Eliseo Guallar
Eliseo Guallar
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Chair and Professor of the Department of Epidemiology
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Professional overview
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Dr. Guallar is an epidemiologist whose research is focused on the study of cardiovascular disease epidemiology and prevention, with an emphasis on evaluating the role of environmental and nutritional exposures in the development of cardiovascular disease. This research has made critically important and novel contributions to our understanding of risk factors for chronic disease both in the US and globally. He has published seminal articles and is a leading figure in an emerging field highlighting the risks of exposure to levels of metals previously considered safe for cardiovascular health. In addition to his work in toxic metals, Dr. Guallar has made important contributions to understanding the effects of certain micronutrients and vitamin supplements on cardiovascular disease risk and outcomes. Publications in this area were influential in changing consumer habits and attitudes towards these products. Much of this research has been funded by the National Institutes of Health, the Agency for Healthcare Research and Quality, the American Heart Association, the CDC, and other funders.
Dr. Guallar was the founding director of the Center for Clinical Epidemiology at the Samsung Medical Center and a lead investigator of the Kangbuk Samsung Cohort Study at the Kangbuk Samsung Hospital since its inception in 2010. Dr. Guallar has published over 500 research papers in peer-reviewed journals. He is also a Deputy Editor for Methods at the Annals of Internal Medicine and a past member and Chair of the Cancer, Heart, and Sleep Study Section at the National Institutes of Health.
Prior to teaching at NYU, Dr. Guallar was a Professor of Epidemiology and Medicine at the Johns Hopkins University Bloomberg School of Public Health and a core faculty member of the Welch Center for Prevention, Epidemiology, and Clinical Research at Johns Hopkins. In the Department of Epidemiology, Dr. Guallar was the Director of the Environmental and Occupational Area of Concentration and the Co-Director of the PhD Program. Dr. Guallar was also an adjunct Professor at the Department of Clinical Research Design and Evaluation of the Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, in Seoul, Korea.
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Education
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Diploma of English, Spanish Official School of Languages at Zaragoza (Escuela Oficial de Idiomas de Zaragoza), Zaragoza, SpainMD, University of Zaragoza, Zaragoza, SpainMPH, University of Minnesota, Minneapolis, MNDrPH, Harvard University, Boston, MA
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Honors and awards
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Six Honor Calls in the MD Program, University of Zaragoza School of Medicine (1981)Fellow of Spain’s Program of Training of Graduate Research of the Ministry of Education and Science, University of Zaragoza (1988)Fulbright Scholar, sponsored by Spain’s Ministry of Health and Consumer Affairs (1989)Faculty Innovation Award, Johns Hopkins University Bloomberg School of Public Health (2001)Scientist Development Award, American Heart Association (2002)Fellow of the American Heart Association, Council on Epidemiology and Prevention (2013)Advising, Mentoring, and Teaching Recognition Award 2014 – 2015, Johns Hopkins University Bloomberg School of Public Health (2015)High Impact Research Icon, University of Malaya (2015)
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Publications
Publications
The association of serum lipids with colorectal adenomas
AbstractYang, M. H., Rampal, S., Sung, J., Choi, Y. H., Son, H. J., Lee, J. H., Kim, Y. H., Chang, D. K., Rhee, P. L., Kim, J. J., Rhee, J. C., Chun, H. K., Guallar, E., & Cho, J. (n.d.).Publication year
2013Journal title
American Journal of GastroenterologyVolume
108Issue
5Page(s)
833-841AbstractObjectives: There is suggestive but sparse evidence that dyslipidemia is associated with colorectal neoplasms. We investigated the association of serum lipid and apolipoprotein concentrations with the prevalence of colorectal adenomas. Methods: Cross-sectional study of 19,281 consecutive participants aged 40-79 years undergoing screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2006 to June 2009. Results: We identified 5,958 participants with colorectal adenomas (30.9%), including 5,504 (28.5%) with non-advanced adenomas and 454 (2.4%) with advanced adenomas. The adjusted relative prevalence ratios (aRPRs) comparing the fourth with the first quartiles of serum triglycerides were 1.35 (95% confidence interval (CI) 1.20-1.52; P trend<0.001) for non-advanced adenomas and 1.45 (95% CI 1.02-2.06; P trend=0.005) for advanced adenomas. Higher levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 (ApoA-1) were significantly associated with 12% (Q4 vs. Q1 aRPR 1.12; 95% CI 1.00-1.26; P trend=0.049) and 17% (Q4 vs. Q1 aRPR 1.17; 95% CI 1.04-1.31; P trend=0.004) higher prevalence of non-advanced adenoma. There was also a non-significant association between higher levels of low-density lipoprotein (LDL) cholesterol (Q4 vs. Q1 aRPR 1.22; 95% CI 0.91-1.66; P trend= 0.12) and apolipoprotein B (ApoB) (Q4 vs. Q1 aRPR 1.32; 95% CI 0.94-1.83; P trend=0.07) with higher prevalence of advanced adenoma. There was no association between total cholesterol levels with colorectal adenoma. Conclusions: In this large cross-sectional study, higher levels of serum triglycerides were significantly associated with an increasing prevalence of both non-advanced and advanced colorectal adenomas, while higher levels of ApoA-1 and HDL cholesterol were significantly associated with an increasing prevalence of non-advanced adenomas.The effects of n-3 long-chain polyunsaturated fatty acid supplementation on biomarkers of kidney injury in adults with diabetes: Results of the GO-FISH trial
AbstractMiller, E. R., Juraschek, S. P., Anderson, C. A., Guallar, E., Henoch-Ryugo, K., Charleston, J., Turban, S., Bennett, M. R., & Appel, L. J. (n.d.).Publication year
2013Journal title
Diabetes CareVolume
36Issue
6Page(s)
