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1. Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program

Author

Hu, Xiaowei, Qiao, Dandi, Kim, Wonji, Moll, Matthew, Balte, Pallavi P, Lange, Leslie A, Bartz, Traci M, Kumar, Rajesh, Li, Xingnan, Yu, Bing, Cade, Brian E, Laurie, Cecelia A, Sofer, Tamar, Ruczinski, Ingo, Nickerson, Deborah A, Muzny, Donna M, Metcalf, Ginger A, Doddapaneni, Harshavardhan, Gabriel, Stacy, Gupta, Namrata, Dugan-Perez, Shannon, Cupples, L Adrienne, Loehr, Laura R, Jain, Deepti, Rotter, Jerome I, Wilson, James G, Psaty, Bruce M, Fornage, Myriam, Morrison, Alanna C, Vasan, Ramachandran S, Washko, George, Rich, Stephen S, O’Connor, George T, Bleecker, Eugene, Kaplan, Robert C, Kalhan, Ravi, Redline, Susan, Gharib, Sina A, Meyers, Deborah, Ortega, Victor, Dupuis, Josée, London, Stephanie J, Lappalainen, Tuuli, Oelsner, Elizabeth C, Silverman, Edwin K, Barr, R Graham, Thornton, Timothy A, Wheeler, Heather E, Group, TOPMed Lung Working, Cho, Michael H, Im, Hae Kyung, and Manichaikul, Ani

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Clinical Research, Lung, Prevention, Tobacco, Chronic Obstructive Pulmonary Disease, Tobacco Smoke and Health, Respiratory, Good Health and Well Being, Humans, National Heart, Lung, and Blood Institute (U.S.), Pulmonary Disease, Chronic Obstructive, Risk Factors, Transcriptome, United States, TOPMed Lung Working Group, cross-ethnic portability, gene expression, integrative analysis, polygenic transcriptome risk score, pulmonary disease, risk prediction, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV1] and its ratio to forced vital capacity [FEV1/FVC]) in the UK Biobank. We examined prediction performance and cross-ethnic portability of PTRS through smoking-stratified analyses both on 29,381 multi-ethnic participants from TOPMed population/family-based cohorts and on 11,771 multi-ethnic participants from TOPMed COPD-enriched studies. Analyses were carried out for two dichotomous COPD traits (moderate-to-severe and severe COPD) and two quantitative lung function traits (FEV1 and FEV1/FVC). While the proposed PTRS showed weaker associations with disease than PRS for European ancestry, the PTRS showed stronger association with COPD than PRS for African Americans (e.g., odds ratio [OR] = 1.24 [95% confidence interval [CI]: 1.08-1.43] for PTRS versus 1.10 [0.96-1.26] for PRS among heavy smokers with ≥ 40 pack-years of smoking) for moderate-to-severe COPD. Cross-ethnic portability of the PTRS was significantly higher than the PRS (paired t test p

Published
2022

3. Age-Dependent Associations Between 25-Hydroxy Vitamin D Levels and COPD Symptoms: Analysis of SPIROMICS.

Author

Burkes, Robert M, Couper, David J, Barjaktarevic, Igor Z, Cooper, Christopher B, Labaki, Wassim W, Han, Meilan K, Woodruff, Prescott G, Lazarus, Stephen C, Parekh, Trisha M, Paine, Robert, Comellas, Alejandro P, Bowler, Russell P, Loehr, Laura R, Putcha, Nirupama, Wise, Robert A, Brown, Todd T, and Drummond, M Bradley

Subjects
Clinical Research, Nutrition, Lung, Complementary and Integrative Health, Chronic Obstructive Pulmonary Disease, Aging, Respiratory, COPD, COPD outcomes, COPD epidemiology, vitamin D, COPD symptoms
Abstract

