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Find video protocols related to scientific articles indexed in Pubmed.
Polygenic Overlap Between Kidney Function and Large Artery Atherosclerotic Stroke.
Stroke
PUBLISHED: 10-30-2014
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Epidemiological studies show strong associations between kidney dysfunction and risk of ischemic stroke (IS), the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability because of a common polygenic basis and whether this differed for IS subtypes.
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High-Sensitivity Troponin T and Cardiovascular Events in Systolic Blood Pressure Categories: Atherosclerosis Risk in Communities Study.
Hypertension
PUBLISHED: 10-29-2014
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Based on observational studies, there is a linear increase in cardiovascular risk with higher systolic blood pressure (SBP), yet clinical trials have not shown benefit across all SBP categories. We assessed whether troponin T measured using high-sensitivity assay was associated with cardiovascular disease within SBP categories in 11?191 Atherosclerosis Risk in Communities study participants. Rested sitting SBP by 10-mm?Hg increments and troponin categories were identified. Incident heart failure hospitalization, coronary heart disease, and stroke were ascertained for a median of 12 years after excluding individuals with corresponding disease. Approximately 53% of each type of cardiovascular event occurred in individuals with SBP<140 mm?Hg and troponin T ?3 ng/L. Higher troponin T was associated with increasing cardiovascular events across most SBP categories. The association was strongest for heart failure and least strong for stroke. There was no similar association of SBP with cardiovascular events across troponin T categories. Individuals with troponin T ?3 ng/L and SBP <140 mm?Hg had higher cardiovascular risk compared with those with troponin T <3 ng/L and SBP 140 to 159 mm?Hg. Higher troponin T levels within narrow SBP categories portend increased cardiovascular risk, particularly for heart failure. Individuals with lower SBP but measurable troponin T had greater cardiovascular risk compared with those with suboptimal SBP but undetectable troponin T. Future trials of systolic hypertension may benefit by using high-sensitivity troponin T to target high-risk patients.
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HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.
Daniel I Swerdlow, David Preiss, Karoline B Kuchenbaecker, Michael V Holmes, Jorgen E L Engmann, Tina Shah, Reecha Sofat, Stefan Stender, Paul C D Johnson, Robert A Scott, Maarten Leusink, Niek Verweij, Stephen J Sharp, Yiran Guo, Claudia Giambartolomei, Christina Chung, Anne Peasey, Antoinette Amuzu, KaWah Li, Jutta Palmen, Philip Howard, Jackie A Cooper, Fotios Drenos, Yun R Li, Gordon Lowe, John Gallacher, Marlene C W Stewart, Ioanna Tzoulaki, Sarah G Buxbaum, Daphne L van der A, Nita G Forouhi, N Charlotte Onland-Moret, Yvonne T van der Schouw, Renate B Schnabel, Jaroslav A Hubacek, Růžena Kubinova, Miglė Bacevičienė, Abdonas Tamosiunas, Andrzej Pająk, Romanvan Topor-Madry, Urszula Stepaniak, Sofia Malyutina, Damiano Baldassarre, Bengt Sennblad, Elena Tremoli, Ulf de Faire, Fabrizio Veglia, Ian Ford, J Wouter Jukema, Rudi G J Westendorp, Gert Jan de Borst, Pim A de Jong, Ale Algra, Wilko Spiering, Anke H Maitland-van der Zee, Olaf H Klungel, Anthonius de Boer, Pieter A Doevendans, Charles B Eaton, Jennifer G Robinson, David Duggan, , John Kjekshus, John R Downs, Antonio M Gotto, Anthony C Keech, Roberto Marchioli, Gianni Tognoni, Peter S Sever, Neil R Poulter, David D Waters, Terje R Pedersen, Pierre Amarenco, Haruo Nakamura, John J V McMurray, James D Lewsey, Daniel I Chasman, Paul M Ridker, Aldo P Maggioni, Luigi Tavazzi, Kausik K Ray, Sreenivasa Rao Kondapally Seshasai, JoAnn E Manson, Jackie F Price, Peter H Whincup, Richard W Morris, Debbie A Lawlor, George Davey Smith, Yoav Ben-Shlomo, Pamela J Schreiner, Myriam Fornage, David S Siscovick, Mary Cushman, Meena Kumari, Nick J Wareham, W M Monique Verschuren, Susan Redline, Sanjay R Patel, John C Whittaker, Anders Hamsten, Joseph A Delaney, Caroline Dale, Tom R Gaunt, Andrew Wong, Diana Kuh, Rebecca Hardy, Sekar Kathiresan, Berta A Castillo, Pim van der Harst, Eric J Brunner, Anne Tybjaerg-Hansen, Michael G Marmot, Ronald M Krauss, Michael Tsai, Josef Coresh, Ronald C Hoogeveen, Bruce M Psaty, Leslie A Lange, Hakon Hakonarson, Frank Dudbridge, Steve E Humphries, Philippa J Talmud, Mika Kivimäki, Nicholas J Timpson, Claudia Langenberg, Folkert W Asselbergs, Mikhail Voevoda, Martin Bobak, Hynek Pikhart, James G Wilson, Alex P Reiner, Brendan J Keating, Aroon D Hingorani, Naveed Sattar.
Lancet
PUBLISHED: 09-29-2014
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Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.
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Circulating fibroblast growth factor-23 and the incidence of atrial fibrillation: the Atherosclerosis Risk in Communities study.
J Am Heart Assoc
PUBLISHED: 09-20-2014
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Increased concentrations of circulating fibroblast growth factor 23 (FGF-23) have been associated with higher risk of cardiovascular disease. The association between FGF-23 and the risk of atrial fibrillation (AF), a common arrhythmia, is less defined. Thus, we explored whether FGF-23 concentration was associated with AF incidence in a large community-based cohort.
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Association of 1,5-anhydroglucitol with diabetes and microvascular conditions.
Clin. Chem.
PUBLISHED: 09-08-2014
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1,5-Anhydroglucitol (1,5-AG) is inversely related to hyperglycemia and may be a useful indicator of short-term (1-2 weeks) hyperglycemia and glycemic excursions, but its prognostic value is unclear. We sought to evaluate the associations of 1,5-AG with risk of diabetes and microvascular disease.
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Diabetes mellitus, prediabetes, and incidence of subclinical myocardial damage.
Circulation
PUBLISHED: 08-22-2014
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Persons with prediabetes and diabetes mellitus are at high risk for cardiovascular events. However, the relationships of prediabetes and diabetes mellitus to the development of subclinical myocardial damage are unclear.
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Association of plasma levels of soluble receptor for advanced glycation end products and risk of kidney disease: the Atherosclerosis Risk in Communities study.
Nephrol. Dial. Transplant.
PUBLISHED: 08-21-2014
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Advanced glycation end products and their cell-bound receptors are thought to mediate the adverse effects of vascular disease through oxidative stress, inflammation and endothelial dysfunction. We examined the association between the soluble form of receptor for advanced glycation end products (sRAGE) and kidney disease.
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Subclinical Atherosclerosis Measures for Cardiovascular Prediction in CKD.
