highest and lowest quintile of non-HDL-C, respectively]. The lowest risk of ICH in women was observed in the fourth quintile, and the lowest risk of embolic infarction was observed in the third quintile. In contrast, non-HDL-C was positively associated with CHD in both sexes.Conclusions: In Japanese men, lower non-HDL-C levels were associated with a decreased risk of large-artery occlusive infarction and an increased risk of ICH, particularly lobar ICH.

Seaweed intake and risk of cardiovascular disease: the Japan Public Health Center–based Prospective (JPHC) Study

The minerals, vitamins, soluble dietary fibers, and flavonoids of seaweed are protective for preventing cardiovascular diseases. However, the association between seaweed intake and risk of cardiovascular disease has not been established. We examined the dietary intake of seaweed and its impact upon stroke and ischemic heart disease risk among a Japanese study population. We surveyed 40,707 men and 45,406 women from 2 large cohorts (age range: 40-69 y). Seaweed intake was determined by FFQ at baseline (1990-1994). Incidences of stroke and ischemic heart disease were ascertained until the end of 2009 (Cohort I) or 2012 (Cohort II). Sex-specific cardiovascular disease HRs (95% CIs) were estimated using Cox proportional hazard models after stratification by area and adjustment for cardiovascular disease risk and dietary factors. During 1,493,232 person-years of follow-up, 4777 strokes (2863 ischemic stroke, 1361 intraparenchymal hemorrhages, and 531 subarachnoid hemorrhages) and 1204 ischemic heart disease cases were identified. Among men, significant multivariable HRs (95% CIs) for almost daily consumption compared with almost no consumption of seaweed were seen in ischemic heart disease [0.76 (0.58, 0.99); P-trend=0.04] and total cardiovascular diseases [0.88 (0.78, 1.00); P-trend=0.08]. Among women, such inverse associations were 0.56 (0.36, 0.85; P-trend=0.006) for ischemic heart disease and 0.89 (0.76, 1.05; P-trend=0.10) for total cardiovascular diseases. No significant associations were observed between seaweed intake and risk of total stroke or stroke types among either men or women. Seaweed intake was inversely associated with risk of ischemic heart disease.

Body Mass Index and Risks of Incident Ischemic Stroke Subtypes: The Japan Public Health Center-Based Prospective (JPHC) Study.

BackgroundThe association of body mass index (BMI) with risks of ischemic stroke subtypes have not been established.MethodsCumulative average BMI was calculated using self-reported body weight and height obtained from baseline (Cohort I in 1990, and Cohort II from 1993–1994) and 5- and 10-year questionnaire surveys of Japan Public Health Center-based prospective (JPHC) study. A total of 42,343 men and 46,413 women aged 40–69 years were followed-up for the incidence of lacunar, large-artery occlusive, and cardioembolic strokes. A sub-distribution hazard model was used to estimate sub-distribution hazard ratios (SHRs) and the 95% confidence intervals (CIs).ResultsDuring a median of 20.0 years of follow-up, we documented 809 and 481 lacunar, 395 and 218 large-artery occlusive, and 568 and 298 cardioembolic strokes in men and women, respectively. After adjustment for baseline age, updated smoking, alcohol consumption, leisure-time physical activity, and histories of hypertension, dyslipidemia, and diabetes mellitus, cumulative average BMI was positively linearly associated with lacunar (trend P = 0.007), large-artery occlusive (trend P = 0.002), and cardioembolic (trend P < 0.001) strokes in men, and with lacunar (trend P < 0.001) and large-artery occlusive (trend P = 0.003) strokes in women. There were approximately two-fold excess risk of cardioembolic stroke in both sexes and of lacunar and large-artery occlusive strokes in women for cumulative average BMI ≥30 kg/m2 compared to BMI 23–<25 kg/m2.ConclusionCumulative average BMI showed a positive linear effect on sub-distribution hazards of lacunar, large-artery occlusive, and cardioembolic strokes in both sexes, except for cardioembolic stroke in women.

