tbuckley/cabot-search huggingface dataset:
Abstract 5499: Promoter Variant of <i>Angiopoietin-2</i> and Plasma Angiopoietin-2 Are Associated With Risk of Stroke Recurrence in Patient With Lacunar Infarction
Authors: Jingzhou Chen, Hui Yu, Kai Sun, Weihua Song, Yongyi Bai, Weili Zhang, Kejia Lou, Yan Song, Yinhui Zhang, Rutai Hui
Journal: Circulation (2009)

Background- Risk factors for stroke recurrence are still not fully defined. Angiopoietin-2 is a very important mediator in the vessel development and repair. We hypothesized that altered expression of angiopoietin-2 will confer risk of stroke recurrence. Methods - The association of plasma angiopoietin-2 (determined by using ELISA) and the variants in angiopoietin-2 promoter with stroke recurrence was tested in 1735 patients with stroke of three subtypes, lacunar infarct (n=475), atherothrombotic (n=794) and hemorrhage (n=466), for a period of following-up 4.5 years (mean), the association was evaluated by using Kaplan-Meier analysis and the Cox regression models. Results -We found that angiopoietin-2 levels were associated with risk of stroke recurrence in lacunar infarct patients. Taking the lowest quartile as reference, the adjusted hazard ratio (HR) and 95% confidence intervals (CI) for stroke recurrence was 1.47 (0.75–2.88) for the second quartile, 2.44 (1.31–4.56) for the third and 2.00 (1.05–3.85) for the fourth. Allele T of rs3739391 in angiopoietin-2 promoter was associated with elevated angiopoietin-2 levels and increased risk of stroke recurrence in patients with lacunar infarct with HR 1.72 (1.09–2.72) relative to the allele C, but neither in those with atherothrombotic nor in those with hemorrhagic stroke. Conclusion- Our results indicate that both angiopoietin-2 and allele T of rs3739391 might be the risk marker for stroke recurrence in the patients with lacunar infarction. These findings may help to improve future prevention or therapy strategies for stroke.
Abstract 5533: Gender Differences in Outcome During Antihypertensive Therapy in Relation to Regression of Electrocardiographic Left Ventricular Hypertrophy: The LIFE Study
Authors: Peter M Okin, Eva Gerdts, Darcy A Hille, Sverre E Kjeldsen, Jonathan M Edelman, Björn Dahlöf, Richard B Devereux
Journal: Circulation (2009)

Background : Men and women have well-established differences in the magnitude of ECG amplitudes and durations and women have less regression of ECG left ventricular hypertrophy (LVH) in response to blood pressure lowering, even after adjusting for gender differences in baseline severity of LVH, treatment effects and blood pressure changes. However, whether women experience less prognostic benefit from their lesser regression of ECG LVH has not been examined. Methods and Results : Cardiovascular (CV) outcomes were examined in relation to regression of Sokolow-Lyon voltage (SLV) in 4963 women and 4230 men randomly assigned to losartan- or atenolol-based treatment. ECGs were performed at baseline, 6 months and then yearly until study end. Regression of LVH was dichotomized using sex-specific median decreases in SLV ≥3.0 mm in women and ≥4.5 mm in men. Women had significantly lower 5-year event rates for CV death (3.8 vs 6.2%, p&lt;0.0001), MI (3.3 vs 6.0%, p&lt;0.0001), stroke (5.5 vs 7.3%, p=0.003) and the LIFE study composite endpoint of these three events (9.8 vs 15.6%, p&lt;0.0001). In Cox regression analyses performed separately in women and men, women and men had similar reductions in risk of all events associated with regression of SLV defined by decreases in SLV exceeding the sex-specific median entered as time-varying covariates (Table ). The absence of gender differences in predictive value of regression of SLV LVH was confirmed by the absence of any significant interaction term between gender and change in SLV, with analyses performed treating SLV as either a sex-specific median decrease or as a continuous variable with no adjustment for gender. Conclusions : Despite lesser regression of ECG LVH than men, women have lower event rates than men and appear to derive the same degree of risk reduction as men from greater regression of SLV, independent of treatment effects, in-treatment blood pressure and the impact of possible gender differences in other risk factors on outcomes. Outcomes in Relation to Sex-Specific Median Regression of Sokolow-Lyon Voltage LVH
Abstract 5511: Natural Regulatory T Cells Control Coronary Arteriolar Endothelial Dysfunction and Hypertension in Mice
Authors: Zakaria T Abd Elmageed, Devika Nair, Romer A Gonzalez-Villalobos, Aziz A Chentoufi, Megan Partyka, Souad Belmadani, Khalid Matrougui
Journal: Circulation (2009)

