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Eliseo Guallar

Eliseo Guallar

Eliseo Guallar

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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

Risk factors control for primary prevention of cardiovascular disease in men : Evidence from the Aragon Workers Health Study (AWHS)

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

Publication year

2018

Journal title

PloS one

Volume

13

Issue

2
Abstract
Abstract
Benefits of cardiovascular disease (CVD) risk factors control are well known, but goals achievement remains low. The objective of this study is to evaluate the prevalence of CVD risk factors among men ina worker’s cohort with no previous CVD, to study control variations across time and the factors associated with poor control. To this end, we conducted a cohort reexamination (2010–2014) within the context of the Aragon Workers Health Study (AWHS). Data from working characteristics, analytical values and pharmacological prescription were included in the analysis. Prevalences of risk factor diagnosis and control were calculated, as well as factors associated with poor control. The prevalence of CVD risk factors was high. In 2014dyslipidaemia was the most prevalent (85.2%) followed by Hypertension (HT) (42.0%). People under treatment increased for the period analysed (p

Serum 25-Hydroxyvitamin D Concentrations Are Associated with Computed Tomography Markers of Subclinical Interstitial Lung Disease among Community-Dwelling Adults in the Multi-Ethnic Study of Atherosclerosis (MESA)

Kim, S. M., Zhao, D., Podolanczuk, A. J., Lutsey, P. L., Guallar, E., Kawut, S. M., Barr, R. G., de Boer, I. H., Kestenbaum, B. R., Lederer, D. J., & Michos, E. D. (n.d.).

Publication year

2018

Journal title

Journal of Nutrition

Volume

148

Issue

7

Page(s)

1126-1134
Abstract
Abstract
Background: Activated vitamin D has anti-inflammatory properties. 25-Hydroxyvitamin D [25(OH)D] deficiency might contribute to subclinical interstitial lung disease (ILD). Objective: We examined associations between serum 25(OH)D concentrations and subclinical ILD among middle-aged to older adults who were free of cardiovascular disease at baseline. Methods: We studied 6302 Multi-Ethnic Study of Atherosclerosis (MESA) participants who had baseline serum 25(OH)D concentrations and computed tomography (CT) imaging spanning ≤ 10 y. Baseline cardiac CT scans (2000–2002) included partial lung fields. Some participants had follow-up cardiac CT scans at exams 2–5 and a full-lung CT scan at exam 5 (2010–2012), with a mean ± SD of 2.1 ± 1.0 scans. Subclinical ILD was defined quantitatively as high-attenuation areas (HAAs) between –600 and –250 Hounsfield units. We assessed associations of 25(OH)D with adjusted HAA volumes and HAA progression. We also examined associations between baseline 25(OH)D and the presence of interstitial lung abnormalities (ILAs) assessed qualitatively (yes or no) from full-lung CT scans at exam 5. Models were adjusted for sociodemographic characteristics, lifestyle factors (including smoking), and lung volumes. Results: The cohort's mean ± SD characteristics were 62.2 ± 10 y for age, 25.8 ± 10.9 ng/mL for 25(OH)D concentrations, and 28.3 ± 5.4 for body mass index (kg/m2); 53% were women, with 39% white, 27% black, 22% Hispanic, and 12% Chinese race/ethnicities. Thirty-three percent had replete (≥30 ng/mL), 35% intermediate (20 to

Serum uric acid levels are associated with cardiovascular risk score : A post hoc analysis of the EURIKA study

Borghi, C., Rodriguez-Artalejo, F., De Backer, G., Dallongeville, J., Medina, J., Nuevo, J., Guallar, E., Perk, J., Banegas, J. R., Tubach, F., Roy, C., & Halcox, J. P. (n.d.).

Publication year

2018

Journal title

International Journal of Cardiology

Volume

253

Page(s)

167-173
Abstract
Abstract
Background Reports are conflicting on whether serum uric acid (sUA) levels are independently associated with increased cardiovascular (CV) death risk. Methods This post hoc analysis assessed the relationship between sUA levels and CV death risk score in 7531 patients from the cross-sectional, multinational EURIKA study (NCT00882336). Patients had at least one CV risk factor but no clinical CV disease. Ten-year risk of CV death was estimated using SCORE-HDL and SCORE algorithms, categorized as low (< 1%), intermediate (1% to < 5%), high (≥ 5% to < 10%) or very high (≥ 10%). Results Mean serum sUA levels increased significantly with increasing CV death risk category in the overall population and in subgroups stratified by diuretics use or renal function (all P < 0.0001). Multivariate ordinal logistic regression analyses, adjusted for factors significantly associated with CV death risk in univariate analyses (study country, body mass index, number of CV risk factors and comorbidities, use of lipid lowering therapies, antihypertensives and antidiabetics), showed a significant association between sUA levels and SCORE-HDL category in the overall population (OR: 1.39 [95% CI: 1.34–1.44]) and all subgroups (using diuretics: 1.32 [1.24–1.40]; not using diuretics: 1.46 [1.39–1.53]; estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2: 1.30 [1.22–1.38]; eGFR ≥ 60 ml/min/1.73 m2: 1.44 [1.38–1.51]; all P < 0.0001). Similar results were obtained when using SCORE. Conclusions Higher sUA levels are associated with progressively higher 10-year CV death risk score in patients with at least one CV risk factor but no CV disease.

