Eliseo Guallar
Eliseo Guallar
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Chair and Professor of the Department of Epidemiology
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Professional overview
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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.
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Education
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Diploma of English, Spanish Official School of Languages at Zaragoza (Escuela Oficial de Idiomas de Zaragoza), Zaragoza, SpainMD, University of Zaragoza, Zaragoza, SpainMPH, University of Minnesota, Minneapolis, MNDrPH, Harvard University, Boston, MA
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Honors and awards
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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)
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Publications
Publications
Metabolically healthy and unhealthy obesity and risk of vasomotor symptoms in premenopausal women : cross-sectional and cohort studies
AbstractNamgoung, 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
2022Journal title
BJOG: An International Journal of Obstetrics and GynaecologyVolume
129Issue
11Page(s)
1926-1934AbstractObjective: 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
AbstractSinn, D. H., Kang, D., Guallar, E., Hong, Y. S., Cho, J., & Gwak, G. Y. (n.d.).Publication year
2022Journal title
BMC MedicineVolume
20Issue
1AbstractBackground: 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
AbstractSinn, 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
2022Journal title
HepatologyVolume
76Issue
6Page(s)
1746-1754AbstractBackground 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
AbstractCho, 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
2022Journal title
NutrientsVolume
14Issue
14AbstractThe 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 ofOutcomes and Revenue Generation of a Community-based Screening at a Center in the United States : The SToP Glaucoma Program
AbstractVaradaraj, 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
2022Journal title
Journal of GlaucomaVolume
31Issue
7Page(s)
523-528AbstractPrécis: 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
AbstractHeravi, 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
2022Journal title
Journal of Women's HealthVolume
31Issue
7Page(s)
1057-1065AbstractBackground: 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
AbstractShafi, 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
2022Journal title
Annals of internal medicineVolume
175Issue
8Page(s)
1073-1082AbstractBackground: 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
AbstractLee, 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
2022Journal title
Journal of Thoracic OncologyVolume
17Issue
7Page(s)
890-899AbstractIntroduction: 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
AbstractSinn, D. H., Kang, D., Guallar, E., Cho, J., & Gwak, G. Y. (n.d.).Publication year
2022Journal title
HepatologyVolume
76Issue
6Page(s)
E121-E122Abstract~Risk factors for hemorrhoidal disease among healthy young and middle-aged Korean adults
AbstractHong, 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
2022Journal title
Scientific reportsVolume
12Issue
1AbstractHemorrhoidal 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
AbstractKang, 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
2022Journal title
Scientific reportsVolume
12Issue
1AbstractWe 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
AbstractZhao, D., & Guallar, E. (n.d.).Publication year
2022Journal title
Annals of internal medicineVolume
175Issue
2Page(s)
287-288Abstract~Toxic Metals and Subclinical Atherosclerosis in Carotid, Femoral, and Coronary Vascular Territories : The Aragon Workers Health Study
AbstractGrau-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
2022Journal title
Arteriosclerosis, Thrombosis, and Vascular BiologyVolume
42Issue
1Page(s)
87-99AbstractOBJECTIVE: 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
AbstractLee, 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
2021Journal title
JAMA - Journal of the American Medical AssociationVolume
326Issue
11Page(s)
1045-1056AbstractImportance: 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
AbstractSinn, D. H., Kang, D., Guallar, E., Chang, Y., Ryu, S., Zhao, D., Hong, Y. S., Cho, J., & Gwak, G. Y. (n.d.).Publication year
2021Journal title
American Journal of GastroenterologyVolume
116Issue
2Page(s)
329-335AbstractINTRODUCTION: 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 interactionAuthor Correction : Nonalcoholic fatty liver disease accelerates kidney function decline in patients with chronic kidney disease: a cohort study (Scientific Reports, (2018), 8, 1, (4718), 10.1038/s41598-018-23014-0)
AbstractJang, H. R., Kang, D., Sinn, D. H., Gu, S., Cho, S. J., Lee, J. E., Huh, W., Paik, S. W., Ryu, S., Chang, Y., Shafi, T., Lazo, M., Guallar, E., Cho, J., & Gwak, G. Y. (n.d.).Publication year
2021Journal title
Scientific reportsVolume
11Issue
1AbstractThe original version of this Article contained a repeated error in Affiliations 1,2,3,4 and 5 where “Kangbuk Samsung Hospital” was incorrectly given as the Organisational name. The correct affiliations are listed below: Affiliation 1 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Affiliation 2 Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea Affiliation 3 Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea Affiliation 4 Center for Health Promotion, Samsung Medical Center, Seoul, South Korea Affiliation 5 Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea The original Article has been corrected.Blood eosinophil counts and the development of obstructive lung disease : The Kangbuk Samsung Health Study
