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Find video protocols related to scientific articles indexed in Pubmed.
Vitamin D Therapy in Individuals with Pre-Hypertension or Hypertension: The DAYLIGHT Trial.
Circulation
PUBLISHED: 11-01-2014
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-A large body of epidemiological and experimental evidence suggests that vitamin D deficiency may promote hypertension. This raises the possibility that vitamin D supplementation could be a simple intervention to reduce blood pressure, but data from prospective, randomized trials are limited.
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Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials.
Lancet
PUBLISHED: 08-19-2014
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Bivalirudin is an alternative to heparin in patients undergoing percutaneous coronary intervention (PCI). We aimed to define the effects of a bivalirudin-based anticoagulation regimen compared with a heparin-based anticoagulation regimen on ischaemic and bleeding outcomes.
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The incidence of kidney injury for patients treated with a high-potency versus moderate-potency statin regimen after an acute coronary syndrome.
J Am Heart Assoc
PUBLISHED: 05-03-2014
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Observational studies have raised concerns that high-potency statins increase the risk of acute kidney injury. We therefore examined the incidence of kidney injury across 2 randomized trials of statin therapy.
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Efficacy and safety of evolocumab (AMG 145), a fully human monoclonal antibody to PCSK9, in hyperlipidaemic patients on various background lipid therapies: pooled analysis of 1359 patients in four phase 2 trials.
Eur. Heart J.
PUBLISHED: 03-04-2014
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Prior trials with monoclonal antibodies to proprotein convertase subtilizin/kexin type 9 (PCSK9) reported robust low density lipoprotein cholesterol (LDL-C) reductions. However, the ability to detect potentially beneficial changes in other lipoproteins such as lipoprotein (a), triglycerides, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein (Apo) A1, and adverse events (AEs) was limited by sample sizes of individual trials. We report a pooled analysis from four phase 2 studies of evolocumab (AMG 145), a monoclonal antibody to PCSK9.
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Fibroblast growth factor-23, cardiovascular prognosis, and benefit of angiotensin-converting enzyme inhibition in stable ischemic heart disease.
J. Am. Coll. Cardiol.
PUBLISHED: 02-19-2014
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This study sought to test 2 hypotheses: 1) fibroblast growth factor (FGF)-23 identifies patients with stable ischemic heart disease (SIHD) at high risk of cardiovascular events independent of clinical factors, renal function, and established cardiovascular biomarkers; and 2) FGF-23 identifies patients who derive greater clinical benefit from angiotensin-converting enzyme inhibitor therapy.
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Prognostic performance of multiple biomarkers in patients with non-ST-segment elevation acute coronary syndrome: analysis from the MERLIN-TIMI 36 trial (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis In M
J. Am. Coll. Cardiol.
PUBLISHED: 02-13-2014
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The aim of this study was to assess the prognostic performance of C-terminal provasopressin (copeptin), midregional pro-adrenomedullin (MR-proADM), and midregional pro-atrial natriuretic peptide (MR-proANP) in a large prospective cohort of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).
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Diagnostic performance of copeptin in patients with acute nontraumatic chest pain: BWH-TIMI ED chest pain study.
Clin Cardiol
PUBLISHED: 01-22-2014
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Arginine-vasopressin (AVP) is an acute marker of physiologic stress. Copeptin is the C-terminal fragment of vasopressin precursor hormone that is more easily measured than AVP. Studies assessing the utility of copeptin in the diagnosis of myocardial infarction (MI) have demonstrated mixed results.
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Clinical implications and correlates of Q waves in patients with ST-elevation myocardial infarction treated with fibrinolysis: observations from the CLARITY-TIMI 28 trial.
Clin Cardiol
PUBLISHED: 01-22-2014
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The relationships between Q waves that appear during the acute phase of ST-elevation myocardial infarction (STEMI), clinical characteristics, ST-segment resolution (STRes), and clopidogrel therapy in patients treated with fibrinolysis are not well described.
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Design and rationale for the Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial.
Am. Heart J.
PUBLISHED: 01-06-2014
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P2Y12 receptor antagonist therapy is recommended in addition to ASA for up to 1 year after acute coronary syndrome to reduce ischemic events. In contrast, the benefit of long-term dual antiplatelet therapy beyond 1 year remains unclear. Ticagrelor is a potent, reversibly binding P2Y12 receptor-antagonist that has been shown to be superior to clopidogrel in patients with acute coronary syndromes for up to 1 year.
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Variability of individual platelet reactivity over time in patients treated with clopidogrel: insights from the ELEVATE-TIMI 56 trial.
J. Am. Coll. Cardiol.
PUBLISHED: 01-02-2014
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The degree of antiplatelet response to clopidogrel has been associated with clinical outcomes. Studies have investigated whether adjustment of antiplatelet therapies based on a single platelet function test is beneficial.
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Increases in myocardial workload induced by rapid atrial pacing trigger alterations in global metabolism.
PLoS ONE
PUBLISHED: 01-01-2014
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To determine whether increases in cardiac work lead to alterations in the plasma metabolome and whether such changes arise from the heart or peripheral organs.
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Efficacy and Safety of Longer-Term Administration of Evolocumab (AMG 145) in Patients With Hypercholesterolemia: 52-Week Results From the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) Randomized Trial.
Circulation
PUBLISHED: 11-19-2013
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Evolocumab (AMG 145), a monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein cholesterol (LDL-C) in phase 2 studies of 12 weeks duration. The longer-term efficacy and safety of PCSK9 inhibition remain undefined.
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Ticagrelor for acute coronary syndromes.