Sex hormone levels and change in left ventricular structure among men and post-menopausal women : The Multi-Ethnic Study of Atherosclerosis (MESA)

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

Publication year

2018

Journal title

Maturitas

Volume

108

Page(s)

37-44
Abstract
Abstract
Objective Sex hormone (SH) levels may contribute to sex differences in the risk of heart failure with preserved ejection fraction (HFpEF). We examined the associations of SH levels with left ventricular mass (LVM) and mass (M):volume (V) ratio, which are risk markers for HFpEF. Study design We studied 1941 post-menopausal women and 2221 men, aged 45–84 years, participating in the Multi-Ethnic Study of Atherosclerosis (MESA). Serum SH levels, cardiac magnetic resonance imaging (MRI) and ejection fraction (EF) ≥50% had been recorded at baseline (2000–2002). Of these participants, 2810 underwent repeat MRI at Exam 5 (2010–2012). Stratified by sex, linear mixed-effect models were used to test associations between SH and sex hormone binding globulin (SHBG) level [per 1 SD greater log-transformed (SH)] with baseline and change in LV structure. Models were adjusted for age, race/ethnicity, center, height, weight, education, physical activity and smoking, and, in women, for hormone therapy and years since menopause. Main outcome measures LVM and M:V ratio. Results After a median of 9.1 years, higher free testosterone levels were independently associated with a modest increase in LVM (g/yr) in women [0.05 (95% CI 0.01, 0.10)] and men [0.16 (0.03, 0.28)], while higher SHBG levels were associated with less LVM change (g/yr) in women [−0.07 (−0.13, −0.01)] and men [−0.15 (−0.27, −0.02)]. In men, higher dehydroepiandrosterone and estradiol levels were associated with increased LVM. Among women, free testosterone levels were positively and SHBG levels inversely associated with change in M:V ratio. Conclusion A more androgenic profile (higher free testosterone and lower SHBG levels) is associated with a greater increase in LVM in men and women and greater increase in M:V ratio in women over the course of 9 years.

Sleep duration and subclinical atherosclerosis : The Aragon Workers' Health Study

Blasco-Colmenares, E., Moreno-Franco, B., Latre, M. L., Mur-Vispe, E., Pocovi, M., Jarauta, E., Civeira, F., Laclaustra, M., Casasnovas, J. A., & Guallar, E. (n.d.).

Publication year

2018

Journal title

Atherosclerosis

Volume

274

Page(s)

35-40
Abstract
Abstract
Background and aims: Few studies have evaluated the association of sleep duration with subclinical atherosclerosis, and with heterogeneous findings. We evaluated the association of sleep duration with the presence of coronary, carotid, and femoral subclinical atherosclerosis in healthy middle-age men with low prevalence of clinical comorbidities. Methods: We performed a cross-sectional analysis of 1968 men, 40–60 years of age, participating in the Aragon Workers' Health Study (AWHS). Duration of sleep during a typical work week was assessed by questionnaire. Coronary artery calcium scores (CACS) was assessed by computed tomography and the presence of carotid plaque and femoral plaque by ultrasound. Results: In fully adjusted models, the odds ratios (95% CI) for CACS >0 comparing sleep durations of ≤5, 6, and ≥8 h with 7 h were 1.34 (0.98–1.85), 1.35 (1.08–1.69) and 1.21 (0.90–1.62), respectively (p = 0.04). A similar U-shaped association was observed for CACS ≥100 and for CACS. The corresponding odds ratios for the presence of at least one carotid plaque were ≤5, 6, and ≥8 h with 7 h were 1.23 (0.88–1.72), 1.09 (0.86–1.38), and 0.86 (0.63–1.17), respectively (p = 0.31), and for the presence of at least one femoral plaque were 1.25 (0.87–1.80), 1.19 (0.93–1.51) and 1.17 (0.86–1.61), respectively (p = 0.39). Conclusions: Middle-aged men reporting 7 h of sleep duration had the lowest prevalence of subclinical coronary atherosclerosis as assessed by CACs. Our results support that men with very short or very long sleep durations are at increased risk of atherosclerosis.

Subclinical Hypothyroidism and Incident Depression in Young and Middle-Age Adults

Kim, J. S., Zhang, Y., Chang, Y., Ryu, S., Guallar, E., Shin, Y. C., Shin, H., Lim, S. W., & Cho, J. (n.d.).

Publication year

2018

Journal title

Journal of Clinical Endocrinology and Metabolism

Volume

103

Issue

5

Page(s)

1827-1833
Abstract
Abstract
Background: The role of subclinical hypothyroidism in the development of depression remains controversial. We examined the prospective association between subclinical hypothyroidism and incident depressive symptoms. Methods: We conducted a prospective cohort study of 220,545 middle-age adults without depression who had undergone at least two comprehensive health examinations between 1 January 2011 and 31 December 2014. Thyroid-stimulating hormone, free triiodothyronine (FT3), and free thyroxine (FT4) levels were measured using an electrochemiluminescent immunoassay. The study outcome was incident depressive symptoms, defined as a Center for Epidemiologic Studies- Depression score .16. Results: During a median follow-up period of 2 years, incident depressive symptoms occurred in 7323 participants. The multivariable-adjusted hazard ratio for incident depressive symptoms comparing subclinical hypothyroid and euthyroid participants was 0.97 (95% confidence interval, 0.87 to 1.09). Similarly, among euthyroid participants (n = 87,822), no apparent association was found between thyroid hormone levels and an increased risk of incident depressive symptoms. Conclusions: No apparent association was found between subclinical hypothyroidism and incident depressive symptoms in a large prospective cohort of middle-age men and women.

