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

Vitamin D deficiency is independently associated with greater prevalence of erectile dysfunction : The National Health and Nutrition Examination Survey (NHANES) 2001–2004

Farag, Y. M., Guallar, E., Zhao, D., Kalyani, R. R., Blaha, M. J., Feldman, D. I., Martin, S. S., Lutsey, P. L., Billups, K. L., & Michos, E. D. (n.d.).

Publication year

2016

Journal title

Atherosclerosis

Volume

252

Page(s)

61-67

10.1016/j.atherosclerosis.2016.07.921

Abstract

Abstract

Background and aims Erectile dysfunction (ED) and atherosclerotic cardiovascular disease (ASCVD) share many common risk factors, and vascular ED is a marker for increased ASCVD risk. Low 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with increased ASCVD risk, but less is known regarding the relationship of low 25(OH)D with ED. We determined whether 25(OH)D deficiency is associated with ED independent of ASCVD risk factors. Methods We performed cross-sectional analyses of 3390 men aged ≥20 years free of ASCVD who participated in NHANES 2001–2004. Serum 25(OH)D was measured by the DiaSorin radioimmunoassay; deficiency was defined as levels

ω-3 Polyunsaturated fatty acid biomarkers and coronary heart disease : Pooling project of 19 cohort studies

Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCe), A., Del Gobbo, L. C., Imamura, F., Aslibekyan, S., Marklund, M., Virtanen, J. K., Wennberg, M., Yakoob, M. Y., Chiuve, S. E., Dela Cruz, L., Frazier-Wood, A. C., Fretts, A. M., Guallar, E., Matsumoto, C., Prem, K., Tanaka, T., Wu, J. H., Zhou, X., Helmer, C., … Mozaffarian, D. (n.d.).

Publication year

2016

Journal title

JAMA internal medicine

Volume

176

Issue

8

Page(s)

1155-1166

10.1001/jamainternmed.2016.2925

Abstract

Abstract

Importance: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. Objective: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5 ω-3), docosapentaenoic acid (DPA; 22:5 ω-3), and docosahexaenoic acid (DHA; 22:6 ω-3) and plant-derived α-linolenic acid (ALA; 18:3 ω-3) for incident CHD. Data Sources: A global consortium of 19 studies identified by November 2014. Study Selection: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. Data Extraction and Synthesis: Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes. Main Outcomes and Measures: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). Results: The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baselinewas 59 years (range, 18-97 years), and 28 660 (62.8%)were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHAwere associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95%CI, 0.84-0.98) for ALA, 0.90 (95%CI, 0.85-0.96) for DPA, and 0.90 (95%CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95%CI, 0.90-0.99), ALA (RR, 1.00; 95%CI, 0.95-1.05), EPA (RR, 0.94; 95%CI, 0.87-1.02), and DHA (RR, 0.95; 95%CI, 0.91-1.00)were not. Significant associations with nonfatal MIwere not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. Conclusions and Relevance: On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

Ambient air pollution and racial/ethnic differences in carotid intima-media thickness in the Multi-Ethnic Study of Atherosclerosis (MESA)

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

Publication year

2015

Journal title

Journal of Epidemiology and Community Health

Volume

69

Issue

12

Page(s)

1191-1198

10.1136/jech-2015-205588

Abstract

Abstract

Background In the USA, ethnic disparities in atherosclerosis persist after accounting for known risk factors. Ambient air pollution is associated with increased levels of atherosclerosis and differs in the USA by race/ethnicity. We estimated the influence of ambient air pollution exposure to ethnic differences in common carotid intima-media thickness (IMT). Methods We cross-sectionally studied 6347 Caucasian- American, African-American, Hispanic and Chinese adults across 6 US cities in 2000-2002. Annual ambient air pollution concentrations (fine particulate matter [PM2.5] and oxides of nitrogen [NOX]) were estimated at each participant's residence. IMT was assessed by ultrasound. Results The mean IMT was 19.4 and 37.6 μm smaller for Hispanic women and men, 53.6 and 7.1 μm smaller for Chinese women and men, and 23.4 and 38.7 μm higher for African-American women and men compared with Caucasian-American women and men. After adjustment for PM2.5, the differences in IMT remained similar for Hispanic and African-American participants but was even more negative for Chinese participants (mean IMT difference of -58.4 μm for women and -15.7 μm for men) compared with Caucasian-American participants. The IMT difference in Chinese participants compared with Caucasian-American participants related to their higher PM2.5 exposures was 4.8 μm (95% CI 0.2 to 10.8) for women and 8.6 μm (95% CI 3.4 to 15.3) for men. NOX was not related to ethnic differences in IMT. Conclusions The smaller carotid IMT levels in Chinese participants were even smaller after accounting for higher PM2.5 concentrations in Chinese participants compared with Caucasian-American participants. Air pollution was not related to IMT differences in African-American and Hispanic participants compared with Caucasian-American participants.

