bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19350: The Decline of the Montreal Cognitive Test Can Detect Post-stroke Cognitive Decline Determined by a Formal Neuropsychological Evaluation
Authors: Xu Kenny , Dong Catherine , Chen Christopher
Published: July 2021

Objective:
We aimed to establish the association of decline in cognitive screening tests scores, the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), with the decline in neuropsychological diagnostic status from 3-6 months to a year later.

Method:
Patients with ischemic stroke/ Transient Ischemic Attack (TIA) received the MoCA and MMSE within 14 days after stroke, then 3-6 months and 1 year later. The decline in MoCA and MMSE scores were defined by reduction of 2 points or more in total scores, while stable/improved MoCA scores referred to reduction of MoCA scores less than 2 or improved scores. The decline in neuropsychological diagnostic status was defined by category transition from no cognitive impairment to any cognitive impairment (≥1 domain), from mild cognitive impairment (impairment in 1-2 domains) to moderate cognitive impairment (impairment >2 domains) and dementia (i.e., functional loss associated with cognitive impairment, DSM-IV criteria), as well as from moderate cognitive impairment to dementia.

Results:
At baseline, most patients were Chinese (70.3%) and males (69.8%) with age of 59.8 ± 11.6 years and education of 7.7 ± 4.3 years. 327 out of 400 stroke/TIA patients completed neuropsychological assessments at 3-6 months and 275 completed at 1 year after their index cerebrovascular events. Of these, 31 (11.3%) had decline in neuropsychological diagnostic status. Logistic regression was used to model the association between probability of decline in neuropsychological diagnostic status and the decline in MMSE or MoCA scores. There were not significant associations between the decline of neuropsychological diagnostic status and the decline in MMSE scores. Controlling baseline MoCA scores and the change scores of MoCA from baseline to 3-6 months, patients with decline in MoCA scores (reduction of 2 points or more) were associated with higher risks of decline in neuropsychological diagnostic status, relative to those with stable/ improved MoCA scores (odd ratio=3.21, p=0.004).

Conclusion:
The decline in MoCA scores are associated with a higher risks for decline in neuropsychological diagnostic status from 3-6 months to 1 year, therefore may be used to detect post-stroke cognitive decline.
Abstract 19375: Rapamycin Treatment Regulates miRNAs Associated With Mitochodrial and Endoplasmic Reticulum Functions in a Pig Model of Miocardial Ischemia-reperfusion Injury
Authors: Bianchi Cesario , Oliveira Paulo S , Lassaletta Antonio D , Sellke Frank W , Franchini Kleber G , Schorl Christoph
Published: July 2021

Introduction:
Previously(Lassaletta et al,PMC3943541)we showed that Rapamycin treatment of normal pigs subjected to an acute myocardial ischemia-reperfusion injury (IRI) was associated with increase myocardial necrosis and refractory left ventricle (LV) defibrillations. In an effort to better understand rapamycin effects we applied a non-bias genomic analysis to determine if microRNAs were modified by rapamycin treatment in this pre-clinical animal model of IRI.

Hypothesis:
We hypothesized that microRNA expression were modified by rapamycin-treated and would identify novel and meaningful pharmacological mechanisms related to its detrimental effects on reperfusion injury.

Methods:
Young male Yorkshire swine (16-19 kg) received either no drug (controls, n=5) or were given 4mg of oral rapamycin daily (n=5). After two weeks of treatment, all animals underwent median sternotomy and the mid-LAD was occluded for 60 minutes followed by 120 minutes of reperfusion. RNA was extracted from LV non-ischemic and ischemic areas from each group and processed (according to the manufacture′s specifications at Brown University Genomic Core facility) for microRNA (miRNA) expression analysis using a Affymetrix GeneChip miRNA3.0 Array containing over 25,000 probe sets of which 257 miRNA probes of domestic pigs. Data were processed using MetaCore version 5.0 (GeneGo, St Joseph, MI) for both statistical (FDR: p<0.05) and pathway analysis.

Results:
miRNA regulated in 5 animals per group were annotated for human orthologs. A total of 23 miRNAs were differentially expressed. Interestingly, all miRNAs were down-regulated in the rapamycin-treated animals. Of those, nine had human orthologs: miR 181c-3p was highly represented followed by miR323a-5p, miR1245b-3p, miR4324, miR331-5p, miR491-5p and miR490-3p.

Conclusions:
Recent studies show that miRNA 181c regulates myocardial mitochondrial function through cytochrome c oxidase and complex IV gene expressions (PMCID: PMC4014556)and regulates Glucose-regulated protein (GRP78)/BiP [an endoplasmic reticulum stress (ER) chaperone](PMID: 24696166). Hence It is likely that rapamycin effects (detrimental or not) are associated with mitochondrial function and ER stress response.
Abstract 19533: The Relationship Between Aortic-brachial Stiffness Mismatch and Mean Blood Pressure
Authors: Fortier Catherine , Agharazii Mohsen
Published: July 2021

Background:
Carotid-femoral pulse wave velocity (cf-PWV) is considered to be the gold standard for assessment of aortic stiffness. The impact of aortic stiffness on peripheral end-organ damage is explained by the loss or reversal of physiological impedance mismatch between aorta and medium-sized muscular conduit arteries. The main limitation of cf-PWV is its positive relationship with mean blood pressure. Recently, we have shown that assessment of aortic-brachial stiffness mismatch (PWV ratio) outperforms cf-PWV for the prediction of mortality in dialysis population. As both carotid-radial PWV (cr-PWV) and cf-PWV depend on blood pressure, we hypothesized that PWV ratio is not influenced by mean blood pressure.

