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

Randomised controlled trial of the effect of long-term selenium supplementation on plasma cholesterol in an elderly Danish population

Cold, F., Winther, K. H., Pastor-Barriuso, R., Rayman, M. P., Guallar, E., Nybo, M., Griffin, B. A., Stranges, S., & Cold, S. (n.d.).

Publication year

2015

Journal title

British Journal of Nutrition

Volume

114

Issue

11

Page(s)

1807-1818

10.1017/S0007114515003499

Abstract

Abstract

Although cross-sectional studies have shown a positive association between Se and cholesterol concentrations, a recent randomised controlled trial in 501 elderly UK individuals of relatively low-Se status found that Se supplementation for 6 months lowered total plasma cholesterol. The Danish PRECISE (PREvention of Cancer by Intervention with Selenium) pilot study (ClinicalTrials.gov ID: NCT01819649) was a 5-year randomised, double-blinded, placebo-controlled trial with four groups (allocation ratio 1:1:1:1). Men and women aged 60-74 years (n 491) were randomised to 100 (n 124), 200 (n 122) or 300 (n 119) μg Se-enriched yeast or matching placebo-yeast tablets (n 126) daily for 5 years. A total of 468 participants continued the study for 6 months and 361 participants, equally distributed across treatment groups, continued for 5 years. Plasma samples were analysed for total and HDL-cholesterol and for total Se concentrations at baseline, 6 months and 5 years. The effect of different doses of Se supplementation on plasma lipid and Se concentrations was estimated by using linear mixed models. Plasma Se concentration increased significantly and dose-dependently in the intervention groups after 6 months and 5 years. Total cholesterol decreased significantly both in the intervention groups and in the placebo group after 6 months and 5 years, with small and nonsignificant differences in changes in plasma concentration of total cholesterol, HDL-cholesterol, non-HDL-cholesterol and total:HDL-cholesterol ratio between intervention and placebo groups. The effect of long-term supplementation with Se on plasma cholesterol concentrations or its sub-fractions did not differ significantly from placebo in this elderly population.

Relation of dietary glycemic index and glycemic load to coronary artery calcium in asymptomatic Korean adults

Choi, Y., Chang, Y., Ryu, S., Cho, J., Kim, M. K., Ahn, Y., Lee, J. E., Sung, E., Kim, B., Ahn, J., Kim, C. W., Rampal, S., Zhao, D., Zhang, Y., Pastor-Barriuso, R., Lima, J. A., Chung, E. C., Shin, H., & Guallar, E. (n.d.).

Publication year

2015

Journal title

American Journal of Cardiology

Volume

116

Issue

4

Page(s)

520-526

10.1016/j.amjcard.2015.05.005

Abstract

Abstract

The relation between glycemic index, glycemic load, and subclinical coronary atherosclerosis is unknown. The aim of the study was to evaluate the associations between energy-adjusted glycemic index, glycemic load, and coronary artery calcium (CAC). This study was cross-sectional analysis of 28,429 asymptomatic Korean men and women (mean age 41.4 years) without a history of diabetes or cardiovascular disease. All participants underwent a health screening examination between March 2011 and April 2013, and dietary intake over the preceding year was estimated using a validated food frequency questionnaire. Cardiac computed tomography was used for CAC scoring. The prevalence of detectable CAC (CAC score >0) was 12.4%. In multivariable-adjusted models, the CAC score ratios (95% confidence intervals) comparing the highest to the lowest quintile of glycemic index and glycemic load were 1.74 (1.08 to 2.81; p trend = 0.03) and 3.04 (1.43 to 6.46; p trend = 0.005), respectively. These associations did not differ by clinical subgroups, including the participants at low cardiovascular risk. In conclusion, these findings suggest that high dietary glycemic index and glycemic load were associated with a greater prevalence and degree of CAC, with glycemic load having a stronger association.

Relation of Physical Activity and Incident Atrial Fibrillation (from the Multi-Ethnic Study of Atherosclerosis)

Bapat, A., Zhang, Y., Post, W. S., Guallar, E., Soliman, E. Z., Heckbert, S. R., Lima, J., Bertoni, A. G., Alonso, A., & Nazarian, S. (n.d.).

