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

Changes in follow-up left ventricular ejection fraction associated with outcomes in primary prevention implantable cardioverter-defibrillator and cardiac resynchronization therapy device recipients

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

Publication year

2015

Journal title

Journal of the American College of Cardiology

Volume

66

Issue

5

Page(s)

524-531

10.1016/j.jacc.2015.05.057

Abstract

Abstract

Background Heart failure patients with primary prevention implantable cardioverter-defibrillators (ICD) may experience an improvement in left ventricular ejection fraction (LVEF) over time. However, it is unclear how LVEF improvement affects subsequent risk for mortality and sudden cardiac death. Objectives This study sought to assess changes in LVEF after ICD implantation and the implication of these changes on subsequent mortality and ICD shocks. Methods We conducted a prospective cohort study of 538 patients with repeated LVEF assessments after ICD implantation for primary prevention of sudden cardiac death. The primary endpoint was appropriate ICD shock defined as a shock for ventricular tachyarrhythmias. The secondary endpoint was all-cause mortality. Results Over a mean follow-up of 4.9 years, LVEF decreased in 13.0%, improved in 40.0%, and was unchanged in 47.0% of the patients. In the multivariate Cox models comparing patients with an improved LVEF with those with an unchanged LVEF, the hazard ratios were 0.33 (95% confidence interval: 0.18 to 0.59) for mortality and 0.29 (95% confidence interval: 0.11 to 0.78) for appropriate shock. During follow-up, 25% of patients showed an improvement in LVEF to >35% and their risk of appropriate shock decreased but was not eliminated. Conclusions Among primary prevention ICD patients, 40.0% had an improved LVEF during follow-up and 25% had LVEF improved to >35%. Changes in LVEF were inversely associated with all-cause mortality and appropriate shocks for ventricular tachyarrhythmias. In patients whose follow-up LVEF improved to >35%, the risk of an appropriate shock remained but was markedly decreased.

Clinical and serum-based markers are associated with death within 1 year of de novo implant in primary prevention ICD recipients

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

Publication year

2015

Journal title

Heart Rhythm

Volume

12

Issue

2

Page(s)

360-366

10.1016/j.hrthm.2014.10.034

Abstract

Abstract

Background Implantable cardioverter-defibrillator (ICD) implantation is contraindicated in those with

Coffee consumption and coronary artery calcium in young and middle-aged asymptomatic adults

Choi, Y., Chang, Y., Ryu, S., Cho, J., Rampal, S., Zhang, Y., Ahn, J., Lima, J. A., Shin, H., & Guallar, E. (n.d.).

Publication year

2015

Journal title

Heart

Volume

101

Issue

9

Page(s)

686-691

10.1136/heartjnl-2014-306663

Abstract

Abstract

Objective To investigate the association between regular coffee consumption and the prevalence of coronary artery calcium (CAC) in a large sample of young and middle-aged asymptomatic men and women. Methods This cross-sectional study included 25 138 men and women (mean age 41.3 years) without clinically evident cardiovascular disease who underwent a health screening examination that included a validated food frequency questionnaire and a multidetector CT to determine CAC scores. We used robust Tobit regression analyses to estimate the CAC score ratios associated with different levels of coffee consumption compared with no coffee consumption and adjusted for potential confounders. Results The prevalence of detectable CAC (CAC score >0) was 13.4% (n=3364), including 11.3% prevalence for CAC scores 1-100 (n=2832), and 2.1% prevalence for CAC scores >100 (n=532). The mean ±SD consumption of coffee was 1.8±1.5 cups/day. The multivariate-adjusted CAC score ratios (95% CIs) comparing coffee drinkers of

Diabetes, fasting glucose, and the risk of glaucoma : A meta-analysis

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

Publication year

2015

Journal title

Ophthalmology

Volume

122

Issue

1

Page(s)

