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

Perceived stress and non-alcoholic fatty liver disease in apparently healthy men and women

Kang, D., Zhao, D., Ryu, S., Guallar, E., Cho, J., Lazo, M., Shin, H., Chang, Y., & Sung, E. (n.d.).

Publication year

2020

Journal title

Scientific reports

Volume

10

Issue

1

10.1038/s41598-019-57036-z

Abstract

Abstract

Psychological stress may have adverse metabolic effects and induce unhealthy behaviors, but the role of stress in the development of non-alcoholic fatty liver disease (NAFLD) is largely unexplored. We investigated the association between perceived stress and the prevalence of NAFLD in a large sample of apparently healthy men and women. We performed a cross-sectional study of 171,321 adults who underwent health screening examination between 2011 and 2013 in one health screening center. Perceived stress was assessed using the short version of the Perceived Stress Inventory (PSI). NAFLD was assessed using ultrasonography in the absence of excessive alcohol use or any other identifiable cause of liver disease. The prevalence of NAFLD was 27.8%. In fully-adjusted multivariable models, the odds ratio (95% confidence intervals) for NAFLD comparing participants in the 5th quintile of PSI score (≥23) with those in the lowest quintile (

Prevalence and Persistence of Uremic Symptoms in Incident Dialysis Patients

Rhee, E. P., Guallar, E., Hwang, S., Kim, N., Tonelli, M., Moe, S. M., Himmelfarb, J., Thadhani, R. I., Powe, N. R., & Shafi, T. (n.d.).

Publication year

2020

Journal title

Kidney360

Volume

1

Issue

2

Page(s)

86-92

10.34067/KID.0000072019

Abstract

Abstract

Background Uremic symptoms are major contributors to the poor quality of life among patients on dialysis, but whether their prevalence or intensity has changed over time is unknown. Methods We examined responses to validated questionnaires in two incident dialysis cohort studies, the Choices for Health Outcomes in Caring for ESRD (CHOICE) study (N926, 1995-1998) and the Longitudinal United States/Canada Incident Dialysis (LUCID) study (N428, 2011-2017). We determined the prevalence and severity of uremic symptoms - anorexia, nausea/vomiting, pruritus, sleepiness, difficulty concentrating, fatigue, and pain - in both cohorts. Results In CHOICE and LUCID, respectively, mean age of the participants was 58 and 60 years, 53% and 60% were male, and 28% and 32% were black. In both cohorts, 54% of the participants had diabetes. Median time from dialysis initiation to the symptoms questionnaires was 45 days for CHOICE and 77 days for LUCID. Uremic symptom prevalence in CHOICE did not change from baseline to 1-year follow-up and was similar across CHOICE and LUCID. Baseline symptom prevalence in CHOICE and LUCID was as follows: anorexia (44%, 44%, respectively), nausea/vomiting (36%, 43%), pruritus (72%, 63%), sleepiness (86%, 68%), difficulty concentrating (55%, 57%), fatigue (89%, 77%), and pain (82%, 79%). In both cohorts, >80% of patients had three or more symptoms and >50% had five or more symptoms. The correlation between individual symptoms was low (ρ

Risk of acute infections in patients with psoriasis : A nationwide population-based cohort study

Kim, B. R., Kang, D., Kang, M., Shim, S., Kang, C. K., Kim, D. W., Guallar, E., Cho, J., & Youn, S. W. (n.d.).

Publication year

2020

Journal title

Journal of the American Academy of Dermatology

Volume

82

Issue

3

Page(s)

764-766

10.1016/j.jaad.2019.10.072

Abstract

Abstract

~

Risk of hepatocellular carcinoma in individuals without traditional risk factors : Development and validation of a novel risk score

Sinn, D. H., Kang, D., Cho, S. J., Paik, S. W., Guallar, E., Cho, J., & Gwak, G. Y. (n.d.).

Publication year

2020

Journal title

International Journal of Epidemiology

Volume

49

Issue

5

Page(s)

1562-1571

10.1093/ije/dyaa089

Abstract

Abstract

Background: Although hepatocellular carcinoma (HCC) occurs mostly in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or heavy alcohol use or cirrhosis, some patients develop HCC without these risk factors. Our objective in this study was to develop and validate a new HCC risk score that could stratify HCC risk in patients who develop HCC without known risk factors. Methods: A new HCC risk score was developed using a nationwide, population-based cohort among individuals without chronic HBV infection, chronic HCV infection, heavy alcohol use or cirrhosis (n = 467 206, derivation cohort). The performance of the HCC risk score was validated using an independent Samsung Medical Center Health Promotion Center cohort (n = 91 357, validation cohort). Results: Multivariable Cox regression analysis identified six independent risk factors: age, sex, smoking, diabetes, total cholesterol level and serum alanine aminotransferase level. A 19-point scale for HCC risk score was developed, with 10-year risk of HCC ranging from 0.0% to 6.16% for the lowest and highest risk scores, respectively. The area under the receiver operating characteristics curve values (AUROCs) to predict HCC development were 0.83 [95% confidence interval (CI): 0.77, 0.88)] and 0.92 (95% CI: 0.89, 0.95) at 10 years in the derivation and validation cohorts, respectively. Predicted risk was well correlated with the Kaplan-Meier observed HCC risk. Conclusions: A simple-to-use, novel HCC risk score was developed for predicting HCC development in individuals without alleged risk factors. It can be used to assess the risk of HCC in this population so that decisions about their clinical management, including risk reduction interventions, can be subsequently made.

