High-sensitivity C reactive protein as a predictor of inhospital mortality in patients with cardiovascular disease at an emergency department: a retrospective cohort study.

OBJECTIVE: We investigated whether serum high-sensitivity C reactive protein (hs-CRP) levels measured in an emergency department (ED) are associated with inhospital mortality in patients with cardiovascular disease (CVD). DESIGN: A retrospective cohort study. SETTING: ED of a teaching hospital in Japan. PARTICIPANTS: 12 211 patients with CVD aged ≥18 years who presented to the ED by an ambulance between 1 February 2006 and 30 September 2014 were evaluated. MAIN OUTCOME MEASURES: Inhospital mortality. RESULTS: 1156 patients had died. The inhospital mortality increased significantly with the hs-CRP levels (<3.0 mg/L: 7.0%, 95% CI 6.4 to 7.6; 3.1-5.4 mg/L: 9.6%, 95% CI 7.9 to 11.3: 5.5-11.5 mg/L: 11.2%, 95% CI 9.4 to 13.0; 11.6-33.2 mg/L: 12.3%, 95% CI 10.5 to 14.1 and ≥33.3 mg/L: 19.9%, 95% CI 17.6 to 22.2). The age-adjusted and sex-adjusted HR for total mortality was increased significantly in the three ≥5.5 mg/L groups compared with the <3.0 mg/L group (5.5-11.5 mg/L: HR=1.32, 95% CI 1.09 to 1.60, p=0.005; 11.6-33.2 mg/L: HR=1.38, 95% CI 1.14 to 1.65, p=0.001 and ≥33.3 mg/L: HR=2.15, 95% CI 1.84 to 2.51, p<0.001). Similar findings were observed for the CVD subtypes of acute myocardial infarction, heart failure, cerebral infarction and intracerebral haemorrhage. This association remained unchanged even after adjustment for age, sex and white cell count and withstood Bonferroni adjustment for multiple testing. When the causes of death were divided into primary CVD and non-CVD deaths, the association between initial hs-CRP levels and mortality remained significant, but the influence of hs-CRP levels was greater in non-CVD deaths than CVD deaths. The percentage of non-CVD deaths increased with hs-CRP levels; among the patients with hs-CRP levels ≥33.3 mg/L, non-CVD deaths accounted for 37.5% of total deaths. CONCLUSION: Our findings suggest that increased hs-CRP is a significant risk factor for inhospital mortality among patients with CVD in an ED. Particular attention should be given to our finding that non-CVD death is a major cause of death among patients with CVD with higher hs-CRP levels.

Trends in the prevalence of type 2 diabetes and prediabetes in community-dwelling Japanese subjects: The Hisayama Study.

AIMS/INTRODUCTION: We examined secular trends in the prevalence of type 2 diabetes and prediabetes in community-dwelling Japanese subjects. MATERIALS AND METHODS: A total of 2,490 subjects in 1988 and 2,852 subjects in 2002 aged 40-79 years underwent a 75-g oral glucose tolerance test, and their glucose tolerance status was defined by the 1998 World Health Organization criteria. RESULTS: The age-adjusted prevalence of type 2 diabetes increased significantly from 1988 to 2002 in men (14.6% in 1988 to 20.8% in 2002, P < 0.001) and women (9.1% in 1988 to 11.2% in 2002, P = 0.002). A significant rise in the age-adjusted prevalence of prediabetes was also observed in both sexes (26.2% in 1988 to 35.3% in 2002, P < 0.001 for men; 22.5% in 1988 to 25.1% in 2002, P = 0.04 for women). In age-stratified analysis, the prevalence of type 2 diabetes increased markedly over time in men aged 60-69 and 70-79 years (both P < 0.001) and women aged 70-79 years (P = 0.02). The prevalence of overall and central obesity increased significantly in men aged 60-69 and 70-79 years, and women aged 70-79 years from 1988 to 2002, whereas the frequency of regular exercise decreased significantly in men aged 70-79 years between the surveys. CONCLUSIONS: Our findings suggest that the prevalence of type 2 diabetes and prediabetes increased significantly in both sexes from the 1980s to the 2000s in a general Japanese population, and that the increasing prevalence of obesity and the decline in physical activity exerted an influence on this rising trend.

Role of endothelial cell-derived angptl2 in vascular inflammation leading to endothelial dysfunction and atherosclerosis progression.