IntroductionAge and vitamin D levels may affect symptom burden in chronic obstructive pulmonary disease (COPD). We used the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) to determine independent associations between vitamin D levels and COPD symptoms in different age strata.MethodsSerum 25-hydroxy (OH)-vitamin D levels were modeled continuously and categorically (65 years old), multivariable modeling was performed to identify relationships between 25-OH-vitamin D levels and the COPD Assessment Test (CAT), the modified Medical Research Council score (mMRC), the St George's Respiratory Questionnaire (SGRQ) total and subdomain scores, the Veterans' Specific Activity Questionnaire, and the 6-minute walk test distance.ResultsInIn the middle-aged group, each 5 ng/ml higher 25-OH-vitamin D level was independently associated with more favorable CAT score (-0.35 [-0.67 to -0.03], P=0.03), total SGRQ (-0.91 [-1.65 to -0.17]; P=0.02), and the SGRQ subdomains (Symptoms:-1.07 [-1.96 to -0.18], P=0.02; Impact: -0.77 [-1.53 to -0.003], P=0.049; Activity: -1.07 [-1.96 to -0.18], P=0.02). These associations persisted after the addition of comorbidity score, reported vitamin D supplementation, outdoor time, or season of blood draw to models. No associations were observed between 25-OH-vitamin D levels and symptom scores in the older age group.DiscussionWhen controlled for clinically relevant covariates, higher 25-OH-vitamin D levels are associated with more favorable respiratory-specific symptoms and quality-of-life assessments in middle-age but not older COPD individuals. Study of the role of vitamin D supplementation in the symptom burden of younger COPD patients is needed.

Published
2021

4. Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants.

Author

Zhao, Xutong, Qiao, Dandi, Yang, Chaojie, Kasela, Silva, Kim, Wonji, Ma, Yanlin, Shrine, Nick, Batini, Chiara, Sofer, Tamar, Taliun, Sarah A Gagliano, Sakornsakolpat, Phuwanat, Balte, Pallavi P, Prokopenko, Dmitry, Yu, Bing, Lange, Leslie A, Dupuis, Josée, Cade, Brian E, Lee, Jiwon, Gharib, Sina A, Daya, Michelle, Laurie, Cecelia A, Ruczinski, Ingo, Cupples, L Adrienne, Loehr, Laura R, Bartz, Traci M, Morrison, Alanna C, Psaty, Bruce M, Vasan, Ramachandran S, Wilson, James G, Taylor, Kent D, Durda, Peter, Johnson, W Craig, Cornell, Elaine, Guo, Xiuqing, Liu, Yongmei, Tracy, Russell P, Ardlie, Kristin G, Aguet, François, VanDenBerg, David J, Papanicolaou, George J, Rotter, Jerome I, Barnes, Kathleen C, Jain, Deepti, Nickerson, Deborah A, Muzny, Donna M, Metcalf, Ginger A, Doddapaneni, Harshavardhan, Dugan-Perez, Shannon, Gupta, Namrata, Gabriel, Stacey, Rich, Stephen S, O'Connor, George T, Redline, Susan, Reed, Robert M, Laurie, Cathy C, Daviglus, Martha L, Preudhomme, Liana K, Burkart, Kristin M, Kaplan, Robert C, Wain, Louise V, Tobin, Martin D, London, Stephanie J, Lappalainen, Tuuli, Oelsner, Elizabeth C, Abecasis, Goncalo R, Silverman, Edwin K, Barr, R Graham, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Lung Working Group, Cho, Michael H, and Manichaikul, Ani

Subjects
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Lung Working Group, Lung, Humans, Pulmonary Disease, Chronic Obstructive, Genetic Predisposition to Disease, Intracellular Signaling Peptides and Proteins, Calcium-Binding Proteins, Small Ubiquitin-Related Modifier Proteins, Follow-Up Studies, Feasibility Studies, Polymorphism, Single Nucleotide, Adult, Aged, Aged, 80 and over, Middle Aged, African Americans, Female, Male, Protein Inhibitors of Activated STAT, Respiratory Physiological Phenomena, Genome-Wide Association Study, Genetic Loci, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Whole Genome Sequencing, and over, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive
Abstract

Chronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans. Four novel common variants within the regions of PIAS1, RGN (two variants) and FTO show evidence of replication in the UK Biobank (European ancestry n ~ 320,000), while colocalization analyses leveraging multi-omic data from GTEx and TOPMed identify potential molecular mechanisms underlying four of the 22 novel loci. Our study demonstrates the value of performing WGS analyses and multi-omic follow-up in cohorts of diverse ancestry.

