bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in Intracranial Stenting Among Medicare Beneficiaries in the United States, 2006–2010
Authors: Gupta Aakriti , Desai Mayur M. , Kim Nancy , Bulsara Ketan R. , Wang Yun , Krumholz Harlan M. 
Published: May 2013

Background

It is uncertain how intracranial stenting (
ICS
) has been adopted nationally during a period characterized by a restrictive payment policy by the Centers for Medicare & Medicaid Services, humanitarian device exemption approval by the Food and Drug Administration, and insufficient evidence of effectiveness. We sought to determine the trends in rates of
ICS
use and associated outcomes in the United States.

Methods and Results

From 65 211 328 Medicare Fee‐for‐Service beneficiaries hospitalized between 2006 and 2010 in acute care hospitals in the United States, we included patients with
ICD
‐9‐
CM
procedure codes for intracranial angioplasty and stenting, excluding those with a principal discharge diagnosis code of cerebral aneurysm or subarachnoid hemorrhage. We report operative rates per 1 000 000 person‐years and outcomes including 30‐day and 1‐year mortality rates. There were 838
ICS
procedures performed among Fee‐for‐Service beneficiaries. The overall hospitalization rate for
ICS
increased significantly from ≈1 per 1 000 000 person‐years (n=35 procedures) in 2006 to 9 per 1 000 000 person‐years (n=258 procedures) in 2010 (
P
=0.0090 for trend). Procedure rates were higher in men than in women, and were highest among patients aged 75 to 84 years and lowest among those ≥85 years. The 30‐day mortality rate increased from 2.9% (95%
CI
, 0.1 to 15.3) to 12.9% (95%
CI
, 9.0 to 17.6),
P
=0.1294 for trend, and the 1‐year mortality rate increased from 14.7% (95%
CI
, 5.0 to 31.1) to 19.5% (95%
CI
, 14.9 to 24.9),
P
=0.0101; however, the annual changes were not significant after adjustment.

Conclusions

ICS
utilization in the United States has modestly increased during a period of inadequate supportive evidence. Humanitarian device exemption and a restrictive payment policy appear to have caused slow adoption of the technology.
The Value of Carotid Artery Plaque and Intima‐Media Thickness for Incident Cardiovascular Disease: The Multi‐Ethnic Study of Atherosclerosis
Authors: Polak Joseph F. , Szklo Moyses , Kronmal Richard A. , Burke Gregory L. , Shea Steven , Zavodni Anna E. H. , O'Leary Daniel H. 
Published: May 2013

Background

Carotid artery plaques are associated with coronary artery atherosclerotic lesions. We evaluated various ultrasound definitions of carotid artery plaque as predictors of future cardiovascular disease (
CVD
) and coronary heart disease (
CHD
) events.

Methods and Results

We studied the risk factors and ultrasound measurements of the carotid arteries at baseline of 6562 members (mean age 61.1 years; 52.6% women) of the Multi‐Ethnic Study of Atherosclerosis (
MESA
). ICA lesions were defined subjectively as >0% or ≥25% diameter narrowing, as continuous intima‐media thickness (
IMT
) measurements (maximum
IMT
or the mean of the maximum
IMT
of 6 images) and using a 1.5‐mm
IMT
cut point. Multivariable
C
ox proportional hazards models were used to estimate hazard ratios for incident
CVD
,
CHD
, and stroke.
H
arrell's
C
‐statistics, Net Reclassification Improvement, and Integrated Discrimination Improvement were used to evaluate the incremental predictive value of plaque metrics. At 7.8‐year mean follow‐up, all plaque metrics significantly predicted
CVD
events (n=515) when added to
F
ramingham risk factors. All except 1 metric improved the prediction of
CHD
(by
C
‐statistic,
Net Reclassification Improvement
, and Integrated Discrimination Improvement. Mean of the maximum
IMT
had the highest
NRI
(7.0%;
P
=0.0003) with risk ratio of 1.43/mm; 95% CI 1.26–1.63) followed by maximum
IMT
with an
NRI
of 6.8% and risk ratio of 1.27 (95% CI 1.18–1.38).

