Edgar R Miller

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (116)886.49 Total impact

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    ABSTRACT: The association between apparent treatment resistant hypertension (ATRH) and clinical outcomes is not well studied in chronic kidney disease. We analyzed data on 3367 hypertensive participants in the Chronic Renal Insufficiency Cohort (CRIC) to determine prevalence, associations, and clinical outcomes of ATRH in nondialysis chronic kidney disease patients. ATRH was defined as blood pressure ≥140/90 mm Hg on ≥3 antihypertensives, or use of ≥4 antihypertensives with blood pressure at goal at baseline visit. Prevalence of ATRH was 40.4%. Older age, male sex, black race, diabetes mellitus, and higher body mass index were independently associated with higher odds of having ATRH. Participants with ATRH had a higher risk of clinical events than participants without ATRH-composite of myocardial infarction, stroke, peripheral arterial disease, congestive heart failure (CHF), and all-cause mortality (hazard ratio [95% confidence interval], 1.38 [1.22-1.56]); renal events (1.28 [1.11-1.46]); CHF (1.66 [1.38-2.00]); and all-cause mortality (1.24 [1.06-1.45]). The subset of participants with ATRH and blood pressure at goal on ≥4 medications also had higher risk for composite of myocardial infarction, stroke, peripheral arterial disease, CHF, and all-cause mortality (hazard ratio [95% confidence interval], (1.30 [1.12-1.51]) and CHF (1.59 [1.28-1.99]) than those without ATRH. ATRH was associated with significantly higher risk for CHF and renal events only among those with estimated glomerular filtration rate ≥30 mL/min per 1.73 m(2). Our findings show that ATRH is common and associated with high risk of adverse outcomes in a cohort of patients with chronic kidney disease. This underscores the need for early identification and management of patients with ATRH and chronic kidney disease.
    No preview · Article · Dec 2015 · Hypertension
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    ABSTRACT: Objective: The effects of carbohydrates on plasma uric acid levels are controversial. We determined the individual and combined effects of carbohydrate quality (glycemic index, GI) and quantity (proportion of total daily energy, %carb) on uric acid. Methods: We conducted a randomized, crossover feeding trial in overweight or obese adults without cardiovascular disease (N=163). Participants were fed each of four diets over 5-week periods separated by 2-week washout periods. Body weight was kept constant. The four diets were: high GI (GI ≥65) with high %carb (58% kcal), low GI (GI ≤45) with low %carb (40% kcal), low GI with high %carb; and high GI with low %carb. Plasma uric acid was measured at baseline and after each feeding period for comparison between the 4 diets. Results: Study participants were 52% women and 50% non-Hispanic black with a mean age of 52.6 years and a mean uric acid of 4.7 (SD, 1.2) mg/dL. Reducing GI lowered uric acid when the %carb was low (-0.24 mg/dL; P <0.001) or high (-0.17 mg/dL; P <0.001). Reducing the %carb marginally increased uric acid only when GI was high (P = 0.05). The combined effect of lowering GI and increasing the %carb was -0.27 mg/dL (P <0.001). This effect was observed even after adjustment for concurrent changes in kidney function, insulin sensitivity, and products of glycolysis. Conclusions: Reducing GI lowers uric acid. Future studies should examine whether reducing GI can prevent gout onset or flares. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · Arthritis and Rheumatology
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    ABSTRACT: Background: The difference between total serum protein and albumin, i.e. the gamma gap, is a frequently used clinical screening measure for both latent infection and malignancy. However, there are no studies defining a positive gamma gap. Further, whether it is an independent risk factor of mortality is unknown. Methods and findings: This study examined the association between gamma gap, all-cause mortality, and specific causes of death (cardiovascular, cancer, pulmonary, or other) in 12,260 participants of the National Health and Nutrition Examination Survey (NHANES) from 1999-2004. Participants had a comprehensive metabolic panel measured, which was linked with vital status data from the National Death Index. Cause of death was based on ICD10 codes from death certificates. Analyses were performed with Cox proportional