Published
2020

7. Albuminuria, Lung Function Decline, and Risk of Incident Chronic Obstructive Pulmonary Disease. The NHLBI Pooled Cohorts Study

Author

Oelsner, Elizabeth C, Balte, Pallavi P, Grams, Morgan E, Cassano, Patricia A, Jacobs, David R, Barr, R Graham, Burkart, Kristin M, Kalhan, Ravi, Kronmal, Richard, Loehr, Laura R, O'Connor, George T, Schwartz, Joseph E, Shlipak, Michael, Tracy, Russell P, Tsai, Michael Y, White, Wendy, and Yende, Sachin

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Clinical Research, Lung, Women's Health, Health Disparities, Chronic Obstructive Pulmonary Disease, Minority Health, 4.1 Discovery and preclinical testing of markers and technologies, Cardiovascular, Respiratory, Good Health and Well Being, Aged, Albuminuria, Cohort Studies, Comorbidity, Female, Humans, Incidence, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, Risk Factors, United States, epidemiology, spirometry, asthma, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

RationaleChronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD.ObjectivesTo test whether albuminuria was associated with lung function decline and incident CLRDs.MethodsSix U.S. population-based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications.Measurements and main resultsAmong 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV1 decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV1 decline (95% confidence interval [CI], 0.86-4.76%; P = 0.0047), 11.02% greater FEV1/FVC decline (95% CI, 4.43-17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2-31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18-34%, P

Published
2019

9. Association of biomarkers of endothelial function, coagulation activation and kidney injury with persistent albuminuria in sickle cell anaemia.

Author

Elsherif, Laila, Tang, Yihan, Patillo, Kammie L., Wichlan, David, Ogu, Ugochi O., Landes, Kristina, McCune, Paula, Scott, Lara C., Gulledge, Whitney, Woodland, Woodi H., Nelson, Marquita, Loehr, Laura R., Cronin, Robert M., Desai, Payal C., Zhou, Laura Y., Pollock, David M., Zou, Fei, Cai, Jianwen, Derebail, Vimal K., and Ataga, Kenneth I.

Subjects
SICKLE cell anemia, CHRONIC kidney failure, FALSE discovery rate, KIDNEY diseases, KIDNEY injuries
Abstract

Summary: Persistent albuminuria (PA) is common in sickle cell anaemia (SCA). With the association of chronic kidney disease (CKD) with increased mortality, biomarkers that predict its development or progression are needed. We evaluated the association of select biomarkers with PA in adults with SCA using Kruskal–Wallis rank‐sum test and logistic regression models, with adjustment for multiple testing. Of 280 subjects, 100 (35.7%) had PA. Median plasma levels of soluble vascular cell adhesion molecule‐1 (VCAM‐1) (1176.3 vs. 953.4 ng/mL, false discovery rate [FDR] q‐value <0.003), thrombin–antithrombin complex (5.5 vs. 4.7 ng/mL, FDR q‐value = 0.04), and urinary angiotensinogen (AGT) (12.2 vs. 5.3 ng/mg, FDR q‐value <0.003), urinary nephrin (30.6 vs. 27.2 ng/mg, FDR q‐value = 0.04), and urinary kidney injury molecule‐1 (KIM‐1) (0.8 vs. 0.5 ng/mg, FDR q‐value <0.003), normalized to urine creatinine, were significantly higher in subjects with PA. In multivariable analysis, only urinary AGT (odds ratio = 1.058, FDR q‐value <0.0001) remained a significant predictor of PA. In addition, soluble VCAM‐1 (FDR q‐value <0.0001), D‐dimer (FDR q‐value <0.0001), urinary AGT (FDR q‐value <0.0001), KIM‐1 (FDR q‐value <0.0001), and nephrin (FDR q‐value <0.0001) were significantly associated with urine albumin–creatinine ratio in multivariable analyses. Longitudinal studies to evaluate the predictive capacity of biomarkers for the development and progression of CKD in SCA are warranted. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Data Resource Profile: Add Health Mortality Outcomes Surveillance.

