bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Anxiety and Depression With All‐Cause Mortality in Individuals With Coronary Heart Disease
Authors: Watkins Lana L. , Koch Gary G. , Sherwood Andrew , Blumenthal James A. , Davidson Jonathan R.T. , O'Connor Christopher , Sketch Michael H. 
Published: May 2013

Background

Depression has been related to mortality in coronary heart disease (
CHD
) patients, but few studies have evaluated the role of anxiety or the role of the co‐occurrence of depression and anxiety. We examined whether anxiety is associated with increased risk of mortality after accounting for depression in individuals with established
CHD
.

Methods and Results

The cohort was composed of 934 men and women with confirmed
CHD
(mean age, 62±11 years) who completed the Hospital Anxiety and Depression scale (
HADS
) during hospitalization for coronary angiography. Over the 3‐year follow‐up period, there were 133 deaths. Elevated scores on the
HADS
anxiety subscale (
HADS
‐A≥8) were associated with increased risk of mortality after accounting for established risk factors including age, congestive heart failure, left ventricular ejection fraction, 3‐vessel disease, and renal disease (hazard ratio [
HR
], 2.27; 95%
CI
, 1.55 to 3.33;
P
<0.001). Elevated scores on the
HADS
depression subscale (
HADS
‐D≥8) were also associated with increased risk of mortality (
HR
, 2.18; 95%
CI
, 1.47 to 3.22;
P
<0.001). When both psychosocial factors were included in the model, each maintained an association with mortality (anxiety,
HR
, 1.83; 95%
CI
, 1.18 to 2.83;
P
=0.006; depression,
HR
, 1.66; 95%
CI
, 1.06 to 2.58;
P
=0.025). Estimation of the
HR
for patients with both anxiety and depression versus those with neither revealed a larger
HR
than for patients with either factor alone (
HR
, 3.10; 95%
CI
, 1.95 to 4.94;
P
<0.001).

Conclusions

Anxiety is associated with increased risk of mortality in
CHD
patients, particularly when comorbid with depression. Future studies should focus on the co‐occurrence of these psychosocial factors as markers of increased mortality risk.
Associations of Glycemic Index and Load With Coronary Heart Disease Events: A Systematic Review and Meta‐Analysis of Prospective Cohorts
Authors: Mirrahimi Arash , de Souza Russell J. , Chiavaroli Laura , Sievenpiper John L. , Beyene Joseph , Hanley Anthony J. , Augustin Livia S. A. , Kendall Cyril W. C. , Jenkins David J. A. 
Published: May 2013

Background

Glycemic index (
GI
) and glycemic load (
GL
) have been associated with coronary heart disease (
CHD
) risk in some but not all cohort studies. We therefore assessed the association of
GI
and
GL
with
CHD
risk in prospective cohorts.

Methods and Results

We searched
MEDLINE
,
EMBASE
, and
CINAHL
(through April 5, 2012) and identified all prospective cohorts assessing associations of
GI
and
GL
with incidence of
CHD
. Meta‐analysis of observational studies in epidemiology (
MOOSE
) methodologies were used. Relative measures of risk, comparing the group with the highest exposure (mean
GI
of cohorts=84.4
GI
units, range 79.9 to 91; mean
GL
of cohorts=224.8, range 166 to 270) to the reference group (mean
GI
=72.3
GI
units, range 68.1 to 77; mean
GL
=135.4, range 83 to 176), were pooled using random‐effects models, expressed as relative risk (
RR
) with heterogeneity assessed by χ
2
and quantified by I
2
. Subgroups included sex and duration of follow‐up. Ten studies (n=240 936) were eligible. Pooled analyses showed an increase in
CHD
risk for the highest
GI
quantile compared with the lowest, with
RR
=1.11 (95% confidence interval [
CI
] 0.99 to 1.24) and for
GL
,
RR
=1.27 (95%
CI
1.09 to 1.49), both with evidence of heterogeneity (I
2
>42%,
P
<0.07). Subgroup analyses revealed only a significant modification by sex, with the female cohorts showing significance for
GI RR
=1.26 (95%
CI
1.12 to 1.41) and for
GL RR
=1.55 (95%
CI
1.18 to 2.03).

