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

Incidence of extrahepatic cancers among individuals with chronic hepatitis B or C virus infection : A nationwide cohort study

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

Publication year

2020

Journal title

Journal of Viral Hepatitis

Volume

27

Issue

9

Page(s)

896-903

10.1111/jvh.13304

Abstract

Abstract

This study examined the association between chronic HBV or HCV infection and the risk of extrahepatic cancers. A total of 537 103 adults aged ≥20 years without history of cancer were identified from the Korean National Health Insurance Service-National Sample Cohort between 2003 and 2013. The difference in cancer incidence was compared between those with and without chronic HBV or HCV infection. During 3 854 130 person-years of follow-up (median follow-up: 8.0 years), 19 089 participants developed cancer. After adjusting for sex, body mass index, smoking, drinking, income percentile, residential area and comorbidities, hazard ratios (HRs) for incident extrahepatic cancer were significantly higher in participants with chronic HBV infection (HR: 1.27, 95% confidence interval [CI]: 1.20-1.35), HCV infection (HR: 1.31, 95% CI: 1.16-1.48) or HBV/HCV dual infection (HR: 1.41, 95% CI: 1.31-1.72) compared to participants without HBV or HCV infection. In chronic HBV infection, the cancer risk was higher for haematologic malignancy [HR (95% CI) = 2.46 (1.92-3.15)], gallbladder [1.55 (1.05-2.29)], pancreas [1.52 (1.07-2.15)], stomach [1.39 (1.22-1.58)], lung [1.27 (1.04-1.55)], colorectum [1.21 (1.03-1.42)] and thyroid cancer [1.20 (1.05-1.36)]. In chronic HCV infection, the cancer risk was higher for testis [10.34 (1.35-79.78)], gallbladder [2.90 (1.62-5.18)], prostate [2.51 (1.65-3.82)] and thyroid cancer [1.46 (1.10-1.93)]. In conclusion, chronic HBV or HCV infection was not only associated with an increased risk of liver cancer, but also associated with an increased risk of multiple extrahepatic cancers.

Keeping up with emerging evidence in (almost) real time

Laine, C., Taichman, D. B., Guallar, E., & Mulrow, C. D. (n.d.).

Publication year

2020

Journal title

Annals of internal medicine

Volume

173

Issue

2

Page(s)

153-154

10.7326/M20-2627

Abstract

Abstract

~

Long-term particulate matter exposure and incidence of arrhythmias : A cohort study

Zhang, Z., Kang, J., Hong, Y. S., Chang, Y., Ryu, S., Park, J., Cho, J., Guallar, E., Shin, H. C., & Zhao, D. (n.d.).

Publication year

2020

Journal title

Journal of the American Heart Association

Volume

9

Issue

22

10.1161/JAHA.120.016885

Abstract

Abstract

BACKGROUND: Studies have shown that short-term exposure to air pollution is associated with cardiac arrhythmia hospitalization and mortality. However, the relationship between long-term particulate matter air pollution and arrhythmias is still unclear. We evaluate the prospective association between particulate matter (PM) air pollution and the risk of incident arrhythmia and its subtypes. METHODS AND RESULTS: Participants were drawn from a prospective cohort study of 178 780 men and women who attended regular health screening exams in Seoul and Suwon, South Korea, from 2002 to 2016. Exposure to PM with an aerodynamic diameter of ≤10 and ≤2.5 μm (PM10 and PM2.5, respectively) was estimated using a land-use regression model. The associations between long-term PM air pollution and arrhythmia were examined using pooled logistic regression models with time-varying exposure and covariables. In the fully adjusted model, the odds ratios (ORs) for any arrhythmia associated with a 10 μg/m3 increase in 12-, 36-, and 60-month PM10 exposure were 1.15 (1.09, 1.21), 1.12 (1.06, 1.18), and 1.14 (1.08, 1.20), respectively. The ORs with a 10 μg/m3 increase in 12-and 36-month PM2.5 exposure were 1.27 (1.15, 1.40) and 1.10 (0.99, 1.23). PM10 was associated with increased risk of incident bradycardia and premature atrial contraction. PM2.5 was associated with increased risk of incident bradycardia and right bundle-branch block. CONCLUSIONS: In this large cohort study, long-term exposure to outdoor PM air pollution was associated with increased risk of arrhythmia. Our findings indicate that PM air pollution may be a contributor to cardiac arrhythmia in the general population.

