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1.
A multi-stage association study of plasma cytokines identifies osteopontin as a biomarker for acute coronary syndrome risk and severity.
Yu, K, Yang, B, Jiang, H, Li, J, Yan, K, Liu, X, Zhou, L, Yang, H, Li, X, Min, X, et al
Scientific reports. 2019;(1):5121
Abstract
Cytokines play a critical role in the pathogenesis and development of cardiovascular diseases. However, data linking cytokines to risk and severity of acute coronary syndrome (ACS) are still limited. We measured plasma profile of 280 cytokines using a quantitative protein microarray in 12 ACS patients and 16 healthy controls, and identified 15 differentially expressed cytokines for ACS. Osteopontin, chemokine ligand 23, brain derived neurotrophic factor and C-reactive protein (CRP) were further validated using immunoassay in two independent case-control studies with a total of 210 ACS patients and 210 controls. We further examined their relations with incident ACS among 318 case-control pairs nested within the Dongfeng-Tongji cohort, and found plasma osteopontin and CRP concentrations were associated with incident ACS, and the multivariable-adjusted odds ratio (95% confidence interval) was 1.29 (1.06-1.57) per 1-SD increase for osteopontin and 1.30 (1.02-1.66) for CRP, respectively. Higher levels of circulating osteopontin were also correlated with higher severity of ACS, and earlier ACS onset time. Adding osteopontin alone or in combination with CRP modestly improved the predictive ability of ACS beyond the Framingham risk scores. Our findings suggested that osteopontin might be a biomarker for incident ACS, using osteopontin adds moderately to traditional cardiovascular risk factors.
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2.
METoclopramide Administration as a Strategy to Overcome MORPHine-ticagrelOr Interaction in PatientS with Unstable Angina PectorIS-The METAMORPHOSIS Trial.
Sikora, J, Niezgoda, P, Barańska, M, Buszko, K, Skibińska, N, Sroka, W, Pstrągowski, K, Siller-Matula, J, Bernd, J, Gorog, D, et al
Thrombosis and haemostasis. 2018;(12):2126-2133
Abstract
Extensive search for methods of overcoming morphine-related delay of the absorption and onset of action of oral P2Y12 inhibitors in patients presenting with acute coronary syndrome is on-going. The aim of the trial was to investigate whether metoclopramide co-administration could reduce this delay and improve the pharmacokinetics (PKs) and pharmacodynamics (PDs) of ticagrelor and its active metabolite AR-C124900XX. Plasma concentration of both compounds and platelet reactivity were evaluated in nine pre-defined time points within 6 hours after administration of ticagrelor loading dose. The results of our study show that mean platelet activity within the first hour was noticeably higher in metoclopramide-naive patients. Moreover, ticagrelor mean plasma concentration was significantly higher within the initial four time points (15, 30, 45, 60 minutes) in patients receiving metoclopramide (p = 0.039; p = 0.009; p = 0.005; p = 0.008, respectively). To conclude, the co-administration of metoclopramide in patients presenting with unstable angina and treated with morphine, has a beneficial effect on the PK/PD profile of ticagrelor and its metabolite; however, its impact on ST-elevation myocardial infarction patients requires further investigation.
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3.
Predictors of obstructive sleep apnoea in patients admitted for acute coronary syndrome.
de Batlle, J, Turino, C, Sánchez-de-la-Torre, A, Abad, J, Duran-Cantolla, J, McEvoy, RD, Antic, NA, Mediano, O, Cabriada, V, Masdeu, MJ, et al
The European respiratory journal. 2017;(3)
Abstract
Identifying undiagnosed obstructive sleep apnoea (OSA) patients in cardiovascular clinics could improve their management. Aiming to build an OSA predictive model, a broad analysis of clinical variables was performed in a cohort of acute coronary syndrome (ACS) patients.Sociodemographic, anthropometric, life-style and pharmacological variables were recorded. Clinical measures included blood pressure, electrocardiography, echocardiography, blood count, troponin levels and a metabolic panel. OSA was diagnosed using respiratory polygraphy. Logistic regression models and classification and regression trees were used to create predictive models.A total of 978 patients were included (298 subjects with apnoea-hypopnoea index (AHI) <15 events·h-1 and 680 with AHI ≥15 events·h-1). Age, BMI, Epworth sleepiness scale, peak troponin levels and use of calcium antagonists were the main determinants of AHI ≥15 events·h-1 (C statistic 0.71; sensitivity 94%; specificity 24%). Age, BMI, blood triglycerides, peak troponin levels and Killip class ≥II were determinants of AHI ≥30 events·h-1 (C statistic of 0.67; sensitivity 31%; specificity 86%).Although a set of variables associated with OSA was identified, no model could successfully predict OSA in patients admitted for ACS. Given the high prevalence of OSA, the authors propose respiratory polygraphy as a to-be-explored strategy to identify OSA in ACS patients.
