bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 6167: Appropriate Timing Enhances the Utility of Plasma Brain Natriuretic Peptide in Predicting Survival in Pulmonary Arterial Hypertension
Authors: Batal Omar , Krasuski Richard A , Dweik Raed A
Published: July 2021

Background:
The natural course of pulmonary arterial hypertension (PAH) is characterized by progressive functional worsening leading to right heart failure and death. Since plasma brain natriuretic peptide (BNP) levels correlate with right ventricular dysfunction, we sought to evaluate the use of BNP as a prognostic indicator in PAH.

Methods and Results:
We examined our prospective pulmonary hypertension registry for patients who underwent right heart catheterization (RHC) between 1998 and 2008. The BNP values from the time of catheterization until date of last visit or death were analyzed in relationship to overall survival. Of the 626 patients who underwent RHC, 559 met the Venice classification of PAH: 83% category I, 10% category III, 5% category IV, and 2 % category V. Baseline mean pulmonary artery pressures were 47±16 mm Hg and cardiac index 2.6±1 l/min/m
2
. During follow up, patients were treated with prostanoids (27%), endothelin blockers (31%), PDE5 inhibitors (40%), calcium channel blockers (2%), and 56% received combination therapy. BNP values during the first 6 months were higher in patients who died in the first 2 years (n=108) compared to patients surviving more than 5 years (n=82) but the levels had no correlation to survival [R
2
=0.03, p=0.2]. Interestingly, the strongest predictor for survival was the BNP level obtained 12–14 months from RHC [R
2
=0.7, p=0.0001]. All patients who survived over 5 years had BNP value less than 150 ng/L at 12 months and all patients with BNP values >330 ng/L at 12 months were dead by 2 years. Furthermore, there was an accelerated rate of increase in BNP levels in patients who did not survive past 2 years [BNP rise rate (ng/L/month): non- survivors 33 ± 14 while, long-term survivors 0.3 ± 1; p=0.008].

Conclusions:
In patients with pulmonary arterial hypertension, initial BNP levels do not appear to have prognostic significance. BNP levels at 1 year, however, are strong predictors of early mortality or long term survival. The rate of rise in BNP levels is a novel concept that may be a useful management tool before the 1 year time point.
Abstract 6175: The Time-delay that Nullify the Advantage of Primary Percutaneous Coronary Angioplasty over Fibrinolysis is Affected by Patients’ Risk: 1-Hour Does Not Fit All
Authors: Tarantini Giuseppe , Gasparetto Nicola , Napodano Massimo , Razzolini Renato , Ramondo Angelo , Iliceto Sabino
Published: July 2021

Abstract:
Background. The mortality benefit of primary percutaneous coronary angioplasty (PPCI) over fibrinolysis is risk and time dependent. A PPCI-delay > 60 minute nullify the mortality advantage of PPCI. Registry data have shown that the acceptable PPCI-delay depends on the risk of the patient. We explored the relationship between the risk and PPCI-delay leading to equivalent 30-day mortality between PPCI and fibrinolysis by the results of published randomized trials comparing PPCI with fibrinolytic therapy using fibrin specific agents

Methods We included 14 trials into final analysis. The DANAMI-2 study, which consisted of 2 substudies was treated as 2 separate trials. When the outcome is mortality, the control (lytic arm) mortality rate can be interpreted as a proxy for mortality risk. We calculated the PPCI-delay as the difference between mean or median door-to-balloon - door-to-needle time and PPCI survival benefit as 30-day mortality after fibrinolysis minus 30-day mortality after PPCI.

Results. Multiple regression analysis showed that fibrinolysis mortality risk (regression coefficient 0.96, p <0.001) and PPCI delay (regression coefficient −0.044, p <0.02) were independently correlated with 30-day survival benefit of PPCI without an interaction (p = 0.6). Figure

shows the P PCI-delays that lead to equivalent 30-day mortality between PPCI and fibrinolysis according to different risk of the STEMI.

Conclusions. The mortality risk of the STEMI patients may modify the acceptable amount of delays to choose a given reperfusion strategy. A longer delay could be justified to choose PPCI instead of fibrinolysis (fibrin specific agents) in high-risk STEMI patients.
Abstract 1196: Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics And Subclinical Vascular Disease: A Population-based Study
Authors: Chirinos Julio A , David Robert , Bralley J. Alexander , Zea-Diaz Humberto , Cuba-Bustinza Carolina , Corrales-Medina Fernando , Najarro Belissa , Ibañez Dionicio , Chirinos-Pacheco Julio , Medina-Lezama Josefina
Published: July 2021

Background:
Asymmetric dimethylarginine (ADMA) and NG-monomethyl-L-arginine (NMMA), endogenous nitric oxide-synthase inhibitors (End-NOSI), have been associated with cardiovascular risk factors (CVRF) and atherosclerosis. In addition, acute administration of NOSI cause hypertension through hemodynamic effects, but whether circulating End-NOSI are associated with these abnormalities is unknown.

Methods:
We studied 922 adults in a population-based study (PREVENCION study). We examined the correlation between End-NOSI/L-arginine and CVRF, as well as the relationship between these biomarkers and arterial hemodynamics, carotid-femoral pulse wave velocity (cf-PWV) and carotid intima-media thickness (c-IMT). We used general linear modeling for statistical analyses. Estimates (β) are standardized.

Results:
In multivariate analyses, LDL-cholesterol and C-reactive protein (CRP) were independent predictors of ADMA, whereas LDL-cholesterol and gender independently predicted NMMA. Age, gender, HDL-cholesterol and CRP were independent predictors of L-arginine. ADMA (β=0.09;p=0.008) and NMMA (β=0.11; p=0.001), but not L-arginine, were strong predictors of c-IMT, even after adjustment for CVRF, CRP and renal function. In contrast, ADMA and NMMA were not predictors of cf-PWV, blood pressure or hemodynamic abnormalities. Higher L-arginine independently predicted higher central (aortic) pulse pressure (β=0.09; p=0.002), incident wave amplitude (β=0.11; p<0.001) and late systolic augmented pressure from wave reflections (β=0.07; p=0.003), but not systemic vascular resistance or cardiac output.