Publication year

2015

Journal title

American Journal of Cardiology

Volume

116

Issue

6

Page(s)

883-888

10.1016/j.amjcard.2015.06.013

Abstract

Abstract

Previous studies have raised the question of whether an association exists between physical activity and atrial fibrillation (AF). We used the Multi-Ethnic Study of Atherosclerosis (MESA) database to examine the association between physical activity and AF in a diverse population without clinically recognized cardiovascular disease (CVD). MESA participants (n = 5,793) with complete baseline physical activity and covariate data were included. Cox proportional hazards models were used to calculate hazard ratios (HRs) for incident AF by levels of total intentional exercise and vigorous physical activity, independently and in combination. Multivariate models were adjusted for demographics and CVD risk factors. During a mean follow-up of 7.7 ± 1.9 years, 199 AF cases occurred. In the overall MESA population, neither vigorous physical activity nor total intentional exercise was independently associated with incident AF after adjusting for covariates. However, within the group that reported any vigorous physical activity, there was a statistically significant inverse association between total intentional exercise (modeled as a continuous variable) and incident AF. In those who reported any vigorous physical activity, the top tertile of total intentional exercise was associated with a significantly lower risk of incident AF compared with the group with no total intentional exercise in the fully adjusted model (HR 0.46, 95% confidence interval 0.22 to 0.98). In conclusion, neither total intentional exercise nor vigorous physical activity alone was associated with incident AF, but greater total intentional exercise was associated with a lower risk of incident AF in those who participated in any vigorous physical activity. As importantly, no subgroup of participants demonstrated an increased risk of incident AF with greater physical activity. The results re-emphasize the beneficial role of physical activity for cardiovascular health.

Sleep duration, sleep quality, and markers of subclinical arterial disease in healthy men and women

Kim, C. W., Chang, Y., Zhao, D., Cainzos-Achirica, M., Ryu, S., Jung, H. S., Yun, K. E., Choi, Y., Ahn, J., Zhang, Y., Rampal, S., Baek, Y., Lima, J. A., Shin, H., Guallar, E., Cho, J., & Sung, E. (n.d.).

Publication year

2015

Journal title

Arteriosclerosis, Thrombosis, and Vascular Biology

Volume

35

Issue

10

Page(s)

2238-2245

10.1161/ATVBAHA.115.306110

Abstract

Abstract

Objective.Short and long sleep duration are associated with increased risk of clinical cardiovascular events, but the association between sleep duration and subclinical cardiovascular disease is not well established. We examined the association between sleep duration and sleep quality with coronary artery calcification (CAC) and with brachial.ankle pulse wave velocity (PWV) in a large sample of young and middle-aged asymptomatic adults. Approach and Results.We conducted a cross-sectional study of adult men and women who underwent a health checkup examination, including assessment of sleep duration and quality and coupled with either CAC (n=29 203) or brachial. ankle PWV (n=18 106). The multivariate-adjusted CAC score ratios (95% confidence interval) comparing sleep durations of ≥5, 6, 8, and ≤9 hours with 7 hours of sleep were 1.50 (1.17.1.93), 1.34 (1.10.1.63), 1.37 (0.99.1.89), and 1.72 (0.90. 3.28), respectively (P for quadratic trend=0.002). The corresponding average differences in brachial.ankle PWV were 6.7 (0.75.12.6), 2.9 (.1.7 to 7.4), 10.5 (4.5.16.5), and 9.6 (.0.7 to 19.8) cm/s, respectively (P for quadratic trend=0.019). Poor subjective sleep quality was associated with CAC in women but not in men, whereas the association between poor subjective sleep quality and brachial.ankle PWV was stronger in men than in women. Conclusions.In this large study of apparently healthy men and women, extreme sleep duration and poor subjective sleep quality were associated with increased prevalence of CAC and higher PWV. Our results underscore the importance of an adequate quantity and quality of sleep to maintain cardiovascular health.

The Association of Urine Arsenic with Prevalent and Incident Chronic Kidney Disease: Evidence from the Strong Heart Study

Zheng, L. Y., Umans, J. G., Yeh, F., Francesconi, K. A., Goessler, W., Silbergeld, E. K., Bandeen-Roche, K., Guallar, E., Howard, B. V., Weaver, V. M., & Navas-Acien, A. (n.d.).

