bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 17978: Mlp Interacting Protein 1 (MIP1) Plays a Role for Cardiomyopathy
Authors: Buyandelger Byambajav , Mansfield Catherine , Kostin Sawa , Choi Onjee , Isaacson Rivka L. , Poon Kar-Lai , Knöll Gudrun , McSweeney Sara , Perrot Andreas , Toliat Mohammad R , Chen Ju , Gould Ian , Lara-Pezzi Enrique , Luther Pradeep , Petretto Enrico , Milting Hendrik , Brand Thomas , Knöll Ralph 
Published: March 2022

Mutations in genes involved in cardiac mechanosensation (mec), such as the muscle LIM protein (MLP) have been shown to cause heart failure. Identification of novel mec genes may provide new insights into underlying mechanisms.
A yeast 2 hybrid screen identified a novel MIP, located at a chromosomal region recently implicated by GWASs in the pathogenesis of dilated cardiomyopathy (DCM), an interaction confirmed by various assays.
We found that MIP1 is a stress inducible transcription factor, binds to the calcineurin promoter and activates NFAT, a known mediator of hypertrophy. Also overexpression of MIP1 in vitro promotes autophagy and activates expression of anti-apoptotic genes in cardiac myocytes.
Mip1 conventional knockout animals die during gastrulation whereas Mip1 conditional knockout (cKO) animals failed to adapt to transverse aortic constriction. Four weeks after intervention, fractional shortening was significantly decreased, whereas LVEDD and LVESD were significantly increased in cKO mice compared to control littermates.
TUNEL assays combined with activated caspase, whole gene expression arrays and qRT-PCR provide strong evidence that Mip1 cKO hearts are unable to undergo autophagy and as a result activate apoptotic processes which are responsible for the observed heart failure phenotype. However, overexpression of MIP1 in vivo resulted in marked cardiac hypertrophy at the organ and single cell levels, pointing to a link between autophagy and hypertrophy.
As MIP1 contains the peak association signal (rs10927875) at the replicated 1p36 cardiomyopathy locus, we sequenced this gene in 575 unrelated individuals affected by DCM and identified 4 MIP1 missense mutations (T106M, G179S, A188V, Q531R) of which 2 co-segregate in two families with DCM and arrhythmia. All 4 variants show abnormalities with regards to their ability to interact with MLP, localization, structure, stability and potential to drive the calcineurin promoter. WT-MIP1 is able to efficiently protect cells from apoptosis, a property missing in all mutants. At least G179S and Q531R cause heart failure in the zebrafish.
MIP1 is important for the initiation of survival pathways and autophagy upon biomechanical stress and represents a novel cardiomyopathy candidate gene.
Abstract 18619: All Advanced Lipid Tests are Not Equal: Prospective Analysis of Discordance Between LDL-P, Small Dense LDL (or Subfractions), and HDL-P (or Subfractions) as Determined by NMR, Ion Mobility, and VAP in Treated Patients
Authors: Mukai Kanae , Rolph Kellie , McCauley Julie C , Triffon Douglas W 
Published: March 2022

Introduction:
LDL-P has been shown to be a better predictor of cardiovascular risk than LDL-C (Framingham Offspring, Jupiter, and MESA). HDL-P has been reported as a better predictor than HDL-C (Jupiter and MESA) and small dense LDL measurements have been reported as more predictive of cardiovascular disease progression than LDL-C (HATS). Clinicians rely on these markers to assess residual risk in treated patients.

Hypothesis:
NMR, ion mobility (IM), and VAP tests will report discordant results for LDL-P, HDL-P (or subfraction), and small dense LDL (or subfraction) in treated patients.

Methods:
This is a prospective study (#SCIML001 on ClinicalTrials.gov), approved by the Scripps Clinic (#IRB-14-6458). We aimed to determine the discordance between Liposcience NMR, Quest CardioIQ, and Atherotech VAP Plus. 102 patients older than 18 years on therapy for at least 30 days were included. A one-time fasting lab draw was obtained with all 3 lipid tests performed simultaneously on fresh samples. Concordance and discordance analysis was performed with the cut-off between normal and abnormal ranges.

Results:
Pearson correlations between LDL-P by VAP and NMR, NMR and IM, and VAP and IM were 0.886, 0.785, and 0.762, respectively.