Author

Lawrence, Elizabeth M, Trani, Elyssa A, Anthony, Kurtis M, Hummer, Robert A, Jensen, Tiffany, Tuder, Sylvie, Loehr, Laura R, Harris, Kathleen Mullan, and Whitsel, Eric A

Subjects
SEPTEMBER 11 Terrorist Attacks, 2001, UNITED States armed forces, ETHNICITY, CULTURAL pluralism, UNITED States census, MIDDLE-aged persons
Published
2024
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11. Lung function decline in former smokers and low-intensity current smokers: a secondary data analysis of the NHLBI Pooled Cohorts Study

Author

Oelsner, Elizabeth C, Balte, Pallavi P, Bhatt, Surya P, Cassano, Patricia A, Couper, David, Folsom, Aaron R, Freedman, Neal D, Jacobs, David R, Jr, Kalhan, Ravi, Mathew, Amanda R, Kronmal, Richard A, Loehr, Laura R, London, Stephanie J, Newman, Anne B, O'Connor, George T, Schwartz, Joseph E, Smith, Lewis J, White, Wendy B, and Yende, Sachin

Published
2020
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14. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author

Loth, Daan W, Artigas, María Soler, Gharib, Sina A, Wain, Louise V, Franceschini, Nora, Koch, Beate, Pottinger, Tess D, Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P, James, Alan L, Huffman, Jennifer E, Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J, Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M, de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K, Fall, Tove, Viñuela, Ana, Launer, Lenore J, Loehr, Laura R, Fornage, Myriam, Li, Guo, Wilk, Jemma B, Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B, North, Kari E, Rudnicka, Alicja R, Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F, Hastie, Nicholas D, Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A, Pietiläinen, Kirsi H, Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G, Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M, Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H, Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G, Eiriksdottir, Gudny, Morrison, Alanna C, Rotter, Jerome I, Gao, Wei, Postma, Dirkje S, White, Wendy B, Rich, Stephen S, Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J, Psaty, Bruce M, Lohman, Kurt, Burchard, Esteban G, Uitterlinden, André G, Garcia, Melissa, Joubert, Bonnie R, McArdle, Wendy L, Musk, A Bill, Hansel, Nadia, Heckbert, Susan R, Zgaga, Lina, van Meurs, Joyce BJ, Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L, Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T, and Ripatti, Samuli

Subjects
Biological Sciences, Genetics, Human Genome, Clinical Research, Lung, Respiratory, Cohort Studies, Databases, Genetic, Follow-Up Studies, Forced Expiratory Volume, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Lung Diseases, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Prognosis, Quantitative Trait Loci, Respiratory Function Tests, Spirometry, Vital Capacity, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

Published
2014

15. Persistent albuminuria and chronic kidney disease in adults with sickle cell anaemia: Results from a multicenter natural history study.

Author

Zhou, Laura Y., Derebail, Vimal K., Desai, Payal C., Elsherif, Laila, Patillo, Kammie L., McCune, Paula, Wichlan, David, Landes, Kristina, Ogu, Ugochi O., Nelson, Marquita, Loehr, Laura R., Cronin, Robert M., Tang, Yihan, Cai, Jianwen, and Ataga, Kenneth I.

Subjects
SICKLE cell anemia, CHRONIC kidney failure, LOGISTIC regression analysis, GLOMERULAR filtration rate, SYSTOLIC blood pressure
Abstract

Summary: Clinical and laboratory correlates of chronic kidney disease (CKD) in sickle cell anaemia remain incompletely defined. In a multicenter cohort study, we evaluated the prevalence of persistent albuminuria (PA) and characteristics associated with PA, albumin–creatinine ratio (ACR) and decreased estimated glomerular filtration rate (eGFR) using logistic, linear and multinomial regression models, respectively. Of 269 participants (median age: 30 years; 57.2% females), the prevalence of PA was 35.7%. Using baseline ACR values of <100 and ≥100 mg/g, the probabilities of PA were 30.0% and 94.6%, respectively. In multivariable logistic regression analyses, male sex (β = 0.80 [SE = 0.36], p = 0.024) and ACE inhibitors/ARBs use (β = 1.54 [SE = 0.43], p < 0.001) were associated with higher likelihoods of PA, while higher haemoglobin (β = −0.33 [SE = 0.13], p = 0.009) and HbF (β = −0.04 [SE = 0.02], p = 0.041) were associated with lower likelihoods of PA. In multivariable multinomial regression analyses, older age (β = 0.06 [SE = 0.02], p = 0.004) and higher alkaline phosphatase (β = 0.01 [SE = 0.00], p = 0.004) were associated with higher odds of having eGFR 60–90 versus eGFR>90 mL/min/1.73 m2 using the cystatin C‐based CKD‐EPI‐2012 equation. Additionally, higher systolic blood pressure (β = 0.11 [SE = 0.03], p = 0.001) and blood urea nitrogen (β = 0.45 [SE = 0.12], p < 0.001) were associated with higher odds, while higher haemoglobin (β = −1.22 [SE = 0.43], p = 0.004) was associated with lower odds of having eGFR<60 versus eGFR>90 mL/min/1.73 m2. PA and decreased eGFR are associated with measures of disease severity and comorbid conditions (Clinicaltrials.gov Identifier: NCT03277547). [ABSTRACT FROM AUTHOR]