1462-1469AbstractOBJECTIVE - Long-chain n-3 polyunsaturated fatty acid (n-3 PUFA) supplements may have renoprotective effects in patients with diabetes, but previous trials have been inconsistent. We performed a randomized controlled trial of n-3 PUFA supplementation on urine albumin excretion and markers of kidney injury in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS - We conducted a randomized, placebo-controlled, two-period crossover trial to test the effects of 4 g/day of n-3 PUFA supplementation on markers of glomerular filtration and kidney injury in adults with adult-onset diabetes and greater than or equal to trace amounts of proteinuria. Each period lasted 6weeks andwas separated by a 2-week washout. The main outcome was urine albumin excretion and, secondarily, markers of kidney injury (kidney injury molecule-1, N-acetyl β-D-glucosaminidase [NAG], neutrophil gelatinase-associated lipocalin [NGAL], and liver fatty acid-binding protein [LFABP]), serum markers of kidney function (cystatin C, β2-microglobulin, and creatinine), and estimated glomerular filtration rate (eGFR). RESULTS - Of the 31 participants, 29 finished both periods. A total of 55% were male, and 61% were African American; mean age was 67 years. At baseline, mean BMI was 31.6 kg/m 2, median eGFR was 76.9 mL/min/1.73 m2, and median 24-h urine albumin excretion was 161 mg/day. Compared with placebo, n-3 PUFA had nonsignificant effects on urine albumin excretion (-7.2%; 95% CI -20.6 to 8.5; P = 0.35) and significant effects on urine NGAL excretion (-16% [-29.1 to -0.5%]; P = 0.04). There was no effect on serum markers of kidney function or eGFR. In subgroup analyses, there were significant decreases in 24-h urinary excretion of albumin, NGAL, LFABP, and NAG among participants taking medications that block the renin-angiotensin-aldosterone system (RAAS). CONCLUSIONS - These results suggest a potential effect of n-3 PUFA supplementation on markers of kidney injury in patients with diabetes and early evidence of kidney disease. In the context of prior studies, these results provide a strong rationale for long-term trials of n-3 PUFA on chronic kidney disease progression.The progression and early detection of subclinical atherosclerosis (PESA) study: Rationale and design
AbstractFernández-Ortiz, A., Jiménez-Borreguero, L. J., Peñalvo, J. L., Ordovás, J. M., Mocoroa, A., Fernández-Friera, L., Laclaustra, M., García, L., Molina, J., Mendiguren, J. M., López-Melgar, B., De Vega, V. M., Alonso-Farto, J. C., Guallar, E., Sillesen, H., Rudd, J. H., Fayad, Z. A., Ibañez, B., Sanz, G., & Fuster, V. (n.d.).Publication year
2013Journal title
American Heart JournalVolume
166Issue
6Page(s)
990-998AbstractBackground The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined. Objective The PESA study examines the presence of subclinical atherosclerosis by means of noninvasive imaging and prospectively analyzes the determinants associated with its development and progression in a middle-aged population. Methods The PESA study is an observational, longitudinal and prospective cohort study in a target population of 4000 healthy subjects (40-54 years old, 35% women) based in Madrid (Spain). Recruitment began in June 2010 and will be completed by the end of 2013. Baseline examination consists of (1) assessment for cardiovascular risk factors (including lifestyle and psychosocial factors); (2) screening for subclinical atherosclerosis using 2D/3D ultrasound in carotid, abdominal aorta and iliofemoral arteries, and coronary artery calcium score (CACS) by computed tomography; and (3) blood sampling for determination of traditional risk factors, advanced "omics" and biobanking. In addition, a subgroup of 1300 participants with evidence of atherosclerosis on 2D/3D ultrasound or CACS will undergo a combined 18F-fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging (18FDG PET/MRI) study of carotid and iliofemoral arteries. Follow-up at 3 and 6 years will include a repetition of baseline measurements, except for the 18FDG PET/MRI study, which will be repeated at 6 years. Conclusions The PESA study is expected to identify new imaging and biological factors associated with the presence and progression of atherosclerosis in asymptomatic people and will help to establish a more personalized management of medical care.Thromboxane A2 generation, in the absence of platelet COX-1 activity, in patients with and without atherothrombotic myocardial infarction
AbstractDeFilippis, A. P., Oloyede, O. S., Andrikopoulou, E., Saenger, A. K., Palachuvattil, J. M., Fasoro, Y. A., Guallar, E., Blumenthal, R. S., Kickler, T. S., Jaffe, A. S., Gerstenblith, G., Schulman, S. P., & Rade, J. J. (n.d.).Publication year
2013Journal title
Circulation JournalVolume
77Issue
11Page(s)
2786-2792AbstractBackground: Aspirin's therapeutic action is via inhibition of platelet cyclooxygenase 1 (COX-1) thromboxane A2 (TxA2) production. The aim of this study was to evaluate TxA2 production, in the absence of platelet COX-1 activity, in coronary atherosclerotic heart disease patients with and without atherothrombotic myocardial infarction (MI). Methods and Results: TxA2 production, in the absence of platelet COX-1 activity, was evaluated in 44 patients taking aspirin on 3 commercially available assays that detect metabolites of TxA2 in the urine. Two assays measure urine 11-dehydro-thromboxane B2 (TxB2) alone and 1 measures urine 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor- TxB2. Platelet COX-1 inhibition was confirmed on <10% platelet aggregation in response to ≥1 mmol/L arachidonic acid. Median urine 11-dehydro-TxB2 was no different in those with and without a diagnosis of atherothrombotic MI (325 vs. 311 pg/mg creatinine, P=0.59 via polyclonal ELISA) and (312 vs. 244 pg/mg creatinine, P=0.11 via LC-MS/MS). Median urine 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2, however, was higher in those with vs. those without a diagnosis of atherothrombotic MI (1,035 vs. 606 pg/mg creatinine, P=0.03 via monoclonal ELISA). Conclusions: Differences in TxA2 production, in the absence of platelet COX-1 activity, between those with vs. without atherothrombotic MI were not observed when TxA2 generation was assessed on 11-dehydro-TxB2 production alone (polyclonal ELISA or LC-MS/MS), but differences were observed when TxA2 generation was assessed using 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2 (monoclonal ELISA). These findings highlight important differences between different commercially available assays for TxA2 generation and suggest that 11-dehydro-2,3-dinor-TxB2 may be critical to the biology of atherothrombosis.Thyroid Hormones and Electrocardiographic Parameters: Findings from the Third National Health and Nutrition Examination Survey
