Background: Post‐treatment platelet reactivity (PR) is associated with ischemic and bleeding events in patients receiving P2Y12 receptor antagonists.
Objectives: We aimed to study the relationship ...between post‐treatment PR after a 60‐mg loading dose (LD) of prasugrel and 1‐year thrombotic and bleeding events.
Method: Patients were prospectively included in this multicenter study if they had a successful percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and received prasugrel. The platelet reactivity index (PRI) was measured using the Vasodilator‐Stimulated Phosphoprotein index (VASP) after a prasugrel LD. Endpoints included the rate of thrombotic events and bleeding events at 1 year.
Results: Among the 301 patients enrolled, 9 (3%) were lost to follow‐up at 1 year. The rates of thrombotic and bleeding events at 1 year were of 7.5% and 6.8%, respectively. Receiver‐operating curve (ROC) analysis demonstrated an optimal cut‐off value of 53.5% of PRI to predict thrombotic events at 1 year. Using this cut‐off value we observed that patients exhibiting high on‐treatment platelet reactivity (HTPR) had a higher rate of thrombotic events (22.4% vs. 2.9%; P < 0.001). In parallel the optimal cut‐off value of PRI to predict bleeding was 16%. Patients with a PRI ≤ 16% had a higher rate of bleeding events compared with those with a PRI > 16% (15.6% vs. 3.3%; P < 0.001). In multivariate analysis, the PRI predicted both thrombotic and bleeding events (OR: 1.44, 95% confidence interval CI: 1.2–1.72; P < 0.001 and OR: 0.75, 95% CI: 0.59–0.96; P = 0.024 respectively, per 10% increase).
Conclusion: Platelet reactivity measurement after a prasugrel LD predicts both ischemic and bleeding events at 1 year follow‐up for ACS patients undergoing PCI.
Background: Despite dual antiplatelet therapy, the rate of major adverse cardiovascular events (MACE) after percutaneous coronary angioplasty remains high. Studies have shown interindividual ...variations in response to clopidogrel. Furthermore, there is an apparent link between clinical outcomes and clopidogrel resistance. Objectives: To investigate the value of platelet reactivity index (PRI), assessed by vasodilator‐stimulated phosphoprotein (VASP) phosphorylation analysis, for predicting MACE after percutaneous coronary intervention (PCI) with stent implantation.Methods: A prospective monocentric study was performed on 144 patients undergoing PCI. PR was evaluated by VASP phosphorylation analysis 24 h after they received a 300‐mg loading dose of clopidogrel. MACE were recorded during a 6‐month follow‐up. Patients were divided into quintiles according to PRI, as assessed by VASP analysis. The receiver operating characteristic (ROC) curve served to determine the optimal cut‐off value of VASP analysis to detect MACE.Results: Of the 144 patients, 34% had stable angina pectoris, 40% silent ischemia, and 26% low‐risk non‐ST‐segment elevation acute coronary syndrome. During the follow‐up, 21 MACE were observed. Patients in quintile 1 of VASP analysis had a significantly lower risk of MACE as compared with those among the four higher quintiles (0 vs. 21, P < 0.01). ROC curve analysis of VASP showed an optimal cut‐off value of 50% PR to exclude MACE. The negative predictive value of the test was 100%.Conclusions: VASP phosphorylation analysis can evaluate the individual response to clopidogrel loading dose prior to PCI and predict postprocedural MACE.
PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine ...diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.
Place de l’angioplastie des artères rénales Armero, S.; Bonello, L.; Paganelli, F. ...