Expert Rev Cardiovasc Ther
PUBLISHED: 10-23-2013
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Ticagrelor is a potent P2Y12 adenosine diphosphate receptor antagonist characterized by a rapid onset, consistent and reversible antiplatelet effect, and an acceptable safety profile compared with existing adenosine diphosphate receptor blockers. In the large Phase III trial, PLATO, ticagrelor significantly reduced the composite of cardiovascular death, myocardial infarction, or stroke as well as cardiovascular and all-cause mortality compared with clopidogrel in patients presenting with acute coronary syndromes. With its favorable impact on mortality, ticagrelor changes the landscape of anti-thrombotic therapy for patients with acute coronary syndromes.
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Circadian variation of stent thrombosis and the effect of more robust platelet inhibition: a post hoc analysis of the TRITON-TIMI 38 trial.
J. Cardiovasc. Pharmacol. Ther.
PUBLISHED: 09-24-2013
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The well-described morning peak in the onset of acute coronary syndromes has been partly attributed to increased platelet activity upon arising. It has been suggested that stent thrombosis (ST) exhibits a similar pattern. We assessed whether a diurnal variation in ST occurs, and whether more robust antiplatelet therapy with prasugrel (vs clopidogrel) can attenuate a morning excess. Methods and Materials: Patients from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38 trial (N = 13 608) with adjudicated ST classified per the Academic Research Consortium definitions of definite (N = 135) and probable (N = 27) were grouped into prespecified 8-hour intervals by time of onset: early (6 am-2 pm), late-day (2 pm-10 pm), and overnight (10 pm-6 am). We compared the rates per 1000 patients of ST across time intervals and stratified by treatment and stent type.
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Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non-ST-Elevation Acute Coronary Syndrome.
Clin. Chem.
PUBLISHED: 09-19-2013
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High-sensitivity assays for cardiac troponin enable more precise measurement of very low concentrations and improved diagnostic accuracy. However, the prognostic value of these measurements, particularly at low concentrations, is less well defined.
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AMG 145, A Monoclonal Antibody Against PCSK9, Facilitates Achievement of NCEP-ATP III LDL-C Goals Among High Risk Patients: An Analysis From the LAPLACE-TIMI 57 Trial.
J. Am. Coll. Cardiol.
PUBLISHED: 07-27-2013
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To define the ability of AMG 145, a monoclonal antibody directed against PCSK9, to enable subjects at high risk for major adverse cardiovascular events to achieve NCEP-ATP III LDL-C and other lipid parameter goals.
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AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9, significantly reduces lipoprotein(a) in hypercholesterolemic patients receiving statin therapy: an analysis from the LDL-C Assessment with Proprotein Convertase Subtilisi
Circulation
PUBLISHED: 07-24-2013
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Lipoprotein(a) [Lp(a)] is an emerging risk factor for cardiovascular disease. Currently, there are few available therapies to lower Lp(a). We sought to evaluate the impact of AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), on Lp(a).
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Balancing the risk of mortality and major bleeding in the treatment of NSTEMI patients - A report from the National Cardiovascular Data Registry.
Am. Heart J.
PUBLISHED: 05-30-2013
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We sought to describe real-world patterns of care in NSTEMI patients across different risk profiles for bleeding and mortality.
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Secretory Phospholipase A2-IIA and Cardiovascular Disease: A Mendelian Randomization Study.
Michael V Holmes, Tabassome Simon, Holly J Exeter, Lasse Folkersen, Folkert W Asselbergs, Montse Guardiola, Jackie A Cooper, Jutta Palmen, Jaroslav A Hubacek, Kathryn F Carruthers, Benjamin D Horne, Kimberly D Brunisholz, Jessica L Mega, Erik P A van Iperen, Mingyao Li, Maarten Leusink, Stella Trompet, Jeffrey J W Verschuren, G Kees Hovingh, Abbas Dehghan, Christopher P Nelson, Salma Kotti, Nicolas Danchin, Markus Scholz, Christiane L Haase, Dietrich Rothenbacher, Daniel I Swerdlow, Karoline B Kuchenbaecker, Eleonora Staines-Urias, Anuj Goel, Ferdinand van 't Hooft, Karl Gertow, Ulf de Faire, Andrie G Panayiotou, Elena Tremoli, Damiano Baldassarre, Fabrizio Veglia, Lesca M Holdt, Frank Beutner, Ron T Gansevoort, Gerjan J Navis, Irene Mateo Leach, Lutz P Breitling, Hermann Brenner, Joachim Thiery, Dhayana Dallmeier, Anders Franco-Cereceda, Jolanda M A Boer, Jeffrey W Stephens, Marten H Hofker, Alain Tedgui, Albert Hofman, André G Uitterlinden, Vera Adamkova, Jan Piťha, N Charlotte Onland-Moret, Maarten J Cramer, Hendrik M Nathoe, Wilko Spiering, Olaf H Klungel, Meena Kumari, Peter H Whincup, David A Morrow, Peter S Braund, Alistair S Hall, Anders G Olsson, Pieter A Doevendans, Mieke D Trip, Martin D Tobin, Anders Hamsten, Hugh Watkins, Wolfgang Koenig, Andrew N Nicolaides, Daniel Teupser, Ian N M Day, John F Carlquist, Tom R Gaunt, Ian Ford, Naveed Sattar, Sotirios Tsimikas, Gregory G Schwartz, Debbie A Lawlor, Richard W Morris, Manjinder S Sandhu, Rudolf Poledne, Anke H Maitland-van der Zee, Kay-Tee Khaw, Brendan J Keating, Pim van der Harst, Jackie F Price, Shamir R Mehta, Salim Yusuf, Jaqueline C M Witteman, Oscar H Franco, J Wouter Jukema, Peter de Knijff, Anne Tybjaerg-Hansen, Daniel J Rader, Martin Farrall, Nilesh J Samani, Mika Kivimäki, Keith A A Fox, Steve E Humphries, Jeffrey L Anderson, S Matthijs Boekholdt, Tom M Palmer, Per Eriksson, Guillaume Paré, Aroon D Hingorani, Marc S Sabatine, Ziad Mallat, Juan P Casas, Philippa J Talmud.
