85 results on '"Umans, Jason G."'
Search Results
2. Longitudinal Lipidomic Profile of Hypertension in American Indians: Findings From the Strong Heart Family Study.
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Chen, Mingjing, Miao, Guanhong, Zhang, Ying, Umans, Jason G., Lee, Elisa T., Howard, Barbara V., Fiehn, Oliver, and Zhao, Jinying
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BACKGROUND: Dyslipidemia is an important risk factor for hypertension and cardiovascular disease. Standard lipid panel cannot reflect the complexity of blood lipidome. The associations of individual lipid species with hypertension remain to be determined in large-scale epidemiological studies, especially in a longitudinal setting. METHODS: Using liquid chromatography-mass spectrometry, we repeatedly measured 1542 lipid species in 3699 fasting plasma samples at 2 visits (1905 at baseline, 1794 at follow-up, ~5.5 years apart) from 1905 unique American Indians in the Strong Heart Family Study. We first identified baseline lipids associated with prevalent and incident hypertension, followed by replication of top hits in Europeans. We then conducted repeated measurement analysis to examine the associations of changes in lipid species with changes in systolic blood pressure, diastolic blood pressure, and mean arterial pressure. Network analysis was performed to identify lipid networks associated with the risk of hypertension. RESULTS: Baseline levels of multiple lipid species, for example, glycerophospholipids, cholesterol esters, sphingomyelins, glycerolipids, and fatty acids, were significantly associated with both prevalent and incident hypertension in American Indians. Some lipids were confirmed in Europeans. Longitudinal changes in multiple lipid species, for example, acylcarnitines, phosphatidylcholines, fatty acids, and triacylglycerols, were significantly associated with changes in blood pressure measurements. Network analysis identified distinct lipidomic patterns associated with the risk of hypertension. CONCLUSIONS: Baseline plasma lipid species and their longitudinal changes are significantly associated with hypertension development in American Indians. Our findings shed light on the role of dyslipidemia in hypertension and may offer potential opportunities for risk stratification and early prediction of hypertension. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Epigenetics of type 2 diabetes and diabetes-related outcomes in the Strong Heart Study.
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Domingo-Relloso, Arce, Gribble, Matthew O., Riffo-Campos, Angela L., Haack, Karin, Cole, Shelley A., Tellez-Plaza, Maria, Umans, Jason G., Fretts, Amanda M., Zhang, Ying, Fallin, M. Daniele, Navas-Acien, Ana, and Everson, Todd M.
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- 2022
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4. Educational and Clinical Associations With Longitudinal Cognitive Function and Brain Imaging in American Indians: The Strong Heart Study.
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Suchy-Dicey, Astrid M., Oziel, Kyra, Sawyer, Charles, Olufadi, Yunusa, Ali, Tauqeer, Fretts, Amanda M., Umans, Jason G., Shibata, Dean K., Longstreth Jr, W.T., Rhoads, Kristoffer, Buchwald, Dedra S., Grabowski, Thomas J., and Longstreth, W T Jr
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- 2022
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5. The Virtual CTSA Visiting Scholar Program to Support Early-Stage Clinical and Translational Researchers: Implementation and Outcomes.
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Bredella, Miriam A., Rubio, Doris M., Attia, Jacqueline, Kelly, Thomas H., McIntosh, Scott, Meagher, Emma A., Pusek, Susan, Rubio, Mercedes, Tsevat, Joel, and Umans, Jason G.
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- 2022
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6. Subclinical atherosclerosis in adolescents and young adults and the risk of cardiovascular disease: The Strong Heart Family Study (SHFS).
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Reese, Jessica A., Roman, Mary J., Deen, Jason F., Ali, Tauqeer, Cole, Shelley A., Devereux, Richard B., Fretts, Amanda M., Howard, Barbara V., Lee, Elisa T., Malloy, Kimberly, Singh, Parmanand, Umans, Jason G., and Zhang, Ying
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Background and Aims: Rates of cardiovascular disease (CVD) among American Indians (AI) have been increasing. Although we have observed an association between atherosclerosis and CVD in older adults, the potential association among young AI is unclear. Therefore, we aim to describe the prevalence of atherosclerosis among young AI and determine its association with CVD and all-cause mortality.Methods and Results: We evaluated AI participants from the Strong Heart Family Study (SHFS), who were <40 years old and CVD free at the baseline examination, 2001-2003 (n = 1376). We used carotid ultrasound to detect baseline atherosclerotic plaque. We identified CVD events and all-cause mortality through 2019, with a median follow-up of 17.8 years. We used shared frailty Cox Proportional Hazards models to assess the association between atherosclerosis and time to CVD event or all-cause mortality, while controlling for covariates. Among 1376 participants, 71 (5.2%) had atherosclerosis at baseline. During follow-up, 120 (8.7%) had CVD events and 104 (7.6%) died from any cause. CVD incidence was higher in participants who had baseline atherosclerosis (13.51/1000 person-years) than in those who did not (4.95/1000 person-years, p = 0.0003). CVD risk and all-cause mortality were higher in participants with atherosclerosis, while controlling for covariates (CVD HR = 1.85, 95%CI = 1.02-3.37, p = 0.0420; all-cause mortality HR = 2.04, 95%CI = 1.07-3.89, p = 0.0291).Conclusions: Among young AI, atherosclerosis was independently associated with incident CVD and all-cause mortality later in life. Thus, atherosclerosis begins early in life and interventions in adolescents and young adults to slow the progression of disease could prevent or delay CVD events later in life. [ABSTRACT FROM AUTHOR]- Published
- 2022
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7. Diet Quality and Kidney Outcomes in Adolescent and Adult American Indians: the Strong Heart Family Study
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Mokiao, Reya H., Fretts, Amanda M., Deen, Jason F., and Umans, Jason G.
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Background: The burden of kidney disease is exceedingly high among American Indians (AIs). We sought to examine the relationship of diet quality, a modifiable risk factor, and kidney outcomes in AI adolescents and adults, hypothesizing that healthier diets are associated with lower odds of incident albuminuria and eGFR decline. Methods: This is an analysis from the Strong Heart Family Study, a longitudinal study of cardiovascular disease and its risk factors among AIs from Arizona, North and South Dakota, and Oklahoma (n= 1720, mean age 39 + / − 16 years, 16% adolescents at baseline). Participants completed two exams (baseline: 2001–2003; follow-up: 2007–2009). The primary exposure was diet quality, expressed as the Alternative Healthy Eating Index 2010 (AHEI), on a 110-point scale (assessed using a 119-item Block food frequency questionnaire). The primary outcomes were as follows: 1) incident albuminuria (albumin to creatinine ratio 30 mg/g or greater); and 2) eGFR decline of 30% or greater. Generalized estimating equations were used to examine the association of AHEI (in quartiles) with outcomes. Results: Ten percent of participants (6% of adolescents) had incident albuminuria and 2% of participants (2% of adolescents) had eGFR decline. For those with normal fasting glucose levels, the odds ratio (OR) for incident albuminuria comparing extreme quartiles of diet quality (least healthy [reference] versus healthiest quartiles) was 0.48 (95% CI 0.28, 0.81) after adjustment for demographics and comorbidities. Conclusions: For American Indians with normal fasting glucose, higher diet quality decreases the odds of developing albuminuria. These findings inform future efforts to prevent CKD in American Indian adolescents and young adults.
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- 2023
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8. Educational and Clinical Associations With Longitudinal Cognitive Function and Brain Imaging in American Indians
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Suchy-Dicey, Astrid M., Oziel, Kyra, Sawyer, Charles, Olufadi, Yunusa, Ali, Tauqeer, Fretts, Amanda M., Umans, Jason G., Shibata, Dean K., Longstreth, W.T., Rhoads, Kristoffer, Buchwald, Dedra S., and Grabowski, Thomas J.
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- 2022
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9. Lipidomic profiling in the Strong Heart Study identified American Indians at risk of chronic kidney disease
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Zeng, Wenjie, Beyene, Habtamu B., Kuokkanen, Mikko, Miao, Guanhong, Magliano, Dianna J., Umans, Jason G., Franceschini, Nora, Cole, Shelley A., Michailidis, George, Lee, Elisa T., Howard, Barbara V., Fiehn, Oliver, Curran, Joanne E., Blangero, John, Meikle, Peter J., and Zhao, Jinying
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Dyslipidemia associates with and usually precedes the onset of chronic kidney disease (CKD), but a comprehensive assessment of molecular lipid species associated with risk of CKD is lacking. Here, we sought to identify fasting plasma lipids associated with risk of CKD among American Indians in the Strong Heart Family Study, a large-scale community-dwelling of individuals, followed by replication in Mexican Americans from the San Antonio Family Heart Study and Caucasians from the Australian Diabetes, Obesity and Lifestyle Study. We also performed repeated measurement analysis to examine the temporal relationship between the change in the lipidome and change in kidney function between baseline and follow-up of about five years apart. Network analysis was conducted to identify differential lipid classes associated with risk of CKD. In the discovery cohort, we found that higher baseline level of multiple lipid species, including glycerophospholipids, glycerolipids and sphingolipids, was significantly associated with increased risk of CKD, independent of age, sex, body mass index, diabetes and hypertension. Many lipid species were replicated in at least one external cohort at the individual lipid species and/or the class level. Longitudinal change in the plasma lipidome was significantly associated with change in the estimated glomerular filtration rate after adjusting for covariates, baseline lipids and the baseline rate. Network analysis identified distinct lipidomic signatures differentiating high from low-risk groups. Thus, our results demonstrated that disturbed lipid metabolism precedes the onset of CKD. These findings shed light on the mechanisms linking dyslipidemia to CKD and provide potential novel biomarkers for identifying individuals with early impaired kidney function at preclinical stages.
