Ayako Yoshimura

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.

Serum vaspin levels are positively associated with carotid atherosclerosis in a general population

OBJECTIVES Vaspin is a novel adipocytokine with potential insulin-sensitizing properties. Insulin resistance (IR) plays a role in the development and progression of atherosclerosis. However, the relationship between serum vaspin levels and atherosclerosis remains unknown. Therefore, we investigated whether vaspin was correlated with carotid intima-media thickness (c-IMT). METHODS Data for fasting vaspin levels of 201 subjects (78 men and 123 women aged over 40 years) were obtained from a general population in Japan. We obtained anthropometric parameters and blood chemistries, and calculated homeostasis model assessment-IR (HOMA-IR) index. C-IMT was measured by B-mode ultrasonography. The mean values of each parameter by tertiles of vaspin were compared with analysis of variance, and the associations of vaspin with IR and c-IMT were evaluated by multiple stepwise regression analysis. RESULTS Univariate analysis revealed that vaspin levels were positively correlated with BMI, insulin, HOMA-IR index, estimated glomerular filtration rate (eGFR), c-IMT and hypertensive medication. Multiple stepwise regression analysis revealed that HOMA-IR index, c-IMT and eGFR were significantly and independently associated with vaspin. We performed multivariate analyses with c-IMT as the dependent variable. Age, hypertensive medication and vaspin were significant for c-IMT. Moreover, a mediation analysis demonstrated that vaspin was significantly related to c-IMT, independently of IR. CONCLUSIONS The present study not only confirmed the previous finding of the positive association of vaspin with IR but also demonstrated that serum vaspin level was positively associated with c-IMT, independently of IR in a general population. Our results may suggest a role of vaspin in atherosclerosis in humans.

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.

High Serum N-Acetyl-ß-D-Glucosaminidase Activity Is a Predictor of 28-Year Mortality in a Population of Community-Dwelling Japanese—The Tanushimaru Study

on blood pressure: 11-year longitudinal population study. Br J Psychiatry 2008;193:108–113. 7. Paterniti S, Verdier-Taillefer MH, Geneste C et al. Low blood pressure and risk of depression in the elderly. A prospective community-based study. Br J Psychiatry 2000;176:464–467. 8. Godin O, Elbejjani M, Kaufman JS. Body mass index, blood pressure, and risk of depression in the elderly: A marginal structural model. Am J Epidemiol 2012;176:204–213. 9. Zimmerman JA, Mast BT, Miles T et al. Vascular risk and depression in the Hispanic Established Population for the Epidemiologic Study of the Elderly (EPESE). Int J Geriatr Psychiatry 2009;24:409–416. 10. Licht CM, de Geus EJ, Seldenrijk A et al. Depression is associated with decreased blood pressure, but antidepressant use increases the risk for hypertension. Hypertension 2009;53:631–638.

High Level of Plasma Remnant-like Particle Cholesterol May Predispose to Development of Hypertension in Normotensive Subjects

BACKGROUND Remnant-like lipoprotein particle cholesterol (RLP-C) is a highly atherogenic factor. RLP-C induces endothelial dysfunction and is associated with hyperinsulinemia. This study was designed to determine whether high plasma RLP-C levels predispose to the development of hypertension in subjects with normal blood pressure (BP). METHODS A total of 1,485 subjects aged >40 years in a Japanese Cohort of the Seven Countries Study received health examinations. We examined BP, anthropometric parameters, and blood chemistries, including fasting RLP-C levels. RLP-C levels were measured by an immune-separation method. We excluded from the analysis 676 subjects who had hypertension (BP ≥ 140/90mm Hg), or were on antihypertensive medication, and/or were on antihyperlipidemic medication at baseline. Ten years later, 681 subjects were re-examined. RESULTS Of 681 normotensive subjects at baseline, 303 subjects had developed hypertension 10 years later. Baseline RLP-C level was significantly higher (P < 0.01) in the subjects who developed hypertension than in those who remained normotensive (3.7±1.9 vs. 3.3±1.6mg/dl). Multivariable logistic regression analysis demonstrated that baseline RLP-C was a significant factor for incident hypertension after adjustments for homeostasis model assessment index and other hypertension-related factors (odds ratio = 1.05, 95% CI = 1.00-1.10; P = 0.04). CONCLUSIONS A high level of plasma RLP-C in normotensive subjects may predispose to the development of hypertension in a population of community-dwelling Japanese.

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.

Circulating Inflammatory and Hemostatic Biomarkers are Associated with All-Cause Death and Cancer Death in a Population of Community-Dwelling Japanese: the Tanushimaru Study.

Background In patients with cardiovascular diseases, inflammatory and hemostatic biomarkers are significant indicators of prognosis. We investigated whether circulating inflammatory and hemostatic biomarkers were predictive markers for all-cause death and cancer death in a population of community-dwelling Japanese. Methods We studied 1,920 healthy Japanese adults who underwent health examinations in 1999. Those who reported a history of inflammatory diseases and malignancy on a baseline questionnaire were excluded. Inflammatory and hemostatic biomarkers were measured in the remaining 1,862 participants, who were followed up periodically for 10 years. Multivariate proportional hazards regression analysis was used to estimate all-cause and cancer mortality. Results A total of 258 participants died during follow-up: 87 from cancer, 38 from cerebro-cardiovascular diseases, and 133 from other diseases. Mean C-reactive protein (CRP) levels at baseline were significantly higher in decedents than in survivors. Mean von Willebrand factor (vWF) levels at baseline were significantly higher in decedents than in survivors. The Cox proportional hazards model after adjustments for age and sex showed that CRP (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.06-1.51) and vWF (HR, 1.01; 95% CI, 1.00-1.01) were independent predictors of all-cause death. CRP (HR, 1.40; 95% CI, 1.06-1.86) and vWF (HR, 1.01; 95% CI, 1.00-1.02) were also independent predictive markers for cancer death. Conclusions Serum CRP and vWF were predictors of all-cause death and cancer death in the population of community dwelling Japanese.