bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Serum Erythropoietin With Cardiovascular Events, Kidney Function Decline, and Mortality
Authors: Garimella Pranav S , Katz Ronit , Patel Kushang V , Kritchevsky Stephen B , Parikh Chirag R , Ix Joachim H , Fried Linda F , Newman Anne B , Shlipak Michael G , Harris Tamara B , Sarnak Mark J 
Published: January 2016

Background—
Studies suggest that in patients with heart failure (HF), high serum erythropoietin is associated with risk of recurrent HF and mortality. Trials of erythropoietin-stimulating agents in persons with kidney disease have also suggested an increased incidence of adverse clinical events. No large studies of which we are aware have evaluated the association of endogenous erythropoietin levels with clinical outcomes in the community-living older adults.

Methods and Results—

Erythropoietin concentration was measured in 2488 participants aged 70–79 years in the Health, Aging and Body Composition Study. Associations of erythropoietin with incident HF, coronary heart disease, stroke, mortality, and ≥30% decline in estimated glomerular filtration rate were examined using Cox proportional hazards and logistic regression over 10.7 years of follow-up. Mean (SD) age was 75 (3) years and median (quartile 1, quartile 3) erythropoietin was 12.3 (9.0, 17.2) mIU/mL. There were 503 incident HF events, and each doubling of serum erythropoietin was associated with a 25% increased risk of incident HF 1.25 (95% confidence interval 1.13, 1.48) after adjusting for demographics, prevalent cardiovascular disease, cardiovascular disease risk factors, kidney function, and serum hemoglobin. There was no interaction of serum erythropoietin with chronic kidney disease or anemia (
P
>0.50). There were 330 incident coronary heart disease events, 161 strokes, 1112 deaths, and 698 outcomes of ≥30% decline in estimated glomerular filtration rate. Serum erythropoietin was not significantly associated with these outcomes.

Conclusions—
Higher levels of endogenous erythropoietin are associated with incident HF in older adults. Studies need to elucidate the mechanisms through which endogenous erythropoietin levels associate with specific outcomes.
Health Literacy Mediates the Relationship Between Age and Health Outcomes in Patients With Heart Failure
Authors: Wu Jia-Rong , Moser Debra K. , DeWalt Darren A. , Rayens Mary Kay , Dracup Kathleen 
Published: January 2016

Background—
Previous studies have linked frequent rehospitalizations for heart failure (HF) and increased mortality with older age, higher severity of HF, lack of an evidence-based medication regimen, and inadequate health literacy. However, the pathway between age and health outcomes in patients with HF remains unknown. Therefore, the purpose of this study was to test whether the association between age and health outcomes can be explained by severity of HF, evidence-based medication use, and health literacy in patients with HF.

Methods and Results—

This was a longitudinal study of 575 rural patients with HF recruited from outpatient clinics and hospitals. Demographics, clinical data, and health literacy were collected at baseline. HF readmissions and cardiac mortality were followed for 2 years; 57% of patients were ≥65 years of age. Older patients with HF were more likely to have low health literacy and less likely to be prescribed angiotensin-converting enzyme inhibitors or β-blockers. Using Kaplan–Meier survival curves with log-rank tests, health outcomes were significantly worse in patients who were ≥65 years and in those with low health literacy. Separate Cox regressions revealed that age and health literacy predicted worse health outcomes (
P
=0.006 and <0.001, respectively). When health literacy was entered into the model, the hazard ratio for age changed from 1.49 to 1.29 (a 41% reduction); age was no longer a significant predictor of health outcomes, but health literacy remained significant (
P
<0.001), demonstrating mediation.

Conclusions—
Health literacy mediates the relationship between age and health outcomes in adults with HF.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00415545.
Antiplatelet Therapy and Adverse Hematologic Events During Heart Mate II Support
Authors: Saeed Omar , Shah Aman , Kargoli Faraj , Madan Shivank , Levin Allison P. , Patel Snehal R. , Jermyn Rita , Guerrero Cesar , Nguyen Jenni , Sims Daniel B. , Shin Julia , D’Alessandro David , Goldstein Daniel J. , Jorde Ulrich P. 
Published: January 2016

Background
—

Hematologic adverse events are common during continuous flow left ventricular assist device support; yet, their relation to antiplatelet therapy, including aspirin (ASA) dosing, is uncertain.

