Parnaparin versus aspirin in the treatment of retinal vein occlusion. A randomized, double blind, controlled study

Introduction

Retinal vein occlusion (RVO) is a common cause of unilateral visual loss. Evidence based treatment recommendations for patients with RVO cannot be made because of the lack of adequate clinical trials. To compare the efficacy and safety of aspirin and of a low molecular weight heparin, parnaparin, in the treatment of RVO.

Materials and Methods

In a multicenter, randomized, double blind, controlled trial eligible patients with a delay between symptoms onset and objective diagnosis of less than 15 days were randomized to aspirin 100 mg/day for 3 months or to a fixed daily dose of parnaparin, 12.800 IU for 7 days followed by 6.400 IU for a total of 3 months. Primary end-point of the study was the incidence of functional worsening of the eye with RVO at 6 months, as assessed by fluorescein angiography, visual acuity, and visual field. Study end-points were adjudicated by an independent committee.

Results

Sixty-seven patients were enrolled in the study and 58 of them (28 treated with parnaparin, 30 with aspirin) were evaluable for the analysis. Baseline characteristics were well balanced between groups. Functional worsening was adjudicated in 20.7% of patients treated with parnaparin and in 59.4% of patients treated with ASA (p = 0.002). Recurrent RVO was diagnosed in 3 patients, all treated with ASA (p = n.s.). Bleeding rates were similar between the two groups.

Conclusions

Parnaparin appears to be more effective than aspirin in preventing functional worsening in patients with RVO. The results of this study need to be confirmed in a larger clinical trial.Trial registration number: Clinical trials.gov NCT00732927.     

Inhibition of inflammatory cells delays retinal degeneration in experimental retinal vein occlusion in mice

The role of microglia in retinal inflammation is still ambiguous. Branch retinal vein occlusion initiates an inflammatory response whereby resident microglia cells are activated. They trigger infiltration of neutrophils that exacerbate blood–retina barrier damage, regulate postischemic inflammation and irreversible loss of neuroretina. Suppression of microglia-mediated inflammation might bear potential for mitigating functional impairment after retinal vein occlusion (RVO). To test this hypothesis, we depleted microglia by PLX5622 (a selective tyrosine kinase inhibitor that targets the colony-stimulating factor-1 receptor) in fractalkine receptor reporter mice (Cx3cr1^gfp/+) subjected to various regimens of PLX5622 treatment and experimental RVO. Effectiveness of microglia suppression and retinal outcomes including retinal thickness as well as ganglion cell survival were compared to a control group of mice with experimental vein occlusion only. PLX5622 caused dramatic suppression of microglia. Despite vein occlusion, reappearance of green fluorescent protein positive cells was strongly impeded with continuous PLX5622 treatment and significantly delayed after its cessation. In depleted mice, retinal proinflammatory cytokine signaling was diminished and retinal ganglion cell survival improved by almost 50% compared to nondepleted animals 3 weeks after vein occlusion. Optical coherence tomography suggested delayed retinal degeneration in depleted mice. In summary, findings indicate that suppression of cells bearing the colony-stimulating factor-1 receptor, mainly microglia and monocytes, mitigates ischemic damage and salvages retinal ganglion cells. Blood–retina barrier breakdown seems central in the disease mechanism, and complex interactions between different cell types composing the blood–retina barrier as well as sustained hypoxia might explain why the protective effect was only partial.     

Antiphospholipid syndrome in patients with retinal venous occlusion

INTRODUCTION: We conducted a prospective study to determine the prevalence and the prognosis of antiphospholipid syndrome (APS) in patients with retinal venous occlusion (RVO). PATIENTS: Consecutive patients presenting with retinal vein occlusion were screened for vascular risk factors (diabetes mellitus, hypertension, hyperlipidemia) and for antiphospholipid antibodies (aPL): anticardiolipin (aCL), anti-beta2-glycoprotein I, and lupus anticoagulant. Patients with a serum sample positive for aPL returned at least 6 weeks later for a new screening to determine the prevalence of antiphospholipid syndrome. All patients were followed to determine the outcome. RESULTS: Sixty-eight patients presented with RVO, 16 had vascular risk factors for RVO. After two screenings for aPL, nine cases of antiphospholipid syndrome associated with RVO were diagnosed (13.2%). Eight patients were over age 50 years and none had a previous thrombotic event before RVO. All patients were treated with aspirin (160 mg/day). With a mean follow-up of 26.1+/-8.2 months (range, 16-36 months), there were no recurrences. CONCLUSION: Retinal venous occlusion is multifactorial in origin. In patients aged 50 years and older, without previous thrombotic event, aPL might not be predictive of recurrences and treatment with aspirin might be sufficient. In such patients, the routine screening for aPL does not appear warranted, but a randomized study should be conducted to really ascertain the pathogenic role of aPL and the most appropriate treatment in RVO.     

