bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19602: Characterization of Tgfβ/BMP-axis in Multiple Animal Models of PH
Authors: Happé Chris , Rol Nina , Da Silva Goncalves Bos Denielli , van der Bruggen Cathelijne , Vonk-Noordegraaf Anton , de Man Frances , Bogaard Harm Jan
Published: July 2021

Introduction:
Mutations in the bone morphogenetic protein recptor type 2 (BMPR2) comprise a large portion of familial Pulmonary Arterial Hypertension (PAH) cases. The transforming growth factor-β (TGF-β)/BMP-axis in PAH has been of interest, which is hypothesized to favor TGF-β signaling due to defective BMPR2 signaling, consequently leading to pro-proliferative signaling within the lung. In addition, it has been proposed that the BMPRII mutations might affect cardiac adaptation. To date none of the available animal models have been fully characterized with regard to the TGF-β/BMP pathway. This study assessed the lung and heart TGF-β/BMP-axis in multiple rat animal models of pulmonary hypertension to ensure translational capability.

Methods:
Heart and lung TGF-β/BMP-axis was assessed by qPCR, western blot and immunofluorescence in the the monocrotaline (MCT), Sugen-hypoxia (SuHx), Sugen-Pneumonectomy (SuPnx) and Pulmonary artery banding model (PAB) and compared to control and PAH patient tissues. Circulating ligands, TGF-β receptor (TGFβR) type 1 and 2 and BMPR2, and canonical downstream signaling (Smad2/3, Smad1/5/8, and transcription factors) were investigated.

Results:
BMPR2 was down-regulated at both transcription and protein levels in the lung of all PH animal models (p<0.05). Transcription of pulmonary TGFβR1 and -2 were increased in the SuPNx-model, compared to control (P<0.001). In both SuHx and SuPnx models an increase in protein Smad2/3 expression was observed by immunofluorescence implying overactivation of TGF-β signaling. Cardiac TGFβR1 was decreased in PAB model, compared to control (P<0.05), while TGFβR2 was decreased in both the MCT and PAB model.

Conclusion:
Early indications reveal differences between several pulmonary hypertension animal models, with regard to the TGF-β/BMP pathway. Additional analysis is needed to fully characterize the regulation of TGF-β and BMP in the rat models.
Abstract 19622: Trans-apical Off-pump Mitral Valve Repair With Neochords Implantation: One Year Clinical and Echocardiographic Follow-up
Authors: Colli Andrea , Besola Laura , Bagozzi Lorenzo , Manzan Erica , Bizzotto Eleonora , Zucchetta Fabio , Bellu Roberto , Sarais Cristiano , Pittarello Demetrio , Gerosa Gino
Published: July 2021

Introduction:
TOP-MINI is a new micro invasive surgical procedure to treat degenerative mitral valve regurgitation due to flail/prolapse.

Hypothesis:
This prospective single centre study sought to assess the safety and effectiveness of the TOP-MINI procedure up to one year follow-up.

Methods:
Clinical and Echocardiographic outcomes were evaluated at 1, 3, 6 months and 1 year follow-up for all patients underwent TOP-MINI procedure from November 2013 to March 2015.

Procedural success was defined as residual MR≤2+ at any time.

Results:
Sixty-one patients were treated during study period. One year survival was 96.7±2.3%. Freedom from MR>2+ is shown in figure 1 Panel A, Freedom from MR>2+ according to valve anatomy (Type A isolated P2 disease, Type B posterior multisegment disease, Type C anterior or bileaflet and/or calcified disease) is shown in Figure 1 Panel B. Freedom from MR>2+ according to STS risk profile is shown in Figure 2. The trend of Echocardiographic parameters is shown in Figure 3.

Conclusions:
TOP-MINI is a safe and effective procedure at 1 year FU. Residual MR is influenced by valve anatomy showing good results in Type A and B patients. Future techniques refinements are needed in order to improve outcomes of Type C patients. The lack of annuloplasty procedure does not influence negatively left ventricle reverse remodeling.
Abstract 19953: Interactions of MyD88 and TRIF-Pathways of Innate Immune Responses Regulate Angiotensin II Hypertension
Authors: Singh Madhu V , Cicha Michael Z , Chapleau Mark W , Abboud François M
Published: July 2021

We have reported that angiotensin II (Ang II) induces toll-like receptors (TLRs) in the innate immune system. Here we tested which of the two major adaptor proteins of TLRs, the myeloid differentiation protein 88 (MyD88) or the TIR-domain containing adaptor inducing interferon β (TRIF) mediates the Ang II-induced responses. Infusion of Ang II (3000 ng/kg/min) subcutaneously for 3 weeks in WT mice (C57BL/6J) increased systolic blood pressure to a peak value of 147 ± 4 mm Hg and resulted in a 40% increase in heart weight to body weight ratio (HW/BW). Surprisingly, in MyD88-/- mice the pressor response was enhanced significantly to 163 ± 6 mm Hg (P<0.05) and the HW/BW was increased by 60%. Cardiac and renal RNA expression of TNF-α, NOX4 and Type IA -Ang II receptor were also significantly more elevated in MyD88-/- than in WT. In contrast, in a mouse strain with nonfunctional TRIF gene, Trifmut (C57BL/6J-Ticam1Lps2/J), all the Ang II responses were either uniformly decreased or abrogated. We tested whether the enhanced response in MyD88-/- mice represented a phenomenon of ‘Signaling Flux Redistribution” whereby blockade of one signaling pathway (i.e., MyD88) results in a flux of signaling substrates through the alternative pathway (TRIF). We found that expression of the RNA for chemokine CXCL10 which is dependent on TRIF pathway, was significantly enhanced in MyD88-/- hearts. We also found that expression of transcripts for TLR3, TLR4 and the TRIF adaptor protein were all enhanced in MyD88-/- and must have contributed to the exaggerated Ang II response. Conversely, Trifmut had enhanced MyD88 expression. These results suggest that: (1) Ang II induced hypertension, hypertrophy and inflammatory gene expression are primarily mediated by the TRIF pathway and (2) the MyD88 pathway is simultaneously activated by Ang II and exerts a negative regulatory influence on the pressor and inflammatory responses. We conclude that dual activation of two innate immune pathways defines the net response in WT mice with a significant translational potential. Accordingly, impairment of MyD88 may contribute to pathogenesis of hypertension. Conversely, targeting the TRIF pathway may be therapeutic by blocking the inflammatory response and enhancing the negative regulatory effects of MyD88.
Abstract 20047: Validation of the Simple Acute Coronary Syndrome (SACS) Score for Identifying Obstructive Coronary Artery Disease
Authors: Matta Daniel , Marsalisi Christina , Ruppert Wayne , Korabathina Ravi
Published: July 2021

