bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated Circulating Adipocyte‐Fatty Acid Binding Protein Levels Predict Incident Cardiovascular Events in a Community‐Based Cohort: A 12‐Year Prospective Study
Authors: Chow Wing Sun , Tso Annette Wai Kwan , Xu Aimin , Yuen Michele Mae Ann , Fong Carol Ho Yi , Lam Tai Hing , Lo Su Vui , Tse Hung Fat , Woo Yu Cho , Yeung Chun Yip , Cheung Bernard Man Yung , Lam Karen Siu Ling 
Published: May 2013

Background

Obesity is closely associated with various cardiovascular diseases (
CVD
s). Adipose tissue inflammation and perturbation of adipokine secretion may contribute to the pathogenesis of
CVD
. This study aimed to evaluate whether the 2 most abundant adipokines, adipocyte‐fatty acid binding protein (A‐
FABP
) and adiponectin, are independent risk factors predisposing to
CVD
.

Method and Results

We investigated prospectively the 12‐year development of
CVD
in relation to the baseline levels of A‐
FABP
and adiponectin in a population‐based community cohort comprising 1847 Chinese subjects recruited from the
H
ong
K
ong
C
ardiovascular
R
isk
F
actors
P
revalence
S
tudy 2 (
CRISPS
2) cohort without previous
CVD
. Baseline serum levels of A‐
FABP
, adiponectin, and
C
‐reactive protein (
CRP
), an established biomarker predictive of
CVD
, were measured. In all, 182 (9.9%) of the 1847 Chinese subjects developed
CVD
during a median follow‐up of 9.4 years. The
CVD
group had more traditional risk factors, higher baseline levels of A‐
FABP
and
CRP
(both
P
<0.001), but similar adiponectin levels (
P
=0.881) compared with the non‐
CVD
group. In
C
ox regression analysis including both biomarkers, the adjusted
HR
for A‐
FABP
and
CRP
for subjects above the optimal cutoff values were 1.57 (95%
CI
, 1.14 to 2.16;
P
=0.006) and 1.60 (95%
CI
, 1.12 to 2.27;
P
=0.01), respectively, after adjustment for traditional risk factors. The category‐free net reclassification index, but not the c‐statistic, showed improvement in predictive performance by the addition of A‐
FABP
to the traditional risk factor model (
P
=0.017).

Conclusions

Circulating A‐
FABP
level predicts the development of
CVD
after adjustment for traditional risk factors in a community‐based cohort. Its clinical use for
CVD
prediction warrants further validation.
Exercise Training for Blood Pressure: A Systematic Review and Meta‐analysis
Authors: Cornelissen Veronique A. , Smart Neil A. 
Published: May 2013

Background
We conducted meta‐analyses examining the effects of endurance, dynamic resistance, combined endurance and resistance training, and isometric resistance training on resting blood pressure (BP) in adults. The aims were to quantify and compare BP changes for each training modality and identify patient subgroups exhibiting the largest BP changes.

Methods and Results

Randomized controlled trials lasting ≥4 weeks investigating the effects of exercise on BP in healthy adults (age ≥18 years) and published in a peer‐reviewed journal up to
F
ebruary 2012 were included. Random effects models were used for analyses, with data reported as weighted means and 95% confidence interval. We included 93 trials, involving 105 endurance, 29 dynamic resistance, 14 combined, and 5 isometric resistance groups, totaling 5223 participants (3401 exercise and 1822 control). Systolic BP (
SBP
) was reduced after endurance (−3.5 mm Hg [confidence limits −4.6 to −2.3]), dynamic resistance (−1.8 mm Hg [−3.7 to −0.011]), and isometric resistance (−10.9 mm Hg [−14.5 to −7.4]) but not after combined training. Reductions in diastolic
BP
(
DBP
) were observed after endurance (−2.5 mm Hg [−3.2 to −1.7]), dynamic resistance (−3.2 mm Hg [−4.5 to −2.0]), isometric resistance (−6.2 mm Hg [−10.3 to −2.0]), and combined (−2.2 mm Hg [−3.9 to −0.48]) training.
BP
reductions after endurance training were greater (
P
<0.0001) in 26 study groups of hypertensive subjects (−8.3 [−10.7 to −6.0]/−5.2 [−6.8 to −3.4] mm Hg) than in 50 groups of prehypertensive subjects (−2.1 [−3.3 to −0.83]/−1.7 [−2.7 to −0.68]) and 29 groups of subjects with normal
BP
levels (−0.75 [−2.2 to +0.69]/−1.1 [−2.2 to −0.068]).
BP
reductions after dynamic resistance training were largest for prehypertensive participants (−4.0 [−7.4 to −0.5]/−3.8 [−5.7 to −1.9] mm Hg) compared with patients with hypertension or normal
BP
.