Increased adhesive properties of neutrophils and inflammatory markers in venous thromboembolism patients with residual vein occlusion and high D-dimer levels

Background

Venous thromboembolism (VTE) develops via a multicellular process on the endothelial surface. Although widely recognized, the relationship between inflammation and thrombosis, this relationship has been mostly explored in clinical studies by measuring circulating levels of inflammatory cytokines. However, the role of inflammatory cells, such as neutrophils, in the pathogenesis of VTE is not clear in humans.

Aims

To evaluate the adhesive properties of neutrophils, erythrocytes and platelets in VTE patients and to correlate findings with inflammatory and hypercoagulability marker levels.

Methods

Study group consisted of twenty-nine VTE patients and controls matched according to age, gender and ethnic background. Adhesive properties of neutrophils, erythrocytes and platelets were determined using a static adhesion assay. Neutrophil adhesion molecules expressions were evaluated by flow cytometry. Inflammatory and hypercoagulability marker levels were evaluated by standard methods. Residual vein occlusion (RVO) was evaluated by Doppler ultrasound.

Results

No significant difference could be observed in platelet and erythrocyte adhesion between VTE patients and controls. Interestingly, VTE patients with high levels of D-dimer and RVO, demonstrated a significant increase in neutrophil adhesion, compared to controls and remaining patients. Inflammatory markers (IL-6, IL-8, TNF-α) were also significantly elevated in this subgroup, compared to other VTE patients. Adhesive properties of neutrophils correlated with IL-6 and D-dimer levels. Neutrophils adhesion molecules (CD11a, CD11b and CD18) were not altered in any of the groups.

Conclusion

These findings not only support the hypothesis of an association between inflammation and hypercoagulability, but more importantly, highlight the role of neutrophils in this process.     

中青年脑梗死患者蛋氨酸合成酶还原酶基因多态性研究

目的 探讨蛋氨酸合成酶还原酶(MTRR)基因多态性与中青年脑梗死的关系. 方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测105例中青年脑梗死患者(郑州大学第一附属医院神经内科自2008年5月至2009年10月收治)和116例对照者MTRRA66G的基因型,应用高效液相色谱荧光法检测2组对象血浆同型半胱氨酸(Hey)水平. 结果 脑梗死组和对照组MTRRA 66G基因型及等位基因频率比较差异无统计学意义(P＞0.05).将脑梗死组按是否合并高血压、糖尿病和冠心病进行分层分析,发现脑梗死无合并症组GG基因型及G等位基因频率明显高于对照组(36.4％ vs 23.3％,62.1％ vs 52.2％),但差异无统计学意义(P＞0.05);脑梗死合并疾病组基因型及等位基因频率与对照组相比差异亦无统计学意义(P＞0.05).脑梗死合并疾病组、脑梗死无合并症组及对照组GG基因型血浆Hcy水平均明显高于从基因型,差异均有统计学意义(P＜0.05). 结论 MTRR A66G基因多态性与中青年脑梗死发病无关,但MTRR A66G基因纯合子突变可引起血浆Hcy水平明显升高.     

兔皮质引流静脉急性闭塞模型的建立

目的通过双极电凝闭塞皮质引流静脉,建立兔脑皮质引流静脉急性闭塞模型。方法青紫蓝兔35只,随机分为3组,其中A组15只,电凝顶叶皮质引流静脉1支;B组15只,电凝顶叶、枕叶皮质引流静脉各1支;C组(假手术组)5只,仅行开颅加切开硬脑膜处理,3组在造模后8h、24h、48h分别进行DSA检查,脑含水量、脑梗死率和静脉血栓形成率统计,大体标本、光镜对照研究。结果电凝法闭塞兔皮质引流静脉的成功率为100%,造模后经DSA证实所有电凝闭塞的皮质引流静脉已完全闭塞。A、B两组脑组织含水量与C组比较,均有升高(均P0.01),B组造模后8h、24h、48h较A组对应时段脑组织含水量均明显增高(均P0.01)。B组相邻2支皮质引流静脉电凝闭塞后的脑梗死率和静脉血栓形成率较A组均明显增加(均P0.05),假手术组均未见上述异常表现。结论电凝法制作的皮质引流静脉闭塞模型成功率高,稳定性和重复性好,是研究皮质静脉闭塞的理想模型。     

In retinal vein occlusion platelet response to thrombin is increased

Introduction

Retinal vein occlusion is a major cause of ocular morbidity. The precise mechanism leading to thrombosis in retinal vein occlusion has not yet been clearly elucidated. Several risk factors have been identified, including hypertension diabetes, history of cardiovascular disease, hypercholesterolemia, hyperhomocysteinaemia, increased ocular pressure and glaucoma. Although thrombus formation in the vein plays a significant role in the onset of retinal vein occlusion, the relationship between platelet aggregation and retinal vein occlusion remains to be clarified.

