bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 1251: Lipophilic Index of Fatty Acid Fluidity in Erythrocyte and Plasma and Risk of Coronary Heart Disease
Authors: Ding Eric L , Sun Qi , Campos Hannia , Hu Frank B
Published: July 2021

Multiple lines of evidence suggest that fatty acid (FA) binding affinity, viscosity, and cellular membrane fluidity together may play important roles in cardiovascular pathophysiology. Conventional classifications also incompletely capture the wide heterogeneity of diverse FAs. Via a novel etiologic paradigm, we investigate the Lipophilic Index (LI) and risk of coronary heart disease (CHD). Prospective nested case-control study in a cohort of 32,826 U.S. women who provided baseline blood in 1989 –1990. During 6-years follow-up, 166 incident CHD cases were matched with 327 controls. Assaying full FA profiles via gas chromatography, 43 FAs were identified in plasma and erythrocytes. We developed a novel FA risk index based on molecular properties of fat lipophilicity, constructed upon FA melting points, and parameterized via individual weighted summation of melting points; the LI was constructed upon 32 unique FAs with official melting points. Among controls, mean (SD) lipophilicity was 16.8°C (2.48) for Plasma-LI and 17.1°C (1.5) for Erythrocyte-LI, r=0.54. In prospective analyses, increasing Plasma-LI and Erythrocyte-LI were strongly associated with greater risk of CHD in both crude and multivariable models: RR=3.56 (95%CI: 1.48 – 8.67, P-trend=0.001) for Plasma-LI, and RR=3.80 (1.12–12.9, P-trend=0.03) for Erythrocyte-LI, comparing extreme quintiles. Individuals with higher LI also exhibited adverse lipid profiles, hyperglycemia, hypertension, and endothelial dysfunction. Notably, higher Plasma-LI was associated with having low HDL<40mg/dl (OR per-SD=2.71, 1.91–3.84; P<0.0001), elevated triglycerides>=150mg/dl (OR=3.89, 2.83–5.35; P<0.0001), hypertension (OR=1.34, 1.07–1.66; P=0.009), elevated HbA1c>=6% (OR=1.50, 1.17–1.91; P=0.001), and highest quintile of E-selectin (OR=1.92, 1.47–2.50; P<0.0001). LI trends with CHD risk also persisted after adjustment for these metabolic risk factors, plus
trans
and total fat intakes. The Lipophilic Index of plasma and erythrocyte fatty acids is strongly associated with adverse metabolic profiles and higher risk of CHD development. Findings support a novel mechanism that fatty acid lipophilicity is important in CHD pathogenesis.
Abstract 5814: Increased arterial 18F-FDG-uptake is associated with future Cardio- and Cerebrovascular Events: Initial Results of a PET-CT Study considering Age and Cardiovascular Risk Factors
Authors: Saam Tobias , Rominger Axel , Wolpers Sarah , Cyran Clemens C , Bartenstein Peter , Reiser Maximilian F , Hacker Marcus , Nikolaou Konstantin
Published: July 2021

Background

Atherosclerosis is a systemic disease which is associated with increased vascular inflammation. The purpose of this study was to correlate glucose-uptake of arterial walls as measured by 18F-FDG PET-CT with the occurrence of cardio- and cerebrovascular events.

Methods:

1000 tumor patients were examined by whole-body 18F-FDG PET-CT between 2004 to 2007. Patients’ clinical follow-up information could be obtained in 650 patients by telephone interviews (mean follow-up time 3,1y). In 22/650 patients (3.3%), cardio- or cerebrovascular events were registered, defined as cardiac death, myocardial infarction or revascularization and stroke. 6 out of 22 patients were not evaluable because of ongoing or prior steroid medication. In total, 16 PET-CT’s of patients with cardiovascular events could be evaluated and compared to PET-CT’s of 300 consecutive patients with known cardiovascular risk factors. Maximum standardized uptake values were measured from arterial walls of the ascending, thoracic and abdominal aorta, iliac and carotid arteries and corrected by dividing with the blood pool uptake in the vena cava (target-to-background ratio, TBR). Occurrence of events was correlated with TBR, age, cardiovascular risk factors and presence of calcified plaques using the Spearman’s correlation coefficient R. Multiple linear regression analysis was used to accommodate for differences in risk factors. Statistical significance was considered to be present when p<0.01.

Results:

Occurrence of events was significantly correlated with coronary heart disease (R=0.33; p<.001), arterial hypertension (R=0.22; p<.001), presence of hard plaques (R=0.15; p=.007) and TBR values (R=0.28; p<.001). No other significant correlations were found. When performing multiple regression analysis the association between the occurrence of events and TBR values/presence of coronary heart disease remained significant (p<.001).

Conclusion:

The findings of this study suggest that a higher arterial wall glucose uptake in tumor patients is associated with the occurrence of future cardio- and cerebrovascular events. TBR values as measured by 18F-FDG PET-CT could be useful for identifying high-risk patients in need of intensified medical or interventional therapy.
Abstract 3117: Subclinical Aortic Atherosclerosis by Cardiovascular Magnetic Resonance Imaging Predicts Increased Cardiovascular Morbidity and Mortality in an Initially Healthy Cohort: The Framingham Heart Study
Authors: Chuang Michael L , Gona Philimon , Jaffer Farouc A , Salton Carol J , Kissinger Kraig V , Botnar Rene M , Blease Susan J , Levy Daniel , O’Donnell Christopher J , Manning Warren J
Published: July 2021

INTRODUCTION: We sought to determine whether subclinical aortic atherosclerosis, detected noninvasively using cardiovascular magnetic resonance (CMR), predicts major adverse cardiovascular events (MACE) in adults without history or clinical manifestation of cardiovascular disease (CVD).

