Eliseo Guallar

Chair and Professor of the Department of Epidemiology

Professional overview

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.

Education

Diploma of English, Spanish Official School of Languages at Zaragoza (Escuela Oficial de Idiomas de Zaragoza), Zaragoza, Spain

MD, University of Zaragoza, Zaragoza, Spain

MPH, University of Minnesota, Minneapolis, MN

DrPH, Harvard University, Boston, MA

Honors and awards

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)

Publications

Publications

Association of arsenic and metals with concentrations of 25-hydroxyvitamin d and 1,25-dihydroxyvitamin D among adolescents in Torreón, Mexico

Zamoiski, R. D., Guallar, E., García-Vargas, G. G., Rothenberg, S. J., Resnick, C., Andrade, M. R., Steuerwald, A. J., Parsons, P. J., Weaver, V. M., Navas-Acien, A., & Silbergeld, E. K. (n.d.).

Publication year

2014

Journal title

Environmental health perspectives

Volume

122

Issue

11

Page(s)

1233-1238

10.1289/ehp.1307861

Abstract

Abstract

Background: Limited data suggest that lead (Pb), cadmium (Cd), and uranium (U) may disrupt vitamin D metabolism and inhibit production of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active vitamin D metabolite, from 25-hydroxyvitamin D [25(OH)D] in the kidney.Objectives: We evaluated the association between blood lead (BPb) and urine arsenic (As), Cd, molybdenum (Mo), thallium (Tl), and U with markers of vitamin D metabolism [25(OH)D and 1,25(OH)2D].Methods: We conducted a cross-sectional study of 512 adolescents in Torreón, a town in Mexico with a Pb smelter near residential areas. BPb was measured using atomic absorption spectrometry. Urine As, Cd, Mo, Tl, and U were measured using inductively coupled plasma mass spectrometry. Serum 25(OH)D and 1,25(OH)2D were measured using a chemiluminescent immunoassay and a radioimmunoassay, respectively. Multivariable linear models with vitamin D markers as the outcome were used to estimate associations of BPb and creatinine-corrected urine As and metal concentrations with serum vitamin D concentrations, controlling for age, sex, adiposity, smoking, socioeconomic status, and time outdoors.Results: Serum 25(OH)D was positively associated with urine Mo and Tl [1.5 (95% CI: 0.4, 2.6) and 1.2 (95% CI: 0.3, 2.1) ng/mL higher with a doubling of exposure, respectively]. Serum 1,25(OH)2D was positively associated with urine As and U [3.4 (95% CI: 0.9, 5.9) and 2.2 (95% CI: 0.7, 3.7) pg/mL higher, respectively], with little change in associations after additional adjustment for serum 25(OH)D. Pb and Cd were not associated with 25(OH)D or 1,25(OH)2D concentrations.Conclusions: Overall, our findings did not support a negative effect of As or metal exposures on serum 1,25(OH)2D concentrations. Additional research is needed to confirm positive associations between serum 1,25(OH)2D and urine U and As concentrations and to clarify potential underlying mechanisms.

Association of electrocardiographic and imaging surrogates of left ventricular hypertrophy with incident atrial fibrillation : MESA (Multi-Ethnic Study of Atherosclerosis)

Chrispin, J., Jain, A., Soliman, E. Z., Guallar, E., Alonso, A., Heckbert, S. R., Bluemke, D. A., Lima, J. A., & Nazarian, S. (n.d.).

Publication year

2014

Journal title

Journal of the American College of Cardiology

Volume

63

Issue

19

Page(s)

2007-2013

10.1016/j.jacc.2014.01.066

Abstract

Abstract

Objectives This study sought to examine the association between left ventricular hypertrophy (LVH), dened by cardiac magnetic resonance (CMR) and electrocardiography (ECG), with incident atrial fibrillation (AF). Background Previous studies of the association between AF and LVH were based primarily on echocardiographic measures of LVH. Methods The MESA (Multi-Ethnic Study of Atherosclerosis) enrolled 4,942 participants free of clinically recognized cardiovascular disease. Incident AF was based on MESA-ascertained hospital-discharge International Classification of Diseases codes and Centers for Medicare and Medicaid Services inpatient hospital claims. CMR-LVH was defined as left ventricular mass ≥95th percentile of the MESA population distribution. Eleven ECG-LVH criteria were assessed. The association of LVH with incident AF was evaluated using multivariable Cox proportional hazards models adjusted for CVD risk factors. Results During a median follow-up of 6.9 years, 214 incident AF events were documented. Participants with AF were more likely to be older, hypertensive, and overweight. The risk of AF was greater in participants with CMR-derived LVH (hazard ratio [HR]: 2.04, 95% confidence interval [CI]: 1.15 to 3.62). AF was associated with ECG-derived LVH measure of Sokolow-Lyon voltage product after adjusting for CMR-LVH (HR: 1.83, 95% CI: 1.06 to 3.14, p = 0.02). The associations with AF for CMR-LVH and Sokolow-Lyon voltage product were attenuated when adjusted for CMR left atrial volumes. Conclusions In a multiethnic cohort of participants without clinically detected cardiovascular disease, both CMR and ECG-derived LVH were associated with incident AF. ECG-LVH showed prognostic significance independent of CMR-LVH. The association was attenuated when adjusted for CMR left atrial volumes.

