Ei-Ichi Toda

Association Between Serum Uric Acid, Metabolic Syndrome, and Carotid Atherosclerosis in Japanese Individuals

Objective—There are few data available on possible independent association between uric acid and carotid atherosclerosis. Here we first sought to investigate association between uric acid levels and metabolic syndrome in Japanese; second, we assessed whether there is an independent association of uric acid with prevalence of carotid atherosclerosis in individuals subdivided according to gender and metabolic syndrome status. Methods and Results—Cross-sectional data from 8144 individuals who underwent general health screening were analyzed. After adjusting for age, total cholesterol, and smoking status, the odds ratios (95% CI) of sex-specific quartiles of serum uric acid for metabolic syndrome were 1.0, 1.06 (0.60 to 1.87), 2.18 (1.30 to 3.64), and 4.17 (2.56 to 6.79) in women, and 1.0, 0.92 (0.74 to 1.14), 1.52 (1.25 to 1.65), and 1.97 (1.61 to 2.40) in men. After adjusting for age, serum levels, total cholesterol, and smoking status, prevalence of carotid plaque was higher in subjects in the second, third, and fourth quartiles of uric acid level with odds ratios (95% CI) of 1.24 (1.01 to 1.52), 1.37 (1.11 to 1.68), and 1.31 (1.05 to 1.63), respectively, in men without metabolic syndrome but not in men with metabolic syndrome or in women with or without metabolic syndrome. Conclusion—The prevalence of metabolic syndrome showed a graded increase according to serum uric acid values in both genders. In men who did not have metabolic syndrome, uric acid was found to be an independent risk factor for incidence of carotid plaque.

Hypertension Is the Most Common Component of Metabolic Syndrome and the Greatest Contributor to Carotid Arteriosclerosis in Apparently Healthy Japanese Individuals

The cluster of metabolic and hemodynamic risk factors known as metabolic syndrome is known to be a risk factor for ischemic cardiovascular diseases and stroke. By analyzing the cross-sectional data from 8,144 individuals (age 19−88 years) who underwent general health screening, we have investigated the prevalence of metabolic syndrome, as diagnosed by modified-National Cholesterol Education Program (NCEP) criteria corresponding to the following five categories: triglycerides ≥150 mg/dl; high density lipoprotein (HDL)-cholesterol <40 mg/dl in men or <50 mg/dl in women; fasting plasma glucose ≥110 mg/dl; systolic/diastolic blood pressure ≥130/85 mmHg; and body mass index >25 kg/m2. We found that the prevalence of metabolic syndrome was 19% in men and 7% in women. After adjustment for age, metabolic syndrome was found to be significantly more prevalent in men than in women, with an odds ratio of 3.08 (95% confidence interval [CI] 2.62−3.61, p<0.0001). Among the five metabolic/hemodynamic risk factor components, hypertension was observed most frequently in individuals with metabolic syndrome, at 85% in men and 87% in women. In addition, multivariate logistic regression analysis adjusted for age, sex, serum total cholesterol levels, and smoking status showed that hypertension possessed the greatest odds ratio (1.43, 95% CI 1.27−1.60) for carotid plaque among the metabolic/hemodynamic risk factors. These data emphasize the importance of controlling blood pressure for reducing the risk of both metabolic syndrome and carotid arteriosclerosis in apparently healthy individuals.

Plasma amino acid profile is associated with visceral fat accumulation in obese Japanese subjects.

What is already known about this subject •  Asians with metabolic complications associated with obesity, a low body mass index and a low waist circumference have a greater proportion of visceral adipose tissue for a given amount of total body fat compared with Europeans. •  Apparent obese humans and obese animal models show an elevation of branched‐chain amino acid levels in plasma. •  A multivariate logistic regression model of plasma free amino acids has been used to screen for several types of cancers in clinical settings.

Association between Cigarette Smoking and Chronic Kidney Disease in Japanese Men

Cigarette smoking may affect urinary albumin excretion and the glomerular filtration rate in both diabetic and nondiabetic subjects. Here we investigated the association between smoking and decreased or elevated glomerular filtration rate (GFR) and albuminuria by analyzing data from 7,078 Japanese men who had undergone a general health screening between 2005 and 2006. GFR was estimated with the Modified Diet in Renal Disease (MDRD) equation, and low estimated GFR (eGFR) and elevated eGFR were defined, respectively, as eGFR <60 and >90.7 mL/min/1.73 m2. Albuminuria was considered present when the urinary albumin excretion ratio (UAER), expressed as mg/g creatinine, was ≥30 mg/g. Multivariate logistic regression analysis showed that current smoking was associated inversely with low eGFR, and positively with albuminuria and elevated eGFR. The association between current smoking and low or elevated GFR was dependent on the number of cigarettes smoked per day. Former smoking was also significantly inversely associated with low eGFR, but the association between former smoking and albuminuria or elevated eGFR was not significant, even in individuals who had stopped smoking less than 1 year before. These data suggest that cigarette smoking may increase the prevalence of albuminuria and elevated eGFR or hyperfiltration, traits that might be reversed by smoking cessation. Although this concept should be verified by future longitudinal studies, our data suggest that we may need to take into account an individuals smoking status when assessing the presence or absence of chronic kidney disease because cigarette smoking may transiently increase eGFR.