hazards models adjusted for mortality risk factors. The mean (SE) age was 46 (0.3) years and the mean gamma gap was 3.0 (0.01) g/dl. The population was 52% women and 10% black. During a median follow-up period of 4.8 years (IQR: 3.3 to 6.2 years), there were 723 deaths. The unadjusted 5-year cumulative incidences across quartiles of the gamma gap (1.7-2.7, 2.8-3.0, 3.1-3.2, and 3.3-7.9 g/dl) were 5.7%, 4.2%, 5.5%, and 7.8%. After adjustment for risk factors, participants with a gamma gap of ≥3.1 g/dl had a 30% higher risk of death compared to participants with a gamma gap <3.1 g/dl (HR: 1.30; 95%CI: 1.08, 1.55; P = 0.006). Gamma gap (per 1.0 g/dl) was most strongly associated with death from pulmonary causes (HR 2.22; 95%CI: 1.19, 4.17; P = 0.01). Conclusions: The gamma gap is an independent risk factor for all-cause mortality at values as low as 3.1 g/dl (in contrast to the traditional definition of 4.0 g/dl), and is strongly associated with death from pulmonary causes. Future studies should examine the biologic pathways underlying these associations.
    Preview · Article · Dec 2015 · PLoS ONE
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    ABSTRACT: Left ventricular hypertrophy (LVH) is prevalent among hypertensive children; however, blood pressure (BP) does not predict its presence. The authors conducted a 1-year prospective cohort study to examine the hypothesis that obesity-related risk factors are associated with left ventricular mass index (LVMI) in hypertensive children, and the association between adiposity and LVMI is mediated by BP-dependent and -independent pathways. A total of 49 hypertensive children were enrolled: 51% were overweight/obese and 41% had LVH at baseline. Children overweight/obese at baseline and follow-up had a greater LVMI increase than those of healthy weight at each visit: mean change of 6.4 g/m(2.7) vs 0.95 g/m(2.7) . Baseline body mass index z score was independently associated with LVMI change (β=4.08, 1.54-6.61; P=.002). Only pulse pressure and serum aldosterone partially mediated this relationship. Hypertensive youth manifest multiple cardiovascular disease risk factors that worsen over time despite treatment. Of these, adiposity is most associated with LVH and increasing LVMI.
    Preview · Article · Nov 2015 · Journal of Clinical Hypertension
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    ABSTRACT: For decades, dietary sodium intake in the United States has remained high, and few studies have examined strategies for maintaining recommended intakes. We examined the effects of a behavioral intervention, which emphasized spices and herbs, on the maintenance of sodium intake at the recommended intake of 1500 mg/d in individuals to whom the US Dietary Guidelines for Americans apply. We conducted a 2-phase study that included adults ≥18 y of age for whom Dietary Guidelines for Americans recommends 1500 mg Na/d. The study was conducted in Baltimore, Maryland, from 2012 to 2014. In phase 1, 55 individuals consumed a low-sodium diet for 4 wk. Participants were provided all foods, snacks, and calorie-containing drinks. In phase 2, 40 participants from phase 1 were randomly assigned to either a behavioral intervention to reduce sodium intake (n = 20) or a self-directed control group (n = 20) for 20 wk. The primary study outcome was the change in mean 24-h urinary sodium excretion during phase 2. Linear regression analyses were used to determine intervention effects on urinary sodium excretion. Participant characteristics were as follows: women: 65%; African American: 88%; hypertension: 63%; diabetes: 18%; mean age: 61 y; and mean body mass index (in kg/m(2)): 30. At the end of phase 2, mean 24-h sodium excretion was lower in the behavioral intervention than in the self-directed group (mean difference: -956.8 mg/d; 95% CI: -1538.7, -374.9 mg/d) after sodium intake at screening was controlled for (P = 0.002). These findings persisted in sensitivity analyses that excluded potentially incomplete urine collections [Mage's equation mean difference: -1090 mg/d (P = 0.001); Joosens' equation mean difference: -796 mg/d (P = 0.04)]. A multifactorial behavioral intervention emphasizing spices and herbs significantly reduced sodium intake. Because of the ubiquity of sodium in the US food supply, multilevel strategies addressing individual behaviors and the food supply are needed to improve adherence to recommendations. This trial was registered at clinicaltrials.gov as NCT01615159. © 2015 American Society for Nutrition.