OBJECTIVE: Cardiovascular disease (CVD), the most common morbidity resulting from atherosclerosis, remains a frequent cause of death. Efforts to develop effective therapeutic strategies have focused on vascular inflammation as a critical pathology driving atherosclerosis progression. Nonetheless, molecular mechanisms underlying this activity remain unclear. Here, we ask whether angiopoietin-like protein 2 (Angptl2), a proinflammatory protein, contributes to vascular inflammation that promotes atherosclerosis progression. APPROACH AND RESULTS: Histological analysis revealed abundant Angptl2 expression in endothelial cells and macrophages infiltrating atheromatous plaques in patients with cardiovascular disease. Angptl2 knockout in apolipoprotein E-deficient mice (ApoE(-/-)/Angptl2(-/-)) attenuated atherosclerosis progression by decreasing the number of macrophages infiltrating atheromatous plaques, reducing vascular inflammation. Bone marrow transplantation experiments showed that Angptl2 deficiency in endothelial cells attenuated atherosclerosis development. Conversely, ApoE(-/-) mice crossed with transgenic mice expressing Angptl2 driven by the Tie2 promoter (ApoE(-/-)/Tie2-Angptl2 Tg), which drives Angptl2 expression in endothelial cells but not monocytes/macrophages, showed accelerated plaque formation and vascular inflammation because of increased numbers of infiltrated macrophages in atheromatous plaques. Tie2-Angptl2 Tg mice alone did not develop plaques but exhibited endothelium-dependent vasodilatory dysfunction, likely because of decreased production of endothelial cell-derived nitric oxide. Conversely, Angptl2(-/-) mice exhibited less severe endothelial dysfunction than did wild-type mice when fed a high-fat diet. In vitro, Angptl2 activated proinflammatory nuclear factor-κB signaling in endothelial cells and increased monocyte/macrophage chemotaxis. CONCLUSIONS: Endothelial cell-derived Angptl2 accelerates vascular inflammation by activating proinflammatory signaling in endothelial cells and increasing macrophage infiltration, leading to endothelial dysfunction and atherosclerosis progression.

Non-high-density lipoprotein cholesterol and the development of coronary heart disease and stroke subtypes in a general Japanese population: the Hisayama Study.

BACKGROUND AND PURPOSE: It has not been fully determined whether non-high-density lipoprotein cholesterol (non-HDLC) levels are involved in vascular events, especially stroke, in general Asian populations. We evaluated the association between non-HDLC levels and the risk of type-specific cardiovascular disease in a prospective cohort study in Japan. METHODS: A total of 2452 community-dwelling Japanese subjects aged≥40 years were followed prospectively for 24 years. RESULTS: The age- and sex-adjusted incidence of coronary heart diseases (CHD) significantly increased with elevating non-HDLC levels (P for trend<0.001), but no such association was observed for ischemic and hemorrhagic strokes. With regard to ischemic stroke subtypes, the age- and sex-adjusted incidence of lacunar infarction significantly increased with elevating non-HDLC levels (P for trend<0.01), and such tendency was seen for atherothrombotic infarction (P for trend=0.098), while a significant inverse association was observed for cardioembolic infarction (P for trend=0.007). After adjustment for confounders, namely, age, sex, diabetes, body mass index, systolic blood pressure, electrocardiogram abnormalities, current drinking, current smoking, and regular exercise, the associations remained significant for CHD [adjusted hazard ratio (HR) for a 1 standard deviation of non-HDLC concentrations=1.17, 95% confidence interval (CI)=1.02 to 1.35], atherothrombotic infarction (adjusted HR=1.39, 95% CI=1.09 to 1.79), and cardioembolic infarction (adjusted HR=0.64, 95% CI=0.47 to 0.85). CONCLUSIONS: Our findings suggest that elevated non-HDLC levels are a significant risk factor for the development of atherothrombotic infarction as well as CHD but reduce the risk of cardioembolic infarction in the general Japanese population.

Haemoglobin A1c even within non-diabetic level is a predictor of cardiovascular disease in a general Japanese population: the Hisayama Study.