AbstractZhang, Y., Post, W. S., Cheng, A., Blasco-Colmenares, E., Tomaselli, G. F., & Guallar, E. (n.d.).Publication year
2013Journal title
PloS oneVolume
8Issue
4AbstractIntroduction: Altered thyroid status exerts a major effect on the heart. Individuals with hypo- or hyperthyroidism showed various changes in electrocardiograms. However, little is known about how variations in thyroid hormone levels within the normal range affect electrical activities of the heart in the general population. Methods and Results: We conducted a cross-sectional analysis of 5,990 men and women from the Third National Health and Nutrition Examination Survey. Serum total T4 was measured by immunoassay and TSH was measured by chemiluminescent assay. We categorized T4 and TSH into 7 groups with cut-offs at the 5th, 20th, 40th, 60th, 80th, and 95th percentiles of the weighted population distribution. Electrocardiographic parameters were measured from the standard 12-lead electrocardiogram. We found a positive linear association between serum total T4 level and heart rate in men, and a U-shape association between T4 and PR interval in men and women. TSH level was positively associated with QRS interval in men, while a U-shape association between TSH and QRS was observed in women. No clear graded association between thyroid hormones and corrected QT or JT was found, except that men in the highest category of T4 levels appeared to have longer corrected QT and JT, and men in the lowest category of T4 appeared to have shorter corrected QT and JT. Conclusions: Variation in thyroid hormone levels in the general population, even within the normal range, was associated with various ECG changes.Urine arsenic and prevalent albuminuria: Evidence from a population-based study
AbstractZheng, L. Y., Umans, J. G., Tellez-Plaza, M., Yeh, F., Francesconi, K. A., Goessler, W., Silbergeld, E. K., Guallar, E., Howard, B. V., Weaver, V. M., & Navas-Acien, A. (n.d.).Publication year
2013Journal title
American Journal of Kidney DiseasesVolume
61Issue
3Page(s)
385-394AbstractBackground: Long-term arsenic exposure is a major global health problem. However, few epidemiologic studies have evaluated the association of arsenic with kidney measures. Our objective was to evaluate the cross-sectional association between inorganic arsenic exposure and albuminuria in American Indian adults from rural areas of Arizona, Oklahoma, and North and South Dakota. Study Design: Cross-sectional. Setting & Partipants: Strong Heart Study locations in Arizona, Oklahoma, and North and South Dakota. 3,821 American Indian men and women aged 45-74 years with urine arsenic and albumin measurements. Predictor: Urine arsenic. Outcomes: Urine albumin-creatinine ratio and albuminuria status. Measurements: Arsenic exposure was estimated by measuring total urine arsenic and urine arsenic species using inductively coupled plasma mass spectrometry (ICPMS) and high-performance liquid chromatography-ICPMS, respectively. Urine albumin was measured by automated nephelometric immunochemistry. Results: The prevalence of albuminuria (albumin-creatinine ratio ≥30 mg/g) was 30%. Median value for the sum of inorganic and methylated arsenic species was 9.7 (IQR, 5.8-15.6) μg per gram of creatinine. Multivariable-adjusted prevalence ratios of albuminuria (albumin-creatinine ratio ≥30 mg/g) comparing the 3 highest to lowest quartiles of the sum of inorganic and methylated arsenic species were 1.16 (95% CI, 1.00-1.34), 1.24 (95% CI, 1.07-1.43), and 1.55 (95% CI, 1.35-1.78), respectively (P for trend <0.001). The association between urine arsenic and albuminuria was observed across all participant subgroups evaluated and was evident for both micro- and macroalbuminuria. Limitations: The cross-sectional design cannot rule out reverse causation. Conclusions: Increasing urine arsenic concentrations were cross-sectionally associated with increased albuminuria in a rural US population with a high burden of diabetes and obesity. Prospective epidemiologic and mechanistic evidence is needed to understand the role of arsenic as a kidney disease risk factor.A cohort study of hyperuricemia in middle-aged South Korean men
AbstractRyu, S., Chang, Y., Zhang, Y., Kim, S. G., Cho, J., Son, H. J., Shin, H., & Guallar, E. (n.d.).Publication year
2012Journal title
American Journal of EpidemiologyVolume
175Issue
2Page(s)
133-143AbstractFew prospective studies have assessed the incidence and determinants of asymptomatic hyperuricemia in free-living populations. The authors' goals in this study were to estimate the incidence of hyperuricemia and quantify the dose-response relations of specific risk factors with hyperuricemia in middle-aged South Korean male workers. The authors followed a cohort of 10,802 hyperuricemia-free men aged 30-59 years, examining them annually or biennially at a university hospital in Seoul, South Korea, from 2002 to 2009. A parametric Cox model and a pooled logistic regression model were used to estimate adjusted hazard ratios for incident hyperuricemia (defined as serum uric acid level ≥7.0 mg/dL) according to prespecified risk factors. During 51,210.6 person-years of follow-up, 2,496 men developed hyperuricemia (incidence rate = 48.7 per 1,000 person-years, 95% confidence interval: 46.8, 50.7). The incidence of hyperuricema increased across baseline categories of age, body mass index, alcohol intake, blood pressure, metabolic syndrome, high-sensitivity C-reactive protein, triglycerides, gamma-glutamyltransferase, and fatty liver, whereas fasting glucose, estimated glomerular filtration rate, and high density lipoprotein cholesterol levels were inversely associated with incident hyperuricemia. Development of hyperuricemia, a very common outcome among apparently healthy South Korean men, was predicted by a variety of cardiovascular and metabolic risk factors, suggesting that lifestyle modification may help reduce the incidence of hyperuricemia.A cohort study of serum bilirubin levels and incident non-alcoholic fatty liver disease in middle aged Korean workers.