J. Am. Soc. Nephrol.
PUBLISHED: 08-21-2014
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Whether inclusion of the coronary artery calcium score improves cardiovascular risk prediction in individuals with CKD, a population with unique calcium-phosphate homeostasis, is unknown. Among 6553 participants ages 45-84 years without prior cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis, coronary artery calcium score was assessed for cardiovascular risk prediction beyond the Framingham predictors in those with (n=1284) and without CKD and contrasted with carotid intima-media thickness and ankle-brachial index (two other measures of subclinical atherosclerosis). During a median follow-up of 8.4 years, 650 cardiovascular events (coronary heart disease, stroke, heart failure, and peripheral artery disease) occurred (236 events in subjects with CKD). In Cox proportional hazards models adjusted for Framingham predictors, each subclinical measure was independently associated with cardiovascular outcomes, with larger adjusted hazard ratios (HRs; per 1 SD) for coronary artery calcium score than carotid intima-media thickness or ankle-brachial index in subjects without and with CKD (HR, 1.69; 95% confidence interval [95% CI], 1.45 to 1.97 versus HR, 1.12; 95% CI, 1.00 to 1.25 and HR, 1.20; 95% CI, 1.08 to 1.32, respectively). Compared with inclusion of carotid intima-media thickness or ankle-brachial index, inclusion of the coronary artery calcium score led to greater increases in C statistic for predicting cardiovascular disease and net reclassification improvement. Coronary artery calcium score performed best for the prediction of coronary heart disease and heart failure, regardless of CKD status. In conclusion, each measure improved cardiovascular risk prediction in subjects with CKD, with the greatest improvement observed with coronary artery calcium score.
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Association of Kidney Function and Albuminuria With Prevalent and Incident Hypertension: The Atherosclerosis Risk in Communities (ARIC) Study.
Am. J. Kidney Dis.
PUBLISHED: 08-20-2014
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Decreased kidney function and kidney damage may predate hypertension, but only a few studies have investigated both types of markers simultaneously, and these studies have obtained conflicting results.
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Temporal trends in the population attributable risk for cardiovascular disease: the Atherosclerosis Risk in Communities Study.
Circulation
PUBLISHED: 08-11-2014
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The extent to which the relative contributions of traditional cardiovascular risk factors to incident cardiovascular disease (CVD) may have changed over time remains unclear.
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Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study.
JAMA Neurol
PUBLISHED: 08-05-2014
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Hypertension is a treatable potential cause of cognitive decline and dementia, but its greatest influence on cognition may occur in middle age.
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Association of urinary KIM-1, L-FABP, NAG and NGAL with incident end-stage renal disease and mortality in American Indians with type 2 diabetes mellitus.
Diabetologia
PUBLISHED: 07-29-2014
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Kidney injury molecule 1 (KIM-1), liver fatty acid-binding protein (L-FABP), N-acetyl-?-D-glucosaminidase (NAG) and neutrophil gelatinase-associated lipocalin (NGAL) are urinary biomarkers of renal tubular injury. We examined their association with incident end-stage renal disease (ESRD) and all-cause mortality in American Indians with type 2 diabetes.
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Serum Fibroblast Growth Factor-23 Is Associated with Incident Kidney Disease.
J. Am. Soc. Nephrol.
PUBLISHED: 07-26-2014
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Fibroblast growth factor-23 is a bone-derived hormone that increases urinary phosphate excretion and inhibits hydroxylation of 25-hydroxyvitamin D. Recent studies suggest that fibroblast growth factor-23 may be an early biomarker of CKD progression. However, its role in kidney function decline in the general population is unknown. We assessed the relationship between baseline (1990-1992) serum levels of intact fibroblast growth factor-23 and incident ESRD in 13,448 Atherosclerosis Risk in Communities study participants (56.1% women, 74.7% white) followed until December 31, 2010. At baseline, the mean age of participants was 56.9 years and the mean eGFR was 97 ml/min per 1.73 m(2). During a median follow-up of 19 years, 267 participants (2.0%) developed ESRD. After adjustment for demographic characteristics, baseline eGFR, traditional CKD risk factors, and markers of mineral metabolism, the highest fibroblast growth factor-23 quintile (>54.6 pg/ml) compared with the lowest quintile (<32.0 pg/ml) was associated with risk of developing ESRD (hazard ratio, 2.10; 95% confidence interval, 1.31 to 3.36; trend P<0.001). In a large, community-based study comprising a broad range of kidney function, higher baseline fibroblast growth factor-23 levels were associated with increased risk of incident ESRD independent of the baseline level of kidney function and a number of other risk factors.
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Stroke incidence and mortality trends in US communities, 1987 to 2011.
JAMA
PUBLISHED: 07-17-2014
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Prior studies have shown decreases in stroke mortality over time, but data on validated stroke incidence and long-term trends by race are limited.
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Serum magnesium, phosphorus, and calcium are associated with risk of incident heart failure: the Atherosclerosis Risk in Communities (ARIC) Study.
Am. J. Clin. Nutr.
PUBLISHED: 07-16-2014
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Heart failure (HF) is a major source of morbidity and mortality, particularly among the elderly. Magnesium, phosphorus, and calcium are micronutrients traditionally viewed in relation to bone health or chronic kidney disease. However, they also may be associated with risk of cardiovascular disease through a broad range of physiologic roles.
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Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.
Michael V Holmes, Caroline E Dale, Luisa Zuccolo, Richard J Silverwood, Yiran Guo, Zheng Ye, David Prieto-Merino, Abbas Dehghan, Stella Trompet, Andrew Wong, Alana Cavadino, Dagmar Drogan, Sandosh Padmanabhan, Shanshan Li, Ajay Yesupriya, Maarten Leusink, Johan Sundström, Jaroslav A Hubacek, Hynek Pikhart, Daniel I Swerdlow, Andrie G Panayiotou, Svetlana A Borinskaya, Chris Finan, Sonia Shah, Karoline B Kuchenbaecker, Tina Shah, Jorgen Engmann, Lasse Folkersen, Per Eriksson, Fulvio Ricceri, Olle Melander, Carlotta Sacerdote, Dale M Gamble, Sruti Rayaprolu, Owen A Ross, Stela McLachlan, Olga Vikhireva, Ivonne Sluijs, Robert A Scott, Vera Adamkova, Leon Flicker, Frank M van Bockxmeer, Christine Power, Pedro Marques-Vidal, Tom Meade, Michael G Marmot, José M Ferro, Sofia Paulos-Pinheiro, Steve E Humphries, Philippa J Talmud, Irene Mateo Leach, Niek Verweij, Allan Linneberg, Tea Skaaby, Pieter A Doevendans, Maarten J Cramer, Pim van der Harst, Olaf H Klungel, Nicole F Dowling, Anna F Dominiczak, Meena Kumari, Andrew N Nicolaides, Cornelia Weikert, Heiner Boeing, Shah Ebrahim, Tom R Gaunt, Jackie F Price, Lars Lannfelt, Anne Peasey, Růžena Kubinova, Andrzej Pająk, Sofia Malyutina, Mikhail I Voevoda, Abdonas Tamosiunas, Anke H Maitland-van der Zee, Paul E Norman, Graeme J Hankey, Manuela M Bergmann, Albert Hofman, Oscar H Franco, Jackie Cooper, Jutta Palmen, Wilko Spiering, Pim A de Jong, Diana Kuh, Rebecca Hardy, André G Uitterlinden, M Arfan Ikram, Ian Ford, Elina Hyppönen, Osvaldo P Almeida, Nicholas J Wareham, Kay-Tee Khaw, Anders Hamsten, Lise Lotte N Husemoen, Anne Tjønneland, Janne S Tolstrup, Eric Rimm, Joline W J Beulens, W M Monique Verschuren, N Charlotte Onland-Moret, Marten H Hofker, S Goya Wannamethee, Peter H Whincup, Richard Morris, Astrid M Vicente, Hugh Watkins, Martin Farrall, J Wouter Jukema, James Meschia, L Adrienne Cupples, Stephen J Sharp, Myriam Fornage, Charles Kooperberg, Andrea Z LaCroix, James Y Dai, Matthew B Lanktree, David S Siscovick, Eric Jorgenson, Bonnie Spring, Josef Coresh, Yun R Li, Sarah G Buxbaum, Pamela J Schreiner, R Curtis Ellison, Michael Y Tsai, Sanjay R Patel, Susan Redline, Andrew D Johnson, Ron C Hoogeveen, Hakon Hakonarson, Jerome I Rotter, Eric Boerwinkle, Paul I W de Bakker, Mika Kivimäki, Folkert W Asselbergs, Naveed Sattar, Debbie A Lawlor, John Whittaker, George Davey Smith, Kenneth Mukamal, Bruce M Psaty, James G Wilson, Leslie A Lange, Ajna Hamidovic, Aroon D Hingorani, Børge G Nordestgaard, Martin Bobak, David A Leon, Claudia Langenberg, Tom M Palmer, Alex P Reiner, Brendan J Keating, Frank Dudbridge, Juan P Casas, .
