bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 5064: Venous Thrombosis after Air Travel: Prevention with Aspirin vs Low-Molecular-Weight Heparin (lmwh) in High-Risk Subjects. A Prospective Study
Authors: Belcaro Gianni , Cesarone Maria Rosaria , Cornelli Umberto
Published: July 2021

LONFLIT studies have observed that in subjects at high-risk (HRS) for deep venous thrombosis (DVT) during/after long (>10 hours) flights, the incidence DVT (by ultrasound scans) may be between 4% and 6% (including subclinical thrombi), This study evaluated DVT prevention in HRS: 886 subjects were approached and 600 were included. They were divided into 3 groups and advised to use during the flights: a:exercise only (no pharmacological prophylaxis) b: aspirin (400 mg tablets, soluble aspirin; one dose daily for 3 days, starting 24 hours before flights) c: low-molecular-weight heparin (LMWH; enoxaparine - Lovenox - injected 2– 4 hours before flights. The single dose was weight-adjusted (1000 IU - equivalent to 0.1 ml per 10kg of weight). Subjects with possible problems due to aspirin or LMWH, using anticoagulants and other drugs (at risk of interactions) were excluded. High-resolotion ultrasound scans included femoral,popliteal and soleal veins and were performed within 24 hours after the second flight. The time separation between the two flights was <8 days (average 6.5;SD1.1). 458 subjects completed the two-flights study. Dropouts were due to low compliance or traveling/connections problems. Age/sex and risk distribution were comparable in the three groups. Mean age was 44.7 (range, 24 – 66; SD 7.1; 54% males). In the control group (160), there were 6.87% of subjects with DVT plus 2 superficial thromboses (SVT)(total events 8.1%). Of 142 subjects in the aspirin treatment group, there were 4.9% of subjects with DVT plus 3 SVTs (total 7% of subjects with a thrombotic event). In the LMWH group (156) there were no cases of DVT and 2 superficial thrombosis (1.28%); (P<0.002 in comparison with the other two groups). DVT was asymptomatic in 64% of subjects; D-dimer was elevated in 78% o subjects with events and in 28% of subjects without events. Mild gastrointestinal symptoms were reported in 15% of patients using aspirin. No side-effects were observed in the LMWH group. In conclusion, one dose of LMWH is an important option to consider for HRS during long-haul flights.
Abstract 5068: A Prospective Randomized Comparative Trial of Bezafibrate and Pravastatin in Patients with Coronary Artery Disease and High Remnant Lipoprotein Levels
Authors: Sano Keita , Nakamura Takamitsu , Takishima Isao , Makino Aritaka , Hirano Mitsumasa , Kodama Yasushi , Kitta Yoshinobu , Kawabata Kenichi , Obata Junei , Kugiyama Kiyotaka
Published: July 2021

Remnant lipoproteinemia is a strong risk factor for atherosclerotic cardiovascular diseases (CVD). However, it remains unclear whether the lowering of remnant lipoprotein levels can prevent CVD events, and it is uncertain which lipid-lowering drug is most effective in reducing remnant lipoprotein levels or CVD events. Thus, this study examined if lowering of remnant lipoprotein levels can reduce CVD risk and which of two common lipid-lowering drugs (fibrate or statin) is more effective. The serum levels of remnant lipoproteins were measured by an immunoseparation method (remnant-like lipoprotein particles cholesterol; RLP-C). This multi-center study recruited 202 patients with chronic coronary artery disease (CAD), high RLP-C levels (≥ 5.0 mg/dL), and mild hypercholesterolemia (≥ 180 and < 260 mg/dL). They were randomly assigned to receive bezafibrate (Beza, 200 ~ 400 mg/day, n = 101) or pravastatin (Prava, 10 ~ 20 mg/day, n = 101), and were prospectively followed-up for 1 year or until the occurrence of a CVD event: cardiac death, nonfatal myocardial infarction, unstable angina pectoris requiring unplanned revascularization, or ischemic stroke. The 2 groups had similar baseline levels of RLP-C (average in total patients, 9.8 ± 0.4 mg/dL), LDL-C (126 ± 6.0 mg/dL), HDL-C (43 ± 1.2 mg/dL), and triglycerides (212 ± 9.7 mg/dL). RLP-C levels at 1 year of treatment were reduced in Beza more than Prava (by - 30% and - 19% from baseline, respectively), whereas reduction of LDL-C levels was less in Beza than Prava (by - 7% and -15%). During follow up, CVD events occurred in 3 patients treated with Beza and in 11 patients with Prava (p = 0.03 by chi-square test) (cardiac death in 0 and 1, unstable angina in 2 and 10, and stroke in 1 and 0, respectively). In a multivariate Cox hazards analysis, reduction of 1-SD (38%) of percent change in RLP-C levels decreased risk of future CVD events by 36% independently of change in LDL-C and HDL-C levels (HR 0.64, 95% CI 0.46 – 0.90, p = 0.01). Bezafibrate therapy decreased RLP-C levels and CVD events to a greater extent than pravastatin in CAD patients with high RLP-C levels and mild hypercholesterolemia. Reduction of remnant lipoprotein levels may improve outcomes in CAD patients with high remnant lipoprotein levels.
Abstract 5070: Progression of Urine Albumin Excretion Despite of Optimized Therapies to Reduce Atherosclerotic Risk Factors has an Adverse Outcome in Patients with Coronary Artery Disease
Authors: Kitta Yoshinobu , Hirano Mitsumasa , Nakamura Takamitsu , Kodama Yasushi , Sano Keita , Kawabata Ken-ichi , Obata Jyun-ei , Kugiyama Kiyotaka
Published: July 2021