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- 2022
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10. An epigenome-wide study of DNA methylation profiles and lung function among American Indians in the Strong Heart Study.
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Domingo-Relloso, Arce, Riffo-Campos, Angela L., Powers, Martha, Tellez-Plaza, Maria, Haack, Karin, Brown, Robert H., Umans, Jason G., Fallin, M. Daniele, Cole, Shelley A., Navas-Acien, Ana, and Sanchez, Tiffany R.
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- 2022
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11. The Virtual CTSA Visiting Scholar Program to Support Early-Stage Clinical and Translational Researchers: Implementation and Outcomes
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Bredella, Miriam A., Rubio, Doris M., Attia, Jacqueline, Kelly, Thomas H., McIntosh, Scott, Meagher, Emma A., Pusek, Susan, Rubio, Mercedes, Tsevat, Joel, and Umans, Jason G.
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In addition to restrictions on conducting research, COVID-19-related travel bans and scientific meeting cancellations have negatively affected scholars in the Clinical and Translational Science Award (CTSA) Mentored Career Development Award (KL2) program. In response, a national virtual visiting scholar program was developed to provide opportunity for KL2 scholars to be virtual visiting professors at another CTSA hub, meet faculty and scholars, and expand networks and build collaborations. This article describes the design and short-term outcomes of the virtual CTSA Visiting Scholar Program. In 2020, a working group designed core program elements and developed an application and selection process. Anonymized surveys were sent to scholars post visit and to scholars and program directors 6 months post visit to evaluate their experience and solicit suggestions for improvements. Between November 2020 and May 2021, 56 KL2 scholars and 27 hubs participated. Forty-five (80.4%) participating scholars responded to the initial survey. Nearly all scholars (44, 97.7%) agreed their experience was valuable. All respondents indicated they would recommend the program to other KL2 scholars. For the 6-month survey, the response rate was 87.5% (49/56). Within 6 months of their visit, 36 (73.5%) respondents had contacted at least one person at the host hub and for 17 (34.7%) respondents, new collaborations with the host hub ensued. Twenty-five of 27 (92.6%) host hubs responded to the survey. Most (21, 84.0%) agreed that hearing visiting scholar talks was valuable to their own scholars and 23 (92%) indicated likelihood of their hub participating in future round of the program. The virtual Visiting Scholar Program provided KL2 scholars an opportunity to virtually visit another CTSA hub, present their research, and meet with faculty and other scholars to expand their networks. Although geared to KL2 scholars, this model is potentially generalizable to other nationally coordinated career development programs.
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- 2022
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12. The cost-efficacy of a healthy food box for managing hypertension within a native American population: a group randomized controlled trial
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Henderson, Austin, Rosenman, Robert, Fyfe-Johnson, Amber L., Taniguchi, Tori, Standridge, Joy, Shackleford, Tyra, Muller, Clemma J., Umans, Jason G, and Jernigan, Valarie Blue Bird
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Background: Dietary interventions are used for the treatment of hypertension. We evaluated the cost-efficacy of delivering boxes of healthy, culturally tailored foods and checks that can only be spent on produce in a Native American population. Methods: We conducted a group randomized controlled trial from 2018 to 2020 with N= 2 treatment counties and N= 2 control counties and a total of N= 160 Native American adults with baseline stage 1 or stage 2 hypertension. Participants in the intervention group received monthly boxes of food that adheres to the Dietary Approaches to Stop Hypertension diet as well as checks that could only be spent on produce for 6 months. We measured blood pressure and quality of life at baseline and at a 6-month follow-up in both intervention and control groups. We used ordered logistic regression to estimate the effect of treatment on probability of blood pressure improvements. We then conducted a cost-efficacy analysis. Results: We found that treatment was effective in reducing blood pressure in women with stage 1 hypertension at baseline. Based on this finding, we also estimate that this intervention satisfies normative cost-effectiveness thresholds, even when lifetime treatment is needed to preserve the impact, so long as treatment is only continued in those who respond to treatment. Conclusions: Direct delivery of healthy foods and checks that can only be spent on produce are a potentially cost-effective intervention for the management of hypertension among Native American women with stage 1 hypertension. Further research is needed to understand why we found an impact only for this group.
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- 2024
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13. Plasma biomarkers, memory impairment, and imaging measures of Alzheimer's disease in American Indians.
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Suchy‐Dicey, Astrid M, Rhoads, Kristoffer, Longstreth, W.T., Umans, Jason G, Blennow, Kaj, Buchwald, Dedra, Grabowski, Thomas J, Reiman, Eric M., and Zetterberg, Henrik
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Background: Alzheimer's disease (AD) is best defined in vivo using quantifiable, objective markers reflecting amyloid deposition (A), pathologic tau (T), and neurodegeneration (N). However, gold standards for ATN (imaging or cerebrospinal proteins) are expensive, invasive, and/or impractical in low resource settings. Circulating proteins offer a practical alternative. Candidate plasma markers include amyloid‐β (Aβ40&42), phosphorylated tau‐181 (ptau), glial fibrillary protein (GFAP), and neurofilament light chain (NfL). However, no such markers have been evaluated in American Indians. Method: The Strong Heart Study recruited 401 American Indians over 3 states in 2017‐2019 for MRI, cognitive testing, and clinical examination. MRI included T1 sequences, which were processed using FreeSurfer to quantify structural volumes. Neuropsychological testing incuded California Verbal Learning Test, which was operationalized into categories of memory impairment using indices of learning and recall. Plasma samples were sent to University of Gothenburg for Simoa Quanterix assay. Statistics included descriptive summary; multivariate regression; and receiver operating characteristic analysis. Result: The study population was mean age 78 (SD 4.7, range 70‐95); majority female (71%); and 21% APOE ε4 allele carriers. An estimated 31% had any memory impairment (13.8% retrieval, 6.5% storage, 10.7% encoding). Median plasma marker values were: ptau 5.0pg/mL (range: 1.5‐442), Aβ40 128pg/mL (116‐175), Aβ42 8.2pg/mL (6.7‐9.7), GFAP 150pg/mL (0‐651), and NfL 31.6pg/mL (9.7‐343); median Aβ42:40 ratio 0.06. Comparing APOEε4 carriers to non‐carriers (Table1), ptau was +12%, Aβ40 ‐0.8%, Aβ42 ‐8.4%, Aβ4240 ‐16.7% (P = 0.006), GFAP +16.1%, NfL +3.2%, but only Aβ4240 was significant. Linear regressions with brain volumes identified significant associations for Aβ42, Aβ40, GFAP, and NfL (but not ptau) with ventricle, cortical, and overall volume; NfL was also associated with entorhinal and hippocampal volume. GFAP and ptau were significantly higher in those with memory encoding deficit; NfL higher with encoding or retrieval deficit (Table2). Although not significant, Aβ40 was lower with storage deficit, and Aβ42 with encoding or storage deficit. AUC range for plasma markers to discriminate memory impaired from intact: 0.4‐0.6. Conclusion: These data are a first look at ATN plasma markers in a population‐based cohort of American Indians, an underrepresented group in AD research. Future research should address generalizability and measurement validity. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Trade-offs Between Accuracy and Health Outcomes in Algorithms for Home Blood Pressure Monitoring Devices
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Henderson, Austin, Fyfe-Johnson, Amber L., Dillard, Denise, Schaefer, Krista, Todd, Michael, Muller, Clemma J., Umans, Jason G., and Rosenman, Robert
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Objectives Home blood pressure monitoring (HBPM) is crucial for managing hypertension, but there is a potential trade-off between measurement accuracy and health/economic outcomes due to asymmetric costs associated with misclassifying an individual as having hypertension or not. We assessed whether adjustments to device readings that increased overall accuracy produced net health and economic benefits.Methods We analyzed data from N = 89 Alaska Native individuals who used 2 HBPM devices and a standard aneroid sphygmomanometer. We modeled changes in expected costs associated with individuals being misclassified as hypertensive or not under 3 different models of adjusting HBPM device readings.Results The gains in accuracy produced by adjusting HBPM readings decreased the overall rate of hypertension misclassification but increased the rate of false-negative readings. Adjusting readings led to a net increase in expected health and economic costs.Discussion Ignoring asymmetric costs of misclassification can escalate overall costs and worsen uncontrolled hypertension. Home blood pressure monitoring algorithms must be cautiously designed, considering both false negatives and positives. Greater transparency in HBPM algorithms is needed for effective coordination among manufacturers, clinicians, and patients.