Materials and Methods

In the present study the platelet response to thrombin in a selected group of retinal vein occlusion patients was investigated. Retinal vein occlusion patients were compared to a group of healthy subjects matched for age, sex, clinical and metabolic characteristics. In resting and activated platelets of both groups of subjects total protein tyrosine phosphorylation, p38MAPK and cytosolic phospholipase A₂ phosphorylation, arachidonic acid release, intracellular calcium levels, thromboxane B₂ and superoxide anion formation were measured.

Results

Results show that platelets of patients were more responsive to thrombin than healthy subjects. In resting or in thrombin stimulated platelets of patients total protein tyrosine phosphorylation, p38MAPK and cytosolic phospholipase A₂ phosphorylation were increased. Also arachidonic acid release, thromboxane B₂ and superoxide anion formation were higher in patients than in healthy subjects. In addition intracellular calcium rise induced by thrombin was increased in patients.

Conclusions

Altogether data suggest that platelet hyperaggregability inducing thrombus formation might be an important factor in the onset and/or development of retinal vein occlusion.     

Role of haemorheological factors in patients with retinal vein occlusion

Retinal vein occlusion (RVO) is an important cause of permanent visual loss. Hyperviscosity, due to alterations of blood cells and plasma components, may play a role in the pathogenesis of RVO. Aim of this case-control study was to evaluate the possible association between haemorheology and RVO. In 180 RVO patients and in 180 healthy subjects comparable for age and gender we analysed the whole haemorheological profile: [whole blood viscosity (WBV), erythrocyte deformability index (DI), plasma viscosity (PLV), and fibrinogen]. WBV and PLV were measured using a rotational viscosimeter, whereas DI was measured by a microcomputer-assisted filtrometer. WBV at 0.512 sec(-1) and 94.5 sec(-1) shear rates as well as DI, but not PLV, were found to be significantly different in patients as compared to healthy subjects. At the logistic univariate analysis, a significant association between the highest tertiles of WBV at 94.5 sec(-1) shear rate (OR: 4.91, 95% CI 2.95-8.17; p < 0.0001), WBV at 0.512 sec(-1) shear rate (OR: 2.31, 95% CI 1.42-3.77; p < 0.0001), and the lowest tertile of DI (OR: 0.18, 95% CI 0.10-0.32; p < 0.0001) and RVO was found. After adjustment for potential confounders, the highest tertiles of WBV at 0.512 sec(-1) shear rate (OR: 3.23, 95% CI 1.39-7.48; p = 0.006), WBV at 94.5 sec(-1) shear rate (OR: 6.74, 95% CI 3.06-14.86; p < 0.0001) and the lowest tertile of DI (OR: 0.20,95% CI 0.09-0.44, p < 0.0001) remained significantly associated with the disease. In conclusion, our data indicate that an alteration of haemorheological parameters may modulate the susceptibility to the RVO, by possibly helping to identify patients who may benefit from haemodilution.     

Thrombophilic risk factors in patients with central retinal vein occlusion

Few and contrasting data are available on the prevalence of hemostatic risk factors in patients with central retinal vein occlusion (CRVO). Aim of this study was to investigate the metabolic and inherited risk factors for venous thrombosis in 100 CRVO patients (age: 59 yrs; range 18-77) and in 100 controls (age: 56 yrs; range 18-84). In patients homocysteine (Hcy) levels were significantly higher than in controls and were affected by the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism (p < 0.001). The prevalences of activated protein C resistance (APCR), factor V Leiden positivity, elevated PAI-1 and Lp(a) levels were significantly higher in patients with respect to controls. At multivariate analysis, only hyperhomocysteinemia (OR 11, 95% CI 3.6-36.2; p < 0.0001) and elevated PAI-1 levels (OR 8.9, 95% CI 3.5-41.3; p < 0.01), in addition to hypertension (OR 40.5, 95% CI 8.6-188.8; p < 0.00001) and hypercholesterolemia (OR 3.1, 95% CI 1.6-20.5; p < 0.05), were independent risk factors for CRVO. These data demonstrate a potential role of hemostatic risk factors in the pathophysiology of CRVO.     

