The Hisayama Study is a population-based prospective cohort study designed to evaluate the risk factors for lifestyle-related diseases, such as stroke, coronary heart disease, hypertension, diabetes, ...and dementia, in a general Japanese population. The prospective follow-up surveys have been conducted in subjects aged 40 or older since 1961. Notable characteristics of this study include its high participation rate (70-80% of all residents aged 40 or older), high follow-up rate (99% or over), and high autopsy rate (approximately 75% of deceased cases). The Hisayama Study has provided valuable evidence of secular change in the prevalence and incidence of several lifestyle-related disease and their risk factors. The study has thereby contributed to elucidation of the preventive strategies for lifestyle-related disease. Research efforts in this cohort are ongoing and will provide additional data for the improvement of human health and longevity.
Growing epidemiological evidence has suggested that subjects with diabetes mellitus are at an increased risk for the development of dementia. However, the results for the subtypes of dementia are ...inconsistent. This review examined the risk of dementia in subjects with diabetes mellitus and discusses the possible mechanism underlying this association. Diabetes mellitus is associated with a 1.5- to 2.5-fold greater risk of dementia among community-dwelling elderly people. Notably, diabetes mellitus is a significant risk factor for not only vascular dementia but also Alzheimer's disease. The mechanisms underlying the association are unclear, but it may be multifactorial in nature, involving factors such as cardiovascular risk factors, glucose toxicity, changes in insulin metabolism, and inflammation. The optimal management of these risk factors in early life may be important to prevent future dementia. Furthermore, novel therapeutic strategies will be needed to prevent or reduce the development of dementia in subjects with diabetes mellitus.
Diabetes mellitus and cancer are diseases of epidemic proportions across the globe. These diseases are influenced by many factors, both genetic and environmental. A possible association between ...diabetes and cancer risk has long been speculated. Increased incidence of several cancers has been observed in diabetes patients, notably pancreatic, hepatic, colorectal, breast, urinary tract, and endometrial cancers. In contrast, a decreased incidence of prostate cancer is observed in diabetes patients, implying a protective effect. Precise knowledge of the complex associations and interactions between these two conditions is of great importance for their prevention and treatment. Multiple potential mechanisms have been proposed, but they have tended to be site‐specific. Possible common mechanisms for a biological link between diabetes and cancer include hyperinsulinemia, hyperglycemia, and inflammation. Today, 366 million people live with diabetes globally, and this figure is expected to increase. Thus, if diabetes is associated with even a small increase in cancer risk, this may have important consequences at the population level. The aim of this review is to summarize recent epidemiological evidence of an association between diabetes and total cancer and specific sites of cancer, and to consider causal associations between these diseases. (Cancer Sci 2013; 104: 9–14)
Summary Chronic kidney disease, defined as a reduced glomerular filtration rate or increased urinary albumin excretion, is recognised as a rapidly growing global health burden, and increasing ...evidence suggests that it contributes to the risk and severity of cerebrovascular diseases. In particular, chronic kidney disease is an established risk factor for stroke and is also strongly associated with subclinical cerebrovascular abnormalities and cognitive impairment, partly because it shares several traditional and non-traditional risk factors, and sometimes uraemia-related and dialysis-related factors, with cerebrovascular diseases. The effect of chronic kidney disease on incident stroke differs among regions and races and is greater in Asian than in non-Asian people. Chronic kidney disease seems to be predictive of severe neurological deficits and poor vital and functional outcomes after both ischaemic and haemorrhagic strokes, which is partly due to the limitations of pharmacotherapies, including limited use and effects of novel oral anticoagulants, other antithrombotic treatments, and reperfusion treatment for hyperacute ischaemic stroke. In view of the strong two-way association between stroke and kidney disease, the pathophysiological interactions between the brain and kidney should be the subject of intensive study.
Summary Background End-stage kidney disease is a leading cause of morbidity and mortality worldwide. Prevalence of the disease and worldwide use of renal replacement therapy (RRT) are expected to ...rise sharply in the next decade. We aimed to quantify estimates of this burden. Methods We systematically searched Medline for observational studies and renal registries, and contacted national experts to obtain RRT prevalence data. We used Poisson regression to estimate the prevalence of RRT for countries without reported data. We estimated the gap between needed and actual RRT, and projected needs to 2030. Findings In 2010, 2·618 million people received RRT worldwide. We estimated the number of patients needing RRT to be between 4·902 million (95% CI 4·438–5·431 million) in our conservative model and 9·701 million (8·544–11·021 million) in our high-estimate model, suggesting that at least 2·284 million people might have died prematurely because RRT could not be accessed. We noted the largest treatment gaps in low-income countries, particularly Asia (1·907 million people needing but not receiving RRT; conservative model) and Africa (432 000 people; conservative model). Worldwide use of RRT is projected to more than double to 5·439 million (3·899–7·640 million) people by 2030, with the most growth in Asia (0·968 million to a projected 2·162 million 1·571–3·014 million). Interpretation The large number of people receiving RRT and the substantial number without access to it show the need to both develop low-cost treatments and implement effective population-based prevention strategies. Funding Australian National Health and Medical Research Council.