Association of global DNA methylation and global DNA hydroxymethylation with metals and other exposures in human blood DNA samples

Tellez-Plaza, M., Tang, W. Y., Shang, Y., Umans, J. G., Francesconi, K. A., Goessler, W., Ledesma, M., Leon, M., Laclaustra, M., Pollak, J., Guallar, E., Cole, S. A., Fallin, M. D., & Navas-Acien, A. (n.d.).

Publication year

2014

Journal title

Environmental health perspectives

Volume

122

Issue

9

Page(s)

946-954

10.1289/ehp.1306674

Abstract

Abstract

Background: The association between human blood DNA global methylation and global hydroxymethylation has not been evaluated in population-based studies. No studies have evaluated environmental determinants of global DNA hydroxymethylation, including exposure to metals. Objective: We evaluated the association between global DNA methylation and global DNA hydroxymethylation in 48 Strong Heart Study participants for which selected metals had been measured in urine at baseline and DNA was available from 1989-1991 (visit 1) and 1998-1999 (visit 3). Methods: We measured the percentage of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in samples using capture and detection antibodies followed by colorimetric quantification. We explored the association of participant characteristics (i.e., age, adiposity, smoking, and metal exposure) with both global DNA methylation and global DNA hydroxymethylation. Results: The Spearman's correlation coefficient for 5-mC and 5-hmC levels was 0.32 (p = 0.03) at visit 1 and 0.54 (p < 0.001) at visit 3. Trends for both epigenetic modifications were consistent across potential determinants. In cross-sectional analyses, the odds ratios of methylated and hydroxymethylated DNA were 1.56 (95% CI: 0.95, 2.57) and 1.76 (95% CI: 1.07, 2.88), respectively, for the comparison of participants above and below the median percentage of dimethylarsinate. The corresponding odds ratios were 1.64 (95% CI: 1.02, 2.65) and 1.16 (95% CI: 0.70, 1.94), respectively, for the comparison of participants above and below the median cadmium level. Arsenic exposure and metabolism were consistently associated with both epigenetic markers in cross-sectional and prospective analyses. The positive correlation of 5-mC and 5-hmC levels was confirmed in an independent study population. Conclusions: Our findings support that both epigenetic measures are related at the population level. The consistent trends in the associations between these two epigenetic modifications and the characteristics evaluated, especially arsenic exposure and metabolism, suggest the need for understanding which of the two measures is a better biomarker for environmental epigenetic effects in future large-scale epidemiologic studies.

Body mass index and mortality in Korean intensive care units : A prospective multicenter cohort study

Lim, S. Y., Choi, W. I., Jeon, K., Guallar, E., Koh, Y., Lim, C. M., Koh, S. O., Na, S., Lee, Y. J., Kim, S. C., Kim, I. H., Kim, J. H., Kim, J. Y., Lim, J., Rhee, C. K., Park, S., Kim, H. C., Lee, J. H., Park, J., … Cho, J. H. (n.d.).

Publication year

2014

Journal title

PloS one

Volume

9

Issue

4

10.1371/journal.pone.0090039

Abstract

Abstract

Background: The level of body mass index (BMI) that is associated with the lowest mortality in critically ill patients in Asian populations is uncertain. We aimed to examine the association of BMI with hospital mortality in critically ill patients in Korea. Methods: We conducted a prospective multicenter cohort study of 3,655 critically ill patients in 22 intensive care units (ICUs) in Korea. BMI was categorized into five groups:

C-reactive protein levels in patients at cardiovascular risk : EURIKA study

Halcox, J. P., Roy, C., Tubach, F., Banegas, J. R., Dallongeville, J., De Backer, G., Guallar, E., Sazova, O., Medina, J., Perk, J., Steg, P. G., Rodríguez-Artalejo, F., & Borghi, C. (n.d.).