72-78

10.1016/j.ophtha.2014.07.051

Abstract

Abstract

Topic: We performed a systematic review to summarize the association of diabetes and blood glucose levels with glaucoma, intraocular pressure (IOP), and ocular hypertension in the general population. Clinical Relevance: Diabetes has been proposed as a risk factor for glaucoma, but epidemiologic studies have been inconsistent, and the association is still controversial. Furthermore, no systematic reviews evaluated other metabolic abnormalities, such as the metabolic syndrome, with the risk of glaucoma. Methods: We identified the studies by searching the PubMed and EMBASE databases. We used inversevariance weighted random-effects models to summarize relative risks across studies. Results: We identified 47 studies including 2 981 342 individuals from 16 countries. The quality of evidence generally was higher in the cohort compared with case-control or cross-sectional studies. The pooled relative risk for glaucoma comparing patients with diabetes with those without diabetes was 1.48 (95% confidence interval [CI], 1.29-1.71), with significant heterogeneity across studies (I2 = 82.3%; P < 0.001). The risk of glaucoma increased by 5% (95% CI, 1%-9%) for each year since diabetes diagnosis. The pooled average difference in IOP comparing patients with diabetes with those without diabetes was 0.18 mmHg (95% CI, 0.09-0.27; I2 = 73.2%), whereas the pooled average increase in IOP associated with an increase in 10 mg/dl in fasting glucose was 0.09 mmHg (95% CI, 0.05-0.12; I2 = 34.8%). Conclusions: Diabetes, diabetes duration, and fasting glucose levels were associated with a significantly increased risk of glaucoma, and diabetes and fasting glucose levels were associated with slightly higher IOP.

Do genes modify the association of selenium and lipid levels?

Galan-Chilet, I., Guallar, E., Martin-Escudero, J. C., De Marco, G., Dominguez-Lucas, A., Gonzalez-Manzano, I., Lopez-Izquierdo, R., Redon, J., Chaves, F. J., & Tellez-Plaza, M. (n.d.).

Publication year

2015

Journal title

Antioxidants and Redox Signaling

Volume

22

Issue

15

Page(s)

1352-1362

10.1089/ars.2015.6248

Abstract

Abstract

The interaction of selenium, a component of antioxidant selenoproteins, with genetic variation in lipid-related pathways has not been evaluated earlier as a potential determinant of blood lipid levels. We aimed at evaluating the effects of gene-environment interactions between plasma levels of selenium and polymorphisms in lipid metabolic pathways on plasma lipid levels in a study population from Spain (N=1,315). We observed statistically significant associations between plasma selenium and lipid levels (differences in total, low-density lipoprotein [LDL]-cholesterol, and triglycerides comparing the 80th with the 20th percentiles of plasma selenium levels were, respectively, 12.0 (95% confidence interval 6.3, 17.8), 8.9 (3.7, 14.2), and 9.0 (2.9, 15.2) mg/dl). We also found statistically significant interactions at the Bonferroni-corrected significance level (p=0.0008) between selenium and rs2290201 in FABP4 for total and LDL cholesterol levels and rs1800774 in CETP for elevated LDL cholesterol. Other polymorphisms showed statistically significant differential associations of plasma selenium levels and lipids biomarkers at the nominal p-value of 0.05. Reported statistical interactions with genes involved in lipid transport and transfer provide biological support to the positive associations of selenium with lipids shown in cross-sectional studies and lead to the hypothesis that selenium and lipid levels share common biological pathways that need to be elucidated in mechanistic studies. Antioxid. Redox Signal. 22, 1352-1362.

Do genes modify the association of selenium and lipid levels?

Galan-Chilet, I., Guallar, E., Martin-Escudero, J. C., De Marco, G., Dominguez-Lucas, A., Gonzalez-Manzano, I., Lopez-Izquierdo, R., Redon, J., Chaves, F. J., & Tellez-Plaza, M. (n.d.).

