Erika Nakao

High plasma fetuin-A levels are associated with metabolic syndrome among males but not females in a Japanese general population.

AIMS Fetuin-A, a protein exclusively secreted from the liver, is associated with insulin resistance and/or metabolic syndrome (MetS). However, few studies have examined this association in Japan. We investigated this issue in a Japanese general population. METHODS We performed an epidemiological survey in a small community in Japan. The participants consisted of 659 subjects (253 males and 406 females). Fetuin-A levels were measured by a sandwich ELISA method and the modified NCEP-ATP III criteria were adopted to diagnose MetS. The homeostasis model assessment index (HOMA-IR) was calculated as a marker of insulin resistance. RESULTS Statistically significant characteristics of the 659 subjects stratified by fetuin-A quartiles were male gender (inversely), age (inversely), insulin, HOMA-IR, uric acid (inversely), alcohol intake (inversely) and the prevalence of MetS. Mean fetuin-A levels were 249.7±45.1μg/ml in males and 262.7±55.8μg/ml in females. In males, the prevalence of MetS was 43.1%, and their mean HOMA-IR level was 1.1. In females, the prevalence of MetS was 17.7%, and their mean HOMA-IR level was 0.9. Multiple stepwise regression analyses showed that fetuin-A levels in males but not females were independently associated with MetS and LDL-c. Multiple logistic regression analysis of fetuin-A (quartile 1 vs. quartile 4) in males showed significant odds ratios of 1.009 (95% C.I.: 1.003-1.015) for MetS and 1.376 (95% C.I.: 1.027-1.844) for 1-SD increment increase in LDL-c. CONCLUSIONS High plasma fetuin-A levels were associated with MetS in community-dwelling Japanese males but not females.

Association of serum eicosapentaenoic acid to arachidonic acid ratio with microalbuminuria in a population of community-dwelling Japanese

BACKGROUND Epidemiological evidence suggests that the increased intake of omega-3 polyunsaturated fatty acids can prevent atherosclerosis-related cardiovascular diseases. Recently, serum eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio has been reported to be a predictive marker of cardiovascular events. Accordingly, we examined the relationship between serum EPA/AA ratio and microalbuminuria. METHODS We enrolled 444 residents (174 males and 270 females, mean age 66.6 ± 9.3 years) who underwent a physical examination in Uku town (fishing area) in Japan. They received blood tests including serum levels of EPA and AA, and urine test to examine microalbuminuria. Eating and drinking patterns were evaluated by a brief self-administered diet history questionnaire. Microalbuminuria was defined as a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g Cr. RESULTS The mean EPA/AA ratio was 0.66 ± 0.3 in males and 0.51 ± 0.2 in females. Multiple stepwise regression analyses revealed that systolic blood pressure (p < 0.0001), high sensitive C-reactive protein (p < 0.01), serum EPA/AA ratio (p < 0.01, inversely), and hemoglobin A1c (p < 0.05) were significantly associated with microalbuminuria. In the group with low serum EPA/AA ratio, the prevalence of microalbuminuria was significantly higher than the other, after the adjustments for confounding factors (odds ratio, 3.45; 95% confidence interval, 1.47-8.13; p < 0.01). CONCLUSION The present study demonstrated that serum EPA/AA ratio was strongly associated with microalbuminuria.

Augmentation index (AI) in a dose-response relationship with smoking habits in males: The Tanushimaru study.

AbstractWe investigated the relationship between augmentation index (AI) and smoking habits in community-dwelling Japanese.This cross-sectional study enrolled 1926 subjects (769 males and 1157 females) aged 40 to 95 years who underwent a health check-up in a Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town in Kyushu Island in 2009. The subjects’ medical history, alcohol intake, smoking habit, and current medications for hypertension, dyslipidemia, and diabetes were ascertained by questionnaire. Radial arterial pressure wave analysis was used to obtain AI. We analyzed the data stratified by gender.Age-adjusted means of AI in males showed a clear dose–response relationship in 4 categories of smoking habits (P = 0.010). There was no significant relationship between AI and smoking habits in females (P = 0.127). The significant dose–response relationship (P = 0.036) in males between AI and 4 categories of smoking habits still remained even after adjustment for age, body mass index, systolic blood pressure, estimated glomerular filtration rate, glucose, hypertensive medication, and alcohol intake.The present study demonstrated that AI values were significantly associated with smoking habits in a dose-dependent manner in Japanese males.