Conclusion

Ultrasound‐derived plaque metrics independently predict cardiovascular events in our cohort and improve risk prediction for
CHD
events when added to
F
ramingham risk factors.
T‐Helper Type 1 Bias in Healthy People Is Associated With Cytomegalovirus Serology and Atherosclerosis: The Multi‐Ethnic Study of Atherosclerosis
Authors: Tracy Russell P. , Doyle Margaret F. , Olson Nels C. , Huber Sally A. , Jenny Nancy S. , Sallam Reem , Psaty Bruce M. , Kronmal Richard A. 
Published: May 2013

Background
Although T‐helper type 1 (Th1) cells are considered important in atherosclerosis, the relationships between Th1 and Th2 cells and atherosclerosis have not been examined in population‐based studies.

Methods and Results

We measured Th cells as a percentage of lymphocytes by flow cytometry using
CD
4 staining (%
CD
4) in 917 participants of the Multi‐Ethnic Study of Atherosclerosis. We also measured interferon gamma–positive and interleukin‐4‐positive
CD
4
+
cells, representing Th1 and Th2 subpopulations (%Th1 and %Th2), respectively. We found that %
CD
4 was 1.5% lower per 10 years of age (
P
<0.0001). Whites had higher %
CD
4 and lower %Th1 and %Th2 values than other race/ethnic groups. Body mass index (
BMI
) and blood pressure were associated with %
CD
4, but no traditional cardiovascular disease (
CVD
) risk factors were associated with %Th1 or %Th2. In multivariable models, the major independent variable associated with %Th1 was cytomegalovirus (
CMV
) antibody titer, with minor contributions from age, sex, seasonality, and interleukin‐6. In models with coronary artery calcification level as the outcome, significant independent variables included age, sex, smoking status, and %Th1 (β=0.25;
P
≤0.01). Both %Th1 and %Th2 were associated with common carotid intimal media thickness (β=0.02 and −0.02, respectively; both
P
<0.05), as were age, sex, race/ethnicity, blood pressure, and
BMI
.

Conclusions

Th1 bias is associated with subclinical atherosclerosis in a multiethnic population. The main Th1 correlate was
CMV
infectious burden. These findings are consistent with a role of Th1 cells in atherosclerosis and suggest the importance of prospective studies of T‐helper cell biasing in
CVD
.
Effects of Recombinant Human Erythropoietin on Resistance Artery Endothelial Function in Stage 4 Chronic Kidney Disease
Authors: Briet Marie , Barhoumi Tlili , Mian Muhammad Oneeb Rehman , Sierra Cristina , Boutouyrie Pierre , Davidman Michael , Bercovitch David , Nessim Sharon J. , Frisch Gershon , Paradis Pierre , Lipman Mark L. , Schiffrin Ernesto L. 
Published: May 2013

Background

Recent studies have raised concern about the safety of erythropoiesis‐stimulating agents because of evidence of increased risk of hypertension and cardiovascular morbidity and mortality in chronic kidney disease (
CKD
) patients. In the present study, we investigated the effects of recombinant human erythropoietin (
EPO
) on endothelial function of gluteal subcutaneous resistance arteries isolated from 17 stage 4 patients (estimated glomerular filtration rate 21.9±7.4 mL/min per 1.73 m
2
) aged 63±13 years.

Methods and Results

Arteries were mounted on a pressurized myograph.
EPO
impaired endothelium‐dependent relaxation in a concentration‐dependent manner. The maximal response to acetylcholine with
EPO
at 1, 10, and 20 IU/mL was reduced by 12%, 34%, and 43%, respectively, compared with the absence of
EPO
(
P
<0.001).
EPO
‐induced endothelial dysfunction was significantly associated with carotid stiffness and history of cardiovascular events.
EPO
had no effect on norepinephrine‐induced vasoconstriction or sodium nitroprusside–induced relaxation.
ABT
‐627, an endothelin type A receptor antagonist, and tempol, a superoxide dismutase mimetic, partially reversed the altered endothelial function in the presence of
EPO
(
P
<0.01). Increased expression of endothelin‐1 was found in the vessel wall after incubation with
EPO
.