Method:
In 310 dialysis patients (median age of 67 years [25
th
-75
th
percentiles: 56 - 76], 185(60%) men, 134 (43%) diabetes and 162 (52%) cardiovascular disease), cf-PWV and cr-PWV were measured using direct distance (Complior) and maximal upstroke algorithm. Mean blood pressure was obtained using arterial tonometry calibrated with brachial systolic and diastolic blood pressures in a controlled environment. In a linear regression analysis, we examined the relationship between MBP and cf-PWV, cr-PWV and PWV ratio.

Results:
The mean cf-PWV, cr-PWV, PWV ratio and MBP were respectively 13.52±4.06 m/s, 8.76±1.68 m/s, 1.59±0.52 and 92±16 mmHg. The linear relationships between MBP, cf-PWV and cr-PWV are shown in figures 1A-B. However, there were no relationship between MBP and PWV ratio (Figure 1C). There were no interaction between age, gender and the absence of a relationship between MBP and PWV ratio.

Conclusion:
As PWV ratio is mechanistically a logical parameter for explaining target organ damage and it has no significant relationship with MBP, it seems to be an ideal index for macro-circulatory disease. These findings need to be validated in independent cohorts.
Abstract 19638: A High Percentage of Patients Referred for Invasive Coronary Angiography Found to Have No Obstructive Coronary Artery Disease are Referred for Appropriate Indications
Authors: Ouellette Michelle , Workman Virginia , Loffler Adrian , Beller George A , Bourque Jamieson M
Published: July 2021

Introduction:
The incidence of normal coronary arteries in patients referred for invasive coronary angiography (ICA) ranges from 30-60%. We sought to evaluate patterns of referral, assess the rate of appropriate catheterization and determine the prevalence of coronary artery disease (CAD) in our population by appropriateness and indication.

Methods:
Retrospective analysis was performed on 930 consecutive patients undergoing diagnostic ICA. Indications for ICA were reviewed and appropriate use criteria (AUC) were applied to the cohort retrospectively. Patients with known CAD, prior MI, CHF, or indication for pre-transplant workup or cardiac surgery were excluded. Rates of non-obstructive (21-49% stenosis) and obstructive CAD (≥50%) were compared by appropriateness status using Fisher’s Exact Testing.

Results:
Of the 930 patients studied, 55.6% were male with median age of 62 and 10-year ASCVD risk score of 17.7%. Acute coronary syndrome (ACS) was the most prevalent indication for referral (48.5%) with a 68.6% prevalence of obstructive CAD. A positive stress test was the indication in 18.9% with a 51.4% rate of obstructive CAD. The rates of the remaining referral indications are given in Figure 1. In those referred appropriately for angiography (n=923), the prevalence of obstructive disease was 55.9% (n=516), non-obstructive disease 13.6% (n=125), and normal coronaries 30.6%(n=282). Inappropriate referral was identified in only 7 patients (0.8%), all of whom had normal coronaries with p<0.001.

Conclusions:
At a single quaternary care academic center the majority of coronary angiographies performed invasively are appropriate by AUC. Despite adherence to AUC, there continues to be a large number of patients with no evidence of obstructive disease, including in those with ACS. Further research is needed to further refine the AUC and its role in risk stratification for obstructive CAD.
Abstract 19644: Dietary Sodium, Potassium Levels and Sodium Potassium Ratios in India Using 24-hour Urinary Excretion Assessment
Authors: Mohan Sailesh , Shivashankar Roopa , Khandelwal Shweta , Anand Shuchi , Kondal Dimple , Krishnan Anand , Amarchand Ritvik , Poulter Neil , Reddy K.Srinath , Prabhakaran Dorairaj
Published: July 2021

Introduction:
Hypertension is a major public health burden in India and most hypertensives are inadequately treated and controlled. Thus, population based sodium reduction strategies are essential for hypertension control. However, contemporary data on sodium consumption, which are essential to implement effective sodium reduction strategies are lacking.

Objective:
To assess the dietary sodium, potassium intakes and sodium potassium ratios using 24 hour urinary samples among a representative sample of adults aged ≥ 20years in urban and rural India.

Methods:
We conducted a population based cross sectional survey among 1397 adults aged ≥ 20 years residing in urban Delhi and rural Haryana, India. Subjects were selected using a systematic random sampling technique (multi stage cluster random sampling in urban area and simple random sampling in rural area). Data were obtained using an interviewer administered questionnaire, anthropometry and a 24-hour urine collection.

Results:
In the urban area, the mean age of the participants was 45 years (SD=14.4) and half of them were women while in the rural area it was 46 years (SD=15.3) and 60% were women. Mean sodium intake as assessed by 24 hour urinary sodium excretion was higher in rural [3798 mg/day (SD=2106)] compared to the urban area [2421 mg/day (SD=1743)]. Mean potassium intake was low in both rural [1607 mg/day (SD=826)] and urban areas [1144 (SD=755)], and the overall sodium potassium ratio was high (2.4).Men had higher sodium intake and sodium potassium ratio.

Conclusion:
Sodium intake in this sample is high and exceeds the current World Health Organization (WHO) recommended levels while potassium intake is low. Sodium reduction efforts combined with policies to increase potassium intake should be initiated in India to prevent and control hypertension as well as to contribute to the proposed United Nations WHO targets for reducing chronic non-communicable diseases by 2025.
Abstract 19746: Identification of Novel microRNA Profiles in Patients With Myxomatous Mitral Valve Disease
Authors: Hagler Michael A , Thalji Nassir M , Russell Nate , Welge Michael , Bushell Colleen , Berry Matthew , White Bryan A , Suri Rakesh M , Miller Jordan D
Published: July 2021

Introduction:
Myxomatous mitral valve disease (MMVD) is a degenerative condition characterized by tissue fibrosis and matrix remodeling which ultimately progresses to leaflet prolapse. While recent work has shown that transforming growth factor beta (TGF-β) signaling contributes to the pathogenesis of MMVD, upstream regulators of this and other pathways remain poorly understood.