Conclusion

Endurance, dynamic resistance, and isometric resistance training lower SBP and DBP, whereas combined training lowers only DBP. Data from a small number of isometric resistance training studies suggest this form of training has the potential for the largest reductions in
SBP
.
Long‐term Outcomes of Catheter Ablation of Atrial Fibrillation: A Systematic Review and Meta‐analysis
Authors: Ganesan Anand N. , Shipp Nicholas J. , Brooks Anthony G. , Kuklik Pawel , Lau Dennis H. , Lim Han S. , Sullivan Thomas , Roberts‐Thomson Kurt C. , Sanders Prashanthan 
Published: May 2013

Background

In the past decade, catheter ablation has become an established therapy for symptomatic atrial fibrillation (
AF
). Until very recently, few data have been available to guide the clinical community on the outcomes of
AF
ablation at ≥3 years of follow‐up. We aimed to systematically review the medical literature to evaluate the long‐term outcomes of
AF
ablation.

Methods and Results

A structured electronic database search (PubMed, Embase, Web of Science, Cochrane) of the scientific literature was performed for studies describing outcomes at ≥3 years after
AF
ablation, with a mean follow‐up of ≥24 months after the index procedure. The following data were extracted: (1) single‐procedure success, (2) multiple‐procedure success, and (3) requirement for repeat procedures. Data were extracted from 19 studies, including 6167 patients undergoing
AF
ablation. Single‐procedure freedom from atrial arrhythmia at long‐term follow‐up was 53.1% (95%
CI
46.2% to 60.0%) overall, 54.1% (95%
CI
44.4% to 63.4%) in paroxysmal
AF
, and 41.8% (95%
CI
25.2% to 60.5%) in nonparoxysmal
AF
. Substantial heterogeneity (I
2
>50%) was noted for single‐procedure outcomes. With multiple procedures, the long‐term success rate was 79.8% (95%
CI
75.0% to 83.8%) overall, with significant heterogeneity (I
2
>50%).The average number of procedures per patient was 1.51 (95%
CI
1.36 to 1.67).

Conclusions

Catheter ablation is an effective and durable long‐term therapeutic strategy for some
AF
patients. Although significant heterogeneity is seen with single procedures, long‐term freedom from atrial arrhythmia can be achieved in some patients, but multiple procedures may be required.
Aliskiren Effect on Plaque Progression in Established Atherosclerosis Using High Resolution 3D MRI (ALPINE): A Double‐Blind Placebo‐Controlled Trial
Authors: Mihai Georgeta , Varghese Juliet , Kampfrath Thomas , Gushchina Liubov , Hafer Lisa , Deiuliis Jeffrey , Maiseyeu Andrei , Simonetti Orlando P. , Lu Bo , Rajagopalan Sanjay 
Published: May 2013

Background

The renin–angiotensin system is well recognized as a mediator of pathophysiological events in atherosclerosis. The benefits of renin inhibition in atherosclerosis, especially when used in combination with angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers (
ACEIs
/
ARB
s) are currently not known. We hypothesized that treatment with the renin inhibitor aliskiren in patients with established cardiovascular disease will prevent the progression of atherosclerosis as determined by high‐resolution magnetic resonance imaging (
MRI
) measurements of arterial wall volume in the thoracic and abdominal aortas of high‐risk patients with preexisting cardiovascular disease.

