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

Ideal Cardiovascular Health Metrics and Risk of Incident Early-Onset Vasomotor Symptoms Among Premenopausal Women

Choi, H. R., Chang, Y., Kim, Y., Cho, Y., Kang, J., Kwon, M. J., Kwon, R., Lim, G. Y., Kim, K. H., Kim, H., Hong, Y. S., Park, J., Zhao, D., Cho, J., Guallar, E., Park, H. Y., & Ryu, S. (n.d.).

Publication year

2022

Journal title

Journal of Clinical Endocrinology and Metabolism

Volume

107

Issue

9

Page(s)

2666-2673

10.1210/clinem/dgac327

Abstract

Abstract

Context: The relationship of ideal cardiovascular health (CVH) behaviors with preventing early-onset vasomotor symptoms (VMSs) is unknown. Objective: We investigated the association between CVH metrics and the development of early-onset VMSs in premenopausal women. Methods: This cohort study included 2541 premenopausal women aged 42 to 52 years without VMSs at baseline. CVH metrics were defined according to the American Heart Association Life Simple 7 metrics. Owing to limited availability of dietary information, CVH metrics were scored from 0 (unhealthy) to 6 (healthy) and classified into 3 groups: Poor (0-2), intermediate (3-4), and ideal (5-6) CVH. VMSs, including hot flashes and night sweats, were assessed using the Menopause-Specific Quality of Life questionnaire. Moderate/severe VMSs was defined as a score of 3 or more points (range, 0 to 6; 6 being most bothersome). Results: During a median follow-up of 4.5 years, 1241 women developed VMSs before menopause. After adjustment for age, parity, education level, and alcohol consumption, the hazard ratio (HR) (95% CI) for developing early-onset VMSs comparing poor CVH group to the ideal group was 1.41 (1.07-1.86). CVH scores were also inversely associated with moderate/severe VMSs in a dose-response manner (P for trend=.004); specifically, multivariable-adjusted HRs comparing intermediate and poor CVH groups to the ideal group were 1.20 (95% CI, 1.02-1.43) and 1.57 (95% CI, 1.08-2.29), respectively. Conclusion: Unfavorable CVH metrics were significantly associated with an increased risk of early-onset VMSs and its more severe forms among premenopausal women.

Impact of nationwide hepatocellular carcinoma surveillance on the prognosis in patients with chronic liver disease

Sohn, W., Kang, D., Kang, M., Guallar, E., Cho, J., & Paik, Y. H. (n.d.).

Publication year

2022

Journal title

Clinical and molecular hepatology

Volume

28

Issue

4

Page(s)

851-863

10.3350/cmh.2022.0037

Abstract

Abstract

Background/Aims: This study aimed to investigate the effect of hepatocellular carcinoma (HCC) surveillance using the Korea National Liver Cancer Screening Program on the receipt of curative treatment for HCC and mortality in patients with chronic liver disease. Methods: This population-based cohort study from the Korean National Health Insurance Service included 2003 to 2015 claims data collected from 1,209,825 patients aged ≥40 years with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis. Patients were divided according to HCC surveillance using ultrasonography and serum alpha-fetoprotein every 6–12 months. The study outcomes were the receipt of curative treatment (surgical resection, radiofrequency ablation, or liver transplantation) and all-cause mortality. Results: The study population consisted of 1,209,825 patients with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis (median age, 52.0 years; interquartile range, 46–55 years; 683,902 men [56.5%]). The proportion of participants who underwent HCC surveillance was 52.7% (n=657,889). During 10,522,940 person-years of follow-up, 74,433 HCC cases developed, including 36,006 patients who underwent curative treatment. The surveillance group had a significantly higher proportion of curative treatment for HCC than the non-surveillance group after adjusting for confounding factors (adjusted hazard ratio [HR], 5.64; 95% confidence interval [CI], 5.48–5.81). The surveillance group had a significantly lower mortality rate than the non-surveillance group (adjusted HR, 0.56; 95% CI, 0.55–0.56). Conclusions: HCC surveillance using the national screening program in patients with chronic viral hepatitis or liver cirrhosis provides better opportunity for curative treatment for HCC and improves overall survival. (Clin Mol Hepatol 2022;28:851-863).

Impact of Renal Replacement Therapy on Mortality and Renal Outcomes in Critically Ill Patients with Acute Kidney Injury: A Population-Based Cohort Study in Korea between 2008 and 2015

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

Publication year

2022

Journal title

Journal of Clinical Medicine

Volume

11

Issue

9

10.3390/jcm11092392

Abstract

Abstract

The outcomes depending on the type of renal replacement therapy (RRT) or pre-existing kidney disease in critically ill patients with acute kidney injury (AKI) have not been fully elucidated. All adult intensive care unit patients with AKI in Korea from 2008 to 2015 were screened. A total of 124,182 patients, including 21,165 patients with pre-existing kidney disease, were divided into three groups: control (no RRT), dialysis, and continuous RRT (CRRT). In-hospital mortality and progression to end-stage kidney disease (ESKD) were analyzed according to the presence of pre-existing kidney disease. The CRRT group had a higher risk of in-hospital mortality. Among the patients with pre-existing kidney disease, the dialysis group had a lower risk of in-hospital mortality compared to other groups. The risk of ESKD was higher in the dialysis and CRRT groups compared to the control group. In the CRRT group, the risk of ESKD was even higher in patients without pre-existing kidney disease. Although both dialysis and CRRT groups showed a higher incidence of ESKD, in-hospital mortality was lower in the dialysis group, especially in patients with pre-existing kidney disease. Our study supports that RRT and pre-existing kidney disease may be important prognostic factors for overall and renal outcomes in patients with AKI.

