bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3546: Cardiac Rehabilitation Improves Blood Flow in the Scarred Myocardium and Decreases Angiogenic Cytokines
Authors: Lee Bai-chin , Chen Ssu-Yuan , Tseng Wen-Yih I , Chen Ming-Fong , Lee Yuan-Teh
Published: July 2021

Background

Cardiac rehabilitation improves myocardial blood flow (MBF) in the patients with myocardial infarction (MI), but the mechanism is unclear. Angiogenic cytokines such as stromal-derived factor-1 (SDF-1), vascular endothelial growth factor (VEGF) and stem cell factor (SCF) could recruit circulating stem cells to improve tissue perfusion. We tested the hypothesis that plasma SDF-1, VEGF or SCF levels were association with MBF in the scarred myocardium in the post-MI patients undergoing cardiac rehabilitation.

Methods and Results

Thirty-nine patients were recruited, and 20 were randomly assigned to undergo a training program. Nineteen age- and sex- matched healthy subjects without any cardiovascular risk factors constituted the normal group. MBF, quantified with cardiac magnetic resonance by model-independent deconvolution methods, was assessed in the scarred myocardium at rest and at stress. Compared to the healthy subjects, peak oxygen uptake (VO
2
) and MBF at stress, but not that at rest were lower; while SDF-1 and VEGF, but not SCF were higher in the post-MI patients. After 3 months, an increased MBF at stress (+30%,
P
<0.01) and peak VO
2
(+15%,
P
=0.01) and decreased SDF-1 (−11%,
P
=0.01) and VEGF (−9%,
P
<0.01) were seen in the training group, but not the MI control or normal group. The change in peak VO
2
correlated with the changes in MBF at stress and SDF-1 and VEGF (
r
=0.48, −0.38, −0.40, respectively; all
P
<0.05).

Conclusions

Cardiac rehabilitation improves myocardial blood flow in the scarred myocardium with a concomitant decrease in plasma angiogenic cytokines.
Abstract 3547: Are U.S. Adults with Heart Disease Meeting Physical Activity Recommendations?
Authors: Zhao Guixiang , Ford Earl S , Li Chaoyang , Mokdad Ali H
Published: July 2021

The benefits of physical activity on risk of cardiovascular disease have led to recommendations to increase its levels in patients with heart disease. We investigated the degree of compliance with national physical activity recommendations, issued by the Centers for Disease Control and Prevention and the American College of Sports Medicine as well as the U.S. Surgeon General, among U.S. adults with coronary heart disease (heart disease) in comparison with people without heart disease using data from 2005 Behavioral Risk Factor Surveillance Survey. Information on heart disease or physical activity was self-reported. Moderate physical activities were those that cause small increases in breathing or heart rate (e.g., brisk walking) while vigorous physical activities were those that cause large increases in breathing or heart rate (e.g., running). Total physical activity was defined as participation in either moderate or vigorous physical activity. A total of 297,145 participants aged 18 years or older were included in our analyses and 24,496 people had heart disease. The age-adjusted prevalence and the odds ratios (ORs) for meeting total, moderate or vigorous physical activity recommendations were calculated in people with or without heart disease. People with heart disease were less likely to engage in physical activity at recommended levels than those without heart disease (41%, 32% and 22% versus 49%, 37% and 29%, respectively, for meeting total, moderate or vigorous physical activity recommendations, P<0.01 for all). The unadjusted ORs for adults with heart disease who met total, moderate or vigorous physical activity were 0.61 [95% confidence interval (CI): 0.58–0.65], 0.76 (95% CI: 0.72–0.80), and 0.45 (95% CI: 0.42–0.49), respectively. These ORs were attenuated but remained significant after adjustment for demographic variables, or after further adjustment for diabetes status and limitations for physical activity performance [The ORs were 0.92 (95% CI: 0.87–0.97), 0.95 (95% CI: 0.89–1.00) and 0.88 (95% CI: 0.81–0.95), respectively]. Our findings demonstrate the need for continuing efforts to promote physical activity in patients with heart disease who do not have limitations for performing physical activity.
Abstract 3560: Obstructive Sleep Apnea Exacerbates Endothelial Dysfunction In Patients With Metabolic Syndrome
Authors: Akishita Masahiro , Ohike Yumiko , Hashimoto Masayoshi , Iijima Katsuya , Eto Masato , Teramoto Shinji , Ouchi Yasuyoshi
Published: July 2021

Background: Both obstructive sleep apnea (OSA) and metabolic syndrome (MS) are well known as the risk factor of cardiovascular diseases, and are prevalent among obese patients. However, whether OSA deteriorates endothelial dysfunction in MS patients has not been determined. We therefore examined flow-mediated vasodilation (FMD) in MS patients with or without OSA.

Methods: We enrolled 49 overweight patients (body mass index ≥25, aged 35–69 years) and categorized into the 3 groups; patients with MS but not OSA (MS group, n=21), Group 2: patients with both MS and OSA (MS+OSA group, n=14), Group 3: patients with no risk factors but overweight (control group, n=14). MS was defined using the IDF criteria and OSA using polysomnography. FMD was measured using ultrasound as the percent change of the brachial artery diameter.

Results: Compared with the control group, MS group showed significantly lower %FMD (6.8±2.4 [mean±SD] vs 5.0±2.7, p<0.001) and HDL cholesterol, and higher triglycerides and hemoglobin A1c. Although there were no significant differences in classical risk factors between MS group and MS+OSA group, %FMD was significantly lower in MS+OSA group than in MS group (3.0±1.3 vs 5.0±2.7, p<0.001). On multiple regression analysis, OSA was significantly related to %FMD, independent of age, body mass index, blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, fasting plasma glucose, and smoking (β=−0.328, p=0.02).