AbstractChang, Y., Ryu, S., Zhang, Y., Son, H. J., Kim, J. Y., Cho, J., & Guallar, E. (n.d.).Publication year
2012Journal title
PloS oneVolume
7Issue
5Page(s)
e37241AbstractSerum bilirubin may have potent antioxidant and cytoprotective effects. Serum bilirubin levels are inversely associated with several cardiovascular and metabolic endpoints, but their association with nonalcoholic fatty liver disease (NAFLD) has not been investigated except for a single cross-sectional study in a pediatric population. We assessed the prospective association between serum bilirubin concentrations (total, direct, and indirect) and the risk for NAFLD. We performed a cohort study in 5,900 Korean men, 30 to 59 years of age, with no evidence of liver disease and no major risk factors for liver disease at baseline. Study participants were followed in annual or biennial health examinations between 2002 and 2009. The presence of fatty liver was determined at each visit by ultrasonography. We observed 1,938 incident cases of NAFLD during 28,101.8 person-years of follow-up. Increasing levels of serum direct bilirubin were progressively associated with a decreasing incidence of NAFLD. In age-adjusted models, the hazard ratio for NAFLD comparing the highest to the lowest quartile of serum direct bilirubin levels was 0.61 (95% CI 0.54-0.68). The association persisted after adjusting for multiple metabolic parameters (hazard ratio comparing the highest to the lowest quartile 0.86, 95% CI 0.76-0.98; P trend = 0.039). Neither serum total nor indirect bilirubin levels were significantly associated with the incidence of NAFLD. In this large prospective study, higher serum direct bilirubin levels were significantly associated with a lower risk of developing NAFLD, even adjusting for a variety of metabolic parameters. Further research is needed to elucidate the mechanisms underlying this association and to establish the role of serum direct bilirubin as a marker for NAFLD risk.A Randomized Trial of Selenium Supplementation and Risk of Type-2 Diabetes, as Assessed by Plasma Adiponectin
AbstractRayman, M. P., Blundell-Pound, G., Pastor-Barriuso, R., Guallar, E., Steinbrenner, H., & Stranges, S. (n.d.).Publication year
2012Journal title
PloS oneVolume
7Issue
9AbstractBackground: Evidence that selenium affects the risk of type-2 diabetes is conflicting, with observational studies and a few randomized trials showing both lower and higher risk linked to the level of selenium intake and status. We investigated the effect of selenium supplementation on the risk of type-2 diabetes in a population of relatively low selenium status as part of the UK PRECISE (PREvention of Cancer by Intervention with SElenium) pilot study. Plasma adiponectin concentration, a recognised independent predictor of type-2 diabetes risk and known to be correlated with circulating selenoprotein P, was the biomarker chosen. Methods: In a randomized, double-blind, placebo-controlled trial, five hundred and one elderly volunteers were randomly assigned to a six-month intervention with 100, 200 or 300 μg selenium/d as high-selenium or placebo yeast. Adiponectin concentration was measured by ELISA at baseline and after six months of treatment in 473 participants with one or both plasma samples available. Results: Mean (SD) plasma selenium concentration was 88.5 ng/g (19.1) at baseline and increased significantly in the selenium-treatment groups. In baseline cross-sectional analyses, the fully adjusted geometric mean of plasma adiponectin was 14% lower (95% CI, 0-27%) in the highest than in the lowest quartile of plasma selenium (P for linear trend = 0.04). In analyses across randomized groups, however, selenium supplementation had no effect on adiponectin levels after six months of treatment (P = 0.96). Conclusions: These findings are reassuring as they did not show a diabetogenic effect of a six-month supplementation with selenium in this sample of elderly individuals of relatively low selenium status. Trial Registration: Controlled-Trials.com ISRCTN25193534.Aragon workers' health study - design and cohort description
AbstractCasasnovas, J. A., Alcaide, V., Civeira, F., Guallar, E., Ibañez, B., Borreguero, J. J., Laclaustra, M., León, M., Peñalvo, J. L., Ordovás, J. M., Pocovi, M., Sanz, G., & Fuster, V. (n.d.).Publication year
2012Journal title
BMC Cardiovascular DisordersVolume
12AbstractBackground: Spain, a Mediterranean country with relatively low rates of coronary heart disease, has a high prevalence of traditional cardiovascular risk factors and is experiencing a severe epidemic of overweight/obesity. We designed the Aragon Workers' Health Study (AWHS) to characterize the factors associated with metabolic abnormalities and subclinical atherosclerosis in a middle aged population in Spain free of clinical cardiovascular disease. The objective of this paper is to describe the study design, aims and baseline characteristics of participants in the AWHS.Methods/Design: Longitudinal cohort study based on the annual health exams of 5,400 workers of a car assembly plant in Figueruelas (Zaragoza, Spain). Study participants were recruited during a standardized clinical exam in 2009-2010 (participation rate 95.6%). Study participants will undergo annual clinical exams and laboratory assays, and baseline and triennial collection of biological materials for biobanking and cardiovascular imaging exams (carotid, femoral and abdominal ultrasonography, coronary calcium score, and ankle-arm blood pressure index). Participants will be followed-up for 10 years.Results: The average (SD) age, body mass index, and waist circumference were 49.3 (8.7) years, 27.7 (3.6) kg/m2 and 97.2 (9.9) cm, respectively, among males (N = 5,048), and 40.8 (11.6) years, 24.4 (3.8) kg/m2, and 81.9 (9.9) cm, among females (N = 351). The prevalence of overweight, obesity, current smoking, hypertension, hypercholesterolemia, and diabetes were 55.0, 23.1, 37.1, 40.3, 75.0, and 7.4%, respectively, among males, and 23.7, 8.3, 45.0, 12.1, 59.5, and 0.6%, respectively, among females. In the initial 587 study participants who completed all imaging exams (94.5% male), the prevalence of carotid plaque, femoral plaque, coronary calcium score >1 to 100, and coronary calcium score >100 was 30.3, 56.9, 27.0, and 8.8%, respectively. 67.7% of study participants had at least one plaque in the carotid or femoral arteries.Discussion: Baseline data from the AWHS show a high prevalence of cardiovascular risk factors and of sublinical atherosclerosis. Follow-up of this cohort will allow the assessment of subclinical atherosclerosis progression and the link of disease progression to traditional and emergent risk factors.Arsenic exposure and cardiovascular disease: An updated systematic review
AbstractMoon, K., Guallar, E., & Navas-Acien, A. (n.d.).Publication year
2012Journal title
Current atherosclerosis reportsVolume
14Issue
6Page(s)
