bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Biomarker Predictors of Expanded Heart Failure Outcomes in Patients With Type 2 Diabetes Mellitus After a Recent Acute Coronary Syndrome: Insights From the EXAMINE Trial
Authors: Sharma Abhinav , Vaduganathan Muthiah , Ferreira João Pedro , Liu Yuyin , Bakris George L. , Cannon Christopher P. , White William B. , Zannad Faiez 
Published: January 2020

Background

Improved heart failure (
HF
) risk stratification after a recent acute coronary syndrome may identify those who can benefit from therapies that reduce
HF
risk. We aimed to identify clinical and biomarker predictors for expanded
HF
outcomes in patients with type 2 diabetes mellitus after recent acute coronary syndrome.

Methods and Results

The EXAMINE (
Ex
amination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial was a multicenter, non‐inferiority, double‐masked, placebo‐controlled study which randomized 5380 patients with type 2 diabetes mellitus after recent acute coronary syndrome to alogliptin or placebo. Baseline biomarkers were measured in 5154 patients: NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity troponin I, adiponectin, growth‐differentiation‐factor‐15, and galectin‐3. Our primary outcome was cardiovascular) death,
HF
hospitalization, elevated NT‐proBNP during follow‐up, or loop diuretics initiation. The association between clinical variables, biomarkers, and outcomes were assessed using Cox regression models. In the study population, the median age was 61.0 years, 67.7% were men, and 28.0% had baseline
HF
(median follow‐up was 18 months). In multivariable analyses, NT‐proBNP had the strongest association with the primary outcome (per log
2
, hazard ratio 1.24; Wald χ
2
67.4;
P
<0.0001) followed by a prior
HF
history (hazard ratio 1.42; Wald χ
2
20.8;
P
<0.0001). A model with clinical variables and biomarkers allowed for risk prediction for expanded
HF
outcomes (C‐statistic=0.72). Discrimination results were similar for cardiovascular death or
HF
hospitalization.

Conclusions

Among patients with type 2 diabetes mellitus after recent acute coronary syndrome, the use biomarkers such as N‐terminal pro‐B‐type natriuretic peptide and clinical variables enables risk stratification for expanded
HF
outcomes.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov/
. Unique identifier:
NCT
00968708.
Sex Differences in Cardiovascular Effectiveness of Newer Glucose‐Lowering Drugs Added to Metformin in Type 2 Diabetes Mellitus
Authors: Raparelli Valeria , Elharram Malik , Moura Cristiano S. , Abrahamowicz Michal , Bernatsky Sasha , Behlouli Hassan , Pilote Louise 
Published: January 2020

Background
Randomized controlled trials showed that newer glucose‐lowering agents are cardioprotective, but most participants were men. It is unknown whether benefits are similar in women.

Methods and Results

Among adults with type 2 diabetes mellitus not controlled with metformin with no prior use of insulin, we assessed for sex differences in the cardiovascular effectiveness and safety of sodium‐glucose‐like transport‐2 inhibitors (
SGLT
‐2i), glucagon‐like peptide‐1 receptor agonists (
GLP
‐1
RA
), dipeptidyl peptidase‐4 inhibitors, initiated as second‐line agents relative to sulfonylureas (reference‐group). We studied type 2 diabetes mellitus American adults with newly dispensed sulfonylureas,
SGLT
‐2i,
GLP
‐1
RA
, or dipeptidyl peptidase‐4 inhibitors (Marketscan‐Database: 2011–2017). We used multivariable Cox proportional hazards models with time‐varying exposure to compare time to first nonfatal cardiovascular event (myocardial infarction/unstable angina, stroke, and heart failure), and safety outcomes between drugs users, and tested for sex–drug interactions. Among 167 254 type 2 diabetes mellitus metformin users (46% women, median age 59 years, at low cardiovascular risk), during a median 4.5‐year follow‐up, cardiovascular events incidence was lower in women than men (14.7 versus 16.7 per 1000‐person‐year). Compared with sulfonylureas, hazard ratios (
HR
s) for cardiovascular events were lower with
GLP
‐1
RA
(adjusted
HR
‐women: 0.57, 95%
CI
: 0.48–0.68;
aHR
‐men: 0.82, 0.71–0.95), dipeptidyl peptidase‐4 inhibitors (
aHR
‐women: 0.83, 0.77–0.89;
aHR
‐men: 0.85, 0.79–0.91) and
SGLT
‐2i (
aHR
‐women: 0.58, 0.46–0.74;
aHR
‐men: 0.69, 0.57–0.83). A sex‐by‐drug interaction was statistically significant only for
GLP
‐1
RA
(
P
=0.002), suggesting greater cardiovascular effectiveness in women. Compared with sulfonylureas, risks of adverse events were similarly lower in both sexes for
GLP
‐1
RA
(
aHR
‐women: 0.81, 0.73–0.89;
aHR
‐men: 0.80, 0.71–0.89), dipeptidyl peptidase‐4 inhibitors (
aHR
‐women: 0.82, 0.78–0.87;
aHR
‐men: 0.83, 0.78–0.87) and
SGLT
‐2i (
aHR
‐women: 0.68, 0.59–0.78;
aHR
‐men: 0.67, 0.59–0.78) (all sex–drug interactions for adverse events
P
>0.05).