J. Am. Coll. Cardiol.
PUBLISHED: 04-24-2013
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This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.
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Evaluation of the diagnostic performance of current and next-generation assays for cardiac troponin I in the BWH-TIMI ED Chest Pain Study.
Eur Heart J Acute Cardiovasc Care
PUBLISHED: 03-05-2013
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Rapid diagnosis of acute coronary syndrome is a clinical and operational priority in busy emergency departments (ED). We examined the performance of an investigational troponin I (TnI) assay with 10-100-times greater sensitivity than current commercial assays.
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Prognostic value of cardiac troponin I measured with a highly sensitive assay in patients with stable coronary artery disease.
J. Am. Coll. Cardiol.
PUBLISHED: 02-13-2013
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The aims of this study were to assess the prognostic value of cardiac troponin I levels, measured with a new high-sensitivity assay, in low-risk patients with stable coronary artery disease (CAD) and to contrast its determinants and prognostic merit with that of high-sensitivity cardiac troponin T (hs-TnT).
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Relation between time of symptom onset of ST-segment elevation myocardial infarction and patient baseline characteristics: from the National Cardiovascular Data Registry.
Clin Cardiol
PUBLISHED: 01-13-2013
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The presence of a morning excess of ST-segment elevation myocardial infarction (STEMI) has been observed. The relation between patient characteristics and timing of STEMI may provide insight into the biological processes responsible for this phenomenon.
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Evaluation of multiple biomarkers of cardiovascular stress for risk prediction and guiding medical therapy in patients with stable coronary disease.
Circulation
PUBLISHED: 12-16-2011
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Circulating biomarkers can offer insight into subclinical cardiovascular stress and thus have the potential to aid in risk stratification and tailoring of therapy.
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Role of ST2 in non-ST-elevation acute coronary syndrome in the MERLIN-TIMI 36 trial.
Clin. Chem.
PUBLISHED: 11-17-2011
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We investigated the prognostic performance of ST2 with respect to cardiovascular death (CVD) and heart failure (HF) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in a large multinational trial.
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Prognostic utility of secretory phospholipase A(2) in patients with stable coronary artery disease.
Clin. Chem.
PUBLISHED: 07-22-2011
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Secretory phospholipase A(2) (sPLA(2)) may contribute to atherogenesis. To date, few prospective studies have examined the utility of sPLA(2) for risk stratification in coronary artery disease (CAD).
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Myocardial ischemia induced by rapid atrial pacing causes troponin T release detectable by a highly sensitive assay: insights from a coronary sinus sampling study.
J. Am. Coll. Cardiol.
PUBLISHED: 06-11-2011
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The purpose of this study was to assess whether: 1) very small increases in troponin T, measured by a new highly sensitive cardiac troponin T (hs-cTnT), may reflect ischemia without necrosis; and 2) serial changes can discriminate ischemia from other causes of cardiac troponin T (cTnT) release.
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A pipeline that integrates the discovery and verification of plasma protein biomarkers reveals candidate markers for cardiovascular disease.
Nat. Biotechnol.
PUBLISHED: 05-20-2011
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We developed a pipeline to integrate the proteomic technologies used from the discovery to the verification stages of plasma biomarker identification and applied it to identify early biomarkers of cardiac injury from the blood of patients undergoing a therapeutic, planned myocardial infarction (PMI) for treatment of hypertrophic cardiomyopathy. Sampling of blood directly from patient hearts before, during and after controlled myocardial injury ensured enrichment for candidate biomarkers and allowed patients to serve as their own biological controls. LC-MS/MS analyses detected 121 highly differentially expressed proteins, including previously credentialed markers of cardiovascular disease and >100 novel candidate biomarkers for myocardial infarction (MI). Accurate inclusion mass screening (AIMS) qualified a subset of the candidates based on highly specific, targeted detection in peripheral plasma, including some markers unlikely to have been identified without this step. Analyses of peripheral plasma from controls and patients with PMI or spontaneous MI by quantitative multiple reaction monitoring mass spectrometry or immunoassays suggest that the candidate biomarkers may be specific to MI. This study demonstrates that modern proteomic technologies, when coherently integrated, can yield novel cardiovascular biomarkers meriting further evaluation in large, heterogeneous cohorts.
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Impact of smoking on antiplatelet effect of clopidogrel and prasugrel after loading dose and on maintenance therapy.
Am. Heart J.
PUBLISHED: 04-16-2011
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Pharmacodynamic studies reported an amplified on-clopidogrel platelet inhibition in smokers potentially caused by an increased metabolic drug activation via induction of cytochrome P450 1A2. The aims of this analysis were to evaluate the impact of smoking on the antiplatelet effect of clopidogrel and prasugrel and to test the potential interaction of smoking with the treatment effect of these drugs.
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Impact of reduced glomerular filtration rate on outcomes in patients with ST-segment elevation myocardial infarction undergoing fibrinolysis: a CLARITY-TIMI 28 analysis.