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- 2024
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15. Blood DNA Methylation and Incident Coronary Heart Disease: Evidence From the Strong Heart Study
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Navas-Acien, Ana, Domingo-Relloso, Arce, Subedi, Pooja, Riffo-Campos, Angela L., Xia, Rui, Gomez, Lizbeth, Haack, Karin, Goldsmith, Jeff, Howard, Barbara V., Best, Lyle G., Devereux, Richard, Tauqeer, Ali, Zhang, Ying, Fretts, Amanda M., Pichler, Gernot, Levy, Daniel, Vasan, Ramachandran S., Baccarelli, Andrea A., Herreros-Martinez, Miguel, Tang, Wan-yee, Bressler, Jan, Fornage, Myriam, Umans, Jason G., Tellez-Plaza, Maria, Fallin, M. Daniele, Zhao, Jinying, and Cole, Shelley A.
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IMPORTANCE: American Indian communities experience a high burden of coronary heart disease (CHD). Strategies are needed to identify individuals at risk and implement preventive interventions. OBJECTIVE: To investigate the association of blood DNA methylation (DNAm) with incident CHD using a large number of methylation sites (cytosine-phosphate-guanine [CpG]) in a single model. DESIGN, SETTING, AND PARTICIPANTS: This prospective study, including a discovery cohort (the Strong Heart Study [SHS]) and 4 additional cohorts (the Women’s Health Initiative [WHI], the Framingham Heart Study [FHS], the Atherosclerosis Risk in Communities Study ([ARIC]–Black, and ARIC-White), evaluated 12 American Indian communities in 4 US states; African American women, Hispanic women, and White women throughout the US; White men and White women from Massachusetts; and Black men and women and White men and women from 4 US communities. A total of 2321 men and women (mean [SD] follow-up, 19.1 [9.2] years) were included in the SHS, 1874 women (mean [SD] follow-up, 15.8 [5.9] years) in the WHI, 2128 men and women (mean [SD] follow-up, 7.7 [1.8] years) in the FHS, 2114 men and women (mean [SD] follow-up, 20.9 [7.2] years) in the ARIC-Black, and 931 men and women (mean [SD] follow-up, 20.9 [7.2] years) in the ARIC-White. Data were collected from May 1989 to December 2018 and analyzed from February 2019 to May 2021. EXPOSURE: Blood DNA methylation. MAIN OUTCOME AND MEASURE: Using a high-dimensional time-to-event elastic-net model for the association of 407 224 CpG sites with incident CHD in the SHS (749 events), this study selected the differentially methylated CpG positions (DMPs) selected in the SHS and evaluated them in the WHI (531 events), FHS (143 events), ARIC-Black (350 events), and ARIC-White (121 events) cohorts. RESULTS: The median (IQR) age of participants in SHS was 55 (49-62) years, and 1359 participants (58.6%) were women. Elastic-net models selected 505 DMPs associated with incident CHD in the SHS beyond established risk factors, center, blood cell counts, and genetic principal components. Among those DMPs, 33 were commonly selected in 3 or 4 of the other cohorts and the pooled hazard ratios from the standard Cox models were significant at P < .05 for 10 of the DMPs. For example, the hazard ratio (95% CI) for CHD comparing the 90th and 10th percentiles of differentially methylated CpGs was 0.86 (0.78-0.95) for cg16604233 (tagged to COL11A2) and 1.23 (1.08-1.39) for cg09926486 (tagged to FRMD5). Some of the DMPs were consistent in the direction of the association; others showed associations in opposite directions across cohorts. Untargeted independent elastic-net models of CHD showed distinct DMPs, genes, and network of genes in the 5 cohorts. CONCLUSIONS AND RELEVANCE: In this multi-cohort study, blood-based DNAm findings supported an association between a complex blood epigenomic signature and CHD that was largely different across populations.
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- 2021
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16. Associations of diet soda and non-caloric artificial sweetener use with markers of glucose and insulin homeostasis and incident diabetes: the Strong Heart Family Study
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Jensen, Paul N., Howard, Barbara V., Best, Lyle G., O’Leary, Marcia, Devereux, Richard B., Cole, Shelley A., MacCluer, Jean W., Ali, Tauqeer, Lee, Elisa T., Yeh, Fawn L., Yeh, Jeunliang, Umans, Jason G., and Fretts, Amanda M.
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Background/Objectives: Non-caloric artificial sweeteners (NAS) are marketed as healthier alternatives to sugar, but the relationship between consumption of NAS and development of diabetes is unclear. This study assessed the associations of diet soda and NAS consumption with (1) early markers of insulin and glucose homeostasis (cross-sectionally) and (2) incident diabetes (over an average of 8 years of follow-up) among American Indians, a population with high rates of obesity. Subjects/Methods: The study population included Strong Heart Family Study participants without cardiovascular disease or diabetes who participated in the 2007–2009 study exam (n= 1359). Diet soda and NAS consumption were assessed using a Block food frequency questionnaire and supplemental NAS questionnaire at the study exam. Fasting plasma glucose and insulin were measured during the study exam after a 12-h overnight fast. Participants were followed for incident diabetes through December 2017 using a single phone interview and medical record review; diabetes was identified by self-report and confirmed by documentation in medical records. Associations of diet soda and NAS consumption with fasting insulin, glucose, and incident diabetes were assessed using generalized estimating equations (fasting insulin and glucose analyses) and parametric survival models with Weibull distributions (incident diabetes analyses). Results: Just under half of participants reported regularly consuming diet soda (40%) or using NAS to sweeten their beverages (41%). During an average 8 years of follow-up, we identified 98 cases of incident diabetes. After correction for multiple comparisons, there were no statistically significant associations of reported diet soda and NAS consumption with fasting insulin, fasting glucose, or incident diabetes. Conclusions: Although reported consumption of diet soda and NAS were high, neither were associated with diabetes risk.
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- 2020
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17. Evaluation of Plasma Sphingolipids as Mediators of the Relationship Between Kidney Diseases and Cardiovascular Events
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Lidgard, Benjamin, Bansal, Nisha, Zelnick, Leila R., Hoofnagle, Andrew N., Fretts, Amanda M., Longstreth, W. T., Shlipak, Michael, Umans, Jason G., and Lemaitre, Rozenn
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- 2023
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18. Smoking, blood DNA methylation sites and lung cancer risk.
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Domingo-Relloso, Arce, Joehanes, Roby, Rodriguez-Hernandez, Zulema, Lahousse, Lies, Haack, Karin, Fallin, M. Daniele, Herreros-Martinez, Miguel, Umans, Jason G., Best, Lyle G., Huan, Tianxiao, Liu, Chunyu, Ma, Jiantao, Yao, Chen, Jerolon, Allan, Bermudez, Jose D., Cole, Shelley A., Rhoades, Dorothy A., Levy, Daniel, Navas-Acien, Ana, and Tellez-Plaza, Maria
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LUNG cancer ,DNA methylation ,DISEASE risk factors ,SMOKING - Abstract
Altered DNA methylation (DNAm) might be a biological intermediary in the pathway from smoking to lung cancer. In this study, we investigated the contribution of differential blood DNAm to explain the association between smoking and lung cancer incidence. Blood DNAm was measured in 2321 Strong Heart Study (SHS) participants. Incident lung cancer was assessed as time to event diagnoses. We conducted mediation analysis, including validation with DNAm and paired gene expression data from the Framingham Heart Study (FHS). In the SHS, current versus never smoking and pack-years single-mediator models showed, respectively, 29 and 21 differentially methylated positions (DMPs) for lung cancer with statistically significant mediated effects (14 of 20 available, and five of 14 available, positions, replicated, respectively, in FHS). In FHS, replicated DMPs showed gene expression downregulation largely in trans, and were related to biological pathways in cancer. The multimediator model identified that DMPs annotated to the genes AHRR and IER3 jointly explained a substantial proportion of lung cancer. Thus, the association of smoking with lung cancer was partly explained by differences in baseline blood DNAm at few relevant sites. Experimental studies are needed to confirm the biological role of identified eQTMs and to evaluate potential implications for early detection and control of lung cancer. [Display omitted] • We found mediated effects of DNA methylation on the association between smoking and lung cancer. • Associated gene expression was down-regulated. • Genomic sites with mediated effects were related to biological pathways in cancer. • Most of the joint mediated effect was driven by AHRR and IER3 genes. [ABSTRACT FROM AUTHOR]
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- 2023
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19. Association of low-moderate urine arsenic and QT interval: Cross-sectional and longitudinal evidence from the Strong Heart Study.