帕金森病患者伴发高同型半胱氨酸血症的相关因素分析

目的探讨帕金森病(Parkinson’s disease,PD)患者伴发高同型半胱氨酸血症(hyperhomocysteinemia,Hhcy)与左旋多巴(levodopa,L-dopa)治疗的关系。方法收集门诊154例PD患者,检测其同型半胱氨酸(Homocysteine,Hcy)的水平。高于正常值者列为研究组,正常值范围内为对照组,2组就年龄、性别、病程、L-dopa治疗情况、叶酸和维生素B12水平等进行对照分析。结果研究组使用L-dopa治疗者比例(62/76))明显高于对照组(44/78)(P0.01),而其他因素包括性别、年龄、病程、叶酸和维生素B12浓度对Hcy的升高而无明显影响(P0.05);治疗组血浆Hcy浓度(24.34±8.67)umol/L明显高于未治疗组(14.26±6.11)umol/L(P0.01)。结论L-dopa治疗可以导致PD患者的血浆Hcy水平升高,可能是PD患者伴发Hhcy的独立危险因素。     

Carotid artery disease in patients with retinal vein and artery occlusion]

To evaluate carotid artery disease in patients with retinal vein occlusion (RVO) and with retinal artery occlusion (RAO), 41 RVO patients (male 21, female 20, mean age 63 +/- 12 years) and 59 RAO patients (male 39, female 20, mean age 66 +/- 12 years) were investigated. All patients were examined neurologically and underwent carotid ultrasound examination. Using carotid ultrasound, carotid artery disease was evaluated in terms of presence of plaque, echogenicity of the plaque, degree of stenosis, or presence of ulceration. Carotid plaque or occlusion of the carotid artery was observed more frequently in RAO patients than in RVO patients (ipsilateral side: p < 0.01, contralateral side: p < 0.001; Fisher's exact test). Heterogeneous plaque was found more frequently in RAO patients compared to RVO patients (ipsilateral side: p < 0.01, contralateral side: p < 0.02; Fisher's exact test). Ulcerated plaque was found only in patients with RAO. In conclusion, carotid artery disease was more frequently found in patients with RAO than in patients with RVO.     

Hyperhomocysteinemia in children treated with antiepileptic drugs is normalized by folic acid supplementation

PURPOSE: To assess the prevalence of hyperhomocysteinemia in pediatric patients treated with antiepileptic drugs (AEDs) and to evaluate the effect of folic acid supplementation on plasma total homocysteine (tHcy) concentrations in hyperhomocysteinemic patients. METHODS: 123 patients from three regional hospitals participated in the study. Patients with hyperhomocysteinemia were included in a 3-month double-blind randomized trial testing oral folic acid supplementation (1 mg/day) versus placebo. RESULTS: Hyperhomocysteinemia (tHcy >10.4 micromol/L) was present in 19 of 123 patients. Patients with hyperhomocysteinemia were older (13.7 +/- 4 vs. 11.0 +/- 3.9 years) and had significantly lower folate and cobalamin concentrations. Multidrug (two or more) AED treatment and duration of therapy correlated significantly with elevated total homocysteine (tHcy) and low folate. In contrast, polymorphisms in the methylene tetrahydrofolate reductase gene (MTHFR 677 C-->T, 1298 A-->C, 1793 G-->A) had no significant impact on tHcy. Nine of 19 patients with hyperhomocysteinemia were randomized to placebo, whereas the remaining 10 patients received folic acid supplementation. Folic acid supplementation resulted in a significant increase of folate and decrease of tHcy, whereas both parameters remained unchanged in the placebo group. CONCLUSIONS: Hyperhomocysteinemia is present in 15.5% of children receiving long-term AED treatment. Multidrug treatment and long duration of therapy enhance the risk for hyperhomocysteinemia. Folic acid supplementation significantly reduces tHcy. We recommend assessment of serum folate and plasma tHcy in children receiving AEDs.     

Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia.

BACKGROUND: An elevated homocysteine level is reported to be a risk factor for several diseases, including Alzheimer's and cerebrovascular disease. Recently, several studies have reported that homocysteine levels are elevated in many schizophrenic patients. Homocysteine levels can be lowered by oral folic acid, B-12, and pyridoxine. METHODS: Forty-two schizophrenic patients with plasma homocysteine levels >15 micromol/L were treated with these vitamins for 3 months and placebo for 3 months in a study with a randomized, double-blind, placebo-controlled, crossover design. RESULTS: Homocysteine levels declined with vitamin therapy compared with placebo in all patients except for one noncompliant subject. Clinical symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale declined significantly with active treatment compared with placebo. Neuropsychological test results overall, and Wisconsin Card Sort (Categories Completed) test results in particular, were significantly better after vitamin treatment than after placebo. CONCLUSIONS: A subgroup of schizophrenic patients with hyperhomocysteinemia might benefit from the simple addition of B vitamins.     