Conclusions:
ADMA and NMMA are differentially associated with CVRF, but both End-NOSI are independently predictors of carotid atherosclerosis. In contrast, they are not associated with large artery stiffness, hypertension or hemodynamic abnormalities. Our findings are consistent with a role for End-NOSI in atherosclerosis, but not in large artery stiffnening, hypertension or long-term hemodynamic regulation. L-arginine is independently associated with abnormal pulsatile hemodynamics, which may reflect abnormal L-arginine transport, leading to decreased intracellular bioavailability for NO synthesis.
Abstract 1241: Tight Glycemic Control Reduces the Incidence of Myocardial Infarction only in Dm Individuals with the Hp 2–2 Genotype
Authors: Milman Uzi , Blum Shany , Shapira Chen , Levy Andrew
Published: July 2021

Background.
The Haptoglobin (Hp) gene is polymorphic in man with two classes of alleles denoted 1 and 2. Several studies have demonstrated that individuals with DM and the Hp 2–2 genotype are at increased risk for MI. We sought to determine if this relationship between Hp genotype and the risk of MI was affected by the degree of glycemic control in a community based longitudinal study.

Methods.
We obtained a Hp genotype on 2230 individuals (283 Hp 1–1, 1241 Hp 2–1 and 706 Hp 2–2), 55 years of age or older with DM from Northern Israel. Study participants were followed for up to 3 years for the incidence of MI.

Results.
At baseline there were no significant differences between groups in their DM characteristics (HbA1c, duration) or in the prevalence of CVD (25%). After stratification of study participants to those with an average HbA1c of above or below 7.0, we found that only in individuals with the Hp 2–2 genotype was strict glycemic control associated with a reduction in the incidence of MI (RR 2.80, 95% CI 1.33– 6.92, p=0.0195, NNT=30.7).

Conclusions.
Optimal utilization of health care resources for risk factor modification should be focused on DM individuals with the Hp 2–2 genotype. Benefit from tight glycemic control only in a subset of the DM cohort defined by the Hp 2–2 genotype may explain the inability to show a benefit from tight glycemic control on reducing MI in all individuals with DM.
Abstract 1248.5: Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Class-Sparing Antiretroviral Therapy: ACTG Study A5152s
Authors: Stein James H , Komarow Lauren , Cotter Bruno R , Currier Judith S , Dube Michael P , Fichtenbaum Carl J , Gerschenson Mariana , Mitchell Carol K , Murphy Robert L , Squires Kathleen , Parker Robert A , Torriani Francesca J
Published: July 2021

Patients with human immunodeficiency virus (HIV) receiving antiretroviral therapy (ART) are at increased risk of cardiovascular disease (CVD). In HIV-infected patients on ART, abnormalities of serum lipoproteins and insulin resistance have been associated with endothelial dysfunction. However, the effects of ART on dyslipidemia and CVD risk have been difficult to study because of the complexity of ART regimens and varying metabolic effects between and within ART classes. This study evaluated the effects of three ART regimens on lipids and lipoproteins, markers of insulin and glucose metabolism, and endothelial function. This was a substudy of A5142, a prospective, multicenter study of 82 treatment-naïve HIV-infected individuals randomly assigned to receive one of 3 class-sparing HIV treatment regimens:

nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz,

NRTIs + the protease inhibitor lopinavir/ritonavir (LPV/r), or

NRTI-sparing regimen of efavirenz + LPV/r.

Lipoprotein particle concentrations were measured by nuclear magnetic resonance spectroscopy. Endothelial function was evaluated by brachial artery flow-mediated vasodilation (FMD) at baseline and after 24 weeks. All values are medians (interquartile range). Total and small low-density lipoprotein concentrations increased by 152 (−49, +407, p<0.01) and 130 (−98, +417, p<0.01) nmol/L, respectively, especially in the 0.04). Very low-density lipoproteins also increased (p+0.01), with larger increases in the arms that contained LPV/r (p
KW
0.022). High-density lipoproteins increased by 6.0 mcmol/L (+2.8, +10.4, p<0.01), similarly in each arm. FMD increased by 1.48% (−0.20, +4.30%, p<0.001) with similar changes in each arm. Changes in lipoproteins were not related to changes in markers of insulin/glucose metabolism or FMD. Effective ART is associated with increases in total and small low-density lipoproteins and very low-density lipoproteins, especially in regimens that contain LPV/r. Over 24 weeks, the vascular effects of ART-related lipid changes may be outweighed by beneficial effects on treatment of HIV infection.
Abstract 3103: A New Epidemic of Heart Failure in the United States: Findings from the National Hospital Discharge Surveys, 1980–2006
Authors: Liu Longjian
Published: July 2021

Introduction:
The most common diagnosis in hospitalized patients aged 65 or older is heart failure (HF). The study aimed to assess the hypothesis that HF hospitalization rates increased significantly in the last 27 years.

Methods:
Data from National Hospital Discharge Surveys (NHDS) between 1980 and 2006 was analyzed in depth. The NHDS was conducted with a multi-stage cross-sectional study design. HF was diagnosed according to ICD 9
th
- CM version. It was then listed from first to seven diagnosis of HF. In the present study, patients with first-listed diagnosis of HF were defined as cases. Census estimated population data were used to estimate age and gender-specific hospitalization rates. Linear and multivariate Poisson regression analysis methods were used to estimate the long-term trend and relative risk of HF hospitalization by age, sex and time periods.