Publication year

2015

Journal title

Epidemiology

Volume

26

Issue

4

Page(s)

601-612

10.1097/EDE.0000000000000313

Abstract

Abstract

Background: Few studies have evaluated associations between low to moderate arsenic levels and chronic kidney disease (CKD). The objective was to evaluate the associations of inorganic arsenic exposure with prevalent and incident CKD in American Indian adults. Methods: We evaluated the associations of inorganic arsenic exposure with CKD in American Indians who participated in the Strong Heart Study in 3,851 adults ages 45-74 years in a cross-sectional analysis, and 3,119 adults with follow-up data in a prospective analysis. Inorganic arsenic, monomethylarsonate, and dimethylarsinate were measured in urine at baseline. CKD was defined as estimated glomerular filtration rate ≤ 60 ml/min/1.73 m2, kidney transplant or dialysis. Results: CKD prevalence was 10.3%. The median (IQR) concentration of inorganic plus methylated arsenic species (total arsenic) in urine was 9.7 (5.8, 15.7) μg/L. The adjusted odds ratio (OR; 95% confidence interval) of prevalent CKD for an interquartile range in total arsenic was 0.7 (0.6, 0.8), mostly due to an inverse association with inorganic arsenic (OR: 0.4 [0.3, 0.4]). Monomethylarsonate and dimethylarsinate were positively associated with prevalent CKD after adjustment for inorganic arsenic (OR: 3.8 and 1.8). The adjusted hazard ratio of incident CKD for an IQR in sum of inorganic and methylated arsenic was 1.2 (1.03, 1.41). The corresponding HRs for inorganic arsenic, monomethylarsonate, and dimethylarsinate were 1.0 (0.9, 1.2), 1.2 (1.00, 1.3), and 1.2 (1.0, 1.4). Conclusions: The inverse association of urine inorganic arsenic with prevalent CKD suggests that kidney disease affects excretion of inorganic arsenic. Arsenic species were positively associated with incident CKD. Studies with repeated measures are needed to further characterize the relation between arsenic and kidney disease development.

The associations of 25-hydroxyvitamin D levels, vitamin D binding protein gene polymorphisms, and race with risk of incident fracture-related hospitalization: Twenty-year follow-up in a bi-ethnic cohort (the ARIC Study)

Takiar, R., Lutsey, P. L., Zhao, D., Guallar, E., Schneider, A. L., Grams, M. E., Appel, L. J., Selvin, E., & Michos, E. D. (n.d.).

Publication year

2015

Journal title

Bone

Volume

78

Page(s)

94-101

10.1016/j.bone.2015.04.029

Abstract

Abstract

Background: Deficient levels of 25-hydroxyvitamin D [25(OH)D] have been associated with increased fracture risk. Racial differences in fracture risk may be related to differences in bioavailable vitamin D due to single nucleotide polymorphism (SNP) variations in the vitamin D binding protein (DBP). Methods: We measured 25(OH)D levels in 12,781 middle-aged White and Black participants [mean age 57. years (SD 5.7), 25% Black] in the ARIC Study who attended the second examination from 1990-1992. Participants were genotyped for two DBP SNPs (rs4588 and rs7041). Incident hospitalized fractures were measured by abstracting hospital records for ICD-9 codes. We used Cox proportional hazards models to evaluate the association between 25(OH)D levels and risk of fracture with adjustment for possible confounders. Interactions were tested by race and DBP genotype. Results: There were 1122 incident fracture-related hospitalizations including 267 hip fractures over a median of 19.6. years of follow-up. Participants with deficient 25(OH)D (<. 20. ng/mL) had a higher risk of any fracture hospitalization [HR = 1.21 (95% CI 1.05-1.39)] and hospitalization for hip fracture [HR = 1.35 (1.02-1.79)]. No significant racial interaction was noted (p-interaction = 0.20 for any fracture; 0.74 for hip fracture). There was no independent association of rs4588 and rs7041 with fracture. However, there was a marginal interaction for 25(OH)D deficiency with rs7041 among Whites (p-interaction = 0.065). Whites with both 25(OH)D deficiency and the GG genotype [i.e. with predicted higher levels of DBP and lower bioavailable vitamin D] were at the greatest risk for any fracture [HR = 1.48 (1.10-2.00)] compared to Whites with the TT genotype and replete 25(OH)D (reference group). Conclusions: Deficient 25(OH)D levels are associated with higher incidence of hospitalized fractures. Marginal effects were seen in Whites for the DBP genotype associated with lower bioavailable vitamin D, but result inconclusive. Further investigation is needed to more directly evaluate the association between bioavailable vitamin D and fracture risk.

A longitudinal study of age-related changes in intraocular pressure: The kangbuk samsung health study

Zhao, D., Kim, M. H., Pastor-Barriuso, R., Chang, Y., Ryu, S., Zhang, Y., Rampal, S., Shin, H., Kim, J. M., Friedman, D. S., Guallar, E., & Cho, J. (n.d.).