Methods and Results

This was a single‐center, randomized, double‐blind, placebo‐controlled trial in patients with established cardiovascular disease. After a 2‐week single‐blind placebo phase, patients were randomized to receive either placebo (n=37, mean±SD age 64.5±8.9 years, 3 women) or 150 mg of aliskiren (n=34, mean±SD age 63.9±11.5 years, 9 women). Treatment dose was escalated to 300 mg at 2 weeks and maintained during the remainder of the study. Patients underwent dark‐blood, 3‐dimensional
MRI
assessment of atherosclerotic plaque in the thoracic and abdominal segments at baseline and on study completion or termination (up to 36 weeks of drug or matching placebo).
A
liskiren use resulted in significant progression of aortic wall volume (normalized total wall volume 5.31±6.57 vs 0.15±4.39 mm
3
,
P
=0.03, and percentage wall volume 3.37±2.96% vs 0.97±2.02%,
P
=0.04) compared with placebo. In a subgroup analysis of subjects receiving
ACEI
/
ARB
therapy, atherosclerosis progression was observed only in the aliskiren group, not in the placebo group.

Conclusions

MRI
quantification of atheroma plaque burden demonstrated that aliskiren use in patients with preexisting cardiovascular disease resulted in an unexpected increase in aortic atherosclerosis compared with placebo. Although preliminary, these results may have implications for the use of renin inhibition as a therapeutic strategy in patients with cardiovascular disease, especially in those receiving
ACEI
/
ARB
therapy.

Clinical Trial Registration

URL:
http://ClinicalTrials.gov
Unique identifier
:
NCT01417104.
Critical Role for the Advanced Glycation End‐Products Receptor in Pulmonary Arterial Hypertension Etiology
Authors: Meloche Jolyane , Courchesne Antony , Barrier Marjorie , Carter Sophie , Bisserier Malik , Paulin Roxane , Lauzon‐Joset Jean‐François , Breuils‐Bonnet Sandra , Tremblay Ève , Biardel Sabrina , Racine Christine , Courture Christian , Bonnet Pierre , Majka Susan M. , Deshaies Yves , Picard Frédéric , Provencher Steeve , Bonnet Sébastien 
Published: May 2013

Background

Pulmonary arterial hypertension (
PAH
) is a vasculopathy characterized by enhanced pulmonary artery smooth muscle cell (
PASMC
) proliferation and suppressed apoptosis. This results in both increase in pulmonary arterial pressure and pulmonary vascular resistance. Recent studies have shown the implication of the signal transducer and activator of transcription 3 (
STAT
3)/bone morphogenetic protein receptor 2 (
BMPR
2)/peroxisome proliferator‐activated receptor gamma (
PPAR
γ) in
PAH
.
STAT
3 activation induces
BMPR
2 downregulation, decreasing
PPAR
γ, which both contribute to the proproliferative and antiapoptotic phenotype seen in
PAH
. In chondrocytes, activation of this axis has been attributed to the advanced glycation end‐products receptor (
RAGE
). As
RAGE
is one of the most upregulated proteins in
PAH
patients' lungs and a strong
STAT
3 activator, we hypothesized that by activating
STAT
3,
RAGE
induces
BMPR
2 and
PPAR
γ downregulation, promoting
PAH
‐
PASMC
proliferation and resistance to apoptosis.

