tbuckley/cabot-search huggingface dataset:
Abstract 19253: Acute Inflammation Following Dental Treatment Alters Endothelial Effects, but not Cholesterol Efflux Capacity of HDL
Authors: Francis P O'Neill, Christian Besler, Sophie Colin, Meliana Riwanto, Jasmin Manz, Kate Madden-Raja, Giulia Chinetti, Bart Staels, Francesco D'Auito, Ulf Landmesser, John E Deanfield
Journal: Circulation (2012)

Background: HDL elevating therapies have thus far failed to improve CV outcome and the loss of anti-atherosclerotic properties of HDL has recently been reported in CAD. This suggests specific biological activities of HDL, rather than its cholesterol content, may be crucial in mediating the anti-atherogenic effects of HDL. Aim: To determine the impact of acute systemic inflammation on various measures of HDL function. Methods: 50 subjects with periodontitis (PD) (Age 49.8 [6.5]) underwent dental treatment. In vivo changes in endothelial function were determined using Flow Mediated Dilatation (FMD). HDL function was assayed at baseline, at the peak of the inflammatory response (24 hours after PD treatment) and following resolution (6 months post PD treatment). HDL-mediated cholesterol efflux was measured in J774 macrophage cells, pre-treated with cAMP. Impact of HDL on cultured endothelial aortic cells was assayed by measuring HDL-dependent Nitric Oxide bioavailibility (NO) and superoxide (SO) production using ESR Spectroscopy. HDL-associated Paraoxonasae-1 (PON1) activity was measured by spectrophotometry. Results and Discussion: 24 hours after dental treatment HDL became dysfunctional, as shown by reduced NO and increased SO production by cultured endothelial cells (P&lt;0.01 for both). In addition, PON1 activity was reduced (P=&lt;0.05), but no difference was found in cholesterol efflux capacity. At 6 months, these changes in HDL function returned to baseline levels, whereas cholesterol efflux capacity remained unchanged. Endothelial effects of HDL tracked with changes in inflammatory markers and FMD. Conclusion: HDL becomes dysfunctional during acute inflammation resulting in abnormal endothelial responses, in the absence of any change in efflux capacity. Furthermore, the acute impairment of HDL function is reversible upon resolution of inflammation and tracks changes in FMD. These results suggest HDL function may contribute to the vascular alterations observed during an inflammatory response and may represent a novel mechanism whereby inflammation may promote atherosclerosis, i.e. by altering the endothelial effects of HDL.
Abstract 19071: Impact of Angiotensin Receptor Blocker on Development of Glucose Intolerance and New-onset Diabetes Mellitus in Asian Population
Authors: Ji Young Park, Seung Woon Rha, Jae Woong Choi, Sung Kee Ryu, Byoung Geol Choi, Se Yeon Choi, Sung Il Im, Sun Won Kim, Jin Oh Na, Seong Woo Han, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Circulation (2012)

Background; Angiotensin receptor blocker (ARB) is being extensively used to control hypertension. But, there have been limited data whether ARB is associated with increased incidence of new-onset diabetes mellitus (DM) or impaired glucose intolerance (IGT). Methods; We investigated total 13,561 patients (pts) that was glycerate hemoglobin level &lt; 6.0% and fasting glucose level &lt; 124 mg/dL (ARB therapy group=3421 and control group=9808) from January 2004 to February 2012. To adjust potential confounders, a propensity score matched analysis was performed using the logistic regression model. The primary end-point was the cumulative incidence of new-onset DM, IGT, and impaired fasting glucose (IFG). Also, multivariable cox-regression analysis by adjusted by aforementioned variables was performed to determine the impact of statin therapy on the incidence of new-onset DM, IGT, and IFG. Results; Mean follow-up duration was 534±604 days in all-pt group, and 608±607 days in propensity score matching group. After propensity score match, total 5632 pts (ARB group=2816 and control group = 2816) were enrolled for analysis. Baseline characteristics was similar between the two groups except the more use of diuretics (38% vs. 35.5%, p=0.047). In Kaplan-Meyer curve, there was no difference between the two groups (p=0.428, figure A). Also, in cox-regression analysis performed in all pts, ARB therapy was not associated with the increased incidence of primary end-point (figure B). Conclusions; In the present study, there was no clear association between ARB therapy and IGT or new-onset DM in a series of cardiovascular pts in Asian population.
Abstract 9961: Semaphorin-induced Inflammation Contributes to Insulin Resistance in Dietary Obesity
Authors: Ippei Shimizu, Yohko Yoshida, Junji Moriya, Taro Katsuno, Masayoshi Suda, Yoshio Kobayashi, Tohru Minamino
Journal: Circulation (2012)

