tbuckley/cabot-search huggingface dataset:
Abstract 18445: Potential Contribution of RANKL System in Adipose Tissue Inflammation and Insulin Resistance
Authors: Mariana K Osako, Futoshi Nakagami, Hironori Nakagami, Ryuichi Morishita
Journal: Circulation (2012)

Hypertension and obesity are related to adipose tissue inflammation and insulin resistance, and both are important factors for the development of type II Diabetes mellitus. High serum osteoprotegerin (OPG) level has been reported in diabetic patients, and is considered a marker for future cardiovascular events. OPG is a decoy receptor of RANKL, and inhibits its binding to the receptor RANK. The RANKL system has been reported in bone, mammary gland development, immune cells communication, and we have previously reported its role in vascular calcification and potential cross-talk with Renin-angiotensin II system via ERK phosphorylation pathway. In this study, we examined the role of RANKL system in adipose tissue. High fat diet significantly increased the RANK-RANKL, ACE, AT1R as well as TNF alpha and MCP-1 mRNA expression in C57/BL6 and db/db mice adipose tissue. In vitro studies showed that RANKL expression increases following human pre adipocyte differentiation, and is further increased in the presence of Angiotensin II. We have found that PMA-activated monocytes (THP1) express higher level of RANK compared to non-stimulated monocytes, and that RANKL stimulation induces inflammatory cytokines expression in the presence of anti-OPG neutralizing antibody. Also, RANKL induced macrophage migration in boyden chamber assay dose dependently. OPG-/- mice under high fat diet presented increased number of crown-like structures in adipose tissue compared to wild type. Interestingly the deletion of AT1R in OPG-/-mice significantly decreased that macrophage infiltration, and inhibited the expression of inflammatory cytokines and RANKL system in adipose tissue. OPG-/- mice, known as the model of continuous activation of RANKL system, showed higher insulin level and insulin resistance compared to WT and AT1R-/-/OPG-/- mice. Overall, we propose that RANKL is activated in adipose tissue under high fat diet, and may contribute to insulin resistance by inducing macrophage recruitment and adipose tissue inflammation. Moreover, blockade of local renin-angiotensin II activation can also inhibit RANKL system activation in adipose tissue.
Abstract 18518: Effect of Medical Treatment for Aortic Dissection on In-Hospital Mortality and Follow-Up Aortic Expansion in Patients with and Without Marfan Syndrome; Observations from the International Registry of Acute Aortic Dissection
Authors: Toru Suzuki, Eric M Isselbacher, Kim A Eagle, Christoph A Nienaber, Daigo Sawaki, Lindsay M Hagan, Daniel G Montgomery, James B Froehlich
Journal: Circulation (2012)

Background: Medical management of acute aortic dissection (AAD) is poorly understood and based mainly on personal experience, expert opinion and observational studies. Society guidelines reaffirm this lack of evidence. We sought to determine the association of specific medications on outcomes in AAD patients. Methods: Prior analyses from the International Registry of Acute Aortic Dissection (IRAD) suggest beta blockers (BB) are associated with lower long-term mortality after AAD, and calcium channel blockers (CCB) are associated with lower long-term mortality after type B AAD. For this abstract, we analyzed factors associated with in-hospital mortality and aortic growth at follow-up, including medication use, using IRAD. We also looked at medication use and long-term survival in AAD patients with Marfan Syndrome (MFS). Results: Among 817 patients with type B AAD, improved in-hospital survival was associated with BB use (OR 23.09, 95% CI 6.62-80.58, p&lt;0.001), absence of mesenteric ischemia (OR 10.53, 95% CI, 1.31-84.7, p=0.03) and absence of hypotension/shock (OR 7.55, 95% CI, 1.15-49.4, p=0.04). No benefit was associated with use of angiotensin converting enzyme inhibitor (ACE). On follow-up, CCB were associated with slower aortic growth in medically treated type B patients (p=0.013), and CCB use during the first two years after AAD is associated with negative growth of the aorta ( -0.07mm/yr for patients on CCB vs. 0.42mm/yr for those not, p=0.008). Analysis of 68 MFS patients showed improved long-term survival in type A patients receiving BB (p=0.01); ACE were associated with increased mortality after 30 months (p=0.008). Conclusions: This analysis suggests BB are associated with improved in-hospital survival in AAD patients. CCB in Type B patients are associated with improved survival and slower descending aortic growth. MFS patients also benefited from BB use. RAS inhibitors were not associated with improved in-hospital or long-term survival in patients (including MFS patients) with AAD. Whether these observed associations between treatment and outcome are due to cause-and effect cannot be determined. Optimal management needs to be confirmed in randomized controlled trials.
Abstract 18473: ApoB-100 Related Peptide Immunization Confers Protection Against Angiotension II-induced Renal Inflammatory Responses
Authors: Tomoyuki Honjo, Paul C Dimayuga, Kuang-Yuh Chyu, Xioaning Zhao, Jianchang Zhou, Juliana Yano, Wai Man Lio, Portia Trinidad, Bojan Cercek, Prediman K Shah
Journal: Circulation (2012)