METHODS: 318 Framingham Heart Study (FHS) Offspring cohort members (60±9 yrs, 51% women) underwent CMR in 1998–1999. Subjects were free of clinical CVD and were recruited from equal strata of age, sex and quintile of Framingham Coronary Risk score (FCRS), with double sampling of the top quintile. CMR of the descending aorta on a 1.5-T system used an ECG-triggered black-blood T2W TSE sequence with 1.03 × 0.64 × 5-mm
3
voxels, 10-mm gap. Aortic-lumen and plaque areas were hand-traced. MACE included CV death, myocardial infarction (MI), stroke or new heart failure (HF). A Cox proportional hazards model adjusted for FCRS was used to determine hazard ratio (HR) for MACE for the (within-sexes) quartile of subjects with greatest plaque burden (Q4) vs other subjects (Q1–3). Log-rank test was used to compare survival.

RESULTS: CMR aortic atherosclerosis was identified in 38% of women and 41% of men. Over median 5.2-yr follow up, 38 MACE (4 deaths, 14 MIs, 12 strokes, 8 HF) occurred among 31 subjects. Greater plaque burden (Q4) was associated with 2.75-fold greater hazard of MACE (95% CI 1.33 – 5.69, p=0.007). The Figure

shows Kaplan-Meier survival, log-rank p=0.0009.

CONCLUSIONS: In a free-living population without history of cardiovascular disease, CMR evidence of subclinical aortic atherosclerosis was a predictor of 5-year MACE, even after adjustment for traditional cardiovascular risk factors.
Abstract 5012: Cystatin C and Cardiovascular Mortality in Patients with Coronary Artery Disease and Maintained Renal Function
Authors: Keller Till , Messow C M , Lubos Edith , Sinning Christoph , Espinola-Klein Christine , Rupprecht Hans J , Bickel Christoph , Tzikas Stergios , Lackner Karl J , Munzel Thomas , Blankenberg Stefan , Schnabel Renate
Published: July 2021

Chronic kidney disease is associated with an increased risk of cardiovascular disease. Cystatin C is a promising marker to reliably detect renal function. The role of cystatin C in patients with coronary artery disease and maintained renal function is less well established. In 2082 consecutive patients with documented coronary artery disease (CAD) (1267 with stable angina (SAP) and 815 with acute coronary syndrome (ACS)) baseline concentrations of cystatin C were measured if MDRD estimated glomerular filtration rate (GFR) was >30ml/min/1.73m
2
. During a median follow-up of 3.65 years cardiovascular mortality was documented (n=90). The median age of the study cohort was 63 years, 78.0% were of male gender. Age, sex, body mass index (BMI), and current smoking were predictors of cystatin C baseline concentration. GFR showed a strong negative association and the biomarkers Nt-proBNP and CRP were positively related to cystatin C measurements. Kaplan-Meier survival analysis showed a stepwise decrease in cardiovascular survival across quartiles of cystatin C baseline concentration (p log rank<0.0005). A similar pattern was observed in the subgroups of patients with SAP and ACS (p log rank<0.0005). A increase in cystatin C concentration by one quartile was associated with a 2.31-fold risk of future cardiovascular death (95% confidence interval 1.87–2.86, p<0.0005). A similar strength of association was seen in the subgroups. This risk association remained robust after adjustment for potential confounders. The addition of cystatin C to a basic model of cardiovascular risk factors increased the c-index from 0.713 (95% bootstrap confidence interval 0.658 – 0.785) to 0.762 (0.705– 0.827), and this strength was similar to the increase achieved by adding Nt-proBNP to the basic model (0.764, 0.724 – 0.833) while GFR only increased the c-index to 0.729 (0.676 – 0.799). Cystatin C is a potent predictor of cardiovascular mortality in patients with CAD and normal kidney function or mild renal impairment.
Abstract 5025: Transition to Menopause and Preclinical Atherosclerosis in Women: A Report from the Los Angeles Atherosclerosis Study (LAAS)
Authors: Johnson B Delia , Dwyer Kathleen , Paul-Labrador Maura , Stanczyk Frank , Bittner Vera , Berga Sarah L , Braunstein Glenn D , Azziz Ricardo , Yang YuChing , Bretsky Philip , Merz C Noel Bairey
Published: July 2021

While the relation between the onset of menopause and accelerated cardiovascular risk has been extensively studied, little information exists on the relationship of the menopausal transition and the development of preclinical atherosclerosis in women. We hypothesized that transition to menopause would be associated with a higher rate of progression of preclinical atherosclerosis.

Methods:
We evaluated 203 women (131 postmenopausal, 20 perimenopausal, and 52 premenopausal at entry) undergoing carotid intimal-media thickness (cIMT) measurement in the LAAS study, a prospective cohort study that included women aged 45– 60 years at entry without diagnosed cardiovascular disease who underwent three measurements (baseline, 1.5 and 3 year followup). cIMT was measured bilaterally in two body positions (lateral and supine), and average thickness over a 1 cm segment of the distal wall 25 mm proximal to the bulb was measured using automated edge-tracking software.

Results:
The mean age was 52±4 years, mean body mass index was 27.2±5.8, and 49% were non-white. At entry, 53% had hypertension, 3% diabetes, 16% were current smokers. Age-adjusted cIMT progression rate was similar among pre-, peri- and postmenopausal women (9±15 μ/yr) at entry, and similar among women who remained premenopausal (n=21) compared to those that transitioned to menopause (n=51) and to those who remained postmenopausal (n=131) during the observation period. Of the 51 transitioning women, age was not related to rate of cIMT progression. However, the rapidity of menopausal transition was related to the rate of IMT progression: women transitioning from pre to postmenopause within the 3 year period had a higher rate of cIMT progression compared to women with a slower transition (progressing from pre- to perimenopause, or from peri- to postmenopause, p=0.03). Additional adjustment of these results for systolic blood pressure and BMI did not alter the results.