Background and Purpose: Coronary arteriolar endothelial dysfunction and hypertension are the main cause for heart disease, and represent a major health problem. The cellular and molecular mechanisms that trigger this pathology are not well understood. Evidence from experimental and clinical research indicates a central role of immune cells and inflammation in cardiovascular diseases. In this study we determined that CD4+CD25+ regulatory T cells, which actively maintain immunological tolerance to self and nonself antigens, are key element in the control of blood pressure and coronary arteriolar endothelial dysfunction in angiotensin-II-dependent hypertensive mice model. Methods and Results: Mice infused with angiotensin-II significantly increased blood pressure determined by telemetry, reduced the number of CD4+CD25+ regulatory T cells apoptosis-dependent mechanism as determined by flow cytometry, increased macrophages inflammatory cytokines release (increased local tumor necrosis factor alpha release), and induction of adhesion molecules (I-CAM and V-CAM) expression facilitating the infiltration of macrophages into coronary arterioles and heart; and induced coronary arteriolar endothelial dysfunction assessed with reduced relaxation in response to dose-response of acetylcholine using arteriograph. Interestingly, hypertensive mice injected with purified CD4+CD25+ regulatory T cells (3 times a week for two weeks) or treated with copolymer-I (which enhances the conversion of CD4+CD25− T cells to CD4+CD25+ RegTC through the induction of transcription factor Foxp3 in CD4+ T cells and Known as glatiramer acetate, novel medication for the treatment of human multiple sclerosis) significantly reduced blood pressure and macrophages inflammatory cytokines release, and improved coronary arteriolar endothelial function. Conclusion: Our novel data strongly indicate that CD4+CD25+ regulatory T cells play a critical role in the regulation of blood pressure and coronary arteriolar endothelial function. These results provide new direction in the investigation of hypertension and coronary arteriolar disease and could lead to new therapeutic approaches that involve immune system modulation using CD4+CD25+ regulatory T cells.
Abstract 5508: Angiotensin Type-2 Receptor-mediated Coronary Arteriolar Dilation is Enhanced in Rats With Type-2 Diabetes Mellitus: A Role of Enhanced Nitric Oxide Mechansim via the Overexpression of Bradykinin B <sub>2</sub> Receptor
Authors: Koichi Oikawa, Motoi Kushibiki, Masahiro Yamada, Tomohiro Osanai, Ken Okumura
Journal: Circulation (2009)

Angiotensin type-2 (AT 2 ) receptor is said to function as a counterregulator against angiotensin type-1 (AT 1 ) receptor, and its expression was shown to be increased in various pathological states. However, the role of AT 2 receptor in type-2 diabetes mellitus (DM) is unclear. We examined AT 2 receptor-mediated coronary arteriolar dilation comparatively in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 DM model, and control Long-Evans Tokushima Otsuka (LETO) rats. At the age of 40 weeks, the coronary arterioles were isolated, cannulated, pressurized with 60 mmHg, and preconstricted with 40 mM potassium chloride. In the presence of valsartan (10 −4 M), each of angiotensin II (10 −11 to 10 −6 M) and a selective AT 2 receptor agonist CGP-42112A (CGP, 10 −11 to 10 −6 M) dilated the coronary arterioles in a dose-dependent manner, and the dilator responses were greater in OLETF than in LETO rats (both p&lt;0.05). An AT 2 receptor antagonist PD 123319 (10 −4 M) and N G -nitro-L-arginine methyl ester (10 −4 M) completely abolished the dilator effects of angiotensin II and CGP. Bradykinin B 2 receptor antagonist HOE-140 significantly attenuated the vasodilator effects of CGP and bradykinin, but did not alter the effect of acetylcholine. Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that AT 1 receptor mRNA level in the coronary arterioles was upregulated by 1.44±0.14 times in OLETF compared with that in LETO (p&lt;0.05). In contrast, AT 2 receptor mRNA level did not differ between LETO and OLETF. Bradykinin B 2 receptor mRNA level was upregulated by 2.56±0.38 times in OLETF compared with that in LETO (p&lt;0.05). In conclusion, in the presence of AT 1 receptor blocker, angiotensin II causes vasodilation in the rat coronary arterioles by a nitric oxide mechanism. This AT 2 receptor-mediated vasodilation is enhanced in rats with type-2 DM, which can be explained, at least in part, by the overexpression of bradykinin B 2 receptor in DM rats.
Abstract 5566: Serum Tenascin-C Levels Might be a Novel Biomarker for Predicting Short-term Prognosis of Type B Acute Aortic Dissection
Authors: Toshihiro Nozato, Akira Sato, Shunsuke Hirose, Kenji Koura, Atsuhiko Yagishita, Yoshihide Takahashi, Tetsuo Kamiishi, Hiroyuki Hikita, Atsushi Takahashi, Mitsuaki Isobe, Michiaki Hiroe
Journal: Circulation (2009)