Publication year

2015

Journal title

Antioxidants and Redox Signaling

Volume

22

Issue

15

Page(s)

1352-1362

10.1089/ars.2015.6248

Abstract

Abstract

The interaction of selenium, a component of antioxidant selenoproteins, with genetic variation in lipid-related pathways has not been evaluated earlier as a potential determinant of blood lipid levels. We aimed at evaluating the effects of gene-environment interactions between plasma levels of selenium and polymorphisms in lipid metabolic pathways on plasma lipid levels in a study population from Spain (N=1,315). We observed statistically significant associations between plasma selenium and lipid levels (differences in total, low-density lipoprotein [LDL]-cholesterol, and triglycerides comparing the 80th with the 20th percentiles of plasma selenium levels were, respectively, 12.0 (95% confidence interval 6.3, 17.8), 8.9 (3.7, 14.2), and 9.0 (2.9, 15.2) mg/dl). We also found statistically significant interactions at the Bonferroni-corrected significance level (p=0.0008) between selenium and rs2290201 in FABP4 for total and LDL cholesterol levels and rs1800774 in CETP for elevated LDL cholesterol. Other polymorphisms showed statistically significant differential associations of plasma selenium levels and lipids biomarkers at the nominal p-value of 0.05. Reported statistical interactions with genes involved in lipid transport and transfer provide biological support to the positive associations of selenium with lipids shown in cross-sectional studies and lead to the hypothesis that selenium and lipid levels share common biological pathways that need to be elucidated in mechanistic studies. Antioxid. Redox Signal. 22, 1352-1362.

Effects of education on aging-related cortical thinning among cognitively normal individuals

Kim, J. P., Seo, S. W., Shin, H. Y., Ye, B. S., Yang, J. J., Kim, C., Kang, M., Jeon, S., Kim, H. J., Cho, H., Kim, J. H., Lee, J. M., Kim, S. T., Na, D. L., & Guallar, E. (n.d.).

Publication year

2015

Journal title

Neurology

Volume

85

Issue

9

Page(s)

806-812

10.1212/WNL.0000000000001884

Abstract

Abstract

Objectives: We aimed to investigate the relationship between education and cortical thickness in cognitively normal individuals to determine whether education attenuated the association of advanced aging and cortical thinning. Methods: A total of 1,959 participants, in whom education levels were available, were included in the final analysis. Cortical thickness was measured on high-resolution MRIs using a surface-based method. Multiple linear regression analysis was performed for education level and cortical thickness, after controlling for possible confounders. Results: High levels of education were correlated with increased mean cortical thickness throughout the entire cortex (p 0.003). This association persisted after controlling for vascular risk factors. Statistical maps of cortical thickness showed that the high levels of education were correlated with increased cortical thickness in the bilateral premotor areas, anterior cingulate cortices, perisylvian areas, right superior parietal lobule, left lingual gyrus, and occipital pole. There were also interactive effects of age and education on the mean cortical thickness (p 0.019). Conclusions: Our findings suggest the protective effect of education on cortical thinning in cognitively normal older individuals, regardless of vascular risk factors. This effect was found only in the older participants, suggesting that the protective effects of education on cortical thickness might be achieved by increased resistance to structural loss from aging rather than by simply providing a fixed advantage in the brain.

Egg consumption and coronary artery calcification in asymptomatic men and women

Choi, Y., Chang, Y., Lee, J. E., Chun, S., Cho, J., Sung, E., Suh, B. S., Rampal, S., Zhao, D., Zhang, Y., Pastor-Barriuso, R., Lima, J. A., Shin, H., Ryu, S., & Guallar, E. (n.d.).