Letter: association of circulating bile acid concentrations and non-alcoholic fatty liver disease—authors’ reply

Rivera-Andrade, A., Petrick, J. L., Alvarez, C. S., Graubard, B. I., Florio, A. A., Kroker-Lobos, M. F., Parisi, D., Freedman, N. D., Lazo, M., Guallar, E., Groopman, J. D., Ramirez-Zea, M., & McGlynn, K. A. (n.d.). In Alimentary Pharmacology and Therapeutics (1–).

Publication year

2022

Volume

56

Issue

2

Page(s)

374-375

10.1111/apt.17059

Letter: is it appropriate to use a fatty liver index >60 as an alternative criterion for non-alcoholic fatty liver disease? Authors’ reply

Rivera-Andrade, A., Petrick, J. L., Alvarez, C. S., Graubard, B. I., Florio, A. A., Kroker-Lobos, M. F., Parisi, D., Freedman, N. D., Lazo, M., Guallar, E., Groopman, J. D., Ramirez-Zea, M., & McGlynn, K. A. (n.d.). In Alimentary Pharmacology and Therapeutics (1–).

Publication year

2022

Volume

56

Issue

2

Page(s)

378-379

10.1111/apt.17060

Low anti-Müllerian hormone levels are associated with an increased risk of incident early-onset vasomotor symptoms among premenopausal women

NamGoung, S. J., Chang, Y., Kim, Y., Kim, H., Cho, I. Y., Kwon, R., Lim, G. Y., Choi, H. R., Kang, J., Kim, K. H., Hong, Y. S., Zhao, D., Park, H. Y., Cho, J., Guallar, E., Kwon, M. J., & Ryu, S. (n.d.).

Publication year

2022

Journal title

Scientific reports

Volume

12

Issue

1

10.1038/s41598-022-16182-7

Abstract

Abstract

The role of anti-Müllerian hormone (AMH) levels in incident vasomotor symptoms (VMS) is largely unknown. This study aimed to investigate the relationship between AMH levels and the development of early-onset VMS among premenopausal women. Our cohort study comprised 2041 premenopausal women aged 42–52 years free of VMS at baseline whose AMH levels were measured. VMS, including hot flushes and night sweats, were assessed using the Korean version of the Menopause-specific Quality of Life questionnaire. Early-onset VMS was defined as the occurrence of VMS prior to menopause. Parametric proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% CI. During a median follow-up of 4.4 years, 708 premenopausal women developed early-onset VMS (incidence rate, 8.0 per 100 person-years). Lower AMH levels were statistically significantly associated with an increased risk of early-onset VMS. After adjusting for age and other confounders, multivariable-adjusted HRs (95% CI) for incident VMS comparing AMH quintiles 4–1 to the highest quintile were 1.02 (0.78–1.33), 1.37 (1.06–1.76), 1.36 (1.04–1.76), and 2.38 (1.84–3.08), respectively (P for trend < 0.001). Our results support an independent role of serum AMH levels in predicting incident early-onset VMS among premenopausal women in the late reproductive stage.

Metabolically healthy and unhealthy obesity and risk of vasomotor symptoms in premenopausal women: cross-sectional and cohort studies

Namgoung, S., Chang, Y., Woo, C. Y., Kim, Y., Kang, J., Kwon, R., Lim, G. Y., Choi, H. R., Kim, K. H., Kim, H., Hong, Y. S., Zhao, D., Cho, J., Guallar, E., Park, H. Y., & Ryu, S. (n.d.).

Publication year

2022

Journal title

BJOG: An International Journal of Obstetrics and Gynaecology

Volume

129

Issue

11

Page(s)

1926-1934

10.1111/1471-0528.17224

Abstract

Abstract

Objective: To examine the relationship between metabolically healthy and unhealthy obesity phenotypes and risk of vasomotor symptoms (VMS) in premenopausal women. Design: Prospective cohort study. Setting: Middle-aged women in a cohort based on regular health screening examinations. Population: Premenopausal Korean women aged 42–52 years were recruited and were followed up for a median of 4.2 years. The cross-sectional and cohort studies comprised 4672 women and 2590 women without VMS at baseline, respectively. Methods: Adiposity measures included body mass index (BMI), waist circumference and percentage body fat. Being metabolically healthy was defined as not having any metabolic syndrome components or a homeostasis model assessment of insulin resistance of 2.5 or more. Main outcomes measures: VMS (hot flushes and night sweats) assessed using the questionnaire. Results: All adiposity measures were positively associated with an increased risk of VMS in both cross-sectional and longitudinal studies. The multivariable-adjusted prevalence ratio (95% confidence interval [CI]) for VMS comparing percentage body fat of 35% or more with the reference was 1.47 (95% CI 1.14–1.90) in metabolically healthy women, and the corresponding prevalence ratio was 2.32 (95% CI 1.42–3.78) in metabolically unhealthy women (Pinteraction = 0.334). The multivariable-adjusted hazard ratio for incident VMS comparing percentage body fat of 35% or more with the reference was 1.34 (95% CI 1.00–1.79) in metabolically healthy women, whereas the corresponding hazard ratio was 3.61 (95% CI 1.81–7.20) in metabolically unhealthy women (Pinteraction = 0.036). The association between BMI, waist circumference and VMS did not significantly differ by metabolic health status. Conclusions: Maintaining normal weight and being metabolically healthy may help to prevent VMS in premenopausal women. Tweetable abstract: Avoiding obesity and a metabolically unhealthy status may help reduce vasomotor symptoms in premenopausal women.