BACKGROUND: There is little information about predictive ability of haemoglobin A1c (HbA1c) for cardiovascular disease (CVD) in Asians. To investigate the discriminatory ability of HbA1c to identify subjects who are at greater risk of developing CVD in a prospective study of a defined community-dwelling Japanese population. METHODS: A total of 2,851 subjects aged 40-79 years were stratified into five groups (HbA1c levels with ≤ 5.0, 5.1-5.4, 5.5-6.4, and ≥ 6.5% and a group with antidiabetic medication) and followed up prospectively for 7 years (2002-2009). RESULTS: During the follow-up, 119 subjects developed CVD. The multivariable-adjusted risk of CVD was significantly increased in subjects with HbA1c levels of 5.5-6.4 and ≥ 6.5% and diabetic medication compared to HbA1c level with ≤ 5.0% (hazard ratio, 2.26 [95% confidence interval, 1.29-3.95] for the 5.5-6.4%; 4.43 [2.09-9.37] for the ≥ 6.5%; and 5.15 [2.65-10.0] for the antidiabetic medication group). With regard to CVD subtype, the positive associations between HbA1c levels and the risk of coronary heart disease (CHD) and ischaemic stroke were also significant, but no such associations were seen for haemorrhagic stroke. The C statistic for developing CVD was significantly increased by adding HbA1c values to the model including other risk factors (0.789 vs. 0762, p = 0.006), and the net reclassification improvement was 0.105 (p = 0.004). CONCLUSIONS: Our findings suggest that elevated HbA1c levels are an independent risk factor for CVD, especially CHD and ischaemic stroke, and that the addition of HbA1c to the model with traditional risk factors significantly improves the predictive ability of CVD.

Elevated depressive symptoms in metabolic syndrome in a general population of Japanese men: a cross-sectional study.

BACKGROUND: Uncertainty still surrounds the association between metabolic syndrome (MetS) and depression. We aimed to evaluate the association between MetS and elevated depressive symptoms in a general Japanese population. METHODS: This is a cross-sectional survey of 3,113 community-dwelling individuals aged 40 years or over. MetS was defined according to the joint interim statement. MetS was diagnosed when a subject had three or more of the following components: 1) central obesity (waist circumference ≥ 90 cm for men, ≥ 80 cm in for women); 2) elevated blood pressure (≥ 130/85 mmHg or current use of antihypertensive medication); 3) hypertriglyceridemia (≥ 1.7 mmol/L); 4) low HDL cholesterol (< 1.0 mmol/L for men, < 1.3 mmol/L for women); and 5) elevated fasting plasma glucose (≥ 5.55 mmol/L or current use of antidiabetic medication). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). The age- and multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using a logistic regression model. RESULTS: Elevated depressive symptoms were observed in 4.3% of male and 6.3% of female participants. In men, the age-adjusted prevalence of elevated depressive symptoms was significantly higher in subjects with MetS than in those without (7.1% versus 3.6%, p = 0.04). The prevalence of elevated depressive symptoms rose progressively as the number of MetS components increased (3.5%, 3.6%, 5.8%, and 9.2% in male subjects with 0-1, 2, 3, and ≥ 4 components, respectively; p = 0.02 for trend). This association remained significant even after adjustment for age, marital status, history of cardiovascular disease, smoking habit, alcohol intake, and regular exercise. In women, on the other hand, there was no clear association between MetS and depressive symptoms. CONCLUSIONS: MetS was associated with elevated depressive symptoms in a general population of Japanese men.

Angiopoietin-like protein 2 is associated with chronic kidney disease in a general Japanese population: the Hisayama Study.

BACKGROUND: Angiopoietin-like protein 2 (Angptl2) is an adipokine that promotes inflammation and endothelial dysfunction of the vessels. The aim of this study was to investigate the relationship between serum Angptl2 level and chronic kidney disease (CKD). METHODS AND RESULTS: A total of 3,169 community-dwelling subjects aged ≥40 years were divided into quintiles by Angptl2 level. CKD was defined as the presence of albuminuria (urine albumin-creatinine ratio ≥30.0mg/g) or decreased estimated glomerular filtration rate (eGFR <60ml·min(-1)·1.73m(-2)). The odds ratio (OR) for the presence of CKD was calculated using a logistic regression model. The overall prevalence of CKD was 37.5%. The age- and sex-adjusted ORs for the presence of CKD increased with higher serum Angptl2 level. This trend remained significant after adjusting for known cardiovascular risk factors (<2.01ng/ml: OR, 1.00 (reference); 2.01-2.48ng/ml: OR, 1.67, 95% confidence interval [CI]: 1.24-2.24; 2.49-2.99ng/ml: OR, 1.70, 95% CI: 1.27-2.28; 3.00-3.65ng/ml: OR, 1.78, 95% CI: 1.32-2.39; ≥3.66ng/ml: OR, 1.79, 95% CI: 1.32-2.43; P-value for trend=0.001). Multivariate-adjusted ORs for the presence of albuminuria increased significantly with elevated serum Angptl2 (P-value for trend=0.004), while there was no evidence of a significant relationship between serum Angptl2 level and decreased eGFR (P-value for trend=0.08). CONCLUSIONS: Elevated serum Angptl2 is associated with the likelihood of CKD in the general population.