Synergistic opportunities in the interplay between cancer screening and cardiovascular disease risk assessment : Together we are stronger

Handy, C. E., Quispe, R., Pinto, X., Blaha, M. J., Blumenthal, R. S., Michos, E. D., Lima, J. A., Guallar, E., Ryu, S., Cho, J., Kaye, J. A., Comin-Colet, J., Corbella, X., & Cainzos-Achirica, M. (n.d.).

Publication year

2018

Journal title

Circulation

Volume

138

Issue

7

Page(s)

727-734
Abstract
Abstract
Cardiovascular disease (CVD) and cancer continue to be the 2 leading causes of death in developed countries despite significant improvements in the prevention, screening, and treatment of both diseases. They remain significant public health problems, growing in importance globally. Despite this threat, the fields of cardiology and oncology have been relatively disconnected. With many shared modifiable risk factors, cancer and CVD often coexist in the same individuals; those diagnosed with lung cancer, breast cancer, and colon cancer are at higher risk of CVD, and those with CVD are at higher risk of developing many types of common cancers. Screening paradigms have been established in parallel, but there are opportunities for combined risk assessments for cancer and CVD risk. Joining forces for combined cardiovascular and hemato-oncological preventive and research efforts will likely have synergistic, worldwide public health benefits.

Systematic review for the 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults a report of the American College of Cardiology/American Heart Association Task Force on Clinical practice guidelines

American College of Cardiology, A., American College of Cardiology/American Heart Association, A., Reboussin, D. M., Allen, N. B., Griswold, M. E., Guallar, E., Hong, Y., Lackland, D. T., Miller, E. R., Polonsky, T., Thompson-Paul, A. M., Vupputuri, S., Levine, G. N., O'Gara, P. T., Halperin, J. L., Past, I., Al-Khatib, S. M., Beckman, J. A., Birtcher, K. K., … Hundley, J. (n.d.).

Publication year

2018

Journal title

Hypertension

Volume

71

Issue

6

Page(s)

E116-E135
Abstract
Abstract
Objective-To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy? Methods-Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses. Results-Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of

Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults : A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

Reboussin, D. M., Allen, N. B., Griswold, M. E., Guallar, E., Hong, Y., Lackland, D. T., Miller, E. (., Polonsky, T., Thompson-Paul, A. M., & Vupputuri, S. (n.d.).

Publication year

2018

Journal title

Journal of the American College of Cardiology

Volume

71

Issue

19

Page(s)

2176-2198
Abstract
Abstract
Objective: To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy? Methods: Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses. Results: Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of

Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults : A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

Reboussin, D. M., Allen, N. B., Griswold, M. E., Guallar, E., Hong, Y., Lackland, D. T., Miller, E. P., Polonsky, T., Thompson-Paul, A. M., & Vupputuri, S. (n.d.).

Publication year

2018

Journal title

Circulation

Volume

138

Issue

17

Page(s)

e595-e616
Abstract
Abstract
Objective To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy? Methods Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses. Results Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of

Usefulness of Lipoprotein-Associated Phospholipase A 2 Activity and C-Reactive Protein in Identifying High-Risk Smokers for Atherosclerotic Cardiovascular Disease (from the Atherosclerosis Risk in Communities Study)

Tibuakuu, M., Kianoush, S., DeFilippis, A. P., McEvoy, J. W., Zhao, D., Guallar, E., Ballantyne, C. M., Hoogeveen, R. C., Blaha, M. J., & Michos, E. D. (n.d.).

Publication year

2018

Journal title

American Journal of Cardiology

Volume

121

Issue

9

Page(s)

1056-1064
Abstract
Abstract
Despite the causal role of cigarette smoking in atherosclerotic cardiovascular disease (ASCVD), the underlying mechanisms are not fully understood. We evaluated the joint relation between smoking and inflammatory markers with ASCVD risk. We tested cross-sectional associations of self-reported smoking status (never, former, current) and intensity (packs/day) with lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) activity and high-sensitivity C-reactive protein (hsCRP) in 10,506 Atherosclerosis Risk in Communities participants at Visit 4 (1996 to 1998). Using Cox hazard models adjusted for demographic and traditional ASCVD risk factors, we examined the associations of smoking status and intensity with incident adjudicated ASCVD events (n = 1,745 cases) over an average of 17 years, stratified by Lp-PLA 2 and hsCRP categories. Greater packs/day smoked was linearly associated with higher levels of both Lp-PLA 2 and hsCRP among current smokers. Compared with never smokers, the hazard ratio for incident ASCVD in current smokers was 2.04 (95% CI 1.76 to 2.35). Among current smokers, the risk for ASCVD per 1 pack/day greater was 1.39 (1.10 to 1.76). Both Lp-PLA 2 activity ≥253 nmol/min/ml and hsCRP >3 mg/L identified current smokers at the highest risk for incident ASCVD, with similar hazard ratios. hsCRP risk-stratified current smokers better based on intensity. Among current smokers, hsCRP improved ASCVD prediction beyond traditional risk factors better than Lp-PLA 2 (C-statistic 0.675 for hsCRP vs 0.668 for Lp-PLA2, p = 0.001). In this large cohort with long follow-up, we found a dose-response relation between smoking intensity with Lp-PLA 2 activity, hsCRP, and ASCVD events. Although both Lp-PLA 2 activity and hsCRP categories identified high risk among current smokers, hsCRP may better stratify risk of future ASCVD.