Conclusion: OSA exacerbates endothelial dysfunction in patients with MS, possibly leading to the increased risk of cardiovascular disease.
Abstract 3573: Higher Soluble Thrombomodulin is Associated with Risk of Coronary Artery Calcification: Longitudinal Analysis of the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Vaidya Dhananjay , Cushman Mary , Holvoet Paul , Polak Joseph F , McClelland Robyn L , Szklo Moyses , Ouyang Pamela
Published: July 2021

Background. A prior cross sectional study reported that higher soluble thrombomodulin (sTM) was associated with subclinical atherosclerosis only in the presence of higher soluble intercellular adhesion molecule-1, sICAM-1. We evaluated this interaction longitudinally with regard to coronary artery calcium (CAC) in the MESA cohort.

Methods: MESA is a multi-center longitudinal study with baseline measurements of endothelial biomarkers in a random sample (n=1000) of the baseline cohort. In the random sample, 374 men and 496 women had CT measurement for CAC (Agatston score) at baseline and a median follow-up of 2.9 years. Among those with no baseline CAC (n=490), we estimated the relative risk of detectable CAC at follow-up using general linear models with Gaussian error and robust standard errors. Among those with detectable baseline CAC (n=380), change in CAC on follow-up was modeled using robust regression that down-weights outliers. Models with log(sTM) as predictor were adjusted for follow-up time, sex, ethnicity and baseline age, BMI, smoking, diabetes, systolic blood pressure, total cholesterol, use of BP or lipid-lowering medications and for hormone replacement (HRT) in women in separate models. Interactions between sTM and sICAM-1, sex and ethnicity was assessed.

Results: The median [interquartile range] of sTM was 38 [28 to 47] ng/mL for persons with incident detectable CAC, and 30 [23 to 41] ng/mL in those without (rank sum p <0.001). On adjustment, a 2-fold higher sTM at baseline (e.g., from 23 to 46 ng/mL) was associated with a 1.36-fold increased risk of detectable CAC on follow-up (95% CI: 1.03, 1.79, p=0.031). Among those with baseline detectable CAC, the rank correlation between sTM level and change in CAC score was 0.10 (p = 0.042), however, on adjustment, a 2-fold higher sTM was associated with a non-significant 0.86 Agatston units greater CAC change (p = 0.84). Higher sICAM-1 did not modify the association of sTM with CAC incidence (interaction p = 0.15) or change (interaction p = 0.26). There was no significant heterogeneity by sex, or ethnicity, or confounding by HRT in women.

Conclusion: High circulating levels of sTM were independently associated with incident calcification of the coronary arteries.
Abstract 479: Disruption of Myosin VI Expression Results in Altered Vasculature and VEGF Signaling
Authors: Lanahan Anthony A , Kerley-Hamilton Joanna S , Moodie Karen L , Zhuang Zhen W , Chittenden Thomas W , Simons Michael
Published: July 2021

Background
: Myosin VI is an actin-based molecular motor that is involved in endocytic trafficking of plasma membrane receptors. Myosin VI has multiple binding partners including the cytoplasmic PDZ protein synectin that has recently been shown to be involved in VEGF signaling and VEGF receptor endocytosis.

Hypothesis
: We assessed the hypothesis that disruption of the myosin VI gene results in altered VEGF signaling and receptor trafficking in endothelial cells (EC), leading to altered arterial morphogenesis.

Methods
: Myosin VI
−/−
mice were used for in vivo and in vitro studies. Primary myosin VI
−/−
(KO) and
+/+
(WT) EC were isolated from mouse heart, lung, inferior vena cava and abdominal aorta by dissection followed by PECAM-1 cell sorting.

Results:
In response to VEGF-A, primary EC treated with an siRNA targeted against myosin VI showed decreased activation of Erk1/2 as determined by Western blotting. Further experiments using myosin VI
−/−
and
+/+
EC confirmed a reduction in the activation of Erk1/2 in response to VEGF in cells lacking myosin VI. Activation of VEGFR-2 in myosin VI
−/−
endothelial cells is also decreased as assessed by diminished phosphorylation of tyrosine 1175 within the cytoplasmic domain of the receptor. To determine whether myosin VI is involved in vascular development and angiogenesis, micro CT analysis of myosin VI
−/−
and
+/+
murine kidney vasculature was performed. Results suggest that myosin VI
−/−
animals have fewer large arterial vessels compared with the WT controls.

Conclusions:
VEGFR-2 activation and downstream signaling is decreased in myosin VI
−/−
endothelial cells in response to VEGF-A. Myosin VI
−/−
mice show altered vasculature structure as assessed by micro CT analysis. Similar perturbations in VEGF signaling and vasculature structure were seen in synectin
−/−
mice and endothelial cells. The decrease in VEGF signaling associated with reduced myosin VI and synectin levels points to a potential role of VEGF receptor trafficking resulting in these defects. Together these results suggest that the interaction of myosin VI and synectin is important in vascular development and angiogenesis.
Abstract 3629: Socioeconomic and Ethnic Disparities in the Use of Biventricular Pacemakers in Heart Failure Patients with Left Ventricular Systolic Dysfunction
Authors: Casale John C , Wolf Flossie , Pei Yanfen , Devereux Richard B
Published: July 2021

Background
: Biventricular pacing (BiV) is an important therapeutic advance for symptomatic heart failure (HF) patients (pts) with reduced left ventricular ejection fraction (EF), but whether socioeconomic and ethnic disparities exist in the use of BiV in HF pts is unknown.

Methods
: Data were collected on all hospitalized HF pts with an EF ≤ 35% from Pennsylvania hospitals that implanted BiVs from Jan. 2004 to Dec. 2005. These hospitals submitted clinical data from chart abstraction and administrative data to the Pennsylvania Health Care Cost Containment Council. Multiple logistic regression analyses used patient clinical data, insurance and hospital characteristics to identify independent predictors of BiV implantation in symptomatic HF pts with EF≤ 35%.