Publication year

2014

Journal title

BMC Cardiovascular Disorders

Volume

14

10.1186/1471-2261-14-25

Abstract

Abstract

Background: Elevated C-reactive protein (CRP) levels are associated with high cardiovascular risk, and might identify patients who could benefit from more carefully adapted risk factor management. We have assessed the prevalence of elevated CRP levels in patients with one or more traditional cardiovascular risk factors.Methods: Data were analysed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov Identifier: NCT00882336), which included patients (aged ≥50 years) from 12 European countries with at least one traditional cardiovascular risk factor but no history of cardiovascular disease. Analysis was also carried out on the subset of patients without diabetes mellitus who were not receiving statin therapy.Results: In the overall population, CRP levels were positively correlated with body mass index and glycated haemoglobin levels, and were negatively correlated with high-density lipoprotein cholesterol levels. CRP levels were also higher in women, those at higher traditionally estimated cardiovascular risk and those with greater numbers of metabolic syndrome markers. Among patients without diabetes mellitus who were not receiving statin therapy, approximately 30% had CRP levels ≥3 mg/L, and approximately 50% had CRP levels ≥2 mg/L, including those at intermediate levels of traditionally estimated cardiovascular risk.Conclusions: CRP levels are elevated in a large proportion of patients with at least one cardiovascular risk factor, without diabetes mellitus who are not receiving statin therapy, suggesting a higher level of cardiovascular risk than predicted according to conventional risk estimation systems.Trial registration: ClinicalTrials.gov Identifier: NCT00882336.

Cadmium exposure and cancer mortality in a prospective cohort : The strong heart study

García-Esquinas, E., Pollan, M., Tellez-Plaza, M., Francesconi, K. A., Goessler, W., Guallar, E., Umans, J. G., Yeh, J., Best, L. G., & Navas-Acien, A. (n.d.).

Publication year

2014

Journal title

Environmental health perspectives

Volume

122

Issue

4

Page(s)

363-370

10.1289/ehp.1306587

Abstract

Abstract

Background: Cadmium (Cd) is a toxic metal classified as a human carcinogen by the International Agency for Research on Cancer. oBjective: We evaluated the association of long-term Cd exposure, as measured in urine, with cancer mortality in American Indians from Arizona, Oklahoma, and North and South Dakota who participated in the Strong Heart Study during 1989-1991. Methods: The Strong Heart Study was a prospective cohort study of 3,792 men and women 45-74 years of age who were followed for up to 20 years. Baseline urinary Cd (U-Cd) was measured using inductively coupled plasma mass spectrometry. We assessed cancer events by annual mortality surveillance. results: The median (interquintile range) U-Cd concentration was 0.93 (0.55, 1.63) μg/g creatinine. After adjusting for sex, age, smoking status, cigarette pack-years, and body mass index, the adjusted hazard ratios (HRs) comparing the 80th versus the 20th percentiles of U-Cd were 1.30 (95% CI: 1.09, 1.55) for total cancer, 2.27 (95% CI: 1.58, 3.27) for lung cancer, and 2.40 (95% CI: 1.39, 4.17) for pancreatic cancer mortality. For all smoking-related cancers combined, the corresponding HR was 1.56 (95% CI: 1.24, 1.96). Cd was not significantly associated with liver, esophagus and stomach, colon and rectum, breast, prostate, kidney, or lymphatic and hematopoietic cancer mortality. On the basis of mediation analysis, we estimated that the percentage of lung cancer deaths due to tobacco smoking that could be attributed to Cd exposure was 9.0% (95% CI: 2.8, 21.8). conclusions: Low-to-moderate Cd exposure was prospectively associated with total cancer mortality and with mortality from cancers of the lung and pancreas. The implementation of population-based preventive measures to decrease Cd exposure could contribute to reducing the burden of cancer.

Controversy over clinical guidelines : Listen to the evidence, not the noise

Guallar, E., & Laine, C. (n.d.).

Publication year

2014

Journal title

Annals of internal medicine

Volume

160

Issue

5

Page(s)

361-362

10.7326/m14-0112

Abstract

Abstract

~

Detección de casos de EPOC en atención primaria en 4 países de Latinoamérica : Metodología del Estudio PUMA

Schiavi, E., Stirbulov, R., Hernández Vecino, R., Mercurio, S., Di Boscio, V., Zabert, G., Aguirre, C., Rey, A., Moreno, D., Montes De Oca, M., Casas, A., Guallar, E., Jardim, J., Varela, M. V., & Venegas, A. R. (n.d.).

Publication year

2014

Journal title

Archivos de Bronconeumologia

Volume

50

Issue

11

Page(s)

469-474

10.1016/j.arbr.2014.09.010

Abstract

Abstract

Introduction: The prevalence of COPD among patients treated in the healthcare system in Latin America is unknown. The PUMA study (Prevalencia y práctica habitUal -diagnóstico y tratamiento- en población de riesgo de EPOC en Médicos generalistas de 4 países de América Latina) screened at-risk patients attending primary care centers to evaluate the prevalence, diagnosis and treatment of COPD in this setting. The aim of this report is to describe the study methodology. Methods: Multicenter, observational, cross-sectional study conducted in Argentina, Colombia, Uruguay and Venezuela. Subjects were. ≥. 40 years, smokers, former smokers and/or exposed to fossil fuels attending primary care centers. Eligible patients underwent pre- and post- bronchodilator spirometry and completed standardized questionnaires on demographics, smoking, exposure to environmental/domestic pollution, symptoms/history and management of respiratory diseases, comorbidities, and use of healthcare resources. Results: A total of 57 centers in 4 countries participated; 1,907 patients were included, 1,743 completed the PUMA questionnaire and 1,540 patients underwent validated spirometry. Conclusions: We describe the methodology used in the PUMA study, the first systematic multicenter study in four Latin American countries aimed at detecting COPD cases confirmed by spirometry in primary care. Approximately 90% of patients who completed the PUMA questionnaire underwent valid spirometry tests. This gives room for reflection on the feasibility of opportunistic screening at the primary care level to detect patients in the early stages of COPD or with undiagnosed COPD, and improve the diagnosis and management of this disease.