Conclusions:
Among women undergoing repeated cIMT measurement in the LAAS, a more rapid menopausal transition (from pre- to postmenopause within 3 years) was associated with a higher rate of preclinical atherosclerosis progression; alternatively, menopausal status itself did not appear to be associated with rate of progression.
Abstract 5026: Gender Differences In The Effect Of Hemoglobin A1c On Mortality In Adults with Diabetes: Findings From A National Population-based Follow-up Study
Authors: Parikh Ankit , Lipsitz Stuart , Natarajan Sundareshwaran
Published: July 2021

Background:
Diabetes is associated with a greater relative risk of cardiovascular mortality in women than in men. Further, diabetes may carry a larger cardiovascular mortality risk than established coronary heart disease in women. It is unclear however if increasing glycosylated hemoglobin (HbA1c) levels are more strongly related to increased mortality in women than men.

Methods:
We examined the relationship between increasing levels of HbA1c and subsequent all-cause and cardiovascular mortality in a cohort of self-reported diabetics using data from the Third National Health and Nutrition Examination Survey. Mortality outcomes were assessed from the national death index. Population hazard ratios (HR) with 95% confidence intervals (CI) for mortality were derived from Cox proportional hazards models adjusting for age, race, education, income, smoking, obesity, hypertension, hyperlipidemia, physical activity, and diabetes duration. The study’s complex survey design was incorporated in all analyses to obtain population estimates by utilizing the appropriate survey weights, strata, and cluster variables.

Results:
There were a total of 1323 adults with diabetes with a mean follow-up time of 7.7 years. Among the 544 male diabetics, there were 235 all-cause deaths, 124 of which were from cardiovascular causes. Among the 779 female diabetics, there were 235 all-cause deaths, 111 of which were due to cardiovascular causes. In fully adjusted Cox models, a 2 percent increase in hemoglobin A1c was more strongly related to mortality in women (all-cause HR 1.23, 95% CI 1.04 –1.44, p=.02, cardiovascular HR 1.42, 95% CI 1.08 –1.85, p=.01) than in men (all-cause HR 1.17, 95% CI 0.88 –1.56, p=.27, cardiovascular HR 1.02, 95% CI 0.69 –1.54, p=.92). However, we did not find significant gender-Hemoglobin A1c interactions for either all-cause or cardiovascular mortality.

Conclusions:
Increasing hemoglobin A1c may be more strongly related to increased all-cause and cardiovascular mortality in women than in men.
Abstract 5067: Responsiveness to Low Dose Aspirin Influences Levels of Inflammatory Biomarkers
Authors: Qayyum Rehan , Faraday Nauder , Yanek Lisa R , Vaidya Dhananjay , Becker Lewis C , Becker Diane M
Published: July 2021

Platelets participate in cellular and humoral immunity; however the effect of low dose aspirin (ASA) therapy on platelet-mediated inflammation is unknown. Healthy family members (N=1934) of patients with premature coronary artery disease (CAD) participated in a 14-day trial of ASA 81 mg/day. Urinary 11-dehydro thromboxane B2 (uTxM), which reflects in vivo platelet activation, was measured at baseline and after ASA. Subjects were dichotomized by post-ASA uTxM levels into ASA responsive (lower quartile) and ASA resistant (upper quartile) groups based on previous studies showing an association between the upper quartile and incident CAD events. Levels of the inflammatory biomarkers, plasma hs-CRP and IL-6, were measured at both time points and compared between the two quartile extremes using multivariable-adjusted models. The study sample had 967 participants (females, 59%; blacks, 43%, age, 43.9±13 years). At baseline, plasma hs-CRP levels were similar between the upper and the lower uTxM quartiles, but IL-6 levels were significantly higher in the upper quartile (Table

). After ASA therapy, hs-CRP and IL-6 decreased in the lowest quartile, but increased in the upper (resistant) quartile, and the between-quartile difference (post-adjusted for pre) became significant for both inflammatory markers. Compared to ASA responsive subjects, those who are ASA “resistant” have higher levels of plasma inflammatory markers after ASA therapy and demonstrate lesser reductions in inflammatory markers from baseline. These extreme quartile differences in hs-CRP and IL-6 may reflect differences in ASA’s ability to suppress platelet-mediated inflammation, and may contribute to the increased CAD risk observed in aspirin resistant persons.

Table.

Comparison of hs-CRP and IL-6 in the Extreme Quartiles of 11-dehydro thromboxane B2 (uTxM)
Abstract 5100: C-Reactive Protein and Parental History Improve Global Cardiovascular Risk Prediction: The Reynolds Risk Score for Men
Authors: Ridker Paul M , Paynter Nina P , Rifai Nader , Gaziano Michael , Cook Nancy R
Published: July 2021

Background.
CRP and family history independently associate with future cardiovascular events and have been incorporated into risk prediction models for women (the Reynolds Risk Score for women). However, no cardiovascular risk prediction algorithm incorporating these variables currently exists for men.

Methods.
Among 10,724 initially healthy American non-diabetic men who were followed prospectively for incident cardiovascular events over a median period of 10.8 years, we developed a cardiovascular risk prediction model that included hsCRP and parental history of myocardial infarction before age 60 years, and compared model fit, discrimination, and reclassification to prediction models limited to age, blood pressure, smoking, total cholesterol, and high-density lipoprotein cholesterol.

Results.
1,294 cardiovascular events accrued during study follow-up. Predictive models incorporating hsCRP and parental history (the Reynolds Risk Score for men) had better global fit (P<0.001), a superior (lower) Bayes Information Criterion (BIC)(23008 vs 23048), and larger C-indexes (0.708 vs 0.699, P < 0.001) than did predictive models without these variables. For the endpoint of all cardiovascular events, the Reynolds Risk Score for men reclassified 17.8 percent of the study population into higher- or lower-risk categories with markedly improved accuracy among those reclassified. In models based on the ATP-III preferred endpoint of coronary heart disease and limited to men not taking lipid-lowering therapy, 16.7 percent of the study population were reclassified to higher- or lower-risk groups, again with significantly improved global fit (P<0.001), smaller BIC (13870 vs 13891), larger C-index (0.714 vs 0.704, P < 0.001), and almost perfect accuracy among those reclassified (99.9 percent). For this model, NRI was 8.4 percent and CNRI 15.8 percent (both P-values < 0.001).