Background:
Each year, up to 136,000 individuals suffering from acute coronary syndrome (ACS) are misdiagnosed and discharged from our nations’ emergency departments. We developed the Simple Acute Coronary Syndrome (SACS) score that tabulates a patient’s symptoms, ECG findings, risk factors, and cardiac markers (Figure 1). Our aim was to validate this novel scoring tool in its ability to identify the presence of obstructive coronary artery disease (CAD).

Methods:
A single-center retrospective chart review was performed after institutional review board approval. The charts of 42 consecutive patients who presented with ACS and who were treated with an invasive strategy were reviewed. Scores were calculated for each patient using the SACS tool as well as the Modified Thrombolysis in Myocardial Infarction (TIMI) ACS calculator. The study endpoint was the presence of at least one vessel obstructive CAD at cardiac catheterization. Descriptive statistics were employed.

Results:
The stratification of SACS and Modified TIMI scores for each of the 42 ACS patients is shown in Figure 2. In patients with a SACS score that was less than 3, none of these patients were found to have obstructive CAD at cardiac catheterization. For patients with a SACS score of 4 or higher, 100% of these patients were shown to have obstructive CAD. For patients with Modified TIMI scores of 1 and 2, 3/11 (27%) were found to have obstructive CAD.

Conclusions:
The novel SACS scoring system identifies ACS patients who will have obstructive CAD more reliably than more traditional scoring systems. The SACS scoring tool needs to be validated in larger scale studies.
Abstract 9772: Antagonism of Rosuvastatin-induced Elevation of Circulating PCSK9 in Hamsters by Liver-specific Knockdown of HNF1α or HNF1β
Authors: Dong Bin , Singh Amar B , Shende Vikram R , Liu Jingwen
Published: July 2021

Proprotein convertase subtilisin/kexin type 9 (PCSK9) induces hepatic LDL receptor (LDLR) degradation and lowers the removal of LDL-cholesterol from circulation. Thus, PCSK9 has become an important therapeutic target for the treatment of hypercholesterolemia. The transcription of PCSK9 is prominently controlled by the HNF1 binding motif embedded in its proximal promoter region that binds to HNF1α or HNF1β as homodimers or heterodimers. Our previous in vivo studies showed that only HNF1α but not HNF1β regulates PCSK9 transcription in mouse liver. Statin has been shown to elevate circulating PCSK9 levels through stimulating PCSK9 gene transcription, which reduces the clinical efficacy of statin in LDL-cholesterol reduction. In this study, we utilized adenoviral shRNA expression vectors (Ad-shHNF1α and Ad-shHNF1β) to generate liver specific knockdown of HNF1α or HNF1β in hamsters to examine the impact of reduced expression of HNF1 transcription factors on statin-induced elevation of PCSK9. Administration of rosuvastatin (RSV) at a daily dose of 15 mg/kg to hamsters infected with a control adenovirus significantly increased liver PCSK9 mRNA levels by 94% and serum PCSK9 levels by 37%. However, injection of Ad-shHNF1α into hamsters largely abolished the RSV-induced elevation of PCSK9 serum levels and hepatic mRNA levels, which was accompanied by a significant increase in liver LDLR protein abundance by 64% as compared to hamsters injected with control virus. Surprisingly, injection of Ad-shHNF1β produced similar inhibitory effects on the RSV-induced PCSK9 expression as that of Ad-shHNF1α. This was different from the negative results of HNF1β knockdown conducted in mice. In addition to changes in PCSK9 levels, we observed a modest but significant reduction in serum non-HDL cholesterol level after knockdown of HNF1α (27%) or HNF1β (32%) in hamsters treated with RSV. Altogether, our study demonstrates that unlike mice, both HNF1α and HNF1β are positive regulators of hepatic PCSK9 transcription in hamster species and that transient, liver specific knockdown of either HNF1α or HNF1β could antagonize the RSV-induced elevation of serum PCSK9 and non-HDL cholesterol levels.
Abstract 9778: Establishing Inter Rater Reliability of the National Early Warning Score (NEWS)
Authors: Miller Donna M
Published: July 2021

A change in patient condition is a dynamic process which can go unrecognized and result in a failure to rescue. Changes in patients’ vital signs can precede adverse events many hours before critical events such as cardiac arrest or emergent transfer to the Intensive Care Unit occurs.

Quantitative assessment tools are used to predict risk and need for additional resources at the bedside. These tools are referred to as Early Warning Scoring Systems. The Royal College of Physicians developed a standardized tool called the National Early Warning Score (NEWS, 2012) that uses a variety of physiologic parameters to assess risk and establish a trigger threshold for summoning additional resources.