Modest alcohol intake and mortality in individuals with elevated alanine aminotransferase levels: a nationwide cohort study

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

Publication year

2022

Journal title

BMC Medicine

Volume

20

Issue

1

10.1186/s12916-021-02215-x

Abstract

Abstract

Background: Alanine aminotransferase (ALT) levels are widely used to screen liver disease, and many asymptomatic individuals show elevated ALT levels. As elevated ALT level indicates liver injury, even a small amount of alcohol intake may be harmful in subjects with elevated ALT levels, but there is limited evidence of the effect of light to moderate amount of alcohol intake in this subgroup. Methods: A cohort of 367,612 men and women without established liver diseases (including chronic viral hepatitis, alcohol-associated liver disease, cirrhosis, liver transplantation, or rare forms of liver disease) who underwent at least 1 health screening exam between 2009 and 2015 were assessed for liver-related and all-cause mortality. Elevated ALT levels were defined as ≥ 34 U/L for men and 25 U/L for women. Results: In participants with normal ALT levels, the fully-adjusted hazard ratios (95% CI) for liver-related mortality comparing light and moderate drinkers to non-drinkers were 0.73 (0.51–1.05), and 1.06 (0.73–1.52), respectively. In participants with elevated ALT levels, the corresponding hazard ratios were 1.57 (1.08–2.28), and 2.09 (CI 1.46–2.99), respectively (p value for alcohol intake by ALT interaction < 0.01). For all-cause mortality, the fully-adjusted hazard ratios comparing light and moderate drinkers to non-drinkers in participants with normal ALT levels were 0.72 (0.66–0.77), and 0.89 (0.82–0.97), respectively. In participants with elevated ALT levels, the corresponding hazard ratios were 0.93 (0.81–1.08), and 1.31 (1.14–1.50), respectively (p value for alcohol intake by ALT interaction < 0.01). Conclusions: Small amounts of alcohol intake were associated with increased liver-related and all-cause mortality among individuals with elevated ALT levels. Subjects with elevated ALT levels should be advised complete abstinence from alcohol.

Nonalcoholic fatty liver disease and accelerated loss of skeletal muscle mass: A longitudinal cohort study

Sinn, D. H., Kang, D., Kang, M., Guallar, E., Hong, Y. S., Lee, K. H., Park, J., Cho, J., & Gwak, G. Y. (n.d.).

Publication year

2022

Journal title

Hepatology

Volume

76

Issue

6

Page(s)

1746-1754

10.1002/hep.32578

Abstract

Abstract

Background and Aims: Whether subjects with NAFLD are at increased risk of sarcopenia is not well established. Approach and Results: This is a cohort study of 52,815 men and women of 20 years of age or older who underwent at least two health check-up exams with bioelectrical impedance analysis and abdominal ultrasound imaging. Bioelectrical impedance analysis was used to calculate appendicular skeletal muscle mass (ASM). NAFLD was assessed by ultrasonography, and its severity was assessed by the NAFLD fibrosis score (NFS). We estimated the 5-year change in ASM comparing participants with and without NAFLD at baseline using mixed linear models. The 5-year change in ASM in participants without and with NAFLD was −225.2 g (95% CI −232.3, −218.0) and −281.3 g (95% CI −292.0, −270.6), respectively (p < 0.001). In multivariable adjusted analysis, the difference in 5-year change in ASM comparing participants with and without NAFLD was −39.9 g (95% CI −53.1, −26.8). When participants with NAFLD were further divided by NAFLD severity, ASM loss was much faster in participants with NAFLD with intermediate to high NFS than in those with low NFS. Conclusions: Participants with NAFLD were at increased risk of sarcopenia, indicated by faster loss of skeletal muscle mass. Patients with NAFLD may need screening and early intervention to mitigate skeletal muscle mass loss.

Nonalcoholic Fatty Liver Disease and Risk of Early-Onset Vasomotor Symptoms in Lean and Overweight Premenopausal Women

Cho, Y., Chang, Y., Choi, H. R., Kang, J., Kwon, R., Lim, G. Y., Ahn, J., Kim, K. H., Kim, H., Hong, Y. S., Zhao, D., Rampal, S., Cho, J., Park, H. Y., Guallar, E., & Ryu, S. (n.d.).

Publication year

2022

Journal title

Nutrients

Volume

14

Issue

14

10.3390/nu14142805

Abstract

Abstract

The role of nonalcoholic fatty liver disease (NAFLD) in vasomotor symptom (VMS) risk in premenopausal women is unknown. We examined the prevalence of early-onset VMSs according to NAFLD status in lean and overweight premenopausal women. This cross-sectional study included 4242 premenopausal Korean women (mean age 45.4 years). VMSs (hot flashes and night sweats) were assessed using the Korean version of the Menopause-Specific Quality of Life questionnaire. Hepatic steatosis was determined using liver ultrasound; lean was defined as a body mass index of <23 kg/m2. Participants were categorized into four groups: NAFLD-free lean (reference), NAFLD-free overweight, lean NAFLD, and overweight NAFLD. Compared with the reference, the multivariable-adjusted prevalence ratios (PRs) (95% confidence intervals (CIs)) for VMSs in NAFLD-free overweight, lean NAFLD, and overweight NAFLD were 1.22 (1.06–1.41), 1.38 (1.06–1.79), and 1.49 (1.28–1.73), respectively. For moderate-to-severe VMSs, the multivariable-adjusted PRs (95% CIs) comparing NAFLD-free overweight, lean NAFLD, and overweight NAFLD to the reference were 1.38 (1.10–1.74), 1.73 (1.16–2.57), and 1.74 (1.37–2.21), respectively. NAFLD, even lean NAFLD, was significantly associated with an increased risk of prevalent early-onset VMSs and their severe forms among premenopausal women. Further studies are needed to determine the longitudinal association between NAFLD and VMS risk.

