Yuko Ishizaka

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.

Association between hepatitis C virus seropositivity, carotid-artery plaque, and intima-media thickening.

We investigated the relation between positivity for hepatitis C virus (HCV) and carotid-artery plaque and carotid intima-media thickening by analysing cross-sectional data of individuals undergoing a general health screening test. Of 4784 individuals enrolled, 104 (2.2%) were seropositive for HCV. After adjustment for confounding risk factors, HCV seropositivity was found to be associated with an increased risk of carotid-artery plaque (odds ratio 1.92 [95% CI 1.56-2.38], p=0.002) and carotid intima-media thickening (2.85 [2.28-3.57], p<0.0001). These findings suggest a possible role for chronic hepatitis C in the pathogenesis of carotid arterial remodelling.

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.

Absolute value of visceral fat area measured on computed tomography scans and obesity-related cardiovascular risk factors in large-scale Japanese general population (the VACATION-J study)

Abstract Background. The management of cardiovascular risk factors is important for prevention of atherosclerotic cardiovascular diseases (ACVD). Visceral fat accumulation plays an important role in the clustering of cardiovascular risk factors, leading to ACVD. The present study investigated the gender- and age-specific relationship between obesity-related cardiovascular risk factor accumulation and computed tomography (CT)-measured fat distribution in a large-scale Japanese general population. Methods and results. Fat distribution was measured on CT scans in 12,443 subjects (males/females = 10,080/2,363), who underwent medical health check-up at 9 centers in Japan. The investigated obesity-related cardiovascular risk factors were hyperglycemia, dyslipidemia, and elevated blood pressure. Visceral fat area (VFA) for all males and old females showed almost symmetric distribution, while that of young females showed skewed distribution with a marked left shift. Only a small proportion of young females had large visceral fat and cardiovascular risk accumulation. The mean number of risk factors exceeded 1.0 at around 100 cm2 for VFA in all groups, irrespective of gender, age (cut-off age 55), and BMI (cut-off BMI 25 kg/m2). Conclusions. In this large-scale Japan-wide general population study, an absolute VFA value of about 100 cm2 equated with obesity-related cardiovascular risk factor accumulation, irrespective of gender, age, and BMI. Clinical trial registration information. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000002780&language=E.

Association Between Insulin Resistance and Carotid Arteriosclerosis in Subjects With Normal Fasting Glucose and Normal Glucose Tolerance

Objective—We examined the possible association between insulin resistance and carotid arteriosclerosis in subjects who had both normal fasting glucose and normal glucose tolerance after intake of a glucose load. Methods and Results—Our subjects were individuals who underwent general health screening at our institute, which included carotid ultrasound and oral glucose tolerance testing. Of the 1238 subjects enrolled in our study, 738 (60%) were classified as normal, defined as a normal fasting glucose level and normal glucose tolerance, and 334 (27%) and 166 (13%) were classified as borderline and diabetic, respectively, according to the criteria of the Japan Diabetes Society. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index to measure insulin resistance. In normal-type subjects, univariate analysis showed that insulin resistance, but not insulin secretion, was associated with the presence of carotid plaque. Multivariate analysis showed that HOMA-IR was positively associated with carotid plaque in normal-type subjects, with an odds ratio of 1.19 (95% confidence interval, 1.00 to 1.41;P <0.05). Conclusions—These data suggest the possibility that the presence of higher insulin resistance could be a risk factor for carotid arteriosclerosis in subjects with normal fasting glucose and normal glucose tolerance.

Plasma Free Amino Acid Profiles Predict Four-Year Risk of Developing Diabetes, Metabolic Syndrome, Dyslipidemia, and Hypertension in Japanese Population.

Plasma free amino acid (PFAA) profile is highlighted in its association with visceral obesity and hyperinsulinemia, and future diabetes. Indeed PFAA profiling potentially can evaluate individuals’ future risks of developing lifestyle-related diseases, in addition to diabetes. However, few studies have been performed especially in Asian populations, about the optimal combination of PFAAs for evaluating health risks. We quantified PFAA levels in 3,701 Japanese subjects, and determined visceral fat area (VFA) and two-hour post-challenge insulin (Ins120 min) values in 865 and 1,160 subjects, respectively. Then, models between PFAA levels and the VFA or Ins120 min values were constructed by multiple linear regression analysis with variable selection. Finally, a cohort study of 2,984 subjects to examine capabilities of the obtained models for predicting four-year risk of developing new-onset lifestyle-related diseases was conducted. The correlation coefficients of the obtained PFAA models against VFA or Ins120 min were higher than single PFAA level. Our models work well for future risk prediction. Even after adjusting for commonly accepted multiple risk factors, these models can predict future development of diabetes, metabolic syndrome, and dyslipidemia. PFAA profiles confer independent and differing contributions to increasing the lifestyle-related disease risks in addition to the currently known factors in a general Japanese population.

Angiographic follow-up after successful percutaneous coronary angioplasty for chronic total coronary occlusion: Experience in 110 consecutive patients

Percutaneous transluminal coronary angioplasty (PTCA) was performed in 110 consecutive patients (111 vessels) with chronically occluded coronary arteries and was successful in 69 patients (69 vessels). Successful initial PTCA was related to the extent of coronary artery disease, the morphology of the proximal surface of the occlusion site, and the clinical duration of occlusion. Repeat angiography was performed for 62 patients, with successful initial PTCA and demonstrated restenosis in 34 (55%) patients, of whom 11 had total occlusion. Repeat PTCA was performed in 30 patients and was successful in 80%. Follow-up angiography after repeat PTCA was carried out in all patients who underwent successful second PTCA, and, it demonstrated re-restenosis in 7 (29%) patients. In this study, among 111 total occlusions, 28 vessels undergoing successful initial PTCA and 17 undergoing successful repeat PTCA were free from restenosis or re-restenosis at the time of follow-up angiography.

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.

Changes in Waist Circumference and Body Mass Index in Relation to Changes in Serum Uric Acid in Japanese Individuals

Objective. Studies have shown that obesity is associated with an increase in serum uric acid; and few data are available on the relationship between changes in measures of obesity and changes in uric acid concentrations. We investigated the relationship among percentage changes in waist circumference (%dWC), body mass index (%dBMI), and serum uric acid (%dUA). Methods. The data of 3153 individuals [1968 men, 1185 women (536 premenopausal, 649 postmenopausal)] who underwent general health screening over a 2-year period and were not taking antihyperuricemic medication were analyzed. Results. Stepwise multiple regression analysis showed that %dBMI was associated positively with %dUA in postmenopausal women and men, and the association retained statistical significance after adjustment for changes in blood pressure and in renal function. Association between %dBMI and %dUA was not significant in premenopausal women. In men, %dWC was a predicting factor for %dUA, although it did not remain significant when %dBMI was used as a covariate in the statistical model. Multivariate logistic regression analysis showed that the odds ratio of the association between the lowest %dBMI quartile (%dBMI < –1.86) and the lowest %dUA quartile (%dUA < –7.41) was 2.04 (95% CI 1.35–3.07) in postmenopausal women and 1.46 (95% CI 1.14–1.86) in men. Conclusion. Weight loss may represent an effective nonmedical strategy for reducing serum UA levels, especially in postmenopausal women and men.