AbstractPark, 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
2021Journal title
European Respiratory JournalVolume
58Issue
4AbstractAim 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)Blood-derived mitochondrial DNA copy number is associated with gene expression across multiple tissues and is predictive for incident neurodegenerative disease
AbstractYang, S. Y., Castellani, C. A., Longchamps, R. J., Pillalamarri, V. K., O'Rourke, B., Guallar, E., & Arking, D. E. (n.d.).Publication year
2021Journal title
Genome ResearchVolume
31Issue
3Page(s)
349-358AbstractMitochondrial 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)
AbstractSubramanya, 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
2021Journal title
BiomarkersVolume
26Issue
4Page(s)
309-317AbstractPurpose: 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
AbstractPark, 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
2021Journal title
BMC public healthVolume
21Issue
1AbstractBackground: 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.In utero exposure to heavy metals and trace elements and childhood blood pressure in a u.S. urban, low-income, minority birth cohort
AbstractZhang, M., Liu, T., Wang, G., Buckley, J. P., Guallar, E., Hong, X., Wang, M. C., Wills-Karp, M., Wang, X., & Mueller, N. T. (n.d.).Publication year
2021Journal title
Environmental health perspectivesVolume
129Issue
6AbstractBACKGROUND: In utero exposure to heavy metals lead (Pb), mercury (Hg), and cadmium (Cd) may be associated with higher childhood blood pressure (BP), whereas trace elements selenium (Se) and manganese (Mn) may have protective antioxidant effects that modify metal-BP associations. OBJECTIVES: We examined the individual and joint effects of in utero exposure to Pb, Hg, Cd, Se, and Mn on childhood BP. METHODS: We used data from the Boston Birth Cohort (enrolled 2002–2013). We measured heavy metals and trace elements in maternal red blood cells collected 24–72 h after delivery. We calculated child BP percentile per the 2017 American Academy of Pediatrics Clinical Practice Guideline. We used linear regression models to estimate the association of each metal, and Bayesian kernel machine regression (BKMR) to examine metal coexposures, with child BP between 3 to 15 years of age. RESULTS: Our analytic sample comprised 1,194 mother-infant pairs (61% non-Hispanic Black, 20% Hispanic). Hg and Pb were not associated with child systolic BP (SBP). Se and Mn were inversely associated with child SBP percentiles, which, on average, were 6.23 points lower with a doubling of Se (95% CI: −11:51, −0:96) and 2.62 points lower with a doubling of Mn (95% CI: −5:20, −0:04). BKMR models showed similar results. Although Cd was not associated with child SBP overall, the inverse association between Mn and child SBP was stronger at higher levels of Cd (p-interaction = 0:04). Consistent with this finding, in utero exposure to cigarette smoke modified the Mn–child SBP association. Among children whose mothers smoked during pregnancy, a doubling of Mn was associated with a 10.09-point reduction in SBP percentile (95% CI: −18:03, −2:15), compared with a 1.49-point reduction (95% CI: −4:21, 1.24) in children whose mothers did not smoke during pregnancy (p-interaction = 0:08). CONCLUSION: Se and Mn concentrations in maternal red blood cells collected 24–72 h after delivery were associated with lower child SBP at 3 to 15 years of age. There was an interaction between Mn and Cd on child SBP, whereby the protective association of Mn on child SBP was stronger among mothers who had higher Cd. The association of Mn and child SBP was also modified by maternal cigarette smoking—a source of Cd—during pregnancy. Optimizing in utero Se levels, as well as Mn levels in women who had high Cd or smoked during pregnancy, may protect offspring from developing high BP during childhood.Patients’ and family members’ perspectives on arrhythmias and sudden death in dialysis : the HeartLink focus groups pilot study
AbstractXu, E. J., Boyer, L. P., Jaar, B. G., Ephraim, P. L., Gimenez, L., Cheng, A., Chrispin, J., Weir, M. R., Raj, D., Guallar, E., & Shafi, T. (n.d.).Publication year
2021Journal title
BMC NephrologyVolume
22Issue
1AbstractBackground: Patients receiving dialysis face a high risk of cardiovascular disease, arrhythmia and sudden cardiac death. Few patients, however, are aware of this risk. Implantable cardiac monitors are currently available for clinical use and can continuously monitor cardiac rhythms without the need for transvenous leads. Our goal was to gauge patients’ and family members’ perceptions of these risks and to identify their concerns about cardiac monitors. Methods: Two 90-minute focus groups were conducted: one with patients receiving in-center hemodialysis and one with their family members. Trained moderators assessed: (1) knowledge of cardiovascular disease; (2) cardiovascular disease risk in dialysis; (3) risk of death due to cardiovascular disease; (4) best ways to convey this risk to patients/families; and (5) concerns about cardiac monitors. The sessions were audiotaped, transcribed, and independently analyzed by two reviewers to identify core themes. Emblematic quotations were chosen to illustrate the final themes. Results: Nine adult patients and three family members participated. Patients felt education was inadequate and had little knowledge of arrhythmias. Patients’/families’ concerns regarding cardiac monitors were related to adverse effects, the notification process, and cosmetic effects. Patients/families felt that nephrologists, not dialysis staff, would be the best source for education. Conclusions: The preliminary data from this small study population suggest that patients/families are not well aware of the high risk of arrhythmia and sudden cardiac death in dialysis. Further investigation is required to gauge this awareness among patients/families and to assess their impressions of implantable cardiac monitors for arrhythmia detection and management.Physical activity and the progression of coronary artery calcification