    No preview · Article · Aug 2015 · American Journal of Clinical Nutrition

  • No preview · Article · Aug 2015
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    ABSTRACT: Uric acid (UA) is associated with high blood pressure in adolescents and with left ventricular hypertrophy (LVH) and cardiovascular disease (CVD) in adults. We sought to determine if UA is independently associated with CVD risk factors and left ventricular mass (LVM) over time in hypertensive youth. This was a 1-year prospective observational study of hypertensive children aged 3-19 years. Cross-sectional and longitudinal associations of serum UA with CVD risk factors and LVM were explored. Of the 49 children who completed both the baseline and 12-month assessments, at baseline the mean age was 13.8 years and mean UA was 5.5 mg/dL; 24 % had elevated UA, 51 % were overweight/obese and 39 % had LVH. Measures of adiposity, low high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, LVM and LVH were all significantly associated with elevated UA at baseline, but not with change over time. Each 1 mg/dL increase in baseline UA was associated with a 2.5 g/m(2.7) increase in the LVM index at follow-up (95 % confidence interval 0.64, 4.39; p = 0.01); after adjustment for age, sex, race, body mass index z-score, change in UA, time, blood pressure and medication use, this association was no longer significant. Hypertensive children with elevated UA have a higher prevalence of obesity-related CVD risk factors. Among hypertensive children, UA may be a marker of adiposity and not an independent CVD risk factor.
    No preview · Article · Jul 2015 · Pediatric Nephrology
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    ABSTRACT: Fruit and vegetable consumption produces changes in several biomarkers in blood. The present study aimed to examine the dose-response curve between fruit and vegetable consumption and carotenoid (α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C concentrations. Furthermore, a prediction model of fruit and vegetable intake based on these biomarkers and subject characteristics (i.e. age, sex, BMI and smoking status) was established. Data from twelve diet-controlled intervention studies were obtained to develop a prediction model for fruit and vegetable intake (including and excluding fruit and vegetable juices). The study population in the present individual participant data meta-analysis consisted of 526 men and women. Carotenoid, folate and vitamin C concentrations showed a positive relationship with fruit and vegetable intake. Measures of performance for the prediction model were calculated using cross-validation. For the prediction model of fruit, vegetable and juice intake, the root mean squared error (RMSE) was 258·0 g, the correlation between observed and predicted intake was 0·78 and the mean difference between observed and predicted intake was - 1·7 g (limits of agreement: - 466·3, 462·8 g). For the prediction of fruit and vegetable intake (excluding juices), the RMSE was 201·1 g, the correlation was 0·65 and the mean bias was 2·4 g (limits of agreement: - 368·2, 373·0 g). The prediction models which include the biomarkers and subject characteristics may be used to estimate average intake at the group level and to investigate the ranking of individuals with regard to their intake of fruit and vegetables when validating questionnaires that measure intake.