Vitamin D deficiency is associated with inferior survival of patients with extranodal natural killer/T-cell lymphoma

Kim, S. J., Shu, C., Ryu, K. J., Kang, D., Cho, J., Ko, Y. H., Lee, S. Y., Guallar, E., Zhao, W., & Kim, W. S. (n.d.).

Publication year

2018

Journal title

Cancer Science

Volume

109

Issue

12

Page(s)

3971-3980
Abstract
Abstract
Vitamin D deficiency is a common health issue; however, the effect of vitamin D deficiency on the survival of T-cell lymphoma is still not clear. We evaluated the impact of serum vitamin D level of patients with peripheral T-cell lymphoma (PTCL) and extranodal natural killer/T-cell lymphoma (ENKTL) on survival outcome. Pretreatment levels of 25-hydroxyvitamin D [25(OH)D] and inflammatory cytokines were measured in serum samples that were archived at diagnosis, and we evaluated their association with survival in newly diagnosed patients with PTCL (n = 137) and ENKTL (n = 114) at a university-based hospital in Korea. An independent cohort from Rui Jin Hospital (Shanghai, China) was used for validation. The median 25(OH)D serum level was 12.0 ng/mL (1.3-60.0 ng/mL), and 40% had less than 10 ng/mL, which was defined as vitamin D deficiency. Median serum 25(OH)D levels were similar between PTCL (11.5 ng/mL) and ENKTL (12.9 ng/mL); however, vitamin D deficiency was associated with inferior survival in ENKTL but not with PTCL. The independent validation cohort (n = 115) also showed a significant association of vitamin D deficiency with poor survival in ENKTL. The 25(OH)D level had an inverse relation with inflammatory cytokines; this association had a negative effect only on survival of ENKTL, and not on PTCL. In conclusion, vitamin D deficiency was associated with inferior survival outcome of patients with ENKTL.

A gene-environment interaction analysis of plasma selenium with prevalent and incident diabetes : The Hortega study

Galan-Chilet, I., Grau-Perez, M., De Marco, G., Guallar, E., Martin-Escudero, J. C., Dominguez-Lucas, A., Gonzalez-Manzano, I., Lopez-Izquierdo, R., Briongos-Figuero, L. S., Redon, J., Chaves, F. J., & Tellez-Plaza, M. (n.d.).

Publication year

2017

Journal title

Redox Biology

Volume

12

Page(s)

798-805
Abstract
Abstract
Background Selenium and single-nucleotide-polymorphisms in selenoprotein genes have been associated to diabetes. However, the interaction of selenium with genetic variation in diabetes and oxidative stress-related genes has not been evaluated as a potential determinant of diabetes risk. Methods We evaluated the cross-sectional and prospective associations of plasma selenium concentrations with type 2 diabetes, and the interaction of selenium concentrations with genetic variation in candidate polymorphisms, in a representative sample of 1452 men and women aged 18–85 years from Spain. Results The geometric mean of plasma selenium levels in the study sample was 84.2 µg/L. 120 participants had diabetes at baseline. Among diabetes-free participants who were not lost during the follow-up (N=1234), 75 developed diabetes over time. The multivariable adjusted odds ratios (95% confidence interval) for diabetes prevalence comparing the second and third to the first tertiles of plasma selenium levels were 1.80 (1.03, 3.14) and 1.97 (1.14, 3.41), respectively. The corresponding hazard ratios (95% CI) for diabetes incidence were 1.76 (0.96, 3.22) and 1.80 (0.98, 3.31), respectively. In addition, we observed significant interactions between selenium and polymorphisms in PPARGC1A, and in genes encoding mitochondrial proteins, such as BCS1L and SDHA, and suggestive interactions of selenium with other genes related to selenoproteins and redox metabolism. Conclusions Plasma selenium was positively associated with prevalent and incident diabetes. While the statistical interactions of selenium with polymorphisms involved in regulation of redox and insulin signaling pathways provide biological plausibility to the positive associations of selenium with diabetes, further research is needed to elucidate the causal pathways underlying these associations.

Aflatoxin and viral hepatitis exposures in Guatemala : Molecular biomarkers reveal a unique profile of risk factors in a region of high liver cancer incidence

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

Publication year

2017

Journal title

PloS one

Volume

12

Issue

12
Abstract
Abstract
Liver cancer is an emerging global health issue, with rising incidence in both the United States and the economically developing world. Although Guatemala experiences the highest rates of this disease in the Western hemisphere and a unique 1:1 distribution in men and women, few studies have focused on this population. Thus, we determined the prevalence and correlates of aflatoxin B1 (AFB1) exposure and hepatitis virus infection in Guatemalan adults. Healthy men and women aged 40 years (n = 461), residing in five departments of Guatemala, were enrolled in a cross-sectional study from May—October of 2016. Serum AFB1-albumin adducts were quantified using isotope dilution mass spectrometry. Multivariate linear regression was used to assess relationships between AFB1-albumin adduct levels and demographic factors. Biomarkers of hepatitis B virus and hepatitis C virus infection were assessed by immunoassay and analyzed by Fisher’s exact test. AFB1-albumin adducts were detected in 100% of participants, with a median of 8.4 pg/mg albumin (range, 0.2–814.8). Exposure was significantly higher (p

Airflow limitation severity and post-operative pulmonary complications following extra-pulmonary surgery in COPD patients

Shin, B., Lee, H., Kang, D., Jeong, B. H., Kang, H. K., Chon, H. R., Koh, W. J., Chung, M. P., Guallar, E., Cho, J., & Park, H. Y. (n.d.).