Sex hormones and incident heart failure in men and postmenopausal women : The atherosclerosis risk in communities study

Zhao, D., Guallar, E., Ballantyne, C. M., Post, W. S., Ouyang, P., Vaidya, D., Jia, X., Ying, W., Subramanya, V., Ndumele, C. E., Hoogeveen, R. C., & Michos, E. D. (n.d.).

Publication year

2020

Journal title

Journal of Clinical Endocrinology and Metabolism

Volume

105

Issue

10

Page(s)

1-10

10.1210/clinem/dgaa500

Abstract

Abstract

Context: Sex differences exist in heart failure (HF) phenotypes, but there is limited research on the role of sex hormones in HF and its subtypes. Objective: To examine the associations of total testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) with incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). Design: Atherosclerosis Risk in Communities (ARIC) study (prospective cohort study). Median follow-up is 19.2 years. Setting: General community. Participants: 4107 men and 4839 postmenopausal women, with mean age of 63.2 (standard deviation [SD] 5.7) and 62.8 (5.5) years, respectively. Exposure: Plasma sex hormone levels were measured at visit 4 (1996-1998). Main Outcome Measures: Incident HF events were identified through hospital discharge codes and death certificates. Results: The Hazard Ratios for HF associated with 1 SD decrease in log-transformed total testosterone, DHEA-S, and SHBG were 1.10 (95% confidence interval 1.03, 1.17), 1.07 (1.00, 1.15), and 1.04 (0.96, 1.11) in men, and 1.05 (0.99, 1.13), 1.17 (1.09, 1.24), and 0.93 (0.85, 1.01) in women, respectively. The associations between sex hormones with subtypes of HF had similar patterns but were attenuated and became statistically insignificant. Conclusion: In this prospective cohort, lower levels of endogenous testosterone and DHEA-S in men and DHEA-S in postmenopausal women were associated with the development of HF.play a role in the development of HF through common pathways regardless of sex.

Studies using randomized trial data to compare nonrandomized exposures

Stack, C. B., Meibohm, A. R., Liao, J. M., & Guallar, E. (n.d.).

Publication year

2020

Journal title

Annals of internal medicine

Volume

172

Issue

7

Page(s)

492-494

10.7326/M20-0071

Abstract

Abstract

~

The effect of bed-to-nurse ratio on hospital mortality of critically ill children on mechanical ventilation : a nationwide population-based study

Jung, M., Park, H., Kang, D., Park, E., Jeon, K., Chung, C. R., Yang, J. H., Suh, G. Y., Guallar, E., Cho, J., & Cho, J. (n.d.).

Publication year

2020

Journal title

Annals of Intensive Care

Volume

10

Issue

1

10.1186/s13613-020-00780-7

Abstract

Abstract

Background: Despite the high workload of mechanical ventilation, there has been a lack of studies on the association between nurse workforce and mortality in mechanically ventilated patients. We evaluated the association of the bed-to-nurse ratio with mortality in ventilated pediatric patients admitted to an intensive care unit (ICU). Methods: We conducted a nationwide retrospective analysis by using the Korean National Health Insurance database, which categorizes the bed-to-nurse ratio into 9 grades according to the number of beds divided by the number of full-time equivalent registered nurses in a unit. Patients of ages between 28 days and 18 years were enrolled. Multiple admissions and transfers from other hospitals were excluded. We evaluated the odds ratios (ORs) of in-hospital mortality using 4 groups (Grade 1: bed-to-nurse < 0.50, Grade 2: < 0.63, Grade 3: < 0.77, Grade 4 or above > 0.77) with adjustment of patient factors, hospital factors, and treatment requirements. Results: Of the 27,849 patients admitted to ICU, 11,628 (41.8%) were on mechanical ventilation. The overall in-hospital mortality rates in Grade 1, Grade 2, Grade 3, and Grade 4 or above group were 4.5%, 6.8%, 6.9%, and 4.7%, respectively. The adjusted ORs (95% CI) for in-hospital mortality of mechanically ventilated patients in the Grade 2, Grade 3, and Grade 4 or above compared to those in Grade 1 were 2.73 (95% CI 1.51–4.95), 4.02 (95% CI 2.23–7.26), and 7.83 (4.07–15.07), respectively. However, for patients without mechanical ventilation, the adjusted ORs of in-hospital mortality were not statistically significant. Conclusion: In mechanically ventilated patients, the adjusted mortality rate increased significantly, as the bed-to-nurse ratio of the ICU increased. Policies that limit the number of ventilated patients per nurse should be considered.

Thinking outside the nucleus : Mitochondrial DNA copy number in health and disease

Castellani, C. A., Longchamps, R. J., Sun, J., Guallar, E., & Arking, D. E. (n.d.).