Results:
A total of 2,225,205 patients aged 65 or older were included in the study. Age-adjusted HF hospitalization rates significantly increased from 1980 to 2006, with an estimated annual percentage increase rates (95%CI) of 1.20% (0.76% ~ 3.17%) in men and of 1.55% (0.42% ~ 3.51%) in women. Poisson regression models indicate that the relative risk (95%CI) of being hospitalized due to HF in subjects living in the last 5-years of period (2002– 06) was 1.37 times higher (95%CI: 1.31 ~ 1.42) than those living in the early years of 1980 – 84. Subjects aged 85+ had 4 times higher risk of being hospitalization due to HF as compared to those aged 65–74. Furthermore, among three major forms of cardiovascular disease (CHD, stroke and HF), HF was the only disease showing a significantly increasing in the recent decades.

In conclusion,
the study for the first time documents the last 27 years trend of HF hospitalization rates among the elderly. It suggests that effective prevention strategies are urgently needed to control the unfavorable new epidemic of the disease.
Abstract 3114: The Ageing Process of the Heart: the Effect of Smoking on Arterial Stiffness and Left Ventricular Diastolic Function - The MONICA/KORA-Study
Authors: Stritzke Jan , Markus Marcello R , Duderstadt Stefanie , Lieb Wolfgang , Luchner Andreas , Döring Angela , München Helmholtz Zentrum , Keil Ulrich , Hense Hans-Werner , Schunkert Heribert
Published: July 2021

Smoking is an important cardiovascular risk factor and thereby strongly related to cerebral ischemia and myocardial infarction. Here we evaluated subclinical effects of smoking behaviors on arterial stiffness and left ventricular diastolic function in middle-aged individuals without known cardiovascular disease. Within a gender and age stratified random sample diastolic function was assessed by standardized echocardiography at baseline and again after ten years. Furthermore pulse wave analysis was performed at the follow-up investigation. Within a healthy subgroup aged 25 to 44 years at baseline (n=400) associations between smoking behaviors and LV diastolic function as well as arterial stiffness were assessed by comparison of non-smokers (nonS, consisted of never smokers and individuals who stopped active smoking at least 10 years before follow-up investigation), ex-smokers (exS, individuals who stopped smoking within 10 years of follow-up), and current smokers (curS). Adjusted mean values were calculated by linear regression models. As compared to non-smokers, current smokers as well as ex-smokers presented with worse diastolic function at follow-up. Specifically, they displayed lower e/a-ratios (curS 1.23 95%-CI [1.19, 1.28]; exS 1.23 [1.15, 1.32]) as compared to nonS (1.33 [1.29, 1.36], p-values 0.001 and 0.041, respectively). Additionally, declines of e/a-ratios associated with ageing by 10 years were also significantly different (curS −0.35 [−0.39, −0.31]; exS −0.39 [−0.46, −0.31]; vs. nonS −0.27 [−0.30, −0.24]; each p=0.006). Furthermore, curS presented with increased arterial stiffness as displayed by higher augmentation index (curS 20.1 [18.5, 21.6]; exS 16.7 [13.9, 19.6]; vs. nonS 16.7 [15.5, 17.9], p<0.001 and p=0.995) and shorter time to reflection (curS 141ms [139, 143]; exS 147ms [143, 151]; vs. nonS 145ms [143, 146], p=0.005 and p=0.265). In middle-aged healthy individuals smoking is strongly related to subclinical changes in arterial stiffness and diastolic function. But even after termination of active smoking these changes partly persist. Consequently, interventional programs addressing younger adults are essential to prevent premature cardiovascular ageing.
Abstract 3119: Insulin Resistance is Associated with Impaired Flow-mediated Vasodilatation in a Multi-ethnic Population: The Northern Manhattan Study
Authors: Hasegawa Takuya , Di Tullio Marco R , Boden-Albala Bernadette , Jin Zhezhen , Elkind Mitchell S , Rundek Tanja , Sacco Ralph L , Homma Shunichi
Published: July 2021

Background:
Metabolic abnormalities, including diabetes mellitus, are associated with impaired endothelial function. However, the relationship between endothelial function and glucose metabolism has not been thoroughly investigated.

Aim:
We tested the hypothesis that insulin resistance is associated with impaired flow-mediated vasodilatation (FMD) in a population-based multi-ethnic cohort.

Methods:
As part of the Northern Manhattan Study, we measured fasting insulin levels and FMD during reactive hyperemia by high-resolution ultrasonography in 601 community participants without diabetes. General linear models were used to test the association of fasting insulin, as a surrogate maker of insulin resistance (IR), with FMD after adjusting for age, sex, race-ethnicity, waist circumference, systolic blood pressure, high-density lipoprotein cholesterol, smoking, and fasting glucose. Mean FMD was also compared among the following three subgroups: normal fasting glucose (NFG) with IR (NFG*IR+), NFG without IR (NFG*IR−), and impaired fasting glucose (IFG). IR was defined as the upper quartile of homeostasis model index of insulin resistance (HOMA-IR).

Results:
The mean age was 66±9 years; 43% were male, 15% white, 16% black, and 68% Hispanic. The mean HOMA-IR was 2.45±1.88. In multiple linear regression analyses, fasting insulin was inversely correlated with FMD (β= −0.05, SE=0.02, p=0.032), after adjustment for other covariates. Race-ethnicity was not a significant modifier of the association of fasting insulin with FMD. The mean FMD was greatest in NFG*IR− even after adjustment [FMD (95% CI) 6.28 (5.91– 6.64) for NFG*IR−, 5.21 (4.43–5.99) for NFG*IR+, and 5.04 (4.33–5.74) for IFG (p<0.001)].

Conclusion:
Insulin resistance was independently associated with impaired FMD. The impairment of FMD was also observed in subjects with insulin resistance even in the presence of normal fasting glucose.