AbstractSung, K. C., Hong, Y. S., Lee, J. Y., Lee, S. J., Chang, Y., Ryu, S., Zhao, D., Cho, J., Guallar, E., & Lima, J. A. (n.d.).Publication year
2021Journal title
HeartVolume
107Issue
21Page(s)
1710-1716AbstractBackground The association of physical activity with the development and progression of coronary artery calcium (CAC) scores has not been studied. This study aimed to evaluate the prospective association between physical activity and CAC scores in apparently healthy adults. Methods Prospective cohort study of men and women free of overt cardiovascular disease who underwent comprehensive health screening examinations between 1 March 2011 and 31 December 2017. Baseline physical activity was measured using the International Physical Activity Questionnaire Short Form (IPAQ-SF) and categorised into three groups (inactive, moderately active and health-enhancing physically active (HEPA)). The primary outcome was the difference in the 5-year change in CAC scores by physical activity category at baseline. Results We analysed 25 485 participants with at least two CAC score measurements. The proportions of participants who were inactive, moderately active and HEPA were 46.8%, 38.0% and 15.2%, respectively. The estimated adjusted average baseline CAC scores (95% confidence intervals) in participants who were inactive, moderately active and HEPA were 9.45 (8.76, 10.14), 10.20 (9.40, 11.00) and 12.04 (10.81, 13.26). Compared with participants who were inactive, the estimated adjusted 5-year average increases in CAC in moderately active and HEPA participants were 3.20 (0.72, 5.69) and 8.16 (4.80, 11.53). Higher physical activity was association with faster progression of CAC scores both in participants with CAC=0 at baseline and in those with prevalent CAC. Conclusion We found a positive, graded association between physical activity and the prevalence and the progression of CAC, regardless of baseline CAC scores.Prior antiviral treatment and mortality among patients with hepatitis C virus-related hepatocellular carcinoma : A national cohort study
AbstractSinn, D. H., Kang, D., Hong, Y. S., Koh, K. C., Guallar, E., Cho, J., & Gwak, G. Y. (n.d.).Publication year
2021Journal title
PloS oneVolume
16Issue
8 AugustAbstractBackground The current antiviral treatments available for hepatitis C virus (HCV) infection decrease the risk of hepatocellular carcinoma (HCC). Hence, patients with HCV infection who have not received antiviral treatment and have developed HCC may be those who missed timely antiviral treatment for HCV. However, the proportion of patients who missed timely antiviral treatment and its implications are largely unexplored. Methods A nationwide retrospective cohort of 4,592 newly diagnosed HCV-related HCC patients (2013-2017) was identified from the Korean National Health Insurance Service database. Prior antiviral treatment for HCV was defined as a history of at least one HCV-specific antiviral treatment before HCC diagnosis. The outcome was all-cause mortality. Results Prior antiviral treatment for HCV was identified in 802 (17.4%) patients, and 16%, 16%, 17%, 19%, and 19% of patients received antiviral treatment in the years 2013, 2014, 2015, 2016, and 2017, respectively (P = 0.21). During 8,085 person-years of follow-up (median, 1.4; maximum, 5.3 years of follow-up), 1,970 patients died. Mortality rates were lower in patients with prior antiviral treatment (15 deaths/100 person-years) than in those without prior antiviral treatment (27 deaths/100 person-years). The adjusted hazard ratio (95% confidence interval) for all-cause mortality on comparing patients who did and did not receive prior antiviral treatment was 0.68 (0.59, 0.79). Conclusion Timely antiviral treatment for HCV was suboptimal at the population level. Prior antiviral treatment for HCV reduced mortality rate in HCV-related HCC patients.Prognostic factors of renal outcomes after heart transplantation : A nationwide retrospective study
AbstractJeon, J., Park, H., Kim, Y., Kang, D., Lee, J. E., Huh, W., Guallar, E., Cho, J., & Jang, H. R. (n.d.).Publication year
2021Journal title
Journal of Clinical MedicineVolume
10Issue
21AbstractRenal dysfunction after heart transplantation (HT) is associated with poor survival. We investigated the predictive factors of renal outcomes after HT using nationwide cohort data. In this retrospective cohort study using the Health Insurance Review and Assessment database of Korea, 654 patients who received HT between 2008 and 2016 and survived until discharge after HT were analyzed. The median (interquartile range) age was 52 (40–60) years, and 68.1% were male. Perioperative renal replacement therapy (RRT) was performed in 27.8% of patients. During 2.8 years of median followup, end-stage kidney disease (ESKD) developed in 12 patients (1.8%). In a fully adjusted model, RRT >3 weeks, the use of inotropes/vasopressors and non-use of ACEi/ARB were associated with ESKD. Preexisting renal disease tended to be associated with ESKD. Among the 561 patients without preexisting CKD, 104 (18.5 %) developed chronic kidney disease (CKD). Age, extracorporeal membrane oxygenation, and RRT were associated with the development of CKD after HT. Our nationwide cohort study demonstrated that perioperative RRT was a predictor of poor renal outcomes after HT. These results suggest that an active renoprotective strategy is required during the perioperative period.