Publication year

2020

Journal title

Mitochondrion

Volume

53

Page(s)

214-223

10.1016/j.mito.2020.06.004

Abstract

Abstract

Mitochondrial DNA copy number (mtDNA-CN) is a biomarker of mitochondrial function and levels of mtDNA-CN have been reproducibly associated with overall mortality and a number of age-related diseases, including cardiovascular disease, chronic kidney disease, and cancer. Recent advancements in techniques for estimating mtDNA-CN, in particular the use of DNA microarrays and next-generation sequencing data, have led to the comprehensive assessment of mtDNA-CN across these and other diseases and traits. The importance of mtDNA-CN measures to disease and these advancing technologies suggest the potential for mtDNA-CN to be a useful biomarker in the clinic. While the exact mechanism(s) underlying the association of mtDNA-CN with disease remain to be elucidated, we review the existing literature which supports roles for inflammatory dynamics, immune function and alterations to cell signaling as consequences of variation in mtDNA-CN. We propose that future studies should focus on characterizing longitudinal, cell-type and cross-tissue profiles of mtDNA-CN as well as improving methods for measuring mtDNA-CN which will expand the potential for its use as a clinical biomarker.

Use of gadoxetic acid–enhanced liver MRI and mortality in more than 30000 patients with hepatocellular Carcinoma : A nationwide analysis

Kang, T. W., Kong, S. Y., Kang, D., Kang, M. W., Kim, Y. K., Kim, S. H., Sinn, D. H., Kim, Y. A., Choi, K. S., Lee, E. S., Woo, S. M., Back, J. H., Guallar, E., & Cho, J. (n.d.).

Publication year

2020

Journal title

Radiology

Volume

295

Issue

1

Page(s)

114-124

10.1148/radiol.2020190639

Abstract

Abstract

Background: The impact on survival of gadoxetic acid–enhanced MRI in addition to multiphase contrast material–enhanced CT for initial staging in patients with hepatocellular carcinoma (HCC) is unknown. Purpose: To compare all-cause mortality in patients with HCC who underwent CT only, CT plus non–gadoxetic acid–enhanced MRI, or CT plus gadoxetic acid–enhanced MRI as part of their initial diagnostic work-up. Materials and Methods: The authors performed a nationwide retrospective cohort study of patients diagnosed with HCC in South Korea between January 2008 and December 2010. Follow-up extended through December 2014. The primary outcome was all-cause mortality. Cox proportional hazards regression model with adjustment of confounding factors was used to estimate hazard ratios (HRs) for all-cause mortality. Results: Among 30 023 patients with HCC (mean age 6 standard deviation, 58.5 years 6 10.7, 23 978 men), the proportions of patients in whom HCC was diagnosed using CT only, CT plus non–gadoxetic acid–enhanced MRI, and CT plus gadoxetic acid–enhanced MRI were 56.1%, 12.9%, and 31.0%, respectively. In adjusted analysis using CT only as the reference category, the HR for mortality for CT plus gadoxetic acid–enhanced MRI was 0.64 (95% confidence interval [CI]: 0.62, 0.67; P , .001), and the HR for CT plus non–gadoxetic acid–enhanced MRI was 0.71 (95% CI: 0.68, 0.75; P , .001). Use of CT plus gadoxetic acid–enhanced MRI was associated with lower mortality compared with CT plus non–gadoxetic acid–enhanced MRI (adjusted HR, 0.90; 95% CI: 0.85, 0.95; P , .001), but this survival advantage was restricted to patients with localized disease. Conclusion: In patients with hepatocellular carcinoma, additional use of contrast-enhanced MRI was associated with lower mortality. Furthermore, CT plus gadoxetic acid–enhanced MRI was associated with better survival than CT plus non–gadoxetic acid–enhanced MRI but only in patients with localized disease.

Weight Change and Development of Subclinical Carotid Atherosclerosis Among Metabolically Healthy Adults : A Cohort Study

Sinn, D. H., Kang, D., Cho, S. J., Chang, Y., Ryu, S., Song, Y. B., Paik, S. W., Hong, Y. S., Zhao, D., Guallar, E., Cho, J., & Gwak, G. Y. (n.d.).

Publication year

2020

Journal title

Journal of Clinical Endocrinology and Metabolism

Volume

105

Issue

3

10.1210/clinem/dgz040

Abstract

Abstract

Background: The benefit of weight loss for reducing cardiovascular disease (CVD) risk in metabolically healthy obese people is unknown. Objectives: We evaluated the association between weight change and incident subclinical carotid atherosclerosis (SCA) in metabolically healthy but overweight or obese subjects. Methods: Cohort study of 3117 metabolically healthy overweight or obese adults who did not have any metabolic syndrome components or insulin resistance at baseline. SCA was assessed using carotid artery ultrasonography. The study outcome was the development of incident SCA among participants free of the disease at baseline. Results: During 12 248 person-years of follow-up (median 3.42 years), 747 participants developed SCA. The proportions of participants with no reduction or increased weight, reduction in weight from 0.1% to 4.9%, and reduction in weight ≥ 5% during follow-up were 47.0%, 44.4%, and 8.6%, respectively. The fully-adjusted hazard ratios (HRs) for incident SCA in participants with a reduction in weight of 0.1% to 4.9% and ≥ 5% compared with those with no reduction or increased weight were 0.84 (95% CI, 0.72-0.98) and 0.66 (95% CI, 0.50-0.87), respectively. Conclusions: In a large cohort study of metabolically healthy but overweight or obese adult men and women, weight reduction was associated with a lower incidence of SCA. Our findings suggest that metabolically healthy overweight or obese subjects may benefit from weight reduction in terms of CVD risk.