This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).

Multivariate analysis of association of FMD with demographic and clinical variables
Abstract 3140: A Variant in the von Willebrand Factor Gene is Associated with Differences in Circulating Protein Levels and Platelet Function
Authors: Vaidya Dhananjay , Herrera-Galeano J E , Yanek Lisa R , Moy Taryn F , Faraday Nauder , Becker Lewis C , Becker Diane M
Published: July 2021

Platelets are recruited to the site of vascular injury by von Willebrand factor (vWF) immobilized on exposed collagen. High circulating vWF levels are associated with myocardial infarction, while low levels are seen in the bleeding disorder von Willebrand’s disease (VWD). We examined the association of single nucleotide polymorphisms (SNPs) in the vWF gene with circulating vWF levels and with collagen-induced aggregation of ex vivo platelets in plasma. We genotyped 51 SNPs (with minor allele frequency >5%, constituting 25 linkage disequilibrium blocks) in the vWF gene in 2077 apparently healthy individuals with a family history of coronary disease (40% Black, 58% female), measured serum vWF levels, and ex vivo platelet aggregation to 10 mM collagen using optical aggregometry. Family-based additive genetic associations for age and sex adjusted vWF levels were assessed using the SAGE software package. Combined p-values for race-stratified analyses using meta-analysis were considered significant at p=0.002 (Bonferroni-corrected). Effect sizes were estimated using generalized estimating equations regression accounting for family structure. SNP
rs216321
encoding the missense variant Q852R (minor allele frequency Whites 8%, Blacks 6%) was associated with vWF levels (p=0.003 [Whites], 0.077[Blacks], 0.002 [combined]). The variant Q852R neighbors a known VWD locus (R854Q). Each copy of Q852R was additively associated with a 13% lower level of vWF (adjusted for age, sex, and race, p=0.0003). However, this variant was recessive in association with collagen-induced aggregation, which was profoundly lower by 23% in minor allele homozygotes as compared to the other two genotypes (p=0.000004). We have discovered a novel association of a missense variant in the vWF gene with vWF blood levels and vWF-mediated platelet function. Whether this variant is adaptive (protecting from cardiovascular disease) or maladaptive (promoting inappropriate bleeding) remains to be determined.
Abstract 3149: Is Plasma B-type Natriuretic Peptide Measurement Valid for Prediction of Cardiovascular Events in Chronic Kidney Disease? A Community-Based Longitudinal Study
Authors: Sakuma Masafumi , Nakamura Motoyuki , Tanaka Fumitaka , Onoda Toshiyuki , Makita Shinji , Kawamura Kazuko , Itai Kazuyoshi , Yoshida Yuuki , Takahashi Tomohiro , Sakata Kiyomi , Okayama Akira
Published: July 2021

Elevated plasma B-type natriuretic peptide (BNP) levels have been reported to be a marker for risk of cardiovascular events (CVE) including heart failure, coronary artery disease and stroke in the general population. However, plasma BNP is increased by renal dysfunction, and it is therefore not known whether plasma BNP might be a reliable biomarker for predicting onset of CVE in the cohort with impaired renal function as represented by chronic kidney disease (CKD). Baseline data including plasma BNP, serum creatinine, and urine protein were determined in 14265 participants from a community-based population. Estimated glomerular filtration rate (eGFR) was calculated using a modified MDRD equation, and CKD was defined by the following two methods (Def 1 = eGFR<60 ml/min/1.73m
2
and/or proteinuria; Def 2 = eGFR<60 ml/min/1.73m
2
). Numbers of CKD subjects were 1927 according to Def 1 and 1604 according to Def 2. CVE endpoint was surveyed prospectively. The mean follow-up duration was 2.9 years. After adjustment for traditional cardiovascular risk factors and atrial fibrillation, relative risk (RR) for CVE was significantly higher in the highest BNP quartile compared to the lowest BNP quartile according to both definitions (Def 1, RR=3.51, p<0.01: Def 2, RR=4.67, p<0.01) (Figure

). Furthermore, the RR for a composite endpoint of CVE and death was also significantly higher in the highest BNP quartile, again by both definitions (Def1, RR=2.71, p<0.01: Def 2, RR=3.09, p<0.02). Measurement of plasma BNP levels provides strong predictive information about future onset of CVE and death, even in CKD subjects selected from the general population.
Abstract 3157: Depletion of Circulating Endothelial Progenitor Cells and Endothelial Dysfunction in Subjects with Depressive Symptoms
Authors: Chen Hua , Qiuwaxi Jianati , Wong Ching-Yuen , Li Sheung-Wai , Chan Hiu-Ting , Tam Sidney , Lau Chu-Pak , Tse Hung-Fat
Published: July 2021

Introduction:
Although the mechanisms remain unclear, depression is associated with endothelial dysfunction and increases risk of cardiovascular disease (CVD). Recent studies suggest that circulating endothelial progenitor cells (EPC) play an important role in endothelial repair and correlate with endothelial function.

Hypothesis:
We assessed the hypothesis that the presence of depressive symptoms in subjects without significant CVD is associated with depletion of circulating EPC and impaired endothelial function.

Methods:
We studied the relationship between the level of circulating EPCs, endothelial function and depression status in 129 healthy normal individuals (54±10 yrs, 54 men) without prior CVD or diabetes. The numbers of circulating CD34/KDR
+
EPCs were determined by flow cytometry, and the depression status was estimated by Depression Anxiety Stress Scales. Brachial artery flow-mediated dilation (FMD) was measured by high-resolution vascular ultrasound imaging.