All 3 tests were concordant 63% and discordant 37% of the time.
IM reported an abnormal LDL-P more commonly (28% of time vs NMR and 20% of the time vs VAP) when using the same cutoff value of 1000 as NMR. When using the cutoff of 1260 for LDL-P for IM, NMR was abnormal 15.6% of the time vs IM and VAP was abnormal 24% of the time vs IM. VAP more frequently reported an abnormal LDL-P vs NMR (27% of the time) and vs IM (32% of the time). VAP small LDL sub-fractions were more commonly reported as abnormal vs NMR and IM (27% and 32% respectively). Ion mobility more consistently reported a lower large HDL-P (48% of the time vs VAP and vs NMR).

Conclusions:
Correlations between advanced markers of residual risk were low and would give discordant signals on decisions to intensify therapy.
Abstract 18880: Inflammation Imaged With [18F]-FDG PET/CTA is Related to 3D Ultrasound Phenotypes of High-risk Carotid Plaque: Sub-study of the Canadian Atherosclerosis Imaging Network (CAIN-2)
Authors: Cocker Myra S , Fenster Aaron , Hammond Robert R , Lim Siok P , deKemp Robert A , Lum Cheemun , Hill Andrew , Nagpal Sudhir , Stotts Grant , Warren Brittany , Garrard Linda , DaSilva Jean , Tardif Jean-Claude , Beanlands Rob S , Spence J. David 
Published: March 2022

Background:
Inflammation may contribute to plaque instability. [18F]-fluorodeoxyglucose (FDG) uptake imaged with positron emission tomography (PET) and computed tomography (CT) may serve as a biomarker of plaque inflammation.

3-dimensional ultrasound (U/S)-derived total plaque volume (TPV) and vessel wall volume (VWV) are measures of plaque volume and vessel wall thickness that are used for monitoring progression and regression of carotid atherosclerosis. Progression of TPV has been related to cardiovascular events.
The volumetric phenotype (TPV and VWV) and extent of the inflammatory burden (FDG uptake) may independently predict carotid plaque vulnerability. However, the interrelationship between FDG uptake and measures of TPV and VWV remains poorly understood.

Methods:
Thirty-seven patients (67±9 years, 9 female) scheduled for carotid endarterectomy were prospectively recruited for 3D U/S and FDG PET/CT imaging of the left and right internal carotid arteries.

Maximum FDG uptake normalized to blood (tissue to blood ratio - TBR) was measured for bilateral carotid plaque.
Manual planimetry was used to measure bilateral TPV and VWV. Each 3-D image were evaluated from the bifurcation to the common carotid, and then to the internal and external carotid arteries.

Results:
Maximum FDG uptake correlated with TPV (r=0.42, p<0.001) and VWV (r=0.30, p=0.015) (Figure 1). FDG uptake was greater in plaque scheduled for endarterectomy (TBR=3.6±1.3 endarterectomy vs. 3.0±1.2 contralateral, p=0.049). There was also a trend for greater TPV at the side of endarterectomy: 799±390mm
3
endarterectomy vs. 672±150mm
3
contralateral (p=0.088).

Conclusion:
FDG uptake in high-risk carotid plaque is related to TPV and VWV. The inflammatory burden and the volumetric phenotype of plaque may synergistically provide a more robust evaluation of plaque vulnerability. Longitudinal follow-up for the assessment of plaque progression in this study cohort is currently underway.
Abstract 19027: Glycation of ApoA-IV is Associated With the Severity of Coronary Artery Disease in Diabetic Patients and Glycated ApoA-IV Protein Promotes Atherogenesis Through Nuclear Receptor NR4A3 Mediation
Authors: Lu Lin , Dai Yang , Shen Ying , Sun Jia Teng , Wang Xiao Qun , Yan Xiao Xiang , Zhang Rui Yan , Shen Wei Feng 
Published: March 2022

Background:
ApoA-IV is associated with HDL in plasma but a large portion circulates lipid free. It has been shown to possess anti-inflammatory and anti-atherosclerotic effects.

Methods and Results:
We isolated HDL from plasma of type 2 diabetic patients and healthy controls, and found that apoA-IV of HDL from diabetic patients was significantly glycated by using Western blot and mass spectrometry. The glycation levels of apoA-IV were higher in diabetic patients than in controls, and were associated with the severity of coronary artery disease. Immunohistochemically, glycation sites co-localized with apoA-IV in atherosclerotic plaques from diabetic patients.