Age-Specific Distribution of Diagnosis and Outcomes of Children Admitted to ICUs : A Population-Based Cohort Study

Jung, M., Park, H., Kang, D., Park, J., Jeon, K., Chung, C. R., Yang, J. H., Cho, Y. H., Suh, G. Y., Guallar, E., Cho, J., & Cho, J. (n.d.).

Publication year

2019

Journal title

Pediatric Critical Care Medicine

Volume

20

Issue

7

Page(s)

e301-e310

10.1097/PCC.0000000000001978

Abstract

Abstract

Objectives: Although several studies have reported outcome data on critically ill children, detailed reports by age are not available. We aimed to evaluate the age-specific estimates of trends in causes of diagnosis, procedures, and outcomes of pediatric admissions to ICUs in a national representative sample. Design: A population-based retrospective cohort study. Setting: Three hundred forty-four hospitals in South Korea. Patients: All pediatric admissions to ICUs in Korea from August 1, 2009, to September 30, 2014, were covered by the Korean National Health Insurance Corporation, with virtually complete coverage of the pediatric population in Korea. Patients less than 18 years with at least one ICUs admission between August 1, 2009, and September 30, 2014. We excluded neonatal admissions (< 28 days), neonatal ICUs, and admissions for health status other than a disease or injury. The final sample size was 38,684 admissions from 32,443 pediatric patients. Intervention: None. Measurements and Main Results: The overall age-standardized admission rate for pediatric patients was 75.9 admissions per 100,000 person-years. The most common primary diagnosis of admissions was congenital malformation (10,897 admissions, 28.2%), with marked differences by age at admission (5,712 admissions [54.8%] in infants, 3,994 admissions [24.6%] in children, and 1,191 admissions [9.9%] in adolescents). Injury was the most common primary diagnosis in adolescents (3,248 admissions, 27.1%). The overall in-hospital mortality was 2,234 (5.8%) with relatively minor variations across age. Neoplasms and circulatory and neurologic diseases had both high frequency of admissions and high in-hospital mortality. Conclusions: Admission patterns, diagnosis, management, and outcomes of pediatric patients admitted to ICUs varied by age groups. Strategies to improve critical care qualities of pediatric patients need to be based on the differences of age and may need to be targeted at specific age groups.

Association between aflatoxin-albumin adduct levels and tortilla consumption in Guatemalan adults

Kroker-Lobos, M. F., Alvarez, C. S., Rivera-Andrade, A., Smith, J. W., Egner, P., Torres, O., Lazo, M., Freedman, N. D., Guallar, E., Graubard, B. I., McGlynn, K. A., Ramírez-Zea, M., & Groopman, J. D. (n.d.).

Publication year

2019

Journal title

Toxicology Reports

Volume

6

Page(s)

465-471

10.1016/j.toxrep.2019.05.009

Abstract

Abstract

Aflatoxin B1 (AFB1) is a known human hepatocarcinogen and a recent study reported elevated AFB1 levels, measured by serum albumin biomarkers, among Guatemalan adults. While AFB1 can contaminate a variety of foodstuffs, including maize, Guatemala's main dietary staple, the relationship of maize intake to serum AFB1-albumin adducts levels in Guatemala has not been previously examined. As a result, a cross-sectional study was conducted among 461 Guatemalan adults living in five geographically distinct departments of the country. Participants provided a serum sample and completed a semi-quantitative food frequency questionnaire and a sociodemographic questionnaire. Multiple linear regression analysis was used to estimate the least square means (LSQ) and 95% confidence intervals (95% CI) of log-transformed AFB1-albumin adducts by quintiles of maize consumption in crude and adjusted models. Additionally, analyses of tortilla consumption and levels of maize processing were conducted. The median maize intake was 344.3 g per day [Interquartile Range (IQR): 252.2, 500.8], and the median serum AFB1-albumin adduct level was 8.4 pg/mg albumin (IQR: 3.8, 22.3). In adjusted analyses, there was no association between overall maize consumption and serum AFB1-albumin levels. However, there was a statistically significant association between tortilla consumption and AFB1-albumin levels (ptrend = 0.01). The LSM of AFB1-albumin was higher in the highest quintile of tortilla consumption compared to the lowest quintile [LSM:9.03 95%CI: 7.03,11.70 vs 6.23, 95%CI: 4.95,8.17, respectively]. These findings indicate that tortilla may be an important source of AFB1 exposure in the Guatemalan population. Therefore, efforts to control or mitigate AFB1 levels in contaminated maize used for tortillas may reduce overall exposure in this population.

Association of High-Sensitivity Troponin with Cardiac CT Angiography Evidence of Myocardial and Coronary Disease in a Primary Prevention Cohort of Men : Results from MACS

Rahman, F., Zhang, Z., Zhao, D., Budoff, M. J., Palella, F. J., Witt, M. D., Evans, R. W., Jacobson, L. P., Korley, F. K., Guallar, E., Post, W. S., & McEvoy, J. W. (n.d.).