Summary Background Recent hypertension guidelines have reversed previous recommendations for lower blood pressure targets in high-risk patients, such as those with cardiovascular disease, renal ...disease, or diabetes. This change represents uncertainty about whether more intensive blood pressure-lowering strategies are associated with greater reductions in risk of major cardiovascular and renal events. We aimed to assess the efficacy and safety of intensive blood pressure-lowering strategies. Methods For this updated systematic review and meta-analysis, we systematically searched MEDLINE, Embase, and the Cochrane Library for trials published between Jan 1, 1950, and Nov 3, 2015. We included randomised controlled trials with at least 6 months' follow-up that randomly assigned participants to more intensive versus less intensive blood pressure-lowering treatment, with different blood pressure targets or different blood pressure changes from baseline. We did not use any age or language restrictions. We did a meta-analysis of blood pressure reductions on relative risk (RR) of major cardiovascular events (myocardial infarction, stroke, heart failure, or cardiovascular death, separately and combined), and non-vascular and all-cause mortality, end-stage kidney disease, and adverse events, as well as albuminuria and progression of retinopathy in trials done in patients with diabetes. Findings We identified 19 trials including 44 989 participants, in whom 2496 major cardiovascular events were recorded during a mean 3·8 years of follow-up (range 1·0–8·4 years). Our meta-analysis showed that after randomisation, patients in the more intensive blood pressure-lowering treatment group had mean blood pressure levels of 133/76 mm Hg, compared with 140/81 mm Hg in the less intensive treatment group. Intensive blood pressure-lowering treatment achieved RR reductions for major cardiovascular events (14% 95% CI 4–22), myocardial infarction (13% 0–24), stroke (22% 10–32), albuminuria (10% 3–16), and retinopathy progression (19% 0–34). However, more intensive treatment had no clear effects on heart failure (15% 95% CI −11 to 34), cardiovascular death (9% –11 to 26), total mortality (9% –3 to 19), or end-stage kidney disease (10% –6 to 23). The reduction in major cardiovascular events was consistent across patient groups, and additional blood pressure lowering had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. The absolute benefits were greatest in trials in which all enrolled patients had vascular disease, renal disease, or diabetes. Serious adverse events associated with blood pressure lowering were only reported by six trials and had an event rate of 1·2% per year in intensive blood pressure-lowering group participants, compared with 0·9% in the less intensive treatment group (RR 1·35 95% CI 0·93–1·97). Severe hypotension was more frequent in the more intensive treatment regimen (RR 2·68 1·21–5·89, p=0·015), but the absolute excess was small (0·3% vs 0·1% per person-year for the duration of follow-up). Interpretation Intensive blood pressure lowering provided greater vascular protection than standard regimens. In high-risk patients, there are additional benefits from more intensive blood pressure lowering, including for those with systolic blood pressure below 140 mmHg. The net absolute benefits of intensive blood pressure lowering in high-risk individuals are large. Funding National Health and Medical Research Council of Australia.
The Hisayama Study is an ongoing epidemiological study of stroke, coronary artery disease (CAD), and other noncommunicable diseases in a general Japanese population established in 1961. According to ...the longitudinal data from the Hisayama Study, average levels of systolic blood pressure among hypertensive individuals have decreased with time since 1961. In contrast, the prevalence of metabolic risk factors such as obesity, hypercholesterolemia, and glucose intolerance has increased with time. The incidence rates of ischemic stroke in this population have declined significantly as a result of improvement in hypertension management, but the proportion of atherothrombotic brain infarction (ATBI) and embolic stroke among the total ischemic stroke cases have increased probably due to the increased prevalence of metabolic risk factors and the increased number of patients with atrial fibrillation (AF) with super-aging population. Therefore, a strategy to reduce the risks of ATBI and embolic stroke by comprehensive management of their risk factors is necessary.In this review, we first show the secular trends in the incidence of stroke and the prevalence of its risk factors using the data from the Hisayama Study. Then, the studies for the association of traditional risk factors with stroke development in the Hisayama Study are introduced. Finally, we developed risk prediction models to estimate the absolute risk of atherosclerotic cardiovascular disease (ASCVD; including ATBI and CAD) and AF, that may be used for the stratification of future risk of ATBI and AF-related stroke in clinical practice or health examination.