    Full-text · Article · Apr 2015 · The British journal of nutrition
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    Full-text · Article · Apr 2015 · American Journal of Kidney Diseases
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    ABSTRACT: Previous reports of the longitudinal association between achieved blood pressure (BP) and end-stage renal disease (ESRD) among patients with chronic kidney disease (CKD) have not incorporated time-updated BP with appropriate covariate adjustment. To assess the association between baseline and time-updated systolic blood pressure (SBP) with CKD progression. Observational, prospective cohort study. (ClinicalTrials.gov: NCT00304148). 7 U.S. clinical centers. Patients in the Chronic Renal Insufficiency Cohort Study (n = 3708) followed for a median of 5.7 years (25th to 75th percentile, 4.6 to 6.7 years). The mean of 3 seated SBP measurements made up the visit-specific SBP. Time-updated SBP was the mean of that and all previous visits. Outcomes were ESRD and the composite end point of ESRD or halving of the estimated glomerular filtration rate. Analyses investigating baseline and time-updated SBP used Cox proportional hazards models and marginal structural models, respectively. Systolic blood pressure was 130 mm Hg or greater at all visits in 19.2% of patients. The hazard ratio for ESRD among patients with SBP of 130 to 139 mm Hg, compared with SBP less than 120 mm Hg, was 1.46 (95% CI, 1.13 to 1.88) using only baseline data and 2.37 (CI, 1.48 to 3.80) using time-updated data. Among patients with SBP of 140 mm Hg or greater, corresponding hazard ratios were 1.46 (CI, 1.18 to 1.88) and 3.37 (CI, 2.26 to 5.03) for models using only baseline data and those using time-updated data, respectively. Blood pressure was measured once annually, and the cohort was not a random sample. Time-updated SBP greater than 130 mm Hg was more strongly associated with CKD progression than analyses based on baseline SBP. National Institute of Diabetes and Digestive and Kidney Diseases.
    No preview · Article · Feb 2015 · Annals of internal medicine
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    ABSTRACT: Foods that have similar carbohydrate content can differ in the amount they raise blood glucose. The effects of this property, called the glycemic index, on risk factors for cardiovascular disease and diabetes are not well understood. To determine the effect of glycemic index and amount of total dietary carbohydrate on risk factors for cardiovascular disease and diabetes. Randomized crossover-controlled feeding trial conducted in research units in academic medical centers, in which 163 overweight adults (systolic blood pressure, 120-159 mm Hg) were given 4 complete diets that contained all of their meals, snacks, and calorie-containing beverages, each for 5 weeks, and completed at least 2 study diets. The first participant was enrolled April 1, 2008; the last participant finished December 22, 2010. For any pair of the 4 diets, there were 135 to 150 participants contributing at least 1 primary outcome measure. (1) A high-glycemic index (65% on the glucose scale), high-carbohydrate diet (58% energy); (2) a low-glycemic index (40%), high-carbohydrate diet; (3) a high-glycemic index, low-carbohydrate diet (40% energy); and (4) a low-glycemic index, low-carbohydrate diet. Each diet was based on a healthful DASH-type diet. The 5 primary outcomes were insulin sensitivity, determined from the areas under the curves of glucose and insulin levels during an oral glucose tolerance test; levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides; and systolic blood pressure. At high dietary carbohydrate content, the low- compared with high-glycemic index level decreased insulin sensitivity from 8.9 to 7.1 units (-20%, P = .002); increased LDL cholesterol from 139 to 147 mg/dL (6%, P ≤ .001); and did not affect levels of HDL cholesterol, triglycerides, or blood pressure. At low carbohydrate content, the low- compared with high-glycemic index level did not affect the outcomes except for decreasing triglycerides from 91 to 86 mg/dL (-5%, P = .02). In the primary diet contrast, the low-glycemic index, low-carbohydrate diet, compared with the high-glycemic index, high-carbohydrate diet, did not affect insulin sensitivity, systolic blood pressure, LDL cholesterol, or HDL cholesterol but did lower triglycerides from 111 to 86 mg/dL (-23%, P ≤ .001). In this 5-week controlled feeding study, diets with low glycemic index of dietary carbohydrate, compared with high glycemic index of dietary carbohydrate, did not result in improvements in insulin sensitivity, lipid levels, or systolic blood pressure. In the context of an overall DASH-type diet, using glycemic index to select specific foods may not improve cardiovascular risk factors or insulin resistance. clinicaltrials.gov Identifier: NCT00608049.