Long-Term β-blocker therapy and clinical outcomes after acute myocardial infarction in patients without heart failure : Nationwide cohort study

Kim, J., Kang, D., Park, H., Kang, M., Park, T. K., Lee, J. M., Yang, J. H., Song, Y. B., Choi, J. H., Choi, S. H., Gwon, H. C., Guallar, E., Cho, J., & Hahn, J. Y. (n.d.).

Publication year

2020

Journal title

European Heart Journal

Volume

41

Issue

37

Page(s)

3521-3529

10.1093/eurheartj/ehaa376

Abstract

Abstract

Aims: To investigate the association between long-Term β-blocker therapy and clinical outcomes in patients without heart failure (HF) after acute myocardial infarction (AMI). Method and results: Between 2010 and 2015, a total of 28 970 patients who underwent coronary revascularization for AMI with β-blocker prescription at hospital discharge and were event-free from death, recurrent myocardial infarction (MI), or HF for 1 year were enrolled from Korean nationwide medical insurance data. The primary outcome was all-cause death. The secondary outcomes were recurrent MI, hospitalization for new HF, and a composite of all-cause death, recurrent MI, or hospitalization for new HF. Outcomes were compared between β-blocker therapy for ≥1 year (N = 22 707) and β-blocker therapy for

Mitochondrial DNA copy number and diabetes : The Atherosclerosis Risk in Communities (ARIC) study

DeBarmore, B., Longchamps, R. J., Zhang, Y., Kalyani, R. R., Guallar, E., Arking, D. E., Selvin, E., & Young, J. H. (n.d.).

Publication year

2020

Journal title

BMJ Open Diabetes Research and Care

Volume

8

Issue

1

10.1136/bmjdrc-2020-001204

Abstract

Abstract

Introduction Mitochondrial DNA copy number (mtDNA-CN) is a measure of mitochondrial dysfunction and is associated with diabetes in experimental models. To explore the temporality of mitochondrial dysfunction and diabetes, we estimated the prevalent and incident association of mtDNA-CN and diabetes. Research design and methods We assessed the associations of mtDNA-CN measured from buffy coat with prevalent and incident diabetes, stratified by race, in 8954 white and 2444 black participants in the Atherosclerosis Risk in Communities (ARIC) study, an observational cohort study. Follow-up for incident analyses was complete through visit 6, 2016. Results Mean age at mtDNA-CN measurement was 57 years and 59% were female. Prevalence of diabetes at time of mtDNA-CN measurement was higher in blacks (563/2444, 23%) than whites (855/8954, 10%). The fully adjusted odds of prevalent diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.05 (95% CI 0.74 to 1.49) among black and 1.49 (95% CI 1.20 to 1.85) among white participants. Over a median follow-up time of 19 years (Q1, Q3: 11, 24 years), we observed 617 incident diabetes cases among 1744 black and 2121 cases among 7713 white participants free of diabetes at baseline. The fully adjusted hazard of incident diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.07 (95% CI 0.84 to 1.38) among black and 0.97 (95% CI 0.86 to 1.10) among white participants. Conclusions Lower mtDNA-CN in buffy coat was associated with prevalent diabetes in white but not black ARIC participants. Lower mtDNA-CN was not associated with incident diabetes over 20 years of follow-up in whites or blacks.

Mitochondrial DNA copy number and incident atrial fibrillation

Zhao, D., Bartz, T. M., Sotoodehnia, N., Post, W. S., Heckbert, S. R., Alonso, A., Longchamps, R. J., Castellani, C. A., Hong, Y. S., Rotter, J. I., Lin, H. J., O'Rourke, B., Pankratz, N., Lane, J. A., Yang, S. Y., Guallar, E., & Arking, D. E. (n.d.).