Diabetes, glucose metabolism, and glaucoma : The 2005-2008 National Health and Nutrition Examination Survey

Zhao, D., Cho, J., Kim, M. H., Friedman, D., & Guallar, E. (n.d.).

Publication year

2014

Journal title

PloS one

Volume

9

Issue

11

10.1371/journal.pone.0112460

Abstract

Abstract

Results:Diabetes was strongly associated with prevalent glaucoma.In fully adjusted models, the odds ratiofor glaucoma comparing participants with diabetes with participants in the reference group with neither pre-diabetes nor diabetes was 2.12 (95% CI: 1.23, 3.67). The corresponding odd ratio comparing participants with pre-diabetes to those in the reference group was 1.01 (95% CI: 0.57, 1.82). Patients with 5 or more years of diabetes duration hadan OR for glaucoma of 3.90 (95% CI: 1.63, 9.32) compared with patients with

Differential methylation of the arsenic (III) methyltransferase promoter according to arsenic exposure

Gribble, M. O., Tang, W. Y., Shang, Y., Pollak, J., Umans, J. G., Francesconi, K. A., Goessler, W., Silbergeld, E. K., Guallar, E., Cole, S. A., Fallin, M. D., & Navas-Acien, A. (n.d.).

Publication year

2014

Journal title

Archives of Toxicology

Volume

88

Issue

2

Page(s)

275-282

10.1007/s00204-013-1146-x

Abstract

Abstract

Inorganic arsenic is methylated in the body by arsenic (III) methyltransferase (AS3MT). Arsenic methylation is thought to play a role in arsenic-related epigenetic phenomena, including aberrant DNA and histone methylation. However, it is unclear whether the promoter of the AS3MT gene, which codes for AS3MT, is differentially methylated as a function of arsenic exposure. In this study, we evaluated AS3MT promoter methylation according to exposure, assessed by urinary arsenic excretion in a stratified random sample of 48 participants from the Strong Heart Study who had urine arsenic measured at baseline and DNA available from 1989 to 1991 and 1998-1999. For this study, all data are from the 1989-1991 visit. We measured AS3MT promoter methylation at its 48 CpG loci by bisulphite sequencing. We compared mean % methylation at each CpG locus by arsenic exposure group using linear regression adjusted for study centre, age and sex. A hypomethylated region in the AS3MT promoter was associated with higher arsenic exposure. In vitro, arsenic induced AS3MT promoter hypomethylation, and it increased AS3MT expression in human peripheral blood mononuclear cells. These findings may suggest that arsenic exposure influences the epigenetic regulation of a major arsenic metabolism gene.

Enough is enough : In response

Guallar, E., Stranges, S., Mulrow, C., Appel, L. J., & Miller, E. R. (n.d.).

Publication year

2014

Journal title

Annals of internal medicine

Volume

160

Issue

11

Page(s)

809-810

10.7326/L14-5011-7

Abstract

Abstract

~

Erratum : Stop wasting money on vitamin and mineral supplements (Annals of Internal Medicine (2013) 159 (850-851))

Guallar, E., Stranges, S., Mulrow, C., Appel, L. J., Miller, E. R., & Guallar, E. (n.d.).

Publication year

2014

Journal title

Annals of internal medicine

Volume

160

Issue

2

Page(s)

143

10.7326/L14-5001-8

Abstract

Abstract

~

Higher serum direct bilirubin levels were associated with a lower risk of incident chronic kidney disease in middle aged Korean men

Ryu, S., Chang, Y., Zhang, Y., Woo, H. Y., Kwon, M. J., Park, H., Lee, K. B., Son, H. J., Cho, J., & Guallar, E. (n.d.).

Publication year

2014

Journal title

PloS one

Volume

9

Issue

2

10.1371/journal.pone.0075178

Abstract

Abstract

Background: The association between serum bilirubin levels and incident chronic kidney disease (CKD) in the general population is unknown. We aimed to examine the association between serum bilirubin concentration (total, direct, and indirect) and the risk of incident CKD. Methods and Findings: Longitudinal cohort study of 12,823 Korean male workers 30 to 59 years old without CKD or proteinuria at baseline participating in medical health checkup program in a large worksite. Study participants were followed for incident CKD from 2002 through 2011. Estimated glomerular filtration rate (eGFR) was estimated by using the CKD-EPI equation. CKD was defined as eGFR

Impact of body mass index, metabolic health and weight change on incident diabetes in a Korean population

Jung, H. S., Chang, Y., Eun Yun, K., Kim, C. W., Choi, E. S., Kwon, M. J., Cho, J., Zhang, Y., Rampal, S., Zhao, D., Soo Kim, H., Shin, H., Guallar, E., & Ryu, S. (n.d.).