Publication year

2015

Journal title

Atherosclerosis

Volume

241

Issue

2

Page(s)

305-312

10.1016/j.atherosclerosis.2015.05.036

Abstract

Abstract

Objective: The association of egg consumption with subclinical coronary atherosclerosis remains unknown. Our aim was to examine the association between egg consumption and prevalence of coronary artery calcium (CAC). Methods: Cross-sectional study of 23,417 asymptomatic adult men and women without a history of cardiovascular disease (CVD) or hypercholesterolemia, who underwent a health screening examination including cardiac computed tomography for CAC scoring and completed a validated food frequency questionnaire at the Kangbuk Samsung Hospital Total Healthcare Centers, South Korea (March 2011-April 2013). Results: The prevalence of detectable CAC (CAC score>0) was 11.2%. In multivariable-adjusted models, CAC score ratio (95% confidence interval [CI]) comparing participants eating≥7 eggs/wk to those eating

Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes : A collaborative meta-analysis of individual participant data

for the CKD Prognosis Consortium, A., Matsushita, K., Coresh, J., Sang, Y., Chalmers, J., Fox, C., Guallar, E., Jafar, T., Jassal, S. K., Landman, G. W., Muntner, P., Roderick, P., Sairenchi, T., Schöttker, B., Shankar, A., Shlipak, M., Tonelli, M., Townend, J., van Zuilen, A., … Landray, M. J. (n.d.).

Publication year

2015

Journal title

The Lancet Diabetes and Endocrinology

Volume

3

Issue

7

Page(s)

514-525

10.1016/S2213-8587(15)00040-6

Abstract

Abstract

Background: The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach. Methods: We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4·2-19·0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both. Findings: The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0·0139 [95% CI 0·0105-0·0174] for ACR and 0·0065 [0·0042-0·0088] for eGFR) and heart failure (0·0196 [0·0108-0·0284] and 0·0109 [0·0059-0·0159]) than for coronary disease (0·0048 [0·0029-0·0067] and 0·0036 [0·0019-0·0054]) and stroke (0·0105 [0·0058-0·0151] and 0·0036 [0·0004-0·0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0·0227 (0·0158-0·0296) after omission of eGFR and ACR compared with less than 0·007 for any single modifiable traditional predictor. Interpretation: Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population.

Glycated hemoglobin, fasting insulin and the metabolic syndrome in males. Cross-sectional analyses of the aragon workers health study baseline

Saravia, G., Civeira, F., Hurtado-Roca, Y., Andres, E., Leon, M., Pocovi, M., Ordovas, J., Guallar, E., Fernandez-Ortiz, A., Casasnovas, J. A., & Laclaustra, M. (n.d.).

Publication year

2015

Journal title

PloS one

Volume

10

Issue

8

10.1371/journal.pone.0132244

Abstract

Abstract

Background and Aims Glycated hemoglobin (HbA1c) is currently used to diagnose diabetes mellitus, while insulin has been relegated to research. Both, however, may help understanding the metabolic syndrome and profiling patients. We examined the association of HbA1c and fasting insulin with clustering of metabolic syndrome criteria and insulin resistance as two essential characteristics of the metabolic syndrome. Methods We used baseline data from 3200 non-diabetic male participants in the Aragon Workers' Health Study.We conducted analysis to estimate age-adjusted odds ratios (ORs) across tertiles of HbA1c and insulin. Fasting glucose and Homeostatic model assessment - Insulin Resistance were used as reference. Here we report the uppermost-to-lowest tertile ORs (95%CI). Results Mean age (SD) was 48.5 (8.8) years and 23% of participants had metabolic syndrome. The ORs for metabolic syndrome criteria tended to be higher across HbA1c than across glucose, except for high blood pressure. Insulin was associated with the criteria more strongly than HbA1c and similarly to Homeostatic model assessment - Insulin Resistance (HOMAIR). For metabolic syndrome, the OR of HbA1c was 2.68, of insulin, 11.36, of glucose, 7.03, and of HOMA-IR, 14.40. For the clustering of 2 or more non-glycemic criteria, the OR of HbA1c was 2.10, of insulin, 8.94, of glucose, 1.73, and of HOMA-IR, 7.83. All ORs were statistically significant. The areas under the receiver operating characteristics curves for metabolic syndrome were 0.670 (across HbA1c values) and 0.770 (across insulin values), and, for insulin resistance, 0.647 (HbA1c) and 0.995 (insulin). Among non-metabolic syndrome patients, a small insulin elevation identified risk factor clustering. Conclusions HbA1c and specially insulin levels were associated with metabolic syndrome criteria, their clustering, and insulin resistance. Insulin could provide early information in subjects prone to develop metabolic syndrome.