Results
: Of the 20,269 HF pts with EF≤ 35%, BiV was implanted in 2,065/15,861 (13%) whites, 182/3107 (5.9%) African-Americans and 175/1301 (13.5%) others. Analysis of 12 clinical variables identified associations of older age, male gender and prior myocardial infarction or bypass surgery with a higher likelihood of BiV implantation (all p<.0001). Pts with diabetes or higher Mediqual Atlas severity score were less likely to have BiV implantation (both p<.01). Pts with lower EF or with intraventricular conduction delay were more likely to have BiV implantation (both p<.0001). After adjusting for these variables, African-American ethnicity (odds ratio (OR) 0.50, [95% confidence interval (CI) 0.42– 0.60], p<.0001) and poverty level (defined as the percentage of residents in a zip code whose household income was below the federal poverty threshold) comparing the poorest quintile to the other quintiles (OR 0.79, [95% CI 0.70 – 0.89], p<.0001), were independently associated with lower likelihood of BiV implantation. Additional independent predictors of a higher likelihood of BiV implantation included commercial and Medicare vs. Medicaid, self-pay or other insurance type, and for-profit hospital status (both p<.05).

Conclusion
: In a large statewide sample, BiV was implanted less frequently in African-Americans and in lower income pts, independent of clinical, hospital and insurance characteristics, identifying persisting disparities in use of advanced cardiac technology.
Abstract 3634: Association of Weight Loss and Changes in Left Ventricular Geometry and Function - Results of the longitudinal population based MONICA/KORA-Survey
Authors: Stritzke Jan , Markus Marcello R , Lieb Wolfgang , Luchner Andreas , Döring Angela , Keil Ulrich , Schunkert Heribert
Published: July 2021

Background: Obesity is related to left ventricular (LV) hypertrophy and diastolic dysfunction. However it remains unclear if changes in life style resulting in loss of body weight also have beneficial effects on left ventricular remodeling. In this study we evaluated the effects of weight loss on left ventricular geometry and function during ten years of follow-up.

Methods: Subjects (n=1005, aged 25 to 74 years) who originated from a gender and age stratified random sample of German residents of the Augsburg area were examined by standardized echocardiography at baseline and again after ten years. The associations between weight loss and long-term changes of left ventricular end-diastolic diameter (LVEDD), wall thickness (WT), left ventricular mass (LVM), and left atrial diameter (LA) were assessed. Mean relative changes and odds ratios were computed by statistical models adjusting for gender, age, body height, systolic blood pressure and body weight at baseline.

Results: After ten years of follow-up 305 individuals presented with a loss of body weight (−3.5+/−3.4kg on average). Whereas 700 subjects presented with an increase of body weight (+5.4+/−4.7kg). Ageing related changes in LV geometry were significantly different in the two groups. Specifically, individuals with weight loss displayed a favorable geometry with relative changes of WT (+5.9% [CI-95% 4.3, 7.5] vs. + 8.1% [7.0, 9.2], p=0.024), LVEDD (−0.6% [−1.5, 0.2] vs. 30.8% [0.2, 1.4], p=0.008), LVM (+6.5% [4.3, 8.8] vs. +11.9% [10.4, 13.5], p<0.001) and LA (−0.9% [−2.1, 0.2] vs. +2.5% [1.7, 3.3], p<0.001), as compared to individuals with weight gain. Moreover, the risk for incident left ventricular hypertrophy (OR 2.5 [1.5– 4.3], p=0.001) and incident diastolic dysfunction (OR 1.9 [1.1–3.4], p=0.023) was significantly higher in individuals presenting with an increase in body weight.

Conclusions: As compared to weight gain, weight loss is associated with a significant deceleration of left ventricular remodeling during ageing of the heart. Nevertheless, even in the weight loss group there was no regression in left ventricular mass detectable. Consequently, early interventions especially in young obese individuals are essential for prevention of premature onset of cardiac remodeling.
Abstract 3640: Diabetes Mellitus is Associated with Increased Risk of Fatal and Non-Fatal Cardiovascular Events in Heart Failure Patients with Preserved Ejection Fraction - Findings From the Irbesartan in Heart Failure with Preserved Systolic Function Trial
Authors: McKelvie Robert S , Komajda Michel , Massie Barry M , McMurray John J , Zile Michael R , Donovan Mark , Ptaszynska Agata , Carson Peter
Published: July 2021

Background:
Diabetes mellitus (DM), present in about a quarter of heart failure (HF) patients with reduced ejection fraction (HF-REF), is associated with increased risk of fatal and non-fatal cardiovascular (CV) events. Less is known about the prevalence and impact of DM in HF patients with preserved ejection fraction (HF-PEF). The prevalence and effect of DM on clinical outcomes were examined in patients enrolled in the Irbesartan in Heart Failure with Preserved Systolic Function Trial (I-PRESERVE).

Methods:
The I-PRESERVE trial randomized 4128 HF-PEF patients (EF≥45%) to receive irbesartan or placebo. The primary outcome of time to all-cause mortality or CV hospitalization (myocardial infarction [MI], stroke, worsening HF, atrial or ventricular arrhythmia or unstable angina) was compared between patients with and without DM over one year of follow-up. A combined HF endpoint (HF mortality and hospitalization) was also evaluated. Comparison of the outcomes between patients with and without DM was expressed as a hazard ratio (HR). The independent predictive role of DM was examined in a multivariable model (which included symptoms, signs, clinical history, CV examination, biochemical, and hematological findings).