542-555AbstractIn epidemiologic studies, high-chronic arsenic exposure has been associated with cardiovascular disease, despite methodological limitations. At low-moderate arsenic levels, the evidence was inconclusive. Here, we update a previous systematic review (Am J Epidemiol 2005;162:1037-49) examining the association between arsenic exposure and cardiovascular disease. Eighteen studies published since 2005 were combined with 13 studies from the previous review. We calculated pooled relative risks by comparing the highest versus the lowest exposure category across studies. For high exposure (arsenic in drinking water>50 μg/L), the pooled relative risks (95 % confidence interval) for cardiovascular disease, coronary heart disease, stroke, and peripheral arterial disease were 1.32 (95 % CI:1.05-1.67), 1.89 (95 % CI:1.33-2.69), 1.08 (95 % CI:0.98-1.19), and 2.17 (95 % CI:1.47-3.20), respectively. At low-moderate arsenic levels, the evidence was inconclusive. Our review strengthens the evidence for a causal association between highchronic arsenic exposure and clinical cardiovascular endpoints. Additional high quality studies are needed at low-moderate arsenic levels.Arsenic exposure and hypertension: A systematic review
AbstractAbhyankar, L. N., Jones, M. R., Guallar, E., & Navas-Acien, A. (n.d.).Publication year
2012Journal title
Environmental health perspectivesVolume
120Issue
4Page(s)
494-500AbstractBackground: Environmental exposure to arsenic has been linked to hypertension in persons living in arsenic-endemic areas. Objective: We summarized published epidemiologic studies concerning arsenic exposure and hypertension or blood pressure (BP) measurements to evaluate the potential relationship. Data sources and extraction: We searched PubMed, Embase, and TOXLINE and applied predetermined exclusion criteria. We identified 11 cross-sectional studies from which we abstracted or derived measures of association and calculated pooled odds ratios (ORs) using inverse-variance weighted random-effects models. Data synthesis: The pooled OR for hypertension comparing the highest and lowest arsenic exposure categories was 1.27 [95% confidence interval (CI): 1.09, 1.47; p-value for heterogeneity = 0.001; I 2 = 70.2%]. In populations with moderate to high arsenic concentrations in drinking water, the pooled OR was 1.15 (95% CI: 0.96, 1.37; p-value for heterogeneity = 0.002; I 2 = 76.6%) and 2.57 (95% CI: 1.56, 4.24; p-value for heterogeneity = 0.13; I 2 = 46.6%) before and after excluding an influential study, respectively. The corresponding pooled OR in populations with low arsenic concentrations in drinking water was 1.56 (95% CI: 1.21, 2.01; p-value for heterogeneity = 0.27; I 2 = 24.6%). A dose-response assessment including six studies with available data showed an increasing trend in the odds of hypertension with increasing arsenic exposure. Few studies have evaluated changes in systolic and diastolic BP (SBP and DBP, respectively) measurements by arsenic exposure levels, and those studies reported inconclusive findings. Conclusion: In this systematic review we identified an association between arsenic and the prevalence of hypertension. Interpreting a causal effect of environmental arsenic on hypertension is limited by the small number of studies, the presence of influential studies, and the absence of prospective evidence. Additional evidence is needed to evaluate the dose-response relationship between environmental arsenic exposure and hypertension.Arsenic exposure, diabetes prevalence, and diabetes control in the strong heart study
AbstractGribble, M. O., Howard, B. V., Umans, J. G., Shara, N. M., Francesconi, K. A., Goessler, W., Crainiceanu, C. M., Silbergeld, E. K., Guallar, E., & Navas-Acien, A. (n.d.).Publication year
2012Journal title
American Journal of EpidemiologyVolume
176Issue
10Page(s)
865-874AbstractThis study evaluated the association of arsenic exposure, as measured in urine, with diabetes prevalence, glycated hemoglobin, and insulin resistance in American Indian adults from Arizona, Oklahoma, and North and South Dakota (1989-1991). We studied 3,925 men and women 45-74 years of age with available urine arsenic measures. Diabetes was defined as a fasting glucose level of 126 mg/dL or higher, a 2-hour glucose level of 200 mg/dL or higher, a hemoglobin A1c (HbA1c) of 6.5 or higher, or diabetes treatment. Median urine arsenic concentration was 14.1 g/L (interquartile range, 7.9-24.2). Diabetes prevalence was 49.4. After adjustment for sociodemographic factors, diabetes risk factors, and urine creatinine, the prevalence ratio of diabetes comparing the 75th versus 25th percentiles of total arsenic concentrations was 1.14 (95 confidence interval: 1.08, 1.21). The association between arsenic and diabetes was restricted to participants with poor diabetes control (HbA1c <8). Arsenic was positively associated with HbA1c levels in participants with diabetes. Arsenic was not associated with HbA1c or with insulin resistance (assessed by homeostatic model assessment to quantify insulin resistance) in participants without diabetes. Urine arsenic was associated with diabetes control in a population from rural communities in the United States with a high burden of diabetes. Prospective studies that evaluate the direction of the relation between poor diabetes control and arsenic exposure are needed.Arsenic species and selected metals in human urine: Validation of HPLC/ICPMS and ICPMS procedures for a long-term population-based epidemiological study
AbstractScheer, J., Findenig, S., Goessler, W., Francesconi, K. A., Howard, B., Umans, J. G., Pollak, J., Tellez-Plaza, M., Silbergeld, E. K., Guallar, E., & Navas-Acien, A. (n.d.).Publication year
2012Journal title
Analytical MethodsVolume
4Issue
2Page(s)
406-413AbstractExposure to high inorganic arsenic concentrations in drinking water has been related to detrimental health effects, including cancers and possibly cardiovascular disease, in many epidemiological studies. Recent studies suggest that arsenic might elicit some of its toxic effects also at lower concentrations. The Strong Heart Study, a large epidemiological study of cardiovascular disease in American Indian communities, collected urine samples and performed medical examinations on 4549 participants over a 10 year period beginning in 1989. We used anion-exchange HPLC/ICPMS to determine concentrations of arsenic species (methylarsonate, dimethylarsinate and arsenate) in 5095 urine samples from the Strong Heart Study. We repeated the chromatography on a portion of the urine sample that had been oxidised, by addition of H 2O 2, to provide additional information on the presence of As(iii) species and thio-arsenicals, and by difference, of arsenobetaine and other non-retained cations. Total concentrations for As, Cd, Mo, Pb, Sb, Se, U, W, and Zn were also determined in the urine samples by ICPMS. The dataset will be used to evaluate the relationships between the concentrations of urinary arsenic species and selected metals with various cardiometabolic health endpoints. We present and discuss the analytical protocol put in place to produce this large and valuable dataset.Cadmium exposure and all-cause and cardiovascular mortality in the U.S. general population