BMJ
PUBLISHED: 07-12-2014
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To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.
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Serum metabolomic profiling and incident CKD among African Americans.
Clin J Am Soc Nephrol
PUBLISHED: 07-10-2014
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Novel biomarkers that more accurately reflect kidney function and predict future CKD are needed. The human metabolome is the product of multiple physiologic or pathophysiologic processes and may provide novel insight into disease etiology and progression. This study investigated whether estimated kidney function would be associated with multiple metabolites and whether selected metabolomic factors would be independent risk factors for incident CKD.
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Association of levels of fasting glucose and insulin with rare variants at the chromosome 11p11.2-MADD locus: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study.
Circ Cardiovasc Genet
PUBLISHED: 06-22-2014
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Common variation at the 11p11.2 locus, encompassing MADD, ACP2, NR1H3, MYBPC3, and SPI1, has been associated in genome-wide association studies with fasting glucose and insulin (FI). In the Cohorts for Heart and Aging Research in Genomic Epidemiology Targeted Sequencing Study, we sequenced 5 gene regions at 11p11.2 to identify rare, potentially functional variants influencing fasting glucose or FI levels.
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ADAM19 and HTR4 variants and pulmonary function: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study.
Circ Cardiovasc Genet
PUBLISHED: 06-22-2014
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The pulmonary function measures of forced expiratory volume in 1 second (FEV1) and its ratio to forced vital capacity (FVC) are used in the diagnosis and monitoring of lung diseases and predict cardiovascular mortality in the general population. Genome-wide association studies (GWASs) have identified numerous loci associated with FEV1 and FEV1/FVC, but the causal variants remain uncertain. We hypothesized that novel or rare variants poorly tagged by GWASs may explain the significant associations between FEV1/FVC and 2 genes: ADAM19 and HTR4.
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Fibroblast growth factor-23 and incident coronary heart disease, heart failure, and cardiovascular mortality: the atherosclerosis risk in communities study.
J Am Heart Assoc
PUBLISHED: 06-13-2014
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Fibroblast growth factor-23 (FGF-23) is a hormone involved in phosphorous regulation and vitamin D metabolism that may be associated with cardiovascular risk, and it is a potential target for intervention. We tested whether elevated FGF-23 is associated with incident coronary heart disease, heart failure, and cardiovascular mortality, even at normal kidney function.
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Parathyroid hormone concentration and risk of cardiovascular diseases: the Atherosclerosis Risk in Communities (ARIC) study.
Am. Heart J.
PUBLISHED: 06-09-2014
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According to a recent meta-analysis, parathyroid hormone (PTH) excess is associated with increased cardiovascular disease (CVD) risk, but existing studies are limited. We examined in a prospective study the association of PTH with the incidence of CVD, taking into account vitamin D and other confounding variables.
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Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.
JAMA
PUBLISHED: 06-04-2014
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The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of ?57% or greater) is a late event.
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Cardiac and kidney markers for cardiovascular prediction in individuals with chronic kidney disease: the Atherosclerosis Risk in Communities study.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 05-29-2014
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Traditional predictors suboptimally predict cardiovascular disease (CVD) in individuals with chronic kidney disease (CKD). This study compared 5 nontraditional cardiac and kidney markers on the improvement of cardiovascular prediction among those with CKD.
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Association of kidney disease measures with ischemic versus hemorrhagic strokes: pooled analyses of 4 prospective community-based cohorts.
Stroke
PUBLISHED: 05-29-2014
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Although low glomerular filtration rate (GFR) and albuminuria are associated with increased risk of stroke, few studies compared their contribution to risk of ischemic versus hemorrhagic stroke separately. We contrasted the association of these kidney measures with ischemic versus hemorrhagic stroke.
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The Impact of Cancer on the Clinical Outcome of Patients After Inferior Vena Cava Filter Placement: A Retrospective Cohort Study.
Am. J. Clin. Oncol.
PUBLISHED: 05-01-2014
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Inferior vena cava (IVC) filters are placed to prevent pulmonary embolism, however, some studies have suggested that IVC filters are associated with exacerbated risks of deep vein/IVC thrombosis in cancer patients. The purpose of this study is to determine if cancer patients develop higher than expected rates of venous thromboembolism complications after filter placement compared with noncancer patients.
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Normative Data for 8 Neuropsychological Tests in Older Blacks and Whites From the Atherosclerosis Risk in Communities (ARIC) Study.
Alzheimer Dis Assoc Disord
PUBLISHED: 04-25-2014
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Accurate assessment of cognitive impairment requires comparison of cognitive performance in individuals to performance in a comparable healthy normative population. Few prior studies have included a large number of black participants and few have excluded participants from the normative sample with subclinical/latent neurological disease or dementia. This study provides age, race, and education-specific normative data for 8 cognitive tests derived from 320 black and 392 white participants aged 61 to 82 years (mean 71 y) in the Atherosclerosis Risk in Communities (ARIC) study without clinical or subclinical/latent neurological disease. Normative data are provided for the Delayed Word Recall Test, Logical Memory Parts I and II, the Word Fluency Test, Animal Naming, the Trail Making Test Parts A and B and the Digit Symbol Substitution Test. Age, race, and education-specific mean and -1.5 SD scores are given in tabular form and graphically, as well as regression-based equations to derive adjusted score cut-points. These robust normative data should enhance comparison across studies of cognitive aging, where these measures are widely used, and improve interpretation of performance on these tests for the diagnosis of cognitive impairment not only within the ARIC cohort, but also among older blacks and whites with similar demographics.
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Trends in prevalence and control of diabetes in the United States, 1988-1994 and 1999-2010.
Ann. Intern. Med.
PUBLISHED: 04-16-2014
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Trends in the prevalence and control of diabetes defined by hemoglobin A1c (HbA1c) levels are important for health care policy and planning.
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Explaining the racial difference in AKI incidence.
J. Am. Soc. Nephrol.
PUBLISHED: 04-10-2014
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African Americans face higher risk of AKI than Caucasians. The extent to which this increased risk is because of differences in clinical, socioeconomic, or genetic risk factors is unknown. We evaluated 10,588 African-American and Caucasian participants in the Atherosclerosis Risk in Communities study, a community-based prospective cohort of middle-aged individuals. Participants were followed from baseline study visit (1996-1999) to first hospitalization for AKI (defined by billing code), ESRD, death, or December 31, 2010. African-American participants were slightly younger (61.7 versus 63.1 years, P<0.001), were more often women (64.5% versus 53.2%, P<0.001), and had higher baseline eGFR compared with Caucasians. Annual family income, education level, and prevalence of health insurance were lower among African Americans than Caucasians. The unadjusted incidence of hospitalized AKI was 7.4 cases per 1000 person-years among African Americans and 5.8 cases per 1000 person-years among Caucasians (P=0.002). The elevated risk of AKI among African Americans persisted after adjustment for demographics, cardiovascular risk factors, kidney markers, and time-varying number of hospitalizations (adjusted hazard ratio, 1.20; 95% confidence interval [95% CI], 1.01 to 1.43; P=0.04); however, accounting for differences in income and/or insurance by race attenuated the association (P>0.05). High-risk APOL1 variants did not associate with AKI among African Americans (demographic-adjusted hazard ratio, 1.07; 95% CI, 0.69 to 1.65; P=0.77). In summary, the higher risk of AKI among African Americans may be related to disparities in socioeconomic status.