J. Thromb. Thrombolysis
PUBLISHED: 02-15-2011
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Reduced glomerular filtration rate (GFR) is associated with adverse outcomes in patients with cardiovascular disease. We explored the relationship between GFR and angiographic and clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients receiving pharamacologic reperfusion, with or without clopidogrel. Data were available to estimate GFR in 3,252 STEMI patients undergoing fibrinolysis, randomized to clopidogrel versus placebo in the CLARITY-TIMI 28 trial. Patients with a creatinine > 2.5 mg/dl were excluded from the trial. We compared outcomes between patients with no, mild or moderate reductions in baseline estimated GFR (ml/min/1.73 m²) of ? 90, 60-89, and <60, respectively. Compared to patients with no (n = 841) or mildly reduced GFR (n = 1897), those with moderately reduced GFR (n = 514) were older, more often female, and were more likely to have diabetes and hypertension (P ? 0.001 for all). The risk of the primary endpoint (an occluded infarct-related artery on angiography or death/myocardial infarction by day 8), 30 day cardiovascular events (death, myocardial infarction, or urgent revascularization for recurrent ischemia) and 30 day Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding increased as GFR declined (P for trend 0.003, <0.0001, and 0.0008 respectively). The adjusted risk of 30 day ischemic complications remained higher in patients with moderately reduced versus normal GFR (OR 1.5, 95% CI 1.0-2.1, P = 0.04). Treatment with clopidogrel tended to yield greater benefit in patients with normal or mildly reduced GFR versus in patients with moderately reduced GFR. In conclusion, STEMI patients with reduced GFR treated with medical reperfusion, including dual antiplatelet therapy, have higher rates of adverse clinical outcome. Further research on optimal STEMI therapy in this high-risk group is warranted.
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Assessment of adiponectin and the risk of recurrent cardiovascular events in patients presenting with an acute coronary syndrome: observations from the Pravastatin Or atorVastatin Evaluation and Infection Trial-Thrombolysis in Myocardial Infarction 22 (PR
Am. Heart J.
PUBLISHED: 02-10-2011
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Adiponectin, an adipocytokine, is secreted by fatty cells and exerts a regulatory role in atherogenesis, modulating foam cell formation and cellular adhesion. In stable atherosclerosis, plasma adiponectin has been reported to be associated with both increased and decreased cardiovascular risk. Recent data have suggested a possible discordant adverse risk relationship in acute coronary syndrome (ACS). Therefore, we investigated the association between adiponectin and cardiovascular events in patients with ACS.
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Assessment of multiple cardiac biomarkers in non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 trial.
Eur. Heart J.
PUBLISHED: 12-22-2010
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The aim of this study is to simultaneously evaluate the incremental prognostic value of multiple cardiac biomarkers reflecting different underlying pathophysiological processes in a well-characterized population of patients with non-ST-segment acute coronary syndrome (NSTE-ACS).
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Genetic regulation of platelet receptor expression and function: application in clinical practice and drug development.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 11-19-2010
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Understanding genetic contributions to platelet function could have profound clinical ramifications for personalizing platelet-directed pharmacotherapy, by providing insight into the risks and possible benefits associated with specific genotypes. This article represents an integrated summary of presentations related to genetic regulation of platelet receptor expression and function given at the Fifth Annual Platelet Colloquium in January 2010. It is supplemented with additional highlights from the literature covering (1) approaches to determining and evidence for the associations of genetic variants with platelet hypo- and hyperresponsive phenotypes, (2) the ramifications of these polymorphisms with regard to clinical responses to antiplatelet therapies, and (3) the role of platelet function/genetic testing in guiding antiplatelet therapy.
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Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis.
JAMA
PUBLISHED: 10-28-2010
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Clopidogrel, one of the most commonly prescribed medications, is a prodrug requiring CYP450 biotransformation. Data suggest its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the clinical risk imparted by specific genotypes.
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Growth differentiation factor-15 and risk of recurrent events in patients stabilized after acute coronary syndrome: observations from PROVE IT-TIMI 22.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 10-21-2010
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To investigate growth differentiation factor (GDF)-15 at hospital discharge for assessment of the risk of death, recurrent myocardial infarction (MI), and congestive heart failure, and to determination of whether these risks can be modified by statins.
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Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height.