Published
2024
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17. The QT interval and risk of incident atrial fibrillation

Author

Mandyam, Mala C, Soliman, Elsayed Z, Alonso, Alvaro, Dewland, Thomas A, Heckbert, Susan R, Vittinghoff, Eric, Cummings, Steven R, Ellinor, Patrick T, Chaitman, Bernard R, Stocke, Karen, Applegate, William B, Arking, Dan E, Butler, Javed, Loehr, Laura R, Magnani, Jared W, Murphy, Rachel A, Satterfield, Suzanne, Newman, Anne B, and Marcus, Gregory M

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Cardiovascular, Aging, Clinical Research, Good Health and Well Being, Aged, Atrial Fibrillation, Cohort Studies, Electrocardiography, Female, Humans, Incidence, Long QT Syndrome, Male, Middle Aged, Risk Factors, Atrial fibrillation, Epidemiology, Risk, QT interval, Electrocardiogram, ECG, AF, ARIC, Atherosclerosis Risk in Communities, CHF, CHS, CI, Cardiovascular Health Study, HR, HTN, Health ABC, Health, Aging, and Body Composition, LQTS, QT corrected by using the Framingham formula, QT(Fram), QTc, REGARDS, Reasons for Geographic and Racial Differences in Stroke, atrial fibrillation, confidence interval, congestive heart failure, corrected QT interval, electrocardiogram, hazard ratio, hypertension, long QT syndrome, Biomedical Engineering, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundAbnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine.ObjectiveTo determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF.MethodsWe examined a prolonged QT interval corrected by using the Framingham formula (QT(Fram)) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by using other formulas.ResultsAmong 14,538 ARIC study participants, a prolonged QT(Fram) predicted a roughly 2-fold increased risk of AF (hazard ratio [HR] 2.05; 95% confidence interval [CI] 1.42-2.96; P < .001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in Cardiovascular Health Study and Health, Aging, and Body Composition study and were similar across various QT correction methods. Also in the ARIC study, each 10-ms increase in QT(Fram) was associated with an increased unadjusted (HR 1.14; 95% CI 1.10-1.17; P < .001) and adjusted (HR 1.11; 95% CI 1.07-1.14; P < .001) risk of AF. Findings regarding a short QT interval were inconsistent across cohorts.ConclusionsA prolonged QT interval is associated with an increased risk of incident AF.

Published
2013

23. Prevalence of infertility and pregnancy loss among individuals with kidney disease in the Hispanic Community Health Study/Study of Latinos.

Author

Reynolds, Monica L, Loehr, Laura R, Hogan, Susan L, Hu, Yichun, Isasi, Carmen R, Cordero, Christina, Ricardo, Ana C, Lash, James P, and Derebail, Vimal K

Subjects
KIDNEY disease treatments, RESEARCH, HYSTERECTOMY, CONFIDENCE intervals, HEALTH services accessibility, MISCARRIAGE, HISPANIC Americans, SELF-evaluation, MULTIPLE regression analysis, MENSTRUATION, PUBLIC health, INFERTILITY, KIDNEY diseases, RISK assessment, DISEASE prevalence, DESCRIPTIVE statistics, RESEARCH funding, STATISTICAL correlation, ODDS ratio, STATISTICAL sampling, DATA analysis software, WOMEN'S health, DISEASE risk factors, DISEASE complications
Abstract