Hypothesis:
We sought to use high-throughput RNA sequencing coupled with microRNA (miRNA) sequencing to identify novel molecular targets as well as upstream regulators contributing to MMVD.

Methods:
We conducted mRNA and miRNA sequencing on normal (n = 10) and myxomatous human mitral valve samples (n = 10). Differential expression was identified using linear modeling and parallel random forest analyses. Canonical pathways were identified by Ingenuity Pathway Analyses (IPA). Predicted miRNA targets were identified using TargetScanHuman 6.2.

Results:
We found 2784 mRNAs that were differentially expressed between normal and myxomatous mitral valves, which IPA largely categorized in to pro-fibrotic, matrix remodeling and cellular proliferation signaling. In miRNA sequenced from the same samples, 67 miRNAs were differentially-expressed between normal and myxomatous mitral valves. Increased expression of TGF-β ligands, collagen isoforms, and matrix metalloproteinases were associated with reductions in miRNAs predicted to target them. Conversely, mRNA levels of the “protective” genes TGFβ-induced factor homeobox 1, salt-inducible kinase 1, TIMP metallopeptidase inhibitor 4, and cyclin-dependent kinase inhibitor 1C mRNA levels were decreased in myxomatous tissue, and miRNAs predicted to target these genes (e.g., miR-656, miR-379-3p, miR-664a-3p, and miR-34c-5p) were significantly increased.

Conclusions:
Collectively, these data not only identify novel genes that are differentially regulated in MMVD, but also suggest miRNAs may play an active role in suppressing key protective molecules in MMVD. Thus, anti-mIRs therapy may be a viable therapeutic target to restore anti-fibrotic and anti-proliferative molecules in the valve and slow progression of MMVD. Future mechanistic studies will lay a critical foundation for translational work in these areas.
Abstract 19770: TAVR Versus Medical Management Among Patients With Severe Aortic Stenosis and Left Ventricular Systolic Dysfunction
Authors: Vora Amit N , Harrison John K , Dunning Allison , Schulte Phillip , Sherwood Matthew W , Kisslo Joseph , Hughes G C , Alenezi Fawaz A , Velazquez Eric , Samad Zainab
Published: July 2021

Background:
The decision for transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis (AS) and left ventricular systolic dysfunction (LSVD) can be challenging. We sought to evaluate mortality differences in patients with AS and LVSD undergoing TAVR compared with a medically matched historical cohort.

Methods:
We studied 206 patients who underwent TAVR and had an echocardiogram that demonstrated LVSD within six months prior to the procedure and a matched medically managed historical cohort (n = 206). All TAVR patients had severe aortic stenosis and high or extreme risk for open surgical AVR as determined by the Duke multidisciplinary team. Patients were matched 1:1 using optimal matching methods by AS resting mean gradient and/or peak velocity, age, gender, LVEF, and EURO score. LVSD was subclassified into mild (LVEF 36-50%) or severe (LVEF ≤35%). We used Cox multivariable modeling to assess the relationship between TAVR and all-cause mortality censored at 3 years.

Results:
The median age of the cohort was 82 (IQR 76-87). Compared with the medically matched cohort, TAVR patients were more likely to be male, have a history of ischemic heart disease, renal insufficiency, CHF, and prior CABG (all p<0.05). TAVR was associated with mortality reduction compared with medical management (HR 0.26, 95% CI 0.17-0.40, p<0.0001), which persisted after multivariable adjustment (HR 0.19, 95% CI 0.12-0.30, p<0.0001) (Figure). After adjustment, TAVR provided a larger decrease in mortality risk in patients with LVEF ≤ 35% (HR 0.25, 95%CI 0.06-1.01), than in patients with LVEF 36-50% (HR 0.42, 95%CI 0.14-1.27), but this difference did not reach statistical significance (p
interaction

= 0.52).

Conclusion:
Compared with medical management, TAVR is associated with higher survival with a trend for benefit in patients with severe LVSD. Given the poor prognosis associated with medical management, TAVR should be explored as a therapeutic option in patients with AS and LSVD.
Abstract 19783: The Impact of Cardiac Sympathetic Nerve Activity Evaluated by Cardiac I-123 Metaiodobenzylguanidine Scintigraphy on the Chronotropic Incompetence
Authors: Goto Toshihiko , Wakami Kazuaki , Mori Kento , Hachiya Kenta , Ikehara Noriyuki , Fujita Hiroshi , Fukuta Hidekatsu , Ohte Nobuyuki
Published: July 2021

Introduction:
Chronotropic incompetence (CI), defined as the inability of the heart to increase its rate commensurate with increased activity, produces exercise intolerance, and is an independent predictor of overall mortality. Cardiac sympathetic nerve (SNS) activity has been suggested to have a relation to CI. However, the mechanisms for CI have not been fully elucidated. Thus, we investigated the cardiac SNS activity in patients with CI using cardiac I-123 metaiodobenzylguanidine (MIBG) scintigraphy.

Methods:
Sixteen patients with CI and 17 subjects who served as controls were enrolled in this study (age 77.5±9.2years; male 57.6%). Patients with CI were defined as who were implanted with pacemaker due to sick sinus syndrome.