Conclusions

High
GI
and
GL
diets were significantly associated with
CHD
events in women but not in men. Further studies are required to determine the relationship between
GI
and
GL
with
CHD
in men.
Racial Differences in Arterial Stiffness and Microcirculatory Function Between Black and White Americans
Authors: Morris Alanna A. , Patel Riyaz S. , Binongo Jose Nilo G. , Poole Joseph , Mheid Ibhar al , Ahmed Yusuf , Stoyanova Neli , Vaccarino Viola , Din‐Dzietham Rebecca , Gibbons Gary H. , Quyyumi Arshed 
Published: May 2013

Background

Compared with whites, black
A
mericans suffer from a disproportionate burden of cardiovascular disease (
CVD
). We hypothesized that racial differences in the prevalence of
CVD
could be attributed, in part, to impaired vascular function in blacks after adjustment for differences in risk factor burden.

Methods and Results

We assessed vascular function in 385 black and 470 white subjects (mean age, 48±11 years; 45% male). Using digital pulse amplitude tonometry (Endo
PAT
) we estimated the reactive hyperemia index (
RHI
), a measure of microvascular endothelial function, and peripheral augmentation index (
PAT
‐
AI
x). Central augmentation index (
C
‐
AI
x) and pulse‐wave velocity (
PWV
) were measured as indices of wave reflections and arterial stiffness, respectively, using applanation tonometry (Sphygmocor). Compared with whites, blacks had lower
RHI
(2.1±0.6 versus 2.3±0.6,
P
<0.001), greater arterial wave reflections assessed as both
PAT
‐
AI
x (20.4±21.5 versus 17.0±22.4,
P
=0.01) and
CAI
x (20.8±12.3 versus 17.5±13.3,
P
=0.001), and greater arterial stiffness, measured as
PWV
(7.4±1.6 versus 7.1±1.6 m/s,
P
=0.001). After adjustment for traditional
CVD
risk factors, black race remained a significant predictor of lower
RHI
and higher
PAT
‐
AI
x and
CAI
x (all
P
<0.001) in all subjects and of higher
PWV
in men (
P
=0.01). Furthermore, these associations persisted in a subgroup analysis of “healthy” individuals free of
CVD
risk factors.

Conclusion

Black race is associated with impaired microvascular vasodilatory function, and greater large arterial wave reflections and stiffness. Because impairment in these vascular indices may be associated with worse long‐term outcomes, they may represent underlying mechanisms for the increased
CVD
risk in blacks.
Near Infrared Imaging and Photothermal Ablation of Vascular Inflammation Using Single‐Walled Carbon Nanotubes
Authors: Kosuge Hisanori , Sherlock Sarah P. , Kitagawa Toshiro , Dash Rajesh , Robinson Joshua T. , Dai Hongjie , McConnell Michael V. 
Published: May 2013

Background

Macrophages are critical contributors to atherosclerosis. Single‐walled carbon nanotubes (
SWNT
s) show promising properties for cellular imaging and thermal therapy, which may have application to vascular macrophages.

Methods and Results

In vitro uptake and photothermal destruction of mouse macrophage cells (
RAW
264.7) were performed with
SWNT
s (14.7 nmol/L) exposed to an 808‐nm light source.
SWNT
s were taken up by 94±6% of macrophages, and light exposure induced 93±3% cell death. In vivo vascular macrophage uptake and ablation were then investigated in carotid‐ligated
FVB
mice (n=33) after induction of hyperlipidemia and diabetes. Two weeks postligation, near‐infrared fluorescence (
NIRF
) carotid imaging (n=12) was performed with
SWNT
‐Cy5.5 (8 nmol of Cy5.5) given via the tail vein. Photothermal heating and macrophage apoptosis were evaluated on freshly excised carotid arteries (n=21).
NIRF
of
SWNT
s showed higher signal intensity in ligated carotids compared with sham, confirmed by both in situ and ex vivo
NIRF
imaging (
P
<0.05, ligation versus sham). Immunofluorescence staining showed colocalization of
SWNT
‐Cy5.5 and macrophages in atherosclerotic lesions. Light (808 nm) exposure of freshly excised carotids showed heating and induction of macrophage apoptosis in ligated left carotid arteries with
SWNT
s, but not in control groups without
SWNT
s or without light exposure.