Methods and Results—

A single-center retrospective review of all patients supported by a continuous flow left ventricular assist device (Heart Mate II) from June 2006 to November 2014 was conducted. Patients were categorized into 3 groups: (1) ASA 81 mg+dipyridamole 75 mg daily (n=26) with a target international normalized ratio (INR) of 2 to 3 from June 2006 to August 2009; (2) ASA 81 mg daily (n=18) from September 2009 to August 2011 with a target INR of 1.5 to 2; and (3) ASA 325 mg daily from September 2011 to November 2014 with a target INR of 2 to 3 (n=70). Hemorrhagic and thrombotic outcomes were retrieved ≤365 days after implantation. Cumulative survival free from adverse events was calculated using Kaplan–Meier curves and Cox proportional hazard ratios were generated. Hemorrhagic events occurred in 6 patients on ASA 81 mg+dipyridamole (26%; 0.42 events per patient year; mean INR at event, 2.2), 4 patients on ASA 81 mg (22%; 0.38 events per patient year; mean INR at event, 2.0), and in 38 patients on ASA 325 mg (54%; 1.4 events per patient year; mean INR at event, 2.2);
P
=0.004. Patients on ASA 325 mg had a higher adjusted hazard ratio of 2.9 (95% confidence interval, 1.2–7.0 versus ASA 81 mg+dipyridamole;
P
=0.02) and 3.4 (95% confidence interval, 1.2–9.5 versus ASA 81 mg;
P
=0.02) for hemorrhagic events. Thrombotic events rates were not different between groups.

Conclusions—
High-dose ASA in Heart Mate II patients treated concomitantly with warfarin is associated with an increased hazard of bleeding but does not reduce thrombotic events.
Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure
Authors: Testani Jeffrey M. , Hanberg Jennifer S. , Cheng Susan , Rao Veena , Onyebeke Chukwuma , Laur Olga , Kula Alexander , Chen Michael , Wilson F. Perry , Darlington Andrew , Bellumkonda Lavanya , Jacoby Daniel , Tang W.H. Wilson , Parikh Chirag R. 
Published: January 2016

Background—
Removal of excess sodium and fluid is a primary therapeutic objective in acute decompensated heart failure and commonly monitored with fluid balance and weight loss. However, these parameters are frequently inaccurate or not collected and require a delay of several hours after diuretic administration before they are available. Accessible tools for rapid and accurate prediction of diuretic response are needed.

Methods and Results—

Based on well-established renal physiological principles, an equation was derived to predict net sodium output using a spot urine sample obtained 1 or 2 hours after loop diuretic administration. This equation was then prospectively validated in 50 acute decompensated heart failure patients using meticulously obtained timed 6-hour urine collections to quantify loop diuretic-induced cumulative sodium output. Poor natriuretic response was defined as a cumulative sodium output of <50 mmol, a threshold that would result in a positive sodium balance with twice-daily diuretic dosing. Following a median dose of 3 mg (2–4 mg) of intravenous bumetanide, 40% of the population had a poor natriuretic response. The correlation between measured and predicted sodium output was excellent (
r
=0.91;
P
<0.0001). Poor natriuretic response could be accurately predicted with the sodium prediction equation (area under the curve =0.95, 95% confidence interval 0.89–1.0;
P
<0.0001). Clinically recorded net fluid output had a weaker correlation (
r
=0.66;
P
<0.001) and lesser ability to predict poor natriuretic response (area under the curve =0.76, 95% confidence interval 0.63–0.89;
P
=0.002).

Conclusions—
In patients being treated for acute decompensated heart failure, poor natriuretic response can be predicted soon after diuretic administration with excellent accuracy using a spot urine sample.
Importance of Abnormal Chloride Homeostasis in Stable Chronic Heart Failure
Authors: Grodin Justin L , Verbrugge Frederik H , Ellis Stephen G , Mullens Wilfried , Testani Jeffrey M , Tang W.H. Wilson 
Published: January 2016

Background—
The aim of this analysis was to determine the long-term prognostic value of lower serum chloride in patients with stable chronic heart failure. Electrolyte abnormalities are prevalent in patients with chronic heart failure. Little is known regarding the prognostic implications of lower serum chloride.