Results:
There were no significant differences in age, sex, or left ventricular ejection fraction (66.3±14.3 vs 58.3±22.2%, ns) between patients with CI and controls. Plasma BNP level was also similar between two groups (79.0[IQR, 41.0-175.3] vs 90.9[IQR, 35.5-185.3]pg/mL, ns). The delayed heart/mediastinum (H/M) ratio was significantly higher in patients with CI than in controls (2.3±0.3 vs 2.0±0.4%, p=0.04). The early H/M ratio did not differ between two groups. The washout rate (WR) was significantly lower in patients with CI compared with that in controls (20.2±11.2 vs 33.3±14.1%, p=0.006).

Conclusions:
Decreased cardiac sympathetic nerve activity was associated with CI, and I-123 MIBG scintigraphy may be a useful modality for understanding the mechanism for CI.
Abstract 19922: Phosphatidylserine Receptor Upregulation in Stroke for Targeted Carrier Delivery
Authors: Peng Tao , McPherson David D , Huang Shao-Ling
Published: July 2021

Introduction:
The phosphatidylserine receptor (PSR) plays an important role in apoptosis and inflammation. Whether this receptor is expressed in damaged brain cells in the early stages of stroke is unknown.

Hypothesis:
The purpose of this study was to determine if this receptor is expressed on ischemic neurovascular endothelial cells and if so, can it bind with PS-containing liposomes (PS-liposomes). The latter would allow for a neurovascular targeting strategy for therapeutic delivery to ischemic brain cells.

Methods:
Sprague Dawley rats (n=22) were randomly divided into sham, cerebral ischemia, and subarachnoid hemorrhage (SAH) injury groups. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 hours using an intraluminal suture method. SAH was induced by an endovascular perforation method. Brain tissue was harvested for immunofluorescence staining at day 2 after surgery. Cultured human umbilical vein endothelial cells (HUVEC) were pre-treated with tumor necrosis factor alpha (TNFα) to stimulated PSR. Fluorescence labeled PS-containing liposomes (FITC-PS-Liposomes) were used. The PSR expression and the adhesion of liposomes were observed using fluorescence microscopy.

Results:
Normal brain tissue did not demonstrate PSR expression (Fig.1A). After brain injury, PSR expression was observed in the injured area and colocalized with the endothelium both in the MCAO (Fig.1B) and SAH animals (Fig.1C). Normal HUVEC did not demonstrate fluorescence (Fig.1D). Weak fluorescence was observed in normal cells that incorporated the PS-liposomes (Fig.1E). Strong fluorescence was observed in the TNFα-activated HUVEC that incorporated the FITC-PS-Liposomes (Fig.1F).

Conclusions:
This is first report that PSR expression occurs in cerebral microvascular endothelial cells in the early stages of stroke and can be recognized by PS-liposomes. This may allow development of a targeted liposomal carrier for novel targeted stroke treatment.
Abstract 19941: Clinical and Demographic Characteristics According to Dosage Among New Initiators and/or Switchers From Warfarin Non-valvular Atrial Fibrillation Patients on Apixaban, Dabigatran and Rivaroxaban
Authors: Tepper Ping , Masseria Cristina , Mardekian Jack , Hemant Phatak , Kamble Shital , Ravee Yaniv , Abdulsattar Younous , Petkun William , Lip Gregory
Published: July 2021

Background:
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia [1-3] with increasing prevalence in the aging [4]. With the advent of the three NOACs including apixaban, dabigatran and rivaroxaban, it is important to characterize patients prescribed with the different dosage of treatment in the real-world setting.

Purpose:
To describe the baseline clinical and demographic characteristics of NVAF patients on apixaban (5 mg vs 2.5 mg -reduced), rivaroxaban (20mg vs reduced dose: 15 mg or 10 mg), and dabigatran (150 mg vs reduced 75 mg).

Methods:
A retrospective cohort study was conducted using MarketScan Earlyview
®
data. NVAF patients ≥18 years with a minimum of 1 year baseline period were included if they either received a NOAC or were switched from warfarin to NOAC during the study period of Jan 1, 2013 to October 31, 2014.

Results:
For NVAF patients , the majority of the patients were on the standard dosage (Table 1). Similarly for each NOAC, patients using low dosage versus standard dosage were older, had a greater stroke risk, had a prior history of bleeding and were sicker in terms of presence of congestive heart disease, renal disease and Charleson comorbidity index. Patients switching from warfarin had on average a large number of missing dosage data, and if switching to apixaban were more likely to be prescribed the reduced dose than the 5 mg dose. No clear trend was observed for patients switching to dabigatran or rivaroxaban. More than 15% Apixaban and rivaroxaban patients switched from warfarin while only <6% dabigatran patients switched from warfarin.

Conclusion:
AF patient initiated with standard dosages of NOACs had better clinical and demographic characteristics than patients initiated with reduced dosages of NOAC.

Table 1.
Abstract 20153: Predicting the Need for Transfusions in Endovascular Aneurysm Repair (EVAR)
Authors: Mahmood Eitezaz , Shahul Sajid , Soden Peter , Schermerhorn Marc , Mahmood Ferozeuddin , Matyal Robina
Published: July 2021

Purpose:
The majority of patients undergoing EVAR do not require blood transfusion, yet blood type and screen (T&S) is routinely performed. Identifying patients in whom T&S can be avoided presents a substantial cost saving opportunity.

Hypothesis:
We hypothesized that intraoperative blood transfusions can be predicted preoperatively.

Methods:
Using the Vascular Study Group of New England database from 2003-2014, we performed a retrospective review of 4700 patients who underwent EVAR. The cohort was split randomly into a training (60%) and validation (40%) set. A backwards logistic regression analysis was performed to identify predictors of intraoperative blood transfusion in the training set. The model was then tested in the validation set to estimate the receiver operating curves (ROC) and goodness of fit.