Arsenic exposure, arsenic metabolism, and incident diabetes in the strong heart study

Kuo, C. C., Howard, B. V., Umans, J. G., Gribble, M. O., Best, L. G., Francesconi, K. A., Goessler, W., Lee, E., Guallar, E., & Navas-Acien, A. (n.d.).

Publication year

2015

Journal title

Diabetes Care

Volume

38

Issue

4

Page(s)

620-627

10.2337/dc14-1641

Abstract

Abstract

OBJECTIVE Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study. RESEARCH DESIGN AND METHODS A total of 1,694 diabetes-free participants aged 45-75 years were recruited in 1989-1991 and followed through 1998-1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ≥126 mg/dL, 2-h glucose ≥200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications. RESULTS Over 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase inMMA% were 0.77 (0.63-0.93) and 0.82 (0.73-0.92) when iAs% and DMA%, respectively,were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations. CONCLUSIONS Arsenicmetabolism, particularly lowerMMA%,was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism.

Arsenic exposure, hyperuricemia, and gout in US adults

Kuo, C. C., Weaver, V., Fadrowski, J. J., Lin, Y. S., Guallar, E., & Navas-Acien, A. (n.d.).

Publication year

2015

Journal title

Environment international

Volume

76

Page(s)

32-40

10.1016/j.envint.2014.11.015

Abstract

Abstract

There is very limited information on the association between arsenic and serum uric acid levels or gout. The aim of this study was to investigate the association of arsenic with hyperuricemia and gout in US adults. Methods: A cross-sectional study was conducted in 5632 adults aged 20. years or older from the National Health and Nutrition Examination Survey (NHANES) 2003-2010 with determinations of serum uric acid and urine total arsenic and dimethylarsinate (DMA). Hyperuricemia was defined as serum uric acid higher than 7.0. mg/dL for men and 6.0. mg/dL for women. Gout was defined based on self-reported physician diagnosis and medication use. Results: After adjustment for sociodemographic factors, comorbidities and arsenobetaine levels, the increase in the geometric means of serum uric acid associated with one interquartile range increase in total arsenic and DMA levels was 3% (95% CI 2-5) and 3% (2-5), respectively, in men and 1% (0-3) and 2% (0-4), respectively, in women. In men, the adjusted odds ratio for hyperuricemia comparing the highest to lowest quartiles of total arsenic was 1.84 (95% CI, 1.26-2.68) and for DMA it was 1.41 (95% CI, 1.01-1.96). The corresponding odds ratios in women were 1.26 (0.77, 2.07) and 1.49 (0.96, 2.31), respectively. The odds ratio for gout comparing the highest to lowest tertiles was 5.46 (95% CI, 1.70-17.6) for total arsenic and 1.98 (0.64-6.15) for DMA among women older than 40. years old. Urine arsenic was not associated with gout in men. Conclusion: Low level arsenic exposures may be associated with the risk of hyperuricemia in men and with the prevalence of gout in women. Prospective research focusing on establishing the direction of the relationship among arsenic, hyperuricemia, and gout is needed.

Association between body mass index and cortical thickness : Among elderly cognitively normal men and women

Kim, H., Kim, C., Seo, S. W., Na, D. L., Kim, H. J., Kang, M., Shin, H. Y., Cho, S. K., Park, S. E., Lee, J., Hwang, J. W., Jeon, S., Lee, J. M., Kim, G. H., Cho, H., Ye, B. S., Noh, Y., Yoon, C. W., & Guallar, E. (n.d.).