Conclusions
Carbon nanotubes accumulate in atherosclerotic macrophages in vivo and provide a multifunctional platform for imaging and photothermal therapy of vascular inflammation.
Fasting Serum C‐Peptide Levels Predict Cardiovascular and Overall Death in Nondiabetic Adults
Authors: Patel Nileshkumar , Taveira Tracey H. , Choudhary Gaurav , Whitlatch Hilary , Wu Wen‐Chih 
Published: May 2013

Background
Insulin resistance, characterized by hyperinsulinemia and normal or elevated serum glucose, is an established precursor to diabetes and cardiovascular disease. Despite fasting serum C‐peptide levels being an accurate and stable marker of endogenous insulin production used in patients with diabetes, it is unknown whether C‐peptide could serve as a marker of insulin resistance and predict outcomes in patients without diabetes.

Method and Results

This is a retrospective cohort study using data from the
NHANES
‐3 (1988–1994) survey with mortality follow‐up through
D
ecember 31, 2006. Participants included 5153 subjects, 40 to 74 years of age with fasting glucose ≥70 mg/dL, without diabetes by history or laboratory testing. Receiver‐operating‐curve analysis compared fasting C‐peptide against known insulin resistance measures such as fasting plasma glucose, serum insulin,
HOMA
‐
IR
, quantitative‐insulin‐sensitivity‐check‐index, and metabolic syndrome for the prediction of cardiovascular and overall death. Subjects were then stratified by quartiles of C‐peptide levels.
C
ox proportional‐hazards modeling compared hazards of cardiovascular and overall death amongst C‐peptide quartiles and adjusted for potential confounders of cardiovascular and diabetes risk. Fasting serum C‐peptide levels predicted cardiovascular and overall death better than other studied measures (
AUC
=0.62 and 0.60 respectively vs the rest, with
AUC
≤0.58 and ≤0.57 respectively,
P
<0.001). When compared with the lowest C‐peptide quartile, subjects in the highest quartile had significantly higher adjusted hazard ratios (
HR
) of cardiovascular death (
HR
=1.60, 95%
CI
1.07 to 2.39) and overall mortality (
HR
=1.72, 95%
CI
1.34 to 2.21) after controlling for confounders.

Conclusions
C‐peptide levels significantly related to hazards of cardiovascular and overall death in nondiabetic adults and was a better predictor of these outcomes than serum insulin and/or glucose derived measures.
High Familial Risk of Atrial Fibrillation/Atrial Flutter in Multiplex Families: A Nationwide Family Study in Sweden
Authors: Zöller Bengt , Ohlsson Henrik , Sundquist Jan , Sundquist Kristina 
Published: May 2013

Background

Although the heritability of atrial fibrillation/atrial flutter (
AF
/
AF
l) has been determined, the familial risk in multiplex families is unclear. The main aim of this nationwide study was to determine the familial risk of
AF
/
AF
l in multiplex families.

Methods and Results

We examined the familial risk of
AF
/
AF
l in the entire Swedish population. We linked Multigeneration Register data on individuals aged 0 to 76 years with Hospital Discharge Register data for 1987–2008 and Outpatient Register data for 2001–2008 to compare
AF
/
AF
l risk among relatives of all 300 586 individuals with
AF
/
AF
l with that among relatives of unaffected individuals. We used conditional logistic regression to investigate differences in exposure between cases and controls. Parents (odds ratio [
OR
] 1.95 [95% CI 1.89 to 2.00]) and siblings (
OR
=3.08 [3.00 to 3.16]) of cases had higher odds of
AF
/
AF
l than did parents and siblings of controls.
AF
/
AF
l
OR
s were increased in both sexes. For 2% of cases, both parents had
AF
/
AF
l, compared with only 0.7% of controls (
OR
=3.60 [3.30 to 3.92]). Moreover, 3% of cases had ≥2 siblings with
AF
/
AF
l, compared with 1% of controls (
OR
=5.72 [5.28 to 6.19]). In premature cases (diagnosed at age <50 years), the
OR
s were 5.04 (4.36 to 5.82) and 8.51 (6.49 to 11.15) for
AF
/
AF
l in both parents and
AF
/
AF
l in ≥2 siblings, respectively. The overall spouse
OR
was 1.16 (1.13 to 1.19).