AbstractTellez-Plaza, M., Navas-Acien, A., Menke, A., Crainiceanu, C. M., Pastor-Barriuso, R., & Guallar, E. (n.d.).Publication year
2012Journal title
Environmental health perspectivesVolume
120Issue
7Page(s)
1017-1022AbstractBackground: Urine cadmium concentrations were associated with all-cause and cardiovascular mortality in men in the 1988-1994 U.S. National Health and Nutrition Examination Survey (NHANES) population. Since 1988, cadmium exposure has decreased substantially in the United States. The associations between blood and urine cadmium and cardiovascular disease (CVD) mortality at more recent levels of exposure are unknown. Objectives: We evaluated the prospective association of blood and urine cadmium concentrations with all-cause and CVD mortality in the 1999-2004 U.S. population. Methods: We followed 8,989 participants who were ≥ 20 years of age for an average of 4.8 years. Hazard ratios for mortality end points comparing the 80th to the 20th percentiles of cadmium distributions were estimated using Cox regression. Results: The multivariable adjusted hazard ratios [95% confidence intervals (CIs)] for blood and urine cadmium were 1.50 (95% CI: 1.07, 2.10) and 1.52 (95% CI: 1.00, 2.29), respectively, for all-cause mortality, 1.69 (95% CI: 1.03, 2.77) and 1.74 (95% CI: 1.07, 2.83) for CVD mortality, 1.98 (95% CI: 1.11, 3.54) and 2.53 (95% CI: 1.54, 4.16) for heart disease mortality, and 1.73 (95% CI: 0.88, 3.40) and 2.09 (95% CI: 1.06, 4.13) for coronary heart disease mortality. The population attributable risks associated with the 80th percentile of the blood (0.80 μg/L) and urine (0.57 μg/g) cadmium distributions were 7.0 and 8.8%, respectively, for all-cause mortality and 7.5 and 9.2%, respectively, for CVD mortality Conclusions: We found strongly suggestive evidence that cadmium, at substantially low levels of exposure, remains an important determinant of all-cause and CVD mortality in a representative sample of U.S. adults. Efforts to further reduce cadmium exposure in the population could contribute to a substantial decrease in CVD disease burden.Cancer incidence in a sample of Maryland residents with serious mental illness
AbstractMcGinty, E. E., Zhang, Y., Guallar, E., Ford, D. E., Steinwachs, D., Dixon, L. B., Keating, N. L., & Daumit, G. L. (n.d.).Publication year
2012Journal title
Psychiatric ServicesVolume
63Issue
7Page(s)
714-717AbstractObjective: Persons with serious mental illness have an increased mortality rate and a higher burden of many medical conditions compared with persons without serious mental illness. Cancer risk in the population with serious mental illness is uncertain, and its incidence was examined by race, sex, and cancer site in a community-based cohort of adults with schizophrenia or bipolar disorder. Methods: The authors calculated standardized incidence ratios of total and site-specific cancers in a cohort of 3,317 Maryland Medicaid adult beneficiaries with schizophrenia or bipolar disorder followed from 1994 through 2004 for comparison with the U.S. population. Results: Total cancer incidence for adults with schizophrenia or bipolar disorder was 2.6 times higher in the cohort. Elevated risk was greatest for cancer of the lung. No differences in risk were found for African-American versus white Medicaid beneficiaries with serious mental illness. Conclusions: These findings suggest that there is a heightened risk of cancer among adults with schizophrenia or bipolar disorder. Clinicians should promote appropriate cancer screening and work to reduce modifiable risk factors, such as smoking, among persons with serious mental illness.Combined cardiac magnetic resonance imaging and C-reactive protein levels identify a cohort at low risk for defibrillator firings and death
AbstractWu, K. C., Gerstenblith, G., Guallar, E., Marine, J. E., Dalal, D., Cheng, A., Marbán, E., Lima, J. A., Tomaselli, G. F., & Weiss, R. G. (n.d.).Publication year
2012Journal title
Circulation: Cardiovascular ImagingVolume
5Issue
2Page(s)
178-186AbstractBackground-Annually, ≈80 000 Americans receive guideline-based primary prevention implantable cardioverterdefibrillators (ICDs), but appropriate firing rates are low. Current selection criteria for ICDs rely on left ventricular ejection fraction, which lacks sensitivity and specificity. Because scar-related myocardial tissue heterogeneity is a substrate for life-threatening arrhythmias, we hypothesized that cardiac magnetic resonance identification of myocardial heterogeneity improves risk stratification through (1) its association with adverse cardiac events independent of clinical factors and biomarker levels and (2) its ability to identify particularly high-and low-risk subgroups. Methods and Results-In 235 patients with chronic ischemic and nonischemic cardiomyopathy with a left ventricular ejection fraction of ≤35% undergoing clinically indicated primary prevention ICD implantation, gadolinium-enhanced cardiac magnetic resonance was prospectively performed to quantify the amount of heterogeneous myocardial tissue (gray zone [GZ]) and dense core scar. Serum high-sensitivity C-reactive protein (hsCRP) and other biomarkers were assayed. The primary end point was appropriate ICD shock for ventricular tachycardia/fibrillation or cardiac death, which occurred in 45 (19%) patients at a 3.6-year median follow-up. On univariable analysis, only diuretics, hsCRP, GZ, and core scar were associated with outcome. After multivariable adjustment, GZ and hsCRP remained independently associated with outcome (P<0.001). Patients in the lowest tertile for both GZ and hsCRP (n=42) were at particularly low risk (0.7% per year event rate), whereas those in the highest tertile for both GZ and hsCRP (n=32) had an event rate of 16.1% per year, P<0.001. Conclusions-In a cohort of primary prevention ICD candidates, combining a myocardial heterogeneity index with an inflammatory biomarker identified a subgroup with a very low risk for adverse cardiac events, including ventricular arrhythmias. This novel approach warrants further investigation to confirm its value as a clinical risk stratification tool. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00181233.Correspondence
Wu, K. C., Gerstenblith, G., Marine, J. E., Dalal, D., Cheng, A., Lima, J. A., Tomaselli, G. F., Weiss, R. G., Guallar, E., & Marban, E. (n.d.). In Circulation: Cardiovascular Imaging (1–).Publication year
2012Volume
5Issue
4Page(s)
e53Effects of vitamin c supplementation on blood pressure: A meta-analysis of randomized controlled trials
AbstractJuraschek, S. P., Guallar, E., Appel, L. J., & Miller, E. R. (n.d.).Publication year
2012Journal title
American Journal of Clinical NutritionVolume