Background: T cells play an important role in angiotensin II (AngII)-induced hypertension and aneurysm formation. Inflammatory responses, typified by reactive oxygen species (ROS) and Interleukin-6 (IL-6), are involved in AngII-induced hypertension and renal damage. We recently demonstrated that immunization with apoB-100 related peptide p210 reduced atherosclerosis through T cell mediated immune response in apoE (-/-) mice. We also reported that immunization with p210 reduced mean arterial blood pressure (p210 = 124±4*, cBSA = 143±6, PBS = 139±3 mmHg. *p&lt;0.05 vs cBSA and PBS.) and aneurysm formation in AngII-infused apoE (-/-) mice. In this study, we assessed the effect of p210 vaccine on AngII-induced renal inflammatory responses in apoE (-/-) mice. Method and Results: ApoE (-/-) mice were immunized with p210/cBSA/Alum (p210; 100 μ g) at 7, 10, and 12 weeks of age. Mice receiving PBS or cBSA/Alum (cBSA) served as controls. At 10 weeks of age, mice were subcutaneously implanted with an osmotic pump which released AngII (1 mg/Kg/min), and were euthanized 4 weeks later. Serum creatinine level was significantly lower in p210 group (p210 = 0.7±0.1*, cBSA = 1.1±0.1, PBS = 1.4±0.1 mg/dL. N=12, 11, and 9 respectively; *p&lt;0.05 vs cBSA and PBS.). IL-6 and monocyte chemotactic protein-1 (MCP-1) mRNA expression in kidneys were significantly down-regulated in p210 group (IL-6: cBSA = 4.1±1.1, PBS = 3.9±1.0 -fold increase compared to p210; MCP-1: cBSA = 2.4±0.6, PBS = 2.2±0.4 -fold increase compared to p210, N=8). Renal glomerular superoxide production measured by in situ dihydroethidium was significantly decreased in p210 group (cBSA = 3.8±0.7, PBS = 3.9±0.6 -fold increase compared to p210, N=4.). The expression of NOX1, a component of NADPH oxidase, mRNA in kidneys was significantly down-regulated in p210 group (cBSA = 2.6±0.5, PBS = 2.8±0.4 -fold increase compared to p210, N=8.). Conclusion: Immunization with p210 significantly attenuated AngII-induced renal damage. These anti-hypertensive and renal protective effects were associated with down-regulation of IL-6 and MCP-1 expression, and ROS production mediated by NADPH oxidase in kidneys.
Abstract 18468: Associations Between Clinical Characteristics and NT-proBNP in Heart Failure with Preserved Ejection Fraction: Data from the KaRen Study
Authors: Lars H Lund, Erwan Donal, Emmanuel Oger, Camilla Hage, Hans Persson, Ida Haugen-Löfman, Jean-Claude Daubert, Cecilia Linde
Journal: Circulation (2012)

Purpose: In heart failure with reduced ejection fraction, N-terminal pro brain natriuretic peptide (NT-proBNP) is useful for diagnosis and prognosis, and is higher with older age, female gender, renal failure and lower in obesity. In heart failure with preserved ejection fraction (HFPEF), NT-proBNP is also useful for diagnosis and prognosis, but clinical correlates are less well established. Methods: KaRen is a multicenter prospective registry of HFPEF. Inclusion criteria are acute presentation with Framingham symptoms and signs of heart failure together with NT-proBNP &gt;300 ng/L and LVEF &gt;=45%. The association between clinical characteristics and log NT-proBNP was assessed with uni- and multivariate linear regression, with backward step-wise selection based on p &lt; 0.05. Results: We studied 400 patients, mean (SD) age 77 (9) years, 56% women. The table lists variables independently associated with log NT-proBNP, their baseline values and Beta coefficients. Conclusions: In HFPEF, NT-proBNP is determined mainly by NYHA class and clinical signs of heart failure. Clinical signs are important predictor of severity of disease. As in reduced ejection fraction, NT-proBNP is inversely associated with BMI and GFR, but unlike in reduced ejection fraction, it is not associated with age or gender.
Abstract 18543: Impaired Coronary Metabolic Dilation Leads to Heart Failure During Pressure Overload
Authors: Vahagn A Ohanyan, Dan Luther, Christopher Kolz, Suzanna Logan, Molly Enrick, Kelly Stevanov, Liya Yin, William Chilian
Journal: Circulation (2012)