Conclusions

EPO
alters endothelial function of resistance arteries in
CKD
patients via a mechanism involving in part oxidative stress and signaling through an endothelin type A receptor.
EPO
‐induced endothelial dysfunction could contribute to deleterious effects of
EPO
described in large interventional trials.
Deficiency of TDAG51 Protects Against Atherosclerosis by Modulating Apoptosis, Cholesterol Efflux, and Peroxiredoxin‐1 Expression
Authors: Hossain Gazi S. , Lynn Edward G. , Maclean Kenneth N. , Zhou Ji , Dickhout Jeffrey G. , Lhoták Šárka , Trigatti Bernardo , Capone John , Rho Jaerang , Tang Damu , McCulloch Christopher A. , Al‐Bondokji Imtisal , Malloy Mary J. , Pullinger Clive R. , Kane John P. , Li Yonghong , Shiffman Dov , Austin Richard C. 
Published: May 2013

Background

Apoptosis caused by endoplasmic reticulum (
ER
) stress contributes to atherothrombosis, the underlying cause of cardiovascular disease (
CVD
).
T
‐cell death‐associated gene 51 (

TDAG51

), a member of the pleckstrin homology‐like domain gene family, is induced by
ER
stress, causes apoptosis when overexpressed, and is present in lesion‐resident macrophages and endothelial cells.

Methods and Results

To study the role of
TDAG51
in atherosclerosis, male mice deficient in

TDAG51

and
apolipoprotein E
(
TDAG51

−/−

/
ApoE

−/−

) were generated and showed reduced atherosclerotic lesion growth (56±5% reduction at 40 weeks, relative to
ApoE

−/−

controls,
P
<0.005) and necrosis (41±4% versus 63±8% lesion area in
TDAG51

−/−

/ApoE

−/−

and
ApoE

−/−

, respectively;
P
<0.05) without changes in plasma levels of lipids, glucose, and inflammatory cytokines.

TDAG51

deficiency caused several phenotypic changes in macrophages and endothelial cells that increase cytoprotection against oxidative and
ER
stress, enhance
PPAR
γ‐dependent reverse cholesterol transport, and upregulate peroxiredoxin‐1 (Prdx‐1), an antioxidant enzyme with antiatherogenic properties (1.8±0.1‐fold increase in Prdx‐1 protein expression, relative to control macrophages;
P
<0.005). Two independent case–control studies found that a genetic variant in the human

TDAG51

gene region (rs2367446) is associated with
CVD
(
OR
, 1.15; 95%
CI
, 1.07 to 1.24;
P
=0.0003).

Conclusions

These findings provide evidence that
TDAG51
affects specific cellular pathways known to reduce atherogenesis, suggesting that modulation of
TDAG51
expression or its activity may have therapeutic benefit for the treatment of
CVD
.
Increased Expression of HCN Channels in the Ventricular Myocardium Contributes to Enhanced Arrhythmicity in Mouse Failing Hearts
Authors: Kuwabara Yoshihiro , Kuwahara Koichiro , Takano Makoto , Kinoshita Hideyuki , Arai Yuji , Yasuno Shinji , Nakagawa Yasuaki , Igata Sachiyo , Usami Satoru , Minami Takeya , Yamada Yuko , Nakao Kazuhiro , Yamada Chinatsu , Shibata Junko , Nishikimi Toshio , Ueshima Kenji , Nakao Kazuwa 
Published: May 2013

Background

The efficacy of pharmacological interventions to prevent sudden arrhythmic death in patients with chronic heart failure remains limited. Evidence now suggests increased ventricular expression of hyperpolarization‐activated cation (
HCN
) channels in hypertrophied and failing hearts contributes to their arrythmicity. Still, the role of induced
HCN
channel expression in the enhanced arrhythmicity associated with heart failure and the capacity of
HCN
channel blockade to prevent lethal arrhythmias remains undetermined.