Conclusions

Newer glucose‐lowering drugs were associated with lower risk of cardiovascular events than sulfonylureas, with greater effectiveness of
GLP
‐1
RA
in women than men. Overall, they appeared safe, with a better safety profile for
SGLT
‐2i than for
GLP
‐1
RA
regardless of sex.
Gender Differences in Risk Factors Associated With Pulmonary Artery Systolic Pressure, Heart Failure, and Mortality in Blacks: Jackson Heart Study
Authors: Lakshmanan Suvasini , Jankowich Matthew , Wu Wen‐Chih , Blackshear Chad , Abbasi Siddique , Choudhary Gaurav 
Published: January 2020

Background

Pulmonary hypertension is prevalent in black individuals, especially women. Elevated pulmonary artery systolic pressure (
PASP
) is associated with significant morbidity and mortality.

Methods and Results

We developed linear and proportional hazards models to examine potential gender‐related differences in risk factors for elevated
PASP
(estimated by transthoracic echocardiography) and
PASP
‐associated clinical outcomes (incident heart failure admissions and mortality) in
JHS
(Jackson Heart Study) participants.
JHS
is a prospective observational cohort study of heart disease in blacks from the Jackson, Mississippi, metropolitan area. The study cohort included participants with measurable transtricuspid gradients (n=3286) at the time of first/baseline examination, 2000–2004. The median age (interquartile range) of patients at baseline was 57.8 years (18.6 years) with 67.5% being women. The median
PASP
at baseline was higher in women (men: 26 mm Hg [interquartile range 8], women: 27 mm Hg [interquartile range 9]. In multivariate linear regression analyses with
PASP
, significant gender interactions were noted for age, chronic lung disease, pulse pressure, and obstructive spirometry. In exploratory analyses stratified by gender, body mass index, and obstructive and restrictive spirometry patterns were associated with
PASP
in women, and chronic lung disease was associated with
PASP
in men. Age and pulse pressure had stronger associations with
PASP
in women compared with men. There was a significant interaction between gender and
PASP
for heart failure admissions but not mortality.

Conclusions

Specific cardiopulmonary risk factors are associated with elevated
PASP
in women and men. Women with elevated
PASP
have a higher risk of incident heart failure admissions. Future research is needed to understand associated gender‐specific mechanisms that can help identify targeted prevention and management strategies for patients with elevated
PASP
.
Human CardioChimeras: Creation of a Novel “Next‐Generation” Cardiac Cell
Authors: Firouzi Fareheh , Sinha Choudhury Sarmistha , Broughton Kathleen , Salazar Adriana , Bailey Barbara , Sussman Mark A. 
Published: January 2020

Background

CardioChimeras produced by fusion of murine c‐kit
+
cardiac interstitial cells with mesenchymal stem cells promote superior structural and functional recovery in a mouse model of myocardial infarction compared with either precursor cell alone or in combination. Creation of human CardioChimeras (
hCCs
) represents the next step in translational development of this novel cell type, but new challenges arise when working with c‐kit
+
cardiac interstitial cells isolated and expanded from human heart tissue samples. The objective of the study was to establish a reliable cell fusion protocol for consistent optimized creation of
hCC
s and characterize fundamental
hCC
properties.

Methods and Results

Cell fusion was induced by incubating human c‐kit
+
cardiac interstitial cells and mesenchymal stem cells at a 2:1 ratio with inactivated Sendai virus. Hybrid cells were sorted into 96‐well microplates for clonal expansion to derive unique cloned
hCC
s, which were then characterized for various cellular and molecular properties.
hCC
s exhibited enhanced survival relative to the parent cells and promoted cardiomyocyte survival in response to serum deprivation in vitro.