In cell and animal studies, in vitro glycated apoA-IV protein promoted inflammatory reactions in human aortic endothelial cells and atherogenesis in apoE-KO mice as compared with control, whereas apoA-IV exhibited anti-inflammatory and anti-atherogenic effects. The pro-inflammatory action of glycated apoA-IV was mediated by receptor for glycation end products in endothelial cells. In microarray analysis and verification in endothelial cells, glycated apoA-IV but not apoA-IV, enhanced the expression of nuclear receptor NR4A3 greatly. Glycated apoA-IV-induced inflammatory reaction and atherogenic effect was significantly attenuated in endothelial cell with siRNA-NR4A3, native endothelial cells and macrophages from NR4A3-KO mice and in NR4A3-KO mice. Co-localization of NR4A3 with CD31 was observed in atherosclerotic plaque from diabetic patients. Moreover, glycated apoA-IV but not apoA-IV induced trans-activation of NR4A3 to the promoter of adhesion molecules (VCAM-1, ICAM-1 and E-selectin).
ESI-Q-TOF-MS identified several glycation sites including K78, K189 and K328 in apoA-IV from diabetic patients, but not in controls. Mutated apoA-IV proteins (m-apoA-IV-K78A/K189A/K328A) were made. In vitro glycated m-apoA-IV displayed significantly attenuated activation of NR4A3 in endothelial cells and atherogenesis in apoE-KO mice, as compared with glycated apoA-IV.

Conclusion:
Glycation of apoA-IV is associated with the severity of coronary artery disease in diabetic patients and glycated apoA-IV protein promotes atherogenesis through nuclear receptor NR4A3 mediation.
Abstract 19833: A New Therapeutic Strategy for Refractory Cardiac Arrest Including Prehospital Ecmo: A Comparison Study
Authors: Lamhaut Lionel , Jouffroy Romain , idialisoa Rado , Ellinger Alexandre , Orsini Jean-Pierre , Hutin Alice , Jaffry Murielle , Dagron Christelle , Loosli Florian , Jouan Jerome , An Kim , Spaulding Christian , Carli Pierre 
Published: March 2022

Introduction:
ECMO is a treatment of refractory cardiac arrest (RCA). The survival rate depends directly on the low flow (LF) period. To reduce LF we have implemented a new RCA management strategy. This work aims to evaluate the impact of this strategy on survival.

Methods:
This is an observational retrospective single-center study. The ECMO team is composed of a doctor, a nurse and a paramedic.The ethical committee validated the study.

During period 1 (11 / 2011-12 / 2014), the strategy associated an ECMO team alert after 10 min of ALS, followed by the implementation of ECMO either in-hospital or out of hospital depending on the ECMO team availability.
During period 2 (01-06 / 2015), the strategy associated an ECMO Team alert at the departure of the BLS Ambulance, with a dedicated ECMO team 24/24 H, and a systematic assessment for ECMO implementation either in hospital or out of hospital according to logistical constraints. A specific training was given to dispatch centers, and all ALS units.
Qualitative variables were compared using the χ2 and Fisher exact tests, whereas quantitative variables were compared by Wilcoxon tests.

Results:
The results are in Table 1. The characteristics are similar. The significant results when comparing periods 1 and 2 include an increased survival rate, a decreased LF.

Conclusions:
The survival rate of RCA treated with ECMO depends on the LF. Unfortunately even by performing a single scoop and run strategy, an important proportion of patients can not be rapidly put on ECMO.

We have developped a LF reduction strategy involving the implementation of ECMO either in hospital or in the out of hospital setting.
The optimization of this strategy by an earlier alert, a dedicated ECMO team and training has a major significant impact on survival. This increase of survival is probably correlated to the decrease of the LF, especially in the prehospital group.
These results need to be confirmed by a RCT comparing in hospital and out of hospital ECMO implementation.
Abstract P294: Higher Obesity Duration and Severity are Associated with Progression to Metabolic Syndrome From Metabolically Healthy Obesity: Discrete Time Survival Evidence From the Multi-Ethnic Study of Atherosclerosis
Authors: Mongraw-Chaffin Morgana , Foster Meredith C , Kalyani Rita R , Vaidya Dhananjay , Burke Gregory L , Woodward Mark , Anderson Cheryl A 
Published: March 2022

While the health risks of obesity compared to normal weight have been well studied, the cumulative risk associated with chronic obesity remains unknown. Specifically, debate continues about the importance of recommending weight loss for those who have metabolically healthy obesity. We therefore hypothesized that longer duration of obesity combined with greater severity of obesity is associated with progression to incident metabolic syndrome.