Methods and Results—

Serum chloride was measured in 1673 consecutively consented stable patients with a history of heart failure undergoing elective diagnostic coronary angiography. All patients were followed for 5-year all-cause mortality, and survival models were adjusted for variables that confounded the chloride–risk relationship. The average chloride level was 102±4 mEq/L. Over 6772 person-years of follow-up, there were 547 deaths. Lower chloride (per standard deviation decrease) was associated with a higher adjusted risk of mortality (hazard ratio 1.29, 95% confidence interval 1.12–1.49;
P
<0.001). Chloride levels net-reclassified risk in 10.4% (
P
=0.03) when added to a multivariable model (with a resultant C-statistic of 0.70), in which sodium levels were not prognostic (
P
=0.30). In comparison to those with above first quartile chloride (≥101 mEq/L) and sodium (≥138 meq/L), subjects with first quartile chloride had a higher adjusted mortality risk, whether they had first quartile sodium (hazard ratio 1.35, 95% confidence interval 1.08–1.69;
P
=0.008) or higher (hazard ratio 1.43, 95% confidence interval 1.12–1.85;
P
=0.005). However, subjects with first quartile sodium but above first quartile chloride had no association with mortality (
P
=0.67).

Conclusions—
Lower serum chloride levels are independently and incrementally associated with increased mortality risk in patients with chronic heart failure. A better understanding of the biological role of serum chloride is warranted.
Heart Failure With Preserved Ejection Fraction Induces Beiging in Adipose Tissue
Authors: Valero-Muñoz María , Li Shanpeng , Wilson Richard M. , Hulsmans Maarten , Aprahamian Tamar , Fuster José J. , Nahrendorf Matthias , Scherer Philipp E. , Sam Flora 
Published: January 2016

Background—
Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there are no evidence-based therapies for HFpEF. Clinical studies suggest a relationship between obesity-associated dysfunctional adipose tissue (AT) and HFpEF. However, an apparent obesity paradox exists in some HF populations with a higher body mass index. We sought to determine whether HFpEF exerted effects on AT and investigated the involved mechanisms.

Methods and Results—

Mice underwent
d
-aldosterone infusion, uninephrectomy, and were given 1% saline for 4 weeks. HFpEF mice developed hypertension, left ventricular hypertrophy, and diastolic dysfunction and had higher myocardial natriuretic peptide expression. Although body weights were similar in HFpEF and sham-operated mice, white AT was significantly smaller in HFpEF than in sham (epididymal AT, 7.59 versus 10.67 mg/g; inguinal AT, 6.34 versus 8.38 mg/g). These changes were associated with smaller adipocyte size and increased beiging markers (ucp-1, cidea, and eva) in white AT. Similar findings were seen in HFpEF induced by transverse aortic constriction. Increased activation of natriuretic peptide signaling was seen in white AT of HFpEF mice. The ratio of the signaling receptor, natriuretic peptide receptor type A, to the clearance receptor, nprc, was increased as was p38 mitogen-activated protein kinase activation. However, HFpEF mice failed to regulate body temperature during cold temperature exposure. In HFpEF, despite a larger brown AT mass (5.96 versus 4.50 mg/g), brown AT showed reduced activity with decreased uncoupling protein 1 (ucp-1), cell death-inducing DFFA-like effector a (cidea), and epithelial V-like antigen (eva) expression and decreased expression of lipolytic enzymes (hormone-sensitive lipase, lipoprotein lipase, and fatty acid binding protein 4) versus sham.

Conclusions—
These findings show that HFpEF is associated with beiging in white AT and with dysfunctional brown AT.
Partial Liver Kinase B1 (LKB1) Deficiency Promotes Diastolic Dysfunction, De Novo Systolic Dysfunction, Apoptosis, and Mitochondrial Dysfunction With Dietary Metabolic Challenge
Authors: Miller Edward J. , Calamaras Timothy , Elezaby Aly , Sverdlov Aaron , Qin Fuzhong , Luptak Ivan , Wang Ke , Sun Xinxin , Vijay Andrea , Croteau Dominique , Bachschmid Markus , Cohen Richard A. , Walsh Kenneth , Colucci Wilson S. 
Published: January 2016

Background

Myocardial hypertrophy and dysfunction are key features of metabolic heart disease due to dietary excess. Metabolic heart disease manifests primarily as diastolic dysfunction but may progress to systolic dysfunction, although the mechanism is poorly understood. Liver kinase B1 (
LKB
1) is a key activator of
AMP
‐activated protein kinase and possibly other signaling pathways that oppose myocardial hypertrophy and failure. We hypothesized that
LKB
1 is essential to the heart's ability to withstand the metabolic stress of dietary excess.