Methods and Results

We examined the effects of ivabradine, a specific
HCN
channel blocker, on survival and arrhythmicity in transgenic mice (dn
NRSF
‐Tg) expressing a cardiac‐specific dominant‐negative form of neuron‐restrictive silencer factor, a useful mouse model of dilated cardiomyopathy leading to sudden death. Ivabradine (7 mg/kg per day orally) significantly reduced ventricular tachyarrhythmias and improved survival among dn
NRSF
‐Tg mice while having no significant effect on heart rate or cardiac structure or function. Ivabradine most likely prevented the increase in automaticity otherwise seen in dn
NRSF
‐Tg ventricular myocytes. Moreover, cardiac‐specific overexpression of
HCN
2 in mice (
HCN
2‐Tg) made hearts highly susceptible to arrhythmias induced by chronic β‐adrenergic stimulation. Indeed, ventricular myocytes isolated from
HCN
2‐Tg mice were highly susceptible to β‐adrenergic stimulation‐induced abnormal automaticity, which was inhibited by ivabradine.

Conclusions

HCN
channel blockade by ivabradine reduces lethal arrhythmias associated with dilated cardiomyopathy in mice. Conversely, cardiac‐specific overexpression of
HCN
2 channels increases arrhythmogenicity of β‐adrenergic stimulation. Our findings demonstrate the contribution of
HCN
channels to the increased arrhythmicity seen in failing hearts and suggest
HCN
channel blockade is a potentially useful approach to preventing sudden death in patients with heart failure.
Cardiovascular Risk Score, Cognitive Decline, and Dementia in Older Mexican Americans: The Role of Sex and Education
Authors: Hazzouri Adina Zeki Al , Haan Mary N. , Neuhaus John M. , Pletcher Mark , Peralta Carmen A. , López Lenny , Pérez Stable Eliseo J. 
Published: May 2013

Background

The purpose of this study was to examine the associations of cardiovascular disease (
CVD
) risk with cognitive decline and incidence of dementia and cognitive impairment but not dementia (
CIND
) and the role of education as a modifier of these effects.

Methods and Results

One thousand one hundred sixteen Mexican American elderly were followed annually in the Sacramento Area Latino Study on Aging. Our sex‐specific 10‐year
CVD
risk score included baseline age, systolic blood pressure, total cholesterol, high‐density lipoprotein, smoking, body mass index, and diabetes. From adjusted linear mixed models, errors on the Modified Mini–Mental State Exam (3
MSE
) were annually 0.41% lower for women at the 25th percentile of
CVD
risk, 0.11% higher at the 50th percentile, and 0.83% higher at the 75th percentile (
P
value of
CVD
risk×time <0.01). In men, 3
MSE
errors were annually 1.76% lower at the 25th percentile of
CVD
risk, 0.96% lower at the 50th percentile, and 0.12% higher at the 75th percentile (
P
value of
CVD
risk×time <0.01). From adjusted linear mixed models, the annual decrease in the Spanish and English Verbal Learning Test score was 0.09 points for women at the 25th percentile of
CVD
risk, 0.10 points at the 50th percentile, and 0.12 points at the 75th percentile (
P
value of
CVD
risk×time=0.02). From adjusted Cox models in women, compared with having <6 years of education, having 12+ years of education was associated with a 76% lower hazard of dementia/
CIND
(95%
CI
, 0.08 to 0.71) at the 25th percentile of
CVD
risk and with a 45% lower hazard (95%
CI
, 0.28 to 1.07) at the 75th percentile (
P
value of
CVD
risk×education=0.05).