The coupling of myocardial blood flow to cardiac work (metabolic dilation) is critical for proper cardiac function. If this coupling is altered, the imbalance could lead micro-areas of hypoxia, ischemia, and fibrosis culminating in heart failure. Accordingly we hypothesized, that when subjected to an extreme metabolic challenge (pressure overload), insufficient dilation of the coronary circulation leads to micro-areas of ischemia and infarction (diffuse fibrosis) and compromised cardiac function. To test this, we studied cardiac function and pathology in Wild Type (WT) and Kv1.5 -/- mice, which have impaired metabolic dilation. To impose a metabolic challenge, transaortic constriction (TAC) was done in Kv1.5 -/- male (n=12), female (n=12) and WT (n=12) mice. TAC increased mean aortic pressure from 98±5 to 142±8 mmHg. Transthoracic echocardiography was performed for evaluation of cardiac function at 7, 28 days after TAC. Masson’s Trichrome and Hypoxyprobe (HP) staining was done at day 28 for evaluation myocardial fibrosis and areas of hypoxia, respectively. After TAC survival rate of Kv 1.5 -/- females was lower (P&lt;0.05) than in males and WT (Panel A). Ejection fraction (EF) was lower (P&lt;0.05) in Kv1.5 -/- (male and female) than WT at all times after TAC (Panel B). In WT, EF was decreased 7 days after TAC, but the reduction was moderate compared to Kv 1.5 -/- . After 28 days of TAC, myocardial fibrosis was markedly higher in Kv1.5 -/- compared to WT (Panel C). In Kv1.5 -/- , fibrosis was in endocardial and perivascular regions, but in WT it was transmural and less developed. HP and DAPI (to locate nuclei) revealed that the number of cells positive for hypoxyprobe was 222% greater in Kv1.5 -/- than in WT, suggesting impaired oxygen delivery. Taken together, we conclude that the absence of Kv1.5 channels, which uncouples myocardial blood flow from cardiac work, compromises coronary and cardiac adaptations to TAC leading to diffuse ischemia, micro-areas of infarction and heart failure. .
Abstract 18466: Anemia is Associated with an Adverse Outcome in Patients with Atrial Fibrillation: Insights Form the Re-ly Trial
Authors: B. Daan Westenbrink, Marco Alings, Stuart Connolly, John Eikelboom, Michael D Ezekowitz, Jonas Oldgren, Sean Yang, Janice Pogue, Salim Yusuf, Lars Wallentin, Wiek H van Gilst
Journal: Circulation (2012)

Background: Anemia may predispose to cardiovascular events. While patients with atrial fibrillation (AF) may be particularly prone to anemia, the impact of anemia on outcome in patients with AF is unclear. Methods: We retrospectively analyzed the RE-LY trial that randomized 18,113 patients with AF to receive dabigatran or warfarin for a median follow-up of 2 years.The association between anemia (Hb &lt;13.0 g/dL in men and &lt;12.0 g/dL in women) and the incidence of cardiovascular and bleeding events was assessed with multivariable Cox regression analysis. Results: Anemia was present in 12% of the population at baseline and the presence of anemia was associated with an increased incidence of all cause mortality or myocardial infarction (adjusted hazard ratio (adj. HR) 1.50, 95% confidence interval (CI) 1.32-1.71). Anemia was also associated with an increased incidence of the primary RE-LY endpoints of stroke or systemic embolism (adj. HR 1.41 95% CI (1.12-1.78)) and major bleeding (adj. HR 2.14, 95% CI 1.87-2.46). The association between anemia and outcome did not differ according to major cardiovascular comorbidities, treatment allocation or prior use of warfarin. After 6 months, anemia had resolved in 35% of anemic patients, while anemia had developed in 10% of patients without prior anemia. Resolution of anemia was associated with a more favorable outcome than sustained anemia (adj HR. 0.71, 95%CI 0.97-0.52), or new onset anemia (adj HR. 0.68, 95%CI 0.50-0.93) Conclusions: Anemia is associated with an increased risk of cardiovascular events and bleeding complications in patients with AF. Accordingly, resolution of anemia is associated with a more favourable outcome than sustained anemia.
Abstract 18485: Relationship Among Pathologic Changes in Patients with Myxomatous Degeneration: Insights from In Vivo Measurement of Mitral Leaflet Geometry Using 3D TEE Data
Authors: Jeong Yoon Jang, Jae-Kwan Song, Dong-Hwan Jun, Chang Hee Kwon, Yong Kyu Park, Byung Joo Sun, Dae Hee Kim, Jong-Min Song, Duk-Hyun Kang
Journal: Circulation (2012)