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Results from the Atherosclerosis Risk in Communities study suggest that low serum magnesium is associated with incident kidney disease.
Kidney Int.
PUBLISHED: 04-04-2014
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Low serum magnesium has been associated with kidney function decline in persons with diabetes as well as cardiovascular disease in the general population. As the association of serum magnesium with incident kidney disease in the general population is unknown, we assessed this in 13,226 participants (aged 45-65) in the Atherosclerosis Risk in Communities study with baseline estimated glomerular filtration rate of at least 60?ml/min per 1.73?m(2) in years 1987-89 and followed through 2010. The risks for incident chronic kidney disease (CKD) and end-stage renal disease (ESRD) associated with baseline total serum magnesium levels were evaluated using Cox regression. There were 1965 CKD and 208 ESRD events during a median follow-up of 21 years. In adjusted analysis, low serum magnesium levels (0.7?mmol/l or less) had significant associations with incident CKD and ESRD compared with the highest quartile with adjusted hazard ratio of 1.58 (95% CI: 1.35-1.87) for CKD and 2.39 (95% CI: 1.61-3.56) for ESRD. These associations remained significant after excluding users of diuretics and across subgroups stratified by hypertension, diabetes, and self-reported race. Thus, in a large sample of middle-aged adults, low total serum magnesium was independently associated with incident CKD and ESRD. Further studies are needed to determine whether modification of serum magnesium levels might alter subsequent incident kidney disease rates.Kidney International advance online publication, 1 October 2014; doi:10.1038/ki.2014.331.
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The association of spousal smoking status with the ability to quit smoking: the Atherosclerosis Risk in Communities Study.
Am. J. Epidemiol.
PUBLISHED: 04-03-2014
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Smoking is the leading cause of preventable death in the United States. Studies have shown that smoking status tends to be concordant within spouse pairs. This study aimed to estimate the association of spousal smoking status with quitting smoking in US adults. We analyzed data from 4,500 spouse pairs aged 45-64 years from the Atherosclerosis Risk in Communities Study cohort, sampled from 1986 to 1989 from 4 US communities and followed up every 3 years for a total of 9 years. Logistic regression with generalized estimating equations was used to calculate the odds ratio of quitting smoking given that one's spouse is a former smoker or a current smoker compared to a never smoker. Among men and women, being married to a current smoker decreased the odds of quitting smoking (for men, odds ratio (OR) = 0.37, 95% confidence interval (CI): 0.29, 0.46; for women, OR = 0.54, 95% CI: 0.43, 0.68). Among women only, being married to a former smoker increased the odds of quitting smoking (OR = 1.26, 95% CI: 1.04, 1.53). In conclusion, spouses of current smokers are less likely to quit, whereas women married to former smokers are more likely to quit. Smoking cessation programs and clinical advice should consider targeting couples rather than individuals.
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Copy number polymorphisms near SLC2A9 are associated with serum uric acid concentrations.
BMC Genet.
PUBLISHED: 03-31-2014
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Hyperuricemia is associated with multiple diseases, including gout, cardiovascular disease, and renal disease. Serum urate is highly heritable, yet association studies of single nucleotide polymorphisms (SNPs) and serum uric acid explain a small fraction of the heritability. Whether copy number polymorphisms (CNPs) contribute to uric acid levels is unknown.
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Troponin I and NT-proBNP and the association of systolic blood pressure with outcomes in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study.
Am. J. Kidney Dis.
PUBLISHED: 03-17-2014
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There is uncertainty regarding treatment of hypertension in hemodialysis patients due to the observed J-shaped association between blood pressure (BP) and death. We hypothesized that this association reflects confounding by cardiovascular disease (CVD) and that stratification by CVD biomarkers, cardiac troponin I (cTnI) and N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP), might change this association.
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Impact of differential attrition on the association of education with cognitive change over 20 years of follow-up: the ARIC neurocognitive study.
Am. J. Epidemiol.
PUBLISHED: 03-13-2014
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Studies of long-term cognitive change should account for the potential effects of education on the outcome, since some studies have demonstrated an association of education with dementia risk. Evaluating cognitive change is more ideal than evaluating cognitive performance at a single time point, because it should be less susceptible to confounding. In this analysis of 14,020 persons from a US cohort study, the Atherosclerosis Risk in Communities (ARIC) Study, we measured change in performance on 3 cognitive tests over a 20-year period, from ages 48-67 years (1990-1992) through ages 70-89 years (2011-2013). Generalized estimating equations were used to evaluate the association between education and cognitive change in unweighted adjusted models, in models incorporating inverse probability of attrition weighting, and in models using cognitive scores imputed from the Telephone Interview for Cognitive Status for participants not examined in person. Education did not have a strong relationship with change in cognitive test performance, although the rate of decline was somewhat slower among persons with lower levels of education. Methods used to account for selective dropout only marginally changed these observed associations. Future studies of risk factors for cognitive impairment should focus on cognitive change, when possible, to allow for reduction of confounding by social or cultural factors.
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Genetic determinants influencing human serum metabolome among African Americans.
PLoS Genet.
PUBLISHED: 03-01-2014
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Phenotypes proximal to gene action generally reflect larger genetic effect sizes than those that are distant. The human metabolome, a result of multiple cellular and biological processes, are functional intermediate phenotypes proximal to gene action. Here, we present a genome-wide association study of 308 untargeted metabolite levels among African Americans from the Atherosclerosis Risk in Communities (ARIC) Study. Nineteen significant common variant-metabolite associations were identified, including 13 novel loci (p<1.6 × 10(-10)). These loci were associated with 7-50% of the difference in metabolite levels per allele, and the variance explained ranged from 4% to 20%. Fourteen genes were identified within the nineteen loci, and four of them contained non-synonymous substitutions in four enzyme-encoding genes (KLKB1, SIAE, CPS1, and NAT8); the other significant loci consist of eight other enzyme-encoding genes (ACE, GATM, ACY3, ACSM2B, THEM4, ADH4, UGT1A, TREH), a transporter gene (SLC6A13) and a polycystin protein gene (PKD2L1). In addition, four potential disease-associated paths were identified, including two direct longitudinal predictive relationships: NAT8 with N-acetylornithine, N-acetyl-1-methylhistidine and incident chronic kidney disease, and TREH with trehalose and incident diabetes. These results highlight the value of using endophenotypes proximal to gene function to discover new insights into biology and disease pathology.
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Vascular Access Type, Inflammatory Markers, and Mortality in Incident Hemodialysis Patients: The Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study.
Am. J. Kidney Dis.
PUBLISHED: 02-26-2014
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Few reports have shown an association between access type and inflammatory marker levels in a longitudinal cohort. We investigated the role of access type on serial levels of inflammatory markers and the role of inflammatory markers in mediating the association of access type and risk of mortality in a prospective study of incident dialysis patients.
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Pleiotropic genes for metabolic syndrome and inflammation.
Mol. Genet. Metab.
PUBLISHED: 02-25-2014
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Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation.
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Identification of incident CKD stage 3 in research studies.
Am. J. Kidney Dis.
PUBLISHED: 02-21-2014
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In epidemiologic research, incident chronic kidney disease (CKD) commonly is determined by laboratory tests performed at planned study visits. Given the morbidity and mortality associated with CKD, persons with incident disease may be less likely to attend scheduled visits, affecting observed associations. The objective of this study was to quantify loss to follow-up by CKD status and determine whether supplementation with diagnostic code data improves capture of incident CKD.
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Relative risks of chronic kidney disease for mortality and end-stage renal disease across races are similar.
Kidney Int.