Publication year

2020

Journal title

BMC Medicine

Volume

18

Issue

1

10.1186/s12916-020-01715-6

Abstract

Abstract

Background: Mechanistic studies suggest that mitochondria DNA (mtDNA) dysfunction may be associated with increased risk of atrial fibrillation (AF). The association between mtDNA copy number (mtDNA-CN) and incident AF in the general population, however, remains unknown. Methods: We conducted prospective analyses of 19,709 participants from the Atherosclerosis Risk in Communities Study (ARIC), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Cardiovascular Health Study (CHS). mtDNA-CN from the peripheral blood was calculated from probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms (SNP) Array 6.0 in ARIC and MESA and from multiplexed real-time quantitative polymerase chain reaction (qPCR) in CHS. Incident AF cases were identified through electrocardiograms, review of hospital discharge codes, Medicare claims, and death certificates. Results: The median follow-up time was 21.4 years in ARIC, 12.9 years in MESA, and 11.0 years in CHS, during which 4021 participants developed incident atrial fibrillation (1761 in ARIC, 790 in MESA, and 1470 in CHS). In fully adjusted models, participants with the lowest quintile of mitochondria DNA copy number had an overall 13% increased risk (95% CI 1 to 27%) of incident atrial fibrillation compared to those with the highest quintile. Dose-response spline analysis also showed an inverse association between mitochondria DNA copy number and hazard for atrial fibrillation for all three cohorts. These associations were consistent across subgroups. Conclusions: Mitochondria DNA copy number was inversely associated with the risk of AF independent of traditional cardiovascular risk factors. These findings implicate mitochondria DNA copy number as a novel risk factor for atrial fibrillation. Further research is warranted to understand the underlying mechanisms and to evaluate the role of mitochondria DNA copy number in the management of atrial fibrillation risk.

Mitochondrial DNA Copy Number and Incident Heart Failure : The Atherosclerosis Risk in Communities (ARIC) Study

Hong, Y. S., Longchamps, R. J., Zhao, D., Castellani, C. A., Loehr, L. R., Chang, P. P., Matsushita, K., Grove, M. L., Boerwinkle, E., Arking, D. E., & Guallar, E. (n.d.).

Publication year

2020

Journal title

Circulation

Volume

141

Issue

22

Page(s)

1823-1825

10.1161/CIRCULATIONAHA.120.046001

Abstract

Abstract

~

Mitochondrial DNA copy number can influence mortality and cardiovascular disease via methylation of nuclear DNA CpGs

Castellani, C. A., Longchamps, R. J., Sumpter, J. A., Newcomb, C. E., Lane, J. A., Grove, M. L., Bressler, J., Brody, J. A., Floyd, J. S., Bartz, T. M., Taylor, K. D., Wang, P., Tin, A., Coresh, J., Pankow, J. S., Fornage, M., Guallar, E., O'Rourke, B., Pankratz, N., … Arking, D. E. (n.d.).

Publication year

2020

Journal title

Genome Medicine

Volume

12

Issue

1

10.1186/s13073-020-00778-7

Abstract

Abstract

Background: Mitochondrial DNA copy number (mtDNA-CN) has been associated with a variety of aging-related diseases, including all-cause mortality. However, the mechanism by which mtDNA-CN influences disease is not currently understood. One such mechanism may be through regulation of nuclear gene expression via the modification of nuclear DNA (nDNA) methylation. Methods: To investigate this hypothesis, we assessed the relationship between mtDNA-CN and nDNA methylation in 2507 African American (AA) and European American (EA) participants from the Atherosclerosis Risk in Communities (ARIC) study. To validate our findings, we assayed an additional 2528 participants from the Cardiovascular Health Study (CHS) (N = 533) and Framingham Heart Study (FHS) (N = 1995). We further assessed the effect of experimental modification of mtDNA-CN through knockout of TFAM, a regulator of mtDNA replication, via CRISPR-Cas9. Results: Thirty-four independent CpGs were associated with mtDNA-CN at genome-wide significance (P < 5 × 10-8). Meta-analysis across all cohorts identified six mtDNA-CN-associated CpGs at genome-wide significance (P < 5 × 10-8). Additionally, over half of these CpGs were associated with phenotypes known to be associated with mtDNA-CN, including coronary heart disease, cardiovascular disease, and mortality. Experimental modification of mtDNA-CN demonstrated that modulation of mtDNA-CN results in changes in nDNA methylation and gene expression of specific CpGs and nearby transcripts. Strikingly, the "neuroactive ligand receptor interaction"KEGG pathway was found to be highly overrepresented in the ARIC cohort (P = 5.24 × 10-12), as well as the TFAM knockout methylation (P = 4.41 × 10-4) and expression (P = 4.30 × 10-4) studies. Conclusions: These results demonstrate that changes in mtDNA-CN influence nDNA methylation at specific loci and result in differential expression of specific genes that may impact human health and disease via altered cell signaling.