The BioBank Japan (BBJ) Project was launched in 2003 with the aim of providing evidence for the implementation of personalized medicine by constructing a large, patient-based biobank (BBJ). This ...report describes the study design and profile of BBJ participants who were registered during the first 5-year period of the project.
The BBJ is a registry of patients diagnosed with any of 47 target common diseases. Patients were enrolled at 12 cooperative medical institutes all over Japan from June 2003 to March 2008. Clinical information was collected annually via interviews and medical record reviews until 2013. We collected DNA from all participants at baseline and collected annual serum samples until 2013. In addition, we followed patients who reported a history of 32 of the 47 target diseases to collect survival data, including cause of death.
During the 5-year period, 200,000 participants were registered in the study. The total number of cases was 291,274 at baseline. Baseline data for 199,982 participants (53.1% male) were available for analysis. The average age at entry was 62.7 years for men and 61.5 years for women. Follow-up surveys were performed for participants with any of 32 diseases, and survival time data for 141,612 participants were available for analysis.
The BBJ Project has constructed the infrastructure for genomic research for various common diseases. This clinical information, coupled with genomic data, will provide important clues for the implementation of personalized medicine.
•The BioBank Japan Project (BBJ) enrolled 200,000 patients with 47 target diseases.•The BBJ is one of the largest patient-based biobanks in the world.•The BBJ may allow for personalized medicine in the future.
Aims: This study aims to investigate the association between serum small dense low-density lipoprotein (sdLDL) cholesterol level and the development of coronary heart disease (CHD) in a Japanese ...community. Methods: A total of 3,080 participants without prior cardiovascular disease, aged 40 years or older, were followed up for 8 years. The participants were divided into the quartiles of serum sdLDL cholesterol levels. The risk estimates were computed using a Cox proportional hazards model. Results: During the follow-up period, 79 subjects developed CHD. Subjects in the highest quartile had a 5.41- fold (95% confidence interval, 2.12–13.82) higher risk of CHD than those in the lowest quartile after controlling for confounders. In the analysis classifying the participants into four groups according to the levels of serum sdLDL cholesterol and serum low-density lipoprotein (LDL) cholesterol levels, the risk of CHD almost doubled in subjects with sdLDL cholesterol of ≥ 32.9 mg/dL (median), regardless of serum LDL cholesterol levels, as compared with subjects with serum sdLDL cholesterol of ＜32.9 mg/dL and serum LDL cholesterol of ＜120.1 mg/dL (median). When serum sdLDL cholesterol levels were incorporated into a model with known cardiovascular risk factors, c-statistics was significantly increased (from 0.77 to 0.79; p=0.02), and the net reclassification improvement was also significant (0.40; p＜0.001). Conclusions: The present findings suggest that the serum sdLDL cholesterol level is a relevant biomarker for the future development of CHD that offers benefit beyond the serum LDL cholesterol level and a possible therapeutic target to reduce the burden of CHD in a Japanese community.
Aim:To develop and validate a new risk prediction model for predicting the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in Japanese adults. Methods: A total of 2,454 participants ...aged 40–84 years without a history of cardiovascular disease (CVD) were prospectively followed up for 24 years. An incident ASCVD event was defined as the first occurrence of coronary heart disease or atherothrombotic brain infarction. A Cox proportional hazards regression model was used to construct the prediction model. In addition, a simplified scoring system was translated from the developed prediction model. The model performance was evaluated using Harrell’s C statistics, a calibration plot with the Greenwood-Nam-D’Agostino test, and a bootstrap validation procedure. Results: During a median of a 24-year follow-up, 270 participants experienced the first ASCVD event. The predictors of the ASCVD events in the multivariable Cox model included age, sex, systolic blood pressure, diabetes, serum high-density lipoprotein cholesterol, serum low-density lipoprotein cholesterol, proteinuria, smoking habits, and regular exercise. The developed models exhibited good discrimination with negligible evidence of overfitting (Harrell’s C statistics: 0.786 for the multivariable model and 0.789 for the simplified score) and good calibrations (the Greenwood-Nam-D’Agostino test: P=0.29 for the multivariable model, 0.52 for the simplified score). Conclusion: We constructed a risk prediction model for the development of ASCVD in Japanese adults. This prediction model exhibits great potential as a tool for predicting the risk of ASCVD in clinical practice by enabling the identification of specific risk factors for ASCVD in individual patients.
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