Results:
In I-PRESERVE 27% had a history of DM at baseline. DM patients more often had a body mass index ≥30 (51% vs 38%), history of stroke (12% vs 9%), history of MI (28% vs 22%), estimated glomerular filtration rate <60 ml/min/1.73m
2
(34% vs 29%), and pulmonary congestion on chest x-ray (46% vs 38%). In patients with DM, 17% and 11% had primary and HF events, respectively within 1 year; for patients without DM, 11% and 6% had primary and HF events. In a multivariate analysis DM remained a significant predictor of primary events (HR 1.48; 95% CI 1.22, 1.79) or HF events (HR 1.67; 95% CI 1.32, 2.12).

Conclusions:
The prevalence of DM in HF-PEF is similar to that reported in HF-REF. HF-PEF patients with DM have a significantly worse outcome than those without DM and this increased risk is independent of other factors associated with a worse prognosis.
Abstract 3644: Moderate Alcohol Consumption Is Associated With Improved Endothelial Function
Authors: Suzuki Keiko , Elkind Michell S , Boden-Albala Bernadette , Jin Zhezhen , Di Tullio Marco R , Sacco Ralph L , Homma Shunichi
Published: July 2021

Background and Purpose: Moderate alcohol intake is protective against coronary artery disease. Endothelial dysfunction contributes to atherosclerosis and the pathogenesis of cardiovascular disease. Effects of alcohol consumption on endothelial function may be relevant to these cardiovascular outcomes, but very few human studies have examined the effect of alcohol consumption on endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery.

Methods: In the population-based Northern Manhattan Study (NOMAS), we performed a cross-sectional analysis of lifetime alcohol intake and brachial artery FMD during reactive hyperemia using high-resolution B-mode ultrasound images among 883 stroke free participants (mean age 66.7 years, women 56.6%, Hispanic 67.5%, black 17.5%, and white 14.9%).

Results: The mean brachial FMD was 5.68% and the median was 5.52%. Reported lifetime alcohol consumption was as follows:147 (16.7%) non-drinkers (<1drink/month), 616 (69.8%) >1drink/mo to 2drinks/day, 59 (6.7%) >2 to 5drinks/day, 60(6.8%) >5drinks/day. Compared to non-drinkers, those who drank >1 drink/mo to 2 drinks/day were more likely to have FMD above the median (5.5%) of FMD (unadjusted OR 1.7, 95% CI 1.2–2.5, p=0.004). In multivariate analysis, the relationship between moderate alcohol consumption and FMD remained significant after adjusting for multiple traditional cardiovascular risk factors, including age, body mass index, hypertension, diabetes and smoking (adjusted OR 1.5, 95%CI 1.1–2.2, p=0.02). No beneficial effect on FMD was seen for those who drank more than 2 drinks/day.

Conclusion: Consumption of up to 2 alcoholic beverages per day independently was associated with improved FMD compared to nondrinkers in this multiethnic population compared to non-drinkers. The effect on FMD may represent an important mechanism in explaining the protective effect of alcohol intake on cardiovascular disease.
Abstract 3666: Remaining Lifetime Risks for Cardiovascular Disease Death by Risk Factor Burden at Selected Ages in Black and White Men and Women
Authors: Berry Jarett D , Garside Daniel B , Cai Xuan , Dyer Alan R , Lloyd-Jones Donald M
Published: July 2021

BACKGROUND: Although the effect of risk factor (RF) burden at age 50 years has been reported, the effect of RF burden measured at other ages on lifetime risk for cardiovascular diseases (CVD) is unknown and no data are available for non-whites.

METHODS: Using limited access data from the National Heart Lung and Blood Institute, we pooled participants from the Framingham Heart Study, the Framingham Offspring Study, the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, and the Chicago Heart Association Detection Project in Industry with RFs measured at or near ages 45, 55, and 65 years for blacks and whites separately in sex-stratified analyses. Blood pressure and cholesterol levels, smoking, and diabetes status were used to stratify the pooled cohort into 5 risk strata. Lifetime risks for CVD events to 85 years of age were estimated for men and women, with death free of CVD as a competing event.

RESULTS: We included 21,534 men (15.7% black) and 24,063 women (9.3% black) who were followed for 651,144 person-years. With more adverse levels of single risk factors, lifetime risks were greater for both men and women in both races. Compared with white participants with ≥2 major RFs, those with all optimal RF levels had substantially lower lifetime risks (see Table

). There was a similar pattern of results observed in blacks for lifetime risks for CVD death. Additional analyses of the endpoints of fatal/non-fatal coronary heart disease and fatal/non-fatal stroke revealed a similar pattern of results.

CONCLUSIONS: Remaining lifetime risks for CVD are dramatically higher with greater RF burden at all ages studied. The absence of established RFs is associated with very low remaining lifetime risk for CVD, particularly for men and women at age 65 years.
Abstract 3710: Stanford GEMS (Girls health Enrichment Multisite Studies): Long-Term Efficacy of After-School Dance and Screen Time Reduction in Low-Income African-American Girls
Authors: Robinson Thomas N , Matheson Donna M , Kraemer Helena C , Obarzanek Eva , Wilson Darrell M , Haskell William L , Pruitt Leslie A , Thompson Nikko S , Haydel K. Farish , Fujimoto Michelle , Varady Ann , Killen Joel D
Published: July 2021

Objective: To test the efficacy of a 2-year, community- & family-based intervention to reduce weight gain in low-income, preadolescent African-American girls

Design: 2 arm, parallel group, randomized controlled trial Setting: Low-income areas of Oakland, CA Participants: 8 –10 year old African-American girls

Interventions: Girls were randomized to a 2 year, culturally-tailored after school dance program and a home/family-based intervention to reduce screen media use (dance/TV) versus an information-based community health education (HE) active-placebo comparison intervention Primary

Outcome: Change in body mass index measured up to 5 times over the course of the study