Conclusions

Family history of
AF
/
AF
l increases the odds of
AF
/
AF
l in first‐degree relatives. High familial risks were observed in multiplex families.
Adipocyte Triglyceride Turnover Is Independently Associated With Atherogenic Dyslipidemia
Authors: Frayn Keith , Bernard Samuel , Spalding Kirsty , Arner Peter 
Published: May 2013

Background
Inappropriate storage of fatty acids as triglycerides in adipocytes and their removal from adipocytes through lipolysis and subsequent oxidation may cause the atherogenic dyslipidemia phenotype of elevated apolipoprotein B levels and subsequent hypertriglyceridemia. We tested whether turnover of triglycerides in fat cells was related to dyslipidemia.

Methods and Results

The age of triglycerides (reflecting removal) and triglyceride storage in adipocytes was determined under free living conditions by measuring incorporation of atmospheric
14
C into these lipids within the adipocytes in 47 women and 26 men with a large interindividual variability in body mass index. Because limited
14
C data were available, triglyceride age was also determined in 97 men and 233 women by using an algorithm based on adipocyte lipolysis, body fat content, waist‐to‐hip ratio, and insulin sensitivity. This cohort consisted of nonobese subjects since obesity per se is related to all components in the algorithm. Triglyceride turnover (age and storage) was compared with plasma levels of apolipoproteins and lipids. Plasma levels of apolipoprotein B and triglycerides were positively related to triglyceride age in adipocytes, when measured directly using radiocarbon analyses (
r
=0.45 to 0.47;
P
<0.0001). This effect was independent of subject age, waist circumference measures, and insulin sensitivity (partial
r
=0.29 to 0.45;
P
from 0.03 to <0.0001). Triglyceride storage showed no independent correlation (partial
r
=0.02 to 0.11;
P
=0.42 to 0.91). Algorithm‐based values for adipocyte removal of triglycerides were positively associated with plasma triglycerides and apolipoprotein B (
r
=0.44 to 0.45;
P
<0.0001) and (also positively) with the inflammation status of adipose tissue (
r
=0.39 to 0.47;
P
<0.05). These correlations were statistically independent of subject age and observed in men and women as well as in lean and overweight subjects when subgroups were examined separately.

Conclusions
Decreased removal of adipocyte triglycerides (as indicated by a high triglyceride age in fat cells) is independently associated with circulating apolipoprotein B and triglycerides. This suggests a hitherto unknown role of triglyceride turnover in adipocytes for the development and/or maintenance of atherogenic dyslipidemia.
Risks of Death and Graft Failure After Surgical Versus Percutaneous Coronary Revascularization in Renal Transplant Patients
Authors: Charytan David M. , Li Shuling , Liu Jiannong , Qiu Yang , Herzog Charles A. 
Published: May 2013

Background

Reliable data regarding absolute and relative risks of death and graft failure after coronary artery bypass graft surgery (
CABG
) and percutaneous coronary intervention (
PCI
) in renal transplant patients are unavailable.

Methods and Results

Renal transplant patients undergoing inpatient
CABG
(n=1400) or
PCI
(n=4097) were identified from
U
nited
S
tates
R
enal
D
ata
S
ystem data. Cumulative incidence of nonfatal graft failure and death was reported for observed events. A
C
ox model with the
F
ine–
G
ray method was used to account for competing risks in assessing relative hazards. Age and race were similarly distributed; patients who underwent
CABG
were more likely to have acute arrhythmia and congestive heart failure but less likely to have acute myocardial infarction on index admission. In‐hospital death was more frequent after
CABG
(5.6% versus 3.0%,
P
<0.001). Cumulative incidence of death, graft failure, and the combined outcome at 3 years were 23.1%, 15.4%, and 38.5% after
CABG
and 22.9%, 13.3%, and 36.1% after
PCI
, respectively. In adjusted analyses,
CABG
was not associated with increased risk of graft failure versus
PCI
during the first 6 months (hazard ratio 1.06, 95% CI 0.79 to 1.43) or from 6 to 36 months (0.98, 0.78 to 1.22). Risk of death increased after
CABG
during the first 3 months (1.37, 1.08 to 1.73), but decreased from 6 months on (0.76, 0.63 to 0.93).