Conclusion.
We developed an improved global risk prediction algorithm for men incorporating hsCRP and parental history that should allow better targeting of preventive therapies to maximize benefit while minimizing toxicity and cost.
Abstract 6207: Derivation of a Novel Prediction Algorithm for Idiopathic Venous Thromboembolism in Women
Authors: Everett Brendan M , Paynter Nina P , Buring Julie E , Glynn Robert J , Cook Nancy R , Ridker Paul M
Published: July 2021

Background
: Established risk factors for idiopathic venous thromboembolism (VTE) include age, prothrombotic mutations, and obesity. A risk prediction algorithm might allow clinicians to focus preventive efforts.

Methods
: We derived a prediction model for idiopathic VTE using 22 possible predictor variables and their interactions in 19,458 initially healthy Caucasian women who were followed for incident idiopathic VTE. Minimization of the Bayes Information Criterion (BIC) was used to help identify the best, most parsimonious model, and estimates of discrimination (C-index) and calibration (Hosmer-Lemeshow (H-L) statistic) comparing observed and predicted risk were computed and compared with a model including only age and weight.

Results:
The mean (SD) age was 54.1 (7.1) years, the mean (SD) weight 69.9 (14.1) kilograms, and 2.8% and 5.3% of participants carried the prothrombin and factor V Leiden mutations, respectively. After a median of 12.4 years of follow up, we observed 130 idiopathic cases of VTE. The best fitting model included log(age), log(weight), log(apolipoprotein A1), and the presence of the prothrombin or factor V Leiden mutations (C-index 0.704; H-L statistic 5.9). When compared to model including only log(age) and log(weight) (C-index 0.636; H-L statistic 3.9), the full model achieved higher discrimination at similar calibration and led to a net reclassification of 34.5 percent (6705) of participants, all correctly.

Conculsion:
In our population of middle-aged, initially healthy Caucasian women, a model that includes age, weight, apolipoprotein A1, and the prothrombin and factor V Leiden mutations predicts incident idiopathic VTE more accurately than one including age and weight alone.

Table.

Idiopathic venous thromboembolism risk reclassification - basic and best-fitting models
Abstract 6254: Nfkb Blockade Attenuates Cardiac Oxidative Stress And Improves Mitochondrial Function In Type II Diabetes
Authors: Mariappan Nithya , Sriramula Srinivas , Haque Masudul , McIlwain Elizabeth , Francis Joseph
Published: July 2021

Type II diabetes is the most important predisposing factor for the development of cardiovascular disease. Recent findings from our lab suggest that cytokines and the nuclear transcription factor (NF-kB) contribute to oxidative stress and cardiac function. In this study, we determined the effect of NF-kB blockade on cardiac pathology in a mouse model of type II diabetes. Five week old obese db/db mice (control) and heterozygous lean mice (n = 8) were treated with PDTC (100mg/kg, orally) for 20 weeks. At the end of the study, left ventricular (LV) function was measured using echocardiography. Subsequently, mice were sacrificed and the LV was used for biochemical and mitochondrial assays. LV tissue and mitochondrial ROS and superoxide (O
2
−
) were measured using electron spin resonance spectroscopy. The structural integrity of the mitochondrial membrane was measured using swelling assay and TEM analysis. Fractional shortening was decreased (24.29 ± 0.48) in control db/db mice relative to that of db/db mice treated with PDTC (38.06 ± 1.3). Control db/db mice had enhanced tissue NFkB activity accompanied by increased production of ROS and O
2
−
. These animals had increased expression of NF-kB, RAGE, and gp91 phox, contributing to increased oxidative stress. Obese db/db mice also showed increased mitochondrial damage and mitochondrial ROS production which was accompanied by decreased ATP production. In contrast, treatment with PDTC attenuated oxidative stress, protected against mitochondrial dysfunction and preserved cardiac function. This study demonstrates that PDTC, a NFkB blocker, can mitigate oxidative stress, and improve mitochondrial structural integrity directly, through down-regulation of increased oxygen free radicals by its superoxide scavenging activity, thereby increasing ATP synthesis and thus restoring cardiac function in type II diabetes.
Abstract 6262: Obesity in Childhood is Associated With an Impaired Regenerative Capacity of Circulating Progenitor Cells and Vascular Dysfunction
Authors: Erbs Sandra , Höllriegel Robert , Linke Axel , Burman Agnieszka , Friebe Daniela , Sandri Marcus , Adams Volker , Töpfer Madlen , Walther Claudia , Schuler Gerhard , Körner Antje
Published: July 2021

The raising prevalence of obesity in childhood appears to preceed the development of atherosclerosis and the increased incidence of cardiovascular diseases in adulthood. This might be related to the fact that already in children, obesity is associated with classical risk factors for coronary disease, like hypertension, hyperlipidemia, or diabetes. Therefore, aim of the present study was to evaluate, whether obese children (compared to lean controls) are characterized by vascular damages and altered regenerative capacity of circulating endothelial progenitor cells (CPCs) as an early indicator of developing atherosclerosis.

Methods:
In 30 obese (11±3 years of age, BMI 28.1±1.3) and 30 lean control children (12±3 years of age, BMI 17.5±0.4) insulin sensitivity was evaluated by oral glucose tolerance testing (OGT). Peripheral flow-mediated dilatation (FMD) and intima media thickness (IMT) of the carotid artery were assessed as measures of vascular integrity. The number of CD34/KDR+ CPCs was quantified using FACS analysis and the functional capacity of CPCs was determined by migration assay.