Backgrounds: Tenascin-C (TN-C), an extracellular matrix glycoprotein, is not normally expressed in adult heart and aorta, but transiently reappears under various pathologic conditions playing important roles in tissue remodeling. The aim of this study is to clarify the clinical implication of serum TN-C levels in patients with type B acute aortic dissection (AD). Methods: We evaluated 43 patients with type B acute AD between May 2005 and January 2008 and 20 normal controls. We measured serum TN-C levels by ELISA on admission, 7 days, 14 days and 28 days after admission. We compared serum TN-C levels with blood biomarkers, and short-term clinical outcome at a discharge. Results: Serum TN-C levels (66.4 ng/ml) in AD was significantly higher than normal controls (27.4 ng/ml) at admission (p&lt;0.01). Serum TN-C levels in AD significantly increased at 7 days (82.4 ng/ml), and then gradually decreased to normal range at 28 days (40.4 ng/ml). Serum TN-C levels at 7 days was positively correlated with peak C-reactive protein levels (R=0.45, p=0.02). Three patients of AD died. Serum TN-C levels at 7 days of the death group were significantly higher than those of survival group (79.8±51.5 vs. 168.6±98.6 ng/ml, p=0.01). Conclusions: We demonstrated that serum TN-C levels are significantly elevated during acute stage after AD, and might be a novel biomarker for prediction of patient prognosis with type B acute AD.
Abstract 5486: High Density Lipoprotein (HDL) From Healthy Subjects, but Not From Patients With Coronary Artery Disease, Exerts Anti-thrombotic Effects on Human Endothelial Cells
Authors: Erik W Holy, Christian Besler, Ulf Landmesser, Thomas F Luscher, Felix C Tanner
Journal: Circulation (2009)

Background: Arterial thrombus formation is determined by the balance between pro-thrombotic mediators such as tissue factor (TF) and plasminogen activator inhibitor type 1 (PAI-1), and anti-thrombotic factors like tissue factor pathway inhibitor (TFPI) or tissue plasminogen activator (tPA). Native HDL from healthy subjects (HS) has anti-thrombotic properties; however, it remains unknown whether this is the case for HDL from patients with stable coronary disease (CAD) or acute coronary syndrome (ACS). Methods: HDL was isolated by sequential ultracentrifugation from HS and patients with CAD and ACD. The effects of HDL (50 μ g/ml) on TF, TFPI, and PAI-1 expression in human endothelial cells were determined by Western blot analysis; tPA release was measured by ELISA. Results: HDL from HS impaired thrombin-induced TF expression (−45±5%, p&lt;0.05, n=16) and activity (−33±8%, p&lt;0.05, n±7); in contrast, HDL from CAD and ACS patients did not (p=NS, n=12 and n=8). Similarly, HDL from HS increased TFPI expression by 2-fold (p&lt;0.01, n=8), while HDL from CAD and ACS patients had no effect (p=NS). HDL from HS enhanced tPA release (+26±3%; p=0.05, n=8); in contrast, HDL from CAD and ACS patients did not (p=NS, n=6). Furthermore, HDL from HS did not affect PAI-1 expression, while HDL from CAD patients enhanced PAI-1 expression by 62% (p&lt;0.05 vs. healthy, n=12) and HDL from ACS patients by 2 fold (p&lt;0.05 vs. control and p&lt;0.05 vs. healthy, n=8). Pretreatment with the inhibitor of NO formation, L-NAME (100 μ M), abolished the anti-thrombotic effects of HDL from HS on TF, TFPI, and tPA expression. The exogenous nitric oxide donor, DETANO, mimicked the effects of HDL from HS on TF, TFPI, and tPA. Conclusion: This study demonstrates that HDL from healthy subjects exerts anti-thrombotic effects on endothelial cells. In contrast, HDL from CAD and ACS patients loses these antithrombotic properties and instead enhances PAI-1 expression, thereby becoming pro-thrombotic. This observation might be highly relevant for HDL-targeted therapies.
Abstract 5524: Progenitor Cell Mobilization is FGF-2 Dependant and Results in the Activation of Osteoclasts
Authors: Martin Steinmetz, Bastian Pelster, Jean-Francois Arnal, Georg Nickenig, Nikos Werner
Journal: Circulation (2009)

