Hiro Kishimoto

Association between ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cardiovascular disease: The Hisayama Study

OBJECTIVE We examined the association between the ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) or the docosahexaenoic acid (DHA)/AA and the development of cardiovascular disease in a general Japanese population. METHODS A total of 3103 community-dwelling Japanese individuals aged ≥40 years were followed up for an average of 5.1 years. Serum EPA/AA ratios were categorized into quartiles. The risk estimates were computed using a Cox proportional hazards model. RESULTS During the follow-up period, 127 subjects experienced cardiovascular events. Age- and sex-adjusted incidence rates of cardiovascular disease increased with lower serum EPA/AA ratios in individuals with high-sensitivity C-reactive protein (HS-CRP) of ≥1.0 mg/L (p for trend = 0.006), whereas no clear association was observed in those with HS-CRP of <1.0 mg/L (p for trend = 0.27). The multivariable-adjusted risk of cardiovascular disease increased significantly, by 1.52 times (95% confidence interval 1.12-2.04) per 0.20 decrement in serum EPA/AA ratio in subjects with HS-CRP of ≥1.0 mg/L. A lower serum EPA/AA ratio was significantly associated with an increased risk of coronary heart disease, but there was no evidence of an association with stroke. The magnitude of the influence of the serum EPA/AA ratio on the cardiovascular risk increased significantly with elevating HS-CRP levels taken as a continuous variable (p for heterogeneity = 0.007). However, no such association was observed for DHA/AA ratio. CONCLUSION Our findings suggest that a lower serum EPA/AA ratio is associated with a greater risk of cardiovascular disease, especially coronary heart disease, among subjects with higher HS-CRP levels in the general Japanese population.

Identifying associations between sedentary time and cardio-metabolic risk factors in working adults using objective and subjective measures: a cross-sectional analysis

BackgroundSedentary behavior has been reported to be associated with metabolic and vascular health independent of moderate-to-vigorous physical activity (MVPA). In order to select appropriate options to measure sedentary behavior in practice and research settings, it is worthwhile to characterize the extent to which objective and subjective measures of sedentary behavior quantify adverse health risks in the same population. This cross-sectional analysis compared accelerometer-derived and self-reported sedentary time to identify their association with cardio-metabolic risk factors.MethodsCross-sectional analysis was conducted using data from 661 Japanese workers (145 women) aged 20–64 years. Participants wore a tri-axial accelerometer device for 10 consecutive days and completed the Japan Atherosclerosis Longitudinal Study Physical Activity Questionnaire. Data on body mass index, waist circumference, resting blood pressure, triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, total:HDL cholesterol ratio, blood glucose, and glycosylated hemoglobin (HbA1c) were obtained from annual health examinations.ResultsBoth accelerometer-derived and self-reported sedentary time were deleteriously associated with triglycerides, HDL-cholesterol, total:HDL ratio, and HbA1c after adjustment for potential confounders including MVPA. There were no significant differences in regression coefficients between the two measures. Thus, the magnitude of the associations of both measures with cardio-metabolic risk factors was similar, despite poor agreement between them. Occupational sedentary time was correlated with both measures of total sedentary time, and more consistently associated with cardio-metabolic risk factors than sedentary leisure time.ConclusionsBoth accelerometer and self-report measurements are similarly associated with cardio-metabolic risk factors in a Japanese working adult population. Subjective and objective measures of sedentary behaviors appear to capture different aspects of behaviors. Further efforts to establish data processing methods integrating objective and subjective measures are needed to more effectively assess sedentary time’s relationship to health outcomes.