Annales de cardiologie et d'angéiologie,
12/2011, Letnik:
60, Številka:
6
Journal Article
Recenzirano
L’athérosclérose des artères rénales est une maladie fréquente associée à une morbimortalité importante, (Kalra et al., 2005 ; Cheung et al., 2002 ; Guo et al., 2007
1–3). Son traitement, très ...débattu depuis de nombreuses années, ne présente pas de consensus. Les études réalisées présentent, en effet, de nombreux biais et leurs conclusions sont souvent décevantes et parfois contradictoires. Nous savons que l’angioplastie est supérieure à la chirurgie dans une très grande majorité des lésions, que l’angioplastie avec pose de stent est supérieure à l’angioplastie au ballon seul, mais la supériorité de l’angioplastie par rapport au traitement médical reste à prouver pour le contrôle tensionnel, la préservation néphronique et la diminution de la récurrence des épisodes d’insuffisance cardiaque. Certaines indications sont, néanmoins, consensuelles : sténoses significatives bilatérales ou sur rein unique anatomiquement ou fonctionnellement ; insuffisance rénale rapidement progressive, OAP flash, HTA résistante sous trithérapie antihypertensive. D’autres études doivent être conduites pour nous aider à mieux sélectionner nos patients ; l’utilisation de la
fractional flow reserve (FFR) dans ce cadre semble très prometteuse.
Atherosclerotic renal artery stenosis is frequent and is associated with a high incidence of morbidity and mortality, with a strong correlation with coronary artery disease, (Kalra et al., 2005; Cheung et al., 2002; Guo et al., 2007
1–3). The atherosclerotic renal artery stenosis is an independent predictive factor of death (Conlon et al., 1998
4). The treatment of this lesion does not have strong evidence. A lot of studies in this area suggest the angioplasty is superior in a big majority between surgery, and angioplasty with stent is superior between balloon angioplasty, but some studies fail to prove the superiority of angioplasty versus medical treatment. These studies have sadly a lot of mistakes and nowadays we don’t know what is the treatment for our patients in a lot of cases. The angioplasty is indicated when there is a failure of antihypertensive medications for control of blood pressure, when it is associated with a renal insufficiency quickly progressive or when there is a lesion on each renal artery. Other studies must be organized for prove the superiority of angioplasty when there is a real stenosis, maybe with the use of fractional flow reserve.
Essentials
Acute coronary syndrome (ACS) with atrial fibrillation (AF) is a therapeutic challenge.
Dual and triple antithrombotic therapy showed a similar thrombotic risk in ACS patients with AF.
The ...omission of aspirin during the first month did not increase the rate of ischemic events.
Replacement of vitamin K antagonist by dabigatran leads to an increased thrombotic risk.
Summary
Background
Dual antithrombotic therapy comprising a vitamin K antagonist (VKA) plus clopidogrel reduces the incidence of major bleeding compared with triple therapy (VKA + clopidogrel + aspirin) in acute coronary syndrome (ACS) patients with atrial fibrillation (AF), with a similar thrombotic risk. The oral thrombin inhibitor dabigatran (150 mg twice a day) showed superiority over VKA in non‐valvular AF, but data supporting its use in AF patients presenting with ACS are limited.
Objective
We sought to evaluate the efficacy of dabigatran vs. VKA in the management of AF patients undergoing percutaneous coronary intervention for an ACS.
Methods
In this open‐label study, 133 consecutive patients received dabigatran plus clopidogrel. Another cohort of 133 patients treated with VKA plus clopidogrel was used as the control group.
Results
After propensity score adjustment, the cumulative incidence of major adverse cardiovascular events over 24 months was higher with dabigatran vs. VKA (adjusted hazard ratio, 2.28; 95% confidence interval, 1.46–3.56). Similar rates of major bleeding were found (adjusted hazard ratio, 1.17; 95% confidence interval, 0.46–2.96).
Conclusions
In AF patients presenting with ACS, replacement of VKA by dabigatran concurrently with clopidogrel is associated with an increased thrombotic risk, without a reduction in major bleeding.
Homing of chronic lymphocytic leukemia (CLL) cells to sites favoring growth, a critical step in disease progression, is principally coordinated by the CXCL12/CXCR4 axis. A cohort of 62 CLL patients ...was divided into migrating and nonmigrating subsets according to chemotaxis toward CXCL12. Migrating patients phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) proteins more than nonmigrating patients (P<0.0002). CD38 expression was the parameter most strongly associated with heightened CXCL12 signaling (P<0.0001), confirmed by independent statistical approaches. Consistent with this observation, CD38(-) CLL cells in samples with bimodal CD38 expression responded less to CXCL12 than the intact clone (P=0.003). Furthermore, lentivirus-induced de novo expression of CD38 was paralleled by increased responses to CXCL12, as compared with cells infected with a control virus. CD38 ligation with agonistic monoclonal antibodies (mAbs) enhanced CXCL12 signaling, whereas blocking anti-CD38 mAbs inhibited chemokine effects in vitro. This is attributed to physical proximity on the membrane between CD38 and CXCR4 (the CXCL12 receptor), as shown by (i) coimmunoprecipitation and (ii) confocal microscopy experiments. Blocking anti-CD38 mAbs significantly compromised homing of CLL cells from blood to lymphoid organs in a mouse model. These results indicate that CD38 synergizes with the CXCR4 pathway and support the working hypothesis that migration is a central step in disease progression.