Although microalbuminuria is considered a strong risk factor of future cardiovascular disease (CVD), it remains unclear whether changes in urine albumin excretion (UAE) in response to a reduction of coronary risk factors may provide prognostic information in patients with coronary artery disease (CAD). Thus, this study assessed the hypothesis that changes in UAE in response to optimized therapy for reduction of CAD risk may predict future CVD events in patients with CAD. This study enrolled of 213 patients with newly diagnosed CAD who had microalbuminuria (30 mg/day ≤ UAE < 300 mg/day) at entry. Patients with late-stage chronic kidney disease (GFR < 60 ml/min/1.73 m
2
) at entry were excluded. All patients had individualized, optimized therapies including medications and recommended life style changes to reduce risk factors for CAD according to AHA guidelines. All patients had a repeated test of UAE at 6 months (2
nd
test) after the 1
st
UAE test. Thereafter, all patients were prospectively followed up for 3 years or until the occurrence of 1 of the following events: CVD death, nonfatal myocardial infarction, unstable angina pectoris requiring revascularization, or ischemic stroke. Progression of UAE at the 2
nd
test was defined as > 50% increase from the UAE at the 1
st
test. UAE at 2
nd
test was progressed in 62 (29%) patients, while it was not progressed in the remaining 151 (71%) patients. UAE at entry was comparable between patients with and without progression of UAE (52 ± 6.2 vs.61 ± 4.7 mg/day, respectively, p = ns). During follow-up period, events occurred in 15 (24%) of the 62 patients with progression of UAE and in 16 (10%) of the 151 patients without progression of UAE (p < 0.01 by chi-square test). Using a multivariate Cox hazards analysis, progression of UAE was a predictor of future CVD events that was independent of UAE at 1
st
test, use of medications, age, and traditional CAD risk factors (HR 2.5, 95%CI 1.2 – 4.8, p = 0.01). Progression of urine albumin excretion despite individualized and optimized therapies to reduce CAD risk factors represents an adverse outcome in CAD patients. Periodic measurement of urine albumin excretion may be useful for risk stratification in CAD.
Abstract 5105: The Relationship of Inflammation and Thrombosis with Right Ventricular Mass and Function: The MESA-Right Ventricle Study
Authors: Kawut Steven M , Barr R G , Johnson Craig , Chahal Harjit , Tandri Harikrishna , Jain Aditya , Kizer Jorge , Bagiella Emilia , Bristow Michael , Lima Joao , Bluemke David
Published: July 2021

Right ventricular (RV) mass reflects response to afterload, whereas RV ejection fraction (RVEF) is an indicator of RV function. Pulmonary vascular disease is characterized by hemostatic abnormalities and inflammation and may affect RV mass and function. We hypothesized that increased levels of inflammatory markers (ICAM-1, TNF-α, E-Selectin, MMP-3, and MMP-9) would be associated with higher RV mass and lower RVEF, and increased levels of hemostatic markers (tissue factor, PAI-1, and CD40L) and decreased levels of TFPI would be associated with higher RV mass and lower RVEF. The Multi-Ethnic Study of Atherosclerosis (MESA) performed interpretable cardiac MRIs on 5,004 participants without clinical cardiovascular disease at six field centers. 785 randomly selected patients had plasma biomarkers measured, 730 of whom had complete interpretation of RV measures. Endocardial margins of the RV were manually contoured on diastolic and systolic images. End-diastolic volume (EDV) and end-systolic volume (ESV) were calculated by using a summation of disks method (“Simpson’s Rule”). RVEF was calculated from (EDV-ESV)/EDV. RV mass was determined from cine images of the heart. Biomarkers were analyzed in quintiles using multivariate linear regression. The 730 participants in the study sample were 59 ± 10 (mean ± SD) years old, 58% female, 45% Caucasian, 21% African-American, 11% Chinese-American, and 23% Hispanic. The RV mass was 22 g ± 5 g and RVEF was 69% ± 7%. Higher PAI-1 levels were associated with lower RV mass, after adjustment for age, gender, race, height, and weight (test for trend, p = 0.036, n = 710). Higher MMP-9 levels were associated with lower RV mass (test for trend, p = 0.006). Neither hemostatic nor inflammatory biomarkers were associated with RVEF. RV mass was inversely associated with PAI-1, a serine protease which inhibits thrombolysis, and MMP-9, which breaks down the extracellular matrix. The mechanism of these determinants of RV structure and function should be investigated.
Abstract 5108: Microalbuminuria is Associated with Progression of Coronary Atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: DeFilippis Andrew P , Kramer Holly J , Katz Ronit , Wong Nathan , Bertoni Alain , Carr Jeffrey J , Budoff Matthew J , Blumenthal Roger S , Nasir Khurram
Published: July 2021

Background:
Microalbuminuria (MA) is associated with an increased risk of cardiovascular disease (CVD) but the mechanism by which microalbuminuria imparts this increased risk is not known. In this study we assessed the relationship between MA and the development and progression of atherosclerosis by measuring the incidence of new CAC and the progression of existing CAC in individuals free of clinical CVD.

Methods
: The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of 6,814 participants free of clinical CVD at entry who underwent assessment of coronary artery calcification (CAC) by computerized tomography at baseline. Overall, 6,775 individuals had data available on urinary albumin creatinine ratio (UACR); 1,109 individuals were excluded for missing data or macroalbuminuria (UACR≥300 mg/g). Incident CAC was defined as detectable CAC at follow-up among those with CAC=0 at baseline, and absolute CAC score change among those with CAC>0 at baseline. Relative risk (RR) regression adjusted for covariates; and multivariable adjusted median regression was employed to assess the independent relationship of MA with CAC incidence and progression.

Results
: Of the 5,666 subjects (mean age 62±10 years, 48% males), baseline MA was seen in 424 (7%) participants, who were more likely to have CAC compared to those with normal UACR (62% vs. 48%, p<0.0001). During a mean follow-up of 2.4±0.8 years, those with MA were more likely to develop CAC (28% vs. 15%, p<0.0001) and they had a higher absolute median increase in CAC (47 vs. 29 Agatston Units, p<0.0001). After adjustment for age, gender, ethnicity, site, follow-up duration, diabetes, hypertension, smoking, family history of heart attack, total cholesterol, lipid lowering medications and body mass index; MA was associated with incident CAC (RR 1.65; 95%CI 1.41–2.48) among those with CAC=0 at baseline. Among those with CAC>0 at baseline, MA was associated with a median increase in CAC of 7.93 (95%CI 0.38 –15.47) Agatston Units in multivariable adjusted analyses (variables noted above).