White-coat and masked hypertension are associated with carotid atherosclerosis in a general population: the Hisayama study.

BACKGROUND AND PURPOSE: On the basis of combined measurements of clinic blood pressure (CBP) and home blood pressure (HBP), blood pressure status can be divided into normotension, white-coat hypertension (WCHT), masked hypertension (MHT), and sustained hypertension (SHT). Despite the clear impact of MHT and SHT on clinical and subclinical arterial disease, uncertainty about the influence of WCHT remains. The objective of this study was to investigate the associations of WCHT, MHT, and SHT with carotid atherosclerosis in a general population. METHODS: This is a cross-sectional survey of 2915 community-dwelling Japanese aged ≥ 40 years. Normotension was defined as CBP<140/90 and HBP<135/85 mm Hg; WCHT, CBP ≥ 140/90 and HBP<135/85 mm Hg; MHT, CBP<140/90 and HBP ≥ 135/85 mm Hg; and SHT, CBP ≥ 140/90 and HBP ≥ 135/85 mm Hg. Mean intima-media thickness of carotid arteries was measured using a computer-automated system, and carotid stenosis was defined as diameter stenosis ≥ 30%. RESULTS: There were 1374 subjects (47.1%) with normotension, 200 (6.9%) with WCHT, 639 (21.9%) with MHT, and 702 (24.1%) with SHT. The geometric average of mean intima-media thickness was significantly higher among subjects with WCHT (0.73 mm), MHT (0.77 mm), and SHT (0.77 mm) than those with normotension (0.67 mm; all P<0.001 versus normotension). Compared with normotension, all types of hypertension were also associated with increased likelihood of carotid stenosis (age- and sex-adjusted odds ratio, 2.36 [95% confidence interval, 1.27-4.37] for WCHT, 1.95 [1.25-3.03] for MHT, and 3.02 [2.01-4.54] for SHT). These associations remained significant even after adjustment for other cardiovascular risk factors. CONCLUSIONS: WCHT, as well as MHT, and SHT were associated with carotid atherosclerosis in a general Japanese population.

Temporal trends in sudden unexpected death in a general population: the Hisayama study.

BACKGROUND: Studies addressing the temporal trends in the prevalence of sudden unexpected death (SUD) and its underlying causes in the general population are limited. METHODS: Among a total of 1934 residents aged ≥20 years of the town of Hisayama, Japan, who died of endogenous causes of death and underwent autopsy examination (autopsy rate 78.5%) from 1962 to 2009, 204 were determined to be cases of SUD within 24 hours. RESULTS: The trend in the age- and sex-adjusted prevalence of SUD among all autopsy subjects was stable over four 12-year periods (13.1% in 1962-1973, 13.4% in 1974-1985, 15.0% in 1986-1997, and 14.6% in 1998-2009; P for trend = .80). Regarding causes of death, the prevalence of SUD from stroke significantly declined with time (8.0%, 5.0%, 2.3%, and 2.1%, respectively; P for trend < .001), whereas significant increments were observed in the prevalence of SUD from heart disease (4.0%, 6.2%, 8.6%, and 9.7%; P for trend = .02) and from aortic aneurysm and dissection (0.2%, 1.2%, 2.9%, and 2.8%; P for trend = .01). In particular, the prevalence of ischemic heart disease increased 3-fold from 2.1% in 1962-1973 to 6.6% in 1998-2009 (P = .04). Reflecting the increment of ischemic heart disease, SUD within 1 hour increased significantly from 2.5% to 7.6% during this period (P = .01). CONCLUSIONS: The trend in the prevalence of SUD was stable across a half century in a general Japanese population. Despite the decrement in the prevalence of SUD from stroke, that from heart disease, especially ischemic heart disease, increased significantly with time.

Brachial-ankle pulse wave velocity predicts the development of cardiovascular disease in a general Japanese population: the Hisayama Study.