Methods and Results

Mice heterozygous for cardiac
LKB
1 were fed a control diet or a high‐fat, high‐sucrose diet for 4 months. On the control diet, cardiac
LKB
1 hearts had normal structure and function. After 4 months of the high‐fat, high‐sucrose diet, there was left ventricular hypertrophy and diastolic dysfunction in wild‐type mice. In cardiac
LKB
1 (versus wild‐type) mice, high‐fat, high‐sucrose feeding caused more hypertrophy (619 versus 553 μm
2
,
P
<0.05), the de novo appearance of systolic dysfunction (left ventricular ejection fraction; 41% versus 59%,
P
<0.01) with left ventricular dilation (3.6 versus 3.2 mm,
P
<0.05), and more severe diastolic dysfunction with progression to a restrictive filling pattern (E/A ratio; 5.5 versus 1.3,
P
=0.05). Myocardial dysfunction in hearts of cardiac
LKB
1 mice fed the high‐fat, high‐sucrose diet was associated with evidence of increased apoptosis and apoptotic signaling via caspase 3 and p53/
PUMA
(p53 upregulated modulator of apoptosis) and more severe mitochondrial dysfunction.

Conclusions

Partial deficiency of cardiac
LKB
1 promotes the adverse effects of a high‐fat, high‐sucrose diet on the myocardium, leading to worsening of diastolic function and the de novo appearance of systolic dysfunction.
LKB
1 plays a key role in protecting the heart from the consequences of metabolic stress.
Circulating Galectin‐3 Is Associated With Cardiometabolic Disease in the Community
Authors: Nayor Matthew , Wang Na , Larson Martin G. , Vasan Ramachandran S. , Levy Daniel , Ho Jennifer E. 
Published: January 2016

Background
Circulating Galectin‐3 (Gal‐3) concentrations are associated with an increased incidence of heart failure, atrial fibrillation, chronic kidney disease, and mortality. Recent evidence suggests that Gal‐3 may also be an important modulator of cardiometabolic traits such as adiposity, insulin resistance, and hyperglycemia. We examined the associations of blood Gal‐3 concentrations and cardiometabolic disease traits in the Framingham Heart Study.

Methods and Results

In cross‐sectional analyses of 2946
Framingham Heart Study
participants (mean age 59 years, 55% women), higher Gal‐3 concentrations were associated with higher body mass index, waist circumference, and triglycerides (
P
<0.0001 for all). Higher Gal‐3 was associated with greater odds of obesity (multivariable‐adjusted odds ratio 1.16 per 1‐SD increase in log–Gal‐3, 95%
CI
1.06–1.28,
P
=0.002) and hypertension (odds ratio 1.18, 95%
CI
1.07–1.29,
P
=0.0006). In prospective analyses, Gal‐3 was associated with incident metabolic syndrome (hazard ratio 1.22, 95%
CI
1.10–1.36,
P
=0.0002) and diabetes (hazard ratio 1.21, 95%
CI
1.04–1.41,
P
=0.02), in age‐ and sex‐adjusted, but not multivariable‐adjusted models.

Conclusions
In this large, community‐based sample, circulating Gal‐3 was associated with abdominal adiposity, dyslipidemia, and hypertension in cross‐sectional analyses, but Gal‐3 did not predict incident cardiometabolic disease after adjusting for cardiometabolic risk factors. Future investigations should focus on further elucidating mechanisms linking Gal‐3 with cardiometabolic disease and on assessing whether modulation of the Gal‐3 pathway might have positive cardiometabolic effects.
Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris
Authors: Ding Yunpeng , Svingen Gard F. T. , Pedersen Eva R. , Gregory Jesse F. , Ueland Per M. , Tell Grethe S. , Nygård Ottar K. 
Published: January 2016

Background

Glycine is an amino acid involved in antioxidative reactions, purine synthesis, and collagen formation. Several studies demonstrate inverse associations of glycine with obesity, hypertension, and diabetes mellitus. Recently, glycine‐dependent reactions have also been linked to lipid metabolism and cholesterol transport. However, little evidence is available on the association between glycine and coronary heart disease. Therefore, we assessed the association between plasma glycine and acute myocardial infarction (
AMI
).