Results:
Obesity in early childhood is associated with peripheral insulin resistance as an early manifestation of diabetes (serum insulin in OGT after 120 min: 543±102 pmol/L in obese vs. 275±39 pmol/L in lean, p<0.05). FMD was significantly impaired in obese compared to lean children (reactive hyperemia index 1.25±0.05 vs. 1.55±0.08, p<0.05). Already in childhood, obesity was accompanied by a gain in IMT (0.40±0.01 mm vs. 0.30±0.01 mm in lean, p<0.05). Obese children had significantly reduced numbers of circulating CPCs compared to lean children (70±7 vs. 119±13 cells/mL blood, p<0.05). There was an inverse correlation between the number of CPCs and the extent of obesity as determined by BMI-SDS (r=−0.27, p<0.05). Additionally, functional capacity of CPCs was significantly reduced in obese children (migration following a SDF-1 gradient: 170±31 CPCs/1000 plated CPCs in obese vs. 258±37 CPCs/1000 plated CPCs in lean, p<0.05).

Conclusion:
Already in childhood, obesity is associated with an impaired endogenous regenerative capacity, which might result in generalized vascular damage as an early stage of atherosclerosis.
Abstract P60: Mortality from Severe Trauma in Patients with Pre-existing Cardiac Disease
Authors: Ferraris Victor A , Ferraris Suellen P , Saha Sibu P
Published: July 2021

BACKGROUND:
We observed significant morbidity and mortality in patients who suffer severe traumatic injuries with pre-existing cardiac disease. We wondered about the cardiac risks factors that predispose to worse outcomes in these patients.

METHODS:
We reviewed 10,144 trauma admissions to the University of Kentucky over a 5 year period (2002 to 2007) in patients 21 years or older. The types and extent of injuries were characterized and risk factors for poor outcome were assessed.

RESULTS:
Of the 10,144 trauma patients, adequate cardiovascular history was obtained before emergency treatment in 5971 patients (58.9%). Of the 700 trauma deaths, 236 (33.7%) had adequate medical history to allow accurate assessment of cardiovascular risk. Severe head & chest injuries caused death in most patients (79.2%). Significant multivariate predictors of trauma-related death in this cohort included Glascow coma score (O.R. = 1.266/score unit), older age (O.R. = 0.931/year), injury severity score (O.R. = 1.096/unit score), major burn (O.R. = 7.36), assault with a weapon (O.R. = 3.236), and female gender (O.R. = 1.561). Importantly, after propensity adjustment, significant cardiovascular mortality risks included pre-injury warfarin therapy, congestive heart failure (CHF), & beta-blocker use. The highest mortality rates occurred in patients with combinations of these cardiovascular risk factors (see table

).

CONCLUSIONS:
Pre-injury cardiac risk factors, especially pre-injury warfarin, beta-blocker use and CHF, are independent multivariate predictors of mortality in patients suffering significant trauma. Patients with more than one pre-injury cardiac risk factor have 2 to 4 times the mortality risk compared to those without cardiac risks. :
Category (Complete)
: Miscellaneous
Keyword (Complete)
: Trauma ; Cardiac risks ; warfarin
Samson Resident Award (Complete): *Paul C. Samson Award (Required)
: No
Status:
Complete

Propensity Adjusted Cardiovascular Risk Factors for Trauma Mortality (C-statistic = 0.940)
Abstract P62: Derangements in Blood Glucose Following Initial Resuscitation from In-Hospital Cardiac Arrest:
A Report from the American Heart Association National Registry of Cardiopulmonary Resuscitation
Authors: Beiser David G , Carr Gordon E , Edelson Dana P , Peberdy Mary A , Hoek Terry L Vanden
Published: July 2021

BACKGROUND:
Hyperglycemia is associated with poor outcomes in a variety of critically-ill patient populations; however, little is known about the role of hyperglycemia in determining outcomes following in-hospital cardiac arrest (IHCA).

METHODS:
We performed a retrospective analysis of 17,800 adult in-hospital cardiac arrests from the National Registry of Cardiopulmonary Resuscitation. Minimum and maximum blood glucose values during the first 24 hours following return of spontaneous circulation (ROSC) were examined.

RESULTS:
Glucose data from 3,226 patients were available for analysis. Post-ROSC maximum blood glucose values were markedly elevated in diabetic (median, 226 mg/dL, [IQR, 165 – 307 mg/dL)] as well as non-diabetic patients (176 mg/dL, 135 – 239 mg/dL). Survival to hospital discharge was higher in non-diabetics than diabetics (45.5% [95% CI, 43.3 – 47.6%] vs. 41.7% [95% CI, 38.9 –44.5%], p = 0.037). In non-diabetics, survival to hospital discharge varied significantly when stratified by glucose value with optimal survival odds occurring across a broad range of minimum (71 – 170 mg/dL) and maximum (111 – 240 mg/dL) glucose values. Cardiac arrest duration quartile was identified as a significant factor associated with the development of post-ROSC hypo- and hyperglycemia in non-diabetics.