Publication year

2015

Journal title

International Psychogeriatrics

Volume

27

Issue

1

Page(s)

121-130

10.1017/S1041610214001744

Abstract

Abstract

Background: There is increasing evidence of a relationship between underweight or obesity and dementia risk. Several studies have investigated the relationship between body weight and brain atrophy, a pathological change preceding dementia, but their results are inconsistent. Therefore, we aimed to evaluate the relationship between body mass index (BMI) and cortical atrophy among cognitively normal participants. Methods: We recruited cognitively normal participants (n = 1,111) who underwent medical checkups and detailed neurologic screening, including magnetic resonance imaging (MRI) in the health screening visits between September 2008 and December 2011. The main outcome was cortical thickness measured using MRI. The number of subjects with five BMI groups in men/women was 9/9, 148/258, 185/128, 149/111, and 64/50 in underweight, normal, overweight, mild obesity, and moderate to severe obesity, respectively. Linear and non-linear relationships between BMI and cortical thickness were examined using multiple linear regression analysis and generalized additive models after adjustment for potential confounders. Results: Among men, underweight participants showed significant cortical thinning in the frontal and temporal regions compared to normal weight participants, while overweight and mildly obese participants had greater cortical thicknesses in the frontal region and the frontal, temporal, and occipital regions, respectively. However, cortical thickness in each brain region was not significantly different in normal weight and moderate to severe obesity groups. Among women, the association between BMI and cortical thickness was not statistically significant. Conclusions: Our findings suggested that underweight might be an important risk factor for pathological changes in the brain, while overweight or mild obesity may be inversely associated with cortical atrophy in cognitively normal elderly males.

Association of cardiovascular health screening with mortality, clinical outcomes, and health care cost : A nationwide cohort study

Lee, H., Cho, J., Shin, D. W., Lee, S. P., Hwang, S. S., Oh, J., Yang, H. K., Hwang, S. H., Son, K. Y., Chun, S. H., Cho, B. L., & Guallar, E. (n.d.).

Publication year

2015

Journal title

Preventive Medicine

Volume

70

Page(s)

19-25

10.1016/j.ypmed.2014.11.007

Abstract

Abstract

Objective: To determine whether a cardiovascular disease (CVD) health screening program is associated with CVD-related health conditions, incidence of cardiovascular events, mortality, healthcare utilization, and costs. Methods: Cohort study of a 3% random sample of all Korea National Health Insurance members 40. years of age or older and free of CVD or CVD-related health conditions was conducted. A total 443,337 study participants were followed-up from January 1, 2005 through December 31, 2010. Results: In primary analysis, the hazard ratios for CVD mortality, all-cause mortality, incident composite CVD events, myocardial infarction, cerebral infarction, and cerebral hemorrhage comparing participants who attended a screening exam during 2003-2004 compared to those who did not were 0.58 (95% CI: 0.53-0.63), 0.62 (95% CI: 0.60-0.64), 0.82 (95% CI: 0.78-0.85), 0.84 (95% CI: 0.75-0.93), 0.84 (95% CI: 0.79-0.89), and 0.73 (95% CI: 0.67-0.80), respectively. Screening attenders had higher rates of newly diagnosed hypertension, diabetes mellitus, and dyslipidemia, lower inpatient days of stay and cost, and lower outpatient cost compared to non-attenders. Conclusions: Participation in CVD health screening was associated with lower rates of CVD, all-cause mortality, and CVD events, higher detection of CVD-related health conditions, and lower healthcare utilization and costs.

Association of ferritin elevation and metabolic syndrome in males. Results from the Aragon Workers' Health Study (AWHS)

Ledesma, M., Hurtado-Roca, Y., Leon, M., Giraldo, P., Pocovi, M., Civeira, F., Guallar, E., Ordovas, J. M., Casasnovas, J. A., & Laclaustra, M. (n.d.).