Publication year

2014

Journal title

Obesity

Volume

22

Issue

8

Page(s)

1880-1887

10.1002/oby.20751

Abstract

Abstract

Objective The aim of this study was to examine an impact of body mass index (BMI) and weight change on the risk of diabetes according to metabolic health status. Methods Cohort study of 34,999 Korean men and women 30-59 years of age free of diabetes at baseline were followed-up annually or biennially for an average of 5.1 years. Being metabolically healthy was defined as not having any metabolic syndrome component. Results During 176,878.6 person-years of follow-up, 889 participants developed diabetes (incidence rate 5.0 per 1000 person-years). Compared to metabolically healthy normal-weight individuals, the adjusted hazard ratios for diabetes in metabolically unhealthy obese and in metabolically healthy obese were 13.7 (95% confidence interval [CI] 9.8-19.0) and 2.7 (95% CI: 1.7-4.3), respectively the aHR (95% CI) for incident diabetes for weight changes of

Impact of continuity of care on mortality and health care costs : A nationwide cohort study in Korea

Shin, D. W., Cho, J., Yang, H. K., Park, J. H., Lee, H., Kim, H., Oh, J., Hwang, S., Cho, B., & Guallar, E. (n.d.).

Publication year

2014

Journal title

Annals of family medicine

Volume

12

Issue

6

Page(s)

534-541

10.1370/afm.1685

Abstract

Abstract

PURPOSE Continuity of care is considered a core element of high-quality primary care, but its impact on mortality and health care costs is unclear. We aimed to determine the impact of continuity of care on mortality, costs, and health outcomes in patients with newly diagnosed cardiovascular risk factors.METHODS We conducted a cohort study of a 3% nationwide random sample of Korean National Health Insurance enrollees. A total of 47,433 patients who had received new diagnoses of hypertension, diabetes, hypercholesterolemia, or their complications in 2003 or 2004 were included. We determined standard indices of continuity of care—most frequent provider continuity (MFPC), modified, modified continuity index (MMCI), and continuity of care index (COC)-and evaluated their association with study outcomes over 5 years of follow-up. Outcome measures included overall mortality, cardiovascular mortality, incident cardiovascular events, and health care costs.RESULTS The multivariable-adjusted hazard ratios (HRs) for all-cause mortality, cardiovascular mortality, incident myocardial infarction, and incident ischemic stroke comparing participants with COC index below the median to those above the median were HR = 1.12 (95% CI, 1.04-1.21), 1.30 (1.13-1.50), 1.57 (1.28- 1.95), and 1.44 (1.27-1.63), respectively. Similar findings were obtained for other indices of continuity of care. Lower continuity of care was also associated with increased inpatient and outpatient days and costs.CONCLUSIONS Lower indices of continuity of care in patients with newly diagnosed hypertension, diabetes, and hypercholesterolemia were associated with higher all-cause and cardiovascular mortality, cardiovascular events, and health care costs. Health care systems should be designed to support long-term trusting relationships between patients and physicians.

Impact of urine concentration adjustment method on associations between urine metals and estimated glomerular filtration rates (eGFR) in adolescents

Weaver, V. M., Vargas, G. G., Silbergeld, E. K., Rothenberg, S. J., Fadrowski, J. J., Rubio-Andrade, M., Parsons, P. J., Steuerwald, A. J., Navas-Acien, A., & Guallar, E. (n.d.).

Publication year

2014

Journal title

Environmental Research

Volume

132

Page(s)

226-232

10.1016/j.envres.2014.04.013

Abstract

Abstract

Positive associations between urine toxicant levels and measures of glomerular filtration rate (GFR) have been reported recently in a range of populations. The explanation for these associations, in a direction opposite that of traditional nephrotoxicity, is uncertain. Variation in associations by urine concentration adjustment approach has also been observed. Associations of urine cadmium, thallium and uranium in models of serum creatinine- and cystatin-C-based estimated GFR (eGFR) were examined using multiple linear regression in a cross-sectional study of adolescents residing near a lead smelter complex. Urine concentration adjustment approaches compared included urine creatinine, urine osmolality and no adjustment. Median age, blood lead and urine cadmium, thallium and uranium were 13.9 years, 4.0μg/dL, 0.22, 0.27 and 0.04g/g creatinine, respectively, in 512 adolescents. Urine cadmium and thallium were positively associated with serum creatinine-based eGFR only when urine creatinine was used to adjust for urine concentration (β coefficient=3.1mL/min/1.73m2; 95% confidence interval=1.4, 4.8 per each doubling of urine cadmium). Weaker positive associations, also only with urine creatinine adjustment, were observed between these metals and serum cystatin-C-based eGFR and between urine uranium and serum creatinine-based eGFR. Additional research using non-creatinine-based methods of adjustment for urine concentration is necessary.