CONCLUSIONS:
Derangements in blood glucose are common following IHCA in both diabetic and non-diabetic patients. Optimal survival odds occur across a relatively broad range of glucose values in non-diabetics; however, both hypo- and hyperglycemia are associated with worse outcomes and associated with longer arrest durations.
Abstract P63: Safety and Feasibility of a New Innovative Cooling Approach for Immediate Induction of Therapeutic Hypothermia in Patients after Successful Resuscitation. Trans-nasal Cooling after Cardiac Arrest
Authors: Busch Hans-Joerg , Janata Andreas , Eichwede F , Födisch Markus , Wöbker G , Stephan T , Schwab Tilmann , Karassimos E , Fritz Harald , Inderbitzen Becky , Barbut Denise , Sterz Fritz
Published: July 2021

Methods
We assessed safety and feasibility of trans-nasal cooling in a multi-centre, single-arm descriptive study of comatose patients who had been successfully resuscitated after cardiac arrest. Forty three patients were treated with a non-invasive cooling device through which cooling was achieved via trans-nasal delivery of an evaporative coolant into the nasopharynx. Initial temperatures, course of cooling, and systemic and local adverse events during cooling were documented. Patients were treated with nasal cooling until they either reached target temperature or were transitioned to treatment according to local standard protocols. Primary outcome was speed of cooling. Survival and cerebral performance category (CPC) at hospital discharge were recorded.

Results
Data are presented as mean ± SD or median (interquartile range (25, 75%)). Mean age was 71.1 ± 10.8 years. VF was the first documented rhythm in 52.4% of the patients, asystole in 31.0%. Temperatures at admission were 35.2±1.2°C tympanic, 35.5±1.1°C, core (arterial or esophageal), and 35.9±1.0°C, bladder. Time from the start of cooling to target temperature (33°C) was 50.0 (35.0 – 68.3) minutes tympanic, and 72.5 (17.3–146.3) minutes, core. Cooling rate of tympanic temperature was 2.4°C/hr., core cooling rate was 1.4°C/hr and bladder 0.9°C/hr. Adverse events affecting the nasal area occurred in 9/43 patients, resolved in 8 (78%) patients spontaneously. One had persistent damage at death, 18 hours later. Systemic adverse events were consistent with the patient population being treated. Twelve patients (30%) had a CPC of 1–2. Twenty-three patients (57.5%) died, none related to the hypothermia procedure, and five patients (12.5%) had a poor outcome. In patients with VF, eight patients (40%) had a CPC of 1–2, eight patients died and four patients had poor outcome.

Conclusions
Trans-nasal cooling for induction of therapeutic hypothermia in patients after successful resuscitation from cardiac arrest is feasible and effective in lowering temperature rapidly in a hospital emergency setting. This method of cooling offers the possibility for immediate introduction and needs now to be investigated in the field setting.
Abstract P108: Orexin-A Improves Arousal and Electroencephalographic Entropy in Rats after Cardiac Arrest
Authors: Koenig Matthew A , Jia Xiaofeng , Kang Xiaxu , Velasquez Adrian , Thakor Nitish V , Geocadin Romergryko G
Published: July 2021

Objective: Cardiac arrest (CA) survivors progress through electroencephalographic (EEG) burst-suppression prior to arousal. Orexin-A, an excitatory neuropeptide, elicits arousal EEG patterns during anesthetic-induced burst-suppression. We hypothesized that intraventricular injection of orexin-A would improve arousal and burst-suppression after CA in rats.

Methods: Eighteen Wistar rats were subjected to 7-minute asphyxial CA and resuscitation by external cardiac massage. Rats were divided into treatment (n=9) and control (n=9) groups. Twenty minutes after resuscitation, the treatment group received 0.1 mL of 1nM orexin-A intraven-tricularly, while controls received saline. EEG was continuously monitored and quantified using Information Quantity (IQ), a measure of entropy validated for detection of burst-suppression and arousal patterns. IQ was normalized to baseline prior to CA (range 0 –1.0). Arousal was quantified using the neurological deficit scale (NDS). Stereologic microscopy was used to determine the ischemic neuronal fraction of hippocampus CA1 and cortex.

Results: Baseline and post-resuscitation characteristics were similar between the 2 groups. Burst frequency by visual inspection was similar after administration of orexin-A or saline. Rats in the orexin-A group demonstrated higher IQ values (mean±SD) compared to controls beginning 10 minutes after drug injection (0.564±0.098 vs. 0.429±0.116, p=0.024). IQ values remained significantly higher in the orexin-A group for the first 60 minutes after drug injection and subsequently converged. The NDS score (mean±SD) at 4 hours was higher in the orexin-A group compared to controls (57.3±5.8 vs. 40.7±5.9, p<0.02), but scores were similar at 72 hours. The ischemic neuronal fraction was similar between groups in cortex (p=0.54) and hippocampus CA1 (p=0.14).

Conclusions: In rats resuscitated from CA, orexin-A hastened improvement of EEG entropy and arousal measures without increasing ischemic neuronal injury. The role of orexin-A in hastening arousal after CA deserves further investigation.
Abstract P111: Applying the Principles of Functional Stimulation to Electrical CPR
Authors: Gilman Byron L , Brewer James , Kroll Mark W , Ristagno Giuseppe , Li Yongqin , Wang Hao , Sun Shijie , Weil Max Harry , Tang Wanchun
Published: July 2021

Background: We have previously reported on a specialized electrical stimulus that produces coronary and carotid blood flow during VF. The values selected for the Current (C), Pulse Width (PW), Pulse Period (PP), Train Width (TW) and Train Rate (TR) are critical to obtaining effective blood flow. An initial experiment in which these parameters were systematically studied in order to identify the optimal parameters has been previously reported. In this study we utilized some of the principles established in the field of NeuroMuscular Electrical Stimulation (NMES) of the extremities to further optimize ECPR. A primary principle of interest is that the force produced is proportional to charge delivered (Coulombs or amp-seconds.) Consequently, higher C, longer PW, shorter PP and longer TW would be predicted to produce greater force.

Hypothsis: We hypothesized that for ECPR as in NMES that: CPP over time would be proportional to the total charge delivered per constriction.

Methods: We applied 118 episodes of ECPR in 7 porcine subjects as previously described. VF was electrically induced and untreated for 10 seconds. ECPR was then applied for 60 seconds or until CPP dropped below 15 mm Hg. The specific ECPR intervention applied was determined according to a factorial design of experiment in which two levels each of C, PW, PP and TW were evaluated. The CPP was recorded at 10-second intervals during ECPR until it was terminated.