Publication year

2017

Journal title

Respirology

Volume

22

Issue

5

Page(s)

935-941
Abstract
Abstract
Background and objective: The association between airflow limitation severity and post-operative pulmonary complications (PPCs) among COPD patients undergoing extra-pulmonary surgery is unknown. We evaluated the association between forced expiratory volume in 1 s (FEV1) and PPC in COPD patients undergoing extra-pulmonary surgery. Methods: Using prospective cohort of PPC evaluation for extra-pulmonary surgery, we identified 694 COPD patients who conducted PPC evaluation before extra-pulmonary surgery between March 2014 and January 2015 at a tertiary hospital, Seoul, Korea. Results: The overall incidence of PPC was 24.4%. The incidence of PPC in quintiles 1–5 of FEV1 (% predicted) was 31.4, 25.8, 23.7, 21.6 and 19.7%, respectively (P for trend: 0.019). In fully adjusted multivariable models, the relative risks (RRs, 95% CI) for PPC comparing participants in quintiles 1–4 of FEV1 (% predicted) with those in quintile 5 were 1.69 (1.03–2.79), 1.41 (0.83–2.37), 1.26 (0.75–2.11) and 1.30 (0.76–2.22), respectively (P for trend: 0.046). The association of severe airflow limitation with respiratory failure and post-operative exacerbations was stronger in participants who did not use bronchodilators compared with those who did. Conclusion: We found a progressive and significant relationship between severity of airflow limitation and the incidence of PPC in COPD patients undergoing extra-pulmonary surgery. Furthermore, perioperative bronchodilator use was associated with a reduced risk of respiratory failure and post-operative exacerbations in patients with severe airflow limitation.

Aortic Arch Pulse Wave Velocity Assessed by Magnetic Resonance Imaging as a Predictor of Incident Cardiovascular Events : The MESA (Multi-Ethnic Study of Atherosclerosis)

Ohyama, Y., Ambale-Venkatesh, B., Noda, C., Kim, J. Y., Tanami, Y., Teixido-Tura, G., Chugh, A. R., Redheuil, A., Liu, C. Y., Wu, C. O., Hundley, W. G., Bluemke, D. A., Guallar, E., & Lima, J. A. (n.d.).

Publication year

2017

Journal title

Hypertension

Volume

70

Issue

3

Page(s)

524-530
Abstract
Abstract
The predictive value of aortic arch pulse wave velocity (PWV) assessed by magnetic resonance imaging for cardiovascular disease (CVD) events has not been fully established. The aim of the present study was to evaluate the association of arch PWV with incident CVD events in MESA (Multi-Ethnic Study of Atherosclerosis). Aortic arch PWV was measured using magnetic resonance imaging at baseline in 3527 MESA participants (mean age, 62±10 years at baseline; 47% men) free of overt CVD. Cox regression was used to evaluate the risk of incident CVD (coronary heart disease, stroke, transient ischemic attack, or heart failure) in relation to arch PWV adjusted for age, sex, race, and CVD risk factors. The median value of arch PWV was 7.4 m/s (interquartile range, 5.6-10.2). There was significant interaction between arch PWV and age for outcomes, so analysis was stratified by age categories (45-54 and >54 years). There were 456 CVD events during the 10-year follow-up. Forty-five to 54-year-old participants had significant association of arch PWV with incident CVD independent of CVD risk factors (hazard ratio, 1.44; 95% confidence interval, 1.07-1.95; P=0.018; per 1-SD increase for logarithmically transformed PWV), whereas >54-year group did not (P=0.93). Aortic arch PWV assessed by magnetic resonance imaging is a significant predictor of CVD events among middle-aged (45-54 years old) individuals, whereas arch PWV is not associated with CVD among an elderly in a large multiethnic population.

Association between mitochondrial DNA copy number and sudden cardiac death : Findings from the Atherosclerosis Risk in Communities study (ARIC)

Zhang, Y., Guallar, E., Ashar, F. N., Longchamps, R. J., Castellani, C. A., Lane, J., Grove, M. L., Coresh, J., Sotoodehnia, N., Ilkhanoff, L., Boerwinkle, E., Pankratz, N., & Arking, D. E. (n.d.).

Publication year

2017

Journal title

European Heart Journal

Volume

38

Issue

46

Page(s)

3443-3448
Abstract
Abstract
Aims Sudden cardiac death (SCD) is a major public health burden. Mitochondrial dysfunction has been implicated in a wide range of cardiovascular diseases including cardiomyopathy, heart failure, and arrhythmias, but it is unknown if it also contributes to SCD risk. We sought to examine the prospective association between mtDNA copy number (mtDNA-CN), a surrogate marker of mitochondrial function, and SCD risk. Methods and results We measured baseline mtDNA-CN in 11 093 participants from the Atherosclerosis Risk in Communities (ARIC) study. mtDNA copy number was calculated from probe intensities of mitochondrial single nucleotide polymorphisms (SNP) on the Affymetrix Genome-Wide Human SNP Array 6.0. Sudden cardiac death was defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual without evidence of a non-cardiac cause of cardiac arrest. Sudden cardiac death cases were reviewed and adjudicated by an expert committee. During a median follow-up of 20.4 years, we observed 361 SCD cases. After adjusting for age, race, sex, and centre, the hazard ratio for SCD comparing the 1st to the 5th quintiles of mtDNA-CN was 2.24 (95% confidence interval 1.58-3.19; P-trend

Association of low-moderate arsenic exposure and arsenic metabolism with incident diabetes and insulin resistance in the strong heart family study

Grau-Perez, M., Kuo, C. C., Gribble, M. O., Balakrishnan, P., Spratlen, M. J., Vaidya, D., Francesconi, K. A., Goessler, W., Guallar, E., Silbergeld, E. K., Umans, J. G., Best, L. G., Lee, E. T., Howard, B. V., Cole, S. A., & Navas-Acien, A. (n.d.).