Purpose:
Early warning scoring tools have been found to be reliable and accurate in predicting patient decompensation. However, data from instruments are only as reliable and accurate as the caregiver who obtains and documents the parameters. The purpose of this study was to establish inter rater reliability between the RN and PCA using NEWS.

Design, Sample, Setting, Procedures:
This study was conducted on the clinical units of a 104 bed Long Term Acute Care Hospital (LTCH) system. These units accept patients directly from Intensive Care Units who require intense services to maintain their trajectory toward recovery. The NEWS provides a way for early detection of patient decompensation which can prevent readmission to acute care and the subsequent financial implications

The convenience sample consisted of 22 RNs and 6 PCAs. Consented subjects reviewed an unfolding case study that portrayed a typical patient on the LTCH unit. Subjects were asked to circle the parameter ranges on the NEWS tool that corresponded to physiologic values in the scenario.

Findings:
Krippendorff’s alpha was utilized to determine the level of agreement among the raters examining the three scenarios. An alpha value of 0.94 was obtained indicating a high level of agreement among the raters.

Conclusion:
The NEWS can serve as a reliable adjunct to the provision of safe patient care. While it is not the sole source for determining
Abstract 9839: Beta Blockers Improve Renal Tissue Oxygenation in Hypertensive Patients Suspected of Renal Artery Stenosis
Authors: Hall Michael E , Rocco Michael V , Morgan Timothy M , Hamilton Craig A , Jordan Jennifer H , Edwards Matthew S , Hall John E , Hundley William G
Published: July 2021

Background:
Chronic renal hypoxia influences the progression of chronic kidney disease (CKD). Blood oxygen level dependent (BOLD) magnetic resonance (MR) is a noninvasive tool for assessment of renal tissue oxygenation. Beta blockers reduce cardiovascular mortality in patients with CKD and systolic heart failure, however the mechanisms of this benefit remain unclear. We sought to determine the association between beta blocker use, renal cortical and medullary oxygenation, and renal blood flow in hypertensive patients suspected of renal artery stenosis.

Hypothesis:
Chronic receipt of beta blockers will be associated with improved renal tissue oxygenation as assessed by BOLD MR.

Methods:
We measured renal cortical and medullary oxygenation using BOLD MR and renal artery blood flow using MR phase contrast techniques in 38 participants suspected of renal artery stenosis.

Results:
Chronic beta blocker therapy was associated with improved renal cortical (p=0.0007) and medullary (p=0.03) oxygenation (Figure). Receipt of angiotensin converting enzyme inhibitors or angiotensin receptor blockers was associated with reduced medullary oxygenation (p=0.01). In a multivariable model including gender, hemoglobin, diabetes, loop diuretic use, and mineralocorticoid use, chronic receipt of beta blockers was the only significant predictor of renal tissue oxygenation (β= 8.4, p=0.008).

Conclusions:
Beta blocker therapy was associated with improved renal oxygenation independent of renal blood flow suggesting may these findings may be related to reduced renal oxygen consumption. In addition to their known benefits to reduce cardiovascular mortality in patients with renal disease, beta blockers may reduce or prevent progression of renal dysfunction in patients with hypertension, diabetes, and renovascular disease. These observations may have important implications for treatment of patients with CKD.
Abstract 9918: Respiration Increases Ventricular Filling at Rest and Exercise via Pulmonary Compliance: A Clinical and Computational Modeling Study
Authors: Kung Ethan , Van De Bruaene Alexander , Claessen Guido , La Gerche Andre , Marsden Alison , De Meester Pieter , Devroe Sarah , Bogaert Jan , Claus Piet , Heidbuchel Hein , Budts Werner , Gewillig Marc
Published: July 2021

Introduction:
Due to the absence of a sub-pulmonary ventricle, the Fontan circulation is sensitive to respiration-induced changes in intrathoracic pressure. However, the importance of a ‘respiratory pump’ in creating forward flow remains controversial. We aim to investigate the effects and mechanisms of respiration on ventricular filling at rest and exercise using clinical data and computational modeling.

Hypothesis:
We assess the hypotheses that (1) changes in intrathoracic pressure due to respiration would aid ventricular filling and output and (2) this effect would be maintained or enhanced during incremental exercise.

Methods:
Ten Fontan patients (6 male, 20±4 years) underwent ungated cardiac magnetic resonance imaging at rest and during supine bicycle exercise (3 incremental intensities) to evaluate systemic ventricular volumes. Patient-specific computational simulations using a lumped-parameter network model of Fontan exercise elucidated resting and exercise physiology in details for each patient at each metabolic state tested.

Results:
Compared to expiration, inspiration increased EDVi (98±16 to 103±15 mL/m2;P=0.001), SVi (55±9 to 59±9 mL/m2;P=0.001) and cardiac index (3.9±0.7 to 4.2±0.8 L/min/m2;P=0.002), but did not affect ESVi (P=0.096). Respiratory-dependent SVi did not change significantly during incremental exercise (3±2% to 5±3%; P=0.084). Computational modeling showed highest caval vein flow return during end-inspiration, and peak SV during expiration, exposing a phased time-delay mechanism at work. Removal of respiration in simulations corresponded to decreases in cardiac index of 0.39±0.037 L/min/m2.