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Moon, Katherine A., Zhang, Yiyi, Guallar, Eliseo, Francesconi, Kevin A., Goessler, Walter, Umans, Jason G., Best, Lyle G., Howard, Barbara V., Devereux, Richard B., Okin, Peter M., and Navas-Acien, Ana
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ARSENIC ,HEART beat ,CARDIOVASCULAR diseases risk factors ,BLOOD pressure ,CREATININE - Abstract
Epidemiologic studies suggest that chronic exposure to arsenic is related to cardiovascular disease (CVD), but the pathophysiological link remains uncertain. We evaluated the association of chronic low-moderate arsenic exposure and arsenic metabolism with baseline difference and annual change in ECG measures (QT interval, JT interval, PR interval, QRS duration, and QT dispersion) using linear mixed models in the Strong Heart Study main cohort (N = 1174, median age 55 years) and family study (N = 1695 diabetes-free, median age 36 years). At baseline, arsenic exposure was measured as the sum of inorganic and methylated species in urine (ΣAs) and arsenic metabolism was measured as the relative percentage of arsenic species. Median ΣAs and Bazett heart rate-corrected QT interval (QTc) were 8.6 μg/g creatinine and 424 ms in the main cohort and 4.3 μg/g and 414 ms in the family study, respectively. In the main cohort, a comparison of the highest to lowest ΣAs quartile (>14.4 vs. <5.2 μg/g creatinine) was associated with a 5.3 (95% CI: 1.2, 9.5) ms higher mean baseline QTc interval but no difference in annual change in QTc interval. In the family study, a comparison of the highest to lowest quartile (>7.1 vs. <2.9 μg/g creatinine) was associated with a 3.2 (95% CI: 0.6, 5.7) ms higher baseline QTc interval and a 0.6 (95% CI: 0.04, 1.2) ms larger annual increase in QTc interval. Associations with JTc interval were similar but stronger in magnitude compared to QTc interval. Arsenic exposure was largely not associated with PR interval, QRS duration or QT dispersion. Similar to arsenic exposure, a pattern of lower %MMA and higher %DMA was associated with longer baseline QTc interval in both cohorts and with a larger annual change in QTc interval in the family study. Chronic low-moderate arsenic exposure and arsenic metabolism were associated with prolonged ventricular repolarization. [ABSTRACT FROM AUTHOR]
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- 2018
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20. In vitro induction of T regulatory cells by a methylated CpG DNA sequence in humans: Potential therapeutic applications in allergic and autoimmune diseases.
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Lawless, Oliver J., Bellanti, Joseph A., Brown, Milton L., Sandberg, Kathryn, Umans, Jason G., Li Zhou, Weiqian Chen, Julie Wang, Kan Wang, and Song Guo Zheng
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T cells ,NUCLEOTIDE sequence ,ALLERGIES ,AUTOIMMUNE diseases ,IMMUNE response ,IMMUNOSUPPRESSIVE agents - Abstract
Background: Allergic and autoimmune diseases comprise a group of inflammatory disorders caused by aberrant immune responses in which CD25
+ Forkhead box P3-positive (FOXP3+ ) T regulatory (Treg) cells that normally suppress inflammatory events are often poorly functioning. This has stimulated an intensive investigative effort to find ways of increasing Tregs as a method of therapy for these conditions. One such line of investigation includes the study of how ligation of Toll-like receptors (TLRs) by CpG oligonucleotides (ODN) results in an immunostimulatory cascade that leads to induction of T-helper (Th) type 1 and Treg-type immune responses. Objective: The present study investigated the mechanisms by which calf thymus mammalian double-stranded DNA (CT-DNA) and a synthetic methylated DNA CpG ODN sequence suppress in vitro lymphoproliferative responses to antigens, mitogens, and alloantigens when measured by [³H]-thymidine incorporation and promote FoxP3 expression in human CD4+ T cells in the presence of transforming growth factor (TGF) beta and interleukin-2 (IL-2). Methods: Lymphoproliferative responses of peripheral blood mononuclear cells from four healthy subjects or nine subjects with systemic lupus erythematosus to CT-DNA or phytohemagglutinin (PHA) was measured by tritiated thymidine ([³H]-TdR) incorporation expressed as a stimulation index. Mechanisms of immunosuppressive effects of CT-DNA were evaluated by measurement of the degree of inhibition to lymphoproliferative responses to streptokinase-streptodornase, phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), or alloantigens by a Con A suppressor assay. The effects of CpG methylation on induction of FoxP3 expression in human T cells were measured by comparing inhibitory responses of synthetic methylated and nonmethylated 8-mer CpG ODN sequences by using cell sorting, in vitro stimulation, and suppressor assay. Results: Here, we showed that CT-DNA and a synthetic methylated DNA 8-mer sequence could suppress antigen-, mitogen-, and alloantigen-induced lymphoproliferation in vitro when measured by [3H]-thymidine. The synthetic methylated DNA CpG ODN but not an unmethylated CpG ODN sequence was shown to promote FoxP3 expression in human CD4+ T cells in the presence of TGF beta and IL-2. The induction of FoxP3+ suppressor cells is dose dependent and offers a potential clinical therapeutic application in allergic and autoimmune and inflammatory diseases. Conclusion: The use of this methylated CpG ODN offers a broad clinical application as a novel therapeutic method for Treg induction and, because of its low cost and small size, should facilitate delivery via nasal, respiratory, gastrointestinal routes, and/or by injection, routes of administration important for vaccine delivery to target sites responsible for respiratory, gastrointestinal, and systemic forms of allergic and autoimmune disease. [ABSTRACT FROM AUTHOR]- Published
- 2018
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21. Drugs to Control Diabetes During Pregnancy
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Feghali, Maisa N., Umans, Jason G., and Catalano, Patrick M.
- Abstract
Diabetes is a common complication of pregnancy associated with both short- and long-term adverse maternal and offspring effects. All types of diabetes in pregnancy are increasing in prevalence. Treatment of diabetes in pregnancy, targeting glycemic control, improves both maternal and offspring outcomes, albeit imperfectly for many women. Pharmacologic treatment recommendations differ between pregestational and gestational diabetes. Improved treatment of diabetes in pregnancy will need to consider maternal disease heterogeneity and comorbidities as well as long-term offspring outcomes. In this review, the authors summarize recent clinical studies to highlight established pharmacologic treatments for diabetes in pregnancy and provide suggestions for further research.
- Published
- 2019
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22. Elevated levels of neuropeptide Y in preeclampsia: A pilot study implicating a role for stress in pathogenesis of the disease.