Conclusion
: MA is independently associated with development of incident CAC and progression of CAC in an asymptomatic multi-ethnic population, and may in part explain its associated increased risk of CVD.
Abstract 5132: Positive Emotions and the Endothelium: Does Joyful Music Improve Vascular Health?
Authors: Miller Michael , Beach Valerie , Mangano Charles , Vogel Robert A
Published: July 2021

Background: Previous studies have demonstrated that music may influence physiologic parameters such as heart rate and blood pressure. However, the extent to which music may also affect endothelial function has not been previously investigated.

Methods: This was a randomized 4-phase crossover and counterbalanced trial in ten healthy, non-smoking volunteers (70% male, mean age= 35.6 yrs) that included self-selections of music evoking joy [joyful music] or anxiety [anxious music]. Two additional phases included video clips to induce laughter and audio tapes to promote relaxation. To minimize emotional desensitization, subjects were asked to refrain from using self-selected tapes and images for at least 2 wks before each study phase. Endothelial function was assessed by brachial artery flow mediated dilation (FMD) and measured as % diameter change after an overnight fast. Following baseline FMD measurements, subjects were randomized to a 30 min phase of the testing stimulus followed by post-study FMD; they returned a minimum of 1 wk later for the next phase. A total of 160 FMD measurements were made.

Results: Compared to baseline, mean upper arm FMD increased 26% during the music phase that evoked joy (
P
=
0.0002
) compared to a 6% decrease in FMD observed after listening to music that elicited anxiety (
P
=
0.005
) (Figure

). Mean FMD also increased 19% during the laughter phase (
P
=
0.08
) and 11% during relaxation (
P
=
NS
). Self-selected joyful music was associated with increased FMD to a magnitude previously observed with aerobic activity or statin therapy.

Conclusion: Listening to joyful music may be a useful adjunctive lifestyle measure to promote vascular health.
Abstract 5135: Influence Of Regular Physical Ativity On Regenerative Capacity Of Endothelial Progenitor Cells In School Children
Authors: Walther Claudia A , Adams Volker , Drechsler Kati , Gaede Luise , Sonnabend Melanie , Botur Inga , Koerner Antje , Toepfer Madlen , Schuler Gerhard
Published: July 2021

Background:
One of the markers associated the cardiovascular risk profile are circulating endothelial progenitor cells (EPCs). In patients (pts) with atherosclerosis the number of EPCs is strongly correlated with endothelial function. Recent studies demonstrated the beneficial effect of acute and chronic exercise on mobilization of circulating progenitor cells in adults. Aim of this study was to investigate the effect of daily school exercise lessons on the amount and function of EPC’s.

Methods:
Eleven 6
th
-grade classes (131 boys, 151 girls) of three different high schools were randomized to an intervention group (IG) or a control group (CG). Students (Stds) of IG received one daily exercise lesson (45 min) with at least 15 minutes of endurance training. Stds of CG had their regular school sports consisting of 2 exercise lessons (each 45 min) per week. Three classes (31 boys, 20 girls) of a high school with special focus on competitive sports and physical education served as reference group (PE). In all children (159 boys and 163 girls, mean age 11.2 ± 0.4 years ) anthropometric data were recorded, laboratory analysis was assessed and a treadmill exercise test with spirometry was performed. The number of EPCs was assessed with FACS analysis and function of EPCs was determined via migration assay.

Results:
After 1 year maximal oxygen consumption (VO2max) increased significantly in children of IG compared to children of CG (47.8 ± 1.7 ml/kg/min vs. 42.2 ± 1.2 ml/kg/min, p<0.001). However values of children of PE (56.2 ± 1.7 ml/kg/min, p<0.001 vs. IG und CG) were not reached. At baseline students of PE demonstrated a significantly higher amount of EPCs compared to students of IG and CG (403 ± 42 number/ml blood vs. 267 ± 38 number/ml blood in IG und KG (p<0.01)). After 1 year the amount of EPCs increased by 69% in Stds of IG, no change was observed in Stds of CG. Migratory capacity was significantly higher in Stds of PE compared to IG and CG.

Conclusion:
The results of this trial demonstrate, that already in childhood, regular exercise and physical activity have a positive influence on exercise capacity and the amount of EPCs. Therefore, to prevent the negative consequences of physical inactivity and overweight/obesity early intervention to support exercise and movement is necessary.
Abstract 5146: Statin Therapy Alters the Relationship Between Apolipoprotein B and Both LDL-C and Non-HDL-C in High-Risk Patients: Effect of Race and Ethnic Background
Authors: Ballantyne Christie M , Nicholls Stephen J , Barter Philip J , Cain Valerie A , Raichlen Joel S
Published: July 2021

Racial and ethnic subgroups are frequently under-represented in clinical trials of statin therapy. Apolipoprotein (Apo) B provides a measure of atherogenic particles in blood, a predictor for coronary heart disease (CHD) events. Reducing LDL-C to current goals may still leave an excess of atherogenic lipoproteins. A study of predominantly Caucasian high-risk patients suggested that statin therapy may alter the relationship between Apo B and commonly measured lipoproteins. Therapeutic responses in non-Caucasians have not been well studied. This study sought to examine the effect of racial and ethnic backgrounds on these relationships. A pooled analysis of data obtained in the rosuvastatin clinical development program was used to identify 12,269 high CHD risk patients of varying race/ethnic descent (Caucasian, African, Asian, and Hispanic Latino). The relationships between Apo B and both LDL-C and non-HDL-C were compared at baseline and after therapy with rosuvastatin, atorvastatin, or simvastatin. At baseline, an Apo B of 90 mg/dL corresponded to an LDL-C of 114.4 mg/dL for blacks and ~109 mg/dL for Asians and Hispanics (Table