Elevated Plasma Transforming Growth Factor β1 Levels Predict the Development of Hypertension in Normotensives: The 14-Year Follow-Up Study

BACKGROUND Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine. There is growing evidence that TGF-β1 is involved in the pathogenesis of hypertension and the development of target organ damage in hypertensives. Although several studies have shown that TGF-β1 induced vascular hypertrophy and remodelling in various vascular diseases, there are no longitudinal data on hypertension in the epidemiological studies. The present study tested the hypothesis whether elevated TGF-β1 levels can predict the development of hypertension. METHODS In 2002-2004, 528 subjects received health examinations in Uku town, southwestern Japan. We examined blood pressure (BP), body mass index, and blood test. Data on fasting plasma TGF-β1 were obtained from 528 individuals. Of these, 149 normotensives (BP <140/90 mm Hg without antihypertensive medications) at baseline were followed-up for 14 years. RESULTS The receiver-operating characteristic curve was used and the calculated cutoff value was 8.9 ng/ml. Of 149 normotensives at baseline, 59 subjects developed hypertension. Plasma TGF-β1 levels were significantly associated with the development of hypertension after adjustment for confounding factors. To further examine the association between them, we performed logistic regression analysis. We divided the baseline plasma TGF-β1 levels into 2 groups using a cutoff value. The significant high odds ratio [3.582 (95% confidence interval, 1.025-12.525)] for the development of hypertension was found in the highest group of TGF-β1 level vs. the lowest group after adjustment for confounders. CONCLUSIONS This is the first report demonstrating the causal relationship between them. Elevated plasma TGF-β1 levels predicted the development of hypertension in normotensives in a population of community-dwelling Japanese.

A Useful Tool As a Medical Checkup in a General Population—Bioelectrical Impedance Analysis

Accumulation of visceral fat leads to metabolic syndrome and increases risks of cerebro-cardiovascular diseases, which should be recognized and improved at the early stage in general population. Accurate measurement of visceral fat area (VFA) is commonly performed by the abdominal cross-sectional image measured by computed tomography scan, which is, however, limited due to the radiation exposure. The bioelectrical impedance analysis (OMRON, HDS-2000 DUALSCANR) has been recently developed to measure VFA, which is more easily accessible modality. In the present study, we investigated the clinical usefulness of DUALSCANR in 226 subjects who received health examination, including blood chemistries, electrocardiography, cardio, and carotid ultrasonography. VFA was measured within only just 5 min. Average of VFA was 83.5 ± 36.3 cm2 in men, and 64.8 ± 28.0 cm2 in women, which was correlated to weight (r = 0.7404, p < 0.0001), body mass index (BMI) (r = 0.7320, p < 0.0001), and waist circumstance (r = 0.7393, p < 0.0001). In multivariate analyses, VFA was significantly associated with weight (p < 0.0001), BMI (p < 0.0001), and waist circumstance (p < 0.0001). Compared to the group of smaller waist and normal BMI, VFA was significantly increased (p < 0.0001) in the group of larger waist and obese subjects. In conclusion, these results indicated that DUALSCANR is useful to measure VFA easily in general population, even in a large number of subjects.

Plasma Renin Activity and Resting Heart Rate in a Population of Community-Dwelling Japanese: The Tanushimaru Study

BACKGROUND Heart rate is a strong predictor of mortality and development of obesity and diabetes. The renin-angiotensin-aldosterone system plays an important role in blood pressure control and volume homeostasis. Although many studies have indicated the association between aldosterone and hypertension or insulin resistance, epidemiological evidence of the association of heart rate with plasma renin activity (PRA) remains scant. Therefore, we investigated whether heart rate is associated with PRA. METHODS A total of 1,943 subjects were enrolled, who underwent a health examination in Tanushimaru in 2009. Plasma renin and aldosterone concentrations were measured by radioimmunoassay. PRA and the homeostasis model assessment (HOMA) were used by natural-log transformed. Resting heart rate was measured using electrocardiography. RESULTS We divided the subjects into four groups by heart rate (<60/min, 60-69/min, 70-79/min, ≥80/ min), and analyzed an association between PRA and heart rate by analysis of covariance after adjustments for age and sex. The adjusted mean PRA and HOMA index showed a significant trend (P < 0.01) as higher heart rate, although there was no significant trend between aldosterone and heart rate (P = 0.26). In multiple linear regression analysis adjusted for age, sex, systolic blood pressure, HOMA index, and hypertensive medication, PRA was positively and strongly associated with elevated heart rate (P < 0.01). CONCLUSIONS This epidemiological study demonstrated that PRA, but not aldosterone, is significantly and positively associated with higher resting heart rate in a general population.

Twenty‐four‐Hour Urinary Potassium Excretion, But Not Sodium Excretion, Is Associated With All‐Cause Mortality in a General Population

