Yu-Sheng Lin

Sex, menopause, metabolic syndrome, and all-cause and cause-specific mortality - cohort analysis from the Third National Health and Nutrition Examination Survey.

OBJECTIVE This study assessed the mortality risk associated with metabolic syndrome (MetS) for participants from the Third National Health and Nutrition Examination Survey. DESIGN, SETTING, AND PATIENTS The study analyzed mortality data from 1364 men and 1321 women aged 40 yr and older based on their MetS status defined by National Cholesterol Education Program Adult Treatment Panel III. Subjects initially using insulin, oral hypoglycemic, antihypertensive, or lipid-lowering medications were excluded. MAIN OUTCOME MEASURES All-cause, cardiovascular, cardiac, and noncardiovascular mortality were obtained from the Third National Health and Nutrition Examination Survey-linked mortality follow-up file through December 31, 2000. RESULTS The prevalence of MetS was 33 and 29% for men and women, respectively. In the male subjects, there was no significant association between MetS and mortality. In the women, MetS was an independent risk factor for all-cause mortality [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.29-2.64, P = 0.001], cardiovascular mortality (HR 1.96, 95% CI 1.21-3.17, P = 0.007), cardiac mortality (HR 1.88, 95% CI 1.15-3.09, P = 0.01), and noncardiovascular mortality (HR 1.80, 95% CI 1.13-2.87, P = 0.01). The HR was stronger when postmenopausal women were analyzed separately and became nonsignificant in the premenopausal cohort. The sex-specific HR remained unchanged, regardless of the MetS criteria used or the inclusion of actively treated subjects. CONCLUSIONS MetS poses a significant increase in mortality risk through an observation period as long as 12 yr, primarily in postmenopausal women, that is not apparent in men and premenopausal women. Sex is an important effect modifier of all-cause and cause-specific death.

Increased Risk of Cancer Mortality Associated with Cadmium Exposures in Older Americans with Low Zinc Intake

Cadmium (Cd) exposure has been associated with increased cancer risk, and zinc (Zn) appears to reduce that risk. However, little is known about the combined influence of Cd and Zn on cancer risk. The aim of this study was to examine relationships between Cd exposure, Zn intake, and cancer mortality risks. The analyses used 5204 subjects aged 50 yr or older from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) and the mortality follow-up through December 31, 2006. Cox proportional hazards models were used to test associations. In total, 569 cancer deaths were recorded during an average follow-up of 12.4 yr, including 155 from lung, 61 from prostate, and 26 from breast cancer. A positive association between Cd and cancer mortality risk was identified for both genders. Despite limited cause-specific deaths, the increased risk associated with Cd was significant for lung cancer in men. All-cause cancer mortality risk was significantly elevated among women with Zn intakes below the recommended dietary allowance (RDA) compared with women who met the RDA. The effect of low dietary Zn was not observed in men. Similar trends for prostate and breast cancer deaths were not significant. There was a significant inverse association between cancer deaths and the Zn-to-Cd ratio for both genders. Cd exposure is an important independent risk factor of cancer mortality in older Americans and the risk appears exaggerated in those with inadequate dietary Zn. Additional studies are required to elucidate the mechanism(s) by which Zn participates in the carcinogenic influence of Cd.

A whole genome methylation analysis of systemic lupus erythematosus: hypomethylation of the IL10 and IL1R2 promoters is associated with disease activity

The etiology of systemic lupus erythematosus (SLE) involves a complex interaction of genetic and environmental factors. Investigations have shown that environmentally driven epigenetic changes contribute to the etiology of SLE. Here, we hypothesize that aberrant DNA methylation may contribute to the activation of the immune machinery and trigger lupus disease activity. A whole genome methylation array was applied to investigate the DNA methylation changes between 12 pairs of active SLE patients and healthy controls. The results were further confirmed in 66 SLE patients, 102 healthy controls. The methylation statuses of the IL10 and IL1R2 genes were significantly reduced in the SLE patient samples relative to the healthy controls (age-adjusted odds ratios, 64.2 and 16.9, respectively, P<0.0001). There was a trend toward SLE patients having hypomethylated IL10 and IL1R2 genes accompanied by greater disease activity. We observed that the methylation degree of IL10 and IL1R2 genes were reduced in the rheumatoid arthritis (RA) patients as well but the hypomethylation change was more significant in IL1R2 genes than in the IL10 genes in RA patients. This study demonstrated that DNA hypomethylation might be associated with SLE. Hypomethylated IL10 and IL1R2 genes may provide potential epigenetic markers as clinical predictors for autoimmune diseases.