OBJECTIVE: We examined the relationship between brachial-ankle pulse wave velocity and the development of cardiovascular disease in a general Japanese population. METHODS: A total of 2916 community-dwelling Japanese individuals without history of cardiovascular disease aged at least 40 years were followed up for an average of 7.1 years, and the relationship between brachial-ankle pulse wave velocity and the cardiovascular risk was estimated using the Cox proportional hazards model. To compare the accuracy of the risk assessment for cardiovascular events between the models adjusted for known cardiovascular risk factors with and without brachial-ankle pulse wave velocity, the area under the receiver-operating characteristic curve and net reclassification improvement were computed. RESULTS: During the follow-up period, 126 patients experienced cardiovascular events. Age and sex-adjusted incidence rates of cardiovascular disease increased linearly with elevating brachial-ankle pulse wave velocity levels (P for trend <0.001). After adjusting for confounding factors, every 20% increment in brachial-ankle pulse wave velocity was associated with a 1.30-fold [95% confidential interval (CI) 1.10-1.53] greater cardiovascular risk. When brachial-ankle pulse wave velocity was incorporated into a model with known cardiovascular risk factors, the area under the receiver-operating characteristic curve was significantly increased (0.776 vs. 0.760; P = 0.01), and the net reclassification improvement was 0.085 (P = 0.008). CONCLUSIONS: Our findings suggest that brachial-ankle pulse wave velocity is a significant predictive factor for cardiovascular disease in the general Japanese population and that information on brachial-ankle pulse wave velocity substantially improves cardiovascular risk assessment beyond that achieved by a model based on potential risk factors in general practice.

Dietary patterns and risk of dementia in an elderly Japanese population: the Hisayama Study.

BACKGROUND: To our knowledge, there are no previous reports that assessed the association between dietary patterns and risk of dementia in Asian populations. OBJECTIVE: We investigated dietary patterns and their potential association with risk of incident dementia in a general Japanese population. DESIGN: A total of 1006 community-dwelling Japanese subjects without dementia, aged 60-79 y, were followed up for a median of 15 y. The reduced rank regression procedure was used to efficiently determine their dietary patterns. Estimated risk conferred by a particular dietary pattern on the development of dementia was computed by using a Cox proportional hazards model. RESULTS: Seven dietary patterns were extracted; of these, dietary pattern 1 was correlated with high intakes of soybeans and soybean products, vegetables, algae, and milk and dairy products and a low intake of rice. During the follow-up, 271 subjects developed all-cause dementia. Of these individuals, 144 subjects had Alzheimer disease (AD), and 88 subjects had vascular dementia (VaD). After adjustment for potential confounders, risks of development of all-cause dementia, AD, and VaD were reduced by 0.66 (95% CI: 0.46, 0.95), 0.65 (95% CI: 0.40, 1.06), and 0.45 (95% CI: 0.22, 0.91), respectively, in subjects in the highest quartile of score for dietary pattern 1 compared with subjects in the lowest quartile. CONCLUSION: Our findings suggest that a higher adherence to a dietary pattern characterized by a high intake of soybeans and soybean products, vegetables, algae, and milk and dairy products and a low intake of rice is associated with reduced risk of dementia in the general Japanese population.

Angiopoietin-like protein 2 and risk of type 2 diabetes in a general Japanese population: the Hisayama study.

OBJECTIVE: To examine, for the first time, the association between a novel inflammatory cytokine, angiopoietin-like protein (ANGPTL) 2, and the development of type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS: A total of 2,164 community-dwelling Japanese individuals aged 40 to 79 years without diabetes were followed up for 7 years. Serum ANGPTL2 levels were divided into quartile categories at baseline: <2.15, 2.16-2.71, 2.72-3.40, and ≥3.41 ng/mL. During follow-up, 221 participants developed T2DM. RESULTS: In multivariate analyses, after adjusting for comprehensive risk factors and high-sensitivity C-reactive protein (hs-CRP) levels, the risk of developing T2DM was significantly higher in the highest ANGPTL2 quartile than in the lowest quartile (hazard ratio, 1.80; 95% CI, 1.14-2.85; P = 0.01). CONCLUSIONS: Elevated serum ANGPTL2 levels were positively associated with the development of T2DM in a general population, independent of other risk factors including hs-CRP levels.

Impact of sleep duration on obesity and the glycemic level in patients with type 2 diabetes: the Fukuoka Diabetes Registry.