We used complementary log-log models of discrete time survival to metabolic syndrome with clustered robust variance for time varying obesity severity and duration in 2,748 Multi-Ethnic Study of Atherosclerosis participants with obesity (BMI≥30kg/m
2
) at any visit. Participants who developed metabolic syndrome before obesity were excluded. We defined obesity duration as the number of visits with measured obesity and obesity severity as the WHO levels I-III based on BMI. We defined metabolic syndrome using Adult Treatment Panel III criteria modified to exclude waist circumference. We assessed whether participants exhibited individual heterogeneity in their risk for metabolic syndrome using a random effects complementary log-log model. We specified an a priori sensitivity analysis to determine if the results were similar in those younger or older than 70 years.

Higher obesity severity and duration were independently associated with incident metabolic syndrome (Table 1). Including random intercepts in the model, while statistically significant, did not attenuate other associations. Estimates for duration were stronger for those under 70 years when compared to those 70 and older (age interaction p=0.039).
While there is significant individual heterogeneity in risk, both duration and severity of obesity are associated with incident metabolic syndrome, suggesting that metabolically healthy obesity is a transient state in the pathway to metabolic risk. Weight loss should be recommended to all individuals with obesity, including those who are currently metabolically healthy.

Table 1. Metabolic syndrome hazard ratios and 95% confidence intervals from complementary log-log models of discrete time survival by obesity duration and severity in MESA participants with measured obesity at any visit (n=2,748)

* All models include age, gender, and race/ethnicity, and indicator variables for study visit (visits 1-5)
** All models, except for the random effects model, use robust variance clustered on participant ID
*** Metabolic syndrome is defined as 2 or more of the following:
1. Triglyceride level ≥150mg/dL
2. HDL cholesterol <40mg/dL in men and <50mg/dL in women
3. Systolic blood pressure ≥130mmHG or diastolic blood pressure ≥85mmHG or use of blood pressure medications
4. Fasting glucose ≥100mg/dL or use of medications for diabetes
Abstract P117: Mexican Reg

i

stry of Risk Factors for Cerebrovascular Disease: The “RISK” (RIESGO) Study, a Mexican Approach
Authors: Espinosa Luis , Rodríguez Beatriz L , Pozas Gerardo E , Cantu-Brito Carlos , León Carolina , Flores Dolores , Castilla-Cortázar Inma , Góngora Jose J , Vargas Socorro ,   RIESGO investigators
Published: March 2022

Background:
The RIESGO (RISK) study was established to investigate associations between lifestyle, risk factors and cerebrovascular diseases in 300 attendees to the annual meeting of the Mexican Academy of Neurology. In these analyses we describe traditional and several new risk factors for Cerebrovascular Disease on the RIESGO participants as well as a novel way to create a cohort.

Methods:
The RIESGO study employed a sample of the Mexican Congress of neurology attendees and intends to follow them prospectively. All attendees were invited to participate (n=1300). A survey on lifestyle questions, and clinical evaluations were conducted at the congress site, non-parametric descriptive statistics were used.

Results:
300 attendees (68.8% physicians) participated in RIESGO, 18-83 years old mean 47.1(DE=13.9) and 59% were men. In the RIESGO study, self-reported Diabetes (DM) was 6.8% compared to 20.1% using Glycated Hemoglobin (HbA1c) for diagnosis (>6.5%) and 40% of those with self-reported DM had elevated HbA1c. Also remarkable is the 20.3% major and minor electrocardiographic abnormalities. Systolic and diastolic hypertension was observed in 14.1% and 4.1% respectively, vs 18.4% for self-reported hypertension. Obesity and overweight was observed 66.2% based on BMI > 25kg/m2. Active and former smoking rates were 14.3% and 24.4% respectively, active exercise (>150min/week) was reported in 48.5% and high alcohol consumption (>25 12Oz Beer or equivalent/30days) was 19.9%.

The subclinical outcomes were: intima-media thickness (≥0.8mm) found in 2.3%, carotid plaque in 6% and ventricular hypertrophy (Sokolow) in 1.8%.
We also explored other new risk factors associated with stroke, and found a high heart rate at rest (>70 beats per minute) in 35%, ventricular premature beats 1.1%, prolonged QTc 0.6% and 0% in men and women respectively, finally on the perceived stress scale 97% “never” or “almost never” felt stressed and only 2.3% felt “fairly often stressed”. We will also discuss the association of traditional vs newer risk factors with subclinical outcomes.