Results:
Preoperative hemoglobin, urgency (elective, symptomatic, or ruptured), age, maximal anterior-posterior AAA diameter, female gender, and history of CHF (asymptomatic, mild, moderate, or severe) were all significant predictors of intraoperative blood transfusions. The c-statistic for our model was .82 in the training set and .84 in the validation set, and the Hosmer-Lemenshow goodness-of-fit statistic was 0.99.

Conclusions:
Intraoperative blood transfusions can be routinely predicted preoperatively. Avoidance of T&S in low risk populations provides a substantial cost-saving opportunity.
Abstract 20173: Cardiac Microrna-208a is Upregulated and Positively Correlates With Cardiomyocyte Apoptosis in End Stage Dilated Cardiomyopathy
Authors: Tony Hasahya , Yu Kunwu , Wenhan Ma , Zhao Xiaoqi , Liu Yuzhou , Zeng Qiutang
Published: July 2021

Introduction:
Cardiac miR-208a is dysregulated in several cardiac diseases in which it is associated with adverse outcomes. Our group has previously demonstrated that miR-208a promotes cardiomyocyte apoptosis. Given that many cardiac diseases end with dilated cardiomyopathy, we investigated if miR-208a is upregulated in end stage dilated cardiomyopathy (DCM), and if its expression correlates with cardiomyocyte apoptosis.

Methods and Results:
Left ventricular samples were collected from nine patients with end stage DCM who underwent cardiac transplant, and 8 normal controls. miR-208a levels were analyzed by real time-PCR, and apoptosis assay done by TUNEL method. miR-208a was 5.8 times higher in left ventricular samples of end stage DCM patients compared to controls, p=0.014. Patients with DCM also had a significantly higher percentage apoptosis compared to controls, p=0.009,(Figure 1A shows representative TUNEL stained images with increased cardiomyocyte apoptosis in DCM). The level of miR-208a showed a significant positive correlation with percentage cardiomyocyte apoptosis rho(0.597), p=0.011.

Conclusion:
Taken together, we showed that miR-208a is elevated in end stage DCM and its levels are positively correlated with cardiomyocyte apoptosis. Targeted silencing of miR-208a may thus be beneficial in DCM and other cardiac diseases that end up in DCM.
Abstract 9850: Cardioprotective Role of Zofenopril in Hypertensive Patients With Acute Myocardial Infarction: A Pooled Individual Data Analysis of Four Randomized, Double-blind, Controlled, Prospective Studies
Authors: Borghi Claudio , Omboni Stefano , Reggiardo Giorgio , Bacchelli Stefano , Degli Esposti Daniela , Ambrosioni Ettore
Published: July 2021

Introduction:
the SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies demonstrated that early administration of zofenopril following acute myocardial infarction (AMI) is prognostically beneficial compared to placebo or other angiotensin-converting enzyme inhibitors (ACE-inhibitors).

Hypothesis:
In the present meta-analysis of individual data of four SMILE studies we evaluated the cumulative efficacy of zofenopril on cardiovascular (CV) morbidity and mortality in the subgroup of hypertensive patients.

Methods:
1880 (53.1%) of the 3542 patients had a positive history for hypertension. 449 hypertensives and 486 normotensives were treated with placebo (SMILE 1 and 3), 980 and 786 with zofenopril 30-60 mg/die (all four studies), 451 and 390 with lisinopril 5-10 mg/die (SMILE 2) or ramipril 10 mg/die (SMILE 4). Treatment was continued for 6 to 48 weeks. For the purpose of this pooled analysis the primary study endpoint was set to 1-year combined occurrence of death or hospitalization for CV causes.

Results:
the risk of CV events was significantly reduced by 35% with zofenopril vs. placebo [HR: 0.65; 95% CI: 0.49-0.86; p=0.003) in hypertensive patients and by 41% in normotensive patients (0.59; 0.44-0.79; p=0.0001). The other ACE-inhibitors reduced CV morbidity and mortality as well, though the reduction (-17%) was not statistically significant vs. placebo either in hypertensives (0.83; 0.57-1.21; p=0.338) or normotensives (reduction: -24%; HR: 0.76; 0.50-1.15; p=0.194). Treatment with zofenopril of hypertensive and normotensive patients was associated with a non-statistically significant reduction in the risk of CV outcomes as compared to the other ACE-inhibitors (hypertensives: 0.78; 0.60-1.01; p=0.062; normotensives: 0.77; 0.55-1.10; p=0.1509.

Conclusions:
in high-risk cardiac patients with arterial hypertension, zofenopril treatment is associated with a clinically relevant reduction in long-term CV morbidity and mortality, compared to placebo, with an efficacy similar to that of other ACE-inhibitors, such as lisinopril and ramipril.
Abstract 9945: Early Ambulation After an Initial Implantable Cardioverter Defibrillator (ICD) is Safe and Efficacious
Authors: Dougherty Cynthia M , Lau Emily T , Burr Robert L , Thompson Elainet A
Published: July 2021

Introduction:
Early ambulation after hospitalization accelerates return to physical functioning and reduces post-hospital complications. After an ICD, patients are discharged with activity restrictions to prevent lead dislodgement, but evidence-based recommendations for safe exercise are not in place.

Methods:
Using a single group pre-post design, 225 patients after an initial ICD were prescribed a nurse-monitored home based walking program at hospital d/c and were followed for 3 months. The mild intensity (Borg rating=3) protocol was designed to increase walking from 10 min/day to 30 min/day. Activity progression was monitored by weekly nurse phone calls. Efficacy was measured in total steps/day (Cyma Step Watch™), self-reported exercise (exercise log), and self-efficacy for walking (SEW). ICD shocks and hospitalizations were verified with medical records. ANOVA was used to determine effects on outcomes from baseline to 3 months.