Methods and Results

In vitro, using
PASMC
s isolated from
PAH
and healthy patients, we demonstrated that
RAGE
is overexpressed in
PAH
‐
PASMC
(6‐fold increase), thus inducing
STAT
3 activation (from 10% to 40% positive cells) and decrease in
BMPR
2 and
PPAR
γ levels (>50% decrease). Pharmacological activation of
RAGE
in control cells by S100A4 recapitulates the
PAH
phenotype (increasing
RAGE
by 6‐fold, thus activating
STAT
3 and decreasing
BMPR
2 and
PPAR
γ). In both conditions, this phenotype is totally reversed on
RAGE
inhibition. In vivo,
RAGE
inhibition in monocrotaline‐ and
S
ugen‐induced
PAH
demonstrates therapeutic effects characterized by
PA
pressure and right ventricular hypertrophy decrease (control rats have an
mPAP
around 15 mm Hg,
PAH
rats have an
mPAP
>40 mm Hg, and with
RAGE
inhibition,
mPAP
decreases to 20 and 28 mm Hg, respectively, in
MCT
and
S
ugen models). This was associated with significant improvement in lung perfusion and vascular remodeling due to decrease in proliferation (>50% decrease) and
BMPR
2/
PPAR
γ axis restoration (increased by ≥60%).

Conclusion

We have demonstrated the implications of
RAGE
in
PAH
etiology. Thus,
RAGE
constitutes a new attractive therapeutic target for
PAH
.
In Vivo Cardiac Cellular Reprogramming Efficacy Is Enhanced by Angiogenic Preconditioning of the Infarcted Myocardium With Vascular Endothelial Growth Factor
Authors: Mathison Megumi , P. Gersch Robert , Nasser Ahmed , Lilo Sarit , Korman Mallory , Fourman Mitchell , Hackett Neil , Shroyer Kenneth , Yang Jianchang , Ma Yupo , Crystal Ronald G. , Rosengart Todd K. 
Published: May 2013

Background

In situ cellular reprogramming offers the possibility of regenerating functional cardiomyocytes directly from scar fibroblasts, obviating the challenges of cell implantation. We hypothesized that pretreating scar with gene transfer of the angiogenic vascular endothelial growth factor (
VEGF
) would enhance the efficacy of this strategy.

Methods and Results

Gata4, Mef2c, and Tbx5 (
GMT
) administration via lentiviral transduction was demonstrated to transdifferentiate rat fibroblasts into (induced) cardiomyocytes in vitro by cardiomyocyte marker studies. Fisher 344 rats underwent coronary ligation and intramyocardial administration of an adenovirus encoding all 3 major isoforms of
VEGF
(Ad
VEGF
‐All6A
+
) or an AdNull control vector (n=12/group). Lentivirus encoding
GMT
or a
GFP
control was administered to each animal 3 weeks later, followed by histologic and echocardiographic analyses.
GMT
administration reduced the extent of fibrosis by half compared with
GFP
controls (12±2% vs 24±3%,
P
<0.01) and reduced the number of myofibroblasts detected in the infarct zone by 4‐fold.
GMT
‐treated animals also demonstrated greater density of cardiomyocyte‐specific marker beta myosin heavy chain 7
+
cells compared with animals receiving
GFP
with or without
VEGF
(
P
<0.01). Ejection fraction was significantly improved after
GMT
vs
GFP
administration (12±3% vs −7±3%,
P
<0.01). Eight (73%)
GFP
animals but no
GMT
animals demonstrated decreased ejection fraction during this interval (
P
<0.01). Also, improvement in ejection fraction was 4‐fold greater in
GMT
/
VEGF
vs
GMT
/null animals (17±2% vs 4±1%,
P
<0.05).

Conclusions

VEGF
administration to infarcted myocardium enhances the efficacy of
GMT
‐mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of
GMT
or
VEGF
alone.
Atrial Fibrillation and Outcomes in Heart Failure With Preserved Versus Reduced Left Ventricular Ejection Fraction
Authors: McManus David D. , Hsu Grace , Sung Sue Hee , Saczynski Jane S. , Smith David H. , Magid David J. , Gurwitz Jerry H. , Goldberg Robert J. , Go Alan S. ,   for the Cardiovascular Research Network PRESERVE Study
Published: May 2013

Background

Atrial fibrillation (
AF
) and heart failure (
HF
) are 2 of the most common cardiovascular conditions nationally and
AF
frequently complicates
HF
. We examined how
AF
has impacts on adverse outcomes in
HF
‐
PEF
versus
HF
‐
REF
within a large, contemporary cohort.