Publication year

2019

Journal title

Journal of Applied Laboratory Medicine

Volume

4

Issue

3

Page(s)

355-369

10.1373/jalm.2018.028860

Abstract

Abstract

Background: High-sensitivity cardiac troponin (hs-cTn) elevations are associated with incident cardiovascular disease events in primary prevention samples. However, the mechanisms underlying this association remain unclear. Methods: We studied 458 men without known cardiovascular disease who participated in the cardiovascular disease substudy of the Multicenter AIDS Cohort Study and had cardiac CT angiography. We used multivariable linear and logistic regression models to examine the cross-sectional associations between coronary artery stenosis, coronary artery plaque, indexed left ventricular mass (LVMi), and the outcome of hs-cTnI. We also evaluated the associations between HIV serostatus or use of highly active antiretroviral therapy (HAART) and hs-cTnI. Results: The mean age was 54 years, 54% were white, and 61% were HIV infected. In multivariable-adjusted logistic models, comparing the highest quartile of LVMi with the lowest quartile, the odds ratio (OR) of hs-cTnI ≥75th percentile was 2.59 (95% CI, 1.20 -5.75). There was no significant association between coronary stenosis severity or plaque type and hs-cTnI in linear models; however, in logistic regression models, coronary artery stenosis =70% (8% of sample) was marginally associated with a higher likelihood (OR, 2.75 [95% CI, 1.03, 7.27]) of having hs-cTnI ≥75th percentile. There were no associations between HIV serostatus or HAART use and hs-cTnI in either linear or logistic models. Conclusion: Among primary prevention men with or at risk for HIV, hs-cTnI concentrations were strongly associated with LVMi but were not associated with HIV infection or treatment status or with coronary plaque type or stenosis until the extremes of severity (=70% stenosis).

Association of statin therapy with clinical outcomes in patients with vasospastic angina : Data from Korean health insurance review and assessment service

Park, S. J., Park, H., Kang, D., Park, T. K., Park, J., Cho, J., Chung, C. R., Jeon, K., Guallar, E., Cho, J., Suh, G. Y., & Yang, J. H. (n.d.).

Publication year

2019

Journal title

PloS one

Volume

14

Issue

1

10.1371/journal.pone.0210498

Abstract

Abstract

There is conflicting evidence for the clinical benefit of statin therapy in patients with vasospastic angina (VSA). We investigated the association of statin therapy with clinical outcomes in relatively large populations with clinically suspected VSA from a nationwide population-based database. Data were collected from the Health Insurance Review and Assessment database records of 4,099 patients that were in an intensive care unit with VSA between January 1, 2008 and May 31, 2015. We divided the patients into a statin group (n = 1,795) and a non-statin group (n = 2,304). The primary outcome was a composite of cardiac arrest and acute myocardial infarction (AMI). The median follow-up duration was 3.8 years (interquartile range: 2.2 to 5.8 years). Cardiac arrest or AMI occurred in 120 patients (5.2%) in the statin group, and 97 patients (5.4%) in the non-statin group (P = 0.976). With inverse probability of treatment weighting, there was no significant difference in the rate of cardiac arrest or AMI between the two groups (adjusted hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.76–1.30; P = 0.937), or even between the non-statin group and high-intensity statin group (adjusted HR, 1.08; 95% CI, 0.69–1.70; P = 0.75). The beneficial association of statin use with the primary outcome was consistently lacking across the various comorbidity types. Statin therapy was not associated with reduced cardiac arrest or AMI in patients with VSA, regardless of statin intensity. Prospective, randomized trials will be needed to confirm our findings.

Associations Between the Cyclic Guanosine Monophosphate Pathway and Cardiovascular Risk Factors : MESA

Ying, W., Zhao, D., Ouyang, P., Subramanya, V., Vaidya, D., Ndumele, C. E., Guallar, E., Sharma, K., Shah, S. J., Kass, D. A., Hoogeveen, R. C., Lima, J. A., Heckbert, S. R., Defilippi, C. R., Post, W. S., & Michos, E. D. (n.d.).

Publication year

2019

Journal title

Journal of the American Heart Association

Volume

8

Issue

24

10.1161/JAHA.119.013149

Abstract

Abstract

Background-—cGMP mediates numerous cardioprotective functions and is a potential therapeutic target for cardiovascular disease. Preclinical studies suggest that plasma cGMP is reflective of natriuretic peptide stimulation. Epidemiologic associations between cGMP and natriuretic peptide, as well as cardiovascular disease risk factors, are unknown. Methods and Results-—We measured plasma cGMP in 542 men and 496 women free of cardiovascular disease and heart failure in MESA (Multi-Ethnic Study of Atherosclerosis). Cross-sectional associations of N-terminal pro-B type natriuretic peptide, sex hormones, and cardiovascular disease/heart failure risk factors with log(cGMP) were analyzed using multivariable linear regression models. Mean (SD) cGMP was 4.7 (2.6) pmol/mL, with no difference between the sexes. After adjusting for cardiovascular risk factors, N-terminal pro-B type natriuretic peptide was significantly positively associated with cGMP (P

Author Correction : Non-alcoholic fatty liver disease and cerebral small vessel disease in Korean cognitively normal individuals (Scientific Reports, (2019), 9, 1, (1814), 10.1038/s41598-018-38357-x)

Jang, H., Kang, D., Chang, Y., Kim, Y., Lee, J. S., Kim, K. W., Jang, Y. K., Kim, H. J., Na, D. L., Shin, H. Y., Kang, M., Guallar, E., Cho, J., & Seo, S. W. (n.d.).