Results: 261 girls were randomized (134 dance/TV, 127 HE) and 225 (86.2%) completed 1 or more follow-up measures (118 dance/TV, 107 HE; mean ± SD follow-up = 25.7 ± 8.5 mos and 25.2 ± 9.6 mos, respectively). Intent-to-treat analysis found no statistically significant differences between groups in BMI change (mean difference in changes= .04 kg/m2 per year, 95% confidence interval [95% CI] =−.19 to .27; P=.72). Similar results were found for waist circumference and triceps skinfold. Compared to girls in HE, girls in the dance/TV group significantly reduced fasting total cholesterol levels (difference in changes = −3.49 mg/dl per year, 95% CI −5.28 to −1.70; P<.001), fasting LDL-cholesterol (−3.02, 95% CI −4.74 to −1.31; P<.001) and depressive symptoms (P<.05). Changes between groups were not statistically significant for HDL-cholesterol, triglycerides and insulin, resting blood pressure and heart rate, dietary energy and fat, accelerometer-measured physical activity, and screen time. Moderator analysis indicated the dance/TV reduction intervention was significantly more effective than HE in reducing BMI gain for girls with single parent families, more screen time and more depressive symptoms at baseline.

Conclusions: A culturally-tailored after school dance and screen time reduction intervention did not slow BMI increases more than a health education intervention in low-income African-American girls. The dance/TV intervention resulted in greater reductions in fasting total and LDL-cholesterol and depressive symptoms, but not in other cardiovascular disease risk factors.
Abstract 3733: Postprandial Free Fatty Acid Metabolism During Fenofibrate Treatment Predicts Postprandial Lipid And Lipoprotein Changes
Authors: Rosenson Robert S
Published: July 2021

Objective:
To determine the effects of fenofibrate (160 mg/d) on fasting and postprandial non-esterified fatty acids (NEFA) and lipoproteins in subjects with hypertriglyceridemia and the metabolic syndrome.

Methods:
Fifty-nine subjects with fasting hypertriglyceridemia (≥1.7 mmol/L and <6.9 mmol/L) and two or more of the Adult Treatment Panel III criteria of the metabolic syndrome were randomized to fenofibrate (160 mg/d) or placebo in a double-blind controlled clinical trial. A standardized fat load (50 g/m
2
) was given after a 12 h fast. Blood specimens were obtained at fasting and 3.5 h and 8 h after the test meal.

Results:
After the test meal, postprandial (area under the curve) NEFA increased (mean ± SEM) by 11.2 ± 5.1% in the placebo group; in contrast NEFA decreased by 18.6 ± 3.8% in the fenofibrate group (
P
=0.0001). No differences in fasting NEFA were observed between groups (
P
=0.16). Fenofibrate reduced postprandial triglycerides (−45.4%,
P
<0.0001) and significantly decreased postprandial large (−40.8%,
P
<0.0001) and medium (−49.5%, p<0.0001) very low-density lipoprotein (VLDL) particles, as well as small LDL (−40.3%,
P
<0.0001) and total LDL particles (−19.0%,
P
<0.005). Reduction in NEFA (AUC) correlated with reductions in postprandial triglycerides (r=0.73,
P
<0.0001), non-HDL-C (r=0.67,
P
<0.0001) and with increases in HDL-C (r=0.38,
P
<0.01). The reduction in NEFA was more strongly correlated with decreased large VLDL (r=0.72,
P
<0.0001) than medium VLDL (r=0.34,
P
<0.02) or small VLDL particles (r=0.22,
P
<0.13). Postprandial reductions in NEFA were also correlated with lowering of small LDL (r=0.53,
P
<0.0001) and total LDL particles (r=0.60,
P
<0.0001).

Conclusions:
Treatment with fenofibrate significantly decreases postprandial NEFA and the reductions in NEFA are highly correlated with reductions in triglycerides, non-HDL-C and an increase in HDL-C. Postprandial NEFA are an important predictor of postprandial lipoprotein changes in subjects with hypertriglyceridemia.
Abstract 3737: The Association Between Therapy With Insulin Glargine Versus Nph And The Risk Of Myocardial Infarction In Patients With Type 2 Diabetes
Authors: Kosiborod Mikhail , Zhang Quanwu , Foody JoAnne
Published: July 2021

Background:
Prior studies have demonstrated that insulin glargine produces less hypoglycemia, as compared with NPH. Whether these results translate into better long-term cardiovascular outcomes in patients with Type 2 diabetes is unknown.

Methods:
Using a national managed care administrative database, we evaluated patients with Type 2 diabetes who were on oral antiglycemic agents within 6 months prior to initiating either insulin glargine (n=15,039) or NPH (n=5,666) and had at least 12 months of subsequent continuous plan enrollment during 03/2001–03/2005. Cox proportional hazard models were used to compare the rate of subsequent myocardial infarction (MI) events (defined by ICD-9 codes) following initiation of glargine vs NPH, after adjusting for demographic characteristics, comorbidities, other medications, insulin adherence and baseline Hemoglobin A1C (A1C).

Results: Mean age was 56 years, 49% were women; mean duration of follow up was 24 months. Among patients who had available A1C (n=2514), those in glargine group had higher A1C at baseline vs. NPH (9.3 vs 8.9 respectively, p<0.0001). During the 1
st
year following insulin initiation, 8.7% patients in NPH vs. 7.5% in glargine group had at least one medical claim for hypoglycemia (OR=1.17, 95% CI: 1.05–1.31). In unadjusted analysis, the rate of MI events was 4.4% in glargine group vs. 7.7% in the NPH group (p<0.0001). After multivariable adjustment, risk of MI events remained lower in glargine group (HR: 0.78, 95% CI: 0.64–0.95). Although hypoglycemic events were associated with higher MI risk (HR 1.3, 95% CI 1.18–1.44 for each quarter with a medical claim for hypoglycemia during 1
st
year of follow up), the association between glargine use and lower risk of MI events remained significant even after adjusting for hypoglycemia (HR: 0.79, 95% CI 0.65–0.96).