Matthew B Lanktree, Yiran Guo, Muhammed Murtaza, Joseph T Glessner, Swneke D Bailey, N Charlotte Onland-Moret, Guillaume Lettre, Halit Ongen, Ramakrishnan Rajagopalan, Toby Johnson, Haiqing Shen, Christopher P Nelson, Norman Klopp, Jens Baumert, Sandosh Padmanabhan, Nathan Pankratz, James S Pankow, Sonia Shah, Kira Taylor, John Barnard, Bas J Peters, Cliona M Maloney, Maximilian T Lobmeyer, Alice Stanton, M Hadi Zafarmand, Simon P R Romaine, Amar Mehta, Erik P A van Iperen, Yan Gong, Tom S Price, Erin N Smith, Cecilia E Kim, Yun R Li, Folkert W Asselbergs, Larry D Atwood, Kristian M Bailey, Deepak Bhatt, Florianne Bauer, Elijah R Behr, Tushar Bhangale, Jolanda M A Boer, Bernhard O Boehm, Jonathan P Bradfield, Morris Brown, Peter S Braund, Paul R Burton, Cara Carty, Hareesh R Chandrupatla, Wei Chen, John Connell, Chrysoula Dalgeorgou, Anthonius de Boer, Fotios Drenos, Clara C Elbers, James C Fang, Caroline S Fox, Edward C Frackelton, Barry Fuchs, Clement E Furlong, Quince Gibson, Christian Gieger, Anuj Goel, Diederik E Grobbee, Claire Hastie, Philip J Howard, Guan-Hua Huang, W Craig Johnson, Qing Li, Marcus E Kleber, Barbara E K Klein, Ronald Klein, Charles Kooperberg, Bonnie Ky, Andrea LaCroix, Paul Lanken, Mark Lathrop, Mingyao Li, Vanessa Marshall, Olle Melander, Frank D Mentch, Nuala J Meyer, Keri L Monda, Alexandre Montpetit, Gurunathan Murugesan, Karen Nakayama, Dave Nondahl, Abiodun Onipinla, Suzanne Rafelt, Stephen J Newhouse, F George Otieno, Sanjey R Patel, Mary E Putt, Santiago Rodriguez, Radwan N Safa, Douglas B Sawyer, Pamela J Schreiner, Claire Simpson, Suthesh Sivapalaratnam, Sathanur R Srinivasan, Christine Suver, Gary Swergold, Nancy K Sweitzer, Kelly A Thomas, Barbara Thorand, Nicholas J Timpson, Sam Tischfield, Martin Tobin, Maciej Tomaszewski, Maciej Tomaszweski, W M Monique Verschuren, Chris Wallace, Bernhard Winkelmann, Haitao Zhang, Dongling Zheng, Li Zhang, Joseph M Zmuda, Robert Clarke, Anthony J Balmforth, John Danesh, Ian N Day, Nicholas J Schork, Paul I W de Bakker, Christian Delles, David Duggan, Aroon D Hingorani, Joel N Hirschhorn, Marten H Hofker, Steve E Humphries, Mika Kivimäki, Debbie A Lawlor, Kandice Kottke-Marchant, Jessica L Mega, Braxton D Mitchell, David A Morrow, Jutta Palmen, Susan Redline, Denis C Shields, Alan R Shuldiner, Patrick M Sleiman, George Davey Smith, Martin Farrall, Yalda Jamshidi, David C Christiani, Juan P Casas, Alistair S Hall, Pieter A Doevendans, Jason D Christie, Gerald S Berenson, Sarah S Murray, Thomas Illig, Gerald W Dorn, Thomas P Cappola, Eric Boerwinkle, Peter Sever, Daniel J Rader, Muredach P Reilly, Mark Caulfield, Philippa J Talmud, Eric Topol, James C Engert, Kai Wang, Anna Dominiczak, Anders Hamsten, Sean P Curtis, Roy L Silverstein, Leslie A Lange, Marc S Sabatine, Mieke Trip, Danish Saleheen, John F Peden, Karen J Cruickshanks, Winfried März, Jeffrey R O'Connell, Olaf H Klungel, Cisca Wijmenga, Anke Hilse Maitland-van der Zee, Eric E Schadt, Julie A Johnson, Gail P Jarvik, George J Papanicolaou, , Struan F A Grant, Patricia B Munroe, Kari E North, Nilesh J Samani, Wolfgang Koenig, Tom R Gaunt, Sonia S Anand, Yvonne T van der Schouw, Nicole Soranzo, Garret A FitzGerald, Alex Reiner, Robert A Hegele, Hakon Hakonarson, Brendan J Keating.
Am. J. Hum. Genet.
PUBLISHED: 09-14-2010
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Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.
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Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis.
Lancet
PUBLISHED: 08-31-2010
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Clopidogrel and prasugrel are subject to efflux via P-glycoprotein (encoded by ABCB1, also known as MDR1). ABCB1 polymorphisms, particularly 3435C?T, may affect drug transport and efficacy. We aimed to assess the effect of this polymorphism by itself and alongside variants in CYP2C19 on cardiovascular outcomes in patients treated with clopidogrel or prasugrel in TRITON-TIMI 38. We also assessed the effect of genotype on the pharmacodynamic and pharmacokinetic properties of these drugs in healthy individuals.
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Genetic variants in the KIF6 region and coronary event reduction from statin therapy.
Hum. Genet.
PUBLISHED: 07-08-2010
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A single nucleotide polymorphism (SNP) in KIF6, a member of the KIF9 family of kinesins, is associated with differential coronary event reduction from statin therapy in four randomized controlled trials; this SNP (rs20455) is also associated with the risk for coronary heart disease (CHD) in multiple prospective studies. We investigated whether other common SNPs in the KIF6 region were associated with event reduction from statin therapy. Of the 170 SNPs in the KIF6 region investigated in the Cholesterol and Recurrent Events trial (CARE), 28 were associated with differential event reduction from statin therapy (P (interaction) < 01 in Caucasians, adjusted for age and sex) and were further investigated in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI22) and West of Scotland Coronary Prevention Study (WOSCOPS). These analyses revealed that two SNPs (rs9462535 and rs9471077), in addition to rs20455, were associated with event reduction from statin therapy (P (interaction) < 0.1 in each of the three studies). The relative risk reduction ranged from 37 to 50% (P < 0.01) in carriers of the minor alleles of these SNPs and from -4 to 13% (P > 0.4) in non-carriers. These three SNPs are in high linkage disequilibrium with one another (r (2) > 0.84). Functional studies of these variants may help to understand the role of KIF6 in the pathogenesis of CHD and differential response to statin therapy.
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Metabolic signatures of exercise in human plasma.
Sci Transl Med
PUBLISHED: 05-28-2010
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Exercise provides numerous salutary effects, but our understanding of how these occur is limited. To gain a clearer picture of exercise-induced metabolic responses, we have developed comprehensive plasma metabolite signatures by using mass spectrometry to measure >200 metabolites before and after exercise. We identified plasma indicators of glycogenolysis (glucose-6-phosphate), tricarboxylic acid cycle span 2 expansion (succinate, malate, and fumarate), and lipolysis (glycerol), as well as modulators of insulin sensitivity (niacinamide) and fatty acid oxidation (pantothenic acid). Metabolites that were highly correlated with fitness parameters were found in subjects undergoing acute exercise testing and marathon running and in 302 subjects from a longitudinal cohort study. Exercise-induced increases in glycerol were strongly related to fitness levels in normal individuals and were attenuated in subjects with myocardial ischemia. A combination of metabolites that increased in plasma in response to exercise (glycerol, niacinamide, glucose-6-phosphate, pantothenate, and succinate) up-regulated the expression of nur77, a transcriptional regulator of glucose utilization and lipid metabolism genes in skeletal muscle in vitro. Plasma metabolic profiles obtained during exercise provide signatures of exercise performance and cardiovascular disease susceptibility, in addition to highlighting molecular pathways that may modulate the salutary effects of exercise.