). On statin therapy, to reach an Apo B of 90 mg/dL, blacks required an LDL-C of 87.2 mg/dL, while Hispanics required an LDL-C of 78.3 mg/dL. The baseline non-HDL-C that corresponded to an Apo B of 90 mg/dL was highest for Caucasians and lowest for Asians, with almost no differences observed among the ethnic groups on statin therapy. To achieve the Apo B target of 90 mg/dL, statin therapy required 20 –30 mg/dL lower targets for both LDL-C and non-HDL-C. The strong correlation between Apo B and non-HDL-C on statin therapy (R
2
=0.88 to 0.92) suggests that non-HDL-C may be a useful surrogate for Apo B in all high-risk patients. For all race/ethnic groups, in order to achieve an Apo B target of 90 mg/dL with statin therapy, LDL-C and non-HDL-C targets need to be closer to those currently recommended for very high CHD risk.
Abstract 5147: A Cluster Randomised Controlled Trial to Evaluate an Ambulatory Primary Care Management Program for Patients with Dyslipidemia: TEAM Study
Authors: Villeneuve Julie , Genest Jacques , Fredette Marc , Blais Lucie , Berbiche Djamal , Lamarre Diane , Lussier Marie-Thérèse , Vanier Marie-Claude , Hudon Eveline , Lalonde Lyne
Published: July 2021

Dyslipidemia management in primary care is often sub-optimal. New Quebec (Canada) legislation increases the potential for family physician-community pharmacist collaborative care (PPCC). We hypothesized that PPCC can improve the management of dyslipidemia. In a randomized controlled trial, clusters of physicians and pharmacists within the same geographical area were randomly assigned to the PPCC or the usual care (UC) group. PPCC pharmacists attended a one-day workshop and successfully completed a clinical skills evaluation. In the PPCC intervention, the physicians are responsible for the diagnosis and the prescription of lipid-lowering pharmacotherapy, while the pharmacists initiate treatment; request appropriate laboratory tests; monitor effectiveness, safety, and adherence to treatment; and adjust medication dosage accordingly. In PPCC, physician-pharmacist communication procedures were pre defined to enhance professional collaboration. Moderate and high CHD risk patients initiating statin treatment or currently on treatment but inadequately controlled were recruited and followed-up for 1 year. The primary endpoint was the mean change difference in LDL between groups after 1 year. Secondary endpoints included the proportion of patients at or below their target LDL and TC/HDL ratio, as defined by the Canadian Lipid Guidelines, after 1 year. Multilevel and multivariate regression models were used. We enrolled 15 clusters of physicians and pharmacists (PPCC: 108 patients; UC: 117 patients). The mean change in LDL after 1 year was -1.11 mmol/L (95%CI: −1.26 to −0.96) and −0.89 mmol/L (−0.95 to −0.83) in PPCC and UC groups, respectively. The adjusted mean change difference in LDL between PPCC and UC groups was −0.11 mmol/L (−0.34 to 0.11). After 1 year, 80.6% of PPCC patients and 72.9% of UC patients were at or below their target lipid levels (adjusted OR 2.1; 1.2 to 3.8; p=0.008). PPCC patients had more lipid-lowering pharmacotherapy changes (OR: 2.0; 1.1 to 3.8) and were more likely to report lifestyle changes (OR: 3.9; 2.4 to 6.3). Our data shows that the Family physician-community pharmacist collaborative care improves the adherence to the Canadian Lipid Guidelines.(
ISRCTN66345533
)
Abstract 5153: Pericardial Fat, Intra-Thoracic Fat, and Left Ventricular Mass: The Framingham Heart Study
Authors: Fox Caroline S , Gona Philimon , Hoffmann Udo , Salton Carol J , Massaro Joseph , Levy Daniel , Larson Martin , D’Agostino Ralph B , O’Donnell Christopher J , Manning Warren J
Published: July 2021

Pericardial fat is in direct anatomic contact with the myocardium and may lead to increased left ventricular mass (LVM). Whether the association of pericardial fat and LVM are independent of the systemic effects of obesity has not been fully explored. Participants from the Framingham Heart Study Offspring cohort (n=1006, mean age 60 years, 54% women) who underwent chest and abdominal computed tomography (CT) scanning and cine cardiac magnetic resonance imaging for left ventricular mass (LVM) quantification were included. CT scans were quantified for pericardial fat (fat within the pericardial sac), intra-thoracic fat (fat adherent to the heart but outside the pericardium), and abdominal visceral adipose tissue (VAT) using a volumetric method. Sex-specific multivariable linear regression was used to model the association of pericardial fat and of intra-thoracic fat with LVM after adjustment for age, smoking, alcohol use, menopausal status, systolic blood pressure, hypertension treatment, and height, and then additionally for VAT. Both pericardial and intra-thoracic fat were correlated with LVM in women (r=0.35, p<0.001 [pericardial fat]; r=0.37, p<0.001 [intra-thoracic fat]) and men (r=0.19, p<0.001 [pericardial fat]; r=0.17, p<0.001 [intra-thoracic fat]). In multivariable-adjusted models, both pericardial and intra-thoracic fat were associated with LVM (Table

). However, after adjusting for VAT, these associations were no longer significant (Table

). Both pericardial fat and intra-thoracic fat are associated with LVM in women and men. However, after accounting for VAT, a measure of systemic adiposity, neither pericardial fat nor intra-thoracic fat remain associated with LVM. These findings suggest that observed associations between pericardial fat and LVM are primarily due to the systemic effects of obesity.

