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

Ambient air pollution as a mediator in the pathway linking race/ethnicity to blood pressure elevation : The multi-ethnic study of atherosclerosis (MESA)

Song, L., Smith, G. S., Adar, S. D., Post, W. S., Guallar, E., Navas-Acien, A., Kaufman, J. D., & Jones, M. R. (n.d.).

Publication year

2020

Journal title

Environmental Research

Volume

180

10.1016/j.envres.2019.108776

Abstract

Abstract

Background: Racial/ethnic disparities in blood pressure and hypertension have been evident in previous studies, as were associations between race/ethnicity with ambient air pollution and those between air pollution with hypertension. The role of air pollution exposure to racial/ethnic differences in hypertension has not been explored. Objective: To assess the potential mediating effects of ambient air pollution on the association between race/ethnicity and blood pressure levels. Methods: We studied 6,463 White, Black, Hispanic and Chinese adults enrolled across 6 US cities. Systolic (SBP) and diastolic blood pressure (DBP) were measured at Exam 1 (2000–2002) and Exam 2 (2002–2004). Household-level annual average concentrations of fine particulate matter (PM2.5), oxides of nitrogen (NOX), and ozone (O3) for the year 2000 were estimated for participants. Results: The difference in SBP levels by race/ethnicity that was related to higher PM2.5 concentrations compared with White men (“indirect associations”) was 0.3 (95% CI: 0.1, 0.6) mmHg for Black men, 0.3 (95% CI: 0.1, 0.6) mmHg for Hispanic men and 1.0 (95% CI: 0.2, 1.8) mmHg for Chinese men. Findings were similar although not statistically significant for women. PM2.5 did not mediate racial/ethnic differences in DBP. Indirect associations were significant for O3 for SBP among women and men and for DBP among men. In contrast, racial/ethnic disparities were attenuated due to exposure to NOX. Conclusion: Racial disparities in blood pressure were reduced after accounting for PM2.5 and ozone while increased after accounting for NOX.

Associations between Helicobacter pylori with nonalcoholic fatty liver disease and other metabolic conditions in Guatemala

Alvarez, C. S., Florio, A. A., Butt, J., Rivera-Andrade, A., Kroker-Lobos, M. F., Waterboer, T., Camargo, M. C., Freedman, N. D., Graubard, B. I., Lazo, M., Guallar, E., Groopman, J. D., Ramírez-Zea, M., & McGlynn, K. A. (n.d.).

Publication year

2020

Journal title

Helicobacter

Volume

25

Issue

6

10.1111/hel.12756

Abstract

Abstract

Background: Previous studies have suggested an association between Helicobacter pylori (H pylori) and nonalcoholic fatty liver disease (NAFLD). The aim of the current study was to examine the association in Guatemala, a region with elevated prevalences of both H pylori and NAFLD. Associations between H pylori and other metabolic conditions were also examined, as were associations between H hepaticus and H bilis and the metabolic conditions. Materials & Methods: The analysis included 424 participants from a cross-sectional study in Guatemala. H pylori seropositivity was defined as positivity for ≥ 4 antigens. Seropositivities for H bilis and H hepaticus were defined as positivity for ≥ 2 antigens. NAFLD was estimated using the Fatty Liver Index and the Hepatic Steatosis Index. Other conditions examined were obesity, central obesity, hypercholesterolemia, low HDL, diabetes and metabolic syndrome (MetSyn). Prevalence odds ratios (POR) and 95% confidence intervals (CIs) were estimated. Results: No overall associations between H pylori, H hepaticus, or H bilis and NAFLD or related metabolic conditions were found. Seropositivity for H pylori antigens CagA and VacA and H hepaticus antigen HH0713 was each significantly associated with NAFLD, however. In addition, associations were observed between the H pylori antigens HyuA, HP1564, and UreA and specified metabolic conditions. Conclusions: While no overall associations between H pylori or Helicobacter species with NAFLD or related conditions were observed, some selected Helicobacter spp. antigens were associated with NAFLD. Further research is warranted to examine whether H. species are associated with any metabolic condition.