Conclusion:
Initiation of insulin glargine in patients with Type 2 diabetes is associated with lower risk of subsequent MI events, as compared with NPH. Lower rate of hypoglycemia associated with glargine use does not completely account for this difference in outcomes. Further studies are needed to validate these results and provide insights into potential physiologic mechanisms.
Abstract 494: Differences in Sarcoplasmic Reticulum Ca
2+
Loading and Spontaneous Ca
2+
Release in Permeabilized Sinoatrial Nodal and Ventricular Myocytes: Effect of cAMP.
Authors: Sirenko Syevda G. , Lyashkov Alexey E. , Yang Dongmei , Lakatta Edward G. , Vinogradova Tatiana M.
Published: July 2021

To maintain their normal automaticity, sinoatrial nodal cells (SANC) have a unique property to generate spontaneous, local Ca
2+
release (LCR) from sarcoplasmic reticulum (SR) under physiological conditions. To further characterize the mechanisms that underlie LCR’s, we compared SR Ca
2+
loading and release in saponin permeabilized, rabbit SANC and ventricular myocytes (VM) over a wide range of free [Ca
2+
] in a physiological buffer containing 0.5 mM EGTA. The SR Ca
2+
load, indexed as Ca
2+
released by a rapid application of caffeine, was assessed by a confocal linescan image as the amplitude of Fluo-4 of Ca
2+
fluorescent transient (F/F
0
); total spontaneous LCR signal mass during a 400 ms period over 100 μm was assessed by integrating the fluorescence of each LCR and summating the integral of all LCR’s. Over a range of free [Ca
2+
] from 50 to 200 nM SR Ca
2+
load was the same in two cell types (Fig. A

), but at 250 nM SR load it doubled in VM, but not in SANC. Failure of SANC SR load to further increase may be attributed to the exaggerated spontaneous LCR: at 200 nM free Ca
2+
, spontaneous LCR signal mass was 4-times greater in SANC than in VM. A greater LCR signal mass in SANC than in VM at an equal or lesser SR Ca
2+
load indicates that spontaneous Ca
2+
release mechanisms differ in 2 cell types, possibly, on the basis of a recent report of high basal levels of cAMP/PKA phosphorylation in SANC. When VM were exposed to cAMP (10 μM) spontaneous LCR signal mass markedly increased (Fig. B

) at a constant Ca
2+
load (150 nM [Ca
2+
]i Fig. A

). Thus, in physiological [Ca
2+
], spontaneous LCR’s differ in SANC vs VM, and this may be explained, in part at least, by high basal cAMP/PKA phosphorylation of Ca
2+
cycling proteins in SANC.
Abstract 3739: The Influence of Albuminuria on Mortality in Patients with Stable Coronary Artery Disease
Authors: Solomon Scott D , Lin Julie , Solomon Caren G , Jablonski Kathleen , Rice Madeline Murguia , Steffes Michael , Domanski Michael , Hsia Judith , Gersh Bernard J , Arnold J. Malcolm O , Rouleau Jean , Pfeffer Marc A
Published: July 2021

Background:
Patients with chronic kidney disease are at increased risk for cardiovascular morbidity and mortality. We assessed the association between albuminuria and death or cardiovascular events among patients with stable coronary disease.

Methods:
We studied patients enrolled in the Prevention of Events with an ACE Inhibitor (PEACE) trial, in which patients with chronic stable coronary disease and preserved systolic function were randomized to trandolapril or placebo and followed for a median of 4.8 years. The urinary albumin to creatinine ratio (ACR) assessed in a core laboratory in 2977 patients at baseline and in 1339 patients at follow-up (mean 34 months) was related to estimated glomerular filtration rate (eGFR) and outcomes.

Results:
The majority of patients (73%) had a baseline albumin/creatinine ratio within the normal range. Independent of the eGFR and other baseline covariates, a higher albumin/creatinine ratio even within the normal range was associated with increased risks for all-cause mortality (p < 0.001) and cardiovascular death (p = 0.01). The effect of trandolapril therapy on outcomes was not significantly modified by the level of albuminuria. Nevertheless, trandolapril therapy was associated with a significantly lower mean follow-up ACR (12.5 ug/mg vs 14.6 ug/mg, p = 0.0002), after adjusting for baseline ACR, time between collections and other covariates. An increase in ACR over time was associated with increased risk of cardiovascular death (HR per log ACR 1.74, 95% confidence intervals 1.08–2.82).

Conclusions:
Albuminuria, even in low levels within the normal range, is an independent predictor of cardiovascular and all-cause mortality.
Abstract 3773: Impact of Chronic Statin Therapy on Arrhythmic Events in Patients With Acute Coronary Syndromes. The GRACE registry
Authors: Vedre Ameeth , Gurm Hitinder S , Froehlich James B , Kline-Rogers Eva , Montalescot Gilles , Gore Joel M , Brieger David , Dedrick Rebecca , Eagle Kim A
Published: July 2021

Background:
Animal studies have demonstrated a reduction in arrhythmias with the use of statins in models of myocardial ischemia. We hypothesized that chronic statin therapy might be associated with a reduction of in-hospital arrhythmic events in patients with acute coronary syndromes (ACS).

Methods:
We evaluated the in-hospital outcomes in 48,930 patients enrolled in the GRACE registry between 1999 and 2006 with an admission diagnosis of ACS. Patients were divided into two groups based on prior statin use. The primary outcome measure for this analysis was in-hospital occurrence of ventricular tachycardia (VT), ventricular fibrillation (VF) and atrial fibrillation (AF).