Publication year

2017

Journal title

Environmental health perspectives

Volume

125

Issue

12
Abstract
Abstract
BACKGROUND: High arsenic exposure has been related to diabetes, but at low-moderate levels the evidence is mixed. Arsenic metabolism, which is partly genetically controlled and may rely on certain B vitamins, plays a role in arsenic toxicity. OBJECTIVE: We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance. METHODS: We included 1,838 American Indian men and women free of diabetes (median age, 36 y). Arsenic exposure was assessed as the sum of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) urine concentrations (RAs). Arsenic metabolism was evaluated by the proportions of iAs, MMA, and DMA over their sum (iAs%, MMA%, and DMA%). Homeostasis model assessment for insulin resistance (HOMA2-IR) was measured at baseline and follow-up visits. Incident diabetes was evaluated at follow-up. RESULTS: Median RAs, iAs%, MMA%, and DMA% was 4:4 lg=g creatinine, 9.5%, 14.4%, and 75.6%, respectively. Over 10,327 person-years of follow-up, 252 participants developed diabetes. Median HOMA2-IR at baseline was 1.5. The fully adjusted hazard ratio [95% confidence interval (CI)] for incident diabetes per an interquartile range increase in RAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. RAs was positively associated with HOMA2-IR at baseline but negatively with HOMA2-IR at follow-up. Increased MMA% was associated with lower HOMA2-IR when either iAs% or DMA% decreased. The association of arsenic metabolism with HOMA2-IR differed by B-vitamin intake and AS3MT genetics variants. CONCLUSIONS: Among participants without baseline prediabetes, arsenic exposure was associated with incident diabetes. Low MMA% was cross-sectional and prospectively associated with higher HOMA2-IR. Research is needed to confirm possible interactions of arsenic metabolism with B vitamins and AS3MT variants on diabetes risk. https://doi.org/10.1289/EHP2566.

Association of mitochondrial DNA copy number with cardiovascular disease

Ashar, F. N., Zhang, Y., Longchamps, R. J., Lane, J., Moes, A., Grove, M. L., Mychaleckyj, J. C., Taylor, K. D., Coresh, J., Rotter, J. I., Boerwinkle, E., Pankratz, N., Guallar, E., & Arking, D. E. (n.d.).

Publication year

2017

Journal title

JAMA Cardiology

Volume

2

Issue

11

Page(s)

1247-1255
Abstract
Abstract
IMPORTANCE: Mitochondrial dysfunction is a core component of the aging process and may play a key role in atherosclerotic cardiovascular disease. Mitochondrial DNA copy number (mtDNA-CN), which represents the number of mitochondria per cell and number of mitochondrial genomes per mitochondrion, is an indirect biomarker of mitochondrial function. OBJECTIVE: To determine whether mtDNA-CN, measured in an easily accessible tissue (buffy coat/circulating leukocytes), can improve risk classification for cardiovascular disease (CVD) and help guide initiation of statin therapy for primary prevention of CVD. DESIGN, SETTING, AND PARTICIPANTS: Prospective, population-based cohort analysis including 21 870 participants (20 163 free from CVD at baseline) from 3 studies: Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities Study (ARIC), and Multiethnic Study of Atherosclerosis (MESA). The mean follow-up was 13.5 years. The study included 11 153 participants from ARIC, 4830 from CHS, and 5887 from MESA. Analysis of the data was conducted from March 10, 2014, to January 29, 2017. EXPOSURES: Mitochondrial DNA-CN measured from buffy coat/circulating leukocytes. MAIN OUTCOMES AND MEASURES: Incident CVD, which combines coronary heart disease, defined as the first incident myocardial infarction or death owing to coronary heart disease, and stroke, defined as the first nonfatal stroke or death owing to stroke. RESULTS: Of the 21 870 participants, the mean age was 62.4 years (ARIC, 57.9 years; MESA, 62.4 years; and CHS, 72.5 years), and 54.7% of participants were women. The hazard ratios for incident coronary heart disease, stroke, and CVD associated with a 1-SD decrease in mtDNA-CN were 1.29 (95% CI, 1.24-1.33), 1.11 (95% CI, 1.06-1.16), and 1.23 (95% CI, 1.19-1.26). The associations persisted after adjustment for traditional CVD risk factors. Addition of mtDNA-CN to the 2013 American College of Cardiology/American Heart Association Pooled Cohorts Equations for estimating 10-year hard atherosclerosis CVD risk was associated with improved risk classification (continuous net reclassification index, 0.194; 95% CI, 0.130-0.258; P < .001). Mitochondrial DNA-CN further improved sensitivity and specificity for the 2013 American College of Cardiology/American Heart Association recommendations on initiating statin therapy for primary prevention of ASCVD (net 221 individuals appropriately downclassified and net 15 individuals appropriately upclassified). CONCLUSIONS AND RELEVANCE: Mitochondrial DNA-CN was independently associated with incident CVD in 3 large prospective studies and may have potential clinical utility in improving CVD risk classification.

Association of parathyroid hormone with 20-year cognitive decline

Kim, S. M., Zhao, D., Schneider, A. L., Korada, S. K., Lutsey, P. L., Guallar, E., Alonso, A., Gwen Windham, B., Gottesman, R. F., & Michos, E. D. (n.d.).