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Effect of pravastatin therapy on coronary events in carriers of the KIF6 719Arg allele from the cholesterol and recurrent events trial.
Am. J. Cardiol.
PUBLISHED: 03-20-2010
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A previous genetic analysis of the Cholesterol and Recurrent Events (CARE) trial found that carriers of the 719Arg allele of the kinesin family member 6 gene (KIF6) (rs20455), but not noncarriers, received significant event reduction from pravastatin therapy. However, that previous analysis of CARE included only Caucasian patients and was limited to the myocardial infarction components of the primary end point. Therefore, the aim of this study was to investigate whether pravastatin therapy reduced primary end point events in KIF6 719Arg carriers and noncarriers, separately, in the combined ethnic groups of CARE. The effect of pravastatin therapy on primary end point events (fatal coronary event or nonfatal myocardial infarction) was investigated in Cox regression models that adjusted for population structure using either self-reported ethnicity or the principal components of genetic heterogeneity. After adjustment for age, gender, and self-reported ethnicity, pravastatin therapy reduced events in carriers of KIF6 719Arg (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.49 to 0.83) but not in noncarriers (HR 1.01, 95% CI 0.69 to 1.45) (p for interaction = 0.049). After adjustment for age, gender, traditional risk factors, and principal components, pravastatin therapy reduced events in carriers of 719Arg (HR 0.64, 95% CI 0.49 to 0.85) but not in noncarriers (HR 0.90, 95% CI 0.62 to 1.32) (p for interaction = 0.14). In conclusion, in an analysis that included CARE patients of all ethnic groups, pravastatin therapy significantly and substantially reduced primary end point events in carriers of the KIF6 719Arg allele but not in noncarriers.
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B-type natriuretic peptide and the effect of ranolazine in patients with non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thr
J. Am. Coll. Cardiol.
PUBLISHED: 03-20-2010
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We designed a prospective evaluation of the interaction between B-type natriuretic peptide (BNP) and the effect of ranolazine in patients with acute coronary syndromes (ACS) as part of a randomized, blinded, placebo-controlled trial.
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Cost-effectiveness analysis of short-term clopidogrel therapy for ST elevation myocardial infarction.
Crit Pathw Cardiol
PUBLISHED: 03-11-2010
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Clopidogrel improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and is recommended in the guidelines. We sought to determine the incremental cost-effectiveness of clopidogrel therapy in this patient population. We used primary patient-level resource use and clinical outcomes data from 3491 STEMI patients treated with fibrinolysis and either clopidogrel or placebo prior to a diagnostic coronary angiogram in the Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial. Costs for each patient were calculated based on diagnosis-related groups-specific Medicare reimbursement rates for all hospitalizations and the average wholesale price of clopidogrel. Cost per event prevented and cost per life year gained (LYG) were calculated using standard methods. The estimate of LYG due to clopidogrel therapy was based on recurrent myocardial infarction and death outcomes. The bootstrap method was used to produce bias-corrected confidence intervals for cost and efficacy estimates as well as the cost per LYG ratio. Total costs and resource use were not significantly different for the clopidogrel and placebo groups ($8128 vs. $8134), indicating that short-term clopidogrel therapy is an economically dominant treatment strategy. Even in a sensitivity analysis accounting for higher long-term medical costs due to greater life expectancy, clopidogrel remained under $6000 per LYG. Clopidogrel therapy was dominant in 35% of the bootstrap simulations and cost less than $50,000 per LYG in 67% of simulations. In conclusion, this analysis finds short-term clopidogrel therapy to be a highly economically attractive therapy, improving patient outcomes at no increase in costs.
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Early dynamic risk stratification with baseline troponin levels and 90-minute ST-segment resolution to predict 30-day cardiovascular mortality in ST-segment elevation myocardial infarction: analysis from CLopidogrel as Adjunctive ReperfusIon TherapY (CLAR
Am. Heart J.
PUBLISHED: 03-06-2010
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Troponin is the preferred biomarker for risk stratification in non-ST elevation ACS. The incremental prognostic use of the initial magnitude of troponin elevation and its value in conjunction with ST-segment resolution (STRes) in ST elevation myocardial infarction (STEMI) is less well defined.
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Extent of ST-segment resolution after fibrinolysis adds improved risk stratification to clinical risk score for ST-segment elevation myocardial infarction.
Am. Heart J.
PUBLISHED: 01-28-2010
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The TIMI risk score (TRS) for ST-segment elevation myocardial infarction (STEMI) is a convenient validated clinical risk score for predicting mortality. Although not part of the risk score, ST-segment resolution (STRes) may provide a simple method of risk stratification based on the response to reperfusion. We sought to determine whether STRes provides incremental risk stratification to the TIMI risk score.
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Prospective evaluation of the prognostic implications of improved assay performance with a sensitive assay for cardiac troponin I.
J. Am. Coll. Cardiol.
PUBLISHED: 01-18-2010
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The purpose of this study was to investigate the prognostic implications of low-level increases in cardiac troponin I (cTnI) using a current-generation sensitive assay in patients with suspected acute coronary syndrome (ACS).
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Integration of proteomic-based tools for improved biomarkers of myocardial injury.
Clin. Chem.
