Kiminori Yamane

Pulse Wave Velocity Predicts Cardiovascular Mortality

Background Arterial stiffness measurements, generally from pulse wave velocity (PWV), are widely used with little knowledge of their relationship to long-term cardiovascular mortality in general populations. Methods and Results We studied a cohort of 492 Japanese-Americans living in Hawaii (mean age: 63.7 ±8.8 years) to assess the relationship between PWV and cardiovascular disease mortality and all-cause mortality. During the 10-year follow-up, 43 patients died (14 from cardiovascular events). The cohort was divided into 2 groups by the cut-off value of PWV (9.9 m/s) represented in the receiver operating characteristic curve. The risk ratio for PWV values >9.9 m/s to all-cause mortality was 1.28 [95% confidence interval (CI): 1.14-1.42], and adjusted for other risk factors this ratio was 1.42 (95% CI: 0.96-2.11). The corresponding risk ratios for cardiovascular mortality was 4.46 (95% CI: 1.61-12.32) and 4.24 (95% CI: 1.39-12.96), respectively. Conclusions The present study demonstrated that an increased PWV value is associated with future cardiovascular disease death in Japanese-Americans living in Hawaii. (Circ J 2005; 69: 259 - 264)

Airflow Limitation in Smokers Is Associated with Subclinical Atherosclerosis

RATIONALE Chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and mortality from cardiovascular disease. Although a close association between COPD and atherosclerosis has been speculated, such scientific information is limited. OBJECTIVES To evaluate subclinical atherosclerosis in smokers with airflow limitation. METHODS The subjects of this study were healthy middle-aged men. Smokers with airflow limitation (n = 61) and age-matched control smokers (n = 122) and control never-smokers (n = 122) without airflow limitation were included in the present study. Subjects with diabetes, acute infection, and respiratory disease other than COPD were excluded beforehand. All subjects underwent chest radiogram, spirometry, blood sampling, and carotid ultrasonography. We determined carotid intima-media thickness and focal atheromatous plaque as indicators of subclinical atherosclerosis. MEASUREMENTS AND MAIN RESULTS Mean carotid intima-media thickness was greater in smokers with airflow limitation than in control smokers (P < 0.01) and control never-smokers (P < 0.005). Focal carotid plaque was significantly more prevalent in smokers with airflow limitation than in control never-smokers (P < 0.005). Multivariate analyses showed significant associations between thickened intima-media thickness and decreased percent predicted FEV(1) (P = 0.001) and between plaque and log(10) C-reactive protein (P = 0.013) independent of age, pack-years of smoking, body mass index, peripheral mean arterial pressure, heart rate, glucose, and low-density lipoprotein cholesterol. CONCLUSIONS Smokers with airflow limitation had exaggerated subclinical atherosclerosis. This study suggests that middle-aged men who are susceptible to COPD may also be susceptible to vascular atherosclerosis by smoking, and atherosclerotic change starts early in the disease process of COPD.

Circulating visfatin level is correlated with inflammation, but not with insulin resistance

Objective  Recent studies, both in vitro and in vivo, have indicated that visfatin is one of the inflammatory cytokines, although the relationship between visfatin and insulin resistance remains inconclusive. Accordingly, we assessed the association between visfatin concentrations in serum and those of interleukin‐6 (IL‐6) and C‐reactive protein (CRP), known as markers of systemic inflammation, and also investigated the relationship between these serum concentrations and insulin resistance.

Westernized food habits and concentrations of serum lipids in the Japanese.

To investigate the association of westernized food habits and concentrations of serum lipids in the Japanese, we studied 1200 healthy Japanese living in Hiroshima prefecture and 1483 ethnic Japanese from Hiroshima prefecture living in the Hawaii Islands and Los Angeles. The nutritional assessments were made by the same dietitians. No major difference was observed in the total energy intake between the Japanese and the Japanese-Americans in both males and females. However, the intake of animal fat and simple carbohydrates (especially fructose) were markedly greater, and that of complex carbohydrates lower, in the Japanese-Americans compared with the Japanese. The mean serum cholesterol (CH), LDL-CH and serum triglyceride (TG) levels were significantly higher in the Japanese-Americans in both sexes. The mean HDL-CH concentration was similar between the two groups in males, but it was approximately 7 mg/dl higher in Japanese-American females. Using the 75 percentile values of CH and TG in the Japanese in Hiroshima, the frequency of WHO types IIa and IIb hyperlipidemia was about twice as high in the Japanese-Americans. These results suggest that westernized food habits in the Japanese include qualitative changes in animal fat, simple carbohydrate and complex carbohydrate diet rather than an increase in the total energy intake. These changes are associated with marked increases in the concentrations of serum CH and TG and increased prevalence of types IIa and IIb hyperlipidemia.