Conclusions

The generation of
hCC
is demonstrated and validated in this study, representing the next step toward implementation of a novel cell product for therapeutic development. Feasibility of creating human hybrid cells prompts consideration of multiple possibilities to create novel chimeric cells derived from cells with desirable traits to promote healing in pathologically damaged myocardium.
Renal Hydrogen Peroxide Production Prevents Salt‐Sensitive Hypertension
Authors: Cuevas Santiago , Asico Laureano D. , Jose Pedro A. , Konkalmatt Prasad 
Published: January 2020

Background

The regulation of sodium excretion is important in the pathogenesis of hypertension and salt sensitivity is predictive of cardiovascular events and mortality. C57Bl/6 and
BALB
/c mice have different blood pressure sensitivities to salt intake. High salt intake increases blood pressure in some C57Bl/6J mouse strains but not in any
BALB
/c mouse strain.

Methods and Results

We determined the cause of the difference in salt sensitivity between C57Bl/6 and
BALB
/c mice. Basal levels of superoxide and H
2
O
2
were higher in renal proximal tubule cells (
RPTC
s) from
BALB
/c than C57Bl/6J mice. High salt diet increased H
2
O
2
production in kidneys from
BALB
/c but C57Bl/6J mice. High sodium concentration (170 mmol/L) in the incubation medium increased H
2
O
2
levels in
BALB
/c‐
RPTC
s but not in C57Bl/6J‐
RPTC
s. H
2
O
2
(10 μmol/L) treatment decreased sodium transport in
RPTC
s from
BALB
/c but not C57Bl/6J mice. Overexpression of catalase in the mouse kidney predisposed
BALB
/c mice to salt‐sensitive hypertension.

Conclusions

Our data show that the level of salt‐induced H
2
O
2
production negatively regulates
RPTC
sodium transport and determines the state of salt sensitivity in 2 strains of mice. High concentrations of antioxidants could prevent H
2
O
2
production in renal proximal tubules, which would result in sodium retention and increased blood pressure.
Normal Systolic Blood Pressure at Presentation With Acute Ischemic Stroke Predicts Cardioembolic Etiology
Authors: Moores Margaret , Yogendrakumar Vignan , Bereznyakova Olena , Alesefir Walid , Pettem Hailey , Stotts Grant , Dowlatshahi Dar , Shamy Michel 
Published: January 2020

Background
Early insight into the possible etiology of ischemic stroke allows for early initiation of mechanism‐specific secondary stroke prevention. Initial systolic blood pressure during acute ischemic stroke may relate to stroke etiology. We sought to determine whether normotension at presentation with acute ischemic stroke predicts cardioembolic etiology.

Methods and Results

All patients presenting with acute ischemic stroke within 12 hours of symptom onset at a comprehensive stroke center from January 2015 to December 2017 were assessed. Normotension was defined as systolic blood pressure ≤130 mm Hg. The primary exposure was blood pressure on arrival at the hospital, and the primary outcome was cardioembolic etiology. Multivariable regression with stepwise selection was used to adjust for relevant covariates. We included 683 patients in our analysis, 303 (44%) of whom were diagnosed with cardioembolic etiology at 6 months. The probability of cardioembolic etiology was inversely associated with
systolic blood pressure
, and initial
systolic blood pressure
was significantly associated with cardioembolic etiology (
odds ratio:
1.15; 95%
CI,
1.05 to 1.26). Normotension was associated with 2.62‐fold increased odds of cardioembolic etiology (95%
CI,
1.46 to 4.72).

Conclusions
Normotension at presentation with acute ischemic stroke strongly predicts cardioembolic etiology. These patients may especially benefit from early and prolonged cardiac investigations.
Progression of Arterial Stiffness is Associated With Midlife Diastolic Blood Pressure and Transition to Late‐Life Hypertensive Phenotypes
Authors: Webb Alastair John Stewart 
Published: January 2020

Background

Hypertension‐associated cardiovascular events are particularly associated with elevated systolic blood pressure (
SBP
) in late life, yet long‐term interactions between
SBP
, diastolic
BP
(
DBP
) and arterial stiffness in development of late‐life hypertensive phenotypes remain unclear.