Results:
Patients were (mean+SD) 64+12 years old, 90% Caucasian, 75% male, EF% 35.7+17.5, having received an ICD for primary (58%) or secondary prevention (42%), with a Charlson score =2.3+1.6. Safety: There were 15 (7.6%) individuals who received 22 ICD shocks, of which 11 were inappropriate for either atrial or supraventricular arrhythmias. There was 1 appropriate ICD shock related to physical activity (elliptical trainer), but none occurred during prescribed home walking. Hospitalization for any cause was 22.8%, with 10(5%) related to ICD shocks, none of which were exercise related. Efficacy: physical activity significantly increased in steps/day (6854+3502 to 7839+4064, p<0.001), exercise times/week (4.2+3.2 to 7.1+4.3, p<0.001), SEW (7.2+2.1 to 8.8+1.5, p<0.001). At 3 months 148/225 (66%) were walking 30 min/day on 4 days/week.

Conclusions:
A mild intensity early ambulation program following initial ICD implant is safe and is related to increased physical activity and self-efficacy for exercise, without being related to ICD shocks or hospitalizations. The walking protocol offers clinicians an algorithm for incorporating ambulation into activity routines in early post-ICD recovery.
Abstract 9967: Altered TGF-β Signalling and Myofibroblast-like Cell Differentiation Contribute to Myxomatous Mitral Valve Disease
Authors: Sahagian Alex , Dilworth Candice , Robertson Elizabeth , Lu Yaxin , Kekic Murat , Maleki Sanaz , Bao Bob , Beijerink Niek , Hambly Brett
Published: July 2021

Upregulated Transforming Growth Factor-beta (TGF-β) signaling has been implicated in the pathogenesis of myxomatous mitral valve disease (MMVD) in both humans and canines. Moreover, it has been postulated that the phenotypic transformation of valve interstitial cells (VICs) in the mitral valve into alpha-smooth muscle actin (α-SMA)-positive myofibroblast-like cells contribute to elevated levels of proteolytic enzymes such as matrix metalloproteinases (MMPs), which subsequently induce pathological remodeling of the extracellular matrix (ECM) in the mitral valve. We hypothesized that, in MMVD, upregulation of TGF-β signaling would induce the transformation of VICs into myofibroblast-like cells, which subsequently express increased levels of MMPs. Computational immunohistochemistry was used to quantify protein expression in mitral valve leaflet tissue from canines affected by MMVD (n=4) and from control canines (n=5). TGF-β and α-SMA expression was significantly increased (p<0.001) in MMVD tissue compared to control tissue. Moreover, a significant positive correlation was found between TGF-β expression and α-SMA expression (p<0.05) across the entire cohort. There were also significant increases in MMP-2 and MMP-9 expression (p<0.05) in MMVD tissue compared to control tissue. No change in MMP-3 expression was detected. These findings are consistent with abnormal TGF-β signaling inducing the differentiation of VICs into α-SMA-positive myofibroblast-like cells. Moreover, the increases in expression of MMP-2 and MMP-9 in MMVD indicate the likely role of these myofibroblast-like cells in mediating pathological remodeling of the ECM throughout the disease process. The paradoxical finding of no change in MMP-3 expression may represent a compensatory mechanism that attempts to limit further degenerative damage to the mitral valve. In conclusion, MMVD is characterized by TGF-β-induced differentiation of VICs into myofibroblast-like cells, which subsequently facilitate ECM degradation via the increased expression of MMPs. This supports the rationale for the use of angiotensin II receptor blockers, capable of attenuating TGF-β signaling, in the treatment of MMVD.
Abstract 13: Economic Impact of Moderate-vigorous Physical Activity Among Those with and without Established Cardiovascular Disease: 2012 Medical Expenditure Panel Survey
Authors: Valero-Elizondo Javier , Salami Joseph A , Osondu Chukwuemeka U , Younus Adnan , Arrieta Alejandro , Spatz Erica S , Rana Jamal S , Virani Salim S , Blankstein Ron , Blaha Michael J , Veledar Emir , Nasir Khurram
Published: July 2021

Background:
Physical activity (PA) is an established factor for favorable cardiovascular disease (CVD) outcomes and quality of life. However, to date little is available on PA’s independent impact on healthcare cost. In this study, we aimed to estimate this effect on medical expenditure from a nationally representative cohort with and without CVD.

Methods:
The 2012 Medical Expenditure Panel Survey data was analyzed. Our study population was limited to non-institutionalized adults ≥ 40 years of age. Variables of interest were CVD (coronary artery disease, stroke, heart failure, dysrhythmias or peripheral artery disease), modifiable risk factors (MRF; hypertension, diabetes mellitus, hypercholesterolemia, smoking, and/or obesity), and PA (dichotomous variable: defined as moderate-vigorous exercise of ≥ 30 minutes, 5 times/week). Two-part econometric models were utilized to study cost data; a generalized linear model with gamma distribution and link log was used to assess expenditures per capita, taking into consideration the survey’s complex design.

Results:
Our final study sample consisted of 15,651 surveyed individuals (mean age: 58.5 ± 12 years, 46% male). Overall, 46% engaged in at least moderate exercise, translating to 21 million physically active adults in the U.S. Of those with CVD, 34% reported PA, vs. 47% without CVD. In those without CVD, a higher prevalence of PA was noted with lower MRF burden (≥ 3: 35%, 2: 44%, 0-1: 53%). Generally, participants reporting moderate-vigorous PA incurred significantly lower healthcare costs, seen both in those with and without CVD. Among those without CVD, those engaged in moderate-vigorous PA with 0-1 & ≥ 3 MRF had $1,038 & $1,785 less healthcare expenditure, respectively, than their less physically active counterparts.

