Minseon Park

Bisphenol A exposure is associated with oxidative stress and inflammation in postmenopausal women

Bisphenol A (BPA) is widely used in the production of polycarbonate plastics and epoxy resins. There is increasing health concerns regarding low-level exposure to BPA among the general population. The aim of this study was to determine the association between BPA exposure with oxidative stress and inflammation in adult populations. A cross-sectional study was conducted. This study included 485 adults (259 men, 92 premenopausal women, and 134 postmenopausal women) living in general communities within large cities. Urinary concentrations of BPA, malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG), white blood cell (WBC) count, and C-reactive protein (CRP) were measured. Multivariate analyses were applied to determine the associations of BPA exposure with oxidative stress and inflammation. The geometric means of urinary BPA for men, premenopausal women, and postmenopausal women were 0.53, 0.61, and 0.58 microg/g cr, respectively. The urinary BPA concentrations were positively associated with MDA, 8-OHdG, and CRP levels in the postmenopausal women; however, such associations did not exist in men and premenopausal women. The findings of this study suggest that BPA exposure would promote oxidative stress and inflammation, in which postmenopausal women are likely to be more susceptible to BPA-induced health effects.

Community level exposure to chemicals and oxidative stress in adult population

Little information is available on the role of environmental chemical exposure in oxidative stress. This study was designed to investigate whether exposure to environmental chemicals, such as polycyclic aromatic hydrocarbons, volatile organic compounds, bisphenol A or phthalates, induces oxidative stress in urban adult populations. A total of 960 adults dwelling in urban areas were evaluated between April and December 2005. To assess environmental chemical exposure, we measured urinary levels of 1-hydroxypyrene, 2-naphthol, hippuric acid, methyl hippuric acid, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-butyl phthalate and bisphenol A. Urinary malondialdehyde and 8-hydroxydeoxyguanosine were also measured to evaluate oxidative stress. Significant dose-responsive relationship was found between urinary concentrations of the chemical exposure biomarkers and oxidative stress levels in simple regression analyses (P<0.05). Regression coefficients of these exposure biomarkers except bisphenol A remained significantly in the multiple regression models after controlling for age, sex, weight, smoking, and exercise for at least one of the two oxidative stress biomarkers (P<0.05). The oxidative stress biomarkers significantly affected the indicators of insulin resistance, particularly glucose level. This study indicates that environmental chemical exposure is associated with oxidative stress in urban adult populations and suggests that exposure to certain environmental chemicals might contribute to insulin resistance.

The Bilirubin Level is Negatively Correlated with the Incidence of Hypertension in Normotensive Korean Population

Reactive oxygen species have been known to be an important factor in the pathogenesis of hypertension. Bilirubin, one of the metabolites of heme degraded by heme oxygenase, is a potent anti-oxidant. We verified the effect of serum bilirubin level on the incidence of hypertension in normotensive subjects. We grouped 1,208 normotensive subjects by the criterion of the highest quintile value of serum bilirubin, 1.1 mg/dL. The incidence of hypertension was higher in group 1 with bilirubin less than 1.1 mg/dL than in group 2 with bilirubin 1.1 mg/dL or more (186/908 vs. 43/300, p=0.018). The relative risk for hypertension was 0.71 (95% confidence interval, 0.51-0.99), p=0.048 in group 2 compared to group 1 by Coxs proportional hazard model. Among the groups stratified by gender, smoking, and liver function status, the group 2 showed a lower risk of hypertension in females and in non-smokers. In conclusion, a mild increase within the physiological range of serum bilirubin concentration was negatively correlated with the incidence of hypertension. The effect of bilirubin on the development of hypertension was more evident in females and in non-smokers.