Conclusions:
Inspiration increased ventricular filling at rest and exercise by similar amounts. A phased time-delay between highest caval vein flow and highest SV suggests an indirect mechanism where respiration aids ventricular filling via pulmonary compliance.
Abstract 9964: Plaque Morphology, Plaque Composition and Spatial Distribution of the Sites of Potential Vulnerability of Culprit Lesions Implicated in Acute Myocardial Infarction
Authors: Zheng Guian , Li Yuxin , Hiro Takafumi , Takayama Tadateru , Higuchi Yoshiharu , Fukamachi Daisuke , Haruta Hironori , Sudo Mitsumasa , Nishida Toshihiko , Saito Satoshi , Hirayama Atsushi
Published: July 2021

Background:
The role of plaque morphology, composition, and spatial distribution in plaque rupture and coronary occlusion in patients suffering acute myocardial infarction (AMI) needs clarification. Using color-mapping iMAP intravascular ultrasound (iMAP-IVUS), we examined culprit lesions to clarify plaque morphology, plaque composition and spatial distribution of the sites of potential vulnerability.

Methods:
Sixty-eight culprit lesions in 64 consecutive AMI patients who underwent angiography and IVUS examinations before intervention were analyzed. Plaque morphology and composition were quantified and compared between totally occlusive (TO) (n=42) and non-TO lesions and between ruptured (n=27) and non-ruptured lesions.

Results:
Both the length and plaque burden (PB) of TO lesions were greater than those of non-TO lesions (54.16 ± 21.16 mm versus 40.01 ± 17.51 mm, respectively, p = 0.006; PB: 0.63 ± 0.07 versus 0.58 ± 0.08, respectively, p = 0.02). Ruptured lesions were coincident with significant vessel remodeling (vessel volume: 745.5 ± 41.3 mm3 versus 635.7 ± 33.5 mm3, p = 0.04) and plaque volume (450.0 ± 23.8 mm3 versus 387.7 ± 19.3 mm3, p = 0.046). Also, the lipidic volume was greater (57.6 ± 3.8 mm3 versus 46.9 ± 3.1 mm3, p = 0.03) and the necrotic volume (152.6 ± 12.1 mm3 versus 125.8 ± 9.8 mm3, p = 0.09) tended to be greater in ruptured lesions. Examination of the longitudinal distribution of the sites of recognized vulnerability, i.e., maximum necrotic area (maxNA), maximum PB (maxPB) and most severely narrowed (minimal luminal area, MLA) revealed that most maxNA sites and maxPB sites were proximal to MLA sites. Ruptures usually occurred very close to maxNA sites (average distance: 0.33mm, 44% were proximal to, 26% overlapped and 30% were distal to a maxNA site) and proximal to maxPB and MLA sites.

Conclusion:
Plaque morphology and composition play critical roles in plaque rupture and coronary occlusion. The maxNA sites are the sites most likely to rupture, and most ruptures occur proximal to maxPB sites and MLA sites.
Abstract 9978: Effect of Balloon Pulmonary Angioplasty on Respiratory Function in Patients With Chronic Thromboembolic Pulmonary Hypertension: Different Effects According to the Lung Field Involved
Authors: Akizuki Mina , Serizawa Naoki , Ueno Atuko , Adachi Taku , Hagiwara Nobuhisa
Published: July 2021

Background:
Treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with balloon pulmonary angioplasty (BPA) reportedly improves hemodynamics, exercise capacity, and right ventricular function. However, the effect of BPA on respiratory functions is unclear.

Methods:
We enrolled consecutive patients with inoperable CTEPH who underwent BPA. BPA was performed primarily on the lower lobe arteries during the first series and on the upper and middle lobe arteries during the second series. We examined right heart catheterization, the respiratory function test, and the cardiopulmonary exercise test, and compared the change in these parameters according to the BPA performed field (divided into the upper-middle and lower lobe before BPA, after BPA, and the follow-up period).

Results:
In total, 62 BPA sessions were performed in 13 CTEPH patients. Hemodynamics significantly improved after BPA (mPAP: 44±8 to 24±5 mmHg, PVR: 818±383 to 293±68 dyne/s/cm-5), and WHO-FC improved from 3.1±0.3 to 2.2±0.6 after BPA. Hemodynamic improvement tended to be larger in BPA in the lower lung field. The %DLco significantly decreased (p=0.001) in BPA in the lower lung field, and did not appear to recover during the follow-up period. In contrast, %DLco significantly increased in BPA in the upper-middle lung field (p=0.030), and tended to increase until the follow-up period (p=0.077) (Fig). In addition, VE/VCO2 slope significantly improved after BPA in the lower lung field (p=0.014), and showed further improvement at the follow-up period (p=0.007); however, VE/VCO2 slope remained unchanged after BPA in the upper-middle lung field (Fig). Furthermore, during follow-up, change in %DLco and VE/VCO2 slope were significantly different between lower and upper-middle lung field BPA performed (p<0.001 and p=0.020, respectively, Fig).

Conclusions:
We observed that the effect of BPA in CTEPH patients may have a different effect on respiratory function according to the lung field.
Abstract 10: Widening Rural Disadvantage in United States Premature Heart Disease Mortality: Trends by Region and Race/Ethnicity, 2000 - 2013
Authors: Pathak Elizabeth B , Forsyth Colin J
Published: July 2021

Objectives:
The purpose of this study was to quantify rural and metropolitan trends in premature heart disease (HD) mortality using the most up-to-date data available (through 2013). To our knowledge this is the first study to analyze these geographic disparities for Hispanics (HSP), Asians/Pacific Islanders (API), and American Indians/Alaska Natives (AI/AN).

Methods:
Annual age-adjusted HD death rates for adults aged 25-64 years were analyzed for 2000-2013. Rates were calculated for 5 racial/ethnic groups (Non-Hispanic Whites (WNH), Non-Hispanic Blacks (BNH), HSP of any race, Non-Hispanic API, and Non-Hispanic AI/AN). County-level data were aggregated by urbanicity: large central metro (LCM), large fringe metro (LFM), medium/small metro (MSM), and micropolitan/rural (RURAL). Region was defined as South (16 states) and Non-South. All data were obtained from the National Vital Statistics System on CDC WONDER. Average annual percent change (AAPC) was calculated by linear regression of the log-transformed death rates using SAS 9.4.