Reproductive history and risk of cognitive impairment in Japanese women

ObjectiveWhile exposure to endogenous estrogen may be associated with better cognitive performance, it is still unclear whether it has an association with mild cognitive impairment (MCI) or dementia. The aim of this study was to clarify the effects of reproductive history, as a surrogate marker of exposure to endogenous estrogen, on the risk of cognitive impairment (MCI or dementia) in women. Study designA total of 747 women aged 40–59 years in the Saku area (Nagano Prefecture) were followed as part of the Japan Public Health Center-based Prospective (JPHC) Study, which started in 1990. Participants had undergone a mental health examination in 2014–2015. Main outcome measuresWe used multiple logistic regression to analyze the association between reproductive history, obtained at baseline and 10-year follow-up, with current cognitive impairment diagnosed by a trained psychiatrist, adjusting for various lifestyle factors. ResultsAmong 670 eligible women, current cognitive impairment was diagnosed in 227, 196 of whom had MCI and 31 dementia. A longer reproductive period had a significantly inverse association with cognitive impairment (P-trend = 0.032). In particular, women with a reproductive period ≥38 years compared with ≤33 years had a significantly lower risk of cognitive impairment (multivariable adjusted odds ratio=0.62, 95% confidence interval=0.40–0.96). ConclusionsA longer reproductive period was associated with a lower risk of cognitive impairment, which suggests that a longer exposure to endogenous estrogen may have a protective effect against cognitive impairment.

Menstrual and reproductive factors and risk of vertebral fractures in Japanese women: the Japan Public Health Center-based prospective (JPHC) study.

This study investigated the association between menstrual and reproductive factors and the risk of later-life vertebral fractures in women. Participants were 43,652 women aged 40-69years who were followed in the 10-year survey of the Japan Public Health Center-based prospective (JPHC) study. Menstrual/reproductive factors were as follows: age at menarche and menopause, menstrual regularity and cycle length, natural or surgical menopause, years since menopause, reproductive years, parity, age at first birth, number of births, breastfeeding, and female hormone use. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression analysis with adjustment for well-known fracture risk factors and menstrual/reproductive factors. During the 10-year period, 250 women reported first onset of vertebral fractures. Menarche at ≥16years [OR (95% CI) = 2.08 (1.24-3.48)] compared to ≤ 13years and irregular menstruation [1.42 (1.01-2.00)] compared to regular menstruation showed significantly higher adjusted ORs. Longer reproductive years had significant inverse association [0.96 (0.92-0.99)] in menopausal women. Women with both menarche ≥ 15years and irregular menstruation had higher adjusted ORs (95% CI) [2.37 (1.51-3.73) in all women, 2.25 (1.35-3.76) in menopausal women] compared to women without these, and both factors had significant interaction, particularly in menopausal women (additive p = 0.025, multiplicative p = 0.0499). Menstrual and reproductive factors, corresponding to the effect of reproductive hormonal disturbance on bone metabolism, might affect the risk of later-life vertebral fractures.

Association of high-density lipoprotein cholesterol concentration with different types of stroke and coronary heart disease: The Japan Public Health Center-based prospective (JPHC) study

Background and aimsAlthough low high-density lipoprotein (HDL) cholesterol concentration is an established risk factor for coronary heart disease (CHD), information regarding subtypes of stroke is very limited, especially in Asian populations. MethodsA prospective study was conducted among 30,736 individuals aged 40–69 years, who lived in nine communities in Japan and did not have a history of cardiovascular disease (CVD). CHD and stroke, including its subtypes, were assessed, and sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated according to quintiles of HDL cholesterol using Cox proportional models adjusted for other CVD risk factors. ResultsWe identified 296 CHD and 1712 stroke events over a median 15 yr of follow-up. HDL cholesterol concentration showed an inverse association with CHD in men and women. A low HDL cholesterol concentration slightly raised the risk for total strokes in men, but not in women. When analyzed by subtypes, we observed an inverse relationship between HDL cholesterol concentration and the incidence of lacunar infarction, with an adjusted HR for the lowest quintile of HDL cholesterol concentration compared with the highest quintile of 1.63 (95% CI, 1.00–2.66) in men and 1.97 (95% CI, 1.19–3.26) in women. HDL cholesterol concentration was positively associated with the risk of intracerebral hemorrhage (ICH) in a linear manner in women (p for trend = 0.028), but not in men. ConclusionsThe associations of HDL cholesterol concentration with lacunar infarction and ICH may be related to different functional properties of HDL rather than to its protective function against lipid-rich atherosclerosis.

Risk and preventive factors for prostate cancer in Japan: The Japan Public Health Center-based prospective (JPHC) study

The incidence of prostate cancer is much lower in Asian than in Western populations. Lifestyle and dietary habits may play a major role in the etiology of this cancer. Given the possibility that risk factors for prostate cancer differ by disease aggressiveness, and the fact that 5-year relative survival rate of localized prostate cancer is 100%, identifying preventive factors against advanced prostate cancer is an important goal.Using data from the Japan Public Health Center-based Prospective Study, the author elucidates various lifestyle risk factors for prostate cancer among Japanese men. The results show that abstinence from alcohol and tobacco might be important factors in the prevention of advanced prostate cancer. Moreover, the isoflavones and green tea intake in the typical Japanese diet may decrease the risk of localized and advanced prostate cancers, respectively.