PUBLISHED: 12-18-2009
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Given the mounting evidence in favor of early pharmacologic and catheter-based interventions for patients across the spectrum of acute coronary syndromes, discovering novel diagnostically sensitive and specific biomarkers that provide biochemical proof of early or reversible myocardial injury could have a substantial positive impact on patient care.
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A sensitive cardiac troponin T assay in stable coronary artery disease.
N. Engl. J. Med.
PUBLISHED: 11-25-2009
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In most patients with stable coronary artery disease, plasma cardiac troponin T levels are below the limit of detection for the conventional assay. The distribution and determinants of very low circulating troponin T levels, as well as their association with cardiovascular events, in such patients are unknown.
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Management of platelet-directed pharmacotherapy in patients with atherosclerotic coronary artery disease undergoing elective endoscopic gastrointestinal procedures.
Am. J. Gastroenterol.
PUBLISHED: 11-24-2009
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The periprocedural management of patients with atherosclerotic coronary heart disease, including those who have heart disease and those who are undergoing percutaneous coronary intervention and stent placement who might require temporary interruption of platelet-directed pharmacotherapy for the purpose of an elective endoscopic gastrointestinal procedure, is a common clinical scenario in daily practice. Herein, we summarize the available information that can be employed for making management decisions and provide general guidance for risk assessment.
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Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials.
Lancet
PUBLISHED: 08-31-2009
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Proton-pump inhibitors (PPIs) are often prescribed in combination with thienopyridines. Conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use, measures of platelet function, and clinical outcomes for patients treated with clopidogrel or prasugrel.
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Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes (SEPIA-ACS1 TIMI 42): a randomised, double-blind, active-controlled, phase 2 trial.
Lancet
PUBLISHED: 08-28-2009
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Otamixaban is an intravenous direct factor Xa inhibitor. We aimed to assess its efficacy and safety in non-ST-elevation acute coronary syndromes and to identify the optimum dose range for further assessment in a phase 3 study.
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Identification of genetic variants associated with response to statin therapy.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 08-10-2009
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The purpose of this study was to test the association between polymorphisms in genes involved in either LDL cholesterol (LDL-C) metabolism or statin pharmacokinetics and LDL-C reduction with statins.
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Detection of acute changes in circulating troponin in the setting of transient stress test-induced myocardial ischaemia using an ultrasensitive assay: results from TIMI 35.
Eur. Heart J.
PUBLISHED: 08-04-2009
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To determine whether an ultrasensitive assay can permit quantification of changes in circulating cardiac troponin (Tn) in the setting of stress test-induced myocardial ischaemia.
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Quantification of cardiovascular biomarkers in patient plasma by targeted mass spectrometry and stable isotope dilution.
Mol. Cell Proteomics
PUBLISHED: 07-13-2009
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Verification of candidate biomarkers requires specific assays to selectively detect and quantify target proteins in accessible biofluids. The primary objective of verification is to screen potential biomarkers to ensure that only the highest quality candidates from the discovery phase are taken forward into preclinical validation. Because antibody reagents for a clinical grade immunoassay often exist for a small number of candidates, alternative methodologies are required to credential new and unproven candidates in a statistically viable number of serum or plasma samples. Using multiple reaction monitoring coupled with stable isotope dilution MS, we developed quantitative, multiplexed assays in plasma for six proteins of clinical relevance to cardiac injury. The process described does not require antibodies for immunoaffinity enrichment of either proteins or peptides. Limits of detection and quantitation for each signature peptide used as surrogates for the target proteins were determined by the method of standard addition using synthetic peptides and plasma from a healthy donor. Limits of quantitation ranged from 2 to 15 ng/ml for most of the target proteins. Quantitative measurements were obtained for one to two signature peptides derived from each target protein, including low abundance protein markers of cardiac injury in the nanogram/milliliter range such as the cardiac troponins. Intra- and interassay coefficients of variation were predominantly <10 and 25%, respectively. The configured multiplex assay was then used to measure levels of these proteins across three time points in six patients undergoing alcohol septal ablation for hypertrophic obstructive cardiomyopathy. These results are the first demonstration of a multiplexed, MS-based assay for detection and quantification of changes in concentration of proteins associated with cardiac injury in the low nanogram/milliliter range. Our results also demonstrate that these assays retain the necessary precision, reproducibility, and sensitivity to be applied to novel and uncharacterized candidate biomarkers for verification of proteins in blood.
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Management of platelet-directed pharmacotherapy in patients with atherosclerotic coronary artery disease undergoing elective endoscopic gastrointestinal procedures.
J. Am. Coll. Cardiol.
PUBLISHED: 06-09-2009
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The periprocedural management of patients with atherosclerotic coronary heart disease, including those who have heart disease and those who are undergoing percutaneous coronary intervention and stent placement who might require temporary interruption of platelet-directed pharmacotherapy for the purpose of an elective endoscopic gastrointestinal procedure, is a common clinical scenario in daily practice. Herein, we summarize the available information that can be employed for making management decisions and provide general guidance for risk assessment.
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Detection of myocardial injury in patients with unstable angina using a novel nanoparticle cardiac troponin I assay: observations from the PROTECT-TIMI 30 Trial.
Am. Heart J.
PUBLISHED: 06-05-2009
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At least 30% of patients with non-ST-elevation acute coronary syndrome present without evidence of myonecrosis using current generation troponin assays. A new generation of research assays for troponin that offer a >10-fold increase in analytical sensitivity has emerged.
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Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes.
Circulation
PUBLISHED: 05-04-2009
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Both clopidogrel and prasugrel require biotransformation to active metabolites by cytochrome P450 (CYP) enzymes. Among persons treated with clopidogrel, carriers of reduced-function CYP2C19 alleles have significantly lower levels of active metabolite, diminished platelet inhibition, and higher rates of adverse cardiovascular events. The effect of CYP polymorphisms on the clinical outcomes in patients treated with prasugrel remains unknown.