Methods and Results

A total of 4109 participants undergoing coronary angiography for suspected stable angina pectoris were studied. Cox regression was used to estimate the association between plasma glycine and
AMI
, obtained via linkage to the
CVDNOR
project. During a median follow‐up of 7.4 years, 616 patients (15.0%) experienced an
AMI
. Plasma glycine was higher in women than in men and was associated with a more favorable baseline lipid profile and lower prevalence of obesity, hypertension, and diabetes mellitus (all
P
<0.001). After multivariate adjustment for traditional coronary heart disease risk factors, plasma glycine was inversely associated with risk of
AMI
(hazard ratio per
SD
: 0.89; 95%
CI
, 0.82–0.98;
P
=0.017). The inverse association was generally stronger in those with apolipoprotein B, low‐density lipoprotein cholesterol, or apolipoprotein A‐1 above the median (all
P
interaction
≤0.037).

Conclusions

Plasma glycine was inversely associated with risk of
AMI
in patients with suspected stable angina pectoris. The associations were stronger in patients with apolipoprotein B, low‐density lipoprotein cholesterol, or apolipoprotein A‐1 levels above the median. These results motivate further studies to elucidate the relationship between glycine and lipid metabolism, in particular in relation to cholesterol transport and atherosclerosis.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov
. Unique identifier:
NCT
00354081.
Comparison of Basiliximab and Anti‐Thymocyte Globulin as Induction Therapy in Pediatric Heart Transplantation: A Survival Analysis
Authors: Ansari David , Höglund Peter , Andersson Bodil , Nilsson Johan 
Published: January 2016

Background
Basiliximab and anti‐thymocyte globulin are widely used drugs for induction therapy after pediatric heart transplantation. The aim of this study was to determine whether any differences could be observed between basiliximab and anti‐thymocyte globulin, with respect to long‐term mortality, in a population of pediatric cardiac transplant recipients.

Methods and Results

An analysis of pediatric heart transplant patients (aged <18 years) from the United Network for Organ Sharing database was conducted that compared patients receiving basiliximab with those that received anti‐thymocyte globulin for the risk of all‐cause mortality. Secondary endpoints included death attributable to graft failure, cardiovascular causes, infection, or malignancy. Of the 2275 patients, 685 received basiliximab and 1590 anti‐thymocyte globulin. One‐year survival was similar for both groups; however, at 5 and 10 years, basiliximab was associated with poorer long‐term survival (68% versus 76% at 5 years [
P
<0.001] and 49% versus 65% at 10 years [
P
<0.001], respectively). Basiliximab was associated with higher risk of death attributable to graft failure (
P
=0.013), but not death attributable to cardiovascular causes (
P
=0.444), infection (
P
=0.095), or malignancy (
P
=0.392). After multivariate analysis, use of basiliximab (versus use of anti‐thymocyte globulin) remained significantly associated with all‐cause mortality (hazard ratio, 1.27; 95% confidence interval, 1.02–1.57;
P
=0.030).

Conclusions
In pediatric heart transplant patients, use of basiliximab for induction therapy was associated with an increased risk of mortality, when compared with those receiving anti‐thymocyte globulin.
Design Culture and Dialogic Design
Authors: Manzini Ezio 
Published: January 2016

The question of culture is virtually absent from the debate on contemporary design and especially from what in this paper I refer to as emerging design: a problem-based, solution-oriented design, the defining characteristic of which is not the products, services, and communicative artifacts it produces, but the tools and methods it uses. But, although rarely discussed, emerging design also has its own culture—a culture that is rather limited and limiting precisely because of this lack of debate. To go beyond this somewhat reductive culture (to which the paper refers with the expressions solution-ism and participation-ism), we need to return to the discussion on issues that are or should be typical of design: from the criteria by which to orient and assess the quality of local solutions, to the broadest visions of the world toward which we work. This discussion, and the design culture it generates, must be undertaken through a dialogic approach, in which the various interlocutors, design experts included, interact as they bring their own ideas and define and accept their own responsibilities.