Results:
In 2013, the national population-at-risk predominantly resided in metro areas. However, there were more than 10 million RURAL adults aged 25-64 years in the South (16.2% of the region) and more than 13.4 million in the non-South (12.9% of the region). Nationwide, HD death rates were lowest in the LFM counties. In the South, the rate ratio (RR) for RURAL vs. LFM areas in 2011-2013 was 1.76 (95% CI 1.73 to 1.79) for WNH, 2.00 (95% CI 1.85 to 2.16) for HSP, 1.78 (95%CI 1.71 to 1.82) for BNH, 1.57 (95% CI 1.22 to 2.03) for API, and 3.13 (95% CI 2.47 to 3.96) for NNH. In the non-South, RURAL vs. LFM RRs were smaller, with the exception of API (RR 2.37, 95% CI 2.07 to 2.71). Temporal trend analyses revealed significantly smaller AAPC in RURAL areas (see Table).

Conclusions:
Higher death rates coupled with slower declines have resulted in a widening rural disadvantage in premature HD mortality in the United States from 2000 to 2013, particularly for WNH, HSP, BNH, and AI/AN in the South, and WNH in the non-South.
Abstract 25: Favorable Modifiable Cardiovascular Risk Profile is Associated with Lower Healthcare Costs: The 2012 Medical Expenditure Panel Survey
Authors: Valero-Elizondo Javier , Salami Joseph A , Ogunmoroti Oluseye , Aneni Ehimen C , Malik Rehan , Spatz Erica S , Rana Jamal S , Virani Salim S , Blankstein Ron , Blaha Michael J , Veledar Emir , Nasir Khurram
Published: July 2021

Background:
The AHA’s 2020 Strategic Goals emphasize the value of favorable modifiable risk factor (MRF) profile to reduce the burden of CVD morbidity and mortality. In this study we aimed to quantify the overall and incremental impact of MRF on health care expenditure in the U.S among those with and without CVD.

Methods:
The study population was derived from the 2012 Medical Expenditure Panel Survey (MEPS), a nationally representative adult sample (≥ 40 years). Direct costs were calculated for all-cause health care resource utilization. Variables of interest included CVD diagnoses (coronary artery disease, stroke, peripheral artery disease, dysrhythmias or heart failure), ascertained by ICD-9-CM codes, and MRF (hypertension, diabetes mellitus, hypercholesterolemia, smoking, physical activity and/or obesity). 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, taking into consideration the survey’s complex design.

Results:
The final study sample consisted of 15,651 MEPS participants (57 ± 12 years, 52% female). Overall, 6,231 (39%) had 0-1, 7,429 (49%) had 2-3, and 1,991 (12%) had ≥ 4 MRF, translating to 55.5, 69.9 and 17.9 million adults ≥ 40 years in U.S, respectively. Generally, there was a direct decrease in health expenditures with favorable MRF across CVD status (Table). These differences persisted after taking into account demographics, insurance status and comorbid conditions. Among those without established CVD, the average medical expenditure was $4,013 (95% CI 5,117, 2,910) and $2,696 (95% CI 4,416, 977) lower for those with 0-1 & 2-3 MRF, as compared to those with ≥ 4 MRF.

Conclusion:
Favorable MRF profile is associated with significantly lower medical expenditure among individuals with and without established CVD. Our study provides robust estimates for potential healthcare savings with nationwide policies focusing on preventing and managing modifiable CV risk factors.
Abstract 47: Weight-loss Diets, Adiponectin, and Changes of Cardiometabolic Risk in the 2-year Pounds Lost Trial
Authors: Ma Wenjie , Huang Tao , Zheng Yan , Wang Molin , Bray George A , Sacks Frank M , Qi Lu
Published: July 2021

Background:
Evidence suggests that the beneficial effects of weight-loss diet interventions on improvement in cardiovascular risk factors may be partly through modulating secretion of adiponectin from adipose tissue. However, it remains unclear whether the long-term weight-loss diets change adiponectin levels; and how such changes, if exist, affect cardiometabolic risk.

Objectives:
To investigate effects of weight-loss diets with different compositions of macronutrients on long-term changes of circulating adiponectin concentrations and cardiometabolic risk factors, as well as dietary interactions with variation in the adiponectin gene.

Methods:
In the 2-year Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, 811 overweight or obese adults were randomly assigned to 1 of 4 diets; the targeted percentages of energy derived from fat, protein, and carbohydrates in the 4 diets were 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%. The current analysis was restricted to participants who had baseline plasma adiponectin measurement (n=768). Circulating adiponectin and cardiometabolic outcomes were repeatedly measured at baseline, 6 months, and 2 years. We genotyped single-nucleotide polymorphism rs266171 in the adiponectin gene. Linear mixed models were used to compare changes in adiponectin concentrations across diet groups over the intervention and predict trajectory of changes in cardiometabolic risk factors.

Results:
Circulating adiponectin concentrations significantly increased over 2 years, similarly in 4 weight-loss diet intervention groups. Change of plasma adiponectin was significantly associated with decreases in weight, waist circumference, triglycerides, fasting insulin, and insulin resistance measured by homeostasis model assessment of insulin resistance (HOMA-IR), and increase in HDL cholesterol, after adjusting for age, gender, ethnicity, follow-up time, diet group, and baseline level of respective outcome trait. The associations remained similar after further controlling for concurrent weight change. In addition, we observed significant interactions between rs266717 genotype and dietary fat on changes in fasting insulin and HOMA-IR (P for interaction=0.03 for both) at 6 months with adjustment for covariates. Participants who are homozygous for T allele of rs266717 had more reductions in fasting insulin and HOMA-IR than those with other genotypes in response to the high-fat diet, but such differences were not observed in the low-fat diet group.