Conclusion:
In addition to tremendously improving CVD risk, moderate-vigorous PA is also associated with significantly less healthcare spending. Our findings further reinforce the importance of physical activity in health promotion and CVD prevention.
Abstract 36: Diet Soda Consumption and Risk of Incident End-stage Renal Disease
Authors: Rebholz Casey M , Grams Morgan E , Steffen Lyn M , Crews Deidra C , Anderson Cheryl A , Appel Lawrence J , Coresh Josef
Published: July 2021

Introduction:
Diet soda consumption may be associated with kidney disease, as shown in Caucasian women, due to phosphorus content, by increasing dietary acid load, or as a proxy for poor diet quality. However, less is known about the relationship between diet soda consumption and end-stage renal disease (ESRD) risk in the general population.

Methods:
We conducted a prospective analysis of time-varying diet soda consumption and incident ESRD in the population-based Atherosclerosis Risk in Communities study (N=15,369) using Cox regression. Usual dietary intake was assessed by a food frequency questionnaire in 1987-89 (baseline) and 1993-95. Incident ESRD was defined as initiation of renal replacement therapy (transplant, dialysis) through 2011.

Results:
Baseline mean age was 54 years, 55% were female, 27% were African-American, 12% had diabetes, and 35% had hypertension. Approximately a third of participants consumed <1 glass of diet soda per month; 42% of participants consumed up to 6 glasses/week; and 22% consumed more than 6 glasses/week. Over a median follow-up of 23 years, 357 incident ESRD cases were observed. Consuming up to 6 glasses of diet soda per week and more than 6 glasses of diet soda per week, respectively, was associated with 1.28-times (95% CI: 0.96, 1.70; p=0.10) and 1.95-times (95% CI: 1.43, 2.64; p<0.001) greater risk of ESRD relative to <1 glass/month after adjusting for total caloric intake, sugar-sweetened beverages, diet quality, age, sex, race-center, estimated glomerular filtration rate, diabetes, hypertension, overweight/obesity status, education level, smoking status, and physical activity (p-value for trend <0.001;
Figure
). For each additional glass of diet soda consumed per day, there was a 26% higher risk of ESRD (HR: 1.26; 95% CI: 1.14, 1.40; p<0.001). Sugar-sweetened beverage consumption was not association with ESRD.

Conclusion:
Diet soda consumption was associated with ESRD risk and may be an important target for dietary interventions aimed at slowing kidney disease progression.
Abstract 45: Weight-related Discrimination Increases the Risk of Multi-system Physiological Dysregulation Among US Adults
Authors: Vadiveloo Maya , Mattei Josiemer
Published: July 2021

Background:
Obesity stigma is prevalent in the US. General discrimination has been shown to trigger a multi-system physiological dysregulation collectively referred to as allostatic load (AL), which independently predicts cardiovascular disease morbidity and mortality. However, it remains unclear whether weight-related discrimination influences AL. We aimed to examine the prospective associations between weight-related discrimination and AL and its individual systems among adults aged 25-75y participating in the national Midlife Development in the US (MIDUS) study over 10-years.

Methods:
Participants from the MIDUS Biomarker Substudy with self-reported information on weight discrimination were analyzed (n=986). At baseline and at 10-years follow-up, participants were asked about the frequency (never, rarely, sometimes, often) of perceived weight discrimination across nine scenarios. A continuous score assigned 1-2 points for discrimination experienced ‘sometimes’ or ‘often’, and an average of the two values at baseline and 10-years were used to estimate long-term discrimination. An AL score (range 0-7) represented the sum of the proportion of 24 dysregulated biomarkers or corresponding medication use within each of 7 systems (cardiovascular, sympathetic and parasympathetic nervous systems, hypothalamic pituitary axis, inflammatory, lipid and general metabolic activity, and glucose metabolism). Estimated relative risks (RR) were obtained from multivariable models adjusted for age, sex, race, education, household income, smoking, physical activity, race and sex discrimination, and baseline BMI.

Results:
Over 41% of the sample was obese, and 6% reported weight discrimination at 10-year follow-up. Both baseline and long-term perceived weight discrimination were associated with more than double the risk of high AL in final multivariable models (RR: 2.06, 95%CI: 1.20, 3.52 for baseline; 2.16, 95%CI: 1.39, 3.36 for long-term discrimination). The associations remained significant when the continuous weight discrimination score was assessed (β=0.11, p=0.01 for baseline; β=0.19, p=0.0001 for long-term discrimination). In sensitivity analyses, when BMI and waist:hip ratio were excluded from the AL definition, long-term weight discrimination remained associated with a 62% greater risk of high AL (1.62, 95%CI: 1.01, 2.62). Weight discrimination was significantly associated with metabolic/lipid dysregulation (1.56, 95%CI: 1.03, 2.41), glucose metabolism (1.99, 95% CI: 1.34, 2.96), and inflammatory parameters (1.76. 95% CI: 1.22, 2.54), but not with the other systems.

Conclusions:
Perceived weight discrimination doubles the risk of high AL. Public health campaigns and individual patient counseling that avoid obesity stigma may help improve obesity-related morbidity and mortality by modulating multi-system physiological dysregulation.
Abstract MP36: Anemia, Chronic Kidney Disease, and Incident Heart Failure: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Ishigami Junichi , Grams Morgan E , Naik Rakhi P , Caughey Melissa C , Loehr Laura R , Coresh Josef , Matsushita Kunihiro
Published: July 2021

Background:
Both chronic kidney disease (CKD) measures, estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR), are associated with incident heart failure (HF). Anemia is thought to play an important role in this association, particularly when eGFR is reduced, but this concept has not been rigorously evaluated.