Methods and Results

We identified all adults diagnosed with
HF
‐
PEF
or
HF
‐
REF
based on hospital discharge and ambulatory visit diagnoses and relevant imaging results for 2005–2008 from 4 health plans in the Cardiovascular Research Network. Data on demographic features, diagnoses, procedures, outpatient pharmacy use, and laboratory results were ascertained from health plan databases. Hospitalizations for
HF
, stroke, and any reason were identified from hospital discharge and billing claims databases. Deaths were ascertained from health plan and state death files. Among 23 644 patients with
HF
, 11 429 (48.3%) had documented
AF
(9081 preexisting, 2348 incident). Compared with patients who did not have
AF
, patients with
AF
had higher adjusted rates of ischemic stroke (hazard ratio [
HR
] 2.47 for incident
AF
;
HR
1.57 for preexisting
AF
), hospitalization for
HF
(
HR
2.00 for incident
AF
;
HR
1.22 for preexisting
AF
), all‐cause hospitalization (
HR
1.45 for incident
AF
;
HR
1.15 for preexisting
AF
), and death (incident
AF HR
1.67; preexisting
AF HR
1.13). The associations of
AF
with these outcomes were similar for
HF
‐
PEF
and
HF
‐
REF
, with the exception of ischemic stroke.

Conclusions

AF
is a potent risk factor for adverse outcomes in patients with
HF
‐
PEF
or
HF
‐
REF
. Effective interventions are needed to improve the prognosis of these high‐risk patients.
Novel Tissue‐Specific Mechanism of Regulation of Angiogenesis and Cancer Growth in Response to Hyperglycemia
Authors: Bhattacharyya Sanghamitra , Sul Kristina , Krukovets Irene , Nestor Carla , Li Jianbo , Adognravi Olga Stenina 
Published: May 2013

Background
Hyperglycemia is an independent risk factor for the development of vascular diabetic complications, which are characterized by endothelial dysfunction and tissue‐specific aberrant angiogenesis. Tumor growth is also dependent on angiogenesis. Diabetes affects several cancers in a tissue‐specific way. For example, it positively correlates with the incidence of breast cancer but negatively correlates with the incidence of prostate cancer. The tissue‐specific molecular mechanisms activated by hyperglycemia that control angiogenesis are unknown. Here we describe a novel tissue‐ and cell‐specific molecular pathway that is activated by high glucose and regulates angiogenesis.

Methods and Results

We have identified micro
RNA
467 (miR‐467) as a translational suppressor of thrombospondin‐1 (
TSP
‐1), a potent antiangiogenic protein that is implicated in the pathogenesis of several diabetic complications. miR‐467 was upregulated by hyperglycemia in a tissue‐specific manner. It was induced by high glucose in microvascular endothelial cells and in breast cancer cells, where it suppressed the production of
TSP
‐1 by sequestering
mRNA
in the nonpolysomal fraction. Mutation of the miR‐467 binding site in
TSP
‐1 3′
UTR
or miR‐467 inhibitor relieved the translational silencing and restored
TSP
‐1 production. In in vivo angiogenesis models, miR‐467 promoted the growth of blood vessels, and
TSP
‐1 was the main mediator of this effect. Breast cancer tumors showed increased growth in hyperglycemic mice and expressed higher levels of miR‐467. The antagonist of miR‐467 prevented the hyperglycemia‐induced tumor growth.

Conclusions
Our results demonstrate that miR‐467 is implicated in the control of angiogenesis in response to high glucose, which makes it an attractive tissue‐specific potential target for therapeutic regulation of aberrant angiogenesis and cancer growth in diabetes.
Acute ST‐Elevation Myocardial Infarction in Patients Hospitalized for Noncardiac Conditions
Authors: Dai Xuming , Bumgarner Joseph , Spangler Andrew , Meredith Dane , Smith Sidney C. , Stouffer George A. 
Published: May 2013

Background

Major advances have been made in the treatment of
ST
‐elevation myocardial infarction (
STEMI
) in outpatients. In contrast, little is known about outcomes in
STEMI
that occur in patients hospitalized for a noncardiac condition.