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Paiva, Sara P.C., Veloso, Clara A., Campos, Fernanda F.C., Carneiro, Márcia M., Tilan, Jason U., Wang, Hongkun, Umans, Jason G., Zukowska, Zofia, and Kitlinska, Joanna
- Abstract
Objective To determine if preeclampsia (PE) is associated with dysregulation of the neuropeptide Y (NPY) system. Methods The study enrolled 114 subjects either with normal pregnancy (NP) or with PE. Systolic blood pressure (SBP) was collected from patients using a standard sphygmomanometer. The PE patients were divided into two groups based on the gestational age (GA) at delivery — placental PE (PLPE, GA < 34 weeks) or maternal PE (MTPE, GA ≥ 34 weeks). NPY was measured in platelet rich plasma (PRP), platelet poor plasma (PPP) and in the serum of NP and PE patients utilizing radioimmunoassay. Serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured in NP and PE subjects by ELISA. Results SBP was higher in PE compared to NP. Circulating NPY in serum and PRP, as well as NPY content per 100,000 platelets, but not its concentrations in PPP, were elevated in PE, as compared to NP. The highest NPY concentrations were observed in sera and PRP of patients with MTPE. PE patients had also elevated levels of sFlt-1, as compared to NP, although no difference between PLPE and MTPL groups were observed. There was no increase in P1GF in PE patients. Conclusion Systemic NPY is elevated in PE patients, as compared to NP. This increase is observed in blood fractions containing platelets, suggesting accumulation of the peptide in these cells. NPY concentrations are particularly high in patients with MTPE, underlying differences in etiology between PLPE and MTPE. Our study implicates NPY as a potential target in antihypertensive therapies for PE patients. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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23. Abstract P170: The Association of Urinary Cadmium and Zinc With Lower Extremity Amputations. Evidence From the Strong Heart Study
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Galvez-Fernandez, Marta, Bhatt, Kishan A, Ravalli, Filippo, Goessler, Walter, Zhang, Ying, Fretts, Amanda M, Umans, Jason G, Sanchez, Tiffany, Ujueta, Francisco, Lamas, Gervasio A, Fabsitz, Richard R, and Navas-Acien, Ana
- Abstract
Background:Cadmium is a cardiotoxic divalent metal that accumulates in the liver and kidney. It resembles the essential metal zinc, replacing it in numerous enzymes and proteins. Zinc plays a major role in insulin function. Glucose dyshomeostasis increases the loss of zinc through the urine. Cadmium has been associated with peripheral artery disease and critical limb ischemia, conditions that lead to limb amputations. Chelation treatment with edetate disodium, an agent that facilitates the excretion of cadmium from the body, was beneficial for individuals with critical limb ischemia and diabetes in several small studies. This study evaluated the association of urinary levels of cadmium and zinc with amputations in a population with a high burden of diabetes from Arizona, Oklahoma, North Dakota and South Dakota.Hypothesis:We hypothesize that urinary cadmium and zinc levels are related to prevalent amputations in the SHS cohort.Methods:We included 2,724 participants from the Strong Heart Study, a population-based cohort study in 12 American Indian communities, recruited in 1989-1991 and followed for amputations through 1998-1999. Trained staff identified amputations of the lower extremity through visual examination at the baseline visit. We censored traumatic amputations. Baseline metal levels in spot urine samples were divided by urinary creatinine to account for urine dilution.Results:Mean age was 56.4 years, 41.5% participants were male, and 42% had diabetes. We identified a total of 35 (1.3%) amputations of the lower extremities during the study period. Median urinary levels were 0.97 μg/g for cadmium and 0.56 mg/g for zinc. Higher levels of urinary cadmium and zinc were positively associated with the presence of amputations. The odds ratios of prevalent amputations for an IQR of cadmium and zinc distribution were 1.54 (1.00, 2.38) and 2.24 (1.48, 3.39), respectively, in models adjusted for sociodemographic, lifestyle (tobacco and alcohol intake), and other factors (BMI, hypertension and diabetes status, HDL and LDL-cholesterol, and estimated glomerular filtration rate). The associations remained after further adjustment for fasting plasma glucose levels. Urinary cadmium and zinc levels were positively correlated (r=0.24, P<0.001).Conclusions:Urinary cadmium and zinc were positively associated with the presence of lower extremity amputations in American Indian adults with a high burden of diabetes. These results support the current evidence of cadmium as a cardiometabolic risk factor, and the potential role of impaired zinc metabolism, reflected as increased urinary zinc excretion, in vascular complications of diabetes.
- Published
- 2023
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24. The association of urine arsenic with prevalent and incident chronic kidney disease: evidence from the Strong Heart Study.
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Zheng, Laura Y, Umans, Jason G, Yeh, Fawn, Francesconi, Kevin A, Goessler, Walter, Silbergeld, Ellen K, Bandeen-Roche, Karen, Guallar, Eliseo, Howard, Barbara V, Weaver, Virginia M, and Navas-Acien, Ana
- Abstract
Background: Few studies have evaluated associations between low to moderate arsenic levels and chronic kidney disease (CKD). The objective was to evaluate the associations of inorganic arsenic exposure with prevalent and incident CKD in American Indian adults.Methods: We evaluated the associations of inorganic arsenic exposure with CKD in American Indians who participated in the Strong Heart Study in 3,851 adults ages 45-74 years in a cross-sectional analysis, and 3,119 adults with follow-up data in a prospective analysis. Inorganic arsenic, monomethylarsonate, and dimethylarsinate were measured in urine at baseline. CKD was defined as estimated glomerular filtration rate ≤ 60 ml/min/1.73 m, kidney transplant or dialysis.Results: CKD prevalence was 10.3%. The median (IQR) concentration of inorganic plus methylated arsenic species (total arsenic) in urine was 9.7 (5.8, 15.7) μg/L. The adjusted odds ratio (OR; 95% confidence interval) of prevalent CKD for an interquartile range in total arsenic was 0.7 (0.6, 0.8), mostly due to an inverse association with inorganic arsenic (OR: 0.4 [0.3, 0.4]). Monomethylarsonate and dimethylarsinate were positively associated with prevalent CKD after adjustment for inorganic arsenic (OR: 3.8 and 1.8). The adjusted hazard ratio of incident CKD for an IQR in sum of inorganic and methylated arsenic was 1.2 (1.03, 1.41). The corresponding HRs for inorganic arsenic, monomethylarsonate, and dimethylarsinate were 1.0 (0.9, 1.2), 1.2 (1.00, 1.3), and 1.2 (1.0, 1.4).Conclusions: The inverse association of urine inorganic arsenic with prevalent CKD suggests that kidney disease affects excretion of inorganic arsenic. Arsenic species were positively associated with incident CKD. Studies with repeated measures are needed to further characterize the relation between arsenic and kidney disease development. [ABSTRACT FROM AUTHOR]- Published
- 2015
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25. The Association of Urine Arsenic with Prevalent and Incident Chronic Kidney Disease.
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Laura Y. Zheng, Umans, Jason G., Yeh, Fawn, Francesconi, Kevin A., Goessler, Walter, Silbergeld, Ellen K., Bandeen-Roche, Karen, Guallar, Eliseo, Howard, Barbara V., Weaver, Virginia M., and Navas-Acien, Ana
- Published
- 2015
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26. Sex-specific T-cell regulation of angiotensin II-dependent hypertension.
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Ji, Hong, Zheng, Wei, Li, Xiangjun, Liu, Jun, Wu, Xie, Zhang, Monan Angela, Umans, Jason G, Hay, Meredith, Speth, Robert C, Dunn, Shannon E, and Sandberg, Kathryn
- Abstract
Studies suggest T cells modulate arterial pressure. Because robust sex differences exist in the immune system and in hypertension, we investigated sex differences in T-cell modulation of angiotensin II-induced increases in mean arterial pressure in male (M) and female (F) wild-type and recombination-activating-gene-1-deficient (Rag1(-/-)) mice. Sex differences in peak mean arterial pressure in wild-type were lost in Rag1(-/-) mice (mm Hg: wild-type-F, 136±4.9 versus wild-type-M, 153±1.7; P<0.02; Rag1(-/-)-F, 135±2.1 versus Rag1(-/-)-M, 141±3.8). Peak mean arterial pressure was 13 mm Hg higher after adoptive transfer of male (CD3(M)→Rag1(-/-)-M) versus female (CD3(F)→Rag1(-/-)-M) T cells. CD3(M)→Rag1(-/-)-M mice exhibited higher splenic frequencies of proinflammatory interleukin-17A (2.4-fold) and tumor necrosis factor-α (2.2-fold)-producing T cells and lower plasma levels (13-fold) and renal mRNA expression (2.4-fold) of interleukin-10, whereas CD3(F)→Rag1(-/-)-M mice displayed a higher activation state in general and T-helper-1-biased renal inflammation. Greater T-cell infiltration into perivascular adipose tissue and kidney associated with increased pressor responses to angiotensin II if the T cell donor was male but not female and these sex differences in T-cell subset expansion and tissue infiltration were maintained for 7 to 8 weeks within the male host. Thus, the adaptive immune response and role of pro- and anti-inflammatory cytokine signaling in hypertension are distinct between the sexes and need to be understood to improve therapeutics for hypertension-associated disease in both men and women. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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27. Cadmium exposure and incident peripheral arterial disease.
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Tellez-Plaza, Maria, Guallar, Eliseo, Fabsitz, Richard R, Howard, Barbara V, Umans, Jason G, Francesconi, Kevin A, Goessler, Walter, Devereux, Richard B, and Navas-Acien, Ana
- Abstract
Background: Cadmium has been associated with peripheral arterial disease (PAD) in cross-sectional studies, but prospective evidence is lacking. Our goal was to evaluate the association of urine cadmium concentrations with incident PAD in a large population-based cohort.Methods and Results: A prospective cohort study was performed with 2864 adult American Indians 45 to 74 years of age from Arizona, Oklahoma, and North and South Dakota who participated in the Strong Heart Study from 1989 to 1991 and were followed through 2 follow-up examination visits in 1993 to 1995 and 1997 to 1999. Participants were free of PAD, defined as an ankle brachial index <0.9 or >1.4 at baseline, and had complete baseline information on urine cadmium, potential confounders, and ankle brachial index determinations in the follow-up examinations. Urine cadmium was measured using inductively coupled plasma mass spectrometry and corrected for urinary dilution by normalization to urine creatinine. Multivariable-adjusted hazard ratios were computed using Cox-proportional hazards models for interval-censored data. A total of 470 cases of incident PAD, defined as an ankle brachial index <0.9 or >1.4, were identified. After adjustment for cardiovascular disease risk factors including smoking status and pack-years, the hazard ratio comparing the 80th to the 20th percentile of urine cadmium concentrations was 1.41 (1.05-1.81). The hazard ratio comparing the highest to the lowest tertile was 1.96 (1.32-2.81). The association persisted after excluding participants with ankle brachial index >1.4 only as well as in subgroups defined by sex and smoking status.Conclusions: Urine cadmium, a biomarker of long-term cadmium exposure, was independently associated with incident PAD, providing further support for cadmium as a cardiovascular disease risk factor. [ABSTRACT FROM AUTHOR]- Published
- 2013
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28. Arsenic Exposure and Cancer Mortality in a US-Based Prospective Cohort: The Strong Heart Study.