95Issue
5Page(s)
1079-1088AbstractBackground: In observational studies, increased vitamin C intake, vitamin C supplementation, and higher blood concentrations of vitamin C are associated with lower blood pressure (BP). However, evidence for blood pressure-lowering effects of vitamin C in clinical trials is inconsistent. Objective: The objective was to conduct a systematic review and meta-analysis of clinical trials that examined the effects of vitamin C supplementation on BP. Design: We searched Medline, EMBASE, and Central databases from 1966 to 2011. Prespecified inclusion criteria were as follows: 1) use of a randomized controlled trial design; 2) trial reported effects on systolic BP (SBP) or diastolic BP (DBP) or both; 3) trial used oral vitamin C and concurrent control groups; and 4) trial had a minimum duration of 2 wk. BP effects were pooled by random-effects models, with trials weighted by inverse variance. Results: Twenty-nine trials met eligibility criteria for the primary analysis. The median dose was 500 mg/d, the median duration was 8 wk, and trial sizes ranged from 10 to 120 participants. The pooled changes in SBP and DBP were -3.84 mm Hg (95% CI: -5.29, -2.38 mm Hg; P < 0.01) and -1.48 mm Hg (95% CI: -2.86, -0.10 mm Hg; P = 0.04), respectively. In trials in hypertensive participants, corresponding reductions in SBP and DBP were -4.85 mm Hg (P < 0.01) and -1.67 mm Hg (P = 0.17). After the inclusion of 9 trials with imputed BP effects, BP effects were attenuated but remained significant. Conclusions: In short-term trials, vitamin C supplementation reduced SBP and DBP. Long-term trials on the effects of vitamin C supplementation on BP and clinical events are needed.Efficacy of an educational material on second primary cancer screening practice for cancer survivors: A randomized controlled trial
AbstractShin, D. W., Cho, J., Kim, Y. W., Oh, J. H., Kim, S. W., Chung, K. W., Lee, W. Y., Lee, J. E., Guallar, E., & Lee, W. C. (n.d.).Publication year
2012Journal title
PloS oneVolume
7Issue
3AbstractBackground: Cancer surivors have limited knowledge about second primary cancer (SPC) screening and suboptimal rates of completion of screening practices for SPC. Our objective was to test the efficacy of an educational material on the knowledge, attitudes, and screening practices for SPC among cancer survivors. Methods: Randomized, controlled trial among 326 cancer survivors from 6 oncology care outpatient clinics in Korea. Patients were randomized to an intervention or an attention control group. The intervention was a photo-novel, culturally tailored to increase knowledge about SPC screening. Knowledge and attitudes regarding SPC screening were assessed two weeks after the intervention, and screening practices were assessed after one year. Results: At two weeks post-intervention, the average knowledge score was significantly higher in the intervention compared to the control group (0.81 vs. 0.75, P&0.01), with no significant difference in their attitude scores (2.64 vs. 2.57, P = 0.18). After 1 year of follow-up, the completion rate of all appropriate cancer screening was 47.2% in both intervention and control groups. Conclusion: While the educatinal material was effective for increasing knowledge of SPC screening, it did not promote cancer screening practice among cancer survivors. More effective interventions are needed to increase SPC screening rates in this population. Trial Registration: ClinicalTrial.gov NCT00948337.Ethnic Differences in the Prevalence of Metabolic Syndrome: Results from a Multi-Ethnic Population-Based Survey in Malaysia
AbstractRampal, S., Mahadeva, S., Guallar, E., Bulgiba, A., Mohamed, R., Rahmat, R., Arif, M. T., & Rampal, L. (n.d.).Publication year
2012Journal title
PloS oneVolume
7Issue
9AbstractIntroduction: The prevalence of metabolic syndrome is increasing disproportionately among the different ethnicities in Asia compared to the rest of the world. This study aims to determine the differences in the prevalence of metabolic syndrome across ethnicities in Malaysia, a multi-ethnic country. Methods: In 2004, we conducted a national cross-sectional population-based study using a stratified two-stage cluster sampling design (N = 17,211). Metabolic syndrome was defined according to the International Diabetes Federation/National Heart, Lung and Blood Institute/American Heart Association (IDF/NHLBI/AHA-2009) criteria. Multivariate models were used to study the independent association between ethnicity and the prevalence of the metabolic syndrome. Results: The overall mean age was 36.9 years, and 50.0% participants were female. The ethnic distribution was 57.0% Malay, 28.5% Chinese, 8.9% Indian and 5.0% Indigenous Sarawakians. The overall prevalence of the metabolic syndrome was 27.5%, with a prevalence of central obesity, raised triglycerides, low high density lipoprotein cholesterol, raised blood pressure and raised fasting glucose of 36.9%, 29.3%, 37.2%, 38.0% and 29.1%, respectively. Among those <40 years, the adjusted prevalence ratios for metabolic syndrome for ethnic Chinese, Indians, and Indigenous Sarawakians compared to ethnic Malay were 0.81 (95% CI 0.67 to 0.96), 1.42 (95% CI 1.19 to 1.69) and 1.37 (95% CI 1.08 to 1.73), respectively. Among those aged ≥40 years, the corresponding prevalence ratios were 0.86 (95% CI 0.79 to 0.92), 1.25 (95% CI 1.15 to 1.36), and 0.94 (95% CI 0.80, 1.11). The P-value for the interaction of ethnicity by age was 0.001. Conclusions: The overall prevalence of metabolic syndrome in Malaysia was high, with marked differences across ethnicities. Ethnic Chinese had the lowest prevalence of metabolic syndrome, while ethnic Indians had the highest. Indigenous Sarawakians showed a marked increase in metabolic syndrome at young ages.Influence of serum selenium concentrations on hypertension: The Lipid Analytic Cologne cross-sectional study
AbstractBerthold, H. K., Michalke, B., Krone, W., Guallar, E., & Gouni-Berthold, I. (n.d.).Publication year
2012Journal title
Journal of HypertensionVolume
30Issue
7Page(s)
