Nagisa Morikawa

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.

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.

PS 02-38 SERUM THROMBOSPONDIN-2 LEVEL IS STRONGLY ASSOCIATED WITH INSULIN RESISTANCE IN A GENERAL POPULATION

Objective: Serum thrombospondin (TSP)-2 is a glycoprotein expressed in extracellular matrix increasing during tissue remodeling. Recent studies have shown that TSP-2 is useful as a prognostic factor of patients with heart failure and associated with cardiovascular death. However, the clinical importance of serum TSP-2 in healthy subjects is still unknown. We examined the relations between TSP-2 and coronary risk factors. Design and method: A periodic epidemiological survey was performed in a community dwelling in Uku town, Nagasaki, Japan. A total of 445 residents received a health check-up examination including blood tests such as fasting serum levels of TSP-2. Insulin resistance was evaluated using HOMA-IR. All statistical analyses were performed using SAS system. Results: The mean age was 67 ± 9.4 years old. There are no significant differences between the ages and sexes and serum TSP-2 level (mean:20.9 ± 8.5ng/ml). We performed uni and multivariate analyses. Serum TSP-2 levels were significantly correlated to plasma glucose (p < 0.001), insulin (p < 0.001), HOMA-IR (p < 0.001), eGFR (p < 0.01; inversely), high sensitive CRP (p < 0.01) and NT-proBNP (p < 0.001). Moreover, in multiple stepwise linear regression analysis, TSP-2 levels were independently and significantly associated with HOMA-IR (p < 0.001), high sensitive CRP (p < 0.05), and NT-proBNP (p < 0.001). Conclusions: To the best of our knowledge, this is the first report to examine the significant relationship between TSP-2 and insulin resistance even in healthy subjects.

PS 09-08 HABITUAL COFFEE INTAKE REDUCES HEART RATE AND DECREASES ALL-CAUSE MORTALITY — THE TANUSHIMARU PROSPECTIVE STUDY —

Objective: Recently, the favorable effects of coffee consumption on atherosclerotic diseases have been discussed. We have reported that coffee consumption was inversely associated with metabolic syndrome, and higher heart rate was strongly associated with all-cause mortality. We hypothesized that higher coffee consumption may reduce resting heart rate and may decrease all-cause death. Design and Method: A total of 1,920 residents aged over 40 years (794 males and 1,126 females) recruited from a population-based survey. We measured components of metabolic syndrome (blood pressure, waist circumference, fasting plasma glucose, and lipid profiles) and eating and drinking patterns were evaluated by a food frequency questionnaire. Resting heart rate was measured using a 12-lead electrocardiogram. Results: Of 1,920 subjects, information on dietary habits was obtained from 1,902 subjects (785 men and 1,117 women). Significant relationships were found between heart rate and coffee consumption (p = 0.004 for trend). Furthermore, we followed these subjects for 15 years. During the periods, 343 of the participants died (102 subjects died of cancer, 48 of cerebro-cardiovascular diseases, and 44 of infectious diseases). Multivariate analyses after adjustments for confounding factors revealed that higher coffee consumption is inversely associated with all-cause death (p < 0.05). Conclusions: Our prospective study indicates that coffee consumption was associated with lower mortality possibly due to a reduction in resting heart rate in a population of community-dwelling Japanese.

PS 09-21 IMPACT OF CYSTATIN C AND MICROALBUMINURIA ON COGNITIVE DYSFUNCTION IN THE POPULATION OF COMMUNITY-DWELLING JAPANESE

Objective: Recent studies have shown that kidney dysfunction is significantly associated with cognitive dysfunction. However, it is rather difficult to recognize an impairment of cognitive function. We, therefore, investigated whether cystatin C and microalbuminuria, sensitive biomarkers of early renal dysfunction, are more significantly related to cognitive dysfunction than renal dysfunction (low eGFR levels). Design and Method: A total of 1,943 subjects were enrolled, who underwent a health examination in Tanushimaru in 2009. All of them were assessed cognitive function with mini-mental state examination (MMSE). We also measured cystatin C and microalbuminuria levels. Results: The mean levels of log-transformed cystatin C were 0.95 (range 0.4–9.1) mg/l, and log-transformed microalbuminuria levels were 3.61 (range 1.1–937.0) mg/g.Cr. The means of MMSE score were 27.6 ± 2.5. Multivariate regression analyses adjusted for age and gender revealed that systolic BP (p = 0.024, inversely), cystatin C (p = 0.046, inversely), and microalbuminuria (p = 0.016, inversely), whereas, eGFR was not significant (p = 0.250). In the multiple logistic regression analyses adjusted for age and gender, the significance of microalbumiuria with MMSE was still remained (odds ratio: 1.251; 95%CI: 1.052–1.486; p = 0.016). Conclusions: We demonstrated for the first time that cognitive function was significantly and inversely associated with microalbuminuria and cystatin C and rather than eGFR in the general population.