Midlife and late-life handgrip strength and risk of cause-specific death in a general Japanese population: the Hisayama Study

Background Decreased handgrip strength has been reported to be a risk factor for all-cause death among the elderly. However, it is unclear whether handgrip strength measured in midlife is associated with risk of all-cause and cause-specific death in the general population. Methods We followed, prospectively, a total of 2527 community-dwelling Japanese (1064 men and 1463 women) aged ≥40 years for 19 years. Participants were divided into three groups according to the age-specific and sex-specific tertiles of handgrip strength (T1, lowest; T3, highest). Results During the follow-up period, 783 participants died, of whom 235 died of cardiovascular disease, 249 of cancer, 154 of respiratory disease and 145 of other causes. In the middle-aged group (40–64 years), multivariable-adjusted HRs (95% CIs) for all-cause death were 0.75 (0.56 to 0.99) in T2 and 0.49 (0.35 to 0.68) in T3 compared with T1 as a reference. Corresponding HRs (95% CI) in the elderly group (≥65 years) were 0.50 (0.40 to 0.62) and 0.41 (0.32 to 0.51), respectively. As regards the cause of death, higher levels of handgrip strength were significantly associated with decreased risks of cardiovascular death, respiratory death and death from other causes, but not of cancer, in the middle-aged and the elderly. Conclusions Our findings suggest that handgrip strength levels in midlife and late life are inversely associated with the risks of all-cause and non-cancer death in the general Japanese population.

Impact of Leisure-Time Physical Activity on Glycemic Control and Cardiovascular Risk Factors in Japanese Patients with Type 2 Diabetes Mellitus: The Fukuoka Diabetes Registry

Aims/hypothesis The effects of leisure-time physical activity (LTPA) on glycemia and cardiovascular risk factors are not fully understood in Asian type 2 diabetic patients, who are typically non-obese. We studied associations between LTPA and glycemia and cardiovascular risk factors in Japanese type 2 diabetic patients. Methods A total of 4,870 Japanese type 2 diabetic patients aged ≥20 years were divided into eight groups according to their LTPA. We investigated associations between the amount and intensity levels of physical activity (PA) and glycemic control, insulin sensitivity, cardiovascular risk factors, and low-grade systemic inflammation in a cross-sectional study. Results LTPA was dose-dependently associated with body mass index (BMI), waist circumference, hemoglobin A1c (HbA1c), fasting plasma glucose, homeostasis model assessment of insulin resistance, triglyceride, high density lipoprotein cholesterol, high sensitivity C-reactive protein, and prevalence of metabolic syndrome, but not with blood pressure, low density lipoprotein cholesterol or adiponectin. The amount of PA required to lower HbA1c was greater than that required to improve cardiovascular risk factors. LTPA was inversely associated with HbA1c in non-obese participants but not in obese participants after multivariate adjustments for age, sex, duration of diabetes, current smoking, current drinking, energy intake, cardiovascular diseases, depressive symptoms, and treatment of diabetes. Higher-intensity LTPA, not lower-intensity LTPA was associated with HbA1c after multivariate adjustments with further adjustment including BMI. Conclusions/interpretation LTPA was dose-dependently associated with better glycemic control and amelioration of some cardiovascular risk factors in Japanese type 2 diabetic patients. In addition, increased higher-intensity LTPA may be appropriate for glycemic control.

Serum Uric Acid as a Risk Factor for Chronic Kidney Disease in a Japanese Community – The Hisayama Study –

BACKGROUND Growing evidence suggests that high serum uric acid (SUA) levels are causally related to increased risk of chronic kidney disease (CKD). However, few studies have investigated the influence of elevated SUA levels on the incidence of kidney dysfunction and albuminuria separately in community-based populations. METHODSANDRESULTS A total of 2,059 community-dwelling Japanese subjects aged ≥40 years without CKD were followed for 5 years. CKD was defined as kidney dysfunction (estimated glomerular filtration rate <60 ml/min/1.73 m(2)) or albuminuria (urine albumin-creatinine ratio ≥30 mg/g). The odds ratio (OR) for the development of CKD was estimated according to quartiles of SUA (≤4.0, 4.1-4.9, 5.0-5.8, and ≥5.9 mg/dl). During the follow-up, 396 subjects developed CKD, of whom 125 had kidney dysfunction and 312 had albuminuria. The multivariable-adjusted risk of developing CKD increased with higher SUA levels (OR 1.00 [reference] for ≤4.0, 1.21 [95% confidence interval, 0.84-1.74] for 4.1-4.9, 1.47 [1.01-2.17] for 5.0-5.8, and 2.10 [1.37-3.23] for SUA ≥5.9 mg/dl, respectively). Similarly, there were positive associations between SUA level and the adjusted risk of developing kidney dysfunction (OR 1.00 [reference], 2.30 [1.10-4.82], 2.81 [1.34-5.88], and 3.73 [1.65-8.44]) and albuminuria (1.00 [reference], 1.12 [0.76-1.65], 1.35 [0.90-2.03], and 1.81 [1.14-2.87], respectively). CONCLUSIONS Higher SUA levels were a significant risk factor for the development of both kidney dysfunction and albuminuria in a general Japanese population. (Circ J 2016; 80: 1857-1862).