Methods and Results

In the
UK
Biobank, we determined associations between arterial stiffness index (
ASI
),
SBP
,
DBP
, and their progression, and transition from normotension (<140/90 mm Hg) to hypertension or elevated
ASI
(>10 m/s). Associations were determined by general linear and logistic regression, adjusted for cardiovascular risk factors and variability of measurements across follow‐ups. Mean values of baseline
SBP
,
DBP
, and
ASI
were determined stratified by deciles of age, blood pressure, and
ASI
, with CIs determined by bootstrapping. In 169 742 participants at baseline,
ASI
was more strongly associated with
DBP
than
SBP
, before and after adjustment for risk factors (β:
SBP
, −0.01 [
P
<0.001];
DBP
, 0.06 [
P
<0.001]), while
DBP
was more strongly associated with progression of
ASI
(n=13 761; β: SBP, 0.013 [
P
=0.01];
DBP
, 0.038 [
P
<0.001]). Baseline
ASI
was associated with increasing
SBP
during follow‐up (β=0.02,
P
<0.001) but not
DBP
(β=0.0004,
P
=0.39), but was associated with a younger age of transition from rising to falling
DBP
(highest versus lowest quartile: 51.2; 95% CI, 49.9–52.3 versus 60.4; 95% CI, 59.6–61.3 [
P
<0.001]).
ASI
predicted the development of isolated systolic hypertension (odds ratio, 1.30; 95% CI, 1.22–1.39), particularly after adjustment for measurement variability (odds ratio, 2.29).

Conclusions

Midlife
DBP
was the strongest predictor of progression of arterial stiffness, while arterial stiffness was associated with earlier transition to a falling
DBP
. Prevention of long‐term harms associated with arterial stiffness may require more intensive control of midlife
DBP
.
Audiovisual Multisensory Processing in Young Adults With Attention-Deficit/Hyperactivity Disorder
Authors: McCracken Heather S. , Murphy Bernadette A. , Burkitt James J. , Glazebrook Cheryl M. , Yielder Paul C. 
Published: January 2020

Abstract
Multisensory integration is a fundamental form of sensory processing that is involved in many everyday tasks. Those with Attention-Deficit/Hyperactivity Disorder (ADHD) have characteristic alterations to various brain regions that may influence multisensory processing. The overall aim of this work was to assess how adults with ADHD process audiovisual multisensory stimuli during a complex response time task. The paradigm used was a two-alternative forced-choice discrimination task paired with continuous 64-electrode electroencephalography, allowing for the measurement of response time and accuracy to auditory, visual, and audiovisual multisensory conditions. Analysis revealed that those with ADHD () respond faster than neurotypical controls () when presented with auditory, visual, and audiovisual multisensory conditions, while also having race model violation in early response latency quantiles. Adults with ADHD also had more prominent multisensory processing over parietal-occipital brain regions at early post-stimulus latencies, indicating that altered brain structure may have important outcomes for audiovisual multisensory processing. The present study is the first to assess how those with ADHD respond to multisensory conditions during a complex response time task, and demonstrates that adults with ADHD have unique multisensory processing when assessing both behavioral response time measures and neurological measures.
Patellofemoral Cartilage Restoration: A Systematic Review and Meta-analysis of Clinical Outcomes
Authors: Hinckel Betina B. , Pratte Eli L. , Baumann Charles A. , Gowd Anirudh K. , Farr Jack , Liu Joseph N. , Yanke Adam B. , Chahla Jorge , Sherman Seth L. 
Published: January 2020