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Validation of an automated safety surveillance system with prospective, randomized trial data.
Med Decis Making
PUBLISHED: 05-01-2009
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We sought to validate 3 methods for automated safety monitoring by evaluating clinical trials with elevated adverse events.
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Developing multiplexed assays for troponin I and interleukin-33 in plasma by peptide immunoaffinity enrichment and targeted mass spectrometry.
Clin. Chem.
PUBLISHED: 04-16-2009
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Protein biomarker candidates from discovery proteomics must be quantitatively verified in patient samples before they can progress to clinical validation. Here we demonstrate that peptide immunoaffinity enrichment coupled with stable isotope dilution mass spectrometry (SISCAPA-MRM) can be used to configure assays with performance suitable for candidate biomarker verification. As proof of principle, we configured SISCAPA assays for troponin I (cTnI), an established biomarker of cardiac injury, and interleukin 33 (IL-33), an emerging immunological and cardiovascular marker for which robust immunoassays are currently not available.
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Interaction between cigarette smoking and clinical benefit of clopidogrel.
J. Am. Coll. Cardiol.
PUBLISHED: 04-11-2009
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The aim of this study was to examine the interaction between cigarette smoking and the clinical efficacy of clopidogrel in ST-segment elevation myocardial infarction (STEMI).
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Effect of intensive statin therapy on clinical outcomes among patients undergoing percutaneous coronary intervention for acute coronary syndrome. PCI-PROVE IT: A PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis I
J. Am. Coll. Cardiol.
PUBLISHED: 04-10-2009
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The goal of this analysis was to determine whether intensive statin therapy, compared with moderate-dose statin therapy, leads to a reduction in major adverse cardiovascular events (MACE) among patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS).
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Novel antiplatelet strategies in acute coronary syndromes.
Cleve Clin J Med
PUBLISHED: 04-01-2009
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Antiplatelet therapies for the treatment of acute coronary syndromes (ACS) act to interrupt various pathways of platelet activation. Clopidogrel, an established thienopyridine antiplatelet medication, inhibits adenosine diphosphate (ADP)-induced platelet aggregation to a modest degree and with wide variability in platelet response. Accumulating data suggest that a 600-mg loading dose of clopidogrel may help overcome the suboptimal response to the standard 300-mg dose seen in some patients. Prasugrel is a third-generation investigational thienopyridine that demonstrates more potent inhibition of platelet aggregation and more consistent platelet response compared with standard- and high-dose clopidogrel. A large clinical trial showed prasugrel to be superior to standard-dose clopidogrel in reducing ischemic events in patients with ACS scheduled for percutaneous coronary intervention, although prasugrel was associated with a significantly higher risk of major bleeding events. Other investigational antiplatelet agents also display more potent and consistent inhibition of platelet aggregation than is seen with clopidogrel. These include AZD6140, a reversible ADP receptor blocker; cangrelor, a rapidly acting intravenous ADP receptor blocker; and the thrombin receptor antagonist SCH 530348.
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Baseline hemoglobin concentration and creatinine clearance composite laboratory index improves risk stratification in ST-elevation myocardial infarction.
Am. Heart J.
PUBLISHED: 03-03-2009
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Hemoglobin (Hgb) and creatinine clearance (CrCl) are readily-available, routinely-obtained laboratory parameters that predict acute coronary syndrome outcomes. We sought to develop a laboratory index (LI) to predict early mortality in ST-elevation myocardial infarction (STEMI) and determine the additional risk stratification offered by adding the LI to the TIMI Risk Score (TRS) for STEMI.
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Relation between myocardial infarct size and ventricular tachyarrhythmia among patients with preserved left ventricular ejection fraction following fibrinolytic therapy for ST-segment elevation myocardial infarction.
Am. J. Cardiol.
PUBLISHED: 03-02-2009
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In the era of early reperfusion therapy for ST-segment elevation myocardial infarction, preserved left ventricular (LV) function is common. Despite preservation of LV ejection fraction (LVEF), there remains a spectrum of risk for adverse cardiovascular events, including ventricular tachycardia (VT) and ventricular fibrillation (VF). Larger infarct size has been independently associated with death, VT/VF, and heart failure in the post-myocardial infarction population. It was hypothesized that infarct size, as estimated by peak serum creatine kinase (CK)-MB concentration, would be associated with the incidence of VT/VF in patients with preserved LV function after ST-segment elevation myocardial infarctions. The Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28 (CLARITY-TIMI 28) study enrolled 3,491 patients with ST-segment elevation myocardial infarctions who underwent fibrinolytic therapy. The association between estimated infarct size (ratio of peak CK-MB to the upper limit of normal), the LVEF (measured using left ventriculography or echocardiography), and the incidence of VT/VF through 30 days was assessed. A total of 1,436 patients underwent assessments of LV function, of whom 1,133 had adequate CK-MB for analysis. The median LVEF in this group was 55% (interquartile range 45% to 65%), and most patients (n = 814 [87.1%]) had LVEF > or =40%. Among patients with LVEF > or =40%, the ratio of peak CK-MB to the upper limit of normal was significantly associated with the incidence of VT/VF through 30 days (2.2%, 3.7%, and 5.5% across tertiles, respectively, p = 0.041 for trend) and the incidence of the composite of cardiovascular death, heart failure, shock, and VT/VF through 30 days (3.7%, 6.0%, 8.5%, respectively, p = 0.018 for trend). In conclusion, in patients with ST-segment elevation myocardial infarction with preserved LV function after reperfusion therapy, larger infarct size, as estimated by peak serum CK-MB concentration, is significantly associated with VT/VF as well as other adverse clinical outcomes.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.