Atrial fibrillation burden and subsequent heart failure events in patients with cardiac resynchronization therapy devices

Tanawuttiwat, T., Lande, J., Smeets, P., Gerritse, B., Nazarian, S., Guallar, E., & Cheng, A. (n.d.).

Publication year

2020

Journal title

Journal of Cardiovascular Electrophysiology

Volume

31

Issue

6

Page(s)

1519-1526

10.1111/jce.14444

Abstract

Abstract

Background: Atrial fibrillation (AF) and heart failure (HF) often coexist but little is known on how AF burden associates with subsequent episodes of HF. Objective: The aim of this study was to quantitatively assess the short- and long-term association of AF burden with subsequent episodes of HF events in patients with reduced ejection fraction. Methods: Patients with cardiac resynchronization therapy (CRT) devices with at least 90 days of device data were included in the study. Time-dependent Cox regression with a 7-day window was used to evaluate the association of short- and long-term AF burden with subsequent HF events. Each patient with HF was matched to two control patients without an HF event based on age, gender, year of implant and CRT defibrillation capability. Results: In our cohort with 2:1 matching (N = 549), 183 patients developed HF events and 275 (50.1%) had AF over an average follow-up of 24 ± 11 months. A 1-hour increase in short-term AF burden was associated with a 3% increased risk of HF events (HR, 1.034; 95% confidence interval [CI], 1.012-1.056; P =.01; HR for 24-hour = 2.23). In contrast, the association between long-term AF burden and subsequent HF events was not statistically significant (HR, 1.009; 95% CI, 0.992-1.026; P =.373). Conclusion: A 24-hour increase in AF burden is associated with a more than two-fold increased risk of HF events over the subsequent week while the long-term AF burden is not significantly associated with HF events.

Author Correction : Perceived stress and non-alcoholic fatty liver disease in apparently healthy men and women (Scientific Reports, (2020), 10, 1, (38), 10.1038/s41598-019-57036-z)

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

Publication year

2020

Journal title

Scientific reports

Volume

10

Issue

1

10.1038/s41598-020-78911-0

Abstract

Abstract

This Article contains an error in the Figure legends of Figure 1, Figure 2 and Figure 3. The legends of these Figures were inadvertently switched. The legend of Figure 1: “Flowchart of study participants.” should read: “Multivariable-adjusted odds ratios (95% CI) for non-alcoholic fatty liver disease (NAFLD) by PSI stress score. The curves represent adjusted odds ratios (solid line) and their 95% confidence intervals (dashed lines) for NAFLD based on restricted cubic splines for PSI stress score with knots at the 5th, 35th, 65th and 95th percentiles (PSI scores 9, 13, 18, and 31, respectively) of their sample distributions. The reference value (diamond dot) was set at the 50th percentile (PSI score 15). The model was adjusted for age, sex, study center, education, marital status, year of visit, smoking, vigorous exercise, alcohol, body mass index, systolic blood pressure, total and HDL cholesterol, triglycerides, and fasting glucose.” The legend of Figure 2: “Multivariable-adjusted odds ratios (95% CI) for non-alcoholic fatty liver disease (NAFLD) by PSI stress score. The curves represent adjusted odds ratios (solid line) and their 95% confidence intervals (dashed lines) for NAFLD based on restricted cubic splines for PSI stress score with knots at the 5th, 35th, 65th and 95th percentiles (PSI scores 9, 13, 18, and 31, respectively) of their sample distributions. The reference value (diamond dot) was set at the 50th percentile (PSI score 15). The model was adjusted for age, sex, study center, education, marital status, year of visit, smoking, vigorous exercise, alcohol, body mass index, systolic blood pressure, total and HDL cholesterol, triglycerides, and fasting glucose.” should read: “Multivariable-adjusted odds ratios (95% confidence interval) comparing the 90th vs the 10th percentiles of PSI stress score (27 vs. 10) by clinically relevant subgroups. Logistic regression models were adjusted for age, sex, study center, education, marital status, year of visit, smoking, vigorous exercise, alcohol, body mass index, systolic blood pressure, total and HDL cholesterol, triglycerides, and fasting glucose.” The legend of Figure 3: “Multivariable-adjusted odds ratios (95% confidence internal) comparing the 90th vs the 10th percentiles of PSI stress score (27 vs. 10) by clinically relevant subgroups. PSI scores were modeled as restricted cubic splines with knots at the 5th, 35th, 65th and 95th percentiles of the sample distribution. Logistic regression models were adjusted for age, sex, study center, education, marital status, year of visit, smoking, vigorous exercise, alcohol, body mass index, systolic blood pressure, total and HDL cholesterol, triglycerides, and fasting glucose.” should read: “Flowchart of study participants.”