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4.
Serum 25-hydroxy vitamin D concentration in acute coronary syndrome.
Anastasi, E, Suppa, M, Viggiani, V, Tartaglione, S, Angeloni, A, Granato, T
Journal of biological regulators and homeostatic agents. 2017;(3):823-827
Abstract
Vitamin D may have prognostic value in cardiovascular disease (CVD) patients and, in addition to conventional biomarkers, could be a valuable tool for disease management. The aim of this study was to assess the association of vitamin D status in patients with acute coronary syndrome (ACS) and to evaluate its prognostic utility. The levels of 25(OH) vitamin D were correlated with troponin T hs. Forty-eight consecutive outpatients (40 Caucasian and 8 Asian) aged between 40 and 70 years (mean 61.5, range 43-77 years) were enrolled in the study. All patients were admitted to the Emergency Department with chest pain and suspected ACS. The main exclusion criteria were age <18 years, kidney failure, onco-haematological disease, hypo-hyperparathyroidism, hypo/hyperthyroidism, osteoporosis, treatment with bisphosphonate or 25(OH) vitamin D supplementation. Of the 48 subjects included in the study, thoracic pain symptoms were described in 12 patients with unstable angina (UA) and in 6 patients with ST elevation myocardial infarction (STEMI) and in 30 patients with non-ST-elevation myocardial infarction (NSTEMI). Low 25(OH) vitamin D levels correlated with the presence of ACS (p< 0.02) and inversely correlated with Troponin T hs (TnT hs) levels (p< 0.03). The determination of 25(OH) vitamin D levels in combination with TnT hs could improve the research for possible underlying conditions, and these should be managed meticulously according to current guidelines.
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5.
Investigating the differences of body mass index and waist circumference in the follow-up assessment of patients to cardiac rehabilitation with acute coronary syndrome.
Zhao, H, Ma, J, Zhou, Q, Chen, W, Zhu, W, Cai, Z, Lei, H, Deng, Y, Xu, L, Qiu, J
Australasian physical & engineering sciences in medicine. 2016;(4):1007-1027
Abstract
Obesity management is a key point during cardiac rehabilitation. The effect of new index, waist circumference (WC), in the obesity management of cardiac rehabilitation is not clear yet. Therefore, our study compared the WC index to the body mass index (BMI) in the evaluation of obesity management for the patients with acute coronary syndrome (ACS) in a well-designed cardiac rehabilitation program (CRP). Totally 61 patients were enrolled into our study between October 2013 and January 2014 in our hospital. All these patients were requested to participate in the CRP actively for 6 months. We collected the BMI, WC, vital signs, fasting blood levels, the results from a sub-maximal exercise treadmill test (ETT) and ultrasonic cardiogram (UCG) through a follow-up visit conducted every 1, 3, and 6 months. We used two-tailed Pearson's test and linear regression to analyze the data from our experiment. Our results show that the grouping of obese individuals based on the WC results in the WC being significantly associated with high-density lipoprotein cholesterol (HDL_C), inter-ventricular septal thickness at diastole (IVSd) and left ventricular posterior wall at diastole (LVPwd) after 1 and 3 months of the CRP (HDL_C after1 month of CRP: r = -0.292, P = 0.022; HDL_C after 3 months of CRP: r = -0.289, P = 0.024; IVSd after1 month of CRP: r = 0.451, P = 0.004; IVSd after 3 months of CRP: r = 0.304, P = 0.035; LVPwd after1 month of CRP: r = 0.468, P = 0.002; LVPwd after 3 months of CRP: r = 0.290, P = 0.045). However, no similar regular associations were found when obesity was stratified using the BMI. In other words, WC could be better than the BMI for reflecting the cardiac status. In conclusion, obesity management using WC can benefit the clinical evaluation, diagnosis, treatment, prevention, and prognosis of obese individuals of ACS when participating in the CRP.