PUBLISHED: 02-12-2014
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Some suggest race-specific cutpoints for kidney measures to define and stage chronic kidney disease (CKD), but evidence for race-specific clinical impact is limited. To address this issue, we compared hazard ratios of estimated glomerular filtration rates (eGFR) and albuminuria across races using meta-regression in 1.1 million adults (75% Asians, 21% Whites, and 4% Blacks) from 45 cohorts. Results came mainly from 25 general population cohorts comprising 0.9 million individuals. The associations of lower eGFR and higher albuminuria with mortality and end-stage renal disease (ESRD) were largely similar across races. For example, in Asians, Whites, and Blacks, the adjusted hazard ratios (95% confidence interval) for eGFR 45-59 versus 90-104?ml/min per 1.73?m(2) were 1.3 (1.2-1.3), 1.1 (1.0-1.2), and 1.3 (1.1-1.7) for all-cause mortality, 1.6 (1.5-1.7), 1.4 (1.2-1.7), and 1.4 (0.7-2.9) for cardiovascular mortality, and 27.6 (11.1-68.7), 11.2 (6.0-20.9), and 4.1 (2.2-7.5) for ESRD, respectively. The corresponding hazard ratios for urine albumin-to-creatinine ratio 30-299?mg/g or dipstick 1+ versus an albumin-to-creatinine ratio under 10 or dipstick negative were 1.6 (1.4-1.8), 1.7 (1.5-1.9), and 1.8 (1.7-2.1) for all-cause mortality, 1.7 (1.4-2.0), 1.8 (1.5-2.1), and 2.8 (2.2-3.6) for cardiovascular mortality, and 7.4 (2.0-27.6), 4.0 (2.8-5.9), and 5.6 (3.4-9.2) for ESRD, respectively. Thus, the relative mortality or ESRD risks of lower eGFR and higher albuminuria were largely similar among three major races, supporting similar clinical approach to CKD definition and staging, across races.
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GFR estimation: from physiology to public health.
Am. J. Kidney Dis.
PUBLISHED: 01-28-2014
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Estimating glomerular filtration rate (GFR) is essential for clinical practice, research, and public health. Appropriate interpretation of estimated GFR (eGFR) requires understanding the principles of physiology, laboratory medicine, epidemiology, and biostatistics used in the development and validation of GFR estimating equations. Equations developed in diverse populations are less biased at higher GFRs than equations developed in chronic kidney disease (CKD) populations and are more appropriate for general use. Equations that include multiple endogenous filtration markers are more precise than equations including a single filtration marker. The CKD-EPI (CKD Epidemiology Collaboration) equations are the most accurate GFR estimating equations that have been evaluated in large diverse populations and are applicable for general clinical use. The 2009 CKD-EPI creatinine equation is more accurate in estimating GFR and prognosis than the 2006 MDRD (Modification of Diet in Renal Disease) Study equation and provides lower estimates of prevalence of decreased eGFR. It is useful as a "first test" for decreased eGFR and should replace the MDRD Study equation for routine reporting of serum creatinine-based eGFR by clinical laboratories. The 2012 CKD-EPI cystatin C equation is as accurate as the 2009 CKD-EPI creatinine equation in estimating GFR, does not require specification of race, and may be more accurate in patients with decreased muscle mass. The 2012 CKD-EPI creatinine-cystatin C equation is more accurate than the 2009 CKD-EPI creatinine and 2012 CKD-EPI cystatin C equations and is useful as a confirmatory test for decreased eGFR as determined by serum creatinine-based eGFR. Further improvement in GFR estimating equations will require development in more broadly representative populations, including diverse racial and ethnic groups, use of multiple filtration markers, and evaluation using statistical techniques to compare eGFR to "true GFR."
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Fructosamine and glycated albumin for risk stratification and prediction of incident diabetes and microvascular complications: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study.
Lancet Diabetes Endocrinol
PUBLISHED: 01-15-2014
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HbA1c is the standard measure by which to monitor long-term (2-3 months) glucose control in people with diabetes and is now used for diagnosis of diabetes. Fructosamine and glycated albumin are markers of short-term (2-4 weeks) glycaemic control that might add complementary prognostic information to HbA1c. Our aim was to clarify the performance of fructosamine and glycated albumin measurements for identifying people at risk of incident diabetes or diabetic complications.
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Racial Differences in Gout Incidence in a Population-Based Cohort: Atherosclerosis Risk in Communities Study.
Am. J. Epidemiol.
PUBLISHED: 12-13-2013
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We examined racial differences in gout incidence among black and white participants in a longitudinal, population-based cohort and tested whether racial differences were explained by higher levels of serum urate. The Atherosclerosis Risk in Communities Study is a prospective, US population-based cohort study of middle-aged adults enrolled between 1987 and 1989 with ongoing annual follow-up through 2012. We estimated the adjusted hazard ratios and 95% confidence intervals of incident gout by race among 11,963 men and women using adjusted Cox proportional hazards models. The cohort was 23.6% black. The incidence rate of gout was 8.4 per 10,000 person-years (15.5/10,000 person-years for black men, 12.0/10,000 person-years for black women, 9.4/10,000 person-years for white men, and 5.0/10,000 person-years for white women; P < 0.001). Black participants had an increased risk of incident gout (for women, adjusted hazard ratio (HR) = 1.69, 95% confidence interval (CI): 1.29, 2.22; for men, adjusted HR = 1.92, 95% CI: 1.44, 2.56). Upon further adjustment for uric acid levels, there was modest attenuation of the association of race with incident gout (for women, adjusted HR = 1.62, 95% CI: 1.24, 2.22; for men, adjusted HR = 1.49, 95% CI: 1.11, 2.00) compared with white participants. In this US population-based cohort, black women and black men were at increased risk of developing gout during middle and older ages compared with whites, which appears, particularly in men, to be partly related to higher urate levels in middle-aged blacks.
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Cystatin C- and creatinine-based estimated glomerular filtration rate, vascular disease, and mortality in persons with diabetes in the United States.
Diabetes Care
PUBLISHED: 11-22-2013
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Introduction:Serum cystatin C is an alternative to serum creatinine for estimating glomerular filtration rate (GFR) since cystatin C is less influenced by age and muscle mass. Among persons with diabetes, we compared the performance of GFR estimated using cystatin C (eGFRcys) with that using creatinine (eGFRcr) for the identification of reduced kidney function and its association with diabetic complications.Research Design & Methods:We analyzed data from adult participants from the 1999-2002 National Health and Nutrition Examination Survey with available cystatin C (N=4457). Kidney function was dichotomized as preserved (eGFR ? 60 ml/min/1.73 m(2)) or reduced (eGFR < 60 ml/min/1.73 m(2)) using the 2012 CKD-EPI cystatin C and the 2009 CKD-EPI creatinine equations.Results:Among 778 persons with diabetes, the prevalence of reduced kidney function was 16.5% using eGFRcr and 22.0% using eGFRcys. More persons with diabetes were reclassified from preserved kidney function by eGFRcr to reduced kidney function by eGFRcys than persons without diabetes (OR 3.1, 95% CI: 1.9-4.9, p<0.001). The associations between lower eGFR and higher prevalence of albuminuria, retinopathy, peripheral arterial disease, and coronary artery disease were robust regardless of filtration marker. Similarly, the risk of all-cause mortality increased with lower eGFRcr and eGFRcys. Only lower eGFRcys was significantly associated with cardiovascular mortality.Conclusions:More persons with diabetes had reduced kidney function by eGFRcys than by eGFRcr, and lower eGFRcys was strongly associated with diabetic complications. Whether eGFRcys is superior to eGFRcr in approximating true kidney function in a diabetic population requires additional study.
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Rationale and Design of a Multicenter Echocardiographic Study to Assess the Relationship Between Cardiac Structure and Function and Heart Failure Risk in a Biracial Cohort of Community Dwelling Elderly Persons: The Atherosclerosis Risk in Communities (ARI
Circ Cardiovasc Imaging
PUBLISHED: 11-08-2013
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-Heart failure (HF) is an important public health concern particularly among persons over 65 years of age. Women and African Americans are critically understudied populations that carry a sizeable portion of the HF burden. Limited normative and prognostic data exist regarding measures of cardiac structure, diastolic function, and novel measures of systolic deformation in older adults living in the community.