Conclusions:
These findings indicate a high prevalence and poor awareness and control of major cardiovascular disease risk factors and subclinical outcomes, despite the fact that RIESGO participants have a substantially higher education level and health information than the general Mexican population. These findings reflect the alarming public health problems that diabetes and cardiovascular diseases represent in the Mexican population, even among the most educated individuals. Recurrent attendance at the annual meeting is a novel and convenient way to establish a low cost follow-up study.
Abstract 10411: Recurrent Spontaneous Coronary Artery Dissection
Authors: Echeverry Tatiana , Mehan Shivalika , Williams Karlene 
Published: March 2022

Spontaneous coronary dissection (SCAD) accounts for 25% of ACS in females <50 years of age. The recurrence rate of SCAD within one to two years is 11%. Currently, there are no universal guidelines for the treatment of SCAD. However, the literature reports higher rates of complications associated with stenting than with medical treatment. Beta-blockers are believed to be protective against SCAD recurrence due to its direct mechanism of action on the vasculature and heart. The following case describes a patient on recommended medical therapy, including a beta-blocker who presented with a dissection of the second diagonal branch.
A 51-year-old female with a history of SCAD in 2007 and right MCA aneurysm on metoprolol, presented with sudden onset of mid-sternal chest pain radiating to the back. The initial EKG showed T wave inversions in lead V2-V3 and elevated troponin of 2.58 which peaked at 9.9. The patient immediately underwent cardiac catheterization which revealed spontaneous dissection in the circumflex marginal. An ECHO revealed EF of 60-65% without wall motion abnormalities. The patient was treated medically with DAPT, and continuation of her home medication metoprolol.
SCAD is a rare etiology of ACS with a predilection for young to middle-aged females. In the United States, SCAD has an approximate yearly incidence of 3.4% in females. The coronary vessels affected more frequently are the LAD and the RAC with 57% and 29% rate of dissection respectively. SCAD was noted to have a recurrence rate of 11% within 2-3 years with an increased recurrence rate of 29% at the 10-year follow-up. While the reasons for recurrence are unclear, there is a clear association between vessel tortuosity and HTN with higher rates of recurrence. A previous study reported that beta-blockers can reduce the risk of recurrence by almost two-thirds. The decreased risk was attributed to the mechanism of action of beta-blockers: decreasing intracoronary shear stress, decreasing heart contractility, and reducing aneurysm degeneration. Our patient suffered a recurrent case of SCAD despite recommended treatment with a beta-blocker. Further research is needed to risk-stratify patients and to clarify if a specific dose or type of beta-blocker will protect against SCAD recurrence.
Abstract 10498: The Use of a Digital Telehealth Platform to Understand the Prevalence and Control of Cardiovascular Disease Risk and Risk Factors in the Indian Population - A Pilot Study
Authors: Vaishnav Aditi S , vaishnav sudhir 
Published: March 2022

Introduction:
Despite the enormous & growing burden of CVD in India, there is still lack of awareness about the importance of guideline based prevention and risk factor control.

Objectives:
To understand the feasibility & utilization pattern of an open-to-public digital health (mHealth) platform designed to assess CVD risk, risk factors (RF), RF control and adequacy of prevention, and provide appropriate education and guidance based on the assessment.

Methods:
Data was collected over 2 months through the mHealth platform that was open to all adults aged 25-80 years. It was accessible at no cost via all web browsers on smart phones, computers & tablets with internet connectivity and was available in 2 languages.

Utilization of the platform was significantly higher in males - 93.7% (251/268) respondents. Therefore, the study population for this study comprised of 251 males (age 45.4
+
11.7 yrs). Females were not included due to the small sample size; hence the corresponding results will be published once adequate sample size is reached.

10 year CVD Risk was calculated using the Framingham Risk Score (FRS). RF, RF control and adequacy of prevention were assessed using national & international guidelines, as appropriate. Statin indicated conditions were atherosclerotic disease, diabetes mellitus, familial hyperlipidemia and FRS-CVD risk >=10%.

Results:
Results are summarized in Fig 1. Overall 186 subjects met the criteria of having statin indicated conditions; however, only 37.6% of them reported taking a Statin.

The commonest RFs were hypertension (68.5%) & sedentary lifestyle (57%). Rates of undiagnosed RFs were high -diabetes 45.7%, hypertension 20%, high normal BP 28%, and pre-diabetes 24.9%.
RF control was poor with only 23.2% of people with hypertension reporting BP <130/80, 38.9% of diabetics reporting HbA1c <7% and 26.2% of those taking Statins reporting LDL <70 mg/dL.

Conclusion:
The use of a digital health tool for CVD prevention is feasible and reveals a large unmet need.