High-Sensitivity C-Reactive Protein Levels and Cancer Mortality

Background: High-sensitivity C-reactive protein (hs-CRP) is an important inflammatory marker, and inflammation is known to be involved in the initiation and progression of cancer. We investigated the association between serum hs-CRP levels and all-cause mortality, cancer mortality, and site-specific cancer mortality in apparently cancer-free Koreans. Methods: A total of 33,567 participants who underwent routine check-ups at a single tertiary hospital health-screening center between May 1995 and December 2006, and whose serum hs-CRP level data were available, were included in the study. Baseline serum hs-CRP levels were obtained and subjects were followed up for mortality from baseline examination until December 31, 2008. Results: During an average follow-up of 9.4 years, 1,054 deaths, including 506 cancer deaths, were recorded. The adjusted HRs (aHR; 95% confidence interval [CI]) of subjects with hs-CRP ≥3 mg/L for all-cause and cancer-related mortality were 1.38 (1.15–1.66) and 1.61 (1.25–2.07) in men, and 1.29 (0.94–1.77) and 1.24 (0.75–2.06) in women, respectively, compared with subjects with hs-CRP ≤1 mg/L. Elevated hs-CRP was also associated with an increased risk of site-specific mortality from lung cancer for sexes combined (2.53 [1.57–4.06]). Conclusions: This study suggests that elevated levels of hs-CRP in apparently cancer-free individuals may be associated with increased mortality from all-causes and cancer, in particular, lung cancer in men, but not in women. Impact: As a marker for chronic inflammation, hs-CRP assists in the identification of subjects with an increased risk of cancer death. Cancer Epidemiol Biomarkers Prev; 21(11); 2076–86. ©2012 AACR.

Physical Activity and Physical Fitness as Predictors of All-Cause Mortality in Korean Men

We examined the associations between physical activity (PA), fitness and all-cause mortality and compared their contributions, taking smoking status into consideration. A retrospective cohort study of 18,775 men was carried out between May 1995 and December 2003. Fitness was measured by maximum oxygen uptake and regular PA was defined as at least three times a week, for more than 30 min of leisure time PA. During the mean 6.4 yr of follow-up, 547 deaths were recorded. The hazard ratio (HR) (95% confidence interval [CI]) of regular PA for all-cause mortality was 0.63 (0.52-0.76). The HRs (95% CIs) for men with middle and highest tertile levels of fitness were decreased by 0.58 (0.47-0.70) and 0.58 (0.45-0.75) in comparison to men with lowest one. The inverse association between fitness and mortality was significant among the men who did not engage in regular PA, but not among those who did (p for interaction=0.031). Smoking status did not influence on the associations between regular PA, fitness and mortality. Our result suggested that regular PA and fitness predicted mortality in men. The influence of fitness on mortality was pronounced in the men who did not engage in regular PA.

Renal Hyperfiltration as a Novel Marker of All-Cause Mortality

Although renal hyperfiltration (RHF) or an abnormal increase in GFR has been associated with many lifestyles and clinical conditions, including diabetes, its clinical consequence is not clear. RHF is frequently considered to be the result of overestimating true GFR in subjects with muscle wasting. To evaluate the association between RHF and mortality, 43,503 adult Koreans who underwent voluntary health screening at Seoul National University Hospital between March of 1995 and May of 2006 with baseline GFR≥60 ml/min per 1.73 m(2) were followed up for mortality until December 31, 2012. GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and RHF was defined as GFR>95th percentile after adjustment for age, sex, muscle mass, and history of diabetes and/or hypertension medication. Muscle mass was measured with bioimpedance analysis at baseline. During the median follow-up of 12.4 years, 1743 deaths occurred. The odds ratio of RHF in participants with the highest quartile of muscle mass was 1.31 (95% confidence interval [95% CI], 1.11 to 1.54) compared with the lowest quartile after adjusting for confounding factors, including body mass index. The hazard ratio of all-cause mortality for RHF was 1.37 (95% CI, 1.11 to 1.70) by Cox proportional hazards model with adjustment for known risk factors, including smoking. These data suggest RHF may be associated with increased all-cause mortality in an apparently healthy population. The possibility of RHF as a novel marker of all-cause mortality should be confirmed.

Insulin Resistance is Associated with Gallstones Even in Non-obese, Non-diabetic Korean Men

It remains unclear as to whether insulin resistance alone or in the presence of well-known risk factors, such as diabetes or obesity, is associated with gallstones in men. The aim of this study was to determine whether insulin resistance is associated independently with gallstone disease in non-diabetic men, regardless of obesity. Study subjects were 19,503 Korean men, aged 30-69 yr, with fasting blood glucose level <126 mg/dL and without a documented history of diabetes. Gallbladder status was assessed via abdominal ultrasonography after overnight fast. Body mass index and waist circumference were measured. Insulin resistance was estimated by the Homeostasis Model Assessment of insulin resistance (HOMA-IR). The prevalence of obesity, abdominal obesity, and metabolic syndrome in the subjects with gallstones were higher than in those without. The prevalence of elevated HOMA (>75 percentile) in subjects with gallstones was significantly higher than in those without, and this association remained even after the obesity stratification was applied. In multiple logistic regression analyses, only age and HOMA proved to be independent predictors of gallstones. Insulin resistance was positively associated with gallstones in non-diabetic Korean men, and this occurred regardless of obesity. Gallstones appear to be a marker for insulin resistance, even in non-diabetic, non-obese men.