Background: Many surgical options for treating patellofemoral (PF) cartilage lesions are available but with limited evidence comparing their results. Purpose: To determine and compare outcomes of PF cartilage restoration techniques. Study Design: Systematic review and meta-analysis. Methods: PRISMA (Preferred Reporting Items for Systematic Meta-Analyses) guidelines were followed by utilizing the PubMed, EMBASE, and Cochrane Library databases. Inclusion criteria were clinical studies in the English language, patient-reported outcomes after PF cartilage restoration surgery, and >12 months’ follow-up. Quality assessment was performed with the Coleman Methodology Score. Techniques were grouped as osteochondral allograft transplantation (OCA), osteochondral autograft transfer (OAT), chondrocyte cell–based therapy, bone marrow–based therapy, and scaffolds. Results: A total of 59 articles were included. The mean Coleman Methodology Score was 71.8. There were 1937 lesions (1077 patellar, 390 trochlear, and 172 bipolar; 298 unspecified). The frequency of the procedures was as follows, in descending order: chondrocyte cell–based therapy (65.7%), bone marrow–based therapy (17.2%), OAT (8%), OCA (6.6%), and scaffolds (2.2%). When compared with the overall pooled lesion size (3.9 cm2; 95% CI, 3.5-4.3 cm2), scaffold (2.2 cm2; 95% CI, 1.8-2.5 cm2) and OAT (1.5 cm2; 95% CI, 1.1-1.9 cm2) lesions were smaller ( P < .001), while chondrocyte cell–based therapy lesions were larger (4.7 cm2; 95% CI, 4.1-5.3 cm2; P = .039). Overall, the instability pool was 11.9%, and the anatomic risk factors pool was 32.1%. Statistically significant improvement was observed on at least 1 patient-reported outcome in chondrocyte cell–based therapy (83%), OAT (78%), OCA (71%), bone marrow–based therapy (64%), and scaffolds (50%). There were no significant differences between any group and the overall pooled change in International Knee Documentation Committee score (30.2; 95% CI, 27.4-32.9) and Lysholm score (25.2; 95% CI, 16.9-33.5). There were no significant differences between any group and the overall pooled rate in minor complication rate (7.6%; 95% CI, 4.7%-11.9%) and major complication rate (8.3%; 95% CI, 5.7%-12.0%); however, OCA had a significantly greater failure rate (22.7%; 95% CI, 14.6%-33.4%) as compared with the overall rate (6.8%; 95% CI, 4.7%-9.5%). Conclusion: PF cartilage restoration leads to improved clinical outcomes, with low rates of minor and major complications. There was no difference among techniques; however, failures were higher with OCA.
Morphologic Variants of Posterolateral Tibial Plateau Impaction Fractures in the Setting of Primary Anterior Cruciate Ligament Tear
Authors: Bernholt David L. , DePhillipo Nicholas N. , Grantham W. Jeffrey , Crawford Matthew D. , Aman Zachary S. , Kennedy Mitchell Iung , LaPrade Robert F. 
Published: January 2020

Background: Impaction fractures of the posterolateral tibial plateau commonly occur in the setting of anterior cruciate ligament (ACL) tears, with considerable variability found in fracture size and morphologic features. Purpose: The primary objective was to characterize different morphologic variants of posterolateral tibial plateau impaction fractures. The secondary objective was to investigate the association between these impaction fracture variants and concomitant meniscal and ligamentous injuries. Study Design: Cross-sectional study; Level of evidence 3. Methods: Patients treated for primary ACL tears and having magnetic resonance imaging available were included in this study, and magnetic resonance images were reviewed with denotation of displaced posterolateral tibial impaction fractures. A classification system was created based on morphologic variants of impaction fractures; associations were evaluated through use of independent chi-square testing. Results: There were 825 knees meeting the inclusion criteria, with displaced posterolateral tibial plateau impaction fractures present in 407 knees (49.3%). We observed 3 distinct morphologic variants of lateral tibial plateau impaction fractures: (I) posterior cortical buckle not involving the articular surface; (II) posterior impaction fracture involving the articular surface, with subtypes based on (A) tibial plateau depth bone loss <10% and (B) bone loss >10%; and (III) displaced osteochondral fragment, with subtypes for (A) shear or (B) depressed fragment. Type IIIA impaction fractures were associated with an increased incidence of lateral meniscus posterior root tears (33.3% vs 12.4%; P = .009) and an increased incidence of lateral meniscal tears (83.3% vs 56.7%; P = .024) compared with all knees without type IIIA impaction fracture. An increased incidence of medial collateral ligament (MCL) tears was noted in patients with type IIIA impaction fractures compared with those who had no fracture or had another fracture type (61.1% vs 20.1%; P < .001). Type IIIB impaction fractures were associated with an increased incidence of lateral meniscal tears (80.0% vs 56.2%; P = .005). Conclusion: A high prevalence of displaced posterolateral tibial plateau impaction fractures occur in the setting of ACL tears, and they can be classified into distinct morphologic subtypes. Posterolateral tibial plateau impaction fractures with displaced depressed or shear fragments were both associated with an increased incidence of lateral meniscal tears, whereas impaction fractures with a shear fragment were associated with an increased incidence of lateral meniscus posterior root tears and MCL tears.