Low rates of both lipid-lowering therapy use and achievement of low-density lipoprotein cholesterol targets in individuals at high-risk for cardiovascular disease across Europe

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

Publication year

2015

Journal title

PloS one

Volume

10

Issue

2

10.1371/journal.pone.0115270

Abstract

Abstract

Aims: To analyse the treatment and control of dyslipidaemia in patients at high and very high cardiovascular risk being treated for the primary prevention of cardiovascular disease (CVD) in Europe. Methods and Results: Data were assessed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov identifier: NCT00882336), which included a randomly sampled population of primary CVD prevention patients from 12 European countries (n = 7641). Patients' 10-year risk of CVD-related mortality was calculated using the Systematic Coronary Risk Evaluation (SCORE) algorithm, identifying 5019 patients at high cardiovascular risk (SCORE ≥5% and/or receiving lipid-lowering therapy), and 2970 patients at very high cardiovascular risk (SCORE ≥10% or with diabetes mellitus). Among high-risk individuals, 65.3% were receiving lipid-lowering therapy, and 61.3% of treated patients had uncontrolled low-density lipoprotein cholesterol (LDL-C) levels (≥2.5 mmol/L). For very-high-risk patients (uncontrolled LDL-C levels defined as ≥1.8 mmol/L) these figures were 49.5% and 82.9%, respectively. Excess 10-year risk of CVD-related mortality (according to SCORE) attributable to lack of control of dyslipidaemia was estimated to be 0.72%and 1.61% among high-risk and very-high-risk patients, respectively. Among high-risk individuals with uncontrolled LDL-C levels, only 8.7% were receiving a high-intensity statin (atorvastatin ≥40 mg/day or rosuvastatin ≥20 mg/day). Among veryhighrisk patients, this figure was 8.4%. Conclusions: There is a considerable opportunity for improvement in rates of lipid-lowering therapy use and achievement of lipid-level targets in high-risk and very-high-risk patients being treated for primary CVD prevention in Europe.

Lower-normal TSH is associated with better metabolic risk factors : A cross-sectional study on Spanish men

Laclaustra, M., Hurtado-Roca, Y., Sendin, M., Leon, M., Ledesma, M., Andres, E., Fernandez-Ortiz, A., Guallar, E., Ordovas, J. M., Casasnovas, J. A., & Guallar, E. (n.d.).

Publication year

2015

Journal title

Nutrition, Metabolism and Cardiovascular Diseases

Volume

25

Issue

12

Page(s)

1095-1103

10.1016/j.numecd.2015.09.007

Abstract

Abstract

Background and aims: Subclinical thyroid conditions, defined by normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels, may be associated with cardiovascular and metabolic risk. More recently, TSH levels within the normal range have been suggested to be associated with metabolic syndrome and cardiovascular risk. This work studies the linearity of the relationship between metabolic syndrome and TSH across the euthyroid range. Methods and results: We studied 3533 male participants of the Aragon Workers' Health Study (AWHS) with normal TSH and free T4 levels, across quintiles of these variables, after adjusting for age, alcohol intake, and smoking. Compared with the lowest TSH quintile, the odds ratios for metabolic syndrome at the higher quintiles, which indicate lower thyroid function, were 1.34 (1.04, 1.73), 1.56 (1.21, 2.01), 1.57 (1.22, 2.03), and 1.71 (1.32, 2.21). The lowest free T4 quintile also showed an odds ratio of 1.49 (1.16, 1.90) with respect to the highest quintile. In addition, spline models showed departures from linearity: the risk of metabolic syndrome mostly increases at TSH values below the median (sample half-closest to subclinical hyperthyroidism). Interestingly, glucose also increases with TSH primarily below the median TSH, diastolic blood pressure shows similar changes across the entire TSH range, whereas body mass index, triglycerides, and high-density lipoprotein (HDL)-cholesterol change only at the highest normal TSH values, which are associated with lower free T4 concentration. Conclusions: TSH and free T4 within the normal range are associated with the metabolic syndrome. The sample half-below the TSH median (with probably higher functional thyroid status) exhibited better metabolic and cardiovascular profiles.