Background Few studies have examined the relationship between accurate monitoring of sodium or potassium consumption and mortality. We aimed to investigate the association between 24‐hour urinary sodium or potassium excretion and ≈30‐year mortality in a Japanese population using 24‐hour urine collection. Methods and Results We enrolled a total of 1291 participants, aged 21 to 85 years, who underwent health checkups, including a blood test and 24‐hour urine collection. They were followed up for 27.5±9.9 years by December 31, 2015, and the final follow‐up rate was 95.8%. Cox proportional hazards regression analysis was used to assess the association between 24‐hour urinary sodium or potassium excretion and all‐cause mortality. At baseline, the mean 24‐hour urinary sodium and potassium excretions were 5.80±2.28 g/d and 1.85±0.82 g/d, respectively. There were 631 deaths during the follow‐up. The cumulative survival rate was significantly decreased in the lowest quartile compared with the other higher groups. In the Cox proportional hazard model after adjustment for age and sex, 24‐hour urinary potassium excretion, but not sodium excretion, was inversely associated with all‐cause mortality. We divided the 24‐hour urinary potassium excretion levels into quartiles. After adjustment for confounding factors, the hazard ratio of all‐cause mortality in the highest quartile of 24‐hour urinary potassium excretion versus the lowest was 0.62 (95% confidence interval, 0.48–0.79; P<0.001). Conclusions The 24‐hour urinary potassium excretion, but not sodium excretion, was significantly associated with all‐cause mortality in the general population.

Trends in coronary risk factors and electrocardiogram findings from 1977 to 2009 with 10-year mortality in Japanese elderly males - The Tanushimaru Study.

BACKGROUND An understanding of the trends in regard to coronary risk factors and electrocardiogram (ECG) findings has an important role in public health. We investigated the trends in coronary risk factors and main ECG findings in 1977, 1989, 1999, and 2009 in the Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town on Kyushu Island. METHODS AND RESULTS A total of 1397 subjects (231 in 1977, 332 in 1989, 389 in 1999, and 445 in 2009) were enrolled in this study, and all of them were males aged over 65 years. In coronary risk factors, total cholesterol levels, diastolic blood pressure, body mass index, and uric acid significantly increased during these 3 decades. The prevalence of smokers markedly decreased from 56.7% in 1977 to 16.8% in 2009. ECG changes during 3 decades were wider QRS interval, increased prevalence of major abnormality, reduced heart rate, shortened PR interval and corrected QT, and decreased prevalence of left ventricular hypertrophy. Age, smoking habits, major and minor abnormalities in ECG were associated with mortality in 1977-1987. Age, total cholesterol levels (inversely) and corrected QT were associated with mortality in 1989-1999. Age, smoking habits, heart rate, and systolic blood pressure were associated with mortality in 1999-2009. CONCLUSIONS Predictors of mortality have changed with the times. Coronary risk factors such as smoking, increased heart rate, and elevated blood pressure have been recently associated with mortalities in elderly male Japanese general population.

PS 09-09 ELEVATED PLASMA TGF-1 LEVELS PREDICTED THE DEVELOPMENT OF HYPERTENSION IN NORMOTENSIVES IN A GENERAL POPULATION

Objective: Transforming growth factor &bgr;1 (TGF-&bgr;1) is a multifunctional cytokine. There is evidence that TGF-&bgr;1 is involved in the pathogenesis of hypertension and the development of hypertensive target organ damage. However, most large scale cross-sectional studies in humans have indicated no relationship between serum TGF-&bgr;1 levels and hypertension. The present study was designed to determine whether elevated TGF-&bgr;1 levels predict the development of hypertension. Design and method: In 2002–2004, in a fishing community in southwestern Japan (Uku town), a total of 528 people received a health examination. We examined blood pressure, body mass index (BMI) and blood chemistries. Data on fasting serum TGF-&bgr;1 were obtained from 528 individuals. Of these, 149 normotensives (blood pressure <140/90 mmHg without anti-hypertensive medications) at baseline were followed-up during over ten years. Results: Of 149 normotensives at baseline, 59 subjects developed hypertension. We divided the baseline serum TGF-&bgr;1 levels into tertiles. The odds ratio [1.126 (95% CI, 0.461–2.752)] for the development of hypertension after 10 years was not statistically significant in the highest tertiles vs. the lowest tertiles of serum TGF-&bgr;1 level after adjustment for confounding factors. However, a significant trend (p = 0.018 for trend) was found among the three groups. Conclusions: Elevated serum TGF-&bgr;1 levels predicted the development of hypertension in normotensives in community-dwelling Japanese.

PS 09-25 ASSOCIATION BETWEEN PHYSICAL ACTIVITY AND MORTALITY THE TANUSHIMARU STUDY

Objective: The relationship between mortality and physical activity in the general population is unclear. Design and Method: Using data from 1,920 men and women aged over 40 years who participated in the Tanushimaru Study, physical activity was assessed by self-report using the Baecke questionnaire at baseline in 1999. The questionnaire was constituted by three physical activity categories: work index, sports index and non-sports index. Total index was summed up by the three indices. Multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression models. Results: During a median follow-up of 13.8 years, a total of 343 died. In conventional coronary risk factors, systolic blood pressure (p = 0.088), fasting plasma glucose (p = 0.027) and smoking habit (p < 0.001) were significantly and marginally associated with mortality. Significant inverse associations were found between total index and mortality after adjustment for age and gender. Compared with poor physical activity, the adjusted HR (95% CI) for ideal physical activity were 0.125 (0.017–0.914). Conclusions: These data suggest that ideal physical activity showed was a reduced risk of mortality as well as conventional coronary risk factors.