Publication year

2019

Journal title

Scientific reports

Volume

9

Issue

1

10.1038/s41598-019-51401-8

Abstract

Abstract

The Acknowledgements section of this Article is incomplete. “This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2017R1A2B2005081) and the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2016M3C7A1913844).” should read: “This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2017R1A2B2005081), the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2016M3C7A1913844), and a fund (2018-ER6203-00) by Research of Korea Centers for Disease Control and Prevention.”

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality : An Individual-Level Pooled Analysis of 30 Cohort Studies

Marklund, M., Wu, J. H., Imamura, F., Del Gobbo, L. C., Fretts, A., De Goede, J., Shi, P., Tintle, N., Wennberg, M., Aslibekyan, S., Chen, T. A., De Oliveira Otto, M. C., Hirakawa, Y., Eriksen, H. H., Kröger, J., Laguzzi, F., Lankinen, M., Murphy, R. A., Prem, K., … Risérus, U. (n.d.).

Publication year

2019

Journal title

Circulation

Volume

139

Issue

21

Page(s)

2422-2436

10.1161/CIRCULATIONAHA.118.038908

Abstract

Abstract

Background: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. Methods: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). Results: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. Conclusions: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

Changes in acute kidney injury epidemiology in critically ill patients : a population-based cohort study in Korea

Hwang, S., Park, H., Kim, Y., Kang, D., Ku, H. S., Cho, J., Lee, J. E., Huh, W., Guallar, E., Suh, G. Y., & Jang, H. R. (n.d.).

Publication year

2019

Journal title

Annals of Intensive Care

Volume

9

Issue

1

10.1186/s13613-019-0534-7

Abstract

Abstract

Background: Although no specific treatment facilitates renal tubular regeneration in acute kidney injury (AKI), the rapid increase in aging populations with more comorbidities and advances in critical care management are expected to change the epidemiology of AKI. However, few recent studies dissected the current epidemiologic characteristics of critically ill patients with AKI. We investigated recent epidemiologic changes in severe AKI in critically ill patients. Methods: All adult admissions to intensive care units (ICUs) in Korea from 2008 to 2015 were screened using the national health insurance review and assessment database, and 1,744,235 patients were included. Clinical characteristics and changes in AKI incidence and mortality rate were analyzed. Results: The incidence of AKI increased from 7.4% in 2008 to 8.3% in 2015 (p for trend < 0.001). Age-standardized AKI rate was 7018.6 per 100,000 person-years. In-hospital mortality significantly decreased from 39.1% in 2008 to 37.2% in 2015 (p for trend < 0.001) with 2427.6 deaths per 100,000 person-years. Patients with AKI showed higher in-hospital mortality, prolonged ICU length of stay, and higher total cost. Multivariable analysis showed increased risk of in-hospital mortality (adjusted odds ratio [OR] 3.74), mechanical ventilation (OR 2.87), ECMO (OR 6.99), and vasopressor requirement (OR 2.75) in patients with AKI. Conclusions: Recent advances in medical management for AKI have improved in-hospital mortality of critically ill patients with AKI despite increases in the elderly population and AKI incidence.

Clinical features and outcomes of invasive breast cancer : Age-specific analysis of a modern hospital-based registry

Kim, J. Y., Kang, D., Nam, S. J., Kim, S. W., Lee, J. E., Yu, J. H., Lee, S. K., Im, Y. H., Ahn, J. S., Guallar, E., Cho, J., & Park, Y. H. (n.d.).

Publication year

2019

Journal title

Journal of global oncology

Volume

2019

Issue

5

Page(s)

1-9

10.1200/JGO.19.00034

Abstract

Abstract

PURPOSE We evaluated the clinical features and outcomes of invasive breast cancer (BC) among different age groups by analyzing a modern BC registry including subtypes and treatment information. METHODS This was a retrospective cohort study of 6,405 women aged 18 years or older with pathologically confirmed stage I, II, or III BC who underwent curative surgery followed by adjuvant therapy at a university-based hospital in Seoul, South Korea, between January 2003 and December 2011. The study end point was all-cause mortality. We used Cox proportional hazards models and hazard ratios (HRs) with 95% CIs calculated after adjusting for age, body mass index, stage, subtype, and treatment, including type of surgery and use of chemotherapy, radiation therapy, hormone therapy, and targeted therapy. RESULTS During 36,360 person-years of follow-up (median follow-up: 5.45 years; interquartile range, 4.3-7.1), 256 deaths were reported (mortality rate, 7.0/1,000 person-years). The adjusted HR for all-cause mortality was higher in patients older than 40 years (HR, 2.03; 95% CI, 1.44 to 2.87) and older than 60 years (HR, 2.35; 95% CI, 1.63 to 3.39) than in patients aged 40 to 49 years. Across age groups, advanced stage at diagnosis, luminal type as well as triple-negative BC, and not receiving adjuvant treatment were associated with increased risk of mortality. CONCLUSION A strong J-shaped relationship was observed between age and mortality, indicating worse clinical outcomes in young and old patients. This study suggested a possible benefit of personalized BC screening examination and precise and active treatment strategies to reduce BC-related mortality.