Methods:
Using data from 5,539 participants in the Atherosclerosis Risk in Communities (ARIC) study at the fourth visit (1996-98), we first assessed the prevalence ratio (PrR) of anemia for eGFR and ACR using cross-sectional Poisson models, and then prospectively quantified the associations of eGFR, ACR, and anemia with incident HF using Cox proportional hazard models.

Results:
Based on the WHO definition, 477 (8.6%) participants had anemia at baseline. Both CKD measures were associated with increased prevalence of anemia independently of each other and other potential confounders (PrR, 1.22 [95% confidence interval, 1.11-1.34] with every 1SD decrease in eGFR; and 1.12 [1.03-1.23] with every 1SD increase in log
10
ACR). There were 724 (13.1%) cases of incident HF over median follow-up of 14.8 years. Lower eGFR and higher ACR were independently associated with increased risk of HF regardless of anemia status (Figure A for eGFR, and B for ACR). The association between anemia and HF risk was generally consistent in the range of eGFR below 90 ml/min/1.73m
2
and ACR between 5 and 300 mg/g, without significant interaction between both CKD measures and anemic status (e.g., hazard ratio for anemia vs. no anemia: 1.40 [0.81-2.41] at eGFR 60 ml/min/1.73m
2
and 1.37 [0.67-2.80] at ACR 30 mg/g).

Conclusions:
Reduced eGFR and elevated ACR were independently associated with higher prevalence of anemia and HF risk. The contribution of anemia to HF risk was overall consistent across CKD ranges of eGFR and ACR. Our results suggest the need of clinical attention on anemia and related HF risk in persons with low eGFR as well as those with high ACR.
Abstract MP41: Disentangling the Effects of Aging and Menopausal Status on Cardiovascular Risk Factors
Authors: Dam Veerle , de Kat Annelien C , Onland-Moret N. C , Eijkemans Marinus J , Broekmans Frank J , van der Schouw Yvonne T
Published: July 2021

Introduction:
Menopause is thought to be associated with adverse cardiovascular disease (CVD) risk factors, in particular lipid levels, but risk factors also deteriorate because of natural aging.

Hypothesis:
We hypothesized that menopausal status has an effect on CVD risk factors independent of age.

Methods:
We used data from LifeLines, a population-based prospective cohort study in the Netherlands. Female participants aged 18-65 years old were divided into groups according to menopausal status: pre- (n=42,987), peri- (n=14,266), natural post- (n=11,175) and surgically postmenopausal (n=5,234). To assess the effect of menopausal status, we compared mean risk factor levels by menopausal status, within one-year age strata, using linear regression. We assessed the effect of age per year on mean CVD risk factor level, within each menopausal status, using linear regression and splines to check for non-linearity. Models were adjusted for oral contraceptive use, smoking status and body mass index (BMI).

Results:
As expected, systolic and diastolic blood pressure (SBP, DBP), and low-density lipoprotein cholesterol (LDL-c) levels increased with age for women in each menopausal status; but high-density lipoprotein cholesterol (HDL-c) also increased. The increase of SBP with age seemed more pronounced in premenopausal women (Figure 1). SBP levels were significantly higher in premenopausal women compared to peri-, natural post- and surgically postmenopausal women. Natural and surgically postmenopausal women had significantly higher LDL-c levels compared to premenopausal women. HDL-c levels were highest in natural postmenopausal women and lowest in surgically postmenopausal women. BMI increased slightly with age, and roughly stabilized from age 45. BMI was lowest in postmenopausal women, higher for pre- and perimenopausal women and highest for surgical postmenopausal women.

Conclusions:
This study provides evidence for an effect of menopausal status on CVD risk factors, independent of biological aging.
Abstract P014: Association Between Serum Resistin Levels and Coronary Artery Disease: A Meta-analysis
Authors: Agasthi Pradyumna , Aloor Sivakanth , Yarlagadda Vivek , Chenna Avantika , Menon Vivek , Purushothaman Kothandaraman
Published: July 2021

Background:
Resistin is a cysteine-rich peptide primarily secreted by inflammatory cells and adipocytes. Recent studies have linked resistin to metabolic syndrome and obesity. It is hypothesized that resistin promotes the expression of adhesion molecules on the vascular wall and induces smooth muscle cell proliferation contributing to coronary atherosclerosis. A meta-analysis was performed to evaluate the association between serum resistin levels and coronary artery disease (CAD).

Methods:
We searched MEDLINE, CINAHL and COCHRANE databases for studies reporting serum-resistin levels in the patients with CAD and healthy controls. Meta-analysis included case controls, cohort and cross-sectional studies. A calculation of weighted standardized mean difference (SMD) in serum resistin level between the CAD and control groups was conducted. Residual maximum likelihood (REML) metaregression was performed on age, body mass index (BMI) and sex covariates.

Results:
A literature search yielded 158 articles, but only 22 studies enrolling 8364 participants were included in the meta-analysis. The median age and BMI of the CAD group was 62 yrs.(IQR 56-64) and 27 kg/m
2
(IQR 26-30) versus 57 yrs.(IQR 51-62) and 26 kg/m
2
(IQR 24-30) in the control group. There were more females in the control group 41% (IQR 31-54) versus 31% (IQR 24-40) in CAD group. The unweighted median serum resistin levels in the CAD group were 9.6 ng/ml (IQR 6.1-15.6) versus 6.4 ng/ml (IQR 3.9-11.5) in the control group. The SMD of serum resistin level was 1.06 (95% CI 0.74-1.37),
P
<0.001 comparing those in the CAD group and control group. None of the covariates (age, BMI and sex) accounted for statistical significance.

Conclusion:
An elevated serum resistin level is significantly and independently associated with presence of CAD. Further studies are needed to confirm this association by adjusting for potential confounders and evaluate the role of resistin in the risk stratifying patients with CAD.