Westernization of lifestyle markedly increases carotid intima-media wall thickness (IMT) in Japanese people.

To illustrate the impact of westernization of lifestyle on the development of pre-clinical atherosclerosis in Japanese people, we compared risk factors for atherosclerosis such as serum lipids, blood pressure, BMI, insulin resistance, and smoking habits between non-diabetic native Japanese and non-diabetic Japanese Americans. Two hundred and twenty two non-diabetic Japanese Americans living in Hawaii and 271 non-diabetic Japanese living in Hiroshima, Japan were studied. Carotid intima-media wall thickness (IMT) was measured in all subjects by one physician. For all measurements the same ultrasound instrumentation was used. Although no significant differences were seen in serum total cholesterol (TC), triglycerides, or LDL-cholesterol (LDL-C) levels between the two groups in the 1998 study, previous to 1998 these three parameters were significantly higher in Japanese Americans than native Japanese in our study which has spanned the past 20 years. IMT was significantly greater in Japanese Americans than native Japanese (1.20+/-0.03 mm vs. 0.98+/-0.03 mm, (mean+/-S.E.) respectively; P<0.0001). Moreover Japanese Americans reach an IMT of 1.1 mm at age 50, whereas the native Japanese reach this value at age 70. These observations indicate more rapid atherosclerosis progression in Japanese Americans. Based on our IMT measurements, the status and the estimated progression of atherosclerosis in Japanese Americans is increased. Since IMT is a validated endpoint for assessment of atherosclerotic disease risk, it can be concluded that Japanese Americans are at increased risk for cardiovascular disease.

Manganese superoxide dismutase Ala16Val polymorphism is associated with the development of type 2 diabetes in Japanese-Americans

AIMS Recent evidence indicates that oxidative stress may play an important role in the pathogenesis of insulin resistance and that gene polymorphism (Ala16Val) of manganese superoxide dismutase (MnSOD) may protect against reactive oxygen species (ROS) function. We aimed to test the hypothesis that the Ala16Val variant could be associated with the development of type 2 diabetes. METHODS We examined 523 nondiabetic Japanese-Americans who underwent a 75g oral glucose tolerance test (OGTT) and were followed for an average of 9.9 years. Cox proportional hazard analysis, stratified by category of OGTT, was used to determine whether the Ala16Val polymorphism was a risk factor in the development of type 2 diabetes. RESULTS During the follow-up period, 65 subjects developed type 2 diabetes. Compared with Ala allele carriers, subjects with a Val homozygote showed significantly higher risk for developing diabetes (stratified hazard ratio=2.05 [95% confidence interval 1.03-4.08]; P=0.041) after adjustment for age, gender, systolic blood pressure, total cholesterol, body mass index, and homeostasis model assessment. CONCLUSIONS We demonstrated that the MnSOD Ala16Val polymorphism might be associated with development of type 2 diabetes among Japanese-Americans. These results suggest that insufficient ROS scavenging might be associated with a susceptibility to glucose intolerance.

White blood cell count, especially neutrophil count, as a predictor of hypertension in a Japanese population.

Although several studies have shown that high WBC count is a risk factor for hypertension, the relationship between WBC count and the incidence of hypertension in Japanese is poorly understood, as are the effects of WBC components on that relationship. Our objective was to verify in a Japanese population whether WBC or differential WBC count predicts hypertension incidence. A total of 9,383 initially hypertension-free subjects (3,356 men and 6,027 women), whose WBC counts were within the normal range (3,000 to <10,000 cells/mm3), were followed from 1965 to 2004. During this 40-year follow-up, 4,606 subjects developed hypertension. After adjusting for conventional risk factors, including smoking status, we found that elevated WBC count was associated with hypertension incidence in a Cox regression model with both fixed and time-varying covariates for women. For men, elevated WBC count was a significant risk factor for hypertension only in the time-varying Cox-regression covariate. We also observed a significant association between increased neutrophil count and hypertension incidence among women. In a fully adjusted model, the relative risks of hypertension incidence, from the lowest to the highest quartiles of neutrophil count, were 1.00, 1.18, 1.28, and 1.22 in women (p for trend <0.001). In conclusion, elevated WBC count predicted an increased incidence of hypertension in Japanese, especially among females. Moreover, neutrophils were the major WBC component contributing to the increased risk.