Background: Although pathologic and imaging studies showed mitral valve leaflet elongation, chordal elongation and rupture (CR), and annular dilatation in patients with myxomatous degeneration (MD), in vivo quantitative analysis of these anatomical changes and their potential relationship has not been reported. Methods: 3D full volume data were obtained during TEE in 20 healthy subjects and 40 patients with severe mitral regurgitation (MR) due to MD confined to a single scallop in posterior mitral leaflet. A customized software (Omni4D) was used to evaluate mitral valve geometry. Results: Twenty one patients had typical prolapse without CR, whereas 19 had flail leaflet with CR. Compared to controls, these patients with MD and severe MR showed larger annular area (AA) and total and individual leaflet surface area (LSA) with smaller anterior/posterior LSA. There was no difference in MR severity, AA, total and individual LSA. Positive correlation was observed between LSA and annular area in both controls and patients with MD. Although correlation between posterior LSA and AA was stronger than that between anterior LSA and AA in patients with MD, there was no difference in controls. Conclusions: Different mechanisms seem to be associated with leaflet elongation in prolapsing and non-prolapsing mitral leaflet and increase in AA and LSA was not different in patients with and those without CR.
Abstract 18489: Abnormal Coronary Findings on Non-Invasive Computed Tomography Coronary Angiography in Adult Patients with Transposition of the Great Arteries Corrected by Arterial Switch Operation
Authors: Caroline E. Veltman, Saskia L. M. A. Beeres, Deborah N. Kalkman, Mark G. Hazekamp, Jeroen J. Bax, Lucia J. Kroft, Philippine Kies, Ernst E. van der Wall, Martin J. Schalij, Arthur J. H. A. Scholte, Hubert W. Vliegen, Monique R. M. Jongbloed
Journal: Circulation (2012)

Purpose: Early mortality and long-term outcome in patients with congenital transposition of the great arteries (TGA) corrected by arterial switch operation (ASO) mainly depend on the perfusion of the myocardium provided by the transferred coronary circulation. This study aimed to assess the prevalence of potential unfavorable coronary findings in adult patients after ASO using non-invasive computed tomography coronary angiography (CTA). Methods: The study population consisted of 30 adult patients after ASO (22 male, 22±3 yrs.) referred for non-invasive evaluation of the coronary anatomy by CTA. First, the post-operative coronary anatomy pattern was described using the classification of Gittenberger-de Groot. Furthermore, all scans were reviewed on the presence of (1) significant coronary stenosis, defined as ≥50% luminal narrowing, (2) an inter-arterial coronary course, and (3) an acute angled coronary origin. Results: A post-operative anatomy patterns of 1R-2LCx was observed in 24 patients (80%), 1RCx-2L in 5 patients (17%) and 2RLCx in 1 patient (3%). A total of 13 patients (43%) had abnormal coronary findings of which 1 patient (3%) had a significant stenosis in the proximal LAD, 5 patients (17%) had an inter-arterial coronary course (case examples in Figure 1) and 7 patients (23%) had an acute angled coronary origin. All 16 patients with a normal CT results had a post-operative coronary pattern of 1R-2LCx, whereas this pattern was only observed in 8/14 (57%) patients with abnormal coronary findings on CTA (P&lt;0.005). Conclusions: The current study demonstrated that abnormal coronary findings are frequently observed in adult patients with TGA corrected by ASO. Moreover, a significant association between the coronary anatomy and the presence of coronary abnormalities on CTA was observed, indicating that patients with a post-operative coronary anatomy pattern other than 1R-2LCx may be at higher risk to have potential malignant coronary findings on CTA.
Abstract 18506: A High Adipose Tissue Arachidonic Acid Content is Associated with a Higher Risk of Myocardial Infarction: A Danish Case Cohort Study
Authors: Michael S Nielsen, Erik B Schmidt, Anders Gorst-Rasmussen, Jakob G Stegger, Kim Overvad
Journal: Circulation (2012)