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Troponin T and N-terminal pro-B-type natriuretic Peptide: a biomarker approach to predict heart failure risk--the atherosclerosis risk in communities study.
Clin. Chem.
PUBLISHED: 09-13-2013
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Among the various cardiovascular diseases, heart failure (HF) is projected to have the largest increases in incidence over the coming decades; therefore, improving HF prediction is of significant value. We evaluated whether cardiac troponin T (cTnT) measured with a high-sensitivity assay and N-terminal pro-B-type natriuretic peptide (NT-proBNP), biomarkers strongly associated with incident HF, improve HF risk prediction in the Atherosclerosis Risk in Communities (ARIC) study.
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Common variants in mendelian kidney disease genes and their association with renal function.
Afshin Parsa, Christian Fuchsberger, Anna Köttgen, Conall M O'Seaghdha, Cristian Pattaro, Mariza de Andrade, Daniel I Chasman, Alexander Teumer, Karlhans Endlich, Matthias Olden, Ming-Huei Chen, Adrienne Tin, Young J Kim, Daniel Taliun, Man Li, Mary Feitosa, Mathias Gorski, Qiong Yang, Claudia Hundertmark, Meredith C Foster, Nicole Glazer, Aaron Isaacs, Madhumathi Rao, Albert V Smith, Jeffrey R O'Connell, Maksim Struchalin, Toshiko Tanaka, Guo Li, Shih-Jen Hwang, Elizabeth J Atkinson, Kurt Lohman, Marilyn C Cornelis, Asa Johansson, Anke Tönjes, Abbas Dehghan, Vincent Couraki, Elizabeth G Holliday, Rossella Sorice, Zoltan Kutalik, Terho Lehtimäki, Tonu Esko, Harshal Deshmukh, Sheila Ulivi, Audrey Y Chu, Federico Murgia, Stella Trompet, Medea Imboden, Barbara Kollerits, Giorgio Pistis, Tamara B Harris, Lenore J Launer, Thor Aspelund, Gudny Eiriksdottir, Braxton D Mitchell, Eric Boerwinkle, Helena Schmidt, Edith Hofer, Frank Hu, Ayse Demirkan, Ben A Oostra, Stephen T Turner, Jingzhong Ding, Jeanette S Andrews, Barry I Freedman, Franco Giulianini, Wolfgang Koenig, Thomas Illig, Angela Döring, H-Erich Wichmann, Lina Zgaga, Tatijana Zemunik, Mladen Boban, Cosetta Minelli, Heather E Wheeler, Wilmar Igl, Ghazal Zaboli, Sarah H Wild, Alan F Wright, Harry Campbell, David Ellinghaus, Ute Nöthlings, Gunnar Jacobs, Reiner Biffar, Florian Ernst, Georg Homuth, Heyo K Kroemer, Matthias Nauck, Sylvia Stracke, Uwe Völker, Henry Völzke, Peter Kovacs, Michael Stumvoll, Reedik Mägi, Albert Hofman, André G Uitterlinden, Fernando Rivadeneira, Yurii S Aulchenko, Ozren Polašek, Nick Hastie, Veronique Vitart, Catherine Helmer, Jie Jin Wang, Bénédicte Stengel, Daniela Ruggiero, Sven Bergmann, Mika Kähönen, Jorma Viikari, Tiit Nikopensius, Michael Province, Helen Colhoun, Alex Doney, Antonietta Robino, Bernhard K Krämer, Laura Portas, Ian Ford, Brendan M Buckley, Martin Adam, Gian-Andri Thun, Bernhard Paulweber, Margot Haun, Cinzia Sala, Paul Mitchell, Marina Ciullo, Peter Vollenweider, Olli Raitakari, Andres Metspalu, Colin Palmer, Paolo Gasparini, Mario Pirastu, J Wouter Jukema, Nicole M Probst-Hensch, Florian Kronenberg, Daniela Toniolo, Vilmundur Gudnason, Alan R Shuldiner, Josef Coresh, Reinhold Schmidt, Luigi Ferrucci, Cornelia M van Duijn, Ingrid Borecki, Sharon L R Kardia, Yongmei Liu, Gary C Curhan, Igor Rudan, Ulf Gyllensten, James F Wilson, Andre Franke, Peter P Pramstaller, Rainer Rettig, Inga Prokopenko, Jacqueline Witteman, Caroline Hayward, Paul M Ridker, Murielle Bochud, Iris M Heid, David S Siscovick, Caroline S Fox, W Linda Kao, Carsten A Böger.
J. Am. Soc. Nephrol.
PUBLISHED: 09-12-2013
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Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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Elevated high-sensitivity C-reactive protein as a risk marker of the attenuated relationship between serum cholesterol and cardiovascular events at older age. The ARIC Study.
Am. J. Epidemiol.
PUBLISHED: 09-10-2013
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The relationship between cholesterol and coronary heart disease (CHD) is attenuated at older age. We analyzed cholesterol level as a predictor of CHD in 8,947 participants from the Atherosclerosis Risk in Communities (ARIC) Study, a large multicenter cohort study that enrolled participants in 1987-1989 at 4 field centers in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis, Minnesota. Participants in the present analysis had no history of CHD and were stratified by age (<65 or ?65 years) and high-sensitivity C-reactive protein (hs-CRP) level (<2 or ?2 mg/L). Visit 4 (1996-1997) was the baseline for this analysis, with follow-up through 2008. Cholesterol level was significantly associated with CHD among younger participants, and cholesterol level was similarly predictive of CHD among older participants with an hs-CRP level of <2 mg/L. In contrast, among older participants with an hs-CRP level of 2 mg/L or higher, the association of CHD with total cholesterol level was borderline significant (hazard ratio = 1.14, 95% confidence interval: 1.00, 1.29), and the association of CHD with low-density lipoprotein cholesterol level was nonsignificant (hazard ratio = 1.10; 95% confidence interval: 0.96, 1.26). Among older persons with an elevated hs-CRP level, cholesterol level was significantly less predictive of CHD (P < 0.05), whereas for those with an hs-CRP level of <2 mg/L, there was no significant difference compared with younger participants. In conclusion, we found that among the young-old, the association of cholesterol level with CHD was strong when hs-CRP level was not elevated and weak when hs-CRP level was elevated. Therefore, hs-CRP level could be useful for stratifying the young-old to assess the strength of cholesterol level in CHD risk prediction.
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Cystatin C versus creatinine in determining risk based on kidney function.
N. Engl. J. Med.
PUBLISHED: 09-06-2013
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Adding the measurement of cystatin C to that of serum creatinine to determine the estimated glomerular filtration rate (eGFR) improves accuracy, but the effect on detection, staging, and risk classification of chronic kidney disease across diverse populations has not been determined.
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Risk factors for incident hyperuricemia during mid-adulthood in African American and White men and women enrolled in the ARIC cohort study.
BMC Musculoskelet Disord
PUBLISHED: 08-08-2013
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Increased serum urate levels are associated with poor outcomes including but not limited to gout. It is unclear whether serum urate levels are the sole predictor of incident hyperuricemia or whether demographic and clinical risk factors also predict the development of hyperuricemia. The goal of this study was to identify risk factors for incident hyperuricemia over 9 years in a population-based study, ARIC.
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Potential Effects of Reclassifying CKD as a Coronary Heart Disease Risk Equivalent in the US Population.
Am. J. Kidney Dis.
PUBLISHED: 07-01-2013
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Persons with chronic kidney disease (CKD) are at high risk for cardiovascular disease events, but are not classified as such in current US cholesterol treatment guidelines. We examined potential effects of modified guidelines in which CKD was considered a "coronary heart disease (CHD) risk equivalent" for risk stratification.
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The association of plasma lactate with incident cardiovascular outcomes: the ARIC Study.
