Tomoshige Hayashi

Visceral Adiposity Is an Independent Predictor of Incident Hypertension in Japanese Americans

Context Central obesity and hypertension are well-established components of the metabolic syndrome, but what exactly is the relationship between visceral adiposity and hypertension? Contribution This prospective study used computed tomography to measure multiple body fat areas of 300 middle-aged, normotensive Japanese Americans. Ninety-two participants developed hypertension within 10 to 11 years. Greater visceral adiposity, independent of other measures of body fat and other risk factors, such as plasma insulin and glucose levels, was associated with increased risk for hypertension. Cautions Relationships between visceral adiposity and the development of hypertension may vary in different ethnic groups. The Editors A central pattern of body fat distribution is now generally considered to play an important role in the metabolic syndrome, which involves obesity, insulin resistance, hyperinsulinemia, dyslipidemia, glucose intolerance, and hypertension (1, 2). In particular, visceral adiposity rather than regional or generalized obesity appears to play a key role in these diseases (3-7). Several cross-sectional and prospective studies have examined associations between hypertension and greater central obesity, as measured by waist circumference, the ratio of waist-to-hip circumference, or the ratio of subscapular-to-triceps skinfold thickness (8-15). The cross-sectional studies have reported a positive association (8, 9), but the prospective studies have been inconclusive (10-15). These studies have posited that visceral adiposity and insulin resistance are the most important factors linking greater abdominal obesity (as assessed by surface measurements) and hypertension. Although visceral fat is thought to affect the prevalence of hypertension, only 3 cross-sectional studies have suggested a possible association between visceral adiposity (measured by using computed tomography [CT]) and blood pressure (3, 4, 16); however, the results of these studies were inconclusive. No prospective studies have examined whether directly measured visceral fat is associated with an increased risk for incident hypertension. Therefore, we prospectively examined the relationship between directly measured visceral adiposity and the risk for incident hypertension, independent of other measurements of total and regional adiposity and fasting plasma insulin. Methods Study Sample Between 1983 and 1988, we enrolled 658 second- and third-generation Japanese Americans who were between 34 and 76 years of age (mean age, 54.2 years) into the Japanese American Community Diabetes Study (17, 18). Participants were chosen from volunteers through community-wide recruitment and were representative of Japanese-American residents of King County, Washington, in age distribution, residential distribution, and parental immigration pattern. A comprehensive mailing list and telephone directory that included almost 95% of the Japanese-American population of King County, Washington, was used. All participants were of 100% Japanese ancestry. Participants returned for follow-up examinations 5 to 6 and 10 to 11 years after a baseline evaluation. For the current analysis, eligible participants had systolic blood pressure less than 140 mm Hg and diastolic blood pressure less than 90 mm Hg and were not taking antihypertensive or oral hypoglycemic medications or insulin. We excluded 277 of the 658 participants in the original cohort because they did not meet the inclusion criteria. We excluded an additional 67 persons because of death, loss to follow-up, or withdrawal from the study. Another 14 persons who completed follow-up but had missing covariate information were also excluded. The analytic cohort consisted of 300 persons (Figure). The follow-up rate in the present study was 91% (345 of 381) at the 5- to 6-year examination and 80% (304 of 381) at the 10- to 11-year examination (Figure). Figure. Flow of participants through the study. Data Collection All measurements were made in the General Clinical Research Center at the University of Washington, Seattle, Washington. The Human Subjects Review Committee at the University of Washington approved the protocol for this research, and we obtained signed informed consent from all participants. At all examinations, blood pressure was measured to the nearest 2 mm Hg with a mercury sphygmomanometer while the participant was in a recumbent position. Systolic blood pressure was determined by the first perception of sound, and diastolic blood pressure was determined at the disappearance of sounds (fifth-phase Korotkoff). Average blood pressure was calculated from the second and third of 3 consecutive measurements. We diagnosed hypertension at baseline or follow-up if the average systolic blood pressure was 140 mm Hg or greater, the average diastolic blood pressure was 90 mm Hg or greater, or the participant was receiving antihypertensive