Mercury Exposure and Heart Rate Variability : a Systematic Review

Gribble, M. O., Cheng, A., Berger, R. D., Rosman, L., & Guallar, E. (n.d.).

Publication year

2015

Journal title

Current environmental health reports

Volume

2

Issue

3

Page(s)

304-314

10.1007/s40572-015-0053-0

Abstract

Abstract

Background: Mercury affects the nervous system and has been implicated in altering heart rhythm and function. We sought to better define its role in modulating heart rate variability, a well-known marker of cardiac autonomic function. Design: This is a systematic review study. Methods: We searched PubMed, Embase, TOXLINE, and DART databases without language restriction. We report findings as a qualitative systematic review because heterogeneity in study design and assessment of exposures and outcomes across studies, as well as other methodological limitations of the literature, precluded a quantitative meta-analysis. Results: We identified 12 studies of mercury exposure and heart rate variability in human populations (ten studies involving primarily environmental methylmercury exposure and two studies involving occupational exposure to inorganic mercury) conducted in Japan, the Faroe Islands, Canada, Korea, French Polynesia, Finland, and Egypt. The association of prenatal mercury exposure with lower high-frequency band scores (thought to reflect parasympathetic activity) in several studies, in particular the inverse association of cord blood mercury levels with the coefficient of variation of the R-R intervals and with low-frequency and high-frequency bands at 14 years of age in the Faroe Islands birth cohort study, suggests that early mercury exposure could have a long-lasting effect on cardiac parasympathetic activity. Studies with later environmental exposures to mercury in children or in adults were heterogeneous and did not show consistent associations. Conclusions: The evidence was too limited to draw firm causal inferences. Additional research is needed to elucidate the effects of mercury on cardiac autonomic function, particularly as early-life exposures might have lasting impacts on cardiac parasympathetic function.

PCSK9 inhibitors : A new era in lipid-lowering treatment?

Cainzos-Achirica, M., Martin, S. S., Cornell, J. E., Mulrow, C. D., & Guallar, E. (n.d.).

Publication year

2015

Journal title

Annals of internal medicine

Volume

163

Issue

1

Page(s)

64-65

10.7326/M15-0920

Abstract

Abstract

~

Predictors of mortality, LVAD implant, or heart transplant in primary prevention cardiac resynchronization therapy recipients : The HF-CRT score

Nauffal, V., Tanawuttiwat, T., Zhang, Y., Rickard, J., Marine, J. E., Butcher, B., Norgard, S., Dickfeld, T., Ellenbogen, K. A., Guallar, E., Tomaselli, G. F., & Cheng, A. (n.d.).

Publication year

2015

Journal title

Heart Rhythm

Volume

12

Issue

12

Page(s)

2387-2394

10.1016/j.hrthm.2015.07.026

Abstract

Abstract

Background Cardiac resynchronization therapy (CRT) reduces morbidity and mortality among individuals with dyssynchronous systolic heart failure (HF). However, patient outcomes vary, with some at higher risk than others for HF progression and death. Objective To develop a risk prediction score incorporating variables associated with mortality, left ventricular assist device (LVAD) implant, or heart transplant in recipients of a primary prevention cardiac resynchronization therapy-defibrillator (CRT-D). Methods We followed 305 CRT-D patients from the Prospective Observational Study of Implantable Cardioverter-Defibrillators for the composite outcome of all-cause mortality, LVAD implant, or heart transplant soon after device implantation. Serum biomarkers and electrocardiographic and clinical variables were collected at implant. Multivariable analysis using the Cox proportional hazards model with stepwise selection method was used to fit the final model. Results Among 305 patients, 53 experienced the composite endpoint. In multivariable analysis, 5 independent predictors ("HF-CRT") were identified: high-sensitivity C-reactive protein >9.42 ng/L (HR = 2.5 [1.4, 4.5]), New York Heart Association functional class III/IV (HR = 2.3 [1.2, 4.5]), creatinine >1.2 mg/dL (HR = 2.7 [1.4, 5.1]), red blood cell count 28 ng/L (HR = 2.7 [1.4, 5.2]). One point was attributed to each predictor and 3 score categories were identified. Patients with scores 0-1, 2-3, and 4-5 had a 3-year cumulative event-free survival of 96.8%, 79.7%, and 35.2%, respectively (log-rank, P