Results:
The median depression score of the study population was 4 (range 0 to 34), and 41 subjects (32 %) had high depression score (DS) ≥8 (defined by ≥ the 75th percentile of the depression score). There were no significant differences in baseline clinical characteristics between subjects with or without high DS (all
P
>
0.05
). However, subjects with high DS had significantly lower FMD (5.4±2.7 vs. 8.0±4.0 %,
P
<
0.001
) and CD34/KDR
+
EPC% (1.24±1.27 vs. 2.02±2.43 %,
P
=
0.037
) than those with normal DS. Multivariate regression analysis revealed that a high DS (OR 1.08, 95%CI: 1.02–1.15,
P
=
0.009
) and old age (OR 1.05, 95%CI: 1.01–1.09,
P
=
0.029
) were independent predictors for decreased FMD.

Conclusions:
The results of this study demonstrated that in subjects without significant CVD, the presence of a high DS was associated with impaired brachial FMD and depletion of circulating EPC. Nevertheless, only depression score, but not the percentage of circulating EPC significantly correlated brachial FMD, and was an independent predictor for impaired brachial FMD.
Abstract 3161: Race/Ethnicity is an Independent Predictor of Atrial Fibrillation among Individuals 60 Years and Older
Authors: Shen Albert Yuh-Jer , Sobnosky Serap , Liu May J , Ichiuji Anne M , Shah Ahmed I , Chen Wansu
Published: July 2021

Atrial fibrillation (AF) is present in 4 – 8% of people 60 years and older based on studies of predominantly white populations. Limited data involving specific disease states (e.g., HF and acute coronary syndromes) suggest that AF prevalence in blacks and Asians are approximately half that of whites. Scarce data exist regarding racial/ethnic differences in AF prevalence in US communities. This is a cross-section, observational study. In 2005, there were 467,087 members in the Kaiser Permanente Southern California health plan aged 60 years or older. By searching ICD-9 codes and electronic ECG archives, we identified all members in this age group with AF. Patients with pulmonary embolism, thyroid, pericardial, rheumatic, other valvular diseases and early post-cardiac surgery AF cases were excluded. Race/ethnicity data was assigned administratively using hospital-based service utilization, surname, and geocoding methods and was available for 74.1% of members (73% of non-AF and 89.8% of AF), 99% of which belonged to one of the following 4 groups: white, black, Asian, and Hispanic. The independent effect of race/ethnicity on AF was analyzed with logistic regression methods adjusting for potential confounders (search period 2003–5): age, gender, duration of membership, education attainment, household income, prior stroke, diabetes, hypertension, heart failure, chronic kidney disease, coronary artery disease, COPD, morbid obesity and sleep apnea. Among members aged 60 years and older, selected prevalent AF risk factors are listed in the table

. The overall AF prevalence was 6.8%. Among members whose race/ethnicity was known, AF was most prevalent in whites. The odds ratios of having AF among nonwhites were substantially lower than whites in our crude and adjusted logistic regression models. White race/ethnicity is associated with a greater risk for AF after adjusting for comorbidities associated with the development of AF.
Abstract 3206: Quantitative Rage Imaging In Diabetic And Non-diabetic ApoE Null Mice
Authors: Tekabe Yared , Luma Joane , Sedler Marija , Rosario Rosa , Schmidt Ann Marie , Johnson Lynne
Published: July 2021

Receptors for Advanced Glycated Endproducts (RAGE) bind AGEs and other inflammatory ligands and are expressed in atherosclerotic plaques in diabetic and non-diabetic subjects. The higher expression in diabetes (DM) corresponds with accelerated course of the disease. This study was designed to test the hypothesis that the level of RAGE expression in atherosclerosis can be detected in-vivo by quantitative in-vivo SPECT imaging.

Methods and Results
: A monoclonal murine antibody was developed against the V-domain of RAGE, fragmented into F(ab′)
2
and labeled with
99m
Tc and dose of 402 ± 18 μCi or 14.8 ± 0.67 MBq injected into eleven 16 –24 week apoE
−/−
mice 5 with streptozotocin induced DM (given at 6 weeks). Four hours later (time based on blood pool clearance) mice were imaged on HiSPECT scanner (Bioscan), sacrificed, the proximal aorta removed, counted, and sectioned. Uptake in the thorax on SPECT corresponding to the proximal aorta was quantified as % ID using Interview XP (Mediso) software. For the total vascular area for each section, lesion size as % area and cells staining positive for RAGE as % total cells were quantified using immunohistomorphometry. Results expressed as mean values for the apoE
−/−
with and without DM are shown below. Lesion morphology was AHA class II-III and size ranged from 4 –56%. Values for % ID/g tissue and for % ID from scans for all mice were plotted against RAGE expression (% RAGE + cells) and the correlations were the following: % ID/g tissue vs. % RAGE + cells, R
2
= 0.80,
P
= 0.0013, and for % ID scan vs. % RAGE + cells, R
2
= 0.83,
P
= 0.0002.

Conclusions
: In this pilot sample
99m
Tc-labeled anti-RAGE F(ab′)
2
SPECT imaging successfully identified early accelerated atherosclerosis in diabetic apoE
−/−
mice compared to age matched non-diabetic apoE
−/−
mice and quantified RAGE expression over a range of lesion severities.