Beta coefficients of LVM (std error), per gram expressed per SD of pericardial/intra-thoracic fat
Abstract 6205: Variants of CYP4V2, SERPINC1 and GP6 Are Associated with Pulmonary Embolism
Authors: Bare Lance A , Bezemer Irene D , Tong Carmen H , Arellano Andre R , Rowland Charles M , Catanese Joseph J , Reitsma Pieter H , Doggen Carine J , Devlin James J , Rosendaal Frits R
Published: July 2021

Background:
Pulmonary Embolism is a potentially fatal manifestation of venous thrombosis that may share genetic risk factors with deep vein thrombosis (DVT). Recently, 3 single nucleotide polymorphisms (SNPs) were reported to be associated with DVT in three studies: rs13146272 in
CYP4V2
, rs2227589 in
SERPINC1
, rs1613662 in
GP6
. We investigated whether these 3 SNPs were also associated with pulmonary embolism.

Methods:
We genotyped 5840 subjects from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study). Cases were 1,206 patients who had a pulmonary embolism without a symptomatic DVT: isolated pulmonary embolism (PE
iso
). Controls were 4,634 subjects who had no history of DVT or pulmonary embolism. We tested the association between genotypes and PE
iso
using logistic regression models that adjusted for age and sex.

Results:
For all three SNPs, the same allele that had been previously found to be associated with increased risk of DVT was also associated with increased risk of PE
iso
. For homozygous carriers of the risk allele, compared with noncarriers, the ORs were 1.34 (95% CI, 1.08–1.67) for rs13146272 in
CYP4V2
, 1.85 (95% CI, 1.08–3.16) for rs2227589 in
SERPINC1
, and 1.20 (95% CI, 1.04–1.39) for rs1613662 in
GP6.
The frequencies of risk allele homozygotes in the controls of the MEGA study were 41% for rs13146272, 1% for rs2227589, and 67% for rs1613662.

Conclusions:
Three SNPs previously reported to be associated with DVT were found to be associated with PE
iso
. Because of the high frequencies of two of these polymorphisms in Caucasians, these SNPs are likely make an appreciable contribution to the population attributable risk for PE
iso
.
Abstract 6238: Clarifying the Opportunities to Improve Survival After MI in Diabetic Patients
Authors: Longmore Lance S , Reid Kimberly J , Kosiborod Mikhail , Masoudi Frederick A , Welch Verna , Amin Alpesh A , Spertus John A
Published: July 2021

While diabetes is known to be associated with increased mortality after MI, whether these differences in outcome are due to patient characteristics, treatment, or other biological factors is unknown. We analyzed a contemporary cohort of MI survivors to comprehensively adjust for demographics, comorbidities, psychosocial, health status, clinical and treatment factors to determine if residual disparities in outcomes exist. We studied 2481 hospital survivors of MI in the prospective, 19-center PREMIER study (29% with diabetes). Multivariable models with sequential adjustment were employed to identify the extent to which variation in a wide range of patient characteristics (Figure

) accounted for differences in 3-year mortality in patients with and without diabetes. Unadjusted mortality was more than 2.5-fold greater for patients with diabetes (HR 2.55, 95% CI 2.08–3.14). Mortality was most attenuated by diabetes-related comorbidities (Figure

). The fully-adjusted model identified a significant, albeit attenuated, excess 3-year mortality among patients with diabetes (HR 1.57, 95% CI 1.22–1.99). Patients with diabetes experience a substantially increased risk for 3-year mortality after MI, even after accounting for a wide range of patient and treatment characteristics. This suggests that unmeasured, biologic variables associated with diabetes may mediate this difference. Further inquiry into the pathogenesis of diabetic cardiovascular disease is needed to identify new opportunities to improve the prognosis of patients with diabetes.
Abstract 6251: Heat Shock Protein 27 is Localized in Intercalated Discs and is Extensively Modified by Methylglyoxal in Human Hearts
Authors: Gawlowski Thomas , Stratmann Bernd , Stork Ines , Körfer Reiner , Tschoepe Diethelm , Milting Hendrik
Published: July 2021

Hyperglycemia plays an important role in the pathogenesis of diabetic complications including accumulation of methylglyoxal (MG), a highly reactive α-dicarbonyl metabolite of glucose degradation pathways. MG reacts in a non-enzymatic reaction with arginine residues of proteins which results in the formation of argpyrimidine. In several cell lines Hsp27 was found to be the most argpyrimidine containing protein. Whether Hsp27, which is high expressed in cardiac tissue, is also modified in heart, remains unclear. The aim of this investigation was to study the extent of Hsp27-modifications in heart failure and diabetes mellitus. Transmural myocardial samples from the left ventricle of explanted terminal failing hearts (diabetic: n=8; non-diabetic: n=8) and non-failing myocardium (NF) (n=6) without apparent signs of cardiac failure were collected. Cardiac tissue samples and rat cardiomyoblast cells H9c2, which were grown under normal and hyperglycaemic conditions, were investigated for the Hsp27-expression and modification by real-time PCR, western blotting and immunohistology. Hsp27 was significantly decreased (p<0.05) in CM/DM (cardiomyopathy and diabetes mellitus) compared to NF. Relating to Hsp27-expression the MG-modification in diabetic hearts was significantly increased 3-fold (p<0.05) compared to CM (cardiomyopathy) and 9-fold (p<0.05) compared to NF. Consistent with the results in human heart samples, high glucose levels induced a down-regulation of Hsp27 in H9c2-cells in a dose-dependent manner. We also found an increased MG-modification of Hsp27 with higher concentrations of glucose. Noteworthy, we detected Hsp27 in the myocardial intercalated disc and in the M-line of the sarcomer in human cardiac tissue by immunohistology. In summary, we observed an increased argpyrimidine-modification of Hsp27 in the myocardium of patients with terminal heart failure and diabetes in comparison to non-failing donor hearts and explanted hearts from patients with cardiomyopathy. The argpyrimidine-modification of Hsp27 probably results from the diabetic myocardial metabolism and might be of impact for the progress of a cardiomyopathy in patients with diabetes mellitus.
Abstract 6256: Absence of Leptin Resistance in Platelets from Obese Individuals Suggests a Mechanism for Increased Thrombosis Risk in Obesity
Authors: Dellas Claudia , Schaefer Katrin , Rohm Ilonka , Lankeit Mareike , Hasenfuss Gerd , Konstantinides Stavros
Published: July 2021