Results:
A total of 13,539 (28%) patients were on prior chronic statins and 35,391 (72%) were not. Those on chronic statins had higher rates of history of angina (69% vs 44%), diabetes (34% vs 22%), heart failure (15% vs 8%), hypertension (74% vs 58%), atrial fibrillation (9% vs 7%) and hyperlipidemia (84% vs 35%). They also had lower rates of in-hospital arrhythmias (Figure

). Chronic statin use remained strongly associated with a reduction in VT/VF (adjusted OR 0.61, 95% CI 0.54 – 0.69; P<0.0001) and AF (adjusted OR 0.71, 95% CI 0.62– 0.80; P<0.0001) in propensity-adjusted multivariable models.

Conclusion:
Patients on prior statins had a lower incidence of in-hospital arrhythmic events following ACS. It is not clear if the relationship is causal. Data from future randomized trials would need to definitively establish this association. Our study suggests another possible benefit from appropriate primary and secondary prevention therapy with statins.
Abstract 522: Specific Oxidized Phospholipids Modulate Platelet Reactivity In Vivo During Hyperlipidemia Via Cd36: A Mechanism Linking Hyperlipidemia, Oxidant Stress And A Pro-thrombotic Phenotype
Authors: Podrez Eugene A , Byzova Tatiana V , Febbraio Maria , Salomon Robert G , Ma Yi , Valiyaveettil Manojkumar , Poliakov Eugenia , Sun Mingjiang , Finton Paula J , Curtiss Brian R , Chen Juhua , Zhang Renliang , Silverstein Roy L , Hazen Stanley L
Published: July 2021

Enhanced platelet reactivity is critical to the pathophysiology of occlusive arterial thrombotic disease. Despite the strong clinical associations between hyperlipidemia, a major risk factor for atherosclerosis, and a pro-thrombotic phenotype, the mechanisms responsible for enhanced platelet reactivity during hyperlipidemia remain unknown. Pro-atherosclerotic lipid abnormalities such as hypercholesterolemia are associated with both enhanced oxidant stress and generation of biologically active oxidized lipids, including potential ligands for the scavenger receptor CD36, a major platelet surface glycoprotein. Using multiple murine in vivo thrombosis models we now demonstrate that hyperlipidemic atherosclerosis prone mice (apolipoprotein E-deficient or LDL receptor-deficient) form occlusive intravascular thrombi faster than wildtype mice, and that genetic deletion of CD36 protects mice from hyperlipidemia-associated enhanced platelet reactivity and accompanying pro-thrombotic phenotype. Structurally defined oxidized choline glycerophospholipid molecular species that serve as endogenous high affinity ligands for CD36 are shown to :

be markedly increased in plasma of hyperlipidemic mice;

be elevated in plasma of subjects with low HDL levels; and

to promote platelet activation and alpha-granule release via CD36 at pathophysiological levels.

These studies thus demonstrate that platelet CD36 interactions with specific endogenous oxidized lipids play a heretofore unrecognized role in the well-known clinical associations between hyperlipidemia, oxidant stress and a prothrombotic phenotype.
Abstract 523: Expression, Activation and Function of Integrin α
M
β
2
on Neutrophil-derived Microparticles
Authors: Woody Neil M , Szpak Dorota , Plow Edward F , Pluskota Elzbieta
Published: July 2021

The levels of circulating leukocyte-derived microparticles (MPs) are elevated in thrombosis and most cardiovascular diseases, and it has been suggested that MPs are not only markers of disease but also active contributors to pathogenesis via their interaction with various cell types. Such interactions will depend on the presence and activity of molecules expressed on the MP surface. In our study we have considered the presence and activation state of a major adhesion receptor on the surface of leukocytes, integrin α
M
β
2
(CD11b/18, Mac-1) on MPs derived from human neutrophils (PMN). MPs were obtained from resting or agonist-stimulated PMNs, and the presence of α
M
β
2
was assessed by FACS. α
M
β
2
expression was significantly enhanced on MPs derived from stimulated PMN (e.g., resting MPs: MFI = 3.5 ± 0.7 vs PMA-MPs: MFI = 20 ± 4, and fLMP-MPs: MFI = 24 ± 5). PSGL-1 was expressed by MPs but levels were not affected by stimulation. Of note, α
M
β
2
expressed on MPs obtained from stimulated PMNs was in active conformation as assessed using mAb (CBRM1/5) to activation-dependent epitope of this integrin. Recognition of a protein ligand, fibrinogen, by activated α
M
β
2
on the MPs was also demonstrable. With evidence of a functionally active integrin, we sought to evaluate its role in mediating MP interaction with platelets. MP binding to isolated, resting platelets was dose and time dependent. However, MPs expressing activated α
M
β
2
bound to more platelets, and only MPs obtained from stimulated PMNs induced platelet activation as assessed P-selectin expression (resting-MPs: MFI = 25.1 ± 6.5 vs PMA-MPS: MFI = 293 ± 60, n = 4). MP binding and platelet activation were reduced by ~40–50% by function-blocking mAbs to α
M
β
2
and GPIbα, implicated as a major counter-receptor for α
M
β
2
. Complete abrogation of these events was achieved by the combination of blocking reagents to both α
M
β
2
/GPIbα and to PSGL-1/P-selectin. In conclusion, MPs released by stimulated PMNs express activated α
M
β
2
. This integrin cooperates with PSGL-1 to mediate interaction with and activation of platelets.
Abstract 14: Pulmonary Hemodynamics in Neonatal Lambs with Pulmonary Hypertension - Effect of Resuscitation with 21% versus 100% Oxygen
Authors: Lakshminrusimha Satyan , Swartz Daniel D , Gugino Sylvia F , Wynn Karen A , Ryan Rita M , Steinhorn Robin H , Russell James A
Published: July 2021

The optimal level of O
2
supplementation during neonatal resuscitation is controversial. We recently published data that resuscitation with 21% or 100% O
2
for 30 min results in similar decreases in pulmonary vascular resistance (PVR) in normal newborn lambs (
Pediatr Res in press)
. However, the effect of resuscitation with 21% or 100% O
2
on pulmonary hemodynamics in lambs with
in-utero
pulmonary hypertension (PH) is not known.