Publication year

2014

Journal title

Investigative Ophthalmology and Visual Science

Volume

55

Issue

10

Page(s)

6244-6250

10.1167/iovs.14-14151

Abstract

Abstract

PURPOSE. To examine the longitudinal association between age and intraocular pressure (IOP) in a large sample of Korean men and women.METHODS. We conducted a prospective cohort study of 274,064 young and middle-aged Korean adults with normal fundoscopic findings, following them from January 1, 2002, to February 28, 2010. Health exams were scheduled annually or biennially. At each visit, IOP was measured in both eyes using automated noncontact tonometers. The longitudinal change in IOP with age was evaluated using three-level mixed models for longitudinal paired-eye data, accounting for correlations between paired eyes and repeated measurements over time.RESULTS. In fully adjusted models, the average longitudinal change in IOP per 1-year increase in age was -0.065 mm Hg (95% confidence interval [CI] -0.068 to -0.063), with marked sex differences (P < 0.001). In men, the average annual IOP change was -0.093 mm Hg (95% CI -0.096 to -0.091) throughout follow-up. In women, the average annual IOP change was -0.006 mm Hg (95% CI -0.010 to -0.003), with a relatively flat association in the age range of 30 to 59 years and more marked annual decreases at younger and older ages.CONCLUSIONS. Intraocular pressure was inversely associated with age in a large cohort of Korean adults attending health-screening visits. For men, this inverse association was observed throughout the entire age range, while for women it was evident only in younger (<30 years of age) and older (‡60 years of age) women, with no association in women aged 30 to 59. Further research is needed to better understand the underlying mechanisms and to reconsider cutoffs for defining high IOP by age and sex groups in Asian populations.

Association between markers of glucose metabolism and risk of colorectal adenoma

Rampal, S., Yang, M. H., Sung, J., Son, H. J., Choi, Y. H., Lee, J. H., Kim, Y. H., Chang, D. K., Rhee, P. L., Rhee, J. C., Guallar, E., & Cho, J. (n.d.).

Publication year

2014

Journal title

Gastroenterology

Volume

147

Issue

1

Page(s)

78-87.e3

10.1053/j.gastro.2014.03.006

Abstract

Abstract

Background & Aims Diabetes is a risk factor for colorectal cancer. We studied the association between markers of glucose metabolism and metabolic syndrome and the presence of colorectal adenomas in a large number of asymptomatic men and women attending a health screening program in South Korea. We also investigated whether these associations depend on adenoma location. Methods In a cross-sectional study, we measured fasting levels of glucose, insulin, hemoglobin A1c, and C-peptide and calculated homeostatic model assessment (HOMA) values (used to quantify insulin resistance) for 19,361 asymptomatic South Korean subjects who underwent colonoscopy examinations from January 2006 to June 2009. Participants completed a standardized self-administered health questionnaire and a validated semiquantitative food frequency questionnaire. Blood samples were collected on the day of the colonoscopy; fasting blood samples were also collected. Robust Poisson regression was used to model the associations of glucose markers with the prevalence of any adenoma. Results Using detailed multivariable-adjusted dose-response models, the prevalence ratios (aPR, 95% confidence interval [CI]) for any adenoma, comparing the 90th with the 10th percentile, were 1.08 (1.00-1.16; P =.04) for fasting glucose, 1.07 (0.99-1.15; P =.10) for insulin, 1.09 (1.02-1.18, P =.02) for HOMA, 1.09 (1.01-1.17; P =.02) for hemoglobin A1c, and 1.14 (1.05-1.24; P =.002) for C-peptide. The corresponding ratios for nonadvanced adenomas were 1.11 (0.99-1.25; P =.08), 1.10 (0.98-1.24; P =.12), 1.15 (1.02-1.29; P =.02), 1.14 (1.01-1.28; P =.03), and 1.20 (1.05-1.37; P =.007), respectively. The corresponding ratios for advanced adenomas were 1.32 (0.94-1.84; P =.11), 1.23 (0.87-1.75; P =.24), 1.30 (0.92-1.85; P =.14), 1.13 (0.79-1.61; P =.50), and 1.67 (1.15-2.42; P =.007), respectively. Metabolic syndrome was associated with the prevalence of any adenoma (aPR, 1.18; 95% CI, 1.13-1.24; P <.001), nonadvanced adenoma (aPR, 1.30; 95% CI, 1.20-1.40; P <.001), and advanced adenoma (aPR, 1.42; 95% CI, 1.14-1.78; P =.002). Associations were similar for adenomas located in the distal versus proximal colon. Conclusions Increasing levels of glucose, HOMA values, levels of hemoglobin A1c and C-peptide, and metabolic syndrome are significantly associated with the prevalence of adenomas. Adenomas should be added to the list of consequences of altered glucose metabolism.