Chronic obstructive pulmonary disease and lung cancer incidence in never smokers : A cohort study

Park, H. Y., Kang, D., Shin, S. H., Yoo, K. H., Rhee, C. K., Suh, G. Y., Kim, H., Shim, Y. M., Guallar, E., Cho, J., & Kwon, O. J. (n.d.).

Publication year

2020

Journal title

Thorax

Volume

75

Issue

6

Page(s)

506-509

10.1136/thoraxjnl-2019-213732

Abstract

Abstract

There has been limited evidence for the association between chronic obstructive pulmonary disease (COPD) and the incidence of lung cancer among never smokers. We aimed to estimate the risk of lung cancer incidence in never smokers with COPD, and to compare it with the risk associated with smoking. This cohort study involved 338 548 subjects, 40 to 84 years of age with no history of lung cancer at baseline, enrolled in the National Health Insurance Service National Sample Cohort. During 2 355 005 person-years of follow-up (median follow-up 7.0 years), 1834 participants developed lung cancer. Compared with never smokers without COPD, the fully-adjusted hazard ratios (95% CI) for lung cancer in never smokers with COPD, ever smokers without COPD, and ever smokers with COPD were 2.67 (2.09 to 3.40), 1.97 (1.75 to 2.21), and 6.19 (5.04 to 7.61), respectively. In this large national cohort study, COPD was also a strong independent risk factor for lung cancer incidence in never smokers, implying that COPD patients are at high risk of lung cancer, irrespective of smoking status.

Coffee and tea consumption in the early adult lifespan and left ventricular function in middle age : the CARDIA study

Nwabuo, C. C., Betoko, A. S., Reis, J. P., Moreira, H. T., Vasconcellos, H. D., Guallar, E., Cox, C., Sidney, S., Ambale-Venkatesh, B., Lewis, C. E., Schreiner, P. J., Lloyd-Jones, D., Kiefe, C. I., Gidding, S. S., & Lima, J. A. (n.d.).

Publication year

2020

Journal title

ESC heart failure

Volume

7

Issue

4

Page(s)

1510-1519

10.1002/ehf2.12684

Abstract

Abstract

Aims: The long-term impact of coffee or tea consumption on subclinical left ventricular (LV) systolic or diastolic function has not been previously studied. We examined the association between coffee or tea consumption beginning in early adulthood and cardiac function in midlife. Methods and results: We investigated 2735 Coronary Artery Risk Development in Young Adults (CARDIA) study participants with long-term total caffeine intake, coffee, and tea consumption data from three visits over a 20 year interval and available echocardiography indices at the CARDIA Year-25 exam (2010–2011). Linear regression models were used to assess the association between caffeine intake, tea, and coffee consumption (independent variables) and echocardiography outcomes [LV mass, left atrial volume, and global longitudinal strain (GLS), LV ejection fraction (LVEF), and transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e´)]. Models were adjusted for standard cardiovascular risk factors, socioeconomic status, physical activity, alcohol use, and dietary factors (calorie intake, whole and refined grain intake, and fruit and vegetable consumption). Mean (standard deviation) age was 25.2 (3.5) years at the CARDIA Year-0 exam (1985–1986), 57.4% were women, and 41.9% were African-American. In adjusted multivariable linear regression models assessing the relationship between coffee consumption and GLS, beta coefficients when comparing coffee drinkers of 4 cups/day with non-coffee drinkers were β = −0.30%, P < 0.05; β = −0.35%, P < 0.05; β = −0.32%, P < 0.05; β = −0.40%, P > 0.05; respectively (more negative values implies better systolic function). In adjusted multivariable linear regression models assessing the relationship between coffee consumption and E/e´, beta coefficients when comparing coffee drinkers of 4 cups/day with non-coffee drinkers were β = −0.29, P < 0.05; β = −0.38, P < 0.01; β = −0.20, P >.05; and β = −0.37, P > 0.05, respectively (more negative values implies better diastolic function). High daily coffee consumption (>4 cups/day) was associated with worse LVEF (β = −1.69, P < 0.05). There were no associations between either tea drinking or total caffeine intake and cardiac function (P > 0.05 for all). Conclusions: Low-to-moderate daily coffee consumption from early adulthood to middle age was associated with better LV systolic and diastolic function in midlife. High daily coffee consumption (>4cups/day) was associated with worse LV function. There was no association between caffeine or tea intake and cardiac function.