Methods:
PH was induced in fetal lambs by antenatal ductal ligation at 126 d of gestation (term ~ 145 d). Lambs were delivered 9 d later by C-section and ventilated with 21% O
2
or 100% O
2
for 30 min. Control lambs without PH were ventilated similarly for comparison (n=4 −7 in each group). The lambs were instrumented to measure PVR prior to delivery. After 30 min, lambs with PH were ventilated with 50% O
2
and pulmonary vasodilator responses to inhaled NO 20 ppm were evaluated.

Results:
PVR was significantly higher in lambs with PH compared to control. The decrease in PVR was similar by 30 min in 21% and 100% O
2
resuscitated control lambs. In contrast, 100% O
2
resuscitation resulted in a significantly greater decrease in PVR in lambs with PH (fig A

). However, 100% O
2
resuscitation impaired subsequent decrease in PVR in response to inhaled NO in both control and PH lambs (fig B

).

Conclusions:
100% O
2
resuscitation results in a greater decrease in PVR but impairs subsequent pulmonary vasodilation to NO in lambs with PH.

Speculation:
Ventilation of PH lambs with 100% O
2
significantly increases lung isoprostane levels (
AJRCCM 2006 174 12:1370
). We speculate that a similar increase in reactive oxygen species following 100% O
2
resuscitation interferes with the vasodilator response to NO.
Abstract 530: Is Severe Hypertriglyceridemia (> 1000 mg/dl) a Risk Factor for Atherosclerosis ?
Authors: Gafinen Katharina , Hoerger Andreas , Hauenschild Annette , Kantner Heike , Kloer Hans
Published: July 2021

Severe Hypertriglyceridemia (SHTG) is believed to be a rare condition difficult to treat, but associated with a relatively low risk of morbidity, except for pancreatitis. In particular, SHTG is not believe to be a risk factor of atherosclerosis . Therefore, we performed a morbidity survey of SHTG patients being followed up for at least 2 years in the lipid clinics of the German Working Group. Evaluation of co-morbid conditions was based on patient chart review. The data of 893 SHTG cases (689 males (m), 204 females (f)) were compiled. As an admission criterion to the study SHTG patients had to have a documented TG > 1000 mg/dl prior to follow-up in the respective lipid clinics. Mean age was 50 ± 12 years, mean BMI was 28.7 ± 4.5. Upon admission to the lipid clinics mean TG was 2800 mg/dl (1000 – 16 000 mg/dl) and mean TC was 480 mg/dl (162–15920 mg/dl). Even after long term treatment in the lipid clinics mean TG and TC were still highly elevated (1190mg/dl and 322mg/dl, respectively). Regarding co-morbid conditions the following prevalence data were obtained: episodes of pancreatitis 24% (21% m,35%f), gallstones 21% (17% m, 32% f),hypertension 70%, diabetes 51 %, hyperuricemia 72 %. The prevalence of clinical manifestations of CVD was as follows : CHD by angiography 24% (27% m , 16 % f), MI 14 % (16% m, 5% f) , angina 21% (23% m, 17% f), PVD 15 % (14% m, 17% f), cerebrovascular disease 20 % (19% m, 24% f ). A total of 36 % of all SHTG patients (37% m, 33% f) showed at least one clinical manifestation of atherosclerotic cardiovascular disease. After excluding other risk factors 19% of remaining SHTG cases (20% m, 16 % f) still had clinical CVD. In conclusion, we were able to demonstrate a significant CVD burden in both male and female SHTG patients. SHTG itself seems to be an independent CVD risk factor.
Abstract 33: Impact of Delayed Time to Defibrillation on Neurological and Functional Status Among Survivors of In-Hospital Cardiac Arrest
Authors: Chan Paul S , Krumholz Harlan M , Nichol Graham , Nallamothu Brahmajee K
Published: July 2021

Background:
Expert guidelines advocate defibrillation within 2 minutes of an in-hospital cardiac arrest due to ventricular arrhythmias. However, the impact of delayed defibrillation on neurological and functional status at discharge among survivors is unknown.

Methods:
We identified 6,744 patients with cardiac arrests due to ventricular fibrillation or pulseless ventricular tachycardia at 369 hospitals within the National Registry of Cardiopulmonary Resuscitation. Using multivariable logistic regression that adjusted for demographics, clinical variables, hospital site, hospital-level variables (hospital size, monitored bed or intensive care status), and admitting diagnoses, we examined the association between delayed defibrillation (>2 minutes) and neurological and functional status at discharge using the previously developed Cerebral and Overall Performance Categories. Performance categories were dichotomized as no major disability vs. major disability and/or vegetative state.

Results:
The median time to defibrillation was 1 minute (interquartile range:< 1 to 3 minutes), with delayed defibrillation found in 2,000 (29.7%) patients. Overall, 2,311 (34.3%) patients survived to hospital discharge [n=1,863 (39.3%) for prompt defibrillation; n=448 (n=22.4%) for delayed defibrillation]. Among those surviving to discharge, delayed defibrillation was associated with a lower likelihood of no major disability in neurological status (adjusted OR of 0.73; 95% CI: 0.57 to 0.94; p=0.01) and functional status (adjusted OR of 0.73; 95% CI: 0.55 to 0.96; p=0.02).

Conclusion
: Delayed defibrillation is associated with worse neurological and functional status among survivors of in-hospital cardiac arrests. Minimizing time to defibrillation represents a major opportunity to improve neurological and functional status in these high-risk patients.