Effect of intensive glycemic control on platelet reactivity in patients with long-standing uncontrolled diabetes

Background

It has been previously shown that platelets of patients with diabetes are more reactive and less responsive to anti-platelet drugs compared with platelets from subjects without diabetes. Studies examining the effect of glycemic control on platelet reactivity have yielded conflicting data. Thus, in this study, we sought to explore the effect of tight glycemic control on platelet reactivity in patients with long standing uncontrolled diabetes.

Methods

The study included 30 patients with long-standing treated diabetes and a baseline HbA1c level of ≥ 8.5%. All patients were treated with aspirin and statins. Patients were tested at baseline and after 3 months of intensive glycemic and metabolic control. The treatment goal was to achieve a HbA1c level of ≤ 7%. Platelet reactivity was assessed by light transmission aggregation in response to 5 and 10 μM ADP and to 0.5 mg/ml arachidonic acid (AA). Additonally, platelet activation was assessed by plasma levels of soluble P-selectin using an enzyme-linked immunosorbent assay.

Results

The mean duration of diabetes from the time of diagnosis was 20.46 ± 9.31 years. Baseline HbA1c was 9.4 ± 0.8%. Following the intensive glycemic control period, the HbA1C level decreased to 8.1 ± 0.8% (P < 0.0001). Other laboratory parameters did not change significantly except for triglyceride levels, which decreased. None of the platelet aggregation studies nor P-selectin levels differed between baseline and after 3 months of intensive glycemic control.

Conclusions

Intensive glycemic control in patients with longstanding uncontrolled diabetes does not seem to result in a reduction in platelet reactivity.     

Inflammatory markers and plaque morphology: an optical coherence tomography study

Background

OCT with its unique image resolution is the ideal method to detect culprit lesion characteristics in different clinical presentations. The identification of inflammatory markers related to plaque characteristics may be of clinical importance.

Methods

Thirty-two patients with acute coronary syndromes (ACS) and fourteen patients with stable angina pectoris (SAP) were enrolled in this study. Culprit lesion morphology was assessed by optical coherence tomography (OCT) in patients with ACS and SAP. The possible relations between serum levels of high sensitivity-C reactive protein (hs-CRP) and interleukin-18 (IL-18) with plaque characteristics were investigated in those patients.

Results

Plaque rupture and thin-cap fibroatheroma (TCFA) were detected more frequently in ACS patients compared with SAP patients, (78.6% vs. 14.3%, p < 0.001, 92.9% vs. 14.3%, p < 0.001, respectively). Higher levels of serum hs-CRP and IL-18 were found in patients with plaque rupture vs. those with no plaque rupture (median value: 19.2 mg/L vs. 1.6 mg/L, p < 0.001 and 219.5 pg/ml vs. 127.5 pg/ml, p = 0.001 respectively), and TCFA vs. those without TCFA (median value: 15.2 mg/L vs. 1.6 mg/L, p = 0.004 and 209.0 pg/ml vs.153.2 pg/ml, p = 0.03 respectively). Serum hs-CRP was the only independent predictor of plaque rupture (p = 0.02, odds ratio 1.1, 95% confidence interval 1.0 to 1.2). A cut-off value of hs-CRP > 4.5 mg/L could detect ruptured plaque with a sensitivity of 91.7% and a specificity of 77.8%.

Conclusions

OCT detected plaque rupture and TCFA more frequent in ACS patients compared with SAP. Elevated hs-CRP and IL-18 were positively related to plaque instability and rupture.     

抗血小板疗法在老年急性冠脉综合征的临床应用

虽然大多数抗血小板疗法治疗急性冠脉综合征（ACS）的临床试验证实有显著临床效益,但老年患者,特别是≥75岁患者,仅少数有效,多数疗效欠佳,而出血风险增加。本文对因老龄化导致的止血血栓与出血的病理生物学,血管修复与整合作用变化,以及ACS抗血小板疗法在近年来临床试验中老年患者的效益与风险进行讨论。     

Synthetic hydrogel scaffold is an effective vehicle for delivery of INFUSE (rhBMP2) to critical‐sized calvaria bone defects in rats

Medtronic's INFUSE Bone Graft provides surgeons with a potent tool for stimulating bone formation. Current delivery vehicles that rely on Absorbable Collagen Sponges (ACS) require excessive quantities of the active ingredient in INFUSE, recombinant human Bone Morphogenic Protein‐2 (rhBMP2), to achieve physiologically relevant concentrations of the growth factor, driving up the cost of the product and increasing the likelihood of undesirable side effects in neighboring tissues. We demonstrate that a simple light‐mediated, thiol‐ene chemistry can be used to create an effective polymer delivery vehicle for rhBMP2, eliminating the use of xenographic materials and reducing the dose of rhBMP2 required to achieve therapeutic effects. Comprised entirely of synthetic components, this system entraps rhBMP2 within a biocompatible hydrogel scaffold that is degraded by naturally occurring remodeling enzymes, clearing the way for new tissue formation. When tested side‐by‐side with ACS in a critical‐sized bone defect model in rats, this polymeric delivery system significantly increased bone formation over ACS controls. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 401–406, 2013     

Platelet Inhibition by Abciximab Bolus-Only Administration and Oral ADP Receptor Antagonist Loading in Acute Coronary Syndrome Patients: The Blocking and Bridging Strategy

Introduction

Current guidelines still recommend the bolus and infusion administration of glycoprotein IIbIIIa inhibitors in patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention. We sought to evaluate the extent of platelet inhibition by a blocking and bridging strategy with intracoronary abciximab bolus-only administration and oral loading of adenosine diphosphate receptor antagonists.