Results: PP and PW showed significant differences in their ability to maintain CPP > 15 mm Hg (T15) for prolonged periods of time (PP=25 ms: 49±15 s to T15 vs PP=50 ms: 41±17 s to T15, p=0.004) (PW=0.2 ms: 42±17 s to T15 vs PW=0.8 ms: 48±16 s to T15, p=0.05). Regression analysis further showed that an increase in PW and a decrease in PP worked independently and without interaction to increase T15 for CPP. These two parameters relate directly to total charge delivered with the result that, for each additional unit of total charge delivered, there was an almost 8 times increase in the T15 time period (coefficient = 7.7, 95% CI=(6.5,8.9))

Conclusions: The increases in charge provided by longer PP and shorter PW produced significantly longer time of CPP > 15 mm Hg within the limits of this test. Further study is required in order to further extend the duration of action ECPR.
Abstract P134: Total Liquid Ventilation Induced Ultrafast Cardioprotective Hypothermia during Prolonged Myocardial Ischemia in Rabbits
Authors: Tissier Renaud , Lidouren Fanny , Chenoune Mourad , Couvreur Nicolas , Ghaleh Bijan , Bizé Alain , Dubois-Randé Jean-Luc , Berdeaux Alain
Published: July 2021

Introduction: Total liquid ventilation with temperature-controlled perfluorocarbons induces an ultra-fast cardioprotective cooling when instituted during a 30-min coronary artery occlusion (CAO) in rabbits.

Hypothesis: We hypothesized that ultra-fast hypothermia instituted with a short total liquid ventilation episode would be still beneficial after a prolonged CAO as compared to conventional low rate surface cooling.

Methods: Anesthetized rabbits underwent a 60-min CAO followed by 4 hours of reperfusion before infarct size and no reflow evaluations. Rabbits randomly underwent either a normothermic CAO (Control group, n=7) or cooling from 5th min of CAO to the end of CAO (target left atrial temperature: 32°C). Cooling procedures were either low rate surface cooling (LRC) using ice-filled cold blankets (LRC group, n=7) or ultra-fast cooling (UFC) initiated by 20 min of hypothermic total liquid ventilation and maintained if necessary by cold blankets (UFC group, n=6). An additional group underwent a similar ultra-fast cooling protocol started at the 20th min of CAO (UFC-delayed group, n=6). After reperfusion, all hypothermic animals were rewarmed.

Results: Left atrial temperature was similar in all groups at baseline (Table

). Hypothermia was modest in LRC vs UFC and UFC-delayed groups at 30-min CAO but reached similar level at the end of ischemia (i.e., 60-min CAO). Interestingly, no reflow and infarct sizes were only significantly reduced in UFC and UFC-delayed but not in LRC groups as compared to Control. Infarct size reduction was significantly better predicted by the integrated decrease in left atrial temperature throughout ischemia than by the temperature at the end of ischemia.

Conclusion: Ultra-fast cooling induced by total liquid ventilation afforded cardioprotection against prolonged ischemia in rabbits, even when instituted later than a low rate surface cooling.

Left atrial temperature (LAT) at different times of the protocol and infarct and no reflow sizes
Abstract P179: Effectiveness of CPR Prior to Electrical Shock to Out-of-hospital Cardiac Arrest with Ventricular Fibrillation: A Population-based Study in a Metropolitan Area in Japan “The Utstein Osaka Project”
Authors: Nishiuchi Tatsuya , Hayashino Yasuaki , Fukuhara Shunichi , Iwami Taku , Hayashi Yasuyuki , Kajino Kentaro , Ikeuchi Hisashi , Hiraide Atsushi , Yukioka Hidekazu , Matsuoka Tetsuya
Published: July 2021

Objective
: To evaluate the effectiveness of CPR prior to electrical shock stratified by the duration from ambulance call to CPR in witnessed out-of-hospital cardiac arrest patients with VF.

Study Design
: Population-based observational study (May 1, 1998–December 31, 2006).

Settings
: Osaka, Japan with a population of 8.8 million.

Subjects
: We analyzed the Utstein Style data on patients who met the following inclusion criteria:

witnessed by citizens,

18 years or older,

initial recorded cardiac rhythm was VF or pulseless VT,

bystander CPR was not performed.

Methods
: Subjects were divided into three groups according to the duration from the initiation of CPR by ambulance personnel to first electrical shock; immediate shock group: first electrical shock were given in 0–1 minute after CPR was initiated; 2–3 min delayed group: first electrical shock were given in 2–3 minutes after CPR initiated; and ≥4 min delayed group: first electrical shock were given in more than 4 minutes.

Main outcome measure
: Survival at one month.

Results
: 909 patients were included in the current analysis. In immediate shock group, survival at one month decreased with an increase in interval between ambulance call and the initiation of CPR. In contrast, 2–3 min delayed group had better prognosis than immediate shock group if CPR was initiated between 8–9 minutes after ambulance call (13% vs. 27% of one month survival; OR 2.50; 95% CI. 1.02–6.00; P=0.045).

Conclusion
: Our findings suggested that 2–3 minute-delayed electrical shock was associated with better prognosis compared with immediate electrical shock if CPR by ambulance personnel was initiated in 8–9 minutes from ambulance call.
Abstract P183: Physical Stress Does Not Increase Ventilation Rate during Resuscitation in a Manikin Model
Authors: Eilevstjønn Joar , Nysæther Jon , Myklebust Helge
Published: July 2021

BACKGROUND:
Studies indicate that trained medical personnel often deliver manual ventilations at excessive rates while performing advanced cardiac life support (ACLS). Excessive ventilation rates may contribute to increased mortality among these patients. We seek to uncover if physical stress affects our perception of ventilation rate.