This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).
Abstract 3264: Remarkable Differences in calculating the Cardiovascular Risk according the Framingham-, Procam- and ESC Risk-Scores. First Results of the DETECT Study
Authors: Silber Sigmund , Richartz Barbara M , Jarre Frauke , Pittrow David , Klotsche Jens , Pieper Lars , Kirch Wilhelm , Wittchen Hans-Ulrich
Published: July 2021

The identification of high-risk patients is of utmost importance for an intensive and effective primary prevention program. Currently, three different scores are used to identify high-risk patients: In the USA, the Framingham risk score, in Germany the Procam risk score and in Europe the European Society of Cardiology ESC) recommended ESC risk score. There is, however, little knowledge how these three risk scores compare to each other in the same population. Therefore we calculated the individual risk of 7519 pats with no known cardiovascular disease according to these three scoring systems. In the DETECT study, 55 518 patients in 3188 primary care offices were enrolled. A representative subgroup of 7,519 randomly chosen patients participated in a cohort sub-study. According to the Framingham-Procam- and ESC-Score, the individual 10-year-risk was determined and patients were _ategorized into groups of high, medium or low risk. The mean 10-year cardiovascular risk is estimated by the PROCAM score at 4.4%, with the ESC score at 8.8% and with the Framingham-Score at 11.5%. The number of patients assigned to a group differs most for the high risk group (please see table

). Unexpectedly, major discrepancies were observed in the same pats, if the Framingham, Procam- or ESC score was used, especially in the identification of high-risk pats. Follow-up will show, which of these risk scores will best predict the actual occurrence of cardiovascular events.

Results:
Abstract 4998: Elevated Oxidized Phospholipids on Apolipoprotein B-100 Particles Predict 6-Year Cardiovascular Events in the Epic-Norfolk Study: Potentiation of Risk with Lipoprotein-Associated (Lp-PLA
2
) and Soluble Phospholipase A2 (sPLA
2
) Activity
Authors: Tsimikas Sotirios , Mallat Ziad , Talmud Philippa J , Kastelein John J , Wareham Nicholas J , Miller Elizabeth R , Witztum Joseph L , Khaw Kay-Tee , Boekholdt S. M
Published: July 2021

Objective: We aimed to assess whether oxidized phospholipids on apoB-100 particles (OxPL/apoB) predict future coronary heart disease (CHD) in the prospective EPIC-Norfolk cohort of apparently healthy men and women aged 45–79 years followed up 1993–2007.

Methods and Results: Cases who developed CHD during follow-up were matched to controls who remained free of cardiovascular disease and who matched to cases by sex, age and enrollment time. OxPL/apoB levels were measured with antibody E06 in 905 cases and 1809 controls. Subjects in the highest quartile of OxPL/apoB at entry in the study had significantly higher risk of future CHD events (OR 1.72, 95%CI 1.32–2.24, p<0.0001) compared to those in the lowest quartile. This relationship was present in both men and women and was also observed after adjustment for sex, age, diabetes, smoking, blood pressure, LDL-C, HDL-C and Framingham Risk Score (FRS). The risk of future CHD events was significantly potentiated by elevated activity levels of sPLA
2
and Lp-PLA
2
. Subjects in the highest tertiles of both OxPL/apoB and LpPLA2 (OR 2.22 [1.51–3.27]) or OxPL/apoB and sPLA
2
(OR 4.34 [2.84 – 6.64]) had significantly higher risk of future CHD than subjects in the lowest tertiles (p<0.0001 for both). Area under receiver operating curves revealed significantly increased values by adding OxPL/apoB and sPLA
2
to traditional risk factors and the FRS. Strong inverse associations were noted between the OxPL/apoB and VLDL and IDL size, CETP mass and RANK Ligand.

Conclusion: Elevated OxPL/apoB levels are a strong, independent predictor of CHD events. The predictive values is further enhanced by elevated activity levels of sPLA
2
and Lp-PLA
2
, which mediate breakdown of OxPL present on lipoproteins and within atherosclerotic lesions. This study links several pathophysiologically related oxidative biomarkers in the prediction of CHD events and suggests novel approaches to predicting CHD risk in apparently health men and women.
Abstract 5017: An Insertion/Deletion Polyporphism in α
2
-Adrenergic Receptor Gene is a Novel Genetic Risk Factors Sudden Cardiac Death
Authors: Laukkanen Jari
Published: July 2021

α
2B
-adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. A variant of the human α
2B
-adrenoceptor gene that encodes a D of three residues in an intracellular acidic motif has been shown to confer decreased receptor desensitization. This receptor variant could, therefore, be involved in cardiovascular diseases associated with enhanced vasoconstriction. Our aim was to study whether an insertion/deletion (I/D) polymorphism in the α
2B
-adrenoceptor gene is associated with the risk for sudden cardiac death. This study was part of a prospective population-based study investigating risk factors for cardiovascular diseases in a cohort of middle-aged men from eastern Finland. The study is based on 1606 men 42 to 60 years of age followed for an average time of 17 years. In this study population, 338 men (21%) had the D/D genotype; 467 (29 %) had the I/I genotype, and 801 (50%) had a heterozygous genotype. There were 76 sudden cardiac deaths during follow-up. In a Cox model adjusting for other coronary risk factors (age, systolic blood pressure, smoking, diabetes, serum LDL and HDL cholesterol, body mass index and exercise-induced myocardial ischemia), men with the D/D or I/D genotype had 1.95 time (95% confidence interval, 1.07 to 3.55, P = 0.029) higher risk to experience sudden cardiac death (20 events for D/D genotype, 13 events for I/I genotype and 43 events for I/D genotype) compared with men carrying the I/I genotype. The α
2B
-adrenoceptor genotype was associated with coronary heart disease death but not with hypertension. The D/D and I/D genotypes of the α
2B
-adrenoceptor are novel genetic risk predictors for sudden cardiac death.
Abstract 5078: Physical Training Reduces the Ability of Serum from Patients with Heart Failure to Induce Endothelial Cell Death
Authors: Mammi Caterina , Caprio Massimiliano , Gorini Stefania , la Sala Andrea , Antelmi Antonella , Gatta Lucia , Marazzi Giuseppe , Caminiti Giuseppe , Volterrani Maurizio , Rosano Giuseppe
Published: July 2021