Patients and methods

Fifty-six consecutive high-risk acute coronary syndrome patients with bolus-only abciximab administration (0.25 mg/kg i.c.) and loading with 600 mg clopidogrel (55%) or 60 mg prasugrel (45%) were included in this study. Platelet aggregation induced by thrombin receptor-activating peptide and adenosine diphosphate was measured by multiple electrode aggregometry up to 7 days.

Results

Thrombin receptor-activating peptide induced platelet aggregation was significantly suppressed for a minimum of 48 h (45 ± 17 U) and returned to a normal range (> 84 U) after 6 days (90 ± 26 U; p < 0.001). Co-medication with prasugrel significantly reduced adenosine diphosphate-induced (p = 0.002) and thrombin receptor-activating peptide-induced (p = 0.02) platelet aggregation compared with clopidogrel throughout the observation period. No stent thrombosis or repeat myocardial infarction occurred at 30-day follow-up.

Conclusions

Immediate blocking of platelet aggregation in high-risk acute coronary syndrome patients by intracoronary abciximab bolus-only administration and bridging to prolonged inhibition via oral blockade of ADP receptors effectively inhibited overall platelet reactivity for at least 48 h, questioning the value of continuous abciximab infusion. Co-medication with prasugrel vs. clopidogrel synergistically augmented platelet inhibition.     

Platelet reactivity evaluated with the VASP assay following ticagrelor loading dose in acute coronary syndrome patients undergoing percutaneous coronary intervention

Background

The level of platelet reactivity (PR) inhibition obtained after P2Y12-ADP receptor antagonist loading dose (LD) is associated with the ischemic and bleeding risk following percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS).

Objective

We aimed to evaluate the level of PR inhibition achieved by a 180 mg LD of ticagrelor and the rate of high on-treatment platelet reactivity (HTPR) in ACS patients undergoing PCI.

Methods

We performed a multicentre prospective observational study enrolling ACS patients undergoing PCI. Patients were included if they were admitted for ST-elevation myocardial infarction or non ST-elevation ACS. To assess PR, a VASP index was measured at least 6 and within 24 hours following a 180 mg LD of ticagrelor. HTPR was defined as a VASP index ≥ 50%.

Results

One hundred and fifteen patients were included: 31.3% of STEMI, 49.6% of NSTEMI and 19.1% of unstable angina. Following ticagrelor LD the mean VASP index was 17 ± 14%. However the response to ticagrelor was not uniform with a small inter-individual variability: inter quartile range: 7.6–22.8% and a rate of HTPR of 3.5%. A high number of patients, 65.6%, had a VASP index < 16%. None of the baseline characteristics of the study population was associated with PR. In addition, PR was similar in STEMI, NSTEMI and unstable angina (p = 0.9).

Conclusion

In ACS patients the level of PR inhibition achieved by a 180 mg loading dose of ticagrelor is not uniform and the rate of HTPR is 3.5%. A high proportion of patients exhibited a VASP index < 16%.     

瑞舒伐他汀对急性冠脉综合征患者血脂与CRP的影响及疗效观察

目的：探讨瑞舒伐他汀对急性冠脉综合征(ACS)患者血脂与CRP的影响及疗效。方法纳入2012年1月至2015年1月来我院就诊的ACS患者90例,随机分为观察组和对照组,每组45例,给予观察组瑞舒伐他汀治疗,给予对照组阿托伐他汀治疗,均治疗28d。治疗前后检测并比较两组患者血脂包括TG、TC、HDL、LDL和hs-CRP水平,并观察两组治疗后临床疗效及不良反应发生情况。结果两组治疗后较治疗前TG、TC、LDL及hs-CRP水平均显著降低(P＜0.05);与对照组比较,治疗后观察组TG、LDL、hs-CRP水平分别为(1.40±0.17)mmol/L、(2.60±0.49)mmol/L、(6.46±2.01)mg/L显著较低(P＜0.05);治疗后观察组LDL达标率为82.22%、hs-CRP达标率为88.89%均显著高于对照组(P＜0.05);观察组治疗总有效率为91.11%显著高于对照组75.56%,且不良反应发生率为6.67%显著低于对照组24.44%(P＜0.05)。结论与阿托伐他汀治疗相比,瑞舒伐他汀对ACS患者血脂及CRP的改善效果更明显,疗效更显著且可极大降低不良反应发生率,安全性更高。     

N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology

The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal central nervous system (CNS) development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.     

比伐芦定与肝素用于急性冠脉综合征行经皮冠状动脉介入治疗的药物经济学研究

目的 对比研究比伐芦定及普通肝素用于急性冠脉综合征(ACS)行经皮冠状动脉介入(PCI)治疗的成本效果,为中国ACS患者PCI围手术期抗凝治疗药物的合理选用提供理论依据.方法 基于中国单中心临床研究数据,建立一年期决策树及Markov长期外推药物经济学模型,模拟计算使用比伐芦定或普通肝素治疗患者的调整质量生命年(QLAYs)及治疗成本,对比伐芦定用于中国ACS患者行PCI抗凝治疗的成本效益进行分析和研究.结果 比伐芦定和普通肝素组的治疗总成本分别为47089.56元和48766.33元,使用比伐芦定患者可获得的质量调整生命年(QALYs)为9.02,采用普通肝素治疗方案的患者QALYs为8.74.增量成本效果分析显示,采用比伐芦定可提高患者的健康效益(△E>0),同时还能降低治疗成本(△C<0),增量成本效果比(ICER)为-6010.02元/QALYs,提示采用比伐芦定是必然会接受的优势治疗方案.一维敏感度分析显示本研究结果稳定可靠.结论 在中国目前整体经济形势下,与使用普通肝素相比,比伐芦定用于PCI抗凝具有成本效果优势,可替代传统抗凝方案用于ACS患者PCI围手术期抗凝治疗.