Semaphorins and their receptors (plexins) are the axon-guiding molecules that also regulate the development of vascular network during embryogenesis. Semaphorin3E (Sema3E) is one of the class 3 semaphorins, and plexinD1 is its receptor. Our recent work shows that Sema3E is up-regulated by p53 under diabetic conditions and inhibits neoangiogenesis in ischemic tissues. Here we show a novel role for Sema3E in adipose tissue inflammation and insulin resistance in obesity. Expression of Sema3E and plexinD1 was up-regulated in adipose tissue of diet-induced obesity (DIO) model. Inhibition of the Sema3E-plexinD1 axis with genetic models or soluble form of the receptors markedly improved adipose tissue inflammation (infiltration of macrophages) and systemic insulin resistance. Conversely, forced expression of sema3E in adipose tissues provoked inflammation and systemic insulin resistance. Disruption of adipose tissue p53 down-regulated the expression of Sema3E and improved adipose tissue inflammation in DIO model. Migration assay showed that Sema3E promoted infiltration of macrophages, and this effect was inhibited when plexinD1 expression was disrupted in macrophages. These results indicate that Sema3E functions as a chemoattractant for macrophages and p53-induced increase of Sema3E-plexinD1 signals provokes adipose tissue inflammation and systemic insulin resistance in DIO model. Inhibition of the Sema3E-plexinD1 axis will be a new therapeutic target for lifestyle-related diseases including diabetes.
Abstract 8994: Elevated C-Reactive Protein Levels Predict Prognosis and Interact With Diabetes and Hypertension in the Development of Coronary Spasm
Authors: Ming Yow Hung, Kuang-Hung Hsu, Wei-Syun Hu, Nen-Chung Chang, Ming Hui Hung
Journal: Circulation (2012)

Introduction: The prognostic significance of high-sensitivity C-reactive protein (hs-CRP) in patients with coronary spasm and its association with diabetes and hypertension on the risk of coronary spasm remain unexplored. Hypothesis: We assessed the hypothesis that elevated hs-CRP level predicts outcomes in patients with coronary spasm and interacts with diabetes and hypertension in coronary spasm development. Methods: Patients undergoing coronary angiography with proven coronary spasm but without coronary stenosis &gt;50% were evaluated. A total of 897 subjects, including 350 women and 547 men, were analyzed and followed up for a median of 5.8 years. The levels of hs-CRP measured before coronary angiography were examined in a subset of 555 patients. Results: In women, only the highest hs-CRP tertile (&gt;3 mg/L) was independently associated with coronary spasm. In men, age, smoking and the highest hs-CRP tertile were independently associated with coronary spasm. Patients with the highest hs-CRP tertile had more coronary events compared with those without (p = 0.021, log-rank test). The highest hs-CRP tertile was a significant independent predictor of poor prognosis. The odds ratios of coronary spasm in both women and men with hs-CRP in the highest tertile reduced from 4.41 (95% confidence interval [CI]=1.77-10.97, p=0.001) to 1.45 and 2.86 (CI=1.47-5.57, p=0.002) to 1.59, respectively, if they had diabetes, and from 9.68 (CI=2.63-35.68, p=0.001) to 2.43 and 2.67 (CI=1.17-6.08, p=0.019) to 1.68, respectively, if they had hypertension. Conclusions: Elevated hs-CRP level predicts adverse outcome in coronary spasm patients. The negative effects of diabetes and hypertension on coronary spasm suggest that the pathogenesis of coronary spasm differs from that of coronary atherosclerosis.
Abstract 8897: Valid Cardiac Strategy for Reversing Focal Cerebral Ischemia Caused by Vasospasm after Subarachnoid Hemorrhage
Authors: Tatsushi Mutoh, Shinya Kobayashi, Tatsuya Ishikawa, Akifumi Suzuki
Journal: Circulation (2012)