medications. We classified participants as hypertensive if they met these criteria at the follow-up examination at 5 to 6 years or 10 to 11 years (Figure). All patients received a 75-g oral glucose tolerance test after a 10-hour fast. We then used the American Diabetes Association criteria (19) to classify patients as having normal glucose tolerance, impaired glucose tolerance, or type 2 diabetes mellitus. Blood samples were drawn after an overnight 10-hour fast and during an oral glucose tolerance test for measurement of plasma glucose and insulin levels. We used an automated glucose oxidase method to assay plasma glucose. Fasting plasma insulin was measured by radioimmunoassay, as reported previously (5, 7). We measured triglyceride and high-density lipoprotein cholesterol levels in the Northwest Lipid Research Laboratory, according to modified procedures of the Lipid Research Clinics (20). We calculated body mass index (BMI) as the weight in kilograms divided by height in meters squared. For CT scans, we used single slices of the thorax, abdomen (at the umbilicus), and mid-thigh to measure cross-sectional subcutaneous thoracic, abdominal, and right thigh and intra-abdominal fat areas (measured in cm2), as described elsewhere (21). We directly estimated visceral adiposity from the intra-abdominal fat area. This measurement has been reported to have a high correlation with directly ascertained total visceral fat volume measured by using CT or magnetic resonance imaging (22, 23). We calculated total subcutaneous fat area as the sum of subcutaneous thoracic and abdominal fat areas and twice the right thigh subcutaneous fat area. We defined total fat area as total subcutaneous fat area plus intra-abdominal fat area. Among Japanese Americans, total fat area correlates highly with fat mass, as measured by hydrodensitometry (r= 0.89 to 0.94) (24). Waist circumference was measured at the level of the umbilicus to the nearest tenth of a centimeter. Participants were questioned about current use of cigarettes and daily consumption of alcoholic beverages, which was converted into grams of alcohol consumed per day. Usual weekly energy expenditure in kilocalories was estimated from questionnaire data on work and recreational activities, strenuous exercise, distance walked, and stairs climbed, as described elsewhere (25). Statistical Analysis We used multiple logistic regression analysis to estimate the odds ratio for incident hypertension in relation to an increase of 1 SD in baseline variables. For rare outcomes, the odds ratio will approximately equal the relative risk. For more frequent outcomes, such as hypertension, the odds ratio will overestimate the relative risk (26). We evaluated nonlinear effects of continuous independent variables by using quadratic and log transformations (27). The linear trends in odds were evaluated by using the median value for each quartile category of continuous variables. To assess departure from linearity, we included linear and quadratic terms (the median and the value squared) in the model (28). To determine whether interaction was present (that is, the relationship between the risk factor and the outcome varied depending on the value of a third variable) (27, 29, 30), we inserted first-order interaction terms into appropriate regression models. We assessed interaction to determine whether the relationship between hypertension status at follow-up and baseline adipose variables, such as intra-abdominal fat area, subcutaneous abdominal fat area, total subcutaneous fat area, BMI, or waist circumference, differed according to the level of an additional variable (for example, sex) in the model. We used the likelihood ratio test to determine the statistical significance of nonlinear effects of continuous independent variables and interaction terms in the logistic regression models. Multicollinearity was assessed by using the variance inflation factor (31). A variance inflation factor exceeding 10 is regarded as indicating serious multicollinearity, and values greater than 4.0 may be a cause for concern (31). We calculated the 95% CI for each odds ratio. P values were 2-tailed. We performed statistical analyses using Stata SE, version 8.0 (Stata Corp., College Station, Texas). Role of the Funding Sources The funding sources had no role in the collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Results Among the 300 eligible men and women followed for 10 to 11 years, there were 92 incident cases of hypertension. In univariate logistic regression analysis, intra-abdominal fat area, abdominal subcutaneous fat area, total subcutaneous fat area, total fat area, BMI, and waist circumference were associated with a higher incidence of hypertension. Fasting plasma insulin level, fasting plasma glucose level, 2-hour plasma glucose level, and high-density lipoprotein cholesterol level were also associated with incidence of hypertension (Table 1). Wealso compared the baseline characteristics of participants included in