Cyclic Guanosine Monophosphate and Risk of Incident Heart Failure and Other Cardiovascular Events : the ARIC Study

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

Publication year

2020

Journal title

Journal of the American Heart Association

Volume

9

Issue

2

10.1161/JAHA.119.013966

Abstract

Abstract

Background: Cyclic guanosine monophosphate (cGMP) is a second messenger regulated through natriuretic peptide and nitric oxide pathways. Stimulation of cGMP signaling is a potential therapeutic strategy for heart failure with preserved ejection fraction (HFpEF) and atherosclerotic cardiovascular disease (ASCVD). We hypothesized that plasma cGMP levels would be associated with lower risk for incident HFpEF, any HF, ASCVD, and coronary heart disease (CHD). Methods and Results: We conducted a case–cohort analysis nested in the ARIC (Atherosclerosis Risk in Communities) study. Plasma cGMP was measured in 875 participants at visit 4 (1996–1998), with oversampling of incident HFpEF cases. We used Cox proportional hazard models to assess associations of cGMP with incident HFpEF, HF, ASCVD (CHD+stroke), and CHD. The mean (SD) age was 62.4 (5.6) years and median (interquartile interval) cGMP was 3.4 pmol/mL (2.4–4.6). During a median follow-up of 9.9 years, there were 283 incident cases of HFpEF, 329 any HF, 151 ASCVD, and 125 CHD. In models adjusted for CVD risk factors, the hazard ratios (95% CI) associated with the highest cGMP tertile compared with lowest for HFpEF, HF, ASCVD, and CHD were 1.88 (1.17–3.02), 2.18 (1.18–4.06), 2.84 (1.44–5.60), and 2.43 (1.19–5.00), respectively. In models further adjusted for N-terminal-proB-type natriuretic peptide, associations were attenuated for HFpEF and HF but remained statistically significant for ASCVD (2.56 [1.26–5.20]) and CHD (2.25 [1.07–4.71]). Conclusions: Contrary to our hypothesis, higher cGMP levels were associated with incident CVD in a community-based cohort. The associations of cGMP with HF or HFpEF may be explained by N-terminal-proB-type natriuretic peptide, but not for ASCVD and CHD.

Diabetes mellitus is associated with an increased risk of gastric cancer : a cohort study

Yang, H. J., Kang, D., Chang, Y., Ahn, J., Ryu, S., Cho, J., Guallar, E., & Sohn, C. I. (n.d.).

Publication year

2020

Journal title

Gastric Cancer

Volume

23

Issue

3

Page(s)

382-390

10.1007/s10120-019-01033-8

Abstract

Abstract

Background: Diabetes mellitus (DM) has been considered a potential risk factor for gastric cancer, but the evidence is conflicting. We evaluated the association of DM with incident gastric cancer in a large cohort of men and women with endoscopic assessment at baseline and during follow-up. Methods: We performed a retrospective cohort study of 195,312 adult men and women who underwent upper endoscopy at baseline and during follow-up between 2003 and 2014. DM was defined as fasting serum glucose ≥ 126 mg/dL, self-reported history of DM or current use of antidiabetic medications. Gastric cancer was confirmed histologically. Results: The prevalence of DM at baseline was 3.0% (n = 5774). Over 865,511 person-years of follow-up, 198 participants developed gastric cancer. The fully adjusted hazard ratio (HR) for incident gastric cancer comparing participants with and without DM at baseline was 1.76 [95% confidence interval (CI) 1.04–2.97; P = 0.033). When we evaluated DM as a time-varying covariate, the fully adjusted HR was 1.66 (95% CI 1.04–2.68; P = 0.036). The association between DM and incident gastric cancer did not differ by the presence of intestinal metaplasia (P for interaction = 0.61). Conclusions: In this large cohort with endoscopic follow-up, DM was independently associated with increased gastric cancer incidence. The increased risk was independent of mucosal atrophy and intestinal metaplasia and was consistent in participants with newly developed DM during follow-up. Patients with DM may require more intensive endoscopic follow-up for gastric cancer screening.