Background Fibroblast growth factor-2 (FGF2) regulates proliferation of bone marrow (BM) stromal cells and has pro-angiogenic effects regulating endothelial cell growth, migration, and reendothelialization. Here we determine the underlying molecular mechanisms of FGF2-dependent statin-mediated progenitor cell mobilization. Methods and Results To determine the molecular mechanisms of FGF2-mediated progenitor cell mobilization, FGF2−/− and wild type (wt) mice were treated with atorvastatin (10mg/kg body weight s.c. per day) and placebo. In contrast to wt mice, the number of Sca1/flk-1 positive EPC in peripheral blood (flow cytometry) of atorvastatin treated FGF2−/− mice did not increase. This was due to an accumulation of Sca1/flk-1 positive cells within the BM. Inhibition of EPC mobilization in FGF2−/− mice was associated with a delay in reendothelialization in a mouse model of a focal endothelial cell denudation and a severe reduction in neoangiogenesis despite statin treatment. BM transplantation experiments demonstrated that reconstitution of FGF2−/− mice with wt stem cells completely restored statin-mediated EPC mobilization while wt mice reconstituted with FGF2−/− stem cells developed a severe mobilization defect associated with an impaired endothelial dependent vasorelaxation (organ chamber) and enhanced neointima formation. In wt mice, statin treatment was associated with an increased number of activated osteoclasts compared to placebo treated mice which are known to play a pivotal role in stem cell mobilization. Treatment with osteoclast-activating RANKL induced an effective mobilization of Sca1/flk1 and Sca1/CD117 positive progenitor cells and enhanced the number of early outgrowth EPC. Conclusion Medullary FGF2 is essential in the statin-mediated mobilization of EPC from BM into peripheral blood. A reduction in the number and activation status of osteoclasts may account for the impairment in EPC mobilization.
Abstract 5562: Renal Resistive Index is Strongly Associated With Poor Outcome After Coronary Bypass Surgery: A Prospective Study
Authors: Victor Aboyans, Bénédicte Tanguy, Vincent Bonnet, Philippe Lacroix, Marc Laskar
Journal: Circulation (2009)

Backgound: The presence of peripheral artery disease and renal failure are known as poor prognostic markers in patients undergoing coronary revascularization. While the presence of renal artery stenosis (RAS) is frequent in patients with coronary artery disease, the prognostic value of this lesion has never been assessed in the setting of coronary revascularization. Hypothesis: We hypothesized that renal vascular disease is associated with poorer postoperative outcome after coronary bypass surgery (CABG), independent of renal function. Methods: We prospectively assessed by Duplex the renal arteries of 401 consecutive patients prior to CABG. We defined RAS by the presence of at least 2 out of the 3 following criteria: maximal velocity &gt;1.8 m/s, reno-aortic velocity ratio &gt;3.5, reno-renal velocity ratio &gt;2.7. Additionally we defined high renal arterial resistance (HRAR) in case of resistive index &gt;0.80. The 30-days post-operative outcome was composite, combining death, stroke or myocardial infarction. Logistic regression models were used to assess associations. Results: Among the 68 women and 333 men enrolled (age 67.6±10.7 years), RAS and HRAR were found in 33 (8.2%) and 45 (11.2%) cases, respectively. Adjusted for age, sex, glomerular filtration rate, CVD risk factors, treatments, the presence of peripheral artery disease, and the presence of chronic pulmonary disease, we did not find any significant association between RAS and the composite outcome (OR=0.90, 95%CI:0.28 –2.95, p=ns). Conversely, in the same model, HRAR was strongly associated with the primary composite outcome (OR=3.97, 95%CI:1.36 –11.02, p=0.01). Conclusion: Beyond the glomerular filtration rate and other usual prognostic markers, renal artery ultrasound provides additional prognostic information. While the presence of renal artery stenosis is not found of any post-operative prognostic value, a high renal arterial resistance is strongly and independently associated with short-term cardiovascular outcomes.
Abstract 5605: Significant Reduction of Hospital Mortality of Stemi in Clinical Practice 1994–2008 Through Improvement of Guideline Adherence: Results of MITRAplus and OPTAMI
Authors: Anselm K Gitt, Uwe Zeymer, Ralf Zahn, Claus Juenger, Jochen Senges
Journal: Circulation (2009)