Outcomes and Revenue Generation of a Community-based Screening at a Center in the United States: The SToP Glaucoma Program

Varadaraj, V., Wahl, M., Gajwani, P., David, J., Dutson, M., Zhao, D., Guallar, E., Swenor, B. K., Johnson, T. V., & Friedman, D. S. (n.d.).

Publication year

2022

Journal title

Journal of Glaucoma

Volume

31

Issue

7

Page(s)

523-528

10.1097/IJG.0000000000002035

Abstract

Abstract

Précis: Of 611 individuals seen at referral clinic visits following community screenings, 76% were diagnosed with ≤1 eye condition needing treatment, generating a total of $213,110 in collections for the institution over 2.5 years. Purpose: The purpose of this study was to examine the outcomes and revenue generation of community-based eye screenings. Materials and Methods: Individuals aged 50 years and above screened at community sites in Baltimore, MD, with abnormal ophthalmic findings were referred for one free-of-charge definitive eye examination at the Wilmer Eye Institute. Diagnoses, treatment, and billing information were abstracted from electronic medical records of patients subsequently seen at Wilmer from January 1, 2016, to July 31, 2018. Results: A total of 611 individuals attended 3696 encounters at Wilmer during this time period. Most patients were female (60.3%) and African American (83.7%). At the screening event, 82.9% reported difficulty seeing when not wearing corrective eyewear, although only 49.8% reported having visited an eye doctor within the last 2 years. The majority (60.2%) reported having Medicare/Medicaid coverage, and 8.1% reported being uninsured. At the definitive eye examination after the screening, 75.5% of patients were diagnosed with ≥1 eye condition, most commonly cataract (30.3%), suspicion of glaucoma (24.9%), manifest glaucoma (11.9%), diabetic retinopathy (5.4%), and ocular hypertension (2.6%). Overall, 430 (70.4%) individuals required treatment including surgery (n=106), intravitreal injections (n=14), laser procedures (n=9), and medications (n=48). A total of $213,110 was collected for visits and procedures after the initial referral visit during the study period. Conclusions: A large community-based vision screening program in Baltimore was able to identify ocular conditions requiring treatment in underserved older adults and connect them to eyecare. Our findings also highlight that this model simultaneously generates new revenue streams for the institution organizing the community screenings.

Oxidative Stress and Menopausal Status: The Coronary Artery Risk Development in Young Adults Cohort Study

Heravi, A. S., Michos, E. D., Zhao, D., Ambale-Venkatesh, B., Doria De Vasconcellos, H., Lloyd-Jones, D., Schreiner, P. J., Reis, J. P., Wu, C., Lewis, C. E., Shikany, J. M., Sidney, S., Guallar, E., Ndumele, C. E., Ouyang, P., Hoogeveen, R. C., Lima, J. A., Vaidya, D., & Post, W. S. (n.d.).

Publication year

2022

Journal title

Journal of Women's Health

Volume

31

Issue

7

Page(s)

1057-1065

10.1089/jwh.2021.0248

Abstract

Abstract

Background: Low endogenous estrogen concentrations after menopause may contribute to higher oxidative stress and greater cardiovascular disease (CVD) risk. However, differences in oxidative stress between similarly aged premenopausal and postmenopausal women are not well-characterized on a population level. We hypothesized that urinary isoprostane concentrations, a standard measure of systemic oxidative stress, are higher in women who have undergone menopause compared to premenopausal women. Methods and Results: We examined differences in urinary 8-isoprostane (iPF2α-III) and 2,3-dinor-8-isoprostane (iPF2α-III-M) indexed to urinary creatinine between 279 postmenopausal and 196 premenopausal women in the Coronary Artery Risk Development in Young Adults (CARDIA) study, using linear regression with progressive adjustment for sociodemographic factors and traditional CVD risk factors. Unadjusted iPF2α-III-M concentrations were higher among postmenopausal compared to premenopausal women (Median [25th, 75th percentile]: 1762 [1178, 2974] vs. 1535 [1067, 2462] ng/g creatinine; p = 0.01). Menopause was associated with 25.5% higher iPF2α-III-M (95% confidence interval [6.5-47.9]) adjusted for age, race, college education, and field center. Further adjustments for tobacco use (21.2% [2.9-42.6]) and then CVD risk factors (18.8% [0.1-39.6]) led to additional partial attenuation. Menopause was associated with higher iPF2α-III in Black but not White women. Conclusions: We conclude that postmenopausal women had higher oxidative stress, which may contribute to greater CVD risk. ClinicalTrials.gov Identifier: NCT00005130.

Quantifying Individual-Level Inaccuracy in Glomerular Filtration Rate Estimation A Cross-Sectional Study

Shafi, T., Zhu, X., Lirette, S. T., Rule, A. D., Mosley, T., Butler, K. R., Hall, M. E., Vaitla, P., Wynn, J. J., Tio, M. C., Dossabhoy, N. R., Guallar, E., & Butler, J. (n.d.).