OBJECTIVE: Few studies are currently available regarding the influence of sleep duration on glycemic control in diabetic patients. The objective of the current study was to examine the relationship between sleep duration, obesity, and the glycemic level in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 4,870 Japanese type 2 diabetic patients aged ≥20 years were divided into six groups according to their self-reported sleep duration: less than 4.5 h, 4.5-5.4 h, 5.5-6.4 h, 6.5-7.4 h, 7.5-8.4 h, and more than 8.5 h. The associations of sleep duration with obesity and the HbA(1c) levels were examined in a cross-sectional manner. RESULTS: The HbA(1c) levels showed a quadratic association with sleep duration; namely, a shorter or longer sleep duration was associated with a higher level compared with a sleep duration of 6.5-7.4 h (P for quadratic trend <0.001). This association remained significant after adjusting for potential confounders, including the total energy intake and depressive symptoms. Furthermore, additional adjustments for obesity, which also showed a U-shaped relationship with sleep duration, did not attenuate the U-shaped sleep-HbA(1c) association. A significant interaction between sleep duration and age or the use of insulin was observed for the HbA(1c) levels. CONCLUSIONS: Sleep duration was shown to have U-shaped associations with obesity and the HbA(1c) levels in type 2 diabetic patients, independent of potential confounders, and therefore may be an important modifiable factor for the clinical management of patients with type 2 diabetes.

Association between glucose tolerance level and cancer death in a general Japanese population: the Hisayama Study.

The authors examined the associations of glucose tolerance status and fasting and 2-hour postload glucose levels with the risk of cancer death in a 19-year follow-up study of 2,438 Japanese subjects aged 40-79 years who underwent a 75-g oral glucose tolerance test (1988-2007). During follow-up, 229 subjects died of cancer. The risk of cancer death was significantly higher in subjects with fasting plasma glucose levels of ≥5.6 mmol/L or 2-hour postload glucose levels of ≥11.1 mmol/L than in those with the lowest fasting or 2-hour postload glucose levels, after adjustment for potentially confounding factors. According to glucose tolerance status, not only diabetes but also impaired fasting glycemia and impaired glucose tolerance were significant risk factors for cancer death (for impaired fasting glycemia, multivariable-adjusted hazard ratio (HR) = 1.49 (95% confidence interval (CI): 1.05, 2.11); for impaired glucose tolerance, HR = 1.52 (95% CI: 1.05, 2.22); and for diabetes, HR = 2.10 (95% CI: 1.41, 3.12)). With regard to site-specific cancers, elevated fasting or 2-hour postload glucose levels were associated with the risks of death from stomach, liver, and lung cancer. These findings suggest that both prediabetic hyperglycemia and diabetes are significant risk factors for cancer death in the general Japanese population.

Prospective study on waist circumference and risk of all-cause and cardiovascular mortality: pooled analysis of Japanese community-based studies.

BACKGROUND: The aim of the present study was to clarify the association between waist circumference and all-cause and cardiovascular disease (CVD) mortality risk in relatively lean Japanese subjects. METHODS AND RESULTS: A total of 3,554 men and 4,472 women who had no history of CVD were examined and their waist circumference measured at baseline. The subjects were aged ≥40 years and were obtained from 3 prospective cohort studies during 1988-1996. Hazard ratios for all-cause and CVD mortality were analyzed over a follow-up period of 14.7 years using a Cox proportional hazards model and penalized spline method, after adjustment for study cohort, age, smoking, alcohol drinking, hypertension, dyslipidemia, and diabetes. Compared with the lowest quintile, the highest quintile of waist circumference in men was associated with a linear reduction in all-cause mortality risk (multivariate-adjusted hazard ratio, 0.73; 95% confidence interval: 0.60-0.89; P for trend=0.001). CVD mortality risk was increased in men aged ≤65 years with a higher waist circumference. This relationship was U-shaped. Waist circumference was not associated with all-cause or CVD mortality risk in women. CONCLUSIONS: Waist circumference was associated inversely with increased risk of all-cause death in men, but not in women. Middle-aged men with a greater waist circumference potentially have an increased risk of CVD mortality.

Self-reported dietary intake of potassium, calcium, and magnesium and risk of dementia in the Japanese: the Hisayama Study.