Erratum : Risk factors control for primary prevention of cardiovascular disease in men: Evidence from the Aragon Workers Health Study (AWHS) (PLoS ONE (2018) 13:2 0e0193541) DOI: 10.1371/journal.pone.0193541)

Aguilar-Palacio, I., Malo, S., Feja, C., Lallana, M., León-Latre, M., Casasnovas, J. A., Rabanaque, M., & Guallar, E. (n.d.).

Publication year

2020

Journal title

PloS one

Volume

15

Issue

2

10.1371/journal.pone.0228906

Abstract

Abstract

In the Funding section, the information provided is incomplete. The complete, correct Funding section is: This work was supported by the Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER). PI13/01668 (http://www.isciii.es).

Evaluation of mitochondrial DNA copy number estimation techniques

Longchamps, R. J., Castellani, C. A., Yang, S. Y., Newcomb, C. E., Sumpter, J. A., Lane, J., Grove, M. L., Guallar, E., Pankratz, N., Taylor, K. D., Rotter, J. I., Boerwinkle, E., & Arking, D. E. (n.d.).

Publication year

2020

Journal title

PloS one

Volume

15

Issue

1

10.1371/journal.pone.0228166

Abstract

Abstract

Mitochondrial DNA copy number (mtDNA-CN), a measure of the number of mitochondrial genomes per cell, is a minimally invasive proxy measure for mitochondrial function and has been associated with several aging-related diseases. Although quantitative real-time PCR (qPCR) is the current gold standard method for measuring mtDNA-CN, mtDNA-CN can also be measured from genotyping microarray probe intensities and DNA sequencing read counts. To conduct a comprehensive examination on the performance of these methods, we use known mtDNA-CN correlates (age, sex, white blood cell count, Duffy locus genotype, incident cardiovascular disease) to evaluate mtDNA-CN calculated from qPCR, two microarray platforms, as well as whole genome (WGS) and whole exome sequence (WES) data across 1,085 participants from the Atherosclerosis Risk in Communities (ARIC) study and 3,489 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). We observe mtDNA-CN derived from WGS data is significantly more associated with known correlates compared to all other methods (p < 0.001). Additionally, mtDNA-CN measured from WGS is on average more significantly associated with traits by 5.6 orders of magnitude and has effect size estimates 5.8 times more extreme than the current gold standard of qPCR. We further investigated the role of DNA extraction method on mtDNA-CN estimate reproducibility and found mtDNA-CN estimated from cell lysate is significantly less variable than traditional phenol-chloroform-isoamyl alcohol (p = 5.44x10-4) and silica-based column selection (p = 2.82x10-7). In conclusion, we recommend the field moves towards more accurate methods for mtDNA-CN, as well as re-analyze trait associations as more WGS data becomes available from larger initiatives such as TOPMed.

Finding the pathway : Mediation analyses in randomized controlled trials

Localio, A. R., Meibohm, A. R., & Guallar, E. (n.d.).

Publication year

2020

Journal title

Annals of internal medicine

Volume

172

Issue

8

Page(s)

553-557

10.7326/M20-0887

Abstract

Abstract

~

Hyperglycemia, duration of diabetes, and intracranial atherosclerotic stenosis by magnetic resonance angiography : The ARIC-NCS study

Fujiyoshi, A., Suri, M. F., Alonso, A., Selvin, E., Chu, H., Guallar, E., Qiao, Y., Zhang, Y., Wasserman, B. A., & Folsom, A. R. (n.d.).