Conclusions:
Regardless of macronutrient compositions, weight-loss diets beneficially increased circulating adiponectin, which was related to improvement of cardiometabolic profiles. Dietary fat intakes modified the effect of adiponectin variant rs266717 on improvement of insulin resistance.
Abstract MP85: Fitbit Provides Valid Measures of Sedentary and Physical Activity in Preschool Children
Authors: Byun Wonwoo , Barry Allison , Lee Jung-Min , Kim Youngdoek
Published: July 2021

Introduction:
Both monitoring and promoting PA in children, two important areas in epidemiologic research, require the use of accurate and feasible measurement tools. The Fitbit activity monitor is one of the most widely commercialized, consumer-based activity monitors and its validity and reliability has been determined in adults; however, little research has determined the validity of Fitbit activity monitor in measuring sedentary behavior and PA in preschool-age children.

Hypothesis:
We hypothesized that, when comparing to the direct observation (DO), the Fitbit Flex (FF) activity monitor would accurately measure the time spent in sedentary, moderate-to-vigorous PA (MVPA), and Total (light-to-vigorous) PA in preschool-age children.

Methods:
A total of 28 preschool age children (Female: 46%, Age: 4.6 ± 1.0 yrs, BMI: 16.4 ± 1.5 kg·m2) wore the FF (on the wrist) and were directly observed while performing a set of unstructured and structured activities with varying intensity levels such as watching TV, drawing, playing with toys, playing soccer, and shooting basket. Breath-by-breath oxygen consumption were also measured using Oxycon Mobile indirect calorimetry (OM). Data from the FF (PA counts) and the OM (VO2 ml·kg·min-1) were summarized in terms of minute-by-minute basis. The validity of FF for measuring the time spent in sedentary behavior, MVPA, and Total PA against DO was examined using three ways: (1) Pearson correlation examining the relatively agreement between FF and DO; (2) Mean absolute percent error (MAPE) examining the measurement errors of FF; and (3) One-sided equivalence test examining the absolute agreement between FF and DO by comparing the 90% confidence intervals (CI) of the estimates from the FF with the respective equivalence zone (EZ; ± 10% of the mean estimates from the DO).

Results:
On average, oxygen consumptions for sedentary, light, MVPA were 9.0 ± 1.6, 14.9 ± 3.9, 23.5 ± 5.5, and 33.8 ± 5.6 ml·kg·min-1, respectively. Correlations between FF and DO were consistently high for sedentary (r = 0.81, P <.001), MVPA (r = 0.62, P <.001), and Total PA (r = 0.81, P <.001). MAPEs were 8.2%, 21.1%, and 8.2% for sedentary, MVPA, and Total PA, respectively. The estimates from the FF were not significantly equivalent to those from the DO; sedentary (FF: Mean (M) = 7.8 min, 90% CI: 7.3 - 8.3 min vs. DO: M = 6 min, EZ: 5.4 - 6.6 min), MVPA (FF: M = 7.2 min, 90% CI: 6.2 - 8.2 min vs. DO: M = 12 min, EZ: 10.8 - 13.2 min), and Total PA (FF: M = 14.0 min, 90% CI: 13.6 - 14.4 min vs. DO: M = 16 min, EZ: 14.4 - 17.6 min).

Conclusions:
The validity of the FF was supported by the consistently high correlations with the criterion measure. However, inconsistent results from equivalence testing warrants subsequent assessment of the validity of the FF as it has a high potential for replacing research-based PA monitors in preschool-age children.
Abstract MP94: Short Sleep Duration Modifies the Relationship Between Cognitive Impairment Associated with Cardiovascular Disease and All-cause Mortality
Authors: Fernandez-Mendoza Julio , He Fan , Vgontzas Alexandros N , Liao Duanping , Bixler Edward O
Published: July 2021

Introduction:
Short sleep duration has been associated with increased risk of cardiovascular and cerebrovascular disease (CVD), cognitive impairment (CI) and mortality. However, the role of sleep duration in predicting mortality in the context of CVD and CI is still not well-understood.

Hypothesis:
Short sleep duration is a key effect modifier of the relationship between CI associated with CVD and all-cause mortality.

Methods:
We addressed this hypothesis in the Penn State Adult Cohort, a random, general population sample of 1,741 middle-aged adults who were studied in the sleep lab and followed-up for 15y. An in-lab, 8-hour polysomnography was performed to ascertain sleep duration. CI associated with CVD was defined by the presence of hypertension, diabetes, heart disease and/or stroke with impaired higher-order, executive cognitive functioning, including slow processing speed. We tested the interaction between sleep duration and CI associated with CVD on all-cause mortality with multiple logistic regression while adjusting for sex, age, race, obesity, smoking, cholesterol, depression, insomnia, dementia, and sleep apnea.

Results:
The odds of mortality associated with CI-alone, CVD-alone, and CI associated with CVD were 1.3 (95% CI: 0.7-2.4), 1.7 (95% CI: 1.1-2.8), and 4.6 (95% CI: 2.8-7.7), respectively. As shown in Figure 1, the interaction between CI associated with CVD and sleep duration was significant (p < .01), indicating that the probability of mortality increased significantly as a function of shorter sleep duration in individuals with CI associated with CVD.