Conclusions

CVD
risk score may provide a useful tool for identifying individuals at risk for cognitive decline and dementia.
Traditional Risk Factors Are Not Major Contributors to the Variance in Carotid Intima-Media Thickness
Authors: Rundek Tatjana , Blanton Susan H. , Bartels Susanne , Dong Chuanhui , Raval Ami , Demmer Ryan T. , Cabral Digna , Elkind Mitchell S.V. , Sacco Ralph L. , Desvarieux Moise 
Published: May 2013

Background and Purpose—
Carotid intima-media thickness (cIMT) was a widely accepted ultrasound marker of subclinical atherosclerosis in the past. Although traditional risk factors may explain ≈50% of the variance in plaque burden, they may not explain such a high proportion of the variance in IMT, especially when measured in plaque-freel ocations. We aimed this study to identify individuals with cIMT unexplained by traditional risk factors for future environmental and genetic research.

Methods—
As part of the Northern Manhattan Study, 1790 stroke-free individuals (mean age, 69±9 years; 60% women; 61% Hispanic; 19% black; 18% white) were assessed for cIMT using B-mode carotid ultrasound. Multiple linear regression models were evaluated: (1) incorporating prespecified traditional risk factors; and (2) including less traditional factors, such as inflammation biomarkers, adiponectin, homocysteine, and kidney function. Standardized cIMT residual scores were constructed to select individuals with unexplained cIMT.

Results—
Mean total cIMT was 0.92±0.09 mm. The traditional model explained 11% of the variance in cIMT. Age (7%), male sex (3%), glucose (<1%), pack-years of smoking (<1%), and low-density lipoprotein cholesterol (<1%) were significant contributing factors. The model, including inflammatory biomarkers, explained 16% of the variance in cIMT. Adiponectin was the only additional significant contributor to the variance in cIMT. We identified 358 individuals (20%) with cIMT unexplained by the investigated risk factors.

Conclusions—
Vascular risk factors explain only a small proportion of variance in cIMT. Identification of novel genetic and environmental factors underlying unexplained subclinical atherosclerosis is of utmost importance for future effective prevention of vascular disease.
Clot Burden Score on Admission T2*-MRI Predicts Recanalization in Acute Stroke
Authors: Legrand Laurence , Naggara Olivier , Turc Guillaume , Mellerio Charles , Roca Pauline , Calvet David , Labeyrie Marc-Antoine , Baron Jean-Claude , Mas Jean-Louis , Meder Jean-François , Touzé Emmanuel , Oppenheim Catherine 
Published: May 2013

Background and Purpose—
To propose a T2*-MR adaptation of the computed tomography angiography-clot burden score (CBS), and assess its value as predictor of 24-hour recanalization and clinical outcome in anterior circulation stroke treated by intravenous thrombolysis ≤4.5 hours from onset.

Methods—
Two independent observers retrospectively analyzed pretreatment T2* images for evaluation of clot burden, using a 10-point scale T2*-CBS. Three points are subtracted for susceptibility vessel sign in the supraclinoid internal carotid artery, 2 points each for susceptibility vessel sign in the proximal and distal part of middle cerebral artery, and 1 point each for susceptibility vessel sign in middle cerebral artery branches (with a maximum of 2 points) and for susceptibility vessel sign in anterior cerebral artery. Associations with 24-hour recanalization and favorable outcome (3-month modified Rankin Scale score, ≤2) were assessed in multivariate analyses.

Results—

We analyzed 184 consecutive patients (mean age, 67 years) with median (interquartile range) admission National Institutes of Health Stroke Scale score and onset-to-treatment time of 15 (9–19) and 151 (120–185) minutes, respectively. The intraclass correlation for T2*-CBS between observers was 0.97 (95% confidence interval, 0.97–0.98). In multivariate analyses, T2*-CBS >6 was significantly associated with 24-hour recanalization (adjusted odds ratio, 5.1 [1.9–13.5];
P
=0.001) or with favorable outcome (adjusted odds ratio, 4.2 [1.7–10.8];
P
=0.003).