Cystatin C and Long-Term Mortality Among Subjects With Normal Creatinine-Based Estimated Glomerular Filtration Rates : NHANES III (Third National Health and Nutrition Examination Survey)

OBJECTIVES The objective was to test the association of cystatin C (Cys-C) with long-term mortality risk in the subjects with normal creatinine-based estimated glomerular filtration rates (eGFR). BACKGROUND Cys-C has been proposed as a sensitive indicator of renal dysfunction that is associated with cardiovascular events. The predictive value of Cys-C for mortality risk (both cardiovascular and noncardiovascular) and its utility among persons with normal kidney function remains unclear. METHODS The analysis included 2,990 subjects over 40 years of age with normal eGFR who participated in NHANES III (Third National Health and Nutrition Examination Survey). Normal eGFR was defined by Modification of Diet in Renal Disease (MDRD) equation ≥60 ml/min/1.73 m(2). Serum Cys-C was categorized as high, medium, or low. In 1 analysis, the high and low groups were the top and bottom 10%, and in the second analysis, they were the upper and lower thirds. All-cause and cause-specific mortality were obtained from the NHANES III-linked follow-up file through December 31, 2006. Multivariate Cox regression models were applied to assess the association of interest. RESULTS Within an average of 13.7 years follow-up, 488 cardiovascular and 719 noncardiovascular deaths occurred. When the first and last deciles were compared, the relative risks were all increased statistically as follows: all-cause, 4.36 (95% confidence interval [CI]: 2.52 to 7.82); cardiovascular, 7.44 (95% CI: 3.06 to 18.1); cancer, 2.45 (95% CI: 0.85 to 7.04); and noncardiovascular 3.15 (95% CI: 1.53 to 6.49) mortalities. Relative risks all moderated to lower values when the comparisons were expanded to include the upper and lower thirds. Similar associations were still present when Cys-C was modeled on a continuous scale, suggesting a linear relationship between Cys-C and mortality outcomes. CONCLUSIONS Serum Cys-C is prognostic of long-term mortality in the subjects with relatively normal renal function, independent of MDRD eGFR and albuminuria.

Cigarette smoking, cadmium exposure, and zinc intake on obstructive lung disorder

Background and objectiveThis study examined whether zinc intake was associated with lower risk of smoking-induced obstructive lung disorder through interplay with cadmium, one of major toxicants in cigarette smoke.MethodsData were obtained from a sample of 6,726 subjects aged 40+ from the Third National Health and Nutrition Examination Survey. The forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured using spirometry. Gender-, ethnicity-, and age-specific equations were used to calculate the lower limit of normal (LLN) to define obstructive lung disorder as: observed FEV1/FVC ratio and FEV1 below respective LLN. Zinc intake was assessed by questionnaire. Logistic regression analysis was applied to investigate the associations of interest.ResultsThe analyses showed that an increased prevalence of obstructive lung disorder was observed among individuals with low zinc intake regardless of smoking status. The adjusted odds of lung disorder are approximately 1.9 times greater for subjects in the lowest zinc-intake tertile than those in the highest tertile (odds ratio = 1.89, 95% confidence interval = 1.22-2.93). The effect of smoking on lung function decreased considerably after adjusting for urinary cadmium. Protective association between the zinc-to-cadmium ratio (log-transformed) and respiratory risk suggests that zinc may play a role in smoking-associated lung disorder by modifying the influence of cadmium.ConclusionsWhile zinc intake is associated with lower risk of obstructive lung disorder, the role of smoking cession and/or prevention are likely to be more important given their far greater effect on respiratory risk. Future research is warranted to explore the mechanisms by which zinc could modify smoking-associated lung disease.

Low serum zinc is associated with elevated risk of cadmium nephrotoxicity

BACKGROUND Despite animal evidence suggests that zinc modulates cadmium nephrotoxicity, limited human data are available. OBJECTIVE To test the hypothesis that low serum zinc concentrations may increase the risk of cadmium-mediated renal dysfunction in humans. METHODS Data from 1545 subjects aged 20 or older in the National Health and Nutrition Examination Survey (NHANES), 2011-2012 were analyzed. Renal function was defined as impaired when estimated glomerular filtration rate (eGFR) fell below 60 ml/min/1.73 m(2) and/or the urinary albumin-to-creatinine ratio surpassed 2.5 in men and 3.5mg/mmol in women. RESULTS Within the study cohort, 117 subjects had reduced eGFR and 214 had elevated urinary albumin. After adjusting for potential confounders, subjects with elevated blood cadmium (>0.53 μg/L) were more likely to have a reduced eGFR (odds ratio [OR]=2.21, 95% confidence interval [CI]: 1.09-4.50) and a higher urinary albumin (OR=2.04, 95% CI: 1.13-3.69) than their low cadmium (<0.18 μg/L) peers. In addition, for any given cadmium exposure, low serum zinc is associated with elevated risk of reduced eGFR (OR=3.38, 95% CI: 1.39-8.28). A similar increase in the odds ratio was observed between declining serum zinc and albuminuria but failed to reach statistical significance. Those with lower serum zinc/blood cadmium ratios were likewise at a greater risk of renal dysfunction (p<0.01). CONCLUSIONS This study results suggest that low serum zinc concentrations are associated with an increased risk of cadmium nephrotoxicity. Elevated cadmium exposure is global public health issue and the assessment of zinc nutritional status may be an important covariate in determining its effective renal toxicity.