Serum Angiopoietin-Like Protein 2 Is a Novel Risk Factor for Cardiovascular Disease in the Community

Objective—Angiopoietin-like protein 2 (ANGPTL2), a proinflammatory mediator, has been reported to accelerate the development of insulin resistance, endothelial dysfunction, and atherosclerosis in mice. However, no cohort studies have examined the relationship between serum ANGPTL2 levels and the development of cardiovascular disease (CVD) in a general population. Approach and Results—A total of 3005 community-dwelling Japanese aged ≥40 years without a history of CVD were divided into 4 groups according to the quartiles of serum ANGPTL2 concentrations (Q1, lowest and Q4, highest) and followed up for 10 years. The hazards ratios and their 95% confidence intervals for the development of CVD (coronary heart disease or stroke) were estimated using a Cox proportional hazards model. During the follow-up, 219 first-ever CVD events were observed. The risk of CVD increased significantly with elevating ANGPTL2 levels after adjustment for age, sex, serum total cholesterol, use of lipid-lowering agents, ECG abnormalities, smoking habits, alcohol intake, and regular exercise (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.27 [0.80–2.04]; Q3, 1.48 [0.95–2.32]; and Q4, 1.85 [1.20–2.85]; P=0.003 for trend). After additional adjustment for metabolic syndrome components and serum high-sensitivity C-reactive protein levels as an inflammatory marker, the association was attenuated but remained significant (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.21 [0.76–1.94]; Q3, 1.38 [0.87–2.17]; and Q4, 1.66 [1.05–2.60]; P=0.02 for trend). Conclusions—Our findings suggest that elevated serum ANGPTL2 levels are a novel risk factor for the development of CVD in the general population. This association is partially mediated by metabolic disorders and inflammation.

Alternative Measures of Hyperglycemia and Risk of Alzheimer’s Disease in the Community: The Hisayama Study

Context and Objective We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), GA/HbA1c ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimers disease (AD). Design and Participants A total of 1187 community-dwelling Japanese subjects aged ≥65 years without dementia were followed up for an average of 4.8 years. Results The age- and sex-adjusted incidence of AD increased significantly with higher quartiles of GA/HbA1c ratio, and a similar tendency was seen for GA, whereas no such association was observed for HbA1c and 1,5-AG. After adjusting for potential confounding factors, positive association of GA/HbA1c ratio with the risk of AD remained significant: the multivariable-adjusted hazard ratio (HR) was significantly higher in the third [HR = 2.11, 95% confidence interval (CI) = 1.16 to 3.82] and fourth (HR = 2.01, 95% CI = 1.09 to 3.68) quartile than in the first quartile. Among subjects with normal glucose tolerance, those with high GA/HbA1c ratio had a higher risk of AD than those with low GA/HbA1c ratio (HR = 1.82, 95% CI = 1.05 to 3.16), and a similar tendency was found in those with glucose intolerance (HR = 1.73, 95% CI = 0.96 to 3.13). No such associations were observed for HbA1c, GA, and 1,5-AG, regardless of glucose tolerance status. Conclusions Our findings suggest that elevated GA/HbA1c ratio-but not HbA1c, GA, or 1,5-AG level-is significantly associated with the risk of AD in subjects both with and without glucose intolerance. GA/HbA1c ratio may be a useful biomarker for predicting incident AD.