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: <18.5, 18.5 to 22.9, 23.0 to 24.9 (the reference category), 25.0 to 29.9, and ≥30.0 kg/m2. Results: The median BMI was 22.6 (IQR 20.3 to 25.1). The percentages of patients with BMI<18.5, 18.5 to 22.9, 23.0 to 24.9, 25.0 to 29.9, and ≥30.0 were 12, 42.3, 19.9, 22.4, and 3.3%, respectively. The Cox-proportional hazard ratios with exact partial likelihood to handle tied failures for hospital mortality comparing the BMI categories <18.5, 18.5 to 22.9, 25.0 to 29.9, and ≥30.0 with the reference category were 1.13 (0.88 to 1.44), 1.03 (0.84 to 1.26), 0.96 (0.76 to 1.22), and 0.68 (0.43 to 1.08), respectively, with a highly significant test for trend (p = 0.02). Conclusions: A graded inverse association between BMI and hospital mortality with a strong significant trend was found in critically ill patients in Korea.

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

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. L., & 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 <5 years of diabetes duration. We also found a hockey-stick shaped associations between biomarkers of glucose metabolisms and the prevalence of glaucoma.Conclusions:Diabetes was associated with higher risk of glaucoma. Participants without diabetes but at the higher levels of fasting glucose, fasting insulin, HbA1c and HOMA-IR spectrum may also be at greater risk of glaucoma.Background:Diabetes may affect vascular autoregulation of the retina and optic nerve and may be associated with an increased risk of glaucoma,but the association of prediabetes, insulin resistance, markers of glucose metabolismwith glaucoma has not beenevaluated in general population samples.Objective:To examine the relation between diabetes, pre-diabetes, metabolic syndrome and its components and the levels of fasting glucose, HbA1c and HOMA-IR with the prevalence of glaucoma in the general U.S. population.Methods: Cross-sectional study of 3,299 adult men and women from the 2005-2008 National Health and NutritionExamination Survey (NHANES). The presence of diabetes, prediabetes, the metabolic syndrome and its individual components and biomarkers of glucose metabolisms were based on standardized questionnaire and physical exam data and laboratory tests. The history of glaucoma was assessed through questionnaire during the home interview.

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.). In Annals of internal medicine (1–).

Publication year

2014

Volume

160

Issue

11

Page(s)

809-810

10.7326/L14-5011-7

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 <60 mL/min per 1.73 m 2. Parametric Cox models and pooled logistic regression models were used to estimate adjusted hazard ratios for incident CKD. We observed 238 incident cases of CKD during 70,515.8 person-years of follow-up. In age-adjusted models, the hazard ratios for CKD comparing quartiles 2-4 vs. quartile 1 of serum direct bilirubin were 0.93 (95% CI 0.67-1.28), 0.88 (0.60-1.27) and 0.60 (0.42-0.88), respectively. In multivariable models, the adjusted hazard ratio for CKD comparing the highest to the lowest quartile of serum direct bilirubin levels was 0.60 (95% CI 0.41-0.87; P trend = 0.01). Neither serum total nor indirect bilirubin levels were significantly associated with the incidence of CKD. Conclusions: Higher serum direct bilirubin levels were significantly associated with a lower risk of developing CKD, even adjusting for a variety of cardiometabolic 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 CKD risk.

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 <-0.9, 0.5 to 2.0, and ≥2.1 kg compared to a weight change of -0.9 to 0.4 kg (reference) were 0.80 (0.66-0.97), 0.99 (0.82-1.20), and 1.24 (1.02-1.49), respectively (P-trend<0.001). Conclusions In this large cohort of young and middle age Koreans, metabolic health status, obesity, and weight change were all independently associated with increased incidence of diabetes over 5 years of follow-up.

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 <2.5. Results MHO individuals had a higher prevalence of coronary calcification than normal weight subjects. In multivariable-adjusted models, the CAC score ratio comparing MHO with normal-weight participants was 2.26 (95% confidence interval: 1.48 to 3.43). In mediation analyses, further adjustment for metabolic risk factors markedly attenuated this association, which was no longer statistically significant (CAC score ratio 1.24; 95% confidence interval: 0.79 to 1.96). These associations did not differ by clinically-relevant subgroups. Conclusions MHO participants had a higher prevalence of subclinical coronary atherosclerosis than metabolically-healthy normal-weight participants, which supports the idea that MHO is not a harmless condition. This association, however, was mediated by metabolic risk factors at levels below those considered abnormal, which suggests that the label of metabolically healthy for obese subjects may be an artifact of the cutoff levels used in the definition of metabolic health.