Conclusion:
We found that objective sleep duration modifies the relationship between CI associated with CVD and all-cause mortality in a dose-response manner. Short sleep duration in individuals with probable vascular cognitive impairment (VCI) may serve as a biomarker of the severity of central autonomic dysfunction. Future studies should examine whether improving sleep reduces the odds of mortality in individuals with VCI.
Abstract P005: Comparative Effectiveness of Rivaroxaban versus Warfarin for the Treatment of Patients with Non-valvular Atrial Fibrillation
Authors: Norby Faye L , Bengtson Lindsay G , Chen Lin Y , MacLehose Richard F , Lutsey Pamela L , Rapson Ian , Alonso Alvaro
Published: July 2021

Background:
Rivaroxaban is a novel oral anticoagulant approved in the US in 2011 for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Information on risks and benefits among rivaroxaban users in real-world populations is limited.

Methods:
We used data from the US MarketScan Commercial and Medicare Supplemental databases between 2010 and 2013. We selected patients with a history of NVAF and initiating rivaroxaban or warfarin. Rivaroxaban users were matched with up to 5 warfarin users by age, sex, database enrollment date and drug initiation date. Ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding outcomes were defined by ICD-9-CM codes in an inpatient claim after drug initiation date. Cox proportional hazards models were used to assess the association between rivaroxaban vs. warfarin use and outcomes adjusting for age, sex, and CHA2DS2-VASc score. Separate models were used to compare a) new rivaroxaban users with new warfarin users, and b) switchers from warfarin to rivaroxaban to continuous warfarin users.

Results:
Our analysis included 34,998 rivaroxaban users matched to 102,480 warfarin users with NVAF (39% female, mean age 71), in which 487 ischemic strokes, 179 ICB, 647 MI, and 1353 GI bleeds were identified during a mean follow-up of 9 months. Associations of rivaroxaban vs warfarin were similar in new users and switchers; therefore we pooled both analyses. Rivaroxaban users had lower rates of ICB (hazard ratio (HR) (95% confidence interval (CI)) = 0.72 (0.46, 1.12))) and ischemic stroke (HR (95% CI) = 0.88 (0.68, 1.13)), but higher rates of GI bleeding (HR (95% CI) = 1.15 (1.01, 1.33)) when compared to warfarin users (table).

Conclusion:
In this large population-based study of NVAF patients, rivaroxaban users had a non-significant lower risk of ICB and ischemic stroke than warfarin users, but a higher risk of GI bleeding. These real-world findings are comparable to results reported in published clinical trials.
Abstract P047: Association of 1,5-anhydroglucitol with Subclinical Cardiovascular Disease
Authors: Liang Menglu , McEvoy John William (Bill) , Chen Yuan , Sharrett A. Richey , Selvin Elizabeth
Published: July 2021

Introduction:
Serum 1,5-anhydroglucitol (1,5-AG) concentrations decrease in the setting of acute hyperglycemia, making 1,5-AG a useful biomarker of glucose peaks. In recent studies, 1,5-AG has been associated with clinical cardiovascular disease events. However, the association between 1,5-AG and subclinical vascular disease is unknown.

Hypothesis:
1,5-AG will be associated with subclinical myocardial damage (assessed by cardiac troponin T measured using a novel highly sensitive assay (hs-cTnT)) and subclinical atherosclerosis (assessed by ultrasound-detected carotid intima-media thickness (cIMT)), particularly in persons with diabetes.

Methods:
We measured 1,5-AG in 10,753 participants in the ARIC Study at visit 2 (1990[[Unable to Display Character: –]]1992) and conducted a cross-sectional analysis to characterize the associations of 1,5-AG with elevated hs-cTnT (≥ 14 ng/L) or thick cIMT (top quartile, ≥0.79 mm) using logistic regression models. We also evaluated the prospective association between baseline 1,5-AG and incident elevated hs-cTnT at 6-years using Poisson regression models.

Results:
Among diabetics, those with 1,5-AG <6 ug/mL were 5 times more likely to have prevalent elevated hs-TnT at baseline compared to non-diabetics with 1,5-AG >10 ug/mL (adjusted OR 4.67, 95%CI, 3.27[[Unable to Display Character: –]]6.68) and almost 2 times more likely to be in the top quartile of the cIMT (adjusted OR 1.75, 95%CI 1.39-2.19). 1,5-AG <6 ug/mL in persons with diabetes was also significantly associated with 6-year incident elevated hs-TnT: RR 2.26 (95%CI, 1.50[[Unable to Display Character: –]]3.39). The associations of 1,5-AG with elevated hs-TnT and thick cIMT were non-linear and mostly driven by persons with diabetes (Figure).

Conclusions:
1,5-AG was associated with prevalent and incident subclinical cardiovascular disease in persons with diabetes in the community. Our results suggest that glucose peaks may be relevant for the development of subclinical cardiac damage and atherosclerosis in persons with diabetes.
Abstract P088: Race is Associated with Endothelial Responses to Acute Mental Stress
Authors: Wilmot Kobina A , Alkhoder Ayman , Isakadze Nino , Obideen Malik , Shah Amit J , Pimple Pratik , Al Mheid Ibhar , Kutner Michael , Long Qi , Lewis Tene , Raggi Paolo , Bremner J. Douglas , Quyyumi Arshed A , Vaccarino I. Viola
Published: July 2021

Introduction:
Endothelial dysfunction is associated with short term and long term cardiovascular events. African Americans (AA) have worse cardiovascular outcomes than Non-African Americans (NAA). AAs have higher chronic stress exposure due to socioeconomic deprivation which may affect vascular responses to stress and contribute to health disparities. Our hypothesis was that AA would have abnormal microvascular function after a standardized mental stress as compared to NAA.