Publication year

2020

Journal title

Journal of Diabetes and its Complications

Volume

34

Issue

9

10.1016/j.jdiacomp.2020.107605

Abstract

Abstract

Aims: The association of hyperglycemia and duration of diabetes with intracranial atherosclerotic stenosis (ICAS) in the general population is not well documented. We examined whether elevated glucose and longer diabetes duration is independently associated with ICAS in a community-based sample. Methods: We cross-sectionally analyzed 1644 participants (age 67–90 years) of the Atherosclerosis Risk in Communities Study who underwent cerebrovascular magnetic resonance angiography in 2011–13. We applied multivariable ordinal logistic regression to evaluate the association of ICAS category (“no stenosis”, “stenosis

Impact of a topical lotion, CG428, on permanent chemotherapy-induced alopecia in breast cancer survivors : a pilot randomized double-blind controlled clinical trial (VOLUME RCT)

Kang, D., Kim, I. R., Park, Y. H., Im, Y. H., Zhao, D., Guallar, E., Ahn, J. S., & Cho, J. (n.d.).

Publication year

2020

Journal title

Supportive Care in Cancer

Volume

28

Issue

4

Page(s)

1829-1837

10.1007/s00520-019-04982-z

Abstract

Abstract

Purpose: This study aimed to evaluate the impact of a topical lotion (CG428) on hair thickness and density in breast cancer survivors with permanent chemotherapy-induced alopecia (PCIA). Methods: The study was a double-blind, randomized controlled trial which conducted from February 2016 to December 2016 at the Samsung Comprehensive Cancer Center in Seoul, South Korea. Breast cancer patients with PCIA were randomized on average of 3.5 years after chemotherapy. Topical lotion (Batch DT023) is a botanical drug under development containing a novel patented blend of 4 botanical ingredients: citrus, cocoa, guarana, and onion. Participants were asked to self-apply the study product or placebo twice per day for 6 months. Changes in hair density and thickness were assessed using a noninvasive bioengineering device, and patient-reported outcomes were evaluated at 3 and 6 months after randomization. Results: A total of 35 patients were randomized to intervention (N = 18) or placebo (N = 17). Patients in the intervention group were older than those in the placebo group (52.1 vs. 41.6 years; P < 0.001). The mean hair density (SD) at baseline was 97.6 (6.4) and 126.8 (30.3) hairs/cm2 in the intervention and placebo group, respectively (P = 0.005). The corresponding values for hair thickness were 49.9 (12.7) and 48.1 (8.4) μm, respectively. After 6 months, hair density had increased by 34.7 and 24.9% compared with baseline in the intervention and control groups, respectively (P = 0.37). Corresponding values for hair thickness were 19.8 and 35.6%, respectively (P = 0.23). Similar findings were observed after age adjustment. Discussion: In this pilot randomized clinical trial, we observed safety, tolerability, and a trend toward the efficacy of CG428 vs. placebo, especially regarding hair density and self-reported improvement.

Impact of fear of cancer recurrence on survival among lymphoma patients

Kim, S. J., Kang, D., Kim, I. R., Yoon, S. E., Kim, W. S., Butow, P. N., Guallar, E., & Cho, J. (n.d.).

Publication year

2020

Journal title

Psycho-Oncology

Volume

29

Issue

2

Page(s)

364-372

10.1002/pon.5265

Abstract

Abstract

Objective: This study aimed to evaluate fear of cancer recurrence (FCR) among lymphoma patients who completed treatment and its impact on survival and quality of life (QOL). Methods: In this prospective cohort study, 467 lymphoma patients were included who completed treatment with curative intent between February 2012 and March 2017. FCR was measured using a question from the Korean version of the QOL in Cancer Survivors Questionnaire. QOL and general health and functioning were measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30. Participants were actively followed up for all-cause and disease-specific mortality. Results: In total, 16.3% of the patients had severe FCR. The adjusted hazard ratio (HR) for all-cause mortality comparing participants with and without severe FCR was 2.52 (95% CI = 1.15-5.54), and the association was stronger in indolent non-Hodgkin lymphoma (NHL) (HR = 6.77; 95% CI = 1.04-43.92). Participants with severe FCR were also at higher risk of lymphoma-specific mortality (HR = 2.62; 95% CI = 1.13-6.05) than patients without severe FCR. Patients with severe FCR had significantly worse general health status (64.3 vs 71.0, P =.03) and physical (82.4 vs 76.7, P

Impact of serum lipid on breast cancer recurrence

Jung, S. M., Kang, D., Guallar, E., Yu, J., Lee, J. E., Kim, S. W., Nam, S. J., Cho, J., & Lee, S. K. (n.d.).