Visceral Adiposity and the Prevalence of Hypertension in Japanese Americans

Background—Visceral adiposity is generally considered to play a key role in the metabolic syndrome, including hypertension. The purpose of this study was to evaluate cross-sectionally whether visceral adiposity is associated with prevalence of hypertension independent of other adipose depots and fasting plasma insulin. Methods and Results—Study subjects included 563 Japanese Americans with normal or impaired glucose tolerance or diabetes but not taking oral hypoglycemic medication or insulin at entry. Variables included plasma glucose and insulin measured after an overnight fast and during an oral glucose tolerance test, and abdominal, thoracic, and thigh fat areas by CT. Total fat area (TFA) was calculated as the sum of these fat areas. Hypertension was defined as having a systolic blood pressure ≥140 mm Hg, having a diastolic blood pressure ≥90 mm Hg, or taking antihypertensive medications. Intra-abdominal fat area (IAFA) was associated with a higher prevalence of hypertension. Adjusted odds ratio of hypertension by IAFA was 1.68 for a 1-SD increase (95% CI, 1.20 to 2.37) after adjusting for age, sex, fasting plasma insulin, a nonlinear transformation of 2-hour plasma glucose, and TFA. IAFA remained a significant predictor of prevalence of hypertension even after adjustment for total subcutaneous fat area, abdominal subcutaneous fat area, body mass index, or waist circumference, but no measure of regional or total adiposity was associated with the odds of prevalence of hypertension in models that contained IAFA. Conclusions—Greater visceral adiposity increases the odds of hypertension in Japanese Americans independent of other adipose depots and fasting plasma insulin.

Both visceral fat and liver fat are independently associated with hyperuricemia: The Ohtori Study

To examine cross‐sectionally whether intraabdominal fat area (IAFA), i.e., visceral fat, and liver fat assessed by computed tomography (CT) are independently associated with hyperuricemia.

Association of Visceral Fat and Liver Fat With Hyperuricemia.

To examine cross‐sectionally whether intraabdominal fat area (IAFA), i.e., visceral fat, and liver fat assessed by computed tomography (CT) are independently associated with hyperuricemia.

Risk factors for type 2 diabetes

Migrant Japanese populations in both the USA and Brazil have for a long time shown a higher prevalence of typeu20032 diabetes than native Japanese, suggesting an interaction of lifestyle and genetic predisposition in the etiology of typeu20032 diabetes. The overall objective of the Seattle Japanese American Community Diabetes Study was to learn more about the etiology and pathogenesis of typeu20032 diabetes in Japanese Americans. This metabolically based epidemiological study included extensive assessments of insulin sensitivity, insulin response, and adiposity with the latter including measurements of body fat distribution by both anthropometry and computed tomography. Because of this, the importance of visceral adiposity as a risk factor for abnormal glucose tolerance, hypertension, coronary heart disease and the metabolic syndrome was shown. In conjunction with an examination of diet and physical activity patterns, the result was a clearer understanding of the etiology and pathogenesis of typeu20032 diabetes in Japanese Americans. We propose that a lifestyle that fosters increased weight gain, especially in the visceral adipose depot, promotes the development of insulin resistance, which in turn exposes an underlying reduced β‐cell reserve in susceptible individuals, resulting in glucose intolerance and, eventually in many, the development of diabetes. We have shown that it might be possible to delay or prevent the development of diabetes through dietary and exercise interventions in individuals identified as having impaired glucose tolerance. The lessons learned from studying migrant Japanese in Seattle might in many ways be applicable to other populations of Asian origin. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00195.x, 2012)

Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years.

PROBLEMnThe role of plasma estradiol in the accumulation of intra-abdominal fat (IAF) in men is uncertain. Cross-sectional studies using imaging of IAF have shown either a positive or no association. In contrast, a randomised controlled trial using an aromatase inhibitor to suppress estradiol production found an association between oestrogen deficiency and short-term IAF accumulation. No longitudinal study has been conducted to examine the relationship between plasma estradiol concentration and the change in IAF area measured using direct imaging.nnnMETHODSnThis is a longitudinal observational study in community-dwelling Japanese-American men (n=215, mean age 52 years, BMI 25.4kg/m2). IAF and subcutaneous fat areas were assessed using computerized tomography (CT) at baseline, 5 and 10 years. Baseline plasma estradiol concentrations were measured using liquid chromatography-tandem mass spectrometry.nnnRESULTSnUnivariate analysis found no association between baseline estradiol concentration and baseline IAF, or 5- or 10-year changes in IAF area (r=-0.05 for both time points, p=0.45 and p=0.43, respectively). Multivariate linear regression analysis of the change in IAF area by baseline estradiol concentration adjusted for age, baseline IAF area, and weight change found no association with either the 5- or 10-year IAF area change (p=0.52 and p=0.55, respectively).nnnCONCLUSIONSnPlasma estradiol concentration was not associated with baseline IAF nor with change in IAF area over 5 or 10 years based on serial CT scans in community-dwelling Japanese-American men. These results do not support a role for oestrogen deficiency in IAF accumulation in men.