Publication year

2017

Journal title

Neurology

Volume

89

Issue

9

Page(s)

918-926
Abstract
Abstract
Objective: We hypothesized that elevated parathyroid hormone (PTH) levels will be independently associated with 20-year cognitive decline in a large population-based cohort. Methods: We studied 12,964 middle-aged white and black ARIC participants without a history of prior stroke who, in 1990-1992 (baseline), had serum PTH levels measured and cognitive function testing, with repeat cognitive testing performed at up to 2 follow-up visits. Cognitive testing included the Delayed Word Recall, the Digit Symbol Substitution, and the Word Fluency tests, which were summed as a global Z score. Using mixed-effects models, we compared the relative decline in individual and global cognitive scores between each of the top 3 quartiles of PTH levels to the reference bottom quartile. We adjusted for demographic variables, education, vascular risk factors, and levels of calcium, phosphate, and vitamin D. We imputed missing covariate and follow-up cognitive data to account for attrition. Results: The mean (SD) age of our cohort was 57 (6) years, 57% were women, and 24% were black. There was no cross-sectional association of elevated PTH with cognitive global Z score at baseline (p > 0.05). Over a median of 20.7 years, participants in each PTH quartile showed a decline in cognitive function. However, there was no significant difference in cognitive decline between each of the top 3 quartiles and the lowest reference quartile (p > 0.05). In a subset, there was also no association of higher mid-life PTH levels with late-life prevalent adjudicated dementia (p > 0.05). Conclusions: Our work does not support an independent influence of PTH on cognitive decline in this population-based cohort study.

Associations of Coffee, Tea, and Caffeine Intake with Coronary Artery Calcification and Cardiovascular Events

Miller, P. E., Zhao, D., Frazier-Wood, A. C., Michos, E. D., Averill, M., Sandfort, V., Burke, G. L., Polak, J. F., Lima, J. A., Post, W. S., Blumenthal, R. S., Guallar, E., & Martin, S. S. (n.d.).

Publication year

2017

Journal title

American Journal of Medicine

Volume

130

Issue

2

Page(s)

188-197.e5
Abstract
Abstract
Background Coffee and tea are 2 of the most commonly consumed beverages in the world. The association of coffee and tea intake with coronary artery calcium and major adverse cardiovascular events remains uncertain. Methods We examined 6508 ethnically diverse participants with available coffee and tea data from the Multi-Ethnic Study of Atherosclerosis. Intake for each was classified as never, occasional (

Associations of Lipoprotein(a) levels with incident atrial fibrillation and Ischemic Stroke : The ARIC (Atherosclerosis Risk in Communities) study

Aronis, K. N., Di Zhao, Z., Hoogeveen, R. C., Alonso, A., Ballantyne, C. M., Guallar, E., Jones, S. R., Martin, S. S., Nazarian, S., Steffen, B. T., Virani, S. S., & Michos, E. D. (n.d.).

Publication year

2017

Journal title

Journal of the American Heart Association

Volume

6

Issue

12
Abstract
Abstract
Background--Lipoprotein(a) (Lp[a]) is proatherosclerotic and prothrombotic, causally related to coronary disease, and associated with other cardiovascular diseases. The association of Lp(a) with incident atrial fibrillation (AF) and with ischemic stroke among individuals with AF remains to be elucidated. Methods and Results--In the community-based ARIC (Atherosclerosis Risk in Communities) study cohort, Lp(a) levels were measured by a Denka Seiken assay at visit 4 (1996-1998). We used multivariable-adjusted Cox models to compare AF and ischemic stroke risk across Lp(a) levels. First, we evaluated incident AF in 9908 participants free of AF at baseline. AF was ascertained by electrocardiography at study visits, hospital International Statistical Classification of Diseases, 9th Revision (ICD-9) codes, and death certificates. We then evaluated incident ischemic stroke in 10 127 participants free of stroke at baseline. Stroke was identified by annual phone calls, hospital ICD-9 Revision codes, and death certificates. The baseline age was 62.7±5.6 years. Median Lp(a) levels were 13.3 mg/dL (interquartile range, 5.2-39.7 mg/dL). Median follow-up was 13.9 and 15.8 years for AF and stroke, respectively. Lp(a) was not associated with incident AF (hazard ratio, 0.98; 95% confidence interval, 0.82-1.17), comparing those with Lp(a) ≥50 with those with Lp(a) < 10 mg/dL. High Lp(a) was associated with a 42% relative increase in stroke risk among participants without AF (hazard ratio, 1.42; 95% confidence interval, 1.07-1.90) but not in those with AF (hazard ratio, 1.06; 95% confidence interval, 0.70-1.61 [P interaction for AF=0.25]). There were no interactions by race or sex. No association was found for cardioembolic stroke subtype. Conclusions--High Lp(a) levels were not associated with incident AF. Lp(a) levels were associated with increased ischemic stroke risk, primarily among individuals without AF but not in those with AF.

Attitudes toward cancer and cancer patients in an Urban Iranian population

Badihian, S., Choi, E. K., Kim, I. R., Parnia, A., Manouchehri, N., Badihian, N., Tanha, J. M., Guallar, E., & Cho, J. (n.d.).