Physical training improves endothelial function and exercise capacity in patients with heart failure (HF). Serum from patients with cardiovascular diseases shows increased ability to induce apoptosis in human endothelial cells potentially contributing to the progression of atherosclerotic and endothelial dysfunction. Aim of this study was to evaluate the effect of cardiac rehabilitation on the pro-apoptotic properties of serum in patients with heart failure. Human Umbilical Vein Endothelial Cells (HUVECs) were incubated with 20% serum from 24 patients with HF (HYHA II) before and after cardiovascular rehabilitation. For apoptosis quantification, fragmented DNA was determined using Cell Death detection ELISA kit and propidium iodide (PI) staining analyzed by flow cytometry. The expression on endothelial cells of proteins involved in apoptotic pathway (bax, caspasi-3, bcl-2) was studied by Western blot analysis. Necrosis was evaluated measuring the lactate dehydrogenase released from damaged cells into the supernatant using a cytotoxicity detection kit. Serum from patients with heart failure showed a significantly greater ability to induce apoptosis (67 ± 4,6% vs 23 ± 5,2%, p<0,001) and necrosis (44 ± 3% vs 32 ± 2,1%, p<0,05) of HUVEC cells compared with controls. Cardiac rehabilitation significantly reduced the ability of patient serum to induce apoptosis (PI: 40.44% ± 3,9 vs 25.22% ± 2,6, p<0,01; ELISA: 67 ± 4,6% vs 42 ± 4,4%, p<0,001) and necrosis (44 ± 3% vs 33 ± 2%, p<0,01) of HUVEC cells compared to baseline. Moreover endothelial cells treated with serum after rehabilitation showed a significant decrease of bax expression (1,12 ± 0,06 vs 0,89 ± 0,08, p<0,05) and a significant decrease of cleaved Caspase-3 expression (0,91 ± 0,16 vs 0,72 ± 0,08, p<0.05). Serum of patients with heart failure has increased pro-apoptotic properties. Physical training reduces the ability of serum-contained factors to induce cell death of endothelial cells in patient with heart failure.
Abstract 5161:β 1 (Arg389Gly, Ser49Gly)- and β2 (Arg16Gly) -adrenoceptor Polymorphisms are Related to Left Ventricular Hypertrophy in Middle-aged, Nonobese, Normotensive Men, but Through Different Mechanisms
Authors: Masuo Kazuko , Katsuya Tomohiro , Sugimoto Ken , Rakugi Hiromi , Ogihara Toshio , Tuck Michael L
Published: July 2021

Objective:
β2-adrenoceptor (ADRB2) polymorphisms are closely linked to hypertension and obesity, and both of them are major cardiac risk. Left ventricular hypertrophy (LVH) is more common in people who have hypertension or obesity. We examined the relationships between ADRB1 and ADRB2 polymorphisms and LVH in nonobese, normotensive subjects.

Methods:
In 447 middle-aged, normotensive, nonobese men, ADRB1 (Arg389Gly, Ser49Gly) and ADRB2 (Arg16Gly, Gln27Glu) polymorphisms, BMI, BP, heart rates (HR), total body fat-mass, waist-to-hip ratio (W/H), plasma norepinephrine (NE) and ECG were measured after overnight fasting in the supine position. LVH was determined by ECG.

Results:
Thirty-nine subjects (8.7%) showed LVH on ECG. Subjects with LVH had higher plasma NE and HR compared to those without LVH (both P<.05). Distributions of Gly389 and Gly49 alleles of ADRB1 polymorphisms were 23.5% (Arg/Arg:Arg/Gly:Gly/Gly=270:144:33) and 14.1% (Ser/Ser:Ser/ Gly:Gly/Gly=327:114:6). Thirty-seven subjects with LVH (94.9%) carried Gly389 and Gly49 alleles, especially homozygous for Gly389 or Gly49. Subjects with Gly389 or Gly49 alleles had higher frequencies of LVH (20.9% vs. 0.7%, 30.8% vs. 0.6%). Subjects carrying Gly389 or Gly49 alleles had higher plasma NE and HR (both P<.05), whereas BMI, fat mass, W/H and BP were similar. The Gly16 and Glu27 alleles of ADRB2 polymorphisms were noted in 42.8% (Arg/Arg :Arg/Gly:Gly/Gly=69:245:133) and 36.6% of the subjects (Gln/Gln:Gln/Glu:Glu/ Glu=176:215:56). Twenty-nine subjects with LVH (74.4%) carried Gly16 allele, especially Gly16 homozygous. Subjects with Gly16 allele had higher frequencies of LVH (P<.05), and they had greater BMI, fat mass, W/H, BP, HR and NE compared to those without Gly16 allele (all P<.05).

Conclusions:
Subjects carrying Gly389 and Gly49 alleles of ADRB1 polymorphisms and Gly16 allele of ADRB2 polymorphism had higher frequency of LVH accompanying high plasma NE. ADRB1 and ADRB2 polymorphisms play important roles in LVH even in nonobese, normotensive subjects. ADRB1 polymorphisms might relate to LVH through heightened sympathetic nerve activity, but ADRB2 polymorphisms might relate to LVH through obesity, hypertension and heightened sympathetic nerve activity.
Abstract 6199: Relationship of Carotid Arterial Compliance and Thoracic Aorta Calcification: Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Blaha Michael J , Budoff Matthew J , Rivera Juan J , Katz Ronit , O’Leary Dan H , Polak Jospeh F , Takasu Junchiro , Blumenthal Roger S , Nasir Khurram
Published: July 2021