Effect of selenium supplementation on changes in HbA1c : Results from a multiple-dose, randomized controlled trial

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

Publication year

2019

Journal title

Diabetes, Obesity and Metabolism

Volume

21

Issue

3

Page(s)

541-549

10.1111/dom.13549

Abstract

Abstract

Aim: To investigate the effect of selenium supplementation at different dose levels on changes in HbA1c after 6 months and 2 years in a population of low selenium status. Materials and Methods: The Denmark PRECISE study was a single-centre, randomized, double-blinded, placebo-controlled, multi-arm, parallel clinical trial with four groups. In total, 491 volunteers aged 60 to 74 years were randomly assigned to treatment with 100, 200 or 300 μg selenium/day as selenium-enriched yeast or placebo-yeast. HbA1c measurements were available for 489 participants at baseline, 435 at 6 months, and 369 after 2 years of selenium supplementation. Analyses were performed by intention to treat. Results: The mean (SD) age, plasma-selenium concentration, and blood HbA1c at baseline were 66.1 (4.1) years, 86.5 (16.3) ng/g and 36.6 (7.0) mmol/mol, respectively. During the initial 6-month intervention period, mean HbA1c (95% CI) decreased by 1.5 (−2.8 to −0.2) mmol/mol for 100 μg/d of selenium supplementation and by 0.7 (−2.0 to 0.6) mmol/mol for the 200 and 300 μg/d groups compared with placebo (P = 0.16 for homogeneity of changes across the four groups). After 2 years of selenium supplementation, HbA1c had decreased significantly in all treatment groups, with no difference between active treatment and placebo. Conclusions: Selenium supplementation in an elderly European population of low selenium status did not significantly affect HbA1c levels after 2 years. Our findings corroborate a possible U-shaped response of selenium supplementation on glucose metabolism.

Effects of nutritional supplements and dietary interventions on cardiovascular outcomes

Khan, S. U., Khan, M. U., Riaz, H., Valavoor, S., Zhao, D., Vaughan, L., Okunrintemi, V., Riaz, I. B., Khan, M. S., Kaluski, E., Murad, M. H., Blaha, M. J., Guallar, E., & Michos, E. D. (n.d.).

Publication year

2019

Journal title

Annals of internal medicine

Volume

171

Issue

3

Page(s)

190-198

10.7326/M19-0341

Abstract

Abstract

Background: The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear. Purpose: To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults. Data Sources: PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists. Study Selection: English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease. Data Extraction: Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. Data Synthesis: Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus Vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B6, Vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low- to moderate-certainty evidence). Limitations: Suboptimal quality and certainty of evidence. Conclusion: Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus Vitamin D might increase risk for stroke.

Endogenous Sex Hormones and Endothelial Function in Postmenopausal Women and Men : The Multi-Ethnic Study of Atherosclerosis

Mathews, L., Subramanya, V., Zhao, D., Ouyang, P., Vaidya, D., Guallar, E., Yeboah, J., Herrington, D., Hays, A. G., Budoff, M. J., & Michos, E. D. (n.d.).

Publication year

2019

Journal title

Journal of Women&#39;s Health

Volume

28

Issue

7

Page(s)

900-909

10.1089/jwh.2018.7441

Abstract

Abstract

Background: The relationship of endogenous sex hormones (SH) with vascular endothelial function and with cardiovascular disease (CVD) is incompletely understood. We examined the associations between SH and endothelial function measured by brachial artery flow-mediated dilation (FMD). Materials and Methods: We included 1368 postmenopausal women and 1707 men, free of clinical CVD, participating in MESA Visit 1 (2000-2002). Serum SH [total testosterone, SH binding globulin (SHBG), dehydroepiandrosterone (DHEA), estradiol] were measured; free testosterone was calculated. The percent FMD difference (%FMD) was measured by high-resolution ultrasound. Using multivariable-adjusted linear regression, we tested the cross-sectional associations of SH (log transformed, compared per one SD increment) with %FMD. Results: The mean age of women and men were 64.2 and 61.4 years, respectively. Among women, after adjusting for demographics, CVD risk factors, and hormone therapy, higher SHBG was associated with greater %FMD [β = 0.215% (95% CI 0.026-0.405)], whereas higher free testosterone was associated with a smaller %FMD [-0.209% (-0.402, -0.017)]. Estradiol and DHEA were not associated with %FMD in women after multivariable adjustment. There was an age interaction, with higher free testosterone and lower SHBG associated with worse FMD in women

Ethnic, geographic and dietary differences in arsenic exposure in the multi-ethnic study of atherosclerosis (MESA)

Jones, M. R., Tellez-Plaza, M., Vaidya, D., Grau-Perez, M., Post, W. S., Kaufman, J. D., Guallar, E., Francesconi, K. A., Goessler, W., Nachman, K. E., Sanchez, T. R., & Navas-Acien, A. (n.d.).