Association between Chronic Kidney Disease and Carotid Intima-Media Thickening in Individuals with Hypertension and Impaired Glucose Metabolism

We investigated whether chronic kidney disease (CKD) was associated with carotid intima-media thickening in 1,351 male individuals undergoing general health screening. Glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease equations using 0.881 as a coefficient for Japanese, and low estimated GFR (eGFR) was defined as an eGFR value of <60 mL/min/1.73 m2. Albuminuria was defined as a urine albumin–to−urine creatinine ratio of ≥30 mg/g, and CKD was defined when low eGFR and/or albuminuria was present. After adjusting for age, CKD was associated with carotid intima-media thickening with an odds ratio of 1.47 (95% confidence interval [CI] 1.05–2.06, p=0.0024). After adjusting for age, fasting plasma glucose, and smoking status, both albuminuria and low eGFR were significantly associated with intima-media thickening in individuals with hypertension with an odds ratio of 1.85 (95% CI 1.13–3.03, p=0.015) and 1.79 (95% CI 1.09–2.94, p=0.022), respectively. On the other hand, neither of them was associated with carotid intima-media thickening in individuals without hypertension. Similarly, after adjusting for age, systolic blood pressure, and smoking status, both albuminuria and low eGFR were significantly associated with intima-media thickening in individuals with high fasting glucose (defined as fasting plasma glucose levels of ≥110 mg/dL or current use of anti-diabetic medication), but not in those without. Our data indicate that CKD or its components (low eGFR and albuminuria) may be associated with early carotid atherosclerosis in low-risk individuals, such as those undergoing general health screening, who have hypertension and/or impaired glucose metabolism.

Are Serum Carcinoembryonic Antigen Levels Associated With Carotid Atherosclerosis in Japanese Men

Objective—Carcinoembryonic antigen (CEA), a serological marker of malignant tumors, may show a modest increase under some nonmalignant conditions, such as ageing and cigarette smoking. We have investigated whether serum CEA levels are associated with early carotid atherosclerosis. Methods and Results—Cross-sectional data from 4181 male individuals who underwent general health screening were analyzed. The interquartile of cutoff values of serum CEA levels were 1.0, 1.6, and 2.5 ng/mL. Cigarette smoking was associated with increased serum CEA levels in a dose- and duration-dependent manner, and this association was more prominent in current than former smokers. Logistic regression analysis adjusted for age, body mass index, serum lipid and glucose profiles, white blood cell count, C-reactive protein, and smoking habits showed that the first, second, third, and fourth CEA quartiles were associated with carotid plaque with an odds ratio of 1 (reference), 1.25 (95% CI 1.03 to 1.52, P=0.023), 1.49 (95% CI 1.23 to 1.82 P<0.001), and 1.34 (95% CI 1.08 to 1.65, P=0.007), respectively. Although serum CEA levels were associated with metabolic syndrome, association between serum CEA and carotid plaque was significant in individuals without metabolic syndrome. Conclusions—Serum CEA was associated with carotid atherosclerosis independently of atherogenic risk factors and markers of inflammation. Our data suggest that a slight elevation of CEA in current smokers, as well as in never smokers, may not be an innocuous observation from the viewpoint of atherosclerosis.

Association between Obesity and Chronic Kidney Disease in Japanese : Differences in Gender and Hypertensive Status?

Obesity is a known risk factor for hypertension and diabetes, both of which ultimately promote renal dysfunction. In the current study, we investigated the association between body mass index (BMI) and chronic kidney disease (CKD) in 8,168 Japanese individuals (2,924 women, 5,244 men) who underwent general health screening. CKD was diagnosed if the estimated glomerular filtration rate (eGFR) was less than 60 mL/min/1.73 m2 (designated as low eGFR) and/or if the urinary albumin/creatinine value was equal to or greater than 30 mg/g (designated as albuminuria). Logistic regression analysis adjusted for age, systolic blood pressure, fasting glucose, and smoking habits showed that, in men, both overweight (BMI 25–29 kg/m2) and obesity (BMI ≥30 kg/m2) were associated with increased prevalence of low eGFR and albuminuria, whereas, in women, obesity was associated with albuminuria, but neither overweight nor obesity was associated with low eGFR. After multivariate adjustment, logistic regression analysis showed that BMI had a graded association with both low eGFR and albuminuria in men. On the other hand, in women, the second and third BMI quartiles were associated with a lower prevalence of albuminuria in comparison with the first BMI quartile. Essentially the same results were obtained when the subjects were subdivided according to the presence and absence of hypertension. Our data showed that overweight and obesity were associated with increased risk for CKD in Japanese individuals undergoing a general health screening, irrespective of the presence or absence of hypertension, although there was a gender difference in these associations.