Delayed cerebral ischemia (DCI) attributable to vasospasm is currently the leading cause of death and disability after subarachnoid hemorrhage (SAH). Therapeutic hemodynamic augmentation by increasing cardiac output (CO) is a valuable method for elevating cerebral blood flow and oxygenation in dysautoregulated territories affected by DCI. Our previous results suggest that the key for successful reversal of focal ischemia is to accomplish hemodynamic acceleration enough to improve cerebral microcirculation. We prospectively assessed more effective strategy for hyperdynamic therapy with dobutamine (DOB) either by intermittent dose-repetition or by continuous step-wise dose increments in the treatment of post-SAH DCI. Real-time CO and regional cerebral oxygenation (rSO 2 ) recordings during the therapy in conjunction with the assessment of neurological improvements were analyzed. Forty patients with SAH treated surgically within 24 hours of ictus and diagnosed to have DCI between postoperative days 4 and 14 were enrolled. DOB was administered at an initial dose of 3 µg/kg/min and then increased in 3 µg/kg/min increments until resolution of the neurologic symptoms. Once the DCI recurred, 1) the DOB dose was reduced to the level where CO and rSO 2 became stable to apply the same dose-repetition (LD) or 2) simply increased the same increments until maximal dose (18 µg/kg/min) (HD). A total of 158 DOB challenges were performed with a maximum therapeutic dose of 9 ± 3 µg/kg/min (LD) and 13 ± 4 µg/kg/min (HD) (p=0.001), respectively. In response to DOB, uptake and stabilization of rSO 2 accompanied by a rapid elevation of CO usually occur, followed by improvement of the symptoms. Calculated peak slope of the CO uptake were greater in LD than in HD (p&lt;0.05). Area under the ROC curve of peak CO slope to discriminate neurological responders for each challenge was not significantly different between the strategies (p&gt;0.05). Patients managed with LD experienced less numbers of tachycardia, arrhythmia and paralytic ileus than those with HD. In conclusion, repeat application strategy with low-dose DOB will play a key role of hyperdynamic therapy in effectively relieving focal ischemia with less drug-induced complications in patients suffering from DCI after SAH.
Abstract 306: Impact of First Medical Contact on Symptom Onset to Door Time in Patients Presenting for Primary Percutaneous Coronary Intervention
Authors: Abdul Moiz Hafiz, Srihari S Naidu, Joshua DeLeon, Shahidul Islam, Basil Alkhatib, Miguel Lorenz, Alexis D’Elia, Barry Rosenthal, Kevin P Marzo
Journal: Circulation (2012)

Background: Shorter pre-hospital delays in ST-elevation myocardial infarction (STEMI) are associated with improved outcomes. Whether first medical contact type is related to symptom onset to door time (SODT) remains unknown. Methods : We performed a retrospective chart review of all consecutive patients treated with primary percutaneous coronary intervention (PCI) for STEMI at our tertiary care suburban teaching hospital from October 1, 2005 to December 31, 2009. We compared SODT in patients whose first medical contact was a private physician, in person or via telephone; and patients who presented to the Emergency Department (ED) directly, in person or via Emergency Medical Services (EMS). Results : Of 366 patients (table), 84 (23%) contacted a physician (group A) while 282 (77.6%) did not (group B). Group A was associated with higher median SODT (239.5 vs. 130 minutes, p=0.0043) and a trend to higher mortality at a median follow-up of 3.85 years (17.86% vs. 10.64%, p=0.089). Multiple linear regression analysis revealed two factors to be independently associated with prolonged SODT: 1) first contact (physician vs. no physician), p=0.002, regression coefficient=0.547, standard error (SE)=0.171, indicating a 73% increase in SODT if patients first contacted physicians and 2) mode of transportation (EMS vs. personal), p=0.016, regression coefficient=0.349, SE=0.144, indicating a 30% decrease in SODT if EMS was used. Patients presenting during “on-hours” (weekdays) were more likely to first contact a physician compared with those presenting during “off-hours” (weeknights and weekends) (66.67% in group A vs. 45.04% in group B, p&lt;0.001). Conclusions : Patients whose first medical contact was a physician had greater pre-hospital delays compared to those who sought emergent medical care directly, and a trend to higher mortality. This pattern occurred more often during “on-hours”. Educational efforts aimed at both patient and physician office practices are warranted.
Abstract 9576: A Nuclear Receptor-microRNA Circuit Links Control of Muscle Fiber Type to Energy Metabolism
Authors: Zhenji Gan, John Rumsey, Bethany C Hazen, Ling Lai, Teresa C Leone, Richard B Vega, Johan Auwerx, Eric N Olson, Anastasia Kralli, Daniel P Kelly
Journal: Circulation (2012)