Publication year

2022

Journal title

Annals of internal medicine

Volume

175

Issue

8

Page(s)

1073-1082

10.7326/M22-0610

Abstract

Abstract

Background: Although the population-level differences between estimated glomerular filtration rate (eGFR) and measured glomerular filtration rate (mGFR) are well recognized, the magnitude and potential clinical implications of individual-level differences are unknown. Objective: To quantify the magnitude and consequences of the individual-level differences between mGFRs and eGFRs. Design: Cross-sectional study. Setting: Four U.S. community-based epidemiologic cohort studies with mGFR. Patients: 3223 participants in 4 studies. Measurements: The GFRs were measured using urinary iothalamate and plasma iohexol clearance; the eGFR was calculated from serum creatinine concentration alone (eGFRCR) and with cystatin C. All GFR results are presented as mL/min/1.73 m2. Results: The participants' mean age was 59 years; 32% were Black, 55% were women, and the mean mGFR was 68. The population-level differences between mGFR and eGFRCR were small; the median difference (mGFR_eGFR) was -0.6 (95% CI, -1.2 to -0.2); however, the individual-level differences were large. At an eGFRCR of 60, 50% of mGFRs ranged from 52 to 67, 80% from 45 to 76, and 95% from 36 to 87. At an eGFRCR of 30, 50% of mGFRs ranged from 27 to 38, 80% from 23 to 44, and 95% from 17 to 54. Substantial disagreement in chronic kidney disease staging by mGFR and eGFRCR was present. Among those with eGFRCR of 45 to 59, 36% had mGFR greater than 60 whereas 20% had mGFR less than 45; among those with eGFRCR of 15 to 29, 30% had mGFR greater than 30 and 5% had mGFR less than 15. The eGFR based on cystatin C did not provide substantial improvement. Limitation: Single measurement of mGFR and serum markers without short-term replicates Conclusion: A substantial individual-level discrepancy exists between the mGFR and the eGFR. Laboratories reporting eGFR should consider including the extent of this uncertainty to avoid misinterpretation of eGFR as an mGFR replacement.

Reclassifying the International Association for the Study of Lung Cancer Residual Tumor Classification According to the Extent of Nodal Dissection for NSCLC: One Size Does Not Fit All

Lee, J., Hong, Y. S., Cho, J., Lee, J., Lee, G., Kang, D., Yun, J., Jeon, Y. J., Shin, S., Cho, J. H., Choi, Y. S., Kim, J., Zo, J. I., Shim, Y. M., Guallar, E., & Kim, H. K. (n.d.).

Publication year

2022

Journal title

Journal of Thoracic Oncology

Volume

17

Issue

7

Page(s)

890-899

10.1016/j.jtho.2022.03.015

Abstract

Abstract

Introduction: The extent of nodal assessment may require risk-based adjustments in NSCLC. We reclassified the International Association for the Study of Lung Cancer Residual tumor classification according to the extent of nodal dissection and evaluated its long-term prognosis by tumor stage and histologic subtype. Methods: We reclassified 5117 patients who underwent resection for clinical stages I to III NSCLC and had complete or uncertain resection by International Association for the Study of Lung Cancer classification into the following 3 groups according to compliance with three components (N1, N2, and subcarinal node) of systematic nodal dissection criteria: fully compliant group (FCG), partially compliant group (PCG), and noncompliant group (NCG). Recurrence-free survival (RFS) and overall survival (OS) were compared. Results: Of the 5117 patients, 2806 (55%), 1959 (38%), and 359 (7%) were FCG, PCG, and NCG, respectively. PCG and NCG were more likely to be of lower clinical stage and adenocarcinoma with lepidic component than FCG. The 5-year RFS and OS were significantly better in NCG than in FCG or PCG (RFS, 86% versus 70% or 74%, p < 0.001; OS, 90% versus 80% or 83%, p < 0.001). In particular, NCG had better RFS and OS than FCG or PCG in clinical stage I and in lepidic-type adenocarcinoma. Conclusions: In early stage NSCLC with low-risk histologic subtype, a less rigorous nodal assessment was not associated with a worse prognosis. Although surgeons should continue to aim for complete resection and thorough nodal assessment, a uniform approach to the extent and invasiveness of nodal assessment may need to be reconsidered.

Reply

Sinn, D. H., Kang, D., Guallar, E., Cho, J., & Gwak, G. Y. (n.d.). In Hepatology (1–).

Publication year

2022

Volume

76

Issue

6

Page(s)

E121-E122

10.1002/hep.32678

Risk factors for hemorrhoidal disease among healthy young and middle-aged Korean adults

Hong, Y. S., Jung, K. U., Rampal, S., Zhao, D., Guallar, E., Ryu, S., Chang, Y., Kim, H. O., Kim, H., Chun, H. K., Sohn, C. I., Shin, H., & Cho, J. (n.d.).

Publication year

2022

Journal title

Scientific reports

Volume

12

Issue

1

10.1038/s41598-021-03838-z

Abstract

Abstract

Hemorrhoidal disease is a highly prevalent anorectal condition causing substantial discomfort, disability, and decreased quality of life. Evidence on preventable risk factors for hemorrhoidal disease is limited. We conducted a cross-sectional study of 194,620 healthy men and women who completed a health screening exam including colonoscopy in 2011–2017. We evaluated potential risk factors of hemorrhoidal disease, including lifestyle factors, medical history, birth history, gastrointestinal symptoms, and anthropometric measurements. The prevalence of hemorrhoidal disease was 16.6%, and it was higher in females than in males (17.2 vs. 16.3%; P < 0.001). Compared to men, the prevalence of hemorrhoidal disease was higher in parous women (adjusted odds ratio [OR] 1.06; 95% confidence interval [CI] 1.02–1.10), and lower in nulliparous women (adjusted OR 0.92; 95% CI 0.86–0.98). In the adjusted analyses, older age, female sex, smoking, overweight, and being hypertensive were independently associated with the presence of hemorrhoidal disease. The prevalence of hemorrhoidal disease was positively associated with body mass index and waist circumference in parous women. The prevalence of hemorrhoidal disease was higher in older age, females, ever-smokers, and hypertensive participants. The association of excess adiposity with the prevalence of hemorrhoidal disease differed by sex and parity.