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García-Esquinas, Esther, Pollán, Marina, Umans, Jason G., Francesconi, Kevin A., Goessler, Walter, Guallar, Eliseo, Howard, Barbara, Farley, John, Best, Lyle G., and Navas-Acien, Ana
- Abstract
The article presents a study that investigated the association between baseline arsenic exposure and cancer mortality in American Indians from Arizona, Oklahoma and North/South Dakota. The study reveals the link between low to moderate exposure to inorganic arsenic and increased mortality for cancers of the lung, prostate, and pancreas, and the lack of association between arsenic and cancers of the esophagus and stomach, colon, and rectum.
- Published
- 2013
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29. The Association of Urine Arsenic with Prevalent and Incident Chronic Kidney Disease
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Zheng, Laura Y., Umans, Jason G., Yeh, Fawn, Francesconi, Kevin A., Goessler, Walter, Silbergeld, Ellen K., Bandeen-Roche, Karen, Guallar, Eliseo, Howard, Barbara V., Weaver, Virginia M., and Navas-Acien, Ana
- Abstract
Supplemental Digital Content is available in the text.
- Published
- 2015
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30. Cadmium exposure and incident cardiovascular disease.
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Tellez-Plaza, Maria, Guallar, Eliseo, Howard, Barbara V, Umans, Jason G, Francesconi, Kevin A, Goessler, Walter, Silbergeld, Ellen K, Devereux, Richard B, and Navas-Acien, Ana
- Abstract
Background: Cadmium is a widespread toxic metal with potential cardiovascular effects, but no studies have evaluated cadmium and incident cardiovascular disease. We evaluated the association of urine cadmium concentration with cardiovascular disease incidence and mortality in a large population-based cohort.Methods: We conducted a prospective cohort study of 3348 American Indian adults 45-74 years of age from Arizona, Oklahoma, and North and South Dakota, who participated in the Strong Heart Study in 1989-1991. Urine cadmium was measured using inductively coupled plasma mass spectrometry. Follow-up extended through 31 December 2008.Results: The geometric mean cadmium level in the study population was 0.94 μg/g (95% confidence interval [CI] = 0.92-0.96). We identified 1084 cardiovascular events, including 400 deaths. After adjustment for sociodemographic and cardiovascular risk factors, the hazard ratios (HRs) (comparing the 80th to the 20th percentile of urine cadmium concentrations) was 1.43 for cardiovascular mortality (95% CI = 1.21-1.70) and 1.34 for coronary heart disease mortality (1.10-1.63). The corresponding HRs for incident cardiovascular disease, coronary heart disease, stroke, and heart failure were 1.24 (1.11-1.38), 1.22 (1.08-1.38), 1.75 (1.17-2.59), and 1.39 (1.01-1.94), respectively. The associations were similar in most study subgroups, including never-smokers.Conclusions: Urine cadmium, a biomarker of long-term exposure, was associated with increased cardiovascular mortality and increased incidence of cardiovascular disease. These findings support that cadmium exposure is a cardiovascular risk factor. [ABSTRACT FROM AUTHOR]- Published
- 2013
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31. Incremental Value of Biochemical and Echocardiographic Measures in Prediction of Ischemic Stroke: The Strong Heart Study.
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Karas, Maria G., Devereux, Richard B., Wiebers, David O., Whisnant, Jack P., Best, Lyle G., Lee, Elisa T., Howard, Barbara V., Roman, Mary J., Umans, Jason G., and Kizer, Jorge R.
- Published
- 2012
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32. Cardiovascular disease prevalence and its relation to risk factors in Alaska Eskimos.
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Howard, Barbara V., Comuzzie, Anthony, Devereux, Richard B., Ebbesson, Sven O.E., Fabsitz, Richard R., Howard, Wm. James, Laston, Sandra, MacCluer, Jean W., Silverman, Angela, Umans, Jason G., Wang, Hong, Weissman, Neil J., and Wenger, Charlotte R.
- Abstract
Abstract: Background and aims: Although Eskimos were thought to be protected from cardiovascular disease (CVD), state health data show a large proportion of deaths from CVD, despite traditional lifestyles and high omega-3 fatty acid intake. This article explores CVD prevalence and its relation to risk factors in Alaska Eskimos. Methods and results: A population-based cohort of 499 Alaska Eskimos > age 45 from the Norton Sound region was examined in 2000–2004 for CVD and associated risk factors as part of the Genetics of Coronary Artery Disease in Alaska Natives study. CVD and atherosclerosis were evaluated and adjudicated using standardized methods. Average age was 58 years; diabetes prevalence was low and high-density lipoprotein cholesterol (HDL-C) concentrations were high, but a large proportion smoked and had high pathogen burden. CVD was higher in men (12.6%) than in women (5.3%) (prevalence ratio 2.4, CI 1.3–4.4). Rates of stroke (6.1% in men, 1.8% in women) were similar to those for coronary heart disease (CHD) (6.1% men, 2.5% women). MI prevalence was low in both genders (1.9% and 0.7%). CVD was higher in men and in those >60 years. Hypertension, diabetes, high LDL-C, high apoB, and low HDL-C were all strong correlates (<.002) and albuminuria and CRP were also correlated with CVD (p <.05) after adjustment for age and gender. Carotid atherosclerosis was correlated with CVD (p =.0079) independent of other risk factors. Conclusion: These data show high CHD and stroke prevalence in Alaska Eskimos, despite low average LDL-C and high HDL-C. Hypertension and high LDL-C were independent correlates; identifying these risk factors early and treating to target is recommended. [Copyright &y& Elsevier]
- Published
- 2010
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33. Effectiveness of doxylamine-pyridoxine for morning sickness.
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Koren, Gideon, Hankins, Gary D.V., Clark, Shannon, Caritis, Steve N., Miodovnik, Menachem, Umans, Jason G., and Mattison, Donald R.
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TREATMENT of pregnancy complications ,BENDECTIN (Trademark) ,PLACEBOS ,VOMITING ,NAUSEA ,RANDOMIZED controlled trials - Published
- 2016
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34. Prevention of atherosclerosis with low-density lipoprotein cholesterol lowering—lipoprotein changes and interactions: the SANDS study.
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Howard, Wm. James, Russell, Marie, Fleg, Jerome L., Mete, Mihriye, Ali, Tauqeer, Devereux, Richard B., Galloway, James M., Otvos, James D., Ratner, Robert E., Roman, Mary J., Silverman, Angela, Umans, Jason G., Weissman, Neil J., Wilson, Charlton, and Howard, Barbara V.
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ATHEROSCLEROSIS prevention ,LOW density lipoproteins ,CHOLESTEROL ,CARDIOVASCULAR diseases risk factors ,STATINS (Cardiovascular agents) ,CAROTID artery ,BLOOD pressure - Abstract
Background: Lowering low-density lipoprotein cholesterol (LDL-C) with statins reduces atherosclerosis. LDL and high-density lipoprotein (HDL) are commonly measured by their cholesterol content, but non-HDL cholesterol, LDL particle number (LDL-P), or total apolipoprotein B (apoB) may be better predictors of cardiovascular risk. Few studies have examined the relationship among lipoprotein levels and composition before and after interventions to lower LDL-C and non-HDL-C. Objective: We sought to measure changes in carotid artery intimal media thickness (CIMT) and lipid concentration and composition during 36 months of statin therapy. Methods: Analyses were conducted on 418 diabetic individuals, with complete data and no previous cardiovascular events, who were randomized to aggressive (AG) versus standard treatment for LDL-C, non-HDL-C, and systolic blood pressure as part of the Stop Atherosclerosis in Native Diabetics Study (SANDS). Results: The AG group achieved average LDL-C and non-HDL-C of 71mg/dL and 100mg/dL and a decrease in CIMT. No significant interactions were observed between treatment effect and initial levels of LDL-C, non-HDL-C, HDL-C, triglycerides, apoB, or LDL-P. Decreases in LDL-C (P < .005) and non-HDL-C (P < .001) were independently correlated with CIMT regression in the AG group. Changes in apoB and LDL-P demonstrated borderline correlations with CIMT regression (P =.07 and P =.09). Conclusions: In diabetic adults with no previous cardiovascular events, treatment to current targets for lipids and systolic blood pressure reduces atherosclerosis progression and when more aggressive targets are met, atherosclerosis regresses. The aggressive targets for LDL-C and non-HDL-C appeared to be the main determinants of CIMT regression and were more predictive of this outcome than changes in LDL-P or apoB. [Copyright &y& Elsevier]
- Published
- 2009
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35. Social- and Behavioral-Specific Genetic Effects on Blood Pressure Traits.