Zhenji Gan, 2012 Finalist and Presenting Author
Abstract 203: Potential Dependence on Type of Bystander Basic Life Support Response and Outcomes in Out-of-Hospital Cardiac Arrests Managed Without Any Involvement of Physicians
Authors: Hideo Inaba, Takahisa Kamikura, Taiki Nishi, Keiko Takase, Manabu Sakagami, Hidetsuyo Hamada, Tetsuo Maeda
Journal: Circulation (2012)

Objectives: The present study was conducted to test our hypothesis that relation of bystander to cardiac arrest victim may affect the BLAs response and outcomes in bystander-witnessed OHCAs. Methods: We obtained the Japanese nation-wide database for 547,218 OHCAs that occurred from Jan. 2005 to Dec. 2009, and extracted a dataset for 139,265 bystander-witnessed OHCAs without any involvement of physicians, that has all information for analysis. We first compared the BLS response of the four bystander groups (family members, friends and colleagues, passers-by and others). Then, we compared the outcomes of bystander-witnessed OHCAs having bystander CPR among the four groups. Results: The intervals between collapse and emergency call and between call and arrival at patient were shortest in OHCAs witnessed by pass-by. The telephone-CPR was most frequently attempted (45.8%, 41,442/90,426) but failed (39.4%, 16,315/41,442) in OHCAs witnessed by family. Consequently, the rate of bystander CPR was lowest (36.5%, 33,008/90,426), CPR was most frequently initiated following the telephone-CPR (76.1%, 25,127/33,008), and type of CPR was most frequently “chest-compression-only” (67.9%, 22,406/33,008) in OHCAs witnessed by family members. Multiple logistic regression analysis revealed that family as a type of bystander was an independent factor associated with lack of bystander CPR (Odds ratio=1.54 against passers-by, 2.09 against friends and colleagues, and 5.15 against others) . In all subcategories, the incidences of shockable initial rhythms and outcomes were lowest in the OHCAs witnessed by family members. Multiple logistic regression disclosed that that family member as a bystander group is one of the independent factor associated with 1-M unfavorable neurological outcomes in all subcategories of bystander-witnessed OHCAs. Conclusions: Family members do not quickly respond to OHCAs and unwilling to perform CPR on their own initiative. OHCAs witnessed by family and having bystander CPR have low incidences of shockable initial rhythm and 1-M favourable neurolofical survival. The first responder system that enable a good BLS performer to quickly reach the scene may be necessary in OHCAs witnessed by family.
Abstract 8816: Comparison of Prognostic Values of Contemporary Contrast-Induced Nephropathy Definitions in Patients with Acute Myocardial Infarction Undergoing Emergency Coronary Angiography
Authors: Masayoshi Kiyokuni, Masami Kosuge, Tsutomu Endo, Toshiaki Ebina, Kiyoshi Hibi, Kengo Tsukahara, Noriaki Iwahashi, Mitsuaki Endo, Nobuhiko Maejima, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2011)

Background: Previous studies have shown that contrast-induced nephropathy (CIN) defined in several ways is associated with poor outcomes. However, there is no consensus on the optimal definition of CIN. Objective: We examined the prognostic significance of 3 contemporary definitions of CIN with respect to long-term major adverse cardiac and cerebrovascular event (MACCE) and mortality after emergency coronary angiography for acute myocardial infarction (AMI). Methods: We measured serum creatinine (SCr) at admission and each day for the following 3 days in 733 patients with AMI who underwent emergency coronary angiography within 12 h after symptom onset. CIN was defined as SCr increase ≥0.5 mg/dl, SCr increase ≥25%, or estimated glomerular filtration rate (eGFR) decrease ≥25%. Results: Of 733 patients (age 64 ± 12 years), 47% were anterior AMI, 31% had renal dysfunction defined as admission eGFR &lt;60 ml/min/1.73m2, and 81% underwent primary percutaneous coronary intervention. The mean volume of contrast medium used was 155 ± 57 ml. The incidence of CIN ranged widely depending on the definition used; 7.8% (SCr increase ≥0.5 mg/dl), 37.4% (SCr increase ≥ 25%), and 29.2% (eGFR decrease ≥ 25%). There were significant differences of 5-year MACCE (all-cause death, non-fatal myocardial infarction, or stroke) and all-cause mortality between patients with and without CIN by the 3 definitions (especially SCr increase ≥0.5 mg/dl). In multivariate analysis, only SCr increase ≥0.5 mg/dl was independently and significantly associated with 5-year MACCE and all-cause mortality; but the other 2 definitions were not. Conclusions: In patients with AMI undergoing emergency coronary angiography, of the 3 contemporary definitions of CIN, only SCr increase ≥0.5 mg/dl strongly predicts 5-year adverse outcomes, suggesting the prognostic importance of this definition.
Abstract 228: Neurological Outcomes of Cardiac Arrest Survivors with Myoclonus Following Resuscitation
Authors: David B Seder, Richard R Riker, Barbara Unger, Kjetil Sunde, Sten Rupertsson, Michael Mooney, Pascal Stammet, Hans Friberg, Niklas Nielsen
Journal: Circulation (2012)