Publication year

2017

Journal title

Oncologist

Volume

22

Issue

8

Page(s)

944-950
Abstract
Abstract
Background. Because of the significant incidence and mortality of cancer in Iran, a Comprehensive National Cancer Control Program for the prevention and early detection of cancer was launched in 2007. However, cancer awareness and screening rates in Iran did not improve. This study aimed to evaluate public attitudes toward cancer and cancer patients in Iran. Materials and Methods.We conducted a cross-sectional survey among 953 non-institutionalized individuals in Isfahan, Iran, from November 2014 to February 2015. We collected data on attitudes toward cancer in three domains (impossibility of recovery, cancer stereotypes, and discrimination), as well as questions on willingness to disclose a cancer diagnosis. Results. Among all participants, 33.9% agreed that it is very difficult to regain one’s health after a cancer diagnosis, 17.4% felt uncomfortable with a cancer patient, and 26.9% said that they would avoid marrying people whose family members had cancer. While 88.9% of study participants said that cancer patients deserve to be protected in society, 53.3% and 48.4% of participants agreed that they would not disclose a cancer diagnosis to neighbors and coworkers, respectively. Conclusion. Negative attitudes with respect to impossibility of recovery and discrimination toward cancer and cancer patients were common among urban Iranians. Most people would not disclose a cancer diagnosis to others in spite of advancements in cancer diagnosis and treatment, reflecting unfavorable attitudes toward cancer and cancer patients in society. Successful implementation of cancer awareness and prevention programs in Iran may require social changes based on adequate information on cancer and cancer patients.

Baseline and change in uric acid concentration over time are associated with incident hypertension in large Korean cohort

Sung, K. C., Byrne, C. D., Ryu, S., Lee, J. Y., Lee, S. H., Kim, J. Y., Kim, S. H., Wild, S. H., & Guallar, E. (n.d.).

Publication year

2017

Journal title

American Journal of Hypertension

Volume

30

Issue

1

Page(s)

42-50
Abstract
Abstract
BACKGROUND It is uncertain whether high-baseline uric acid (UA) or change in UA concentration over time is related to development of incident hypertension. To investigate relationships between: (i) baseline serum UA concentration and (ii) change in UA concentration and incident hypertension. METHODS About 96,606 Korean individuals (with follow-up UA data available for 56,085 people) participating in a health check program was undertaken. Cox regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident hypertension according to UA quartiles regarding the lowest UA quartile as the reference, and also according to change in UA concentration comparing individuals with an increase in UA to those with a decrease in UA concentration over time. RESULTS Total follow up time was 8 years (median follow-up 3.3 years; interquartile range, 1.9-5.1). About 10,405 cases of incident hypertension occurred. In the fully adjusted regression models, the HRs (95% CI) for incident hypertension comparing the highest vs. the lowest quartiles of UA were 1.29 (1.19-1.38) in men and 1.24 (1.09-1.42) in women, with statistically significant P for trend for both gender. Additionally, stable or increasing UA concentration over time was associated with increased risk of incident hypertension, particularly in participants with baseline UA concentration ≥median (aHRs 1.14; 95% CI (1.03-1.26) and 1.18; 95% CI (0.98-1.40) in men and women, respectively). CONCLUSIONS High initial UA concentration and increases in UA concentration over time should be considered independent risk factors for hypertension.

Cardiovascular Event Prediction by Machine Learning : The Multi-Ethnic Study of Atherosclerosis

Ambale-Venkatesh, B., Yang, X., Wu, C. O., Liu, K., Gregory Hundley, W., McClelland, R., Gomes, A. S., Folsom, A. R., Shea, S., Guallar, E., Bluemke, D. A., & Lima, J. A. (n.d.).

Publication year

2017

Journal title

Circulation research

Volume

121

Issue

9

Page(s)

1092-1101
Abstract
Abstract
Rationale: Machine learning may be useful to characterize cardiovascular risk, predict outcomes, and identify biomarkers in population studies. Objective: To test the ability of random survival forests, a machine learning technique, to predict 6 cardiovascular outcomes in comparison to standard cardiovascular risk scores. Methods and Results: We included participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Baseline measurements were used to predict cardiovascular outcomes over 12 years of follow-up. MESA was designed to study progression of subclinical disease to cardiovascular events where participants were initially free of cardiovascular disease. All 6814 participants from MESA, aged 45 to 84 years, from 4 ethnicities, and 6 centers across the United States were included. Seven-hundred thirty-five variables from imaging and noninvasive tests, questionnaires, and biomarker panels were obtained. We used the random survival forests technique to identify the top-20 predictors of each outcome. Imaging, electrocardiography, and serum biomarkers featured heavily on the top-20 lists as opposed to traditional cardiovascular risk factors. Age was the most important predictor for all-cause mortality. Fasting glucose levels and carotid ultrasonography measures were important predictors of stroke. Coronary Artery Calcium score was the most important predictor of coronary heart disease and all atherosclerotic cardiovascular disease combined outcomes. Left ventricular structure and function and cardiac troponin-T were among the top predictors for incident heart failure. Creatinine, age, and ankle-brachial index were among the top predictors of atrial fibrillation. TNF-α (tissue necrosis factor-α) and IL (interleukin)-2 soluble receptors and NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) levels were important across all outcomes. The random survival forests technique performed better than established risk scores with increased prediction accuracy (decreased Brier score by 10%-25%). Conclusions: Machine learning in conjunction with deep phenotyping improves prediction accuracy in cardiovascular event prediction in an initially asymptomatic population. These methods may lead to greater insights on subclinical disease markers without apriori assumptions of causality. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Contact

eliseo.guallar@nyu.edu 708 Broadway New York, NY, 10003