Prevalence, vascular distribution, and multiterritorial extent of subclinical atherosclerosis in a middle-aged cohort the PESA (Progression of Early Subclinical Atherosclerosis) study

Fernández-Friera, L., Peñalvo, J. L., Fernández-Ortiz, A., Ibañez, B., López-Melgar, B., Laclaustra, M., Oliva, B., Mocoroa, A., Mendiguren, J., De Vega, V. M., García, L., Molina, J., Sánchez-González, J., Guzmán, G., Alonso-Farto, J. C., Guallar, E., Civeira, F., Sillesen, H., Pocock, S., … Fuster, V. (n.d.).

Publication year

2015

Journal title

Circulation

Volume

131

Issue

24

Page(s)

2104-2113

10.1161/CIRCULATIONAHA.114.014310

Abstract

Abstract

Background-Data are limited on the presence, distribution, and extent of subclinical atherosclerosis in middle-aged populations. Methods and Results-The PESA (Progression of Early Subclinical Atherosclerosis) study prospectively enrolled 4184 asymptomatic participants 40 to 54 years of age (mean age, 45.8 years; 63% male) to evaluate the systemic extent of atherosclerosis in the carotid, abdominal aortic, and iliofemoral territories by 2-/3-dimensional ultrasound and coronary artery calcification by computed tomography. The extent of subclinical atherosclerosis, defined as presence of plaque or coronary artery calcification ≥1, was classified as focal (1 site affected), intermediate (2-3 sites), or generalized (4-6 sites) after exploration of each vascular site (right/left carotids, aorta, right/left iliofemorals, and coronary arteries). Subclinical atherosclerosis was present in 63% of participants (71% of men, 48% of women). Intermediate and generalized atherosclerosis was identified in 41%. Plaques were most common in the iliofemorals (44%), followed by the carotids (31%) and aorta (25%), whereas coronary artery calcification was present in 18%. Among participants with low Framingham Heart Study (FHS) 10-year risk, subclinical disease was detected in 58%, with intermediate or generalized disease in 36%. When longer-term risk was assessed (30-year FHS), 83% of participants at high risk had atherosclerosis, with 66% classified as intermediate or generalized. Conclusions-Subclinical atherosclerosis was highly prevalent in this middle-aged cohort, with nearly half of the participants classified as having intermediate or generalized disease. Most participants at high FHS risk had subclinical disease; however, extensive atherosclerosis was also present in a substantial number of low-risk individuals, suggesting added value of imaging for diagnosis and prevention.

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 (

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 (

Arsenic, obesity, and inflammation cytokines in Mexican adolescents

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

Publication year

2014

Page(s)

622-624

10.1201/b16767-230

Abstract

Abstract

The aim of this work was to determine the associations among arsenic (As) exposure, adiposity, and inflammatory cytokines in 384 adolescents aged 12-15 years in a cross-sectional study. As was measured by total As concentration in urine adjusted by creatinine, adiposity was assessed using Body Mass Index (BMI) and bioimpedance segmental body composition, cytokines were determined by standard procedures. Our results show prevalence of overweight and obesity of 39.5%. Median (interquartile range) of total As in urine was 36.2 (26.01, 46.8) μg/g creatinine. We found an inverse association between As exposure and the percentage of total body fat, which was no dependent from inflammatory cytokines.

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