Conclusions

CABG
does not appear to be associated with a difference in risk of graft failure compared with
PCI
in renal transplant patients. Compared with
PCI
, adjusted risk of early death is higher after
CABG
; however, mortality from 6 months on is lower.
Defects of mtDNA Replication Impaired Mitochondrial Biogenesis During
Trypanosoma cruzi
Infection in Human Cardiomyocytes and Chagasic Patients: The Role of Nrf1/2 and Antioxidant Response
Authors: Wan Xianxiu , Gupta Shivali , Zago Maria P. , Davidson Mercy M. , Dousset Pierre , Amoroso Alejandro , Garg Nisha Jain 
Published: May 2013

Background

Mitochondrial dysfunction is a key determinant in chagasic cardiomyopathy development in mice; however, its relevance in human
C
hagas disease is not known. We determined if defects in mitochondrial biogenesis and dysregulation of peroxisome proliferator‐activated receptor gamma (
PPAR
γ) coactivator‐1 (
PGC
‐1)–regulated transcriptional pathways constitute a mechanism or mechanisms underlying mitochondrial oxidative‐phosphorylation (
OXPHOS
) deficiency in human
C
hagas disease.

Methods and Results

We utilized human cardiomyocytes and left‐ventricular tissue from chagasic and other cardiomyopathy patients and healthy donors (n>6/group). We noted no change in citrate synthase activity, yet
mRNA
and/or protein levels of subunits of the respiratory complexes were significantly decreased in

T
rypanosoma cruzi

–infected cardiomyocytes (0 to 24 hours) and chagasic hearts. We observed increased
mRNA
and decreased nuclear localization of
PGC
‐1‐coactivated transcription factors, yet the expression of genes for
PPAR
γ‐regulated fatty acid oxidation and nuclear respiratory factor (
NRF
1/2)–regulated
mtDNA
replication and transcription machinery was enhanced in infected cardiomyocytes and chagasic hearts. The
D
‐loop formation was normal or higher, but
mtDNA
replication and
mtDNA
content were decreased by 83% and 40% to 65%, respectively. Subsequently, we noted that reactive oxygen species (
ROS
), oxidative stress, and
mtDNA
oxidation were significantly increased, yet
NRF
1/2‐regulated antioxidant gene expression remained compromised in infected cardiomyocytes and chagasic hearts.

Conclusions

The replication of
mtDNA
was severely compromised, resulting in a significant loss of
mtDNA
and expression of
OXPHOS
genes in
T cruzi–
infected cardiomyocytes and chagasic hearts. Our data suggest increased
ROS
generation and selective functional incapacity of
NRF
2‐mediated antioxidant gene expression played a role in the defects in
mtDNA
replication and unfitness of
mtDNA
for replication and gene expression in
C
hagas disease.
Plasma Fibulin‐1 Is Linked to Restrictive Filling of the Left Ventricle and to Mortality in Patients With Aortic Valve Stenosis
Authors: Dahl Jordi S. , Møller Jacob E. , Videbæk Lars , Poulsen Mikael K. , Rudbæk Torsten R. , Pellikka Patricia A. , Scott Argraves W. , Rasmussen Lars Melholt 
Published: May 2013

Background

Plasma fibulin‐1 levels have been associated with
N‐terminal pro–B‐type natriuretic peptide
levels and left atrial size and shown to be predictive of mortality in patients with diabetes. The mechanisms behind these connections are not fully understood but are probably related to its roles as an extracellular matrix protein in cardiovascular tissues.

Methods and Results

One hundred twenty‐five patients with severe aortic stenosis who were scheduled for aortic valve replacement (
AVR
) were evaluated with preoperative echocardiography and their plasma fibulin‐1 levels were determined with
ELISA
. The cohort was followed for a median of 4 years after
AVR
. Increased restrictive left ventricular (
LV
) filling pattern was observed with increased plasma fibulin‐1 levels (2% versus 29% versus 24% in low, middle, and high plasma fibulin‐1 tertile groups,
P
=0.004). Likewise, reduced longitudinal systolic
LV
function (6.6±1.1 versus 6.1±1.3 versus 5.7±1.5 cm/s,
P
=0.05) and increased
LV
filling pressures was systolic velocity of the mitral annulus observed with increasing plasma fibulin‐1 concentrations (ratio of early transmitral flow velocity to early diastolic flow velocity of the mitral annulus 13±4 versus 15±5 versus 16±6 in the fibulin‐1 tertile groups,
P
=0.04).