Background: Data from national and international myocardial infarction registries have identified the gaps between recommendations of guidelines for the management of ST-elevation myocardial infarction (STEMI) and treatment in clinical practice. Participation in continuous STEMI registries with benchmarking reports to the centres might improve implementation of guidelines into practice. Methods: Between 1994 and 2008, 37,876 consecutive patients with STEMI were enrolled into the MI-registries MITRAplus and OPTAMI to document patients’ characteristics, acute treatment and outcome in clinical practice. We examined the impact of guideline adherence for acute treatment of STEMI including reperfusion as well as adjunctive medical treatment on hospital outcome over time in Germany 1994 –2008. Results: From 1994 to 2008, the rate of acute reperfusion therapy in Germany increased from minimal 49% to 90% of consecutive patients with STEMI in 2008 with a significant shift from fibrinolysis to primary PCI. In parallel, the use of adjunctive medical treatment with aspirin, beta-blockers, ACE-inhibitors and clopidogrel was significantly improved over time. This improvement of guideline adherence for the acute treatment of STEMI was associated with a significant reduction of hospital mortality from initially 16.2% in 1994 to 6.2% in 2008. Limitation: In the currently conducted OPTAMI-Registry, 84% of participating centres provide 24h PCI-service. The data from 2006 –2008 therefore reflects the treatment and outcome of STEMI in tertiary centres in Germany, but clearly demonstrates that implementation of current practice guidelines is feasible. Conclusion: The improvements of guideline adherence for the management of STEMI, especially the increased rates of primary PCI as well as acute adjunctive medical treatment were associated with a significant decrease of hospital mortality in clinical practice in Germany.
Abstract 5490: Contemporary Risk of In-Hospital Events in Dialysis Patients Undergoing Percutaneous Coronary Interventions: Insights From the NCDR Cath-PCI Registry
Authors: Thomas T Tsai, Thomas M Maddox, Matthew T Roe, David Dai, Ivan P Casserly, P. Michael Ho, John C Messenger, Brahmajee K Nallamothu, Eric D Peterson, John S Rumsfeld
Journal: Circulation (2009)

Background: While chronic renal insufficiency is associated with poor outcomes in patients undergoing percutaneous coronary intervention (PCI), little is known about the in-hospital outcomes of chronic dialysis patients due to very small numbers of patients. Methods: 1,361,183 consecutive patients underwent PCI at 896 sites participating in the Cath-PCI registry from January 2004-September 2008. Patients were stratified by creatinine clearance (CrCl) into 4 groups: Normal renal function (CrCl ≥60 ml/min); Mild to moderate renal insufficiency (31≤CrCl&lt;60 ml/min); severe renal insufficiency (CrCl≤30 ml/min) and dialysis dependent. Using multivariable regression analysis with generalized estimating equations, the associations between renal insufficiency and in-hospital bleeding, vascular complications and death were explored. Results: Overall, 24,711 (1.8%) patients were dialysis dependent. In-hospital bleeding increased with worsening renal function (1.5% vs 2.8% vs 5.5% vs 3.7%, p&lt;0.001) as did vascular complications (0.6% vs 0.9% vs 1.4% vs 1.3%, p&lt;0.001) and in-hospital death (0.5% vs 1.6% vs 5.3% vs 4.7%, p&lt;0.001). After multivariable adjustment, patients with worsening levels of renal insufficiency had progressively higher odds of in-hospital bleeding, vascular complications and death ( Table ). Patients on dialysis represented the highest risk group overall. Conclusion: Approximately 2% of PCI patients are on chronic dialysis and have high rates of in-hospital adverse events. Compared to patients with normal renal function, dialysis is strongly associated with increased bleeding, vascular complications and death. Strategies to improve the care and outcomes of dialysis patients receiving PCI are warranted. Table: Adjusted Odds Ratio of In-Hospital Events By Creatinine Clearance (CrCl) in Patients Who Receive PCI