Publication year

2020

Journal title

Journal of Clinical Medicine

Volume

9

Issue

9

Page(s)

1-14

10.3390/jcm9092846

Abstract

Abstract

The association between serum lipid level and prognosis of breast cancer is controversial. The purpose of this study was to evaluate the impact of serum lipid level in breast cancer recurrence. We analyzed a total of 4190 patients with operable breast cancer who had baseline serum lipid profiles; total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A-1, and apolipoprotein B. Recurrence-free survival is defined as the elapsed time from the date of curative surgery to the detection of any recurrence, and recurrence includes locoregional recurrence, distant metastasis, or both local and distant metastasis. Cox-proportional hazard analysis was used to estimate hazard ratios with 95% confidence intervals (CI) for study outcomes comparing the three lowest quartiles of each lipid parameter to the highest quartile adjusting for age, body mass index (BMI), and pathologic stage, estrogen receptor (ER), progesterone receptor (PR), comorbidities (hypertension, diabetes, or vascular event) at time of breast cancer diagnosis. Patients with dyslipidemia (high bad cholesterol and low good cholesterol level) had worse prognostic factors (i.e., negative hormone receptor status, positive human epidermal growth factor receptor 2 (HER2) expression, higher nuclear grade). After adjusting for these poor prognostic factors, the patients with dyslipidemia showed good prognosis for breast cancer recurrence. Our study showed that baseline high lipid level could be a good prognostic factor of breast cancer. This study indicates that desirable changes in lipid profile for cardiovascular disease risk are not always beneficial for patients with breast cancer. However, as proper control of lipid level has advantages for cardiovascular disease, these findings require careful interpretation.

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

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

Publication year

2020

Journal title

Journal of Viral Hepatitis

Volume

27

Issue

9

Page(s)

896-903

10.1111/jvh.13304

Abstract

Abstract

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

Keeping up with emerging evidence in (almost) real time

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

Publication year

2020

Journal title

Annals of internal medicine

Volume

173

Issue

2

Page(s)

153-154

10.7326/M20-2627

Abstract

Abstract

~

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

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

Publication year

2020

Journal title

Journal of the American Heart Association

Volume

9

Issue

22

10.1161/JAHA.120.016885

Abstract

Abstract

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

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

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

Publication year

2020

Journal title

European Heart Journal

Volume

41

Issue

37

Page(s)

3521-3529

10.1093/eurheartj/ehaa376

Abstract

Abstract

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

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

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

Publication year

2020

Journal title

BMJ Open Diabetes Research and Care

Volume

8

Issue

1

10.1136/bmjdrc-2020-001204

Abstract

Abstract

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

Mitochondrial DNA copy number and incident atrial fibrillation

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

Publication year

2020

Journal title

BMC Medicine

Volume

18

Issue

1

10.1186/s12916-020-01715-6

Abstract

Abstract

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

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

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

Publication year

2020

Journal title

Circulation

Volume

141

Issue

22

Page(s)

1823-1825

10.1161/CIRCULATIONAHA.120.046001

Abstract

Abstract

~

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

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

Publication year

2020

Journal title

Genome Medicine

Volume

12

Issue

1

10.1186/s13073-020-00778-7

Abstract

Abstract

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

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

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

Publication year

2020

Journal title

Archives of Medical Science

Volume

16

Issue

6

Page(s)

1279-1287

10.5114/AOMS.2019.86964

Abstract

Abstract

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

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

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

Publication year

2020

Journal title

Journal of Gastroenterology and Hepatology (Australia)

Volume

35

Issue

5

Page(s)

833-839

10.1111/jgh.14856

Abstract

Abstract

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