Association of cold ambient temperature and cardiovascular markers.

Cardiovascular mortality has been shown to increase in the winter. However, it is unclear whether cold temperature affects indicators known as cardiovascular markers. We evaluated the association between ambient temperature and cardiovascular markers using data collected retrospectively from 55,567 adults who had visited a health check-up clinic between 1995 and 2008. Non-parametric smoothing regressions were fitted to determine the shapes of association between temperature and cardiovascular markers such as blood pressure, lipid profiles, platelet count, and high sensitivity C-reactive protein (hsCRP). Mixed effect model was used to investigate the significance of the relationship between temperature and cardiovascular markers. Decreased ambient temperature was associated with an increase in systolic and diastolic blood pressures, platelet count and serum low density lipoprotein-cholesterol concentration. In contrast, high density lipoprotein-cholesterol level declined with decreasing temperature. The hsCRP level increased with decreasing temperature in the minimum temperatures below 0°C, but revealed a reverse association above. Our study suggests that excess cardiovascular mortality in cold weather might be associated with temperature-related variations of cardiovascular markers.

The differential effect of cigarette smoking on glomerular filtration rate and proteinuria in an apparently healthy population

The detrimental effects of cigarette smoking on the kidney in healthy individuals without established renal diseases have not been established. We evaluated the effects of smoking on renal function and proteinuria in 35 288 apparently healthy participants who were not on antihypertensive and/or antidiabetic medication and who had undergone a health examination at the Health Promotion Center, Seoul National University Hospital from 1995 to 2006. Renal function was estimated using the simplified Modification of Diet in Renal Disease Study equation for estimated glomerular filtration rate (eGFR), and proteinuria was determined by the spot urine dipstick test. Adjusted eGFR was higher in current smokers (mean±s.e.m., 79.3±0.1 ml min−1) than in ex-smokers (77.3±0.2 ml min−1, P<0.001) and non-smokers (77.7±0.1 ml min−1, P<0.001). The adjusted eGFR of smokers who smoked >20 cigarettes per day were higher than that of individuals who smoked ⩽20 cigarettes per day (P<0.001). In participants with an eGFR of <50 ml min−1, current smoking (38.3±1.9 ml min−1) and past smoking (39.5±1.9 ml min−1) were associated with significantly lower eGFR values than non-smoking (45.1±1.2 ml min−1; P=0.007 and P=0.027, respectively). Current smoking was associated with a higher risk of proteinuria (urine dipstick for albuminuria ⩾1+) than non-smoking (odds ratio=1.380, P<0.001). In conclusion, cigarette smoking is associated with a higher eGFR in the general population, whereas it might reduce eGFR in a small subset of the population and increase the risk of proteinuria. These subsets should be better defined to prevent chronic kidney diseases related to smoking in the general population.

Association between the markers of metabolic acid load and higher all-cause and cardiovascular mortality in a general population with preserved renal function

Although metabolic acid load has been associated with many well-known risk factors for mortality, its clinical implications are not yet clear. To evaluate the association between biomarkers of metabolic acid load, such as serum bicarbonate, serum anion gap and urine pH and mortality, we analyzed the health records of 31 590 adults who underwent a health screening between January 2001 and December 2010 and had an estimated glomerular filtration rate ⩾60 ml min−1 per 1.73 m2. Urine pH was measured by a dipstick test performed on fast morning urine sample and categorized as acidic (urine pH ⩽5.5), neutral and alkaline (urine pH ⩾8.0). Using the Cox proportional hazard model, the adjusted hazard ratio (aHR) of all-cause mortality of the lowest quartile of serum bicarbonate was 1.460 (95% confidence interval (CI) 1.068–1.995) compared with the highest quartile, after a median follow-up of 93 months. The aHRs of cardiovascular and cancer mortality of the lowest quartile of serum bicarbonate were 2.647 (95% CI 1.148–6.103) and 1.604 (95% CI 1.024–2.513), respectively, compared with the highest quartile. Acidic and neutral urine pH were significantly associated with a higher all-cause mortality (aHR 2.550, 95% CI 1.316–4.935; aHR 2.376 95% CI 1.254–4.501, respectively), compared with an alkaline urine pH. In conclusion, higher metabolic acid load was associated with an increased all-cause and cardiovascular mortality in a healthy population. The association between metabolic acid load and mortality and the causality of the relationship need to be confirmed.