Background: Hispanic/Latino individuals are less likely to receive optimal treatment for chronic kidney disease than non-Hispanic whites. This may be particularly detrimental for women of reproductive age as chronic kidney disease increases risk for infertility, menstrual irregularities, and pregnancy loss. While these maternal outcomes have been associated with advanced chronic kidney disease, their occurrence in early chronic kidney disease is unclear. Objectives/Design: Using baseline (2008–2011) and second study visit (2014–2017) data from the Hispanic Community Health Study/Study of Latinos, we retrospectively assessed the prevalence of chronic kidney disease as well as the association between chronic kidney disease and self-reported infertility, cessation of menses, hysterectomy, and nonviable pregnancy loss (experienced at less than 24 weeks gestation) in women of reproductive age (18–45 years). Methods: Multivariable survey logistic regression analyses determined the unadjusted and multivariable-adjusted prevalence odds ratios with 95% confidence intervals between chronic kidney disease and the separate outcomes. Results: Among 2589 Hispanic/Latino women included (mean age = 31.4 years), 4.6% were considered to have chronic kidney disease. In adjusted analyses, women with chronic kidney disease did not have a significantly increased odds of infertility (odds ratio = 1.02, 95% confidence interval = 0.42–2.49), cessation of menses (odds ratio = 1.25, 95% confidence interval = 0.52–3.04), or hysterectomy (odds ratio = 1.17, 95% confidence interval = 0.61–2.25) compared to those without chronic kidney disease. In those with chronic kidney disease, the adjusted odds of a nonviable pregnancy loss occurring after baseline visit were increased (odds ratio = 2.11, 95% confidence interval = 0.63–7.02) but not statistically significance. Conclusion: The presence of early stage chronic kidney disease did not confer a significant risk of infertility, cessation of menses, or nonviable pregnancy loss. Plain language summary: The Hispanic Community Health Study/Study of Latinos is a population-based study of over 16,000 Hispanic/Latino individuals throughout the United States. Within this cohort, we assessed the prevalence of chronic kidney disease in women of reproductive age (18–45 years old) and the associations between kidney disease and infertility, cessation of menses, and nonviable pregnancy loss (loss occurring before the 24th week of pregnancy). We found that kidney disease affected 1 in 20 women of reproductive age and those with kidney disease were more likely to have obesity, diabetes, and hypertension. Compared to those without kidney disease, the presence of kidney disease did not increase risk of infertility, cessation of menses, or nonviable pregnancy loss. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