Publication year

2015

Journal title

Journal of Clinical Endocrinology and Metabolism

Volume

100

Issue

5

Page(s)

2081-2089

10.1210/jc.2014-4409

Abstract

Abstract

Context: Ferritin concentration is associated with metabolic syndrome, but the possibility of a nonlinear association has never been explored. Objective: This study aimed to examine the relationship between serum ferritin levels and the metabolic syndrome in Spanish adult males. Design: This was a cross-sectional analysis of baseline data from the Aragon Workers' Health Study. Setting: Healthy workers from a factory were studied during their annual checkup. Participants: Spanish male adults (n = 3386) between the ages of 19 and 65 years participated. We excluded participants with ferritin > 500 μ/L, ferritin < 12 μg/L, or C-reactive protein > 10 mg/L. Main Outcome Measure: Metabolic syndrome was defined according to the 2009 consensus definition from the Joint Interim Statement of several international societies. Results: Metabolic syndrome prevalence was 27.1%. We found a positive association between elevated iron stores, measured as serum ferritin concentration, and metabolic syndrome and its criteria. Participants within the highest serum ferritin quintile had a higher risk than those in the lowest quintile for central obesity (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.46-2.42), hypertriglyceridemia (OR, 2.15; 95% CI, 1.69-2.74), and metabolic syndrome (OR, 1.92; 95% CI, 1.48-2.49). The association was nonlinear and occurred at serum ferritin concentrations > 100 μg/L (∼ 33th percentile). Ferritin was also associated with insulin resistance, measured by homeostatic model assessment-insulin resistance (HOMA-IR) (P trend < .001). Conclusions: Our findings suggest that serum ferritin is significantly associated with metabolic syndrome and its criteria (especially central obesity and hypertriglyceridemia), suggesting that ferritin could be an early marker of metabolic damage in the development of metabolic syndrome.

Baseline Troponin T Levels Modulate the Effects of ICD Shocks on All-Cause Mortality

Nauffal, V., Zhang, Y., Blasco-Colmenares, E., Spragg, D. D., Marine, J. E., Butcher, B., Norgard, S., Guallar, E., Tomaselli, G. F., & Cheng, A. (n.d.).

Publication year

2015

Journal title

Journal of the American College of Cardiology

Volume

66

Issue

25

Page(s)

2911-2912

10.1016/j.jacc.2015.10.048

Abstract

Abstract

~

Brachial-ankle pulse wave velocity is associated with coronary calcium in young and middle-aged asymptomatic adults : The Kangbuk Samsung Health Study

Cainzos-Achirica, M., Rampal, S., Chang, Y., Ryu, S., Zhang, Y., Zhao, D., Cho, J., Choi, Y., Pastor-Barriuso, R., Lim, S. Y., Bruguera, J., Elosua, R., Lima, J. A., Shin, H., & Guallar, E. (n.d.).

Publication year

2015

Journal title

Atherosclerosis

Volume

241

Issue

2

Page(s)

350-356

10.1016/j.atherosclerosis.2015.05.031

Abstract

Abstract

Objective: To evaluate the association between brachial-ankle pulse wave velocity (baPWV), a convenient, non-radiating, readily available measurement of arterial stiffness, and coronary artery calcium (CAC), a reliable marker of coronary atherosclerosis, in a large sample of young and middle-aged asymptomatic adults; and to assess the incremental value of baPWV for detecting prevalent CAC beyond traditional risk factors. Methods: Cross-sectional study of 15,185 asymptomatic Korean adults who voluntarily underwent a comprehensive health screening program including measurement of baPWV and CAC. BaPWV was measured using an oscillometric method with cuffs placed on both arms and ankles. CAC burden was assessed using a multi-detector CT scan and scored following Agatston's method. Results: The prevalence of CAC > 0 and CAC > 100 increased across baPWV quintiles. The multivariable-adjusted odds ratios (95% CI) for CAC > 0 comparing baPWV quintiles 2-5 versus quintile 1 were 1.06 (0.87-1.30), 1.24 (1.02-1.50), 1.39 (1.15-1.69) and 1.60 (1.31-1.96), respectively (P trend < 0.001). Similarly, the relative prevalence ratios for CAC > 100 were 1.30 (0.74-2.26), 1.59 (0.93-2.71), 1.74 (1.03-2.94) and 2.59 (1.54-4.36), respectively (P trend < 0.001). For CAC > 100, the area under the ROC curve for baPWV alone was 0.71 (0.68-0.74), and the addition of baPWV to traditional risk factors significantly improved the , and calibration of models for detecting prevalent CAC > 0 and CAC > 100. Conclusions: BaPWV was independently associated with the presence and severity of CAC in a large sample of young and middle-aged asymptomatic adults. BaPWV may be a valuable tool for identifying apparently low-risk individuals with increased burden of coronary atherosclerosis.

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

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