Clinical studies have demonstrated that elevated leptin levels, such as frequently found in obesity, are an independent cardiovascular risk factor. We and others have shown that leptin promotes platelet aggregation and thrombosis. However, little is known about the existence of platelet resistance to leptin, particularly in the setting of obesity and central leptin resistance. In the present study, we examined the effects of leptin on platelet aggregation in morbidly obese subjects (n=40; BMI 41.6±1.1 kg/m2; leptin 49.7±3.4 ng/mL) in comparison to normal-weight controls (n=36; BMI 23.3±0.4; leptin 6.5±0.7). The aggregatory response to ADP was significantly increased in platelets from obese donors compared to controls as shown by a left-shift in the ADP dose curves. Thus, percent platelet aggregation at 2, 3, 4, and 5 μM ADP was 18.7±4.8 in the obese vs. 4.7±2.0 in controls (P=0.01), 37.2±6.6 vs. 17.1±4.4 (P=0.01), 60.8±6.0 vs. 37.8±6.5 (P=0.01), and 80.2±6.5 vs. 44.5±8.8 (P=0.002), respectively. Plasma leptin levels, but not the body-mass-index, were significantly higher in subjects with stronger (above the median) platelet aggregation in response to ADP compared to those with weaker (below the median) aggregation (35.9±5.1 vs. 22.4±4.1 ng/mL; P=0.04). In further experiments, exogenous leptin stimulation promoted ADP-induced platelet aggregation by 25% on average, and there was no difference in the responsiveness to leptin between platelets from obese and those from lean donors (controls; P=0.99). Using Western blot analysis we found that leptin induced phosphorylation of the signaling molecules JAK2 and STAT3 to a similar extent in platelets from both groups. Expression of potential mediators of leptin resistance (SOCS3 and PTP1B) also did not differ in platelets from obese and control subjects. Taken together, our data indicate that platelets from obese donors show increased aggregatory response to ADP, which might partly result from the increased circulating leptin levels. Platelets from obese individuals were not resistant to the enhancing effects of leptin on ADP-induced aggregation. Our results thus support the existence of a direct link between obesity, hyperleptinemia and thrombosis.
Abstract 6273: Changes in Metabolic Parameters, Adiponectin, and High Sensitivity C-reactive Protein in South Asian Women Migrating to the United States: A 3-Year Follow-Up Study
Authors: Arora Anjali , Vora Aaditya , Eapen Danny J , Khan Bobby
Published: July 2021

Background: The incidence of cardiovascular disease in South Asian women is increasing, both in native and migrant populations. The reasons for this finding may be in part related to changes in lifestyle and alterations in cultural behavior.

Methods: We studied 301 healthy women (average age 28) recently migrated to the United States from the South Asian countries of India, Bangladesh, Pakistan, and Sri Lanka within 3 months of the time of arrival and at 3 years (31– 41 months) following their arrival. A questionnaire regarding activities pertaining to diet, physical activity, and socioeconomic status was performed. Measurements included changes in blood pressure (BP), total body weight, lipids, glucose, and determinations of high sensitivity CRP (hsCRP) and adiponectin from frozen serum specimen at these time points.

Results: In this diverse population, subjects reported an increase in food intake (including added salt and fat quantities) and no overall change in physical activity. Accordingly, there was a significant increase in total body weight after a 3 year period (119.7±14.4 to 127.9±15.3 pounds, p<0.005). There was a significant increase in serum LDL cholesterol (103.8±17.6 to 111.0±15.9 mg/dl, p=0.018), triglycerides (136.1±25.3 to 157.5±20.0 mg/dl, p=0.023), and glycosylated hemoglobin (4.9±0.7 to 5.3±0.6%, p=0.029). Moreover, the prevalence of diabetes mellitus (fasting glucose>125 mg/dl) increased from 3.3 to 9.7% in the 3-year follow-up period. There was an increase in serum hsCRP (1.80±0.19 to 2.05±0.18 mg/l, p=0.010) and a decrease in serum adiponectin (10.8±0.9 to 9.5±1.0 mg/l, p=0.022) in these subjects.

Conclusions: The population of South Asian women is at increased risk for cardiovascular disease and diabetes mellitus. Changes in lifestyle, including dietary intake and physical activity, affect parameters that may be crucial in the pathogenesis of these disease states.
Abstract 6275: Increased Mortality after Primary Percutaneous Coronary Intervention for Acute ST Segment Elevation Myocardial Infarction During Off-Hours
Authors: Cubeddu Roberto J , Cruz-Gonzalez Ignacio , Kiernan Thomas J , Leinbach Robert C , Truong Quynh A , Rosenfield Kenneth , Cadigan Mary E , Pomerantsev Eugene V , Palacios Igor F
Published: July 2021

Background:
Higher mortality has been reported in patients admitted with acute myocardial infarction during off-hours, and has been related to a lower use of primary percutaneous coronary intervention (PCI).

Methods:
We thus conducted a study, where primary PCI is routinely performed in all patients with ST elevation myocardial infarction (STEMI) regardless of the day and time of admission. Patients admitted during on-hours (Monday through Friday 7am–6pm) where compared to off-hours (including weekends). The outcome of in-hospital mortality, cardiogenic shock and recurrent myocardial infarction was explored. The different components of door-to-balloon (DTB) time were examined and compared between both groups.