Methods:
We evaluated 692 patients (208 AA) with confirmed coronary artery disease (CAD), who underwent a standardized mental stress challenge. Endothelial function measurements were obtained before and 30 minutes after mental stress testing using a speaking task. Reactive hyperemia index (RHI) was measured using peripheral arterial tonometry (PAT) (Itamar Inc) as the ratio of hyperemic to baseline finger-tip microvascular blood flow signal. Flow-mediated dilation (FMD) was measured using ultrasound as the ratio of hyperemic to baseline brachial artery diameter.

Results:
As compared to NAA, AA patients were younger, had lower levels of education, and income, and a higher prevalence of co-morbidities. AA patients prior to stress had similar mean RHI (2.07 vs 2.13, p=0.3) but lower mean FMD (3.54 vs 4.76, p=0.0005) as compared to NAA. However, after mental stress, mean RHI was significantly lower in AA, (1.98 vs 2.2, p=0.0002) and mean FMD continued to be lower in AA (2.87 vs 3.81, p=0.005). After adjusting for baseline RHI in addition to age, sex, BMI, cardiovascular risk factors, and depression in a multivariable model, race remained significantly associated with post-stress RHI (p= 0.004). However, race was no longer associated with post-stress FMD after adjusting for pre-stress FMD. (p=0.37).

Conclusion:
AA patients with CAD, compared with NAA, have worse baseline endothelial-dependent function, which persists after mental stress. Furthermore, AA have a more pronounced decrease in endothelial function with mental stress compared with NAA. Whether this more adverse vascular reactivity with stress is implicated in race-based disparities in cardiovascular disease requires further study.
Abstract P099: Association Between Arsenic And Heart Failure
Authors: Sivakumar Kalaivani , Adedinsewo Demilade , Onwuanyi Anekwe
Published: July 2021

Background:
Heart failure is a major contributor to morbidity and mortality in the United States. Arsenic, a ubiquitous element, found in drinking water, rice, flour and other grains, has been shown to play a role in the development of arrhythmias and coronary heart disease through vascular endothelial dysfunction and free radical injury. Studies have shown that arsenic induces interstitial myocardial fibrosis and we hypothesize that this may contribute to the development of heart failure.

Methods:
We conducted an analysis of the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Urinary arsenic was evaluated as a combination of inorganic arsenic, and methylated arsenic species (Monomethylarsonic acid and Dimethylarsinic acid) in microgram per gram of urine creatinine. We used a logistic regression model to evaluate the relationship between quartiles of urinary arsenic and heart failure while controlling for confounders. Analyses were conducted using SAS survey procedures and data evaluated at α=0.05.

Results:
The total number of study participants were 2065 adults with the mean age of 40.2 years, approximately half were male (48.8%) and 64.1% were white. There was no significant association between urinary arsenic measures and incidence of heart failure. Persons with high arsenic levels (>75th percentile) were less likely to develop heart failure after controlling for confounders.

Conclusion:
Our results show a statistically significant decrease in the odds of developing heart failure among persons with high arsenic levels (>24ug/g). This is in contrast to other studies, which have shown high arsenic levels to have a toxic effect on the heart. Limitations of our study include the inability to determine the chronicity of exposure and exclude persons with increased levels of organic arsenic from seafood, which are nontoxic. Additional observational and prospective studies are needed to further evaluate this association.
Abstract P106: Dense Low-density and Remnant Lipoprotein Cholesterol are Associated with Adiposity: The Elsa-Brasil Study
Authors: Suemoto Claudia , Bensenor Isabela M , Santos Raul , Bittencourt Marcio S , Martin Seth , Toth Peter , Jones Steven , Blaha Michael , Lotufo Paulo A
Published: July 2021

Introduction:
Obesity is a known risk factor for coronary heart disease, and this relationship may be mediated by the presence of small dense low-density (LDL-3+LDL-4) and remnant (VLDL-3+IDL) lipoproteins. However, few studies with limited sample sizes have investigated the association of small dense low-density (SDLDL) and remnant lipoproteins (RL) with adiposity. One question is about these markers are only an epiphenomenon of high triglycerides or insulin resistance.

Hypothesis:
to verify if these associations are mediated by levels of triglycerides and / or insulin resistance

Methods:
We included 4,189 participants (50.6±8.6 years, 554% women, 58% White) from the ELSA-Brasil study who had no prior history of cardiovascular diseases were not currently using lipid-lowering medications, and had a BMI>18.5kg/m2. We measured the fasting lipoprotein cholesterol fractions using the vertical auto profile ultracentrifugation method. We investigated the association of BMI and WC with SDLDL and RL, using linear regression with a quadratic term for BMI and WC and adjusted for age, gender, HOMA-estimated insulin resistance, and fasting serum triglycerides.

Results:
The mean LDL-3, LDL-4, VLDL-3, and IDL were respectively (mg/dL): 47.5±20.2, 10.5±10.8, 14.9±5.1, and 17.3±7.8. SDLDL had a quadratic association with BMI (linear:β=2.72, SE=0.53, p<0.0001; quadratic:β=-0.04, SE=0.01, p<0.0001), and WC (linear:β=1.94, SE=0.32, p<0.0001; quadratic:β=-0.01, SE=0.002, p<0.0001). RL showed also a quadratic association, mainly with WC (WC-linear:β=0.40, SE=0.13, p=0.002; quadratic:β=-0.002, SE=0.001, p=0.005; and BMI-linear:β=0.51, SE=0.21, p=0.01; quadratic:β=-0.01, SE=0.003, p=0.03).

Conclusion:
In a large cohort of asymptomatic individuals, SDLDL and RL were both associated with measures of adiposity. These results occurred independently of plasma triglycerides and insulin resistance.