Am. J. Epidemiol.
PUBLISHED: 06-30-2013
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We examined the association of plasma lactate at rest, a marker of oxidative capacity, with incident cardiovascular outcomes in 10,006 participants in the Atherosclerosis Risk in Communities (ARIC) Study visit 4 (1996-1998). We used Cox proportional-hazards models to estimate hazard ratios of incident coronary heart disease, stroke, heart failure, and all-cause mortality by quartiles of plasma lactate (Q1, ?5.3 mg/dL; Q2, 5.4-6.6; Q3, 6.7-8.6; and Q4 ?8.7). During a median follow-up time of 10.7 years, there were 1,105 coronary heart disease cases, 379 stroke cases, 820 heart failure cases, and 1,408 deaths. A significant graded relation between lactate level and cardiovascular events was observed in the demographically adjusted model (all P for trend < 0.001). After further adjustment for traditional and other potential confounders, the association remained significant for heart failure (Q4 vs. Q1: hazard ratio (HR) = 1.35, 95% confidence interval (CI): 1.07, 1.71) and all-cause mortality (HR = 1.27, 95% CI: 1.07, 1.51) (P for trend < 0.02 for these outcomes) but not for coronary heart disease (HR = 1.02, 95% CI: 0.84, 1.24) and stroke (HR = 1.26, 95% CI: 0.91, 1.75). The results for heart failure were robust across multiple subgroups, after further adjustment for N-terminal pro-B-type natriuretic peptide and after exclusion of participants with incident heart failure within 3 years. The independent associations of plasma lactate with heart failure and all-cause mortality suggest an important role for low resting oxidative capacity.
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Socioeconomic measures and CKD in the United States and The Netherlands.
Clin J Am Soc Nephrol
PUBLISHED: 06-27-2013
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According to the cost of health care utilization systems, there may be regional differences in the relative strength of association of income and education-based socioeconomic status measures with CKD. This study investigated the relative strength of the association of income and education with CKD in a United States and a Dutch population.
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Associations between metabolomic compounds and incident heart failure among African Americans: the ARIC Study.
Am. J. Epidemiol.
PUBLISHED: 06-20-2013
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Heart failure is more prevalent among African Americans than in the general population. Metabolomic studies among African Americans may efficiently identify novel biomarkers of heart failure. We used untargeted methods to measure 204 stable serum metabolites and evaluated their associations with incident heart failure hospitalization (n = 276) after a median follow-up of 20 years (1987-2008) by using Cox regression in data from 1,744 African Americans aged 45-64 years without heart failure at baseline from the Jackson, Mississippi, field center of the Atherosclerosis Risk in Communities (ARIC) Study. After adjustment for established risk factors, we found that 16 metabolites (6 named with known structural identities and 10 unnamed with unknown structural identities, the latter denoted by using the format X-12345) were associated with incident heart failure (P < 0.0004 based on a modified Bonferroni procedure). Of the 6 named metabolites, 4 are involved in amino acid metabolism, 1 (prolylhydroxyproline) is a dipeptide, and 1 (erythritol) is a sugar alcohol. After additional adjustment for kidney function, 2 metabolites remained associated with incident heart failure (for metabolite X-11308, hazard ratio = 0.75, 95% confidence interval: 0.65, 0.86; for metabolite X-11787, hazard ratio = 1.23, 95% confidence interval: 1.10, 1.37). Further structural analysis revealed X-11308 to be a dihydroxy docosatrienoic acid and X-11787 to be an isoform of either hydroxyleucine or hydroxyisoleucine. Our metabolomic analysis revealed novel biomarkers associated with incident heart failure independent of traditional risk factors.
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Estimated GFR Decline as a Surrogate End Point for Kidney Failure: A Post Hoc Analysis From the Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan (RENAAL) Study and Irbesartan Diabetic Nephropathy Trial
Am. J. Kidney Dis.
PUBLISHED: 06-16-2013
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A doubling of serum creatinine value, corresponding to a 57% decline in estimated glomerular filtration rate (eGFR), is used frequently as a component of a composite kidney end point in clinical trials in type 2 diabetes. The aim of this study was to determine whether alternative end points defined by smaller declines in eGFR would improve the statistical power of these clinical trials.
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APOL1 variants associate with increased risk of CKD among African Americans.
J. Am. Soc. Nephrol.
PUBLISHED: 06-13-2013
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Although case-control studies suggest that African Americans with common coding variants in the APOL1 gene are 5-29 times more likely than those individuals without such variants to have focal segmental glomerulosclerosis, HIV-associated nephropathy, or ESRD, prospective studies have not yet evaluated the impact of these variants on CKD in a community-based sample of African Americans. Here, we studied whether the APOL1 G1 and G2 risk alleles associate with the development of CKD and progression to ESRD by analyzing data from 3067 African Americans in the Atherosclerosis Risk in Communities Study who did not have CKD at baseline. Carrying two risk alleles associated with a 1.49-fold increased risk of CKD (95% CI=1.02 to 2.17) and a 1.88-fold increased risk of ESRD (95% CI=1.20 to 2.93) compared with zero or one risk allele; associations persisted after adjusting for European ancestry. Among participants who developed CKD, those participants with two risk alleles were more likely to progress to ESRD than their counterparts with zero or one risk allele (HR=2.22, 95% CI=1.01 to 4.84). In conclusion, APOL1 risk variants are risk factors for the development of CKD and progression from CKD to ESRD among African Americans in the general population.
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NH2-terminal pro-brain natriuretic peptide and risk of diabetes.
Diabetes
PUBLISHED: 06-03-2013
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Brain natriuretic peptide (BNP) has an established role in cardiovascular disease (CVD). However, recent animal studies suggest direct metabolic effects of BNP. To determine the association of BNP with the risk of diabetes, we conducted a prospective analysis of participants from the Atherosclerosis Risk in Communities (ARIC) study. We included 7,822 men and women without history of diabetes, CVD, or reduced kidney function at baseline. At baseline, NH2-terminal (NT)-proBNP, a cleavage product of BNP, was inversely associated with adiposity, fasting glucose, insulin, and cholesterol but positively associated with blood pressure and C-reactive protein levels. During a median follow-up of 12 years, 1,740 participants reported a new diagnosis of diabetes or medication use for diabetes. Baseline quartiles of NT-proBNP were inversely associated with diabetes risk, even after multivariable adjustment including fasting glucose. The adjusted HRs for diabetes were 1.0 (reference), 0.84 (95% CI 0.74-0.96), 0.79 (95% CI 0.68-0.90), and 0.75 (95% CI 0.64-0.87) for the 1st, 2nd, 3rd, and 4th quartiles of baseline NT-proBNP, respectively (P for trend <0.001). This inverse association was robust across sex, race, and obesity subgroups. Our results extend animal studies and support a direct and important metabolic role of BNP in humans.
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Evolving importance of kidney disease: from subspecialty to global health burden.
Lancet
PUBLISHED: 05-31-2013
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In the past decade, kidney disease diagnosed with objective measures of kidney damage and function has been recognised as a major public health burden. The population prevalence of chronic kidney disease exceeds 10%, and is more than 50% in high-risk subpopulations. Independent of age, sex, ethnic group, and comorbidity, strong, graded, and consistent associations exist between clinical prognosis and two hallmarks of chronic kidney disease: reduced glomerular filtration rate and increased urinary albumin excretion. Furthermore, an acute reduction in glomerular filtration rate is a risk factor for adverse clinical outcomes and the development and progression of chronic kidney disease. An increasing amount of evidence suggests that the kidneys are not only target organs of many diseases but also can strikingly aggravate or start systemic pathophysiological processes through their complex functions and effects on body homoeostasis. Risk of kidney disease has a notable genetic component, and identified genes have provided new insights into relevant abnormalities in renal structure and function and essential homoeostatic processes. Collaboration across general and specialised health-care professionals is needed to fully address the challenge of prevention of acute and chronic kidney disease and improve outcomes.