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6.
Absorption kinetics of low-dose chewable aspirin--implications for acute coronary syndromes.
Hobl, EL, Schmid, RW, Stimpfl, T, Ebner, J, Jilma, B
European journal of clinical investigation. 2015;(1):13-7
Abstract
BACKGROUND This study describes the implications of the pharmacokinetics of low-dose chewable aspirin for acute coronary syndromes. Current guidelines recommend the administration of 162-325 mg aspirin chewing tablets for the treatment of acute myocardial infarction. Although aspirin is widely used and a cornerstone in myocardial infarction, there is no information available on the pharmacokinetics of low doses of chewable aspirin. MATERIALS AND METHODS This prospective trial assessed the pharmacokinetics of acetylsalicylic acid and its metabolite salicylic acid after intake of 162 mg chewable low-dose aspirin in 35 healthy volunteers. Plasma drug and metabolite levels were analysed using high-performance liquid chromatography, and corresponding pharmacodynamics were determined by impedance aggregometry. RESULTS Acetylsalicylic acid was rapidly absorbed with a mean Tmax of 27 ± 8 min. Tmax of salicylic acid was 69 ± 21 min. Mean Cmax was 1·8 ± 0·6 mg/L and 7·6 ± 1·4 for acetylsalicylic acid and salicylic acid, respectively. Arachidonic acid-induced aggregation showed maximum platelet inhibition 30 min after drug ingestion. CONCLUSIONS The characterization of the plasma-time profile fills the gap between the lack of data on pharmacokinetics and the pharmacodynamics and the recommendation for using low-dose chewable aspirin for acute coronary syndromes. We describe for the first time that a 162-mg dose of chewable aspirin is rapidly absorbed and achieves plasma concentrations of the active metabolite salicylic acid required to maximally inhibit platelet aggregation. However, a 162-mg dose is truly a minimum, and doubling this dose might be better for patients with myocardial infarction.
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7.
The effect of cholesteryl ester transfer protein inhibition on lipids, lipoproteins, and markers of HDL function after an acute coronary syndrome: the dal-ACUTE randomized trial.
Ray, KK, Ditmarsch, M, Kallend, D, Niesor, EJ, Suchankova, G, Upmanyu, R, Anzures-Cabrera, J, Lehnert, V, Pauly-Evers, M, Holme, I, et al
European heart journal. 2014;(27):1792-800
Abstract
AIMS: The effects of cholesteryl ester transfer protein (CETP) inhibition on lipids, inflammation, and markers of high-density lipoprotein (HDL) function, following an acute coronary syndrome (ACS), are unknown. METHODS AND RESULTS The dal-ACUTE study randomized 300 patients (1 : 1) to dalcetrapib 600 mg/day or placebo within 1 week of an ACS. The primary endpoint was per cent change in HDL-cholesterol (HDL-C) after 4 weeks. Secondary endpoints included apolipoprotein levels, markers of HDL function, and inflammation. Dalcetrapib treatment increased HDL-C and apolipoprotein A1 by 33.7 and 11.8%, respectively (both P < 0.001) and total cholesterol efflux by 9.5% (P = 0.003) after 4 weeks, principally via an increase in non-ATP-binding cassette transporter (ABC) A1-mediated efflux, without statistically significant changes in pre-β1-HDL levels. The increase in total efflux with dalcetrapib correlated most strongly with increases in apolipoprotein A1 and HDL-C (r = 0.46 and 0.43, respectively) rather than the increase in pre-β1-HDL (r = 0.32). Baseline and on-treatment ABCA1-mediated efflux correlated most strongly with pre-β1-HDL levels; in contrast, non-ABCA1-mediated efflux correlated better with apolipoprotein A1 and HDL-C levels. CONCLUSIONS High-density lipoprotein raised through CETP inhibition with dalcetrapib improves cholesterol efflux, principally via a non-ABCA1-mediated pathway. While HDL-C was increased by one-third, apolipoprotein A1 and total efflux were increased only by one-tenth, supporting the concept of dissociation between improvements in HDL function and HDL-C levels, which may be of relevance to ongoing trials and the development of therapeutic interventions targeting HDL.