Plasma 25-hydroxy vitamin D and subsequent prostate cancer risk in a nested Case-Control study in Japan: The JPHC study.

Although vitamin D has been experimentally reported to inhibit tumorigenesis, cell growth and prostate cancer invasion, epidemiologic data regarding prostate cancer risk are inconsistent, and some studies have suggested positive but nonsignificant associations. Further, the impact of vitamin D on prostate cancer between Western and Japanese populations may differ due to different plasma vitamin D levels. We performed a nested case-control study within the Japan Public Health Center-based Prospective (JPHC) Study in 14,203 men (40-69 years) who answered a self-administered questionnaire at baseline (1990-1994) and gave blood samples, and were followed until 2005. We identified 201 prostate cancers which are newly diagnosed during follow-up (mean 12.8 years). We selected two matched controls for each case from the cohort. We used a conditional logistic regression model to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer with respect to levels of 25-hydroxy vitamin D (25(OH)D) in plasma. We did not observe statistically significant association between 25(OH)D level and total prostate cancer (multivariate OR=1.13 (95%CI=0.66-1.94, Ptrend=0.94) for the highest versus lowest tertile) However, 25(OH) levels were slightly positively associated with advanced cancer. The results remained substantially unchanged after stratification by intake of fish or calcium intake. 25(OH)D level showed no association with overall prostate cancer among Japanese men in this large cohort.

Association between mortality and incidence rates of coronary heart disease and stroke: The Japan Public Health Center-based prospective (JPHC) study

BackgroundIt is essential to have information on incidence rates to estimate the burden of cardiovascular diseases (CVD); however, it is not clear whether mortality measurements are eligible for incidence estimations. MethodsWe performed eight cohort studies from 1990 to 2010 in Japan, which consisted of total 94,657 residents aged 40–59years who were followed-up for a median of 18.5years. Incidence and mortality rates for coronary heart disease (CHD) and stroke events were ascertained. Sex-specified incidence rates were regressed to the mortality rates, adjusting for differences in community and age group. Further, incidence-to-mortality rate ratios were estimated using the Poisson regression with random intercepts. ResultsCHD or stroke mortality rates were highly associated with incidence rates in communities. Incidence-to-mortality rate ratios were 2.06 (95% confidence interval, 1.56–2.73) in men and 1.41 (1.01–1.95) in women for CHD; and 3.99 (3.32–4.80) in men and 4.44 (3.73–5.29) in women for stroke. There were no significant geographical variations in the ratio among the 8 areas. ConclusionsWe determined that it is possible to estimate CHD and stroke occurrences in the population from their mortality rates reported in vital statistics. Accordingly, we should pay attention to the communities in which mortality rates due to CHD or stroke reported in vital statistics are higher, and promote CVD prevention positively.

Development of a Risk Equation for the Incidence of Coronary Artery Disease and Ischemic Stroke for Middle-Aged Japanese　- Japan Public Health Center-Based Prospective Study.

Global risk assessment for the prevention of atherosclerotic cardiovascular diseases helps guide the intensity of behavioral and pharmacological interventions. The Japan Public Health Center-based prospective (JPHC) Study Cohort II (age range: 40-69 years at baseline in 1993-1994, n=15,672) was used to derive the risk equations for coronary artery disease (CAD) and ischemic stroke incidence via hazard regression. The model discrimination was evaluated by the area under the receiver-operating curve (AUC), and model goodness-of-fit by the Grønnesby-Borgan chi-squared statistic. During a mean of 16.4 years of follow up, 192 incident CAD cases and 552 ischemic stroke cases occurred. Variables selected for the CAD equation were age, sex, current smoking, systolic blood pressure, antihypertensive medication use, diabetes, and high-density lipoprotein cholesterol (HDLC) and non-HDLC. The same variables, except non-HDLC, were selected for the ischemic stroke equation. The equations discriminated incidence reasonably well (AUC: 0.81 for CAD, 0.78 for ischemic stroke). The AUC of the equation applied externally to Cohort I (n=11,598) was also good: 0.77 and 0.76 for CAD and ischemic stroke, respectively. Risk calculator application and color charts to visualize estimated risk according to the combinations of risk factors were prepared. Risk equations were developed to estimate the 10-year probability of CAD and ischemic stroke in Japanese people, using variables that are routinely obtained. (Circ J 2016; 80: 1386-1395).