Author

Demenais, Florence, Margaritte-Jeannin, Patricia, Barnes, Kathleen C., Cookson, William O. C., Altmüller, Janine, Ang, Wei, Barr, R. Graham, Beaty, Terri H., Becker, Allan B., Beilby, John, Bisgaard, Hans, Bjornsdottir, Unnur Steina, Bleecker, Eugene, Bønnelykke, Klaus, Boomsma, Dorret I., Bouzigon, Emmanuelle, Brightling, Christopher E., Brossard, Myriam, Brusselle, Guy G., Burchard, Esteban, Burkart, Kristin M., Bush, Andrew, Chan-Yeung, Moira, Chung, Kian Fan, Couto Alves, Alexessander, Curtin, John A., Custovic, Adnan, Daley, Denise, de Jongste, Johan C., Del-Rio-Navarro, Blanca E., Donohue, Kathleen M., Duijts, Liesbeth, Eng, Celeste, Eriksson, Johan G., Farrall, Martin, Fedorova, Yuliya, Feenstra, Bjarke, Ferreira, Manuel A., Freidin, Maxim B., Gajdos, Zofia, Gauderman, Jim, Gehring, Ulrike, Geller, Frank, Genuneit, Jon, Gharib, Sina A., Gilliland, Frank, Granell, Raquel, Graves, Penelope E., Gudbjartsson, Daniel F., Haahtela, Tari, Heckbert, Susan R., Heederik, Dick, Heinrich, Joachim, Heliövaara, Markku, Henderson, John, Himes, Blanca E., Hirose, Hiroshi, Hirschhorn, Joel N., Hofman, Albert, Holt, Patrick, Hottenga, Jouke, Hudson, Thomas J., Hui, Jennie, Imboden, Medea, Ivanov, Vladimir, Jaddoe, Vincent W. V., James, Alan, Janson, Christer, Jarvelin, Marjo-Riitta, Jarvis, Deborah, Jones, Graham, Jonsdottir, Ingileif, Jousilahti, Pekka, Kabesch, Michael, Kähönen, Mika, Kantor, David B., Karunas, Alexandra S., Khusnutdinova, Elza, Koppelman, Gerard H., Kozyrskyj, Anita L., Kreiner, Eskil, Kubo, Michiaki, Kumar, Rajesh, Kumar, Ashish, Kuokkanen, Mikko, Lahousse, Lies, Laitinen, Tarja, Laprise, Catherine, Lathrop, Mark, Lau, Susanne, Lee, Young-Ae, Lehtimäki, Terho, Letort, Sébastien, Levin, Albert M., Li, Guo, Liang, Liming, Loehr, Laura R., London, Stephanie J., Loth, Daan W., Manichaikul, Ani, Marenholz, Ingo, Martinez, Fernando J., Matheson, Melanie C., Mathias, Rasika A., Matsumoto, Kenji, Mbarek, Hamdi, McArdle, Wendy L., Melbye, Mads, Melén, Erik, Meyers, Deborah, Michel, Sven, Mohamdi, Hamida, Musk, Arthur W., Myers, Rachel A., Nieuwenhuis, Maartje A. E., Noguchi, Emiko, O’Connor, George T., Ogorodova, Ludmila M., Palmer, Cameron D., Palotie, Aarno, Park, Julie E., Pennell, Craig E., Pershagen, Göran, Polonikov, Alexey, Postma, Dirkje S., Probst-Hensch, Nicole, Puzyrev, Valery P., Raby, Benjamin A., Raitakari, Olli T., Ramasamy, Adaikalavan, Rich, Stephen S., Robertson, Colin F., Romieu, Isabelle, Salam, Muhammad T., Salomaa, Veikko, Schlünssen, Vivi, Scott, Robert, Selivanova, Polina A., Sigsgaard, Torben, Simpson, Angela, Siroux, Valérie, Smith, Lewis J., Solodilova, Maria, Standl, Marie, Stefansson, Kari, Strachan, David P., Stricker, Bruno H., Takahashi, Atsushi, Thompson, Philip J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiesler, Carla M. T., Torgerson, Dara G., Tsunoda, Tatsuhiko, Uitterlinden, André G., van der Valk, Ralf J. P., Vaysse, Amaury, Vedantam, Sailaja, von Berg, Andrea, von Mutius, Erika, Vonk, Judith M., Waage, Johannes, Wareham, Nick J., Weiss, Scott T., White, Wendy B., Wickman, Magnus, Widén, Elisabeth, Willemsen, Gonneke, Williams, L. Keoki, Wouters, Inge M., Yang, James J., Zhao, Jing Hua, Moffatt, Miriam F., Ober, Carole, and Nicolae, Dan L.

Published
2018
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27. Mortality Outcomes Surveillance, Part I: Ascertaining Decedents (2021 Update)

Author

Hummer, Robert A., Loehr, Laura R., Lawrence, Elizabeth M., Trani, Elyssa A., Whitsel, Eric A., and Hill, Mary Jane

Abstract

Mortality Outcomes Surveillance, Part I: Ascertaining Decedents (2021 Update) summarizes the data stemming from the protocol used to (1) trace sample members and then (2) screen, match, and score all decedents in the National Longitudinal Study of Adolescent to Adult Health (Add Health). Mortality Outcomes Surveillance, Part II: Adjudicating Causes of Death & In-Hospital Cardiovascular Outcomes summarizes data stemming from the protocol used to (3) assemble and abstract decedent cohort histories, obituaries, death certificates, healthcare provider questionnaires, coroner/medical examiner autopsy reports, next-of-kin interviews, and hospital records; and then (4) review, classify, and adjudicate all deaths and in-hospital cardiovascular outcomes ≤ 1 month before dates of death.