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8.
Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial.
Oldgren, J, Budaj, A, Granger, CB, Khder, Y, Roberts, J, Siegbahn, A, Tijssen, JG, Van de Werf, F, Wallentin, L, ,
European heart journal. 2011;(22):2781-9
Abstract
AIM: After an acute coronary syndrome, patients remain at risk of recurrent ischaemic events, despite contemporary treatment, including aspirin and clopidogrel. We evaluated the safety and indicators of efficacy of the novel oral direct thrombin inhibitor dabigatran. METHODS AND RESULTS In this double-blind, placebo-controlled, dose-escalation trial, 1861 patients (99.2% on dual antiplatelet treatment) in 161 centres were enrolled at mean 7.5 days (SD 3.8) after an ST-elevation (60%) or non-ST-elevation (40%) myocardial infarction and randomized to twice daily treatment with dabigatran 50 mg (n = 369), 75 mg (n = 368), 110 mg (n = 406), 150 mg (n = 347), or placebo (n = 371). Primary outcome was the composite of major or clinically relevant minor bleeding during the 6-month treatment period. There were 96 primary outcome events and, compared with placebo, a dose-dependent increase with dabigatran, hazard ratio (HR) 1.77 (95% confidence intervals 0.70, 4.50) for 50 mg; HR 2.17 (0.88, 5.31) for 75 mg; HR 3.92 (1.72, 8.95) for 110 mg; and HR 4.27 (1.86, 9.81) for 150 mg. Compared with placebo, D-dimer concentrations were reduced in all dabigatran dose groups by an average of 37 and 45% at weeks 1 and 4, respectively (P< 0.001). Fourteen (3.8%) patients died, had a myocardial infarction or stroke in the placebo group compared with 17 (4.6%) in 50 mg, 18 (4.9%) in 75 mg, 12 (3.0%) in 110 mg, and 12 (3.5%) in the 150 mg dabigatran groups. CONCLUSIONS Dabigatran, in addition to dual antiplatelet therapy, was associated with a dose-dependent increase in bleeding events and significantly reduced coagulation activity in patients with a recent myocardial infarction.
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9.
Iodofiltic acid I 123 (BMIPP) fatty acid imaging improves initial diagnosis in emergency department patients with suspected acute coronary syndromes: a multicenter trial.