The effect of polymorphism in the intestinal fatty acid-binding protein 2 gene on fat metabolism is associated with gender and obesity amongst non-diabetic Japanese-Americans.

Aim:  The role of the codon 54 polymorphism of the fatty acid‐binding protein 2 (FABP2) gene on fat metabolism has been controversial. Assuming that the effects of the polymorphism were modulated by gender and obesity which were related to lipid and glucose metabolism, we investigated this polymorphism and its effect on fat metabolism according to such factors.

The single nucleotide polymorphism upstream of insulin-induced gene 2 ( INSIG2) is associated with the prevalence of hypercholesterolaemia, but not with obesity, in Japanese American women.

Insulin-induced gene 2 (insig-2) protein is known to play important roles in cholesterol and TAG metabolism both in vivo and in vitro. One particularly interesting single nucleotide polymorphism (SNP), rs7566605, located 10 kb upstream of INSIG2 was reported to have the strongest association with obesity among 86 604 SNP, while the relationship with dyslipidaemia is uncertain. Eight hundred and eighty-five Japanese Americans (347 men and 538 women) and 378 Japanese (182 men and 196 women) were enrolled, and the rs7566605 SNP, which is consistent with either G or C, was determined. We investigated the association between the rs7566605 SNP and the prevalence of hypercholesterolaemia or hypertriacylglycerolaemia, or obesity parameters, as assessed by BMI, waist girth and percentage body fat. There were no significant differences in BMI, waist girth and percentage body fat according to the genotype in each of the four groups, which was divided by population and sex. The prevalence of hypercholesterolaemia was significantly different between the genotypes in Japanese American female subjects (GG, 62.2 %; GC, 57.1 %; CC, 42.1 %; P = 0.021), but not in the other subjects. In Japanese American women, the subjects with the CC genotype had a 0.43-fold decreased risk (95 % CI 0.24, 0.80) for hypercholesterolaemia compared with the GG genotype after adjustment for age, percentage body fat, smoking status and hormone replacement therapy. The CC genotype of the rs7566605 SNP is suggested to be a protective genetic factor against the progression of hypercholesterolaemia on a high-fat diet, especially in Japanese female subjects.

Low serum levels of total and high-molecular-weight adiponectin predict the development of metabolic syndrome in Japanese-Americans.

Background: Adiponectin is thought to play a significant role in the development of both insulin resistance and metabolic syndrome. Yet, there is very few evidence about the association plasma adiponectin and metabolic syndrome in the prospective study. Adiponectin exists as multimers in serum, and high-molecular-weight (HMW) adiponectin is particularly considered to be the active form of the protein. Aim: We investigated whether serum HMW adiponectin as well as total adiponectin is associated with the development of metabolic syndrome in a longitudinal study. Subjects and methods: We enrolled 224 men and 312 women of Japanese-Americans without metabolic syndrome at baseline who were followed for an average of 3.2 yr. The association of plasma total and HMW adiponectin with a progression to metabolic syndrome was examined. Results: Subjects who developed metabolic syndrome had significantly lower plasma total and HMW adiponectin levels at baseline than those who did not develop metabolic syndrome. In a Cox proportional hazards model, lower total and HMW adiponectin levels were independent risk factors for the development of metabolic syndrome after adjusting for age, body mass index, classification of 75-g glucose tolerance test, and homeostasis model assessment (hazards ratio: total, 0.684, p=0.017, in men; 0.606, p=0.003, in women; HMW, 0.687, p=0.014, in men; 0.704, p=0.029, in women, respectively). Conclusions: Low circulating levels of total and HMW adiponectin may be a possible predictor for the development of metabolic syndrome.