Conclusions

In patients with symptomatic severe aortic stenosis undergoing AVR, plasma fibulin‐1 is associated with restrictive filling of the
LV
, decreased longitudinal systolic function of the
LV
, and increased
LV
filling pressures.

Clinical Trial Registration

URL:
www.clinicaltrial.gov
with Identifier: NCT00294775
Prevalence, Distribution, and Risk Factor Correlates of High Thoracic Periaortic Fat in the Framingham Heart Study
Authors: Britton Kathryn A. , Pedley Alison , Massaro Joseph M. , Corsini Erin M. , Murabito Joanne M. , Hoffmann Udo , Fox Caroline S. 
Published: May 2013

Background

Thoracic periaortic adipose tissue (
TAT
) is associated with atherosclerosis and cardiovascular disease (
CVD
) risk factors and may play a role in obesity‐mediated vascular disease. We sought to determine the prevalence, distribution, and risk factor correlates of high
TAT
.

Methods and Results

Participants from the
F
ramingham
H
eart
S
tudy (n=3246, 48% women, mean age 51.1 years) underwent multidetector computed tomography; high
TAT
and visceral adipose tissue (
VAT
) were defined on the basis of sex‐specific 90th percentiles in a healthy referent sample. The prevalence of high
TAT
was 38.1% in women and 35.7% in men. Among individuals without high
VAT
, 10.1% had high
TAT
. After adjustment for age and
VAT
, both women and men with high
TAT
in the absence of high
VAT
were older and had a higher prevalence of
CVD
(
P
<0.0001) compared with those without high
TAT
. In addition, men in this group were more likely to be smokers (
P
=0.02), whereas women were more likely to have low high‐density lipoprotein cholesterol (
P
=0.005).

Conclusions

Individuals in our community‐based sample with high
TAT
in the absence of high
VAT
were characterized by an adverse cardiometabolic profile. This adipose tissue phenotype may identify a subset of individuals with distinct metabolic characteristics.
Delayed Treatment With Hypothermia Protects Against the No‐Reflow Phenomenon Despite Failure to Reduce Infarct Size
Authors: Hale Sharon L. , Herring Michael J. , Kloner Robert A. 
Published: May 2013

Background

Many studies have shown that when hypothermia is started after coronary artery reperfusion (
CAR
), it is ineffective at reducing necrosis. However, some suggest that hypothermia may preferentially reduce no‐reflow. Our aim was to test the effects of hypothermia on no‐reflow when initiated close to reperfusion and 30 minutes after reperfusion, times not associated with a protective effect on myocardial infarct size.

Methods and Results

Rabbits received 30 minutes coronary artery occlusion/3 hours
CAR
. In protocol 1, hearts were treated for 1 hour with topical hypothermia (myocardial temperature ≈32°C) initiated at 5 minutes before or 5 minutes after
CAR
, and the results were compared with a normothermic group. In protocol 2, hypothermia was delayed until 30 minutes after
CAR
and control hearts remained normothermic. In protocol 1, risk zones were similar and infarct size was not significantly reduced by hypothermia initiated close to
CAR
. However, the no‐reflow defect was significantly reduced by 43% (5 minutes before CAR) and 38% (5 minutes after CAR) in hypothermic compared with normothermic hearts (
P
=0.004,
ANOVA
,
P
=ns between the 2 treated groups). In protocol 2, risk zones and infarct sizes were similar, but delayed hypothermia significantly reduced no‐reflow in hypothermic hearts by 30% (55±6% of the necrotic region in hypothermia group versus 79±6% with normothermia,
P
=0.008).

Conclusion
These studies suggest that treatment with hypothermia reduces no‐reflow even when initiated too late to reduce infarct size and that the microvasculature is especially receptive to the protective properties of hypothermia and confirm that microvascular damage is in large part a form of true reperfusion injury.