Published
2023
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28. Abstract P624: Peripheral Artery Disease and Long-Term Risk of Femur Fracture Among Older Adults: The Atherosclerosis Risk in Communities Study

Author

Chen, Mengkun, primary, Ballew, Shoshana, additional, Mok, Yejin, additional, Sang, Yingying, additional, Schneider, Andrea, additional, Grams, Morgan, additional, Loehr, Laura R, additional, Tanaka, Hirofumi, additional, Selvin, Elizabeth, additional, Coresh, Josef, additional, and Matsushita, Kuni, additional

Published
2023
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34. Sex differences in progression of kidney disease in sickle cell disease

Author

Ataga, Kenneth I., primary, Zhou, Qingning, additional, Saraf, Santosh L., additional, Hankins, Jane S., additional, Ciccone, Emily J., additional, Loehr, Laura R., additional, Garrett, Melanie E., additional, Ashley-Koch, Allison E., additional, Cai, Jianwen, additional, Telen, Marilyn J., additional, and Derebail, Vimal K., additional

Published
2022
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35. Evaluating Equations for Estimated Glomerular Filtration Rate (eGFR) in Patients with Sickle Cell Disease (SCD)

Author

Derebail, Vimal K, primary, Zhou, Laura Y, additional, Elsherif, Laila, additional, Patillo, Kammie L, additional, Wichlan, David, additional, Landes, Kristina, additional, McCune, Paula, additional, Loehr, Laura R, additional, Cronin, Robert M, additional, Desai, Payal C, additional, Cai, Jianwen, additional, and Ataga, Kenneth I, additional

Published
2022
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40. Genome-wide association study of lung function decline in adults with and without asthma

Author

Imboden, Medea, Bouzigon, Emmanuelle, Curjuric, Ivan, Ramasamy, Adaikalavan, Kumar, Ashish, Hancock, Dana B., Wilk, Jemma B., Vonk, Judith M., Thun, Gian A., Siroux, Valerie, Nadif, Rachel, Monier, Florent, Gonzalez, Juan R., Wjst, Matthias, Heinrich, Joachim, Loehr, Laura R., Franceschini, Nora, North, Kari E., Altmüller, Janine, Koppelman, Gerard H., Guerra, Stefano, Kronenberg, Florian, Lathrop, Mark, Moffatt, Miriam F., O’Connor, George T., Strachan, David P., Postma, Dirkje S., London, Stephanie J., Schindler, Christian, Kogevinas, Manolis, Kauffmann, Francine, Jarvis, Debbie L., Demenais, Florence, and Probst-Hensch, Nicole M.

Published
2012
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43. Mortality Outcomes Surveillance, Part I: Ascertaining Decedents

Author

Trani, Elyssa A., Hummer, Robert A., Hill, Mary Jane, Whitsel, Eric A., and Loehr, Laura R.

Abstract

Mortality Outcomes Surveillance, Part I: Ascertaining Decedents summarizes the data stemming from the protocol used to (1) trace sample members and then (2) screen, match, and score all decedents in the National Longitudinal Study of Adolescent to Adult Health (Add Health). Mortality Outcomes Surveillance, Part II: Adjudicating Causes of Death & In-Hospital Cardiovascular Outcomes summarizes data stemming from the protocol used to (3) assemble and abstract decedent cohort histories, obituaries, death certificates, healthcare provider questionnaires, coroner/medical examiner autopsy reports, next-of-kin interviews, and hospital records; and then (4) review, classify, and adjudicate all deaths and in-hospital cardiovascular outcomes ≤ 1 month before dates of death.

Published
2022
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47. Racial Differences in Trends and Prognosis of Guideline-Directed Medical Therapy for Heart Failure with Reduced Ejection Fraction: the Atherosclerosis Risk in Communities (ARIC) Surveillance Study

Author

Mathews, Lena, primary, Ding, Ning, additional, Sang, Yingying, additional, Loehr, Laura R., additional, Shin, Jung-Im, additional, Punjabi, Naresh M., additional, Bertoni, Alain G., additional, Crews, Deidra C., additional, Rosamond, Wayne D., additional, Coresh, Josef, additional, Ndumele, Chiadi E., additional, Matsushita, Kunihiro, additional, and Chang, Patricia P., additional

Published
2022
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50. Replication and fine mapping of asthma-associated loci in individuals of African ancestry

Author

Kantor, David B., Palmer, Cameron D., Young, Taylor R., Meng, Yan, Gajdos, Zofia K., Lyon, Helen, Price, Alkes L., Pollack, Samuela, London, Stephanie J., Loehr, Laura R., Smith, Lewis J., Kumar, Rajesh, Jacobs Jr., David R., Petrini, Marcy F., O’Connor, George T., White, Wendy B., Papanicolaou, George, Burkart, Kristin M., Heckbert, Susan R., Barr, R. Graham, and Hirschhorn, Joel N.

Published
2013
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