Metabolic Syndrome May Not Associate With Carotid Plaque in Subjects With Optimal, Normal, or High-Normal Blood Pressure

Much evidence indicates that metabolic syndrome is a risk factor for the development of cardiovascular disease, but whether metabolic syndrome is an independent risk factor for early atherosclerosis in the individuals with only minor hemodynamic abnormalities, if any, is not well investigated. Here we have investigated the association between metabolic syndrome and carotid atherosclerosis in individuals with blood pressure of <140/90 mm Hg. Between 1994 and 2003, 8143 subjects underwent general health screening including carotid ultrasonography. Of 8143 individuals, 5661 individuals without antihypertensive medications who had blood pressure of <140/90 mm Hg were considered to have optimal, normal, or high-normal blood pressure. After adjustment for age, systolic blood pressure, body mass index, total and high-density lipoprotein cholesterol, triglycerides, fasting glucose, and smoking status, metabolic syndrome was not found to be an independent risk factor for carotid plaque (odds ratio: 1.65; 95% CI; 0.72 to 3.76 in women and odds ratio: 0.95; 95% CI: 0.70 to 1.28 in men) or for carotid intima-media thickening (odds ratio: 0.56; 95% CI: 0.18 to 1.72 in women and odds ratio: 0.93 95% CI: 0.62 to 1.38 in men) in these subjects. Thus, presence of metabolic syndrome may not increase the prevalence of carotid atherosclerosis independent of other cardiovascular risk factors in Japanese individuals with optimal, normal, or high-normal blood pressure.

Relationship between Albuminuria, Low eGFR, and Carotid Atherosclerosis in Japanese Women

In this cross-sectional study, we have investigated whether chronic kidney disease components were associated with carotid plaque and carotid intima-media thickening in women. Between April 2005 and May 2006, 830 women underwent general health screening including carotid ultrasonography and urinary albumin excretion, and were enrolled in the study. Of these individuals examined, 83 (10%) had albuminuria, 203 (24%) had low estimated GFR (eGFR), and 24 (3%) had both albuminuria and low eGFR. Univariate analysis showed that albuminuria, but not low eGFR, was associated with carotid plaque, and that both albuminuria and low eGFR were positively associated with carotid intima-media thickening. Age-adjusted logistic regression analysis showed that albuminuria was positively associated with carotid plaque with an odds ratio of 2.48 (95% CI 1.49–4.11, p < 0.001). On the other hand, association between albuminuria and carotid intima-media thickening was not statistically significant after age adjustment. Positive association between albuminuria and carotid plaque was present when either hypertension or high fasting glucose was absent. In conclusion, in Japanese women who underwent general health screening, albuminuria, but not low eGFR, was positively associated with carotid plaque.

Impacts of Changes in Obesity Parameters for the Prediction of Blood Pressure Change in Japanese Individuals

Aims and Methods: By analyzing data from 2,861 individuals who underwent general health screening 2 years running, we have investigated the impact of changes in waist circumference (WC) and body mass index (BMI) over a 1-year period on systolic blood pressure (BPs). We termed WC, BMI, and BPs at the first visit as WC1, BMI1, and BPs1, respectively, and those at the second visit as WC2, BMI2, and BPs2, respectively. The %dWC, %dBMI, and %dBPs was defined as (WC2 – WC1)/WC1 × 100, (BMI2 – BMI1)/BMI1 × 100, and (BPs2 – BPs1)/BPs1 × 100, respectively. Results: In multivariate regression analysis using age, BPs1, WC1, and %dWC as independent variables, %dWC was a significant predictor for %BPs only in men. %dBMI was a significant predictor for %BPs in both genders when age, BPs1, BMI1, and %dBMI were used as independent variables. Compared with individuals with both %dWC <0 and %dBMI <0, age-adjusted %dBPs was significantly greater in those with both %dWC <0 and %dBMI ≧0; however, it did not significantly differ in those with both %dWC ≧0 and %dBMI <0. Conclusion: Our data suggest that the impact of BMI change might be greater than WC change in terms of BPs change during this short period.