Kontos, MC, Dilsizian, V, Weiland, F, DePuey, G, Mahmarian, JJ, Iskandrian, AE, Bateman, TM, Heller, GV, Ananthasubramaniam, K, Li, Y, et al
Journal of the American College of Cardiology. 2010;(4):290-9
Abstract
OBJECTIVES The aim of this study was to assess the performance of beta-methyl-p-[123I]-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) to detect acute coronary syndromes (ACS) in emergency department patients with chest pain. BACKGROUND Emergency department diagnosis of chest pain is problematic, often requiring prolonged observation and stress testing. BMIPP SPECT detects abnormalities in fatty acid metabolism resulting from myocardial ischemia, even many hours after symptom cessation. METHODS Emergency department patients with suspected ACS were enrolled at 50 centers. Patients received 5 mCi BMIPP within 30 h of symptom cessation. BMIPP SPECT images were interpreted semiquantitatively by 3 blinded readers. Initial clinical diagnosis was based on symptoms, initial electrocardiograms, and troponin, whereas the final diagnosis was based on all available data (including angiography and stress SPECT) but not BMIPP SPECT. Final diagnoses were adjudicated by a blinded committee as ACS, intermediate likelihood of ACS, or negative for ACS. RESULTS A total of 507 patients were studied and efficacy was evaluated in 448 patients with sufficient data. The sensitivity of BMIPP by 3 blinded readers for a final diagnosis of ACS and intermediate likelihood of ACS was 71% (95% confidence interval [CI]: 64% to 79%), 74% (95% CI: 68% to 81%), and 69% (95% CI: 62% to 77%); the corresponding specificity of BMIPP was 67% (95% CI: 61% to 73%), 54% (95% CI: 48% to 60%), and 70% (95% CI: 64% to 76%). Compared with the initial diagnosis alone, BMIPP+initial diagnosis increased sensitivity from 43% to 81% (p<0.001), negative predictive value from 62% to 83% (p<0.001), and positive predictive value from 41% to 58% (p<0.001), whereas specificity was unchanged (61% to 62%, p=NS). CONCLUSIONS The addition of BMIPP data to the initially available clinical information adds incremental value toward the early diagnosis of an ACS, potentially allowing determination of the presence or absence of ACS to be made earlier in the evaluation process. (Safety and Efficacy Iodofiltic Acid I 123 in the Treatment of Acute Coronary Syndrome [Zeus-ACS]; NCT00514501).
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10.
Increased platelet inhibition after switching from maintenance clopidogrel to prasugrel in patients with acute coronary syndromes: results of the SWAP (SWitching Anti Platelet) study.
Angiolillo, DJ, Saucedo, JF, Deraad, R, Frelinger, AL, Gurbel, PA, Costigan, TM, Jakubowski, JA, Ojeh, CK, Effron, MB, ,
Journal of the American College of Cardiology. 2010;(13):1017-23
Abstract
OBJECTIVES The objective was to evaluate the pharmacodynamic response of switching patients on maintenance phase clopidogrel therapy after an acute coronary syndrome (ACS) to prasugrel. BACKGROUND Prasugrel P2Y(12) receptor blockade is associated with greater pharmacodynamic platelet inhibition and reduction of ischemic complications compared with that of clopidogrel in ACS patients undergoing percutaneous coronary intervention. The pharmacodynamic effects of switching patients during maintenance phase clopidogrel therapy after an ACS event to prasugrel are unknown. METHODS The SWAP (SWitching Anti Platelet) study was a phase 2, multicenter, randomized, double-blind, double-dummy, active-control trial. After a run-in of daily open-label clopidogrel 75 mg with aspirin therapy for 10 to 14 days, patients were randomly assigned to 1 of the following 3 treatments: placebo loading dose (LD)/clopidogrel 75 mg maintenance dose (MD), placebo LD/prasugrel 10 mg MD, or prasugrel 60 mg LD/10 mg MD. Platelet function was evaluated at 2 h, 24 h, 7 days, and 14 days using light transmittance aggregometry, VerifyNow P2Y(12) assay, and vasodilator-stimulated phosphoprotein phosphorylation. RESULTS A total of 139 patients were randomized, of whom 100 were eligible for analysis. Maximum adenosine diphosphate-induced platelet aggregation (20 μM) by light transmittance aggregometry at 1 week (primary end point) was lower after prasugrel MD compared with clopidogrel MD (41.1% vs. 55.0%, p < 0.0001), and was also lower in the prasugrel LD+MD group compared with clopidogrel MD (41.0% vs. 55.0%, p < 0.0001). At 2 h, a prasugrel LD resulted in higher platelet inhibition compared with the other regimens. Similar results were found using light transmittance aggregometry with 5 μM adenosine diphosphate, VerifyNow P2Y(12), and vasodilator-stimulated phosphoprotein phosphorylation assays. CONCLUSIONS For patients receiving maintenance clopidogrel therapy after an ACS event, switching from clopidogrel to prasugrel is associated with a further reduction in platelet function by 1 week using prasugrel MD or within 2 h with the administration of a prasugrel LD. (A Pharmacodynamic Comparison of Prasugrel [LY640315] Versus Clopidogrel in Subjects With Acute Coronary Syndrome Who Are Receiving Clopidogrel [SWAP]; NCT00356135).