Metabolic Syndrome, Testosterone, and Cardiovascular Mortality in Men

INTRODUCTION Interactions among testosterone, metabolic syndrome (MetS), and mortality risk in men remain to be elucidated. AIM To examine relationships among testosterone, MetS, and cardiovascular mortality risk in U.S. men, middle-aged and older. METHODS The analysis included the men aged 40 years and above in Phase 1 (1988-1991) of the Third National Health and Nutrition Examination Survey (NHANES III). Serum testosterone and sex hormone binding globulin were measured, and free testosterone and bioavailable testosterone were calculated. MetS was determined according to the Adult Treatment Panel III (ATP-III) criteria. MAIN OUTCOME MEASURES Cardiovascular and other causes of mortality were obtained from the NHANES III-linked follow-up file through December 31, 2006. Multivariate Cox regression models were applied to assess associations of interest. RESULTS Of 596 men included in the analysis, 187 men were found to have MetS. During a median follow-up of 15.6 years, 97 men died of cardiovascular causes (cardiovascular mortality rate: 9.84 and 5.77 per 1,000 person-years for those with and without MetS, respectively). Higher calculated bioavailable testosterone (CBT) was associated with a lower odds of MetS (odds ratio: 0.80 for each ng/mL, 95% confidence interval [CI]: 0.76-0.84, P < 0.001) and lower risk of cardiovascular mortality (hazard ratios [HRs]: 0.72 for each log ng/mL, 95% CI: 0.54-0.96, P = 0.03) in subjects with MetS. The influence of CBT was not observed in those without MetS (HR: 0.84 for each log ng/mL, 95% CI: 0.68-1.04, P = 0.10). CONCLUSIONS The combination of lower bioavailable testosterone and ATP-III-defined MetS is associated with an increased cardiovascular mortality in the men aged 40 years and above.

Epigenome: Biosensor of Cumulative Exposure to Chemical and Nonchemical Stressors Related to Environmental Justice

Understanding differential disease susceptibility requires new tools to quantify the cumulative effects of environmental stress. Evidence suggests that social, physical, and chemical stressors can influence disease through the accumulation of epigenetic modifications. Geographically stable epigenetic alterations could identify plausible mechanisms for health disparities among the disadvantaged and poor. Relations between neighborhood-specific epigenetic markers and disease would identify the most appropriate targets for medical and environmental intervention. Complex interactions among genes, the environment, and disease require the examination of how epigenetic changes regulate susceptibility to environmental stressors. Progress in understanding disparities in disease susceptibility may depend on assessing the cumulative effect of environmental stressors on genetic substrates. We highlight key concepts regarding the interface between environmental stress, epigenetics, and chronic disease.

Body Mass Index May Modify Asthma Prevalence Among Low-Birth-Weight Children

Childhood asthma, a growing health concern, has been associated with low birth weight and elevated body mass index. This study tested the hypothesis that overweight and obese adolescents with a history of low birth weight are at even greater risk of developing asthma. A cohort of 75,871 junior high school students was screened for asthma during 1995-1996 in Taiwan. Birth weight and estimated gestational age were obtained from the birth registry. Logistic regression and simple regression analyses were adjusted for confounding variables. Asthma was more prevalent in those with birth weights below 3,000 g and higher adolescent body mass indexes. Furthermore, those with both characteristics were consistently most likely to have asthma. Whether the asthma diagnosis among low-birth-weight subjects was assigned by physicians or medical questionnaire, the risks were elevated for both overweight (physician diagnosis: odds ratio = 1.41; medical questionnaire: odds ratio = 1.25) and obese (physician diagnosis: odds ratio = 1.38; medical questionnaire: odds ratio = 1.47) boys as well as overweight (physician diagnosis: odds ratio = 1.63; medical questionnaire: odds ratio = 1.30) and obese (physician diagnosis: odds ratio = 1.44; medical questionnaire: odds ratio = 1.32) girls (P < 0.05). Low birth weight predisposes one to develop asthma, and excess body mass amplifies the risk. A sex difference was observed. This study suggests that prenatal care and nutritional counseling could reduce asthma prevalence.

Environmental exposure to dioxin-like compounds and the mortality risk in the U.S. population

BACKGROUND Little is known about the mortality risk associated with chronic dioxin exposure in the general U.S. populations. OBJECTIVE To explore the association between dioxin-like chemicals and mortality risk in a large population-based cohort study. METHODS The analysis included 2361 subjects aged 40 years or older from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). Exposure to a mixture of dioxin-like chemicals, including dibenzo-p-dioxins, dibenzofurans, and polychlorinated biphenyls was estimated using toxic equivalency values (TEQs) calculated with 2005 World Health Organization toxic equivalency factors. All-cause and cause-specific mortalities were obtained from the NHANES-linked follow-up data through December 31, 2006. Cox proportional-hazards models were applied to assess the associations of interest. RESULTS A total of 242 deaths occurred during the follow-up period, including 75 from cardiovascular disease and 72 from cancer. There was an increased mortality risk associated with logarithmically expressed dioxin TEQs for all-cause deaths (hazard ratio=1.19, 95% confidence interval=1.02-1.39, p=0.02). Similar graded dose-response trends were found for cardiovascular and cancer mortality which did not reach statistical significance. CONCLUSIONS In general, higher dioxin exposure is associated with an increased mortality risk among subjects aged 40 and above. The cause-specific analyses and responsible mechanisms will require further investigation.