Temporal patterns of chronic disease incidence after breast cancer: a nationwide population-based cohort study

Kang, D., Kang, M., Hong, Y. S., Park, J., Lee, J., Seo, H. J., Kim, D. W., Ahn, J. S., Park, Y. H., Lee, S. K., Shin, D. W., Guallar, E., & Cho, J. (n.d.).

Publication year

2022

Journal title

Scientific reports

Volume

12

Issue

1

10.1038/s41598-022-09542-w

Abstract

Abstract

We conducted a retrospective cohort study to evaluate the temporal pattern of incidence of chronic conditions after developing breast cancer using a population-based national registry. We selected 84,969 women with newly diagnosed breast cancer between 2002 and 2016 and a 1:10 sample of age-matched non-breast cancer controls (N = 1,057,674). The main study exposure was incident breast cancer, considered as a time-varying exposure. The outcomes were incident cases of leukemia, endometrial cancer, myeloma, cardiomyopathy, osteoporosis, end stage renal disease (ESRD), pulmonary fibrosis, hypothyroidism, type 2 diabetes, hypertension and hyperlipidemia. The development of breast cancer was associated with a significantly increased risk of all outcomes analyzed except for ESRD and hypertension. The fully-adjusted risks of leukemia (HR 3.09; 95% CI 2.11–4.51), cardiomyopathy (HR 2.65; 95% CI 1.90–3.68), endometrial cancer (HR 3.53; 95% CI 2.76–4.53), hypothyroidism (HR 1.29; 95% CI 1.19–1.40), pulmonary fibrosis (HR 1.84; 95% CI 1.12–3.02), and hyperlipidemia (HR 1.24; 95% CI 1.20–1.28) remained significantly elevated after more than 5 years since diagnosis. Optimal care for breast cancer survivors requires close collaboration between oncologists and allied health care professionals to identify and manage the long-term morbidity and mortality associated with these chronic conditions.

Testosterone and Cardiovascular Disease in Men

Zhao, D., & Guallar, E. (n.d.).

Publication year

2022

Journal title

Annals of internal medicine

Volume

175

Issue

2

Page(s)

287-288

10.7326/M21-4777

Toxic Metals and Subclinical Atherosclerosis in Carotid, Femoral, and Coronary Vascular Territories: The Aragon Workers Health Study

Grau-Perez, M., Caballero-Mateos, M. J., Domingo-Relloso, A., Navas-Acien, A., Gomez-Ariza, J. L., Garcia-Barrera, T., Leon-Latre, M., Soriano-Gil, Z., Jarauta, E., Cenarro, A., Moreno-Franco, B., Laclaustra, M., Civeira, F., Casasnovas, J. A., Guallar, E., & Tellez-Plaza, M. (n.d.).

Publication year

2022

Journal title

Arteriosclerosis, Thrombosis, and Vascular Biology

Volume

42

Issue

1

Page(s)

87-99

10.1161/ATVBAHA.121.316358

Abstract

Abstract

OBJECTIVE: Studies evaluating the association of metals with subclinical atherosclerosis are mostly limited to carotid arteries. We assessed individual and joint associations of nonessential metals exposure with subclinical atherosclerosis in 3 vascular territories. APPROACH AND RESULTS: One thousand eight hundred seventy-three Aragon Workers Health Study participants had urinary determinations of inorganic arsenic species, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten. Plaque presence in carotid and femoral arteries was determined by ultrasound. Coronary Agatston calcium score ≥1 was determined by computed tomography scan. Median arsenic, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten levels were 1.83, 1.98, 0.27, 1.18, 0.05, 9.8, 0.03, 0.66, and 0.23 μg/g creatinine, respectively. The adjusted odds ratio (95% CI) for subclinical atherosclerosis presence in at least one territory was 1.25 (1.03-1.51) for arsenic, 1.67 (1.22-2.29) for cadmium, and 1.26 (1.04-1.52) for titanium. These associations were driven by arsenic and cadmium in carotid, cadmium and titanium in femoral, and titanium in coronary territories and mostly remained after additional adjustment for the other relevant metals. Titanium, cadmium, and antimony also showed positive associations with alternative definitions of increased coronary calcium. Bayesian Kernel Machine Regression analysis simultaneously evaluating metal associations suggested an interaction between arsenic and the joint cadmiumtitanium exposure. CONCLUSIONS: Our results support arsenic and cadmium and identify titanium and potentially antimony as atherosclerosis risk factors. Exposure reduction and mitigation interventions of these metals may decrease cardiovascular risk in individuals without clinical disease.

A Guideline for Reporting Mediation Analyses of Randomized Trials and Observational Studies: The AGReMA Statement

Lee, H., Cashin, A. G., Lamb, S. E., Hopewell, S., Vansteelandt, S., Vanderweele, T. J., MacKinnon, D. P., Mansell, G., Collins, G. S., Golub, R. M., McAuley, J. H., Localio, A. R., Van Amelsvoort, L., Guallar, E., Rijnhart, J., Goldsmith, K., Fairchild, A. J., Lewis, C. C., Kamper, S. J., … Henschke, N. (n.d.).