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Franceschini, Nora, Rose, Kathryn M., Storti, Kristi L., Rutherford, Sue, Voruganti, V. Saroja, Laston, Sandy, Grring, Harald H.H., Dyer, Thomas D., Umans, Jason G., Lee, Elisa T., Best, Lyle G., Fabsitz, Richard R., Cole, Shelley A., MacCluer, Jean W., and North, Kari E.
- Subjects
GENETICS ,EMBRYOLOGY ,BLOOD pressure ,VITAL signs ,PHYSICAL activity - Abstract
The article investigates the genetic interaction of social, behavioral and environmental factors that may help identify common blood pressure (BP) susceptibility alleles. The study analyzed the interaction of additive genetic effects, physical activity, smoking, alcohol use and education among 3,600 American Indians using variance component models. The results suggest that behavioral and socioeconomic factors can alter the genetic effects on BP phenotypes and accounting for dependent factors can clarify the complexities of the gene effects on BP.
- Published
- 2009
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36. Prevalence and correlates of subclinical atherosclerosis in Alaska Eskimos: the GOCADAN study.
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Cutchins A, Roman MJ, Devereux RB, Ebbesson SO, Umans JG, Zhu J, Weissman NJ, Howard BV, Cutchins, Alexis, Roman, Mary J, Devereux, Richard B, Ebbesson, Sven O E, Umans, Jason G, Zhu, Jianhui, Weissman, Neil J, and Howard, Barbara V
- Published
- 2008
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37. Subjective and objective sleep quality in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the sleep heart health study.
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Unruh ML, Sanders MH, Redline S, Piraino BM, Umans JG, Chami H, Budhiraja R, Punjabi NM, Buysse D, Newman AB, Unruh, Mark L, Sanders, Mark H, Redline, Susan, Piraino, Beth M, Umans, Jason G, Chami, Hassan, Budhiraja, Rohit, Punjabi, Naresh M, Buysse, Daniel, and Newman, Anne B
- Abstract
Background: Studies examining sleep in the hemodialysis (HD) population have largely lacked an adequate comparison group. It therefore is uncertain whether poor sleep quality in the HD population reflects age, chronic health conditions, or effects of conventional HD therapy.Study Design: Cross-sectional matched-group study.Setting& Participants: Forty-six in-center HD patients were compared with 137 community participants participating in the Sleep Heart Health Study matched for age, sex, body mass index, and race.Predictor: HD patients compared with community-dwelling non-HD participants.Outcomes& Measurements: Home unattended polysomnography was performed and scored by using similar protocols. Sleep habits and sleepiness were assessed by using the Sleep Habits Questionnaire and Epworth Sleepiness Scale.Results: Average age of study samples was 63 years, 72% were white, and average body mass index was 28 +/- 5 kg/m(2). HD patients were significantly more likely than community participants to have short sleep (odds ratio, 3.27; 95% confidence interval, 1.16 to 9.25) and decreased sleep efficiency (odds ratio, 5.5; 95% confidence interval, 1.5 to 19.6). HD patients reported more difficulty getting back to sleep (odds ratio, 2.25; 95% confidence interval, 1.11 to 4.60) and waking up too early (odds ratio, 2.39; 95% confidence interval, 1.01 to 5.66). There was no association between polysomnography sleep time and self-reported sleep time (r = 0.09; P = 0.6) or between the Epworth Sleepiness Scale and severity of sleep apnea (r = 0.10; P = 0.5) in the HD population.Limitations: The study was limited to participants older than 45 years.Conclusions: Kidney failure treated with thrice-weekly HD is significantly associated with poor subjective and objective sleep quality. [ABSTRACT FROM AUTHOR]- Published
- 2008
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38. A longitudinal study of risk factors for incident albuminuria in diabetic American Indians: the Strong Heart Study.
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Xu J, Lee ET, Devereux RB, Umans JG, Bella JN, Shara NM, Yeh J, Fabsitz RR, Howard BV, Xu, Jiaqiong, Lee, Elisa T, Devereux, Richard B, Umans, Jason G, Bella, Jonathan N, Shara, Nawar M, Yeh, Jeunliang, Fabsitz, Richard R, and Howard, Barbara V
- Abstract
Background: There have been no studies that use longitudinal data with more than 2 measurements and methods of longitudinal data analysis to identify risk factors for incident albuminuria over time more effectively.Study Design: Longitudinal study.Settings& Participants: A subgroup of participants in the Strong Heart Study, a population-based sample of American Indians, in central Arizona, Oklahoma, and North and South Dakota. Participants with diabetes without albuminuria were followed up for a mean of 4 years.Predictors: Age, sex, study center, high-density lipoprotein and low-density lipoprotein cholesterol levels, triglyceride level, body mass index, systolic blood pressure, use of antihypertensive medication, smoking, hemoglobin A(1c) level, fasting glucose level, type of diabetes therapy, diabetes duration, plasma creatinine level, and urinary albumin-creatinine ratio (UACR).Outcomes& Measurements: Albuminuria was defined as UACR of 30 mg/g or greater. Urine creatinine and albumin were measured by using the picric acid method and a sensitive nephelometric technique, respectively.Results: Of 750 and 568 participants with diabetes without albuminuria and with normal plasma creatinine levels at the first and second examinations, 246 and 132 developed albuminuria by the second and third examinations, respectively. Incident albuminuria was predicted by baseline UACR, fasting glucose level, systolic blood pressure, plasma creatinine level, study center, current smoking, and use of angiotensin-converting enzyme inhibitors and antidiabetic medications. UACR of 10 to 30 mg/g increased the odds of developing albuminuria 2.7-fold compared with UACR less than 5 mg/g.Limitations: Single random morning urine specimen.Conclusions: Many risk factors identified for incident albuminuria can be modified. Control of blood pressure and glucose level, smoking cessation, and use of angiotensin-converting enzyme inhibitors may reduce the incidence of albuminuria. [ABSTRACT FROM AUTHOR]- Published
- 2008
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39. Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the Strong Heart Study.
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Roman, Mary J., Devereux, Richard B., Kizer, Jorge R., Lee, Elisa T., Galloway, James M., Ali, Tauqeer, Umans, Jason G., and Howard, Barbara V.
- Abstract
Brachial blood pressure is predictive of cardiovascular outcome; however central pressure may better represent the load imposed on the coronary and cerebral arteries and thereby bear a stronger relationship to vascular damage and prognosis. Relations of brachial and central pressures to carotid artery hypertrophy (intimal-medial thickness and vascular mass), extent of atherosclerosis (plaque score), and incident cardiovascular events were examined in the Strong Heart Study. Central pressures were calculated using radial applanation tonometry. Among 3520 participants, central and brachial pulse pressures were more strongly related to vascular hypertrophy and extent of atherosclerosis than were systolic pressures. Central pulse pressure was more strongly related to all 3 arterial measures than was brachial pulse pressure (r=0.364 versus 0.309 for plaque score; P<0.001 for comparison of Spearman correlation coefficient; r=0.293 versus 0.249 for intimal-medial thickness; P<0.002; r=0.320 versus 0.289 for vascular mass; P<0.05). Among the 2403 participants free of clinical cardiovascular disease at baseline, 319 suffered fatal or nonfatal cardiovascular events during mean follow-up of 4.8+/-1.3 years. After adjustment for age, gender, current smoking, body mass index, cholesterol:HDL ratio, creatinine, fibrinogen, diabetes, and heart rate, central pulse pressure predicted cardiovascular events more strongly than brachial pulse pressure (hazards ratio=1.15 per 10 mm Hg, chi(2)=13.4, P<0.001 versus hazards ratio=1.10, chi(2)=6.9, P=0.008). In conclusion, noninvasively-determined central pulse pressure is more strongly related to vascular hypertrophy, extent of atherosclerosis, and cardiovascular events than is brachial blood pressure. These findings support prospective examination of use of central blood pressure as a treatment target in future trials. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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40. Genetic variants in nicotinic acetylcholine receptor genes jointly contribute to kidney function in American Indians
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Zhu, Yun, Yang, Jingyun, Li, Shengxu, Cole, Shelley A., Haack, Karin, Umans, Jason G., Franceschini, Nora, Howard, Barbara V., Lee, Elisa T., and Zhao, Jinying
- Abstract
Cigarette smoking negatively affects kidney function. Genetic variants in the nicotinic acetylcholine receptor (nAChR) genes have been associated with nicotine dependence, and are likely to influence renal function and related traits. Whereas each single variant may only exert a small effect, the joint contribution of multiple variants to the risk of disease could be substantial.
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- 2014
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41. Approaches to Preparing Young Scholars for Careers in Interdisciplinary Team Science
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Begg, Melissa D., Crumley, Gene, Fair, Alecia M., Martina, Camille A., McCormack, Wayne T., Merchant, Carol, Patino-Sutton, Cecilia M., and Umans, Jason G.