Is carotid intima-media thickness as predictive as other noninvasive techniques for the detection of coronary artery disease?

Zhang, Y., Guallar, E., Qiao, Y., & Wasserman, B. A. (n.d.).

Publication year

2014

Journal title

Arteriosclerosis, Thrombosis, and Vascular Biology

Volume

34

Issue

7

Page(s)

1341-1345

10.1161/ATVBAHA.113.302075

Abstract

Abstract

Carotid intima-media thickness (CIMT) measured by B-mode ultrasound is the most widely used noninvasive imaging method to assess atherosclerosis and cardiovascular risk. CIMT has been consistently associated with coronary artery disease and stroke; however, recent meta-analyses and systematic reviews suggest that its clinical usefulness may be limited because the addition of CIMT to traditional risk factors has not improved the risk prediction of cardiovascular events in the general population. Characterizing the carotid wall by MRI may have greater clinical utility compared with CIMT measurements by ultrasound. Unlike CIMT, MRI measurements of wall thickness include the adventitia and may be sensitive to adventitial thickening that results from vasa vasorum proliferation as a sign of early plaque development. MRI also has the ability to image the entire circumference of the carotid wall, including the outer wall of the carotid bulb where plaque forms in its earliest stage, and identify plaque components such as the lipid core, fibrous cap, and intraplaque hemorrhage that are closely related to plaque vulnerability and cardiovascular risk. Additional research is needed to assess the added prognostic value of MRI measurements of wall and plaque features in risk prediction beyond traditional risk factors.

Metabolically-healthy obesity and coronary artery calcification

Chang, Y., Kim, B. K., Yun, K. E., Cho, J., Zhang, Y., Rampal, S., Zhao, D., Jung, H. S., Choi, Y., Ahn, J., Lima, J. A., Shin, H., Guallar, E., & Ryu, S. (n.d.).

Publication year

2014

Journal title

Journal of the American College of Cardiology

Volume

63

Issue

24

Page(s)

2679-2686

10.1016/j.jacc.2014.03.042

Abstract

Abstract

Objectives The purpose of this study was to compare the coronary artery calcium (CAC) scores of metabolically-healthy obese (MHO) and metabolically healthy normal-weight individuals in a large sample of apparently healthy men and women. Background The risk of cardiovascular disease among obese individuals without obesity-related metabolic abnormalities, referred to as MHO, is controversial. Methods We conducted a cross-sectional study of 14,828 metabolically-healthy adults with no known cardiovascular disease who underwent a health checkup examination that included estimation of CAC scores by cardiac tomography. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance

Outcomes in African Americans undergoing cardioverter-defibrillator implantation for primary prevention of sudden cardiac death : Findings from the Prospective Observational Study of Implantable Cardioverter-Defibrillators (PROSE-ICD)

Zhang, Y., Kennedy, R., Blasco-Colmenares, E., Butcher, B., Norgard, S., Eldadah, Z., Dickfeld, T., Ellenbogen, K. A., Marine, J. E., Guallar, E., Tomaselli, G. F., & Cheng, A. (n.d.).

Publication year

2014

Journal title

Heart Rhythm

Volume

11

Issue

8

Page(s)

1377-1383

10.1016/j.hrthm.2014.04.039

Abstract

Abstract

Background Implantable cardioverter-defibrillators (ICDs) reduce the risk of death in patients with left ventricular dysfunction. Little is known regarding the benefit of this therapy in African Americans (AAs). Objective The purpose of this study was to determine the association between AA race and outcomes in a cohort of primary prevention ICD patients. Methods We conducted a prospective cohort study of patients with systolic heart failure who underwent ICD implantation for primary prevention of sudden cardiac death. The primary end-point was appropriate ICD shock defined as a shock for rapid ventricular tachyarrhythmias. The secondary end-point was all-cause mortality. Results There were 1189 patients (447 AAs and 712 non-AAs) enrolled. Over a median follow-up of 5.1 years, a total of 137 patients experienced an appropriate ICD shock, and 343 died (294 of whom died without receiving an appropriate ICD shock). The multivariate adjusted hazard ratio (95% confidence interval) comparing AAs vs non-AAs were 1.24 (0.96-1.59) for all-cause mortality, 1.33 (1.02, 1.74) for all-cause mortality without receiving appropriate ICD shock, and 0.78 (0.51, 1.19) for appropriate ICD shock. Ejection fraction, diabetes, and hypertension appeared to explain 24.1% (10.1%-69.5%), 18.7% (5.3%-58.0%), and 13.6% (3.8%-53.6%) of the excess risk of mortality in AAs, with a large proportion of the mortality difference remaining unexplained. Conclusion In patients with primary prevention ICDs, AAs had an increased risk of dying without receiving an appropriate ICD shock compared to non-AAs.