Background: Some, but not all studies have reported a positive association between the content of arachidonic acid (AA) in adipose tissue and the risk of coronary heart disease. However, unlike most other polyunsaturated fatty acids, the content of AA in adipose tissue does not seem to reflect the dietary intake of neither AA nor the endogenous source and precursor of AA, linoleic acid (LA). Aim: The primary aim of the study was to evaluate the association between adipose tissue AA content and the risk of myocardial infarction (MI). The secondary aim was to assess the correlation between adipose tissue AA and dietary intake of AA and LA, as assessed from a validated 192 item food frequency questionnaire. Methods: We conducted a case-cohort study nested within the Danish Prospective Diet, Cancer and Health (DCH) study. After appropriate exclusions, the study included 2,134 incident MI cases and 3,021 control subjects. Gluteal adipose tissue biopsies were collected at recruitment, and the fatty acid composition (in percentage of total fatty acids) was determined by gas chromatography. A weighted Cox proportional hazards model with sex-specific baseline hazards and age as time axis, was used to evaluate the association between adipose tissue AA content and the risk of MI. Results: In the crude analysis we observed a significant positive association between adipose AA content and the risk of MI. Although attenuated, the association remained significant when relevant potential confounders were included, where the hazard ratios (HR) of MI relative to the lowest quintile increased across quintiles; two (HR 1.16 95%CI: 0.95-1.41), three (HR 1.18 95%CI: 0.97-1.43) four (HR 1.20 95%CI: 0.97-1.49), and five (HR 1.29 95%CI: 1.03-1.61) (P for trend = 0.048). Adipose tissue AA levels were not correlated with dietary intake of AA (r = 0.03, 95%CI: -0.01, 0.06) and negatively correlated with dietary intake of LA (r = -0.12, 95%CI: -0.15, -0.08). Conclusions: The adipose tissue content of AA was positively associated with the risk of MI. Adipose tissue AA was not associated with dietary intake of neither AA nor LA and this apparently complex regulation of AA levels in adipose tissue is not well understood and needs to be explored further in future studies.
Abstract 18509: Right Atrial Reservoir and Booster Strain Correlate Better Than Right Atrial Area with Tricuspid Annular Plane Systolic Excursion
Authors: Aasha S Gopal, Samir K Saha, Anatoli Kiotsekoglou, Satish C Govind, Per Lindqvist, Stefan Soderberg
Journal: Circulation (2012)

Background: Mechanical and volumetric dynamics and the mutual interdependence of right sided cardiac structures (right ventricle, RV: right atrium, RA) have not been adequately studied in routine clinical practice. Methods: 36 human subjects (56 ±10 years) referred for routine echocardiography for various clinical indications were included in the study. The echo-Doppler measurements included E/E, RV systolic pressure (pulmonary artery systolic pressure PASP), left ventricular ejection fraction LVEF%, TAPSE (tricuspid annular plane systolic excursion), RA area, RA active emptying fraction (RA AEF %), RA expansion index (RA EI), and, RA passive emptying fraction ( RA PEF%). Speckle tracking echocardiography was used to obtain RA booster, RA reservoir, and RA conduit strain (Fig) as well as RV basal, mid and apical strain. Results: LVEF, TAPSE, E/E, PASP, RA area were 60±8%, 23± 4 mm , 8±3, 29± 9mmHg, and 16±3 cm2 respectively. RA active emptying fraction (RA AEF %;) was 43 ±16%. RA booster, reservoir, and conduit strain respectively were -16± 3%, 33± 10%, and 15 ±7%. RV basal, mid, and apical strain were -23± 8%, -24± 6%, and -22± 7% respectively. Multiple regression analysis showed strongest correlation between TAPSE and RA AEF% (r= 0.48; p= 0.001) and between TAPSE and RA reservoir strain (r= 0.45; p= 0.001) while RA AEF and RA booster strain also correlated significantly ( r= 0.39; p = 0.01). Mid RV strain correlated with TAPSE ( r= 0.40; p= 0.005). RA area, RA expansion index showed no correlation on either RV or RA volumes or mechanics. Conclusion: In a group of patients with well-preserved LV and RV function and pressures, RA booster and reservoir strain predicted RV systolic function as measured by TAPSE. RA AEF% and mid RV S% significantly impacted tricuspid annular plane systolic excursion. RA area alone did not correlated with surrogate measures of right ventricular systolic function.