- Abstract
To succeed as a biomedical researcher, the ability to flourish in interdisciplinary teams of scientists is becoming ever more important. Institutions supported by the Clinical and Translational Science Awards (CTSAs) from the National Institutes of Health have a specific mandate to educate the next generation of clinical and translational researchers. While they strive to advance integrated and interdisciplinary approaches to education and career development in clinical and translational science, general approaches and evaluation strategies may differ, as there is no single, universally accepted or standardized approach. It is important, therefore, to learn about the different approaches used to determine what is effective. We implemented a Web-based survey distributed to education leaders at the 60 funded CTSA institutions; 95% responded to the survey, which included questions on the importance of preparation for interdisciplinary team science careers, methods used to provide such training, and perceived effectiveness of these training programs. The vast majority (86%) of education leaders reported that such training is important, and about half (52%) of the institutions offer such training. Methods of training most often take the form of courses and seminars, both credit bearing and noncredit. These efforts are, by and large, perceived as effective by the training program leaders, although long-term follow-up of trainees would be required to fully evaluate ultimate effectiveness. Results from the survey suggest that CTSA education directors believe that specific training in interdisciplinary team science for young investigators is very important, but few methodologies are universally practiced in CTSA institutions to provide training or to assess performance. Four specific recommendations are suggested to provide measurable strategic goals for education in team science in the context of clinical and translational research.
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- 2014
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42. Cadmium Exposure and Incident Peripheral Arterial Disease
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Tellez-Plaza, Maria, Guallar, Eliseo, Fabsitz, Richard R., Howard, Barbara V., Umans, Jason G., Francesconi, Kevin A., Goessler, Walter, Devereux, Richard B., and Navas-Acien, Ana
- Abstract
Cadmium has been associated with peripheral arterial disease (PAD) in cross-sectional studies, but prospective evidence is lacking. Our goal was to evaluate the association of urine cadmium concentrations with incident PAD in a large population-based cohort.
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- 2013
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43. Cadmium Exposure and Incident Cardiovascular Disease
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Tellez-Plaza, Maria, Guallar, Eliseo, Howard, Barbara V., Umans, Jason G., Francesconi, Kevin A., Goessler, Walter, Silbergeld, Ellen K., Devereux, Richard B., and Navas-Acien, Ana
- Abstract
Cadmium is a widespread toxic metal with potential cardiovascular effects, but no studies have evaluated cadmium and incident cardiovascular disease. We evaluated the association of urine cadmium concentration with cardiovascular disease incidence and mortality in a large population-based cohort.
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- 2013
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44. Interpreting Tacrolimus Concentrations During Pregnancy and Postpartum
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Hebert, Mary F., Zheng, Songmao, Hays, Karen, Shen, Danny D., Davis, Connie L., Umans, Jason G., Miodovnik, Menachem, Thummel, Kenneth E., and Easterling, Thomas R.
- Abstract
Pregnancy after solid organ transplantation, although considered high risk for maternal, fetal, and neonatal complications, has been quite successful. Tacrolimus pharmacokinetic changes during pregnancy make interpretation of whole blood trough concentrations particularly challenging. There are multiple factors that can increase the fraction of unbound tacrolimus, including but not limited to low albumin concentration and low red blood cell count. The clinical titration of dosage to maintain whole blood tacrolimus trough concentrations in the usual therapeutic range can lead to elevated unbound concentrations and possibly toxicity in pregnant women with anemia and hypoalbuminemia. Measurement of plasma or unbound tacrolimus concentrations for pregnant women might better reflect the active form of the drug, although these are technically challenging and often unavailable in usual clinical practice. Tacrolimus crosses the placenta with in utero exposure being approximately 71 of maternal blood concentrations. The lower fetal blood concentrations are likely due to active efflux transport of tacrolimus from the fetus toward the mother by placental P-glycoprotein. To date, tacrolimus has not been linked to congenital malformations but can cause reversible nephrotoxicity and hyperkalemia in the newborn. In contrast, very small amounts of tacrolimus are excreted in the breast milk and are unlikely to elicit adverse effects in the nursing infant.
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- 2013
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45. Urine Arsenic and Prevalent Albuminuria: Evidence From a Population-Based Study
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Zheng, Laura Y., Umans, Jason G., Tellez-Plaza, Maria, Yeh, Fawn, Francesconi, Kevin A., Goessler, Walter, Silbergeld, Ellen K., Guallar, Eliseo, Howard, Barbara V., Weaver, Virginia M., and Navas-Acien, Ana
- Abstract
Long-term arsenic exposure is a major global health problem. However, few epidemiologic studies have evaluated the association of arsenic with kidney measures. Our objective was to evaluate the cross-sectional association between inorganic arsenic exposure and albuminuria in American Indian adults from rural areas of Arizona, Oklahoma, and North and South Dakota.
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- 2013
- Full Text
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46. Pharmacokinetics of Tacrolimus During Pregnancy
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Zheng, Songmao, Easterling, Thomas R., Umans, Jason G., Miodovnik, Menachem, Calamia, Justina C., Thummel, Kenneth E., Shen, Danny D., Davis, Connie L., and Hebert, Mary F.
- Abstract
Information on the pharmacokinetics of tacrolimus during pregnancy is limited to case reports despite the increasing number of pregnant women being prescribed tacrolimus for immunosuppression.
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- 2012
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47. Estimated GFR and Incident Cardiovascular Disease Events in American Indians: The Strong Heart Study
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Shara, Nawar M., Wang, Hong, Mete, Mihriye, Al-Balha, Yaman Rai, Azalddin, Nameer, Lee, Elisa T., Franceschini, Nora, Jolly, Stacey E., Howard, Barbara V., and Umans, Jason G.
- Abstract
In populations with high prevalences of diabetes and obesity, estimating glomerular filtration rate (GFR) by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation may predict cardiovascular disease (CVD) risk better than by using the Modification of Diet in Renal Disease (MDRD) Study equation.
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- 2012
- Full Text
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48. Determinants of Adherence to Delayed-Release Doxylamine and Pyridoxine in Patients With Nausea and Vomiting of Pregnancy
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Costantine, Maged M., Matok, Ilan, Chiossi, Guisseppe, Clark, Shannon, Miodovnik, Menachem, Umans, Jason G., Caritis, Steve, Hankins, Gary D. V., and Koren, Gideon
- Abstract
Women often hesitate to take medications in pregnancy due to fears of perceived potential fetal damage. The authors’ objective is to identify the determinants of adherence to delayed-release doxylamine–pyridoxine (Diclectin) in patients with nausea and vomiting of pregnancy (NVP).
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- 2012
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49. Incremental Value of Biochemical and Echocardiographic Measures in Prediction of Ischemic Stroke
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Karas, Maria G., Devereux, Richard B., Wiebers, David O., Whisnant, Jack P., Best, Lyle G., Lee, Elisa T., Howard, Barbara V., Roman, Mary J., Umans, Jason G., and Kizer, Jorge R.
- Abstract
American Indians have high rates of stroke. Improved risk stratification could enhance prevention, but the ability of biochemical and echocardiographic markers of preclinical disease to improve stroke prediction is not well-defined.
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- 2012
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50. Arsenic species and selected metals in human urine: validation of HPLC/ICPMS and ICPMS procedures for a long-term population-based epidemiological study
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Scheer, Jürgen, Findenig, Silvia, Goessler, Walter, Francesconi, Kevin A., Howard, Barbara, Umans, Jason G., Pollak, Jonathan, Tellez-Plaza, Maria, Silbergeld, Ellen K., Guallar, Eliseo, and Navas-Acien, Ana
- Abstract
Exposure to high inorganic arsenic concentrations in drinking water has been related to detrimental health effects, including cancers and possibly cardiovascular disease, in many epidemiological studies. Recent studies suggest that arsenic might elicit some of its toxic effects also at lower concentrations. The Strong Heart Study, a large epidemiological study of cardiovascular disease in American Indian communities, collected urine samples and performed medical examinations on 4549 participants over a 10 year period beginning in 1989. We used anion-exchange HPLC/ICPMS to determine concentrations of arsenic species (methylarsonate, dimethylarsinate and arsenate) in 5095 urine samples from the Strong Heart Study. We repeated the chromatography on a portion of the urine sample that had been oxidised, by addition of H2O2, to provide additional information on the presence of As(iii) species and thio-arsenicals, and by difference, of arsenobetaine and other non-retained cations. Total concentrations for As, Cd, Mo, Pb, Sb, Se, U, W, and Zn were also determined in the urine samples by ICPMS. The dataset will be used to evaluate the relationships between the concentrations of urinary arsenic species and selected metals with various cardiometabolic health endpoints. We present and discuss the analytical protocol put in place to produce this large and valuable dataset.
- Published
- 2012
- Full Text
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