1328-1335AbstractAims: Selenium is an antioxidant micronutrient with potential associations with hypertension. Few studies have investigated the association of serum selenium concentrations with blood pressure and hypertension in countries with low dietary selenium intake such as Germany, with inconsistent findings. Methods: We undertook a cross-sectional analysis of participants in the Lipid Analytic Cologne (LIANCO) cohort. To reduce potential confounding, we restricted the analysis to 792 participants who were never smokers, who did not use antihypertensive medications, and who did not have diabetes or known atherosclerotic disease. Hypertension was defined as blood pressure at least 140 and/or at least 90 mmHg. About half of the cohort was diagnosed as hypertensive. Selenium was measured by inductively coupled plasma-dynamic reaction cell-mass spectrometry (ICP-DRC-MS). Results: Mean ± standard deviation (SD) serum selenium concentration was 68 ± 32 μg/l. The multivariable adjusted differences (95% confidence intervals) in blood pressure levels comparing the highest (>91.9 μg/l) to the lowest (≤42.8 μg/l) quartile of serum selenium were 5.2 (1.4 to 8.9), 2.8 (0.7 to 4.8), and 2.4 (-0.4 to 5.2) mmHg for systolic, diastolic, and pulse pressure, respectively (P for trend for all <0.003). The corresponding multivariable adjusted odds ratio for the presence of hypertension was 1.52 (0.98 to 2.36; P trend = 0.004). Conclusions: The data suggest that even in a population with very low serum selenium concentrations higher serum selenium concentrations are associated with higher blood pressure levels and a higher prevalence of hypertension. These findings call for careful evaluation of the effects of selenium on blood pressure endpoints in randomized clinical trials.Post-myocardial-infarction quality of care among disabled Medicaid beneficiaries with and without serious mental illness
AbstractMcGinty, E. E., Blasco-Colmenares, E., Zhang, Y., DosReis, S. C., Ford, D. E., Steinwachs, D. M., Guallar, E., & Daumit, G. L. (n.d.).Publication year
2012Journal title
General Hospital PsychiatryVolume
34Issue
5Page(s)
493-499AbstractObjective: The objective was to examine the association between serious mental illness and quality of care for myocardial infarction among disabled Maryland Medicaid beneficiaries. Methods: We conducted a retrospective cohort study of disabled Maryland Medicaid beneficiaries with myocardial infarction from 1994 to 2004. Cardiac procedures and guideline-based medication use were compared for persons with and without serious mental illness. Results: Of the 633 cohort members with myocardial infarction, 137 had serious mental illness. Serious mental illness was not associated with differences in receipt of cardiac procedures or guideline-based medications. Overall use of guideline-based medications was low; 30 days after the index hospitalization for myocardial infarction, 19%, 35% and 11% of cohort members with serious mental illness and 22%, 37% and 13% of cohort members without serious mental illness had any use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers and statins, respectively. Study participants with and without serious mental illness had similar rates of mortality. Overall, use of beta-blockers [hazard ratio 0.93, 95% confidence interval (CI) 0.90-0.97] and statins (hazard ratio 0.93, 95% CI 0.89-0.98) was associated with reduced risk of mortality. Conclusions: Quality improvement programs should consider how to increase adherence to medications of known benefit among disabled Medicaid beneficiaries with and without serious mental illness.Reduction in cadmium exposure in the United States population, 1988-2008: The contribution of declining smoking rates
AbstractTellez-Plaza, M., Navas-Acien, A., Caldwell, K. L., Menke, A., Muntner, P., & Guallar, E. (n.d.).Publication year
2012Journal title
Environmental health perspectivesVolume
120Issue
2Page(s)
204-209AbstractBackground: Public health policies such as tobacco control, air pollution reduction, and hazardous waste remediation may have reduced cadmium exposure among U.S. adults. However, trends in urine cadmium, a marker of cumulative cadmium exposure, have not been evaluated. Objectives: We estimated the trends in urine cadmium concentrations in U.S. adults using data from the National Health and Nutrition Examination Surveys (NHANES) from 1988 to 2008. We also evaluated the impact of changes in the distribution of available cadmium determinants (age, sex, race, education, body mass index, smoking, and occupation) at the population level to explain cadmium trends. Methods: The study population included 19,759 adults ≥ 20 years of age with measures of urine cadmium and cadmium determinants. Results: Age-adjusted geometric means of urine cadmium concentrations were 0.36, 0.35, 0.27, 0.27, 0.28, 0.25, and 0.26 μg/g creatinine in 1988-1991, 1991-1994, 1999-2000, 2001-2002, 2003-2004, 2005-2006, and 2007-2008, respectively. The age, sex, and race/ethnicity-adjusted percent reduction in urine cadmium geometric means comparing 1999-2002 and 2003-2008 with 1988-1994 were 27.8% (95% confidence interval: 22.3%, 32.9%) and 34.3% (29.9%, 38.4%), respectively (p-trend < 0.001), with reductions in all participant subgroups investigated. In never smokers, reductions in serum cotinine accounted for 15.6% of the observed reduction. In ever smokers, changes in smoking cessation, and cumulative and recent dose accounted for 17.1% of the observed reduction. Conclusions: Urine cadmium concentrations decreased markedly between 1988 and 2008. Declining smoking rates and changes in exposure to tobacco smoke may have played an important role in the decline of urine cadmium concentrations, benefiting both smokers and nonsmokers. Cadmium has been associated to several health outcomes in NHANES 1999-2008. Consequently, despite the observed decline, further reduction in cadmium exposure is needed.Serum sex steroid hormones and frailty in older American men of the Third National Health and Nutrition Examination Survey (NHANES III)
AbstractEichholzer, M., Barbir, A., Basaria, S., Dobs, A. S., Feinleib, M., Guallar, E., Menke, A., Nelson, W. G., Rifai, N., Platz, E. A., & Rohrmann, S. (n.d.).Publication year
2012Journal title
Aging MaleVolume
15Issue
4Page(s)
208-215AbstractObjective: To determine whether frailty is associated with circulating total and free testosterone, total and free estradiol, and sex hormone-binding globulin (SHBG) in older men. Methods: With NHANES III data of 461 men aged 60 years and older, we used logistic regression to analyze the associations between serum concentrations of sex steroid hormones, SHBG and frailty. Participants meeting any three or more of the five frailty criteria were classified as "frail", all others were considered as non-frail. Results: 2.5% of men were frail. Men with SHBG ≥66 nmol/L had three times the odds of frailty (OR = 2.97; 95% CI 1.28-6.86) compared to men with SHBG <66 nmol/L. Men with free testosterone levels below 243 pmol/L had an increased odds of frailty (OR = 3.92; 95% CI 1.29-11.89). None of these associations was statistically significant after additionally adjusting for body mass index, smoking and history of cardiovascular diseases (CVD). Total testosterone, and total and free estradiol serum levels were not statistically significantly associated with frailty. Conclusions: In this US nationally representative study of older men, low free testosterone and high SHBG serum levels were associated with a significantly increased odds of frailty after adjustment for age and race/ethnicity. These associations may, however, be explained by confounding due to obesity, smoking, and the higher prevalence of CVD in frail men or by low hormones or high SHBG mediating the association between obesity, smoking, CVD and frailty.