Association between serum vitamin D and All-Cause and Cause-Specific death in a general Japanese population ― the hisayama study ―

BACKGROUND Few studies have investigated the association between serum vitamin D levels and mortality in general Asian populations.Methods and Results:We examined the association of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) levels with the risk of all-cause and cause-specific death in an average 9.5-year follow-up study of 3,292 community-dwelling Japanese subjects aged ≥40 years (2002-2012). The multivariable-adjusted hazard ratio (HR) for all-cause death increased significantly with lower serum 1,25(OH)2D levels (HR 1.54 [95% confidence interval, 1.18-2.01] for the lowest quartile, 1.31 [0.99-1.73] for the 2nd quartile, 0.94 [0.70-1.25] for the 3rd quartile, 1.00 [Ref.] for highest quartile; P for trend <0.001). A similar association was observed for cardiovascular and respiratory infection death (both P for trend <0.01), but not for cancer death or death from other causes. In the stratified analysis, the association between lower serum 1,25(OH)2D levels and the risk of respiratory infection death was stronger in subjects with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2than in those with eGFR ≥60 mL/min/1.73 m2; there was a significant heterogeneity in the association between eGFR levels (P for heterogeneity=0.04). CONCLUSIONS The findings suggested that a lower serum 1,25(OH)2D level is a potential risk factor for all-cause death, especially cardiovascular and respiratory infection death, in the general Japanese population, and that lower serum 1,25(OH)2D levels greatly increase the risk of respiratory infection death in subjects with kidney dysfunction.

Association Between Daily Sleep Duration and Risk of Dementia and Mortality in a Japanese Community: SLEEP AND RISK OF DEMENTIA AND DEATH

To investigate the association between daily sleep duration and risk of dementia and death in a Japanese elderly population.

Albuminuria increases the risks for both Alzheimer disease and vascular dementia in community-dwelling Japanese elderly: The hisayama study

Background Epidemiologic evidence has emerged to reveal an association of albuminuria and low estimated glomerular filtration rate (eGFR) with dementia, but the findings are inconsistent. In addition, there are limited studies addressing the association between albuminuria and Alzheimer disease (AD). Methods and Results A total of 1562 community‐dwelling Japanese subjects aged ≥60 years without dementia were followed up for 10 years. The outcomes were incidence of all‐cause dementia and its subtypes, namely, AD and vascular dementia (VaD). The hazard ratios for the outcomes were estimated according to urine albumin–creatinine ratio (UACR) and eGFR levels using a Cox proportional hazards model. During the follow‐up, 358 subjects developed all‐cause dementia (238 AD and 93 VaD). Higher UACR level was significantly associated with greater multivariable‐adjusted risks of all‐cause dementia (hazard ratios [95% confidence intervals]: 1.00 [reference], 1.12 [0.78–1.60], 1.65 [1.18–2.30], and 1.56 [1.11–2.19] for UACR of ≤6.9, 7.0–12.7, 12.8–29.9, and ≥30.0 mg/g, respectively), AD (1.00 [reference], 1.20 [0.77–1.86], 1.75 [1.16–2.64], and 1.58 [1.03–2.41], respectively), and VaD (1.00 [reference], 1.03 [0.46–2.29], 1.94 [0.96–3.95], and 2.19 [1.09–4.38], respectively). On the other hand, lower eGFR level was marginally associated with greater risk of VaD, but not AD. Subjects with UACR ≥12.8 mg/g and eGFR of <60 mL/min per 1.73 m2 had 3.3‐fold greater risk of VaD than those with UACR <12.8 mg/g and eGFR of ≥60 mL/min per 1.73 m2. Conclusions Albuminuria is a significant risk factor for the development of both AD and VaD in community‐dwelling Japanese elderly. Moreover, albuminuria and low eGFR are mutually associated with a greater risk of VaD.