Publication year

2019

Journal title

Journal of Exposure Science and Environmental Epidemiology

Volume

29

Issue

3

Page(s)

310-322

10.1038/s41370-018-0042-0

Abstract

Abstract

Differences in residential location as well as race/ethnicity and dietary habits may result in differences in inorganic arsenic (iAs) exposure. We investigated the association of exposure to iAs with race/ethnicity, geography, and dietary intake in a random sample of 310 White, Black, Hispanic, and Chinese adults in the Multi-Ethnic Study of Atherosclerosis from 6 US cities with inorganic and methylated arsenic (ΣAs) measured in urine. Dietary intake was assessed by food-frequency questionnaire. Chinese and Hispanic race/ethnicity was associated with 82% (95% CI: 46%, 126%) and 37% (95% CI: 10%, 70%) higher urine arsenic concentrations, respectively, compared to White participants. No differences were observed for Black participants compared to Whites. Urine arsenic concentrations were higher for participants in Los Angeles, Chicago, and New York compared to other sites. Participants that ate rice ≥2 times/week had 31% higher urine arsenic compared to those that rarely/never consumed rice. Participants that drank wine ≥2 times/week had 23% higher urine arsenic compared to rare/never wine drinkers. Intake of poultry or non-rice grains was not associated with urinary arsenic concentrations. At the low-moderate levels typical of the US population, exposure to iAs differed by race/ethnicity, geographic location, and frequency of rice and wine intake.

GlycA, a novel inflammatory marker, is associated with subclinical coronary disease

Tibuakuu, M., Fashanu, O. E., Zhao, D., Otvos, J. D., Brown, T. T., Haberlen, S. A., Guallar, E., Budoff, M. J., Palella, F. J., Martinson, J. J., Akinkuolie, A. O., Mora, S., Post, W. S., & Michos, E. D. (n.d.).

Publication year

2019

Journal title

AIDS

Volume

33

Issue

3

Page(s)

547-557

10.1097/QAD.0000000000002079

Abstract

Abstract

GlycA, a novel NMR biomarker of inflammation, has been associated with incident cardiovascular disease (CVD) in the general population, but its association with CVD among HIV-infected individuals is unknown. We examined the associations between GlycA and subclinical coronary plaque among HIV-infected and HIV-uninfected men participating in Multicenter AIDS Cohort Study (MACS).Design:Cross-sectional analysis of 935 men with plasma measurement of GlycA and noncontrast cardiac computed tomography (CT) and/or coronary CT angiography.Methods:We used multivariable Poisson and linear regression to assess associations of GlycA with prevalent coronary atherosclerosis and plaque extent, respectively.Results:Mean±SD age was 54±7 years; 31% were black; 63% HIV-infected. GlycA levels were higher in HIV-infected compared with HIV-uninfected men (397±68 vs. 380±60μmol/l, P=0.0001) and higher for men with detectable viral load vs. undetectable (413±79 vs. 393±65μmol/l, P=0.004). After adjusting for HIV serostatus, demographic and CVD risk factors, every 1SD increment in GlycA level was associated with a higher prevalence of coronary artery calcium (CAC >0) [prevalence ratio 1.09 (95% CI 1.03-1.15)] and coronary stenosis at least 50% [1.20 (1.02-1.41)]. These associations were not significantly altered after adjusting for traditional inflammatory biomarkers or differ by HIV serostatus. Among men with plaque, GlycA was positively associated with the extent of CAC and total plaque.Conclusion:HIV infection was associated with higher GlycA levels. In both HIV-infected and HIV-uninfected individuals, GlycA was significantly associated with several measures of subclinical coronary atherosclerosis, independent of other CVD risk factors and inflammatory biomarkers. These findings suggest the potential role of GlycA in CVD risk stratification among HIV patients.

High prevalence of non-alcoholic fatty liver disease and metabolic risk factors in Guatemala : A population-based study

Rivera-Andrade, A., Kroker-Lobos, M. F., Lazo, M., Freedman, N. D., Smith, J. W., Torres, O., McGlynn, K. A., Groopman, J. D., Guallar, E., Ramirez-Zea, M., & Guallar, E. (n.d.).

Publication year

2019

Journal title

Nutrition, Metabolism and Cardiovascular Diseases

Volume

29

Issue

2

Page(s)

191-200

10.1016/j.numecd.2018.10.008

Abstract

Abstract

Background: There are no data on the prevalence of non-alcoholic fatty liver disease (NAFLD) in general population samples in Guatemala or in other Central American countries. The prevalence and distribution of NAFLD and its associated risk factors were evaluated in a population-based sample of adults in Guatemala. Methods: Cross-sectional study of 411 men and women 40 years of age or older residing in urban and rural areas of Guatemala. Metabolic outcomes included obesity, central obesity, hypercholesterolemia, diabetes, and metabolic syndrome (MetS). Liver disease outcomes included elevated liver enzymes, elevated Fatty Liver Index (FLI), and elevated FIB-4 score. Results: The overall prevalence of obesity, central obesity, diabetes, and MetS were 30.9, 74.3, 21.6, and 64.2%, respectively. The fully-adjusted prevalence ratios (95% CI) for obesity, central obesity, diabetes, and MetS comparing women to men were 2.83 (1.86–4.30), 1.72 (1.46–2.02), 1.18 (1.03–1.34), and 1.87 (1.53–2.29), respectively. The overall prevalence of elevated liver enzymes (ALT or AST), elevated FLI, and elevated FIB-4 scores were 38.4, 60.1, and 4.1%, respectively. The fully-adjusted prevalence ratios (95% CI) for elevated liver enzymes (either ALT or AST) and elevated FLI score comparing women to men were 2.99 (1.84–4.86) and 1.47 (1.18–1.84), respectively. Conclusions: The prevalence of metabolic abnormalities and liver outcomes in this general population study was very high. The prevalence of metabolic and liver abnormalities was particularly high among women, an observation that could explain the atypical 1:1 male to female ratio of liver cancer in Guatemala.