    No preview · Article · Dec 2014 · JAMA The Journal of the American Medical Association
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    ABSTRACT: Objective. Pediatric hypertension remains largely unrecognized. We hypothesized that an electronic medical record (EMR) alert would increase elevated blood pressure (BP) recognition in a pediatric primary care setting. Study Design. Pre-post evaluation of a real-time EMR alert and one-time provider educational session. A total of 1305 encounters of children 3 to 21 years with elevated intake BP and no prior hypertension diagnosis were included. Elevated BP recognition and relationship of recognition with cardiovascular disease (CVD) risk factors during the intervention was compared with an historical control. Results. Recognition increased from 12.5% to 42% (P < .001). Recognition increased soon after alert implementation and was sustained without evidence of "alert fatigue." During both periods, presence of CVD risk factors was associated with recognition. However, the magnitude was lesser in the intervention period. Conclusions. Real-time EMR alerts substantially increase elevated BP recognition in children. However, underrecognition of elevated BP persisted, highlighting the need for additional strategies to improve provider recognition. © The Author(s) 2014.
    No preview · Article · Nov 2014 · Clinical Pediatrics
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    ABSTRACT: Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria).
    No preview · Article · Oct 2014 · American Journal of Kidney Diseases
  • Edgar R Miller · Lawrence J Appel
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    ABSTRACT: Orthostatic hypotension (OH) is common in adults, and when accompanied by symptoms (dizziness, light-headedness, or fainting) carries an increased risk of falls, fractures, and mortality.(1) Symptoms are attributed to transiently reduced cerebral perfusion. The underlying causes of OH are numerous and include dehydration, "autonomic dysfunction", and medications that affect vascular compliance or responsiveness to autonomic reflexes.(2) Risk factors for OH in population-based studies include age, hypertension, hypertension treatment, diabetes, and sedative/hypnotic medication use.(3.)
    No preview · Article · Oct 2014 · Circulation
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    ABSTRACT: Poverty is associated with chronic kidney disease (CKD) in the United States and worldwide. Poor dietary habits may contribute to this disparity.
    No preview · Article · Sep 2014 · Journal of Renal Nutrition
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    ABSTRACT: Objective Evidence strongly suggests that delivery of gout care is suboptimal. The 2012 American College of Rheumatology (ACR) guidelines emphasize a serum uric acid (SUA) target of <6 mg/dl when utilizing urate-lowering therapy (ULT). However, the proportion and characteristics of Americans with gout receiving ULT, or with a ULT indication, who are achieving this target is unknown. Methods We identified US adults with gout receiving ULT, and those with an indication for ULT, using the National Health and Nutrition Examination Surveys from 2007-2010. Using the ACR guidelines, a ULT indication comprised chronic kidney disease (CKD) stage 2-5, a history of nephrolithiasis, or current ULT use. Demographic and clinical factors associated with an SUA 6 mg/dl were determined using Poisson regression. ResultsIn 2007-2010, an estimated 4.5 million US adults with gout had an indication for ULT; two-thirds had an SUA 6 mg/dl. In adjusted analyses among those with gout and CKD or nephrolithiasis, those age 70 years were less likely (prevalence ratio [PR] 0.77, 95% confidence interval [95% CI] 0.61-0.97) to have an SUA 6 mg/dl. Regarding those taking ULT, hypertension was related to a reduced prevalence (PR 0.51, 95% CI 0.30-0.87), whereas diabetes mellitus (PR 1.42, 95% CI 1.06-1.90) and obesity (PR 1.74, 95% CI 1.19-2.56) were each associated with a higher prevalence of an SUA value 6 mg/dl. Conclusion Half of all Americans with gout receiving ULT, and two-thirds with an indication for ULT, have an SUA above target. This study furnishes a meaningful baseline for assessing the effectiveness of the ACR guidelines in future years.