Background: Endothelial lesion and regeneration are critical events in the process leading to in‐stent restenosis (ISR) after bare metal stent (BMS) percutaneous coronary intervention (PCI).
...Objectives: To prospectively investigate the relationship between biomarkers reflecting endothelial turnover and the occurrence of ISR.
Methods: We performed a multicenter prospective observational study that included 156 patients undergoing elective PCI with BMS. Endothelial lesion was assessed by the enumeration of circulating endothelial cells (CECs). Endothelial regeneration was evaluated by enumeration of circulating CD34+ progenitor cells (CD34+ PCs) and CD34+KDR+ endothelial progenitor cells (EPCs). Measurements were performed before PCI, and 6 and 24 h after PCI. Dynamic changes were evaluated by calculating the delta value of each marker. The primary and secondary endpoints of the study were clinical target lesion revascularizations (TLRs) and major adverse cardiovascular events (MACEs) after 6 months of follow‐up.
Results: During follow‐up, 28 MACEs were recorded, including 27 TLRs. PCI induced a significant rise in the numbers of CECs, CD34+ PCs, and CD34+KDR+ EPCs. Baseline, 6‐h and 24‐h levels of these markers did not differ between patients with and without TLR. The delta percentage of CD34+KDR+ EPCs was significantly reduced in patients with TLR as compared with patients without TLR (− 0.56 ± 8.1 vs. 2.91 ± 6.2; P = 0.015). In multivariate analysis, the delta percentage of CD34+KDR+ EPCs independently predicted the occurrence of TLR and MACEs (P = 0.02 and P = 0.014, respectively).
Conclusion: The endothelial regenerative response to injury induced by PCI, assessed by CD34+KDR+ EPCs mobilized among progenitor cells, determines the risk of TLR and MACEs in stable coronary artery disease patients.
.
Background. Periodontal disease (PD) has been recognized as a risk factor for systemic diseases, but its involvement in the pathogenesis of coronary artery disease (CAD) remains debated.
...Objectives. We sought to evaluate the potential relations between severity of the PD, inflammatory response and angiographic lesions extent in patients with stable CAD.
Design. A total of 131 subjects referred to our centre for coronary angiography were evaluated for presence and extension of CAD, then divided into two groups, one with presence of lesions (cases, n = 85) and other one with absence of lesions (controls, n = 46). Mean periodontal pocket depth (PPkD), high sensitivity C reactive protein (hs‐CRP), serum amyloid A protein (SAA) and fibrinogen levels were measured in all patients.
Results. Cases and controls did not differ according to their baseline characteristics and prevalence of traditional cardiovascular risk factors. PPkD was greater in patients with CAD than in controls (2.24 ± 1.28 mm vs 1.50 ± 0.93 mm, P < 0.001 by Student’s t‐test). Systemic inflammatory response was more pronounced in cases than in controls, with higher values of hs‐CRP, SAA and fibrinogen. Furthermore, PPkD values correlated with hs‐CRP (r = 0.80, P < 0.001), SAA (r = 0.71, P < 0.001), fibrinogen levels (r = 0.72, P < 0.001) and the American College of Cardiology/American Heart Association angiographic score (r = 0.68, P < 0.001) in cases. Multivariate analysis indicated a persistent independent correlation between PPkD and angiographic score after adjustment for inflammatory markers levels.
Conclusion. In the present study, PD lesions predicted presence of CAD stenosis in patients with cardiovascular risk factors. PD severity was correlated to angiographic extent of coronary lesions, independent of systemic inflammatory status. Those results suggest that these patients might benefit from an intensive periodontal therapy to prevent CAD progression.
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