Decreased arterial compliance is one of the earliest manifestations of adverse structural and functional changes within the vessel wall. Prior studies have shown that indirect measures of arterial stiffness predict severity of atherosclerosis as well as subsequent cardiovascular events. Ultrasonography of the common carotid artery however enables a direct measurement of compliance and stiffness and may be a more sensitive marker of subclinical vascular disease. MESA is a longitudinal, population-based study of 6,814 men and women aged 45–84 without clinical cardiovascular disease at enrollment. Of these, 3,540 (62± 10 years, 47% males) individuals underwent arterial compliance assessment via calculation of the distensibility coefficient (DC, in 1/mmHg ×10
3
), which uses carotid ultrasonographic measurements of cardiac cycle-dependent vessel size and upper arm measurements of blood pressure. All patients had their thoracic artery calcium (TAC) calculated using non-contrast cardiac CT. The cross-sectional association between decreasing quartiles of DC (4
th
quartile as reference group) and TAC was assessed by multivariable relative risk regression using a generalized linear model and binomial error distribution. The mean DC in the study population was 2.51± 1.11. Overall, 1,828 (28%) individuals had detectable TAC. A lower DC was observed among those with vs. without TAC (2.06± 0.90 vs. 2.69± 1.13, p<0.0001). The prevalence of TAC increased significantly across decreasing quartiles of DC (4
th
: 11%, 3
rd
: 21%, 2
nd
: 32%, 1
st
: 11%, p<0.0001). The table

below demonstrates the adjusted relative risk for presence of TAC with decreasing quartiles of DC. Decreased arterial compliance measured by carotid ultrasonography is independently correlated with thoracic aortic atherosclerosis. Further studies are in progress to assess the prognostic value of this marker of subclinical atherosclerosis.
Abstract 6225: Cost of Improvement of Angina-Related Health Status by Health Care System: A Secondary Analysis from the COURAGE Trial
Authors: Zhang Zugui , Kolm Paul , Goeree Ron , Jurkovitz Claudine , Teo Koon , Spertus John , Maron David , O’Rourke Robert , Hartigan Pamela , Barnett Paul , Boden William , Weintraub William
Published: July 2021

Background:
COURAGE compared percutaneous coronary intervention (PCI) plus intensive pharmacologic and lifestyle intervention (optimal medical therapy, OMT) to OMT alone in reducing the risk of cardiovascular events in patients with stable coronary disease. In this post hoc study, we assessed the cost of treating angina across the three health care systems from which patients were enrolled: Canada, US non-Veterans Affairs (VA) and U.S. VA.

Methods:
A total of 2,287 patients were enrolled and followed for a median of 4.6 years. Angina-related health status was assessed with the Seattle Angina Questionnaire (SAQ) and RAND-36. The cost of resource use was evaluated by DRG for hospitalizations and CPT for outpatient visits and tests. Analyses were conducted using the U.S. non-VA costing system in 2004 U.S. dollars. Clinically significant differences in the Physical Limitation, Angina Frequency, and Quality of Life domains of the SAQ were defined as scores ≥8, ≥20, and ≥16 respectively. Absolute net benefit, number of patients needed to treat (NNT) to achieve one patient with clinically significant angina improvement, and the cost of improvement in angina-related health status were estimated.

Results:
Added cost of PCI per patient and results for Angina Frequency are presented in the table

. Results for Quality of Life were similar. Physical Limitation results varied more widely among health care systems with net benefit ranging from <1% (U.S. non-VA) to 18% (Canada), and cost per patient in angina improvement from $55,700 (Canada) to over $1,000,000 (U.S. non-VA).

Conclusions:
The improvement of angina-related health status and corresponding costs were relatively similar across health care systems and among SAQ Angina Frequency and Quality of Life domains, but varied widely for the Physical Limitation Domain. Adding PCI to OMT improved angina-related health status, but at a cost generally considered to be prohibitive as a routine initial management strategy.

Cost of Improvement of Angina-Related Health Status by Health Care System
Abstract 6255: Adiponectin Deficiency Profoundly Exacerbates Sepsis-Related Mortality through Endothelial Activation: A Novel Mechanistic Link between Adiposity and Sepsis
Authors: Teoh Hwee , Quan Adrian , Bang K W , Wang Guilin , Lovren Fina , Vu Vivian , Haitsma Jack J , Szmitko Paul E , Wang Chao H , Errett Lee , Gupta Milan , Zhang Haibo , Chan Lawrence , Freedman John , Sweeney Gary , Verma Subodh
Published: July 2021

INTRODUCTION:
Sepsis is a multifactorial, and often fatal disorder, characterized by widespread inflammation with resultant endothelial activation. Adiposity and diabetes are strong negative predictors of sepsis related cardiovascular dysregulation and mortality, however, the mechanisms remain unclear. We postulated that alterations in adipokine biology, particularly adiponectin, are essential modulators of survival and endothelial activation in sepsis.

METHODS AND RESULTS:
We evaluated both loss-of-function (adiponectin gene-deficient mice) and subsequent gain-of-function (recombinant adiponectin reconstitution) strategies in two well-established inflammatory models, cecal ligation perforation (CLP) and thioglyocollate-induced peritonitis.
Adipoq
−/−
mice, subjected to CLP, exhibited a profound (~8 fold) reduction in survival compared to their wild-type
Adipoq
−/−
littermates after 48 hours. Furthermore, compared to wild-type controls, thioglycollate challenge resulted in a markedly greater influx of peritoneal neutrophils in
Adipoq
−/−
mice accompanied by an excess production of key chemoattractant cytokines (IL-12p70, TNFalpha, MCP-1 and IL-6) and upregulation of aortic endothelial adhesion molecule expression, VCAM-1 and ICAM-1. Importantly, all of these effects were blunted by recombinant total adiponectin administration given three days prior to thioglycollate challenge. The protective effects of adiponectin were largely ascribed to higher order adiponectin oligomers, since administration of recombinant trimeric adiponectin did not attenuate endothelial adhesion molecule expression in thioglycollate-challenged
Adipoq
−/−
mice.

CONCLUSIONS:
These data suggest a critical role of adiponectin as a modulator of survival and endothelial inflammation in experimental sepsis and suggest one of the first mechanistic links between adiposity and sepsis related death.