Objectives: Historically, myoclonus was thought to portend a hopeless prognosis after cardiac arrest (CA). We evaluated the outcomes and characteristics of CA survivors with myoclonus in a large prospective registry. Methods: Retrospective review of the International Cardiac Arrest Registry (INTCAR) Findings: Of 2564 patients entered into INTCAR between 12/2008-12/2011, 466 (18%) had myoclonus, with an average age of 61.8 (SD 15.9) years, 84% OHCA, initial rhythm VT/VF in 47%, asystole in 28%, and PEA in 21%. Mean “no flow” interval was 8.6 (7.2) minutes, “low flow” interval 17 (15.2) minutes, and total time to return of circulation (TTROSC) 25.6 (15.5) minutes. Therapeutic hypothermia (TH) was applied in 444 (95%) patients, and 334 (72%) had EEG monitoring. Good Outcome (GO) with CPC1-2 occurred in 27 patients at ICU discharge, increasing to 43 (9.2%) at hospital discharge. For patients with GO, mean age was 53.6 (15.6), 79% VT/VF, and TTROSC was 18.6 (12.8) minutes. The EEG showed continuous activity with diffuse slowing in 61% of GO patients, and median hospital LOS was 14.5 days [IQR 9-22]. Of 423 myoclonus patients with poor outcome (PO = CPC3-5), life support was withdrawn in 330 (78%); due to neurological futility in 293 (89%), and the EEG (n=306) showed burst suppression in 152 (49.7%), status epilepticus in 102 (33.3%), severe background attenuation in 75 (24.5%) and continuous activity with diffuse slowing in 75 (24.5%). Among PO patients, 49 (11.6%) did not receive or complete TH. Median hospital LOS in this cohort was 5 [IQR3-7] days. Of 293 patients that died of “neurological futility”, 131 (45%) died less than 5 days after CA. Conclusions: Myoclonus after cardiac arrest should not be considered uniformly fatal. Despite early withdrawal or less than fully aggressive life supportive measures in many patients, 9.2% of myoclonus patients in a large registry population had good outcomes.
Abstract 8284: Brain-Derived Neurotrophic Factor Protects Against Cardiac Dysfunction After Myocardial Infarction via a Central Nervous System-Mediated Pathway
Authors: Sho Okada, Tohru Minamino, Masataka Yokoyama, Kaoru Tateno, Junji Moriya, Ippei Shimizu, Aika Nojima, Takashi Ito, Yoko Ogasawara, Issei Komuro, Yoshio Kobayashi
Journal: Circulation (2011)

The central nervous system (CSN) is thought to influence regulation of the cardiovascular system in response to humoral and neural signals from peripheral tissues, but our understanding of the molecular mechanisms involved is still quite limited. Here we demonstrate a novel CNS-mediated mechanism by which brain-derived neurotrophic factor (Bdnf) has a protective effect against cardiac remodeling after myocardial infarction (MI). We generated conditional Bdnf knockout (CKO) mice, in which expression of Bdnf was systemically reduced, by using the inducible Cre-loxP system. Two weeks after MI was induced surgically in these mice, systolic function was significantly impaired and cardiac size was markedly increased in CKO mice compared with controls. Cardiomyocyte death was increased in these mice, along with decreased expression of survival molecules. Deletion of the Bdnf receptor (TrkB) from the heart also led to exacerbation of cardiac dysfunction after MI. The plasma levels of Bdnf were markedly increased after MI and this increase was associated with up-regulation of Bdnf expression in the brain, but not in the heart. Ablation of afferent nerves from the heart or genetic disruption of neuronal Bdnf expression inhibited the increase of plasma Bdnf after MI and led to exacerbation of cardiac dysfunction. Peripheral administration of Bdnf significantly restored the cardiac phenotype of neuronal Bdnf-deficient mice, suggesting that Bdnf expression is up-regulated by neural signals from the heart after MI and then protects the myocardium against ischemic injury. These findings also suggest that activation of neuronal Bdnf may become a therapeutic strategy for cardiac disease.