Placental transfer and concentrations of cadmium, mercury, lead, and selenium in mothers, newborns, and young children

Chen, Z., Myers, R., Wei, T., Bind, E., Kassim, P., Wang, G., Ji, Y., Hong, X., Caruso, D., Bartell, T., Gong, Y., Strickland, P., Navas-Acien, A., Guallar, E., & Wang, X. (n.d.).

Publication year

2014

Journal title

Journal of Exposure Science and Environmental Epidemiology

Volume

24

Issue

5

Page(s)

537-544

10.1038/jes.2014.26

Abstract

Abstract

There is an emerging hypothesis that exposure to cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in utero and early childhood could have long-term health consequences. However, there are sparse data on early life exposures to these elements in US populations, particularly in urban minority samples. This study measured levels of Cd, Hg, Pb, and Se in 50 paired maternal, umbilical cord, and postnatal blood samples from the Boston Birth Cohort (BBC). Maternal exposure to Cd, Hg, Pb, and Se was 100% detectable in red blood cells (RBCs), and there was a high degree of maternal-fetal transfer of Hg, Pb, and Se. In particular, we found that Hg levels in cord RBCs were 1.5 times higher than those found in the mothers. This study also investigated changes in concentrations of Cd, Hg, Pb, and Se during the first few years of life. We found decreased levels of Hg and Se but elevated Pb levels in early childhood. Finally, this study investigated the association between metal burden and preterm birth and low birthweight. We found significantly higher levels of Hg in maternal and cord plasma and RBCs in preterm or low birthweight births, compared with term or normal birthweight births. In conclusion, this study showed that maternal exposure to these elements was widespread in the BBC, and maternal-fetal transfer was a major source of early life exposure to Hg, Pb, and Se. Our results also suggest that RBCs are better than plasma at reflecting the trans-placental transfer of Hg, Pb, and Se from the mother to the fetus. Our study findings remain to be confirmed in larger studies, and the implications for early screening and interventions of preconception and pregnant mothers and newborns warrant further investigation.

Plasma selenium levels and oxidative stress biomarkers : A gene-environment interaction population-based study

Galan-Chilet, I., Tellez-Plaza, M., Guallar, E., De Marco, G., Lopez-Izquierdo, R., Gonzalez-Manzano, I., Carmen Tormos, M., Martin-Nuñez, G. M., Rojo-Martinez, G., Saez, G. T., Martín-Escudero, J. C., Redon, J., & Javier Chaves, F. (n.d.).

Publication year

2014

Journal title

Free Radical Biology and Medicine

Volume

74

Page(s)

229-236

10.1016/j.freeradbiomed.2014.07.005

Abstract

Abstract

The role of selenium exposure in preventing chronic disease is controversial, especially in selenium-repleted populations. At high concentrations, selenium exposure may increase oxidative stress. Studies evaluating the interaction of genetic variation in genes involved in oxidative stress pathways and selenium are scarce. We evaluated the cross-sectional association of plasma selenium concentrations with oxidative stress levels, measured as oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8-oxo-7,8-dihydroguanine (8-oxo-dG) in urine, and the interacting role of genetic variation in oxidative stress candidate genes, in a representative sample of 1445 men and women aged 18-85 years from Spain. The geometric mean of plasma selenium levels in the study sample was 84.76 μg/L. In fully adjusted models the geometric mean ratios for oxidative stress biomarker levels comparing the highest to the lowest quintiles of plasma selenium levels were 0.61 (0.50-0.76) for GSSG/GSH, 0.89 (0.79-1.00) for MDA, and 1.06 (0.96-1.18) for 8-oxo-dG. We observed nonlinear dose-responses of selenium exposure and oxidative stress biomarkers, with plasma selenium concentrations above ~110 μg/L being positively associated with 8-oxo-dG, but inversely associated with GSSG/GSH and MDA. In addition, we identified potential risk genotypes associated with increased levels of oxidative stress markers with high selenium levels. Our findings support that high selenium levels increase oxidative stress in some biological processes. More studies are needed to disentangle the complexity of selenium biology and the relevance of potential gene-selenium interactions in relation to health outcomes in human populations.

Protein biomarkers identify patients unlikely to benefit from primary prevention implantable cardioverter defibrillators : Findings from the prospective observational study of implantable cardioverter defibrillators (PROSE-ICD)

Cheng, A., Zhang, Y., Blasco-Colmenares, E., Dalal, D., Butcher, B., Norgard, S., Eldadah, Z., Ellenbogen, K. A., Dickfeld, T., Spragg, D. D., Marine, J. E., Guallar, E., & Tomaselli, G. F. (n.d.).