Modern prevalence of the fredrickson-levy-lees dyslipidemias : Findings from the very large database of lipids and national health and nutrition examination survey

Sathiyakumar, V., Pallazola, V. A., Park, J., Vakil, R. M., Toth, P. P., Lazo-Elizondo, M., Quispe, R., Guallar, E., Banach, M., Blumenthal, R. S., Jones, S. R., & Martin, S. S. (n.d.).

Publication year

2020

Journal title

Archives of Medical Science

Volume

16

Issue

6

Page(s)

1279-1287

10.5114/AOMS.2019.86964

Abstract

Abstract

Introduction: Five decades ago, Fredrickson, Levy, and Lees (FLL) qualitatively characterized clinical dyslipidemias with specific implications for cardiovascular and non-cardiovascular morbidity and mortality. They separated disorders of elevated cholesterol and triglycerides into five phenotypes (types I-V) based on their lipoprotein profile. Although clinicians generally consider them rare entities, modern FLL prevalence may be greater than previously reported. Material and methods: We performed a cross-sectional analysis in 5,272 participants from the 2011-2014 National Health and Nutrition Examination Survey and 128,506 participants from the Very Large Database of Lipids study with complete, fasting lipid profiles. We used a validated algorithm to define FLL phenotypes employing apolipoprotein B, total cholesterol, and triglycerides. Results: Overall prevalence of FLL phenotypes was 33.9%. FLL prevalence in the general population versus clinical lipid database was: type I (0.05 vs. 0.02%), type IIa (3.2 vs. 3.9%), type IIb (8.0 vs. 10.3%), type III (2.0 vs. 1.7%), type IV (20.5 vs. 24.1%), and type V (0.15 vs. 0.13%). Those aged 40-74 years had a higher overall prevalence compared to other age groups (p < 0.001) and men had overall higher prevalence than women (p < 0.001). Those with diabetes (51.6%) or obese BMI (49.0%) had higher prevalence of FLL phenotypes compared to those without diabetes (31.3%; p < 0.001) and normal BMI (18.3%; p < 0.001). Conclusions: FLL phenotypes are likely far more prevalent than appreciated in clinical practice, in part due to diabetes and obesity epidemics. Given the prognostic and therapeutic importance of these phenotypes, their identification becomes increasingly important in the era of precision medicine.

Non-alcoholic fatty liver disease and the incidence of myocardial infarction : A cohort study

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

Publication year

2020

Journal title

Journal of Gastroenterology and Hepatology (Australia)

Volume

35

Issue

5

Page(s)

833-839

10.1111/jgh.14856

Abstract

Abstract

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease associated with an increased risk of cardiovascular disease (CVD), diabetes, and chronic kidney disease. Indeed, CVD is the most common cause of death in NAFLD patients. This study aimed to evaluate the association between NAFLD and the risk of incident myocardial infarction. Methods: This is a retrospective cohort study involving 111 492 adults over 40 years old without history of CVD, liver disease, or cancer at baseline who participated in a regular health screening exam between 2003 and 2013. Fatty liver was diagnosed by ultrasonography. Results: During 725 706.9 person-years of follow-up, 183 participants developed myocardial infarction (incidence rate 0.3 cases per 1000 person-years). The age, sex, and year of visit-adjusted hazard ratio (HR) for incident myocardial infarction comparing participants with NAFLD with those without it was 2.14 (95% confidence interval 1.59, 2.89). This association remained significant in fully adjusted models (HR 1.54; 95% confidence interval 1.11, 2.14). Compared with participants without NAFLD, in participants with low NAFLD fibrosis score (NFS) (< −1.455) and with intermediate-to-high NFS (≥ −1.455), the fully adjusted HRs for incident myocardial infarction were 1.70 (1.22, 2.36) and 1.88 (1.24, 2.87), respectively. Conclusion: In this large cohort study, NAFLD was associated with an increased incidence of myocardial infarction independently of established risk factors. In addition, this association was similar in participants with and without evidence of more advanced NAFLD as indicated by the NFS. NAFLD patients may need to be carefully monitored and managed early to prevent myocardial infarction.

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