Conclusions—
T2*-CBS, a new reproducible semiquantitative score adapted from the computed tomography angiography-CBS, is associated with 24-hour recanalization and 3-month outcome after intravenous thrombolysis. This score needs external validation and could be useful to identify poor responders to intravenous thrombolysis.
Systemic Inflammatory Response Syndrome in Tissue-Type Plasminogen Activator–Treated Patients is Associated With Worse Short-term Functional Outcome
Authors: Boehme Amelia K. , Kapoor Niren , Albright Karen C. , Lyerly Michael J. , Rawal Pawan V. , Bavarsad Shahripour Reza , Alvi Muhammad , Houston J. Thomas , Sisson April , Beasley T. Mark , Alexandrov Anne W. , Alexandrov Andrei V. , Miller David W. 
Published: May 2013

Background and Purpose—
Systemic inflammatory response syndrome (SIRS) is a generalized inflammatory state. The primary goal of the study was to determine whether differences exist in outcomes in SIRS and non-SIRS intravenous tissue-type plasminogen activator–treated patients.

Methods—
Consecutive patients were retrospectively reviewed for the evidence of SIRS during their admission. SIRS was defined as the presence of ≥2 of the following: body temperature <36°C or >38°C, heart rate >90, respiratory rate >20, and white blood cells <4000/mm or >12 000 mm, or >10% bands. Patients diagnosed with infection (via positive culture) were excluded.

Results—

Of the 241 patients, 44 had evidence of SIRS (18%). Adjusting for pre–tissue-type plasminogen activator National Institutes of Health Stroke Scale, age, and race, SIRS remained a predictor of poor functional outcome at discharge (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.16–5.73;
P
=0.0197).

Conclusions—
In our sample of tissue-type plasminogen activator–treated (tPA) patients, ~1 in 5 patients developed SIRS. Furthermore, we found the presence of SIRS to be associated with poor short-term functional outcomes and prolonged length of stay.
Onset Headache Predicts Good Outcome in Patients With First-Ever Ischemic Stroke
Authors: Chen Ping-Kun , Chiu Pai-Yi , Tsai I-Ju , Tseng Hung-Pin , Chen Jiunn-Rong , Yeh Shoou-Jeng , Yeh Shin-Joe , Sheu Jau-Jiuan , Chung Chih-Ping , Wu Ming-Hisu , Hu Chaur-Jong , Chang Chun-Yuan , Wei Cheng-Yu , Yip Ping-Keung , Sung Sheng-Feng , Wang Shuu-Jiun , Hsu Chung Y. 
Published: May 2013

Background and Purpose—
The study aimed to assess whether onset headache is an ominous sign in patients with first-ever ischemic stroke.

Methods—
A large population of ischemic stroke patients was obtained from the Taiwan Stroke Registry. Stroke subtypes were classified by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. On the basis of the International Classification of Headache Disorders, second version, onset headache was defined as a new headache that developed at the onset of ischemic stroke. Clinical features and impact on stroke outcomes, including in-hospital stroke in evolution, changes in National Institutes of Health Stroke Scale on discharge, and Barthel index and modified Rankin scale ≤6 months after stroke were compared between those with and without onset headache.

Results—

Among 11 523 patients with first-ever ischemic stroke, 848 had onset headache (7.4%). Patients with specific cause, large-artery atherosclerosis, or cardioembolism were more likely to have onset headache. Patients with onset headache were younger, predominantly female, and more likely to have posterior circulation ischemic lesions. Compared with patients without onset headache, those with onset headache had a lower frequency of stroke in evolution (4.5% versus 6.7%; adjusted relative risk, 0.64; 95% confidence interval, 0.52–0.79), greater improvement in National Institutes of Health Stroke Scale score on discharge (0.08 versus −0.20;
P
=0.02), higher mean Barthel index scores (86.5±20.0 versus 83.9±23.3; adjusted difference, 1.43; 95% confidence interval, 0.28–2.89), and a lower frequency of modified Rankin scale higher than 2 (27.6% versus 31.5%; adjusted relative risk, 0.85; 95% confidence interval, 0.72–0.95) at 1-month follow-up. There was also a trend for better functional outcome in 3- and 6-month follow-ups.

Conclusions—
By adopting standard classification criteria, this large-scale study demonstrated that onset headache was associated with modest but significantly better outcomes after ischemic stroke.