Results:
Between 2003 and 2007, 747 STEMI patients (46% on-hours vs. 56% off-hours) underwent primary PCI. Patient baseline demographic characteristics were similar during on-vs. off-hours. Admissions during off-hours were associated with longer DTB times (134 vs. 109 minutes, p<0.0001). Furthermore, patients admitted during off-hours had significantly greater in-hospital mortality (8% vs. 3.7%, p=0.01), and higher rates of cardiogenic shock (37% vs. 24%, p=0.0001). Multivariate analysis identified admission arrival time as an independent predictor of in-hospital mortality (HR 3.98; 95% CI 1.10 –14.38; p=0.035). Longer DTB times were attributed to the increased “engagement time” during off-hours (27 vs. 47 minutes, p<0.00001).

Conclusion:
1) This study is the first to show that even when treated equally with primary PCI, off-hours STEMI admissions have higher mortality than on-hours. Longer DTB time during off-hours likely explain our findings. Strategies to optimize hospital protocols, reperfusion therapies, and perhaps a dedicated in-house “STEMI team” during off-hours need to be revised.
Abstract 6277: Predictive Value of Estimated Glomerular Filtration Rate for Cardiovascular Events: The Treating to New Targets Study
Authors: Shepherd James , Wun Chuan-Chuan , Wilson Daniel J , Zuckerman Andrea L
Published: July 2021

We previously demonstrated a dose-dependent improvement in renal function and reduction in cardiovascular risk in TNT with intensive lipid lowering with atorvastatin (ATV) 80 mg vs 10 mg. This post hoc analysis examines the relationship between the observed improvement in estimated glomerular filtration rate (eGFR) and reduction of major cardiovascular events (MCVE). After 8 weeks open-label therapy with ATV 10 mg, 10,001 patients with CHD were randomized to double-blind therapy with either ATV 10 or 80 mg. Patients were followed for a median of 4.9 years for the occurrence of MCVEs (CHD death, nonfatal MI, and stroke). The relationship between change from baseline eGFR (using the MDRD equation) at the final visit prior to a MCVE and the risk of MCVE was assessed using a Cox proportional hazards model adjusting for baseline eGFR and other baseline characteristics. Of 9656 patients with complete renal data, 156 had a MCVE before follow-up eGFR assessment and were excluded. In the remaining 9500 patients, mean baseline eGFR was 65.3 mL/min/1.73 m
2
and mean change from baseline was 4.3 mL/min/1.73 m
2
. This represented a reduction in the risk of MCVE of 2.7% per mL increase in eGFR (HR 0.973, 95% CI 0.967– 0.980,
P
<0.0001). This association remained significant in patients with eGFR <60 and those with eGFR ≥60 mL/min/1.73 m
2
at baseline, with no significant interaction between eGFR change and baseline renal status (
P
=0.98). A 5 mL/min on-treatment improvement in eGFR was associated with a 12.6% reduction in MCVE, while a 5 mL/min reduction was associated with a 14.4% increase in MCVE. Mean change from baseline eGFR was 3.5 mL/min/1.73 m
2
with ATV 10 mg and 5.2 mL/min/1.73 m
2
with ATV 80 mg, representing significant 9.3% and 12.4% reductions in risk, respectively. Analysis of interaction between treatment and eGFR change for prediction of MCVE demonstrated a stronger association between eGFR change and MCVE in the ATV 80 mg treatment group (
P
=0.011). Improvement in eGFR was highly associated with a reduction in MCVE, irrespective of baseline renal function. This relationship was dose dependent. Improvement in eGFR may be a biomarker for the response to atorvastatin, and for the stabilization of atherosclerotic cardiovascular disease.
Abstract 8: Influence of Receiving Hospital Characteristics on Survival after Cardiac Arrest
Authors: Callaway Clifton W , Schmicker Rob , Kampmeyer Mitch , Powell Judy , Nichol Graham , Rea Thomas D , Daya Mohamud , Aufderheide Tom , Davis Dan , Rittenberger Jon , Idris Ahamed H
Published: July 2021

Hospital management of out-of-hospital cardiac arrest (OHCA) patients after return of spontaneous circulation (ROSC) can influence patient survival via interventions such as hypothermia and cardiac catheterization (CATH). This study tested the hypothesis that survival differed between different types of hospitals for subjects with ROSC after OHCA.

Methods: Adult (≥ 18 years) subjects with paramedic-documented ROSC or who lived >1 day after OHCA were identified with their receiving hospital in a prospective database from 9 regions in the US and Canada. Hospitals were characterized using the American Hospital Directory or the Guide to Canadian Healthcare Facilities. Hospitals were categorized by bed number (large >400; medium 250 – 400; small <250) and CATH capability. Associations between clinical variables, hospital categories, survival time, and survival to hospital discharge were determined using Cox regression and analysis of variance.

Results: Between December 2005 and July 2007, 3644 OHCA subjects were treated in 254 hospitals, with similar numbers in large (1026), medium (1094) and small (1276) hospitals. CATH hospitals treated 2123 (58%) subjects, and patient features (63% male, 42% VF/VT, 67% witnessed collapse, and mean call-arrival interval of 5.7 (SD 2.8) minutes) did not differ between hospital categories. CATH hospitals had higher survival than non-CATH hospitals in large (35.1% vs. 27.7%), medium (34.4% vs. 30.7%) and small (38.6% vs. 26.5%) categories (F=19.55; p<0.001). VF/VT (p < 0.001), age (p < 0.001) and witnessed collapse (p < 0.001) were associated with survival time. When adjusted for initial rhythm, call-arrival interval, witnessed collapse, age, sex, region, teaching institution, and trauma center level, there was no significant effect of CATH. However, the interaction of large hospital and CATH was associated with lower hazard of death (0.71, 95% CI [0.54, 0.93]).