Publication year

2021

Journal title

JAMA - Journal of the American Medical Association

Volume

326

Issue

11

Page(s)

1045-1056

10.1001/jama.2021.14075

Abstract

Abstract

Importance: Mediation analyses of randomized trials and observational studies can generate evidence about the mechanisms by which interventions and exposures may influence health outcomes. Publications of mediation analyses are increasing, but the quality of their reporting is suboptimal. Objective: To develop international, consensus-based guidance for the reporting of mediation analyses of randomized trials and observational studies (A Guideline for Reporting Mediation Analyses; AGReMA). Design, Setting, and Participants: The AGReMA statement was developed using the Enhancing Quality and Transparency of Health Research (EQUATOR) methodological framework for developing reporting guidelines. The guideline development process included (1) an overview of systematic reviews to assess the need for a reporting guideline; (2) review of systematic reviews of relevant evidence on reporting mediation analyses; (3) conducting a Delphi survey with panel members that included methodologists, statisticians, clinical trialists, epidemiologists, psychologists, applied clinical researchers, clinicians, implementation scientists, evidence synthesis experts, representatives from the EQUATOR Network, and journal editors (n = 19; June-November 2019); (4) having a consensus meeting (n = 15; April 28-29, 2020); and (5) conducting a 4-week external review and pilot test that included methodologists and potential users of AGReMA (n = 21; November 2020). Results: A previously reported overview of 54 systematic reviews of mediation studies demonstrated the need for a reporting guideline. Thirty-three potential reporting items were identified from 3 systematic reviews of mediation studies. Over 3 rounds, the Delphi panelists ranked the importance of these items, provided 60 qualitative comments for item refinement and prioritization, and suggested new items for consideration. All items were reviewed during a 2-day consensus meeting and participants agreed on a 25-item AGReMA statement for studies in which mediation analyses are the primary focus and a 9-item short-form AGReMA statement for studies in which mediation analyses are a secondary focus. These checklists were externally reviewed and pilot tested by 21 expert methodologists and potential users, which led to minor adjustments and consolidation of the checklists. Conclusions and Relevance: The AGReMA statement provides recommendations for reporting primary and secondary mediation analyses of randomized trials and observational studies. Improved reporting of studies that use mediation analyses could facilitate peer review and help produce publications that are complete, accurate, transparent, and reproducible..

Alcohol Intake and Mortality in Patients With Chronic Viral Hepatitis: A Nationwide Cohort Study

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

Publication year

2021

Journal title

American Journal of Gastroenterology

Volume

116

Issue

2

Page(s)

329-335

10.14309/ajg.0000000000000966

Abstract

Abstract

INTRODUCTION: We evaluated the association between alcohol intake and all-cause and cause-specific mortality in subjects with chronic viral hepatitis, using nationwide population-based cohort study. METHODS: A total of 364,361 men and women aged 40-84 years who underwent health screening examination between January 2002 and December 2013 that included assessment of frequency and amount of alcohol consumption were assessed for all-cause and cause-specific mortality. RESULTS: In participants without chronic viral hepatitis, the fully adjusted hazard ratios (HRs) for all-cause mortality comparing light, moderate, and heavy drinkers with nondrinkers were 0.92 (95% confidence interval [CI] 0.87-0.98), 1.08 (95% CI 1.01-1.16), and 1.51 (95% CI 1.33-1.72), respectively. In participants with chronic viral hepatitis, the corresponding HRs were 1.19 (95% CI 1.05-1.36), 1.23 (95% CI 1.06-1.43), and 1.69 (95% CI 1.28-2.24), respectively (P value for alcohol intake by chronic viral hepatitis interaction <0.001). Compared with participants without chronic viral hepatitis, those with chronic viral hepatitis had substantially elevated liver cancer or liver disease (HR 10.85, 95% CI 9.74-12.09) and extrahepatic cancer mortality (HR 1.37, 95% CI 1.26-1.49). In patients with chronic viral hepatitis, the high mortality due to liver cancer or liver disease and the positive association of alcohol intake with liver cancer or liver disease mortality explained the positive association of alcohol intake with all-cause mortality. DISCUSSION: Even light to moderate alcohol intake was associated with increased all-cause mortality in individuals with chronic viral hepatitis. Clinicians and public health campaigns should advise against any amount of alcohol intake in individuals with chronic viral hepatitis.

Blood eosinophil counts and the development of obstructive lung disease: The Kangbuk Samsung Health Study

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

Publication year

2021

Journal title

European Respiratory Journal

Volume

58

Issue

4

10.1183/13993003.03823-2020

Abstract

Abstract

Aim The impact of blood eosinophil counts on the development of chronic obstructive lung disease (COPD) is unknown. We investigated whether a higher blood eosinophil count was associated with the risk of developing obstructive lung disease (OLD) in a large cohort of men and women free from lung disease at baseline. Methods This was a cohort study of 359 456 Korean adults without a history of asthma and without OLD at baseline who participated in health screening examinations including spirometry. OLD was defined as pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and FEV1 <80% predicted. Results After a median (interquartile range) follow-up of 5.6 (2.9-9.2) years, 5008 participants developed incident OLD (incidence rate 2.1 (95% CI 2.1-2.2) per 1000 person-years). In the fully adjusted model, the hazard ratios for incident OLD comparing eosinophil counts of 100- <200, 200- <300, 300-<500 and ≥500 versus <100 cells μL-1 were 1.07 (95% CI 1.00-1.15), 1.30 (95% CI 1.20-1.42), 1.46 (95% CI 1.33-1.60) and 1.72 (95% CI 1.51-1.95), respectively (ptrend<0.001). These associations were consistent in clinically relevant subgroups, including never-, ex- and current smokers. Conclusion In this large longitudinal cohort study, blood eosinophil counts were positively associated with the risk of developing of OLD. Our findings indicate a potential role of the eosinophil count as an independent risk factor for developing COPD.