HYPOTHESIS:
We hypothesized that physical stress would increase the ventilation rate during simulated cardiac arrest in a manikin model.

METHOD:
Six persons at Laerdal Medical were asked to ventilate an intubated manikin (Laerdal ResuciAnne PC SkillReporting system) for three minutes under two different conditions. For the first condition the participants were asked to perform strenuous physical exercise (running up and down a stairway for several minutes) immediately prior to ventilating the manikin. For the second condition all participants were allowed to rest before performing ventilations. Participants had to deliver ventilations at what they felt were 10 ventilations per minute (vpm). No clock or other time keeping means were available. Heart rate and breathing rate of the participants were measured using ECG and trans-thoracic impedance signals from a defibrillator (Philips HeartStart MRx). Statistics are derived using the average rate values from each participant.

RESULTS:
The participants did not ventilate faster after physical stress (Mean rate =7.00 vpm, SD =1.94) than during the condition at rest (Mean rate =7.14 vpm, SD =1.10;
t
(5)
=−0.20, 95% CI of mean difference −1.83, 1.57; Cohen’s
d
=0.085;
p
=0.85). On the average, no participants ventilated faster than the recommended rate of 10–12 vpm during any condition. Both the participants’ heart rate and respiration rate were significantly different during the two conditions; mean (SD) heart rate 112 (10.7) vs. 82 (5.3) bpm (p=0.002), mean (SD) respiration rate 21.2 (5.98) vs. 14.5 (3.44) breaths per minute (p=0.010).

CONCLUSIONS:
Ventilation rates do not seem to be elevated by physical stress of the provider. Causes of hyperventilation should be sought elsewhere, e.g. amongst mental stressors.
Abstract P200: Optimal Phase Relationship Between Defibrillation and Manual Chest Compression Improves Shock Success
Authors: Li Yongqin , Wang Hao , Cho Jun Hwi , Quan Weilun , Freeman Gary , Bisera Joe , Weil Max Harry , Tang Wanchun
Published: July 2021

Introduction
A newly developed blanket provides the protection for rescuer from shock during cardiopulmonary resuscitation (CPR) and allow for uninterrupted chest compression. We examined relationships between the phase of manual compression and the timing of defibrillation based on measurement of the 50% defibrillation threshold (DFT50).

Methods
Ventricular fibrillation (VF) was electrically induced and untreated for 10 seconds in 8 domestic male pigs weighing between 22–31 kg. The depth and frequency of manual chest compression utilizing the isolated blanket initiated and continued for 25 seconds guided by a CPR prompter (iCPR, ZOLL Medical Corporation, Chelmsford, MA). A biphasic electrical shock of variable energies ranging from 30~150J was delivered at 5 phases of the compression period as shown in Figure 1–A

. A group in which defibrillation was attempted at a constant 2 seconds following discontinued of chest compression served as a control.

Results
No difference between coronary perfusion pressures (CPP) prior to delivering of the shock were observed between the 6 groups. The calculated energy required for defibrillation, however, was significantly lower during the latter half of decompression as represented by group C and D (Figure 1–B

).

Conclusion
Defibrillation efficacy is maximal when an electrical shock is delivered during the latter phase of decompression.
Abstract 212: Globular Domain of Adiponectin Attenuates Post-Ischemia Myocardial Oxidative/Nitrative Stress in an AMPK-Independent Fashion
Authors: Wang Yajing , Gao Erhe , Tao Ling , Lau Wayne B , Yuan Yuexing , Goldstein Barry J , Tian Rong , Koch Walter , Ma Xin L
Published: July 2021

Reduced plasma adiponectin (APN) level not only contributes to the increased incidence of MI in diabetic patients, but also plays a causative role in increased cardiac injury after MI in these patients. However, singling mechanisms by which APN achieves its cardioprotection remains incompletely understood. Here, we investigated the role of AMP activated protein kinase (AMPK), the molecule that transfers APN’s metabolic signaling, in APN’s cardioprotection. Male adult mice with cardiac specific overexpression of a dominant negative AMPK α
2
subunit (AMPK-DN) or wild type (WT) littermates controls were subjected to 30 min of MI followed by reperfusion (R) and treated with vehicle (V) or globular domain of APN (gAPN, 2 μg/g) 10 min before R. Comparing with WT mice, MI/R caused greater cardiac injury including larger infarct size, more apoptosis and poorer cardiac function (P<0.05) in AMPK-DN mice. Treatment of WT mice with gAPN significantly attenuated MI/R injury (P<0.01). Most interestingly, although the metabolic regulatory effect of gAPN is completely lost in AMPK-DN mice, a significant portion of cardioprotection of gAPN retained in the transgenic animals. Specifically, treatment of AMPK-DN mice with gAPN reduced infarct size (54±4.7% vs. 81±3.6% in V group, P<0.01), decreased apoptosis (lesser TUNEL positive labeling, weaker DNA fragmentation, and lower caspase 3 activity. P value all <0.01) and improved cardiac function after MI/R (higher LVEF, lower LVEDP and higher dP/dt
max
. P value all <0.01). To further delineate the mechanisms responsible for gAPN’s AMPK-independent cardioprotection, effect of gAPN on cardiac oxidative/nitrative stress following MI/R were examined. Treatment of AMPK-DN mice with gAPN reduced superoxide and nitric oxide overproduction, decreased peroxynitrite formation (from 0.38±0.04 to 0.23±0.02 ng/mg protein in WT and from 0.50±0.06 to 0.32±0.02 ng/mg protein in AMPK-DN mice), and inhibited NADPH oxidase and iNOS expression to the same extent as that seen in WT mice. Taken together, our results demonstrated for the first time that a significant portion of gAPN cardioprotection is not mediated by the traditional AMPK signaling pathway and that the anti-oxidative/anti-nitrative effects of gAPN are AMPK-independent.