    No preview · Article · Sep 2014
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    Full-text · Article · Jun 2014 · Annals of internal medicine
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    ABSTRACT: Diabetes and hypertension, common conditions in antiretroviral-treated HIV-infected individuals, are associated with glomerular hyperfiltration, which precedes the onset of proteinuria and accelerated kidney function decline. In the Multicenter AIDS Cohort Study, we examined the extent to which hyperfiltration is present and associated with metabolic, cardiovascular, HIV and treatment risk factors among HIV-infected men. Cross-sectional cohort using direct measurement of glomerular filtration rate by iohexol plasma clearance for 367 HIV-infected men and 241 HIV-uninfected men who were free of chronic kidney disease. Hyperfiltration was defined as glomerular filtration rate above 140-1 ml/min per 1.73 m per year over age 40. Multivariate logistic regression was used to estimate the odds ratios (ORs) of prevalent hyperfiltration for metabolic, cardiovascular, HIV and cumulative antiretroviral exposure factors. Among individuals without chronic kidney disease, the prevalence of hyperfiltration was higher for HIV-infected participants (25%) compared to uninfected participants (17%; P = 0.01). After adjustment, HIV infection remained associated with hyperfiltration [OR 1.70, 95% confidence interval (CI) 1.11-2.61] and modified the association between diabetes and hyperfiltration, such that the association among HIV-uninfected men (OR 2.56, 95% CI 1.33-5.54) was not observed among HIV-infected men (OR 1.19, 95% CI 0.69-2.05). These associations were independent of known risk factors for hyperfiltration. Indicators of hyperglycemia and hypertension were also associated with hyperfiltration as was cumulative zidovudine exposure. Hyperfiltration, a potential modifiable predictor of kidney disease progression, is significantly higher among antiretroviral-treated HIV-infected men. Furthermore, HIV-infection nullifies the association of diabetes and hyperfiltration present in HIV-uninfected men.
    No preview · Article · Jan 2014 · AIDS (London, England)
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    ABSTRACT: Some observational studies have identified elevated uric acid concentration as a risk factor for diabetes, while others have found an inverse relationship. We examined both the association of uric acid level with incident diabetes and the change in uric acid concentration after a diabetes diagnosis. We analyzed data from the Atherosclerosis Risk in Communities (ARIC) Study and quantified the independent association between uric acid level and incident diabetes via Cox proportional hazards models. The association between duration of diabetes and change in uric acid level was examined via linear regression. Among 11,134 participants without diagnosed diabetes at baseline (1987-1989), there were 1,294 incident cases of diabetes during a median of 9 years of follow-up (1987-1998). Uric acid level was associated with diabetes even after adjustment for risk factors (per 1 mg/dL, hazard ratio = 1.18, 95% confidence interval: 1.13, 1.23), and the association remained significant after adjustment for fasting glucose and insulin levels. Among participants with diabetes (n = 1,510), every additional 5 years' duration of diabetes was associated with a 0.10-mg/dL (95% confidence interval: 0.04, 0.15) lower uric acid level after adjustment. We conclude that uric acid concentration rises prior to diagnosis of diabetes and then declines with diabetes duration. Future studies investigating uric acid as a risk factor for cardiovascular disease should adequately account for the impact and timing of diabetes development.
    No preview · Article · Jan 2014 · American journal of epidemiology

  • No preview · Article · Dec 2013 · Annals of internal medicine

Publication Stats

8k Citations
886.49 Total Impact Points

Institutions

  • 2003-2015
    • Johns Hopkins University
      • • Department of Epidemiology
      • • Department of Medicine
      Baltimore, Maryland, United States
  • 1997-2015
    • Johns Hopkins Medicine
      • • Department of Medicine
      • • Department of Epidemiology
      • • Welch Center for Prevention, Epidemiology and Clinical Research
      Baltimore, Maryland, United States
  • 2002-2012
    • Johns Hopkins Bloomberg School of Public Health
      • Department of Epidemiology
      Baltimore, Maryland, United States
  • 2006
    • National Institutes of Health
      베서스다, Maryland, United States
    • National Institute on Aging
      Baltimore, Maryland, United States
  • 2005
    • Yonsei University
      • Graduate School of Public Health
      Seoul, Seoul, South Korea
  • 2004
    • Duke University
      Durham, North Carolina, United States