Methods and Results

This was a retrospective, single‐center study of inpatient
STEMI
s from January 1, 2007, to July 31, 2011. Forty‐eight cases were confirmed to be inpatient
STEMI
s of a total of 139 410 adult discharges. These patients were older and more often female and had higher rates of chronic kidney disease and prior cerebrovascular events compared with 227 patients with outpatient
STEMI
s treated during the same period. Onset of inpatient
STEMI
was heralded most frequently by a change in clinical status (60%) and less commonly by patient complaints (33%) or changes on telemetry. Coronary angiography and percutaneous coronary intervention were performed in 71% and 56% of patients, respectively. The median time to obtain
ECG
(41 [10, 600] versus 5 [2, 10] minutes;
P
<0.001),
ECG
to angiography time (91 [26, 209] versus 35 [25, 46] minutes;
P
<0.001) and
ECG
to first device activation (
FDA
) (129 [65, 25] versus 60 [47, 76] minutes;
P
<0.001) were longer for inpatient versus outpatient
STEMI
. Survival to discharge was lower for inpatient
STEMI
(60% versus 96%;
P
<0.001), and this difference persisted after adjusting for potential confounders.

Conclusions

Patients who develop a
STEMI
while hospitalized for a noncardiac condition are older and more often female, have more comorbidities, have longer
ECG
‐to‐
FDA
times, and are less likely to survive than patients with an outpatient
STEMI
.
Mechanical Unloading Activates FoxO3 to Trigger Bnip3‐Dependent Cardiomyocyte Atrophy
Authors: Cao Dian J. , Jiang Nan , Blagg Andrew , Johnstone Janet L. , Gondalia Raj , Oh Misook , Luo Xiang , Yang Kai‐Chun , Shelton John M. , Rothermel Beverly A. , Gillette Thomas G. , Dorn Gerald W. , Hill Joseph A. 
Published: May 2013

Background
Mechanical assist device therapy has emerged recently as an important and rapidly expanding therapy in advanced heart failure, triggering in some patients a beneficial reverse remodeling response. However, mechanisms underlying this benefit are unclear.

Methods and Results

In a model of mechanical unloading of the left ventricle, we observed progressive myocyte atrophy, autophagy, and robust activation of the transcription factor FoxO3, an established regulator of catabolic processes in other cell types. Evidence for FoxO3 activation was similarly detected in unloaded failing human myocardium. To determine the role of FoxO3 activation in cardiac muscle in vivo, we engineered transgenic mice harboring a cardiomyocyte‐specific constitutively active FoxO3 mutant (
caFoxO3

flox

;α
MHC‐Mer‐Cre‐Mer
). Expression of caFoxO3 triggered dramatic and progressive loss of cardiac mass, robust increases in cardiomyocyte autophagy, declines in mitochondrial biomass and function, and early mortality. Whereas increases in cardiomyocyte apoptosis were not apparent, we detected robust increases in Bnip3 (Bcl2/adenovirus E1B 19‐
kD
a interacting protein 3), an established downstream target of FoxO3. To test the role of Bnip3, we crossed the
caFoxO3

flox

;α
MHC‐Mer‐Cre‐Mer
mice with Bnip3‐null animals. Remarkably, the atrophy and autophagy phenotypes were significantly blunted, yet the early mortality triggered by FoxO3 activation persisted. Rather, declines in cardiac performance were attenuated by proteasome inhibitors. Consistent with involvement of FoxO3‐driven activation of the ubiquitin‐proteasome system, we detected time‐dependent activation of the atrogenes program and sarcomere protein breakdown.

Conclusions
In aggregate, these data point to FoxO3, a protein activated by mechanical unloading, as a master regulator that governs both the autophagy‐lysosomal and ubiquitin‐proteasomal pathways to orchestrate cardiac muscle atrophy.