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No racial differences in the association of glycated hemoglobin with kidney disease and cardiovascular outcomes.
Diabetes Care
PUBLISHED: 05-30-2013
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There is debate regarding the clinical significance of well-established racial differences in HbA1c. We compared the associations of diabetes diagnostic categories for HbA1c and fasting glucose with clinical outcomes in black and white persons in the community.
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Quality of care for heart failure patients hospitalized for any cause.
J. Am. Coll. Cardiol.
PUBLISHED: 05-21-2013
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To assess the quality of care for heart failure patients who are hospitalized for all causes.
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CKD and cardiovascular disease in the Atherosclerosis Risk in Communities (ARIC) study: interactions with age, sex, and race.
Am. J. Kidney Dis.
PUBLISHED: 04-24-2013
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Estimated glomerular filtration rate (eGFR) and albuminuria are central for diagnosis, staging, and risk evaluation in chronic kidney disease (CKD). Universal thresholds regardless of age, sex, and race are recommended, but relatively little is known about how these demographic factors alter the relationship of eGFR and albuminuria to cardiovascular outcomes.
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Cardiovascular risk factor burden, treatment, and control among adults with chronic kidney disease in the United States.
Am. Heart J.
PUBLISHED: 03-26-2013
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Cardiovascular disease is a major concern in persons with chronic kidney disease (CKD). We assessed the current burden of cardiovascular risk factors and differences in risk factor treatment and control in the general US adult population by CKD status.
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Trends in the prevalence of reduced GFR in the United States: a comparison of creatinine- and cystatin C-based estimates.
Am. J. Kidney Dis.
PUBLISHED: 03-15-2013
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The US prevalence of reduced estimated glomerular filtration rate (eGFR) based on serum creatinine level increased during the decade ending in 2002. National Health and Nutrition Examination Survey (NHANES) cystatin C measurements recently were calibrated to the international standard, allowing for an independent test of the trend in prevalence of reduced eGFR using cystatin C level.
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Association of a Cystatin C Gene Variant With Cystatin C Levels, CKD, and Risk of Incident Cardiovascular Disease and Mortality.
Am. J. Kidney Dis.
PUBLISHED: 02-20-2013
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Carriers of the T allele of the single-nucleotide polymorphism rs13038305 tend to have lower cystatin C levels and higher cystatin C-based estimated glomerular filtration rate (eGFRcys). Adjusting for this genetic effect on cystatin C concentrations may improve GFR estimation, reclassify cases of chronic kidney disease (CKD), and strengthen risk estimates for cardiovascular disease (CVD) and mortality.
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Retained organic solutes, patient characteristics and all-cause and cardiovascular mortality in hemodialysis: results from the retained organic solutes and clinical outcomes (ROSCO) investigators.
BMC Nephrol
PUBLISHED: 01-10-2013
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Multiple solutes are retained in uremia, but it is currently unclear which solutes are toxic. Small studies suggest that protein-bound solutes, such as p-cresol sulfate and indoxyl sulfate and intracellular solutes, such as methylamine (MMA) and dimethylamine (DMA), may be toxic. Our objective was to test whether elevated levels of these solutes were associated with mortality.
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Interaction between the NOS3 Gene and Obesity as a Determinant of Risk of Type 2 Diabetes: The Atherosclerosis Risk in Communities Study.
PLoS ONE
PUBLISHED: 01-01-2013
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Endothelial nitric oxide synthase 3 (NOS3) catalyzes the production of nitric oxide from L-arginine in endothelial cells. Obesity is a modifiable risk factor for diabetes, and obese individuals have been reported to have reduced nitric oxide availability compared to controls whose weight is in the normal range. Since homozygous carriers of the NOS3 G894T variant are predicted to have decreased enzyme activity, the association between NOS3 genotype and type 2 diabetes, and possible effect modification by body mass index (BMI) were evaluated. The prevalence of diabetes and BMI was determined at baseline in 14,374 participants 45-66 years of age from the prospective biracial population-based Atherosclerosis Risk in Communities (ARIC) Study of the development of atherosclerosis in four communities in the United States. Individuals with a BMI ?30 kg/m(2) were considered obese. Those subjects not meeting the case definition were the comparison groups for the 728 African American and 980 white participants with diabetes. Multivariable logistic regression models adjusted for age, sex, and field center were used to test for main genetic effects and interaction with obesity. Although the NOS3 G894T variant was not independently associated with diabetes in either African Americans or whites, significant interaction between BMI and the NOS3 polymorphism indicated that obesity was an effect modifier of diabetes risk for white individuals with the TT genotype (odds ratio (OR) for interaction?=?1.65, p?=?0.04). In stratified analyses, homozygosity for the NOS3 T allele in obese white participants but not in those whose BMI <30 kg/m(2) was associated with an elevated risk of diabetes (OR?=?1.47, p?=?0.02) when compared to the common GG genotype. These results suggest that interaction between obesity and NOS3 genotype may be a determinant of diabetes case status in whites in the ARIC cohort. Replication in other populations will be required to confirm these observations.
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Orthostatic change in blood pressure and incidence of atrial fibrillation: results from a bi-ethnic population based study.
PLoS ONE
PUBLISHED: 01-01-2013
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Autonomic fluctuations are associated with the initiation and possibly maintenance of atrial fibrillation (AF). However, little is known about the relationship between orthostatic blood pressure change, a common manifestation of autonomic dysfunction, and incident AF.
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Filtration markers may have prognostic value independent of glomerular filtration rate.
J. Am. Soc. Nephrol.
PUBLISHED: 12-15-2011
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Serum levels of creatinine, cystatin C, or ? trace protein allow estimation of GFR, but whether these markers contribute additional prognostic information beyond that reflected in GFR is unknown. Here, we analyzed data from the Modification of Diet in Renal Disease study, which provided baseline levels of these markers for 816 participants with a median follow-up of 16.6 years. We examined associations between the reciprocals of these filtration markers and (125)I iothalamate GFR, expressed per SD, with kidney failure and mortality. In univariate analysis, lower GFR and higher levels of each filtration marker associated with a higher risk for all outcomes. After adjustment for GFR in a Cox proportional hazards model, higher creatinine associated with a higher risk for kidney failure but a lower risk for all-cause mortality. Higher cystatin C and ? trace protein associated with a higher risk for both kidney failure and all-cause mortality. In models including either cystatin C or ? trace protein, the association of GFR with all-cause mortality was no longer significant after the addition of the filtration marker, suggesting the possibility of multicollinearity. In summary, after adjustment for GFR, levels of creatinine, cystatin C, and ? trace protein, each remained directly associated with kidney failure but differed with respect to their associations with mortality. These differences may be a result of non-GFR-related associations of filtration markers, residual confounding by GFR, or collinearity between the filtration markers and GFR. ? trace protein and cystatin C seem to provide more consistent prognostic information than creatinine.
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Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects: the Atherosclerosis Risk in Communities (ARIC) Study.
Circulation
PUBLISHED: 11-29-2011
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On the basis of studies with limited statistical power, lipoprotein(a) [Lp(a)] is not considered a risk factor for cardiovascular disease (CVD) in blacks. We evaluated associations between Lp(a) and incident CVD events in blacks and whites in the Atherosclerosis Risk in Communities (ARIC) study.
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Relation of lipid gene scores to longitudinal trends in lipid levels and incidence of abnormal lipid levels among individuals of European ancestry: the Atherosclerosis Risk in Communities (ARIC) study.
Circ Cardiovasc Genet
PUBLISHED: 11-04-2011
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Multiple genetic loci have been associated with blood lipid levels. We tested the hypothesis that persons with an unfavorable lipid gene profile would experience a greater increase in lipid levels and a higher incidence of abnormal lipid levels relative to those with more-favorable lipid gene profiles.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.