Blood-derived mitochondrial DNA copy number is associated with gene expression across multiple tissues and is predictive for incident neurodegenerative disease

Yang, S. Y., Castellani, C. A., Longchamps, R. J., Pillalamarri, V. K., O’Rourke, B., Guallar, E., & Arking, D. E. (n.d.).

Publication year

2021

Journal title

Genome Research

Volume

31

Issue

3

Page(s)

349-358

10.1101/GR.269381.120

Abstract

Abstract

Mitochondrial DNA copy number (mtDNA-CN) is a proxy for mitochondrial function and is associated with aging-related diseases. However, it is unclear how mtDNA-CN measured in blood can reflect diseases that primarily manifest in other tissues. Using the Genotype-Tissue Expression Project, we interrogated relationships between mtDNA-CN measured in whole blood and gene expression from whole blood and 47 additional tissues in 419 individuals. mtDNA-CN was significantly associated with expression of 700 genes in whole blood, including nuclear genes required for mtDNA replication. Significant enrichment was observed for splicing and ubiquitin-mediated proteolysis pathways, as well as target genes for the mitochondrial transcription factor NRF1. In nonblood tissues, there were more significantly associated genes than expected in 30 tissues, suggesting that global gene expression in those tissues is correlated with blood-derived mtDNA-CN. Neurodegenerative disease pathways were significantly associated in multiple tissues, and in an independent data set, the UK Biobank, we observed that higher mtDNA-CN was significantly associated with lower rates of both prevalent (OR = 0.89, CI =0.83; 0.96) and incident neurodegenerative disease (HR =0.95, 95% CI= 0.91;0.98). The observation that mtDNA-CN measured in blood is associated with gene expression in other tissues suggests that blood-derived mtDNACN can reflect metabolic health across multiple tissues. Identification of key pathways including splicing, RNA binding, and catalysis reinforces the importance of mitochondria in maintaining cellular homeostasis. Finally, validation of the role of mtDNA CN in neurodegenerative disease in a large independent cohort study solidifies the link between bloodderived mtDNA-CN, altered gene expression in multiple tissues, and aging-related disease.

Cyclic guanosine monophosphate and 10-year change in left ventricular mass: the Multi-Ethnic Study of Atherosclerosis (MESA)

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

Publication year

2021

Journal title

Biomarkers

Volume

26

Issue

4

Page(s)

309-317

10.1080/1354750X.2021.1893811

Abstract

Abstract

Purpose: Cyclic guanosine monophosphate (cGMP) is a second messenger for natriuretic peptide (NP) and nitric oxide pathways; its enhancement a target for heart failure and cardiovascular disease (CVD). We evaluated whether plasma cGMP was associated with change in left ventricular mass (LVM) among individuals free of CVD and if this differed by sex. Methods and Results: In 611 men and 612 women aged 45–84 years with plasma cGMP measured at baseline and cardiac MRI performed at baseline and 10 years later, we tested associations of cGMP [log-transformed, per 1 SD increment] with LVM, adjusting for CVD risk factors and N-terminal pro-B-type-NP (NT-proBNP). Participants had mean (SD) age of 63.1(8.5) years and cGMP 4.8(2.6) pmol/mL. Cross-sectionally, higher cGMP was associated with lesser LVM, non-lin- early. In contrast, longitudinally, higher cGMP was associated with increase in LVM [1.70g (0.61, 2.78)] over 10 years. Higher cGMP was associated with greater LVM change in men [2.68g (1.57, 3.79)] but not women [0.24g ((−0.92, 1.39); p-interaction < 0.001]. Conclusion: In conclusion, in a community-based cohort, higher cGMP levels were associated with increase in LVM over 10 years independent of CVD risk factors and NT-proBNP in men, perhaps reflecting compensatory changes. Further studies are needed to understand mechanistic roles of cGMP in LV remodelling and associated sex differences.

Health disparities of critically ill children according to poverty: the Korean population-based retrospective cohort study

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

Publication year

2021

Journal title

BMC public health

Volume

21

Issue

1

10.1186/s12889-021-11324-4

Abstract

Abstract

Background: There is a lack of nationwide studies on critically ill patients’ health disparity under the National Health Insurance (NHI) system. We evaluated health disparities in intensive care unit (ICU) admission, outcomes, and readmission in impoverished children. Methods: We conducted a retrospective cohort study using a national database from the Korean NHI and Medical Aid Program (MAP). MAP supports the population whose household income is lower than 40% of the median Korean household income. We defined poverty as being a MAP beneficiary and compared the poverty and non-poverty groups. Patients between 28 days and 18 years old who were admitted to the ICU were included. Hospital mortality and readmission were analyzed with adjustment for patient characteristics, hospital type, and management procedures. Results: Out of 17,893 patients, 1153 (6.4%) patients were in poverty. The age-standardized ICU admission rate was higher in the poverty group (126.9 vs. 80.2 per 100,000 person-years). There was more age-standardized mortality in the poverty group (11.8 vs. 4.3 per 100,000 person-years). Patients in the poverty group did not have a statistically different risk of adjusted in-hospital mortality to those in the non-poverty group (odds ratio: 1.15, confidence interval [CI]: 0.84–1.55) but had a higher readmission rate (hazard ratio 1.25, CI 1.09–1.42). Conclusion: Under the NHI system, the disparity in pediatric critical care outcomes according to poverty is not definite, but the healthcare disparity in pre- and post-hospital care is a concern. Further studies are required to improve pre- and post-hospital healthcare quality of impoverished children.