Publication year

2014

Journal title

Circulation: Arrhythmia and Electrophysiology

Volume

7

Issue

6

Page(s)

1084-1091

10.1161/CIRCEP.113.001705

Abstract

Abstract

Background: Primary prevention implantable cardioverter defibrillators (ICDs) reduce all-cause mortality, but the benefits are heterogeneous. Current risk stratification based on left ventricular ejection fraction has limited discrimination power. We hypothesize that biomarkers for inflammation, neurohumoral activation, and cardiac injury can predict appropriate shocks and all-cause mortality in patients with primary prevention ICDs. Methods and Results: The Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSe-ICD) enrolled 1189 patients with systolic heart failure who underwent ICD implantation for primary prevention of sudden cardiac death. The primary end point was an ICD shock for adjudicated ventricular tachyarrhythmia. The secondary end point was all-cause mortality. After a median follow-up of 4.0 years, 137 subjects experienced an appropriate ICD shock and 343 participants died (incidence rates of 3.2 and 5.8 per 100 person-years, respectively). In multivariableadjusted models, higher interleukin-6 levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, interleukin-6, tumor necrosis factor-α receptor II, pro-brain natriuretic peptide (pro-BNP), and cardiac troponin T showed significant linear trends for increased risk of all-cause mortality across quartiles. A score combining these 5 biomarkers identified patients who were much more likely to die than to receive an appropriate shock from the ICD. Conclusions: An increase in serum biomarkers of inflammation, neurohumoral activation, and myocardial injury increased the risk for death but poorly predicted the likelihood of an ICD shock. These findings highlight the potential importance of serum-based biomarkers in identifying patients who are unlikely to benefit from primary prevention ICDs.

Race/ethnicity, residential segregation, and exposure to ambient air pollution : The Multi-Ethnic Study of Atherosclerosis (MESA)

Jones, M. R., Diez-Roux, A. V., Hajat, A., Kershaw, K. N., O'Neill, M. S., Guallar, E., Post, W. S., Kaufman, J. D., & Navas-Acien, A. (n.d.).

Publication year

2014

Journal title

American journal of public health

Volume

104

Issue

11

Page(s)

2130-2137

10.2105/AJPH.2014.302135

Abstract

Abstract

Objectives. We described the associations of ambient air pollution exposure with race/ethnicity and racial residential segregation. Methods. We studied 5921 White, Black, Hispanic, and Chinese adults across 6 US cities between 2000 and 2002. Household-level fine particulate matter (PM2.5) and nitrogen oxides (NOX) were estimated for 2000. Neighborhood racial composition and residential segregation were estimated using US census tract data for 2000. Results. Participants in neighborhoods with more than 60% Hispanic populations were exposed to 8% higher PM2.5and 31% higher NOXconcentrations compared with those in neighborhoods with less than 25% Hispanic populations. Participants in neighborhoods with more than 60% White populations were exposed to 5% lower PM2.5and 18% lower NOXconcentrations compared with those in neighborhoods with less than 25% of the population identifying as White. Neighborhoods with Whites underrepresented or with Hispanics overrepresented were exposed to higher PM2.5and NOXconcentrations. No differences were observed for other racial/ethnic groups. Conclusions. Living in majority White neighborhoods was associated with lower air pollution exposures, and living in majority Hispanic neighborhoods was associated with higher air pollution exposures. This new information highlighted the importance of measuring neighborhood-level segregation in the environmental justice literature.

Random-effects meta-analysis of inconsistent effects : A time for change

Cornell, J. E., Mulrow, C. D., Localio, R., Stack, C. B., Meibohm, A. R., Guallar, E., & Goodman, S. N. (n.d.).

Publication year

2014

Journal title

Annals of internal medicine

Volume

160

Issue

4

Page(s)

267-270

10.7326/m13-2886

Abstract

Abstract

A primary goal of meta-analysis is to improve the estimation of treatment effects by pooling results of similar studies. This article explains how the most widely used method for pooling heterogeneous studies-the DerSimonian-Laird (DL) estimator-can produce biased estimates with falsely high precision. A classic example is presented to show that use of the DL estimator can lead to erroneous conclusions. Particular problems with the DL estimator are discussed, and several alternative methods for summarizing heterogeneous evidence are presented. The authors support replacing universal use of the DL estimator with analyses based on a critical synthesis that recognizes the uncertainty in the evidence, focuses on describing and explaining the probable sources of variation in the evidence, and uses random-effects estimates that provide more accurate confidence limits than the DL estimator.

Reply

Zhao, D., Guallar, E., Cho, J., & Kim, M. H. (n.d.).

Publication year

2014

Journal title

American Journal of Ophthalmology

Volume

158

Issue

6

Page(s)

1363

10.1016/j.ajo.2014.09.022

Abstract

Abstract

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