Conclusions: Transport to a CATH hospital is associated with increased probability of survival to discharge after OHCA. These data cannot determine whether cardiac catheterization was performed or if CATH hospital is a surrogate for more comprehensive cardiac care. Therefore, further work should examine what aspects of in-hospital care affected outcome.
Abstract P15: Periodic Acceleration (pGz) Preconditioning in Swine Increases Endothelial Derived NO and Phosphorylated eNOS via Akt Pathway
Authors: Adams Jose A , Arias Jaqueline , Bassuk Jorge , Wu Heng , Uryash Arkady , Webster Keith , Lamas Gervasio , Kurlansky Paul
Published: July 2021

Periodic acceleration (pGz) is the motion of the supine body using a motorized platform (3Hz & ±0.4G). pGz produces pulsatile shear stress increasing release of endothelial derived NO (eNO) which, also decreases myocardial stunning and improves outcomes from ventricular fibrillation (VF) cardiac arrest. Preconditioning with pGz (PRE-pGz) prior to VF cardiac arrest ameliorates global post resuscitation cardiac dysfunction and reduces arrhythmias. To test whether pGz and PRE-pGz increase eNOS and phosphorylated eNOS (p-eNOS) via the PI3-kinase-Akt pathway, anesthetized, intubated male swine (40 –50lbs) were studied. Five animals had no intervention (BL) and 5 received 1 hr pGz preconditioning (pGz) followed by Western Blot of myocardial tissue. Additional animals (10 per group) received 1 hr pGz (PRE-pGz) or no treatment (CPR-CONT). In the latter groups VF was electrically induced and unsupported for 8 min followed by continuous manual chest compression and defibrillation for 10 min or until return of spontaneous circulation (ROSC). PRE-pGz animals showed less hemodynamically significant arrhythmias after ROSC than CPR-CONT (35 vs 7; p<0.05) and less myocardial stunning. eNOS and phosphorylated-eNOS (p-eNOS) significantly increased after pGz and after CPR but were significantly higher in pGz preconditioned animals along with increased phosphorylated Akt (p-Akt). The graph below shows % changes relative to BL (M±SD). *p < 0.01 PRE-pGz vs CPR-CONT.

Conclusion: pGz applied prior to ischemia reperfusion injury increases eNOS and p-eNOS expression and increased p-Akt. Thus, pGz preconditioning protects myocardium during I-R in part by activating eNOS through p-Akt
Abstract P18: Automated High Frequency Ventilation During Experimental CPR: A New Approach to Resuscitation
Authors: Hu Xudong , Mangat Iqwal , Leong-Poi Howard , Ramadeen Andrew , Dorian Paul
Published: July 2021

Purpose:
Experimental and clinical studies suggest manual over-ventilation during cardiopulmonary resuscitation (
CPR
) is common and reduces maximum obtainable ‘cardiac output’ from chest compressions. Automated ventilation during CPR has not been previously tested.

Methods:
This study compared hemodynamic (using solid state Millar transducers), gas exchange, and ventilation parameters during experimental CPR using 100% O
2
and manual bag ventilation (6 – 8 breaths/min) compared to automated ventilation using a compressed gas powered, non-electronic, pressure limited, pressure and flow triggered device (Oxylator, CPR Medical Devices) set at maximum inspiratory pressure of 12 mmHg, PEEP = 1.5 mmHg, max flow 30 L/min. The device automatically delivers inhalations when airway pressure falls to 1.5 mmHg and stops when pressure reaches 12 mmHg, delivering 1 breath for every decompression during manual chest compression. Twelve pigs underwent 5 min of electrically induced, untreated ventricular fibrillation (VF). They were randomly assigned to CPR using manual or automated ventilations (n = 6 each), together with continuous manual chest compressions at 95 – 110/min, 3 – 5 cm depth. Carotid artery flow was measured using a Doppler flow probe. All measures were made after 2 min of CPR.

Results:
Ventilatory and hemodynamic parameters for manual vs. automated ventilation during CPR

Conclusion:
Automated high frequency, low pressure ventilation during experimental CPR is associated with hemodynamics and gas exchange similar to that achieved with guideline recommended manual ventilation and avoids the risk of over-ventilation and barotrauma.
Abstract P21: Free Radicals Mediate Post-shock Contractile Impairment in Cardiomyocytes
Authors: Tsai Min S , Sun Shijie , Ristagno Giuseppe , Castillo Carlos , Weil Max H , Tang Wanchun
Published: July 2021

Background
Previous studies demonstrated myocardial dysfunction after electrical shock and indicated that it may be related to the generation of free radicals. Whether the free radicals are generated after electrical shock has not been documented at the cellular level and its effect on post-shock contractile function has not been clarified.

Hypothesis
: Electrical shock generates intracellular free radicals inside cardiomyocytes. Reducing intracellular free radicals by pre-treatment of ascorbic acid (AA) would reduce the contractile dysfunction following electrical shock.

Methods
: Cardiomyocytes isolated from adult male rats were divided into 4 groups, (1) electrical shock alone, (2) electrical shock pre-treated with AA, (3) pre-treated with AA alone and (4) control. AA was administered in an amount of 0.2 mM into the perfusate of the AA + electrical shock and AA groups. Electrical shock of 2 J was delivered in the electrical shock and AA+ electrical shock groups.

Results
: DCFH-DA loaded cardiomyocytes showed increased intracellular free radicals after electrical shock. The length shortening and Ca
2+
transients were recorded optically with fura-2 loading. Within 4 minutes following electrical shock in the electrical shock group, the length shortening decreased from 8.4±2.5% to 5.6±3.4% (
P
=0.000) and the Ca
2+
transient decreased from 1.15±0.13 au to 1.08±0.1 au (
P
=0.038). Compared with control, a significant difference in length shortening (
P
=0.001) and Ca
2+
transient (
P
=0.052) was observed. In the presence of AA, electrical shock did not affect length shortening and Ca
2+
transient.

Conclusion:
Electrical shock generates intracellular free radicals inside the cardiomyocyte. This is associated with contractile impairment and decrease of Ca
2+
transient. Administering AA may decrease such damage by eliminating free radicals.