OBJECTIVES: To investigate whether higher intake of potassium, calcium, and magnesium reduces the risk of incident dementia. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, in Japan. PARTICIPANTS: One thousand eighty-one community-dwelling Japanese individuals without dementia aged 60 and older. MEASUREMENTS: A 70-item semiquantitative food frequency questionnaire was used to assess potassium, calcium, and magnesium intakes. Hazard ratios (HRs) for the development of all-cause dementia and its subtypes were estimated using Cox proportional hazards model. RESULTS: During a 17-year follow-up, 303 participants experienced all-cause dementia; of these, 98 had vascular dementia (VaD), and 166 had Alzheimer's disease (AD). The multivariable-adjusted HRs for the development of all-cause dementia were 0.52 (95% confidence interval [CI] = 0.30-0.91), 0.64 (95% CI = 0.41-1.00), and 0.63 (95% CI = 0.40-1.01) for the highest quartiles of potassium, calcium, and magnesium intake, respectively, compared with the corresponding lowest quartiles. Similarly, the HRs for the development of VaD were 0.20 (95% CI = 0.07-0.56), 0.24 (95% CI = 0.11-0.53), and 0.26 (95% CI = 0.11-0.61) for the highest quartiles of potassium, calcium, and magnesium intake, respectively. There was no evidence of a linear association between these mineral intakes and the risk of AD. CONCLUSION: Higher self-reported dietary intakes of potassium, calcium, and magnesium reduce the risk of all-cause dementia, especially VaD, in the general Japanese population.

Insulin resistance and the development of cardiovascular disease in a Japanese community: the Hisayama study.

AIMS: Although several surrogate measures of insulin resistance have been proposed, their associations with cardiovascular disease (CVD) have not been evaluated sufficiently. METHODS: A total of 2,356 community-dwelling Japanese individuals aged 40 to 79 years who underwent a 75 g oral glucose tolerance test were followed up for 14 years. The status of insulin resistance was estimated by using the Matsuda index or homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: During follow-up, 260 subjects developed CVD. The age- and sex-adjusted hazard ratios of CVD significantly decreased with an increasing Matsuda index and rose with increasing HOMA-IR levels (both p for trend <0.05). After adjustment for age, sex, serum total cholesterol, electrocardiogram abnormalities, proteinuria, smoking habits, alcohol intake, and regular exercise, the risk of CVD was significantly lower in the third to fifth quintiles of the Matsuda index and higher in the fifth quintile of HOMA-IR values compared with the first quintile of the corresponding index (Matsuda index Q3: hazard ratio (HR)= 0.59 [95% confidence interval 0.40-0.87]; Q4: HR= 0.66 [0.45-0.97]; and Q5: HR= 0.67 [0.47-0.97]; HOMA-IR Q5: HR= 1.55 [1.05-2.29]); however, these associations were attenuated after further adjustment for the metabolic syndrome status. In regard to CVD subtypes, the risks for stroke and coronary heart disease significantly decreased with an increasing Matsuda index, while elevated HOMA-IR levels were a significant risk factor for stroke, but not for coronary heart disease. CONCLUSION: Our findings suggest that insulin resistance significantly increases the risk of incident CVD through metabolic syndrome in Japanese.

Optimal cutoff value of the serum pepsinogen level for prediction of gastric cancer incidence: the Hisayama Study.

BACKGROUND: Serum pepsinogen (sPG) levels have been established as a good marker of chronic atrophic gastritis and the sequential occurrence of gastric cancer. However, there have been few prospective investigations which investigated the predictive performance of sPG for future gastric cancer incidence. SUBJECTS AND METHODS: We prospectively followed-up a total of 2446 community-dwelling Japanese aged ≥ 40 years for 10 years and used the Youden's index to determine the cutoff values of the pepsinogen I level and pepsinogen I/II ratio to accurately discriminate gastric cancer events. Predictive performance of sPG was assessed by ROC curve. RESULTS: During the follow-up, 69 subjects developed gastric cancer. The most predictive sPG test criteria were determined to be a pepsinogen I level ≤ 59 ng/ml and pepsinogen I/II ratio ≤ 3.9. The sensitivity and specificity of these criteria to discriminate the actual occurrence of gastric cancer were 71.0% and 69.2%, respectively. The area under the ROC curve for gastric cancer occurrence increased significantly by adding the sPG test to the model that included the status of Helicobater pylori infection and other potential risk factors (from 0.742 to 0.809; p for difference in the area < 0.001). CONCLUSIONS: This study determined the optimal sPG test criteria for predicting gastric cancer occurrence over 10 years in a general Japanese population. These criteria would be effective to screen for individuals at high risk of this disease.