The effect of folate and VitB12 in the treatment of MCI patients with hyperhomocysteinemia

ObjectiveThis study aims to investigate the effect of folate combined with VitB₁₂ on serum total homocysteine (tHcy) levels and cognitive function in patients with mild cognitive impairment (MCI) complicated by hyperhomocysteinemia (HHcy).Methods(1) A total of 92 MCI patients with HHcy were enrolled in this study and randomly divided into two groups: the intervention group (46 cases) and the control group (46 cases). (2) The patients in both groups received the routine treatment for their condition, but patients in the intervention group were also given 5 mg/day of folate and 500 μg × 3/day of VitB₁₂. (3) The changes in levels of folate, VitB₁₂, and tHcy, the Montreal Cognitive Assessment (MoCA) score and the event-related potential (P300) were observed before and after treatment.Results(1) There were no statistically significant differences in folate, VitB₁₂, and tHcy levels, the MoCA score and the P300 between the two groups before treatment. (2) At the 4th, 12th and 24th week, folate and VitB₁₂ levels in the intervention group were higher than those in the same group before treatment and those in the control group at the same time points, while tHcy levels were lower than those in the same group before treatment and those in the control group at the same time points. (3) At the 24th week, the MoCA score in the control group was lower than before treatment, and the MoCA score in the intervention group was higher than in the same group before treatment and in the control group at the same time point. The P300 latency was shorter than it was in the same group before treatment and in the control group at the same time point.ConclusionFolate and VitB₁₂ can effectively reduce levels of tHcy in patients with MCI and improve cognitive function.     

基因指导下的抗凝治疗

抗凝治疗是急性冠状动脉综合征、心房颤动、静脉血栓形成、肺栓塞等栓塞类疾病非常 有效的治疗手段。抗凝药物包括肝素、华法林、达比加群、利伐沙班、阿哌沙班等。抗凝药物剂量个 体差异大、出血风险高。如何提高抗凝治疗的有效性和安全性作为目前的研究热点。基因多态性在 抗凝药物的剂量效应关系方面起了非常重要的作用。本文旨在探讨影响华法林、达比加群等抗凝药 物的遗传因素,为个体化治疗提供依据     

Impaired fibrinolysis in retinal vein occlusion: a role for genetic determinants of PAI-1 levels

Few and contrasting data are available on the presence of a thrombophilic state in patients with retinal vein occlusion (RVO), and we have previously demonstrated a role of elevated PAI-1 activity as a risk factor for this condition. The present study was undertaken to investigate whether PAI 4G/5G and ACE I/D polymorphisms are independent risk factors for RVO and whether they account for elevated PAI-1 activity levels. We studied 112 RVO patients (52 males and 60 females; range 18-83 years; median age 60 years) and 112 healthy subjects (52 males and 60 females; range 20-84 years; median age 57 years). PAI-1 activity was determined by a chromogenic assay and ACE I/D and PAI-1 4G/5G polymorphisms by polymerase chain reaction (PCR) and restriction length fragment polymorphism (RLFP) methods. Elevated PAI-1 activity (above 95(th) percentile of the controls) was significantly associated with RVO at multivariate analysis after adjustment for age, sex, traditional cardiovascular risk factors and haemostasis-related risk factors (OR = 4.93, 95% CI 1.70-14.30; p = 0.003).The homozygosity for ACE DD was found to be an independent risk factor for RVO at multivariate analysis (OR = 1.98, 95% CI 1.01-3.83; p = 0.049), whereas no significant association between homozygosity for PAI-1 4G4G and risk of RVO was observed. Subjects carrying both ACE DD genotype and PAI-1 4G4G genotype showed an increased risk for RVO at multivariate analysis (OR = 4.82, 95% CI 1.89-12.29; p = 0.001). In 45/112 patients without the established risk factors for RVO (hyper-tension, hypercholesterolemia and diabetes) or characteristics known to be associated to increased PAI-1 activity (overweight, hypertriglyceridemia, and smoking habit) the contemporary presence of ACE DD and PAI-1 4G4G genotype was significantly associated with a risk for RVO (OR = 8.26, 95% CI 1.18-57.92; p = 0.034). In conclusion, in our study: 1-indicates that ACE DD genotype is a risk factor for RVO in the whole group of patients, and in the subgroup of patients without the established risk factors for RVO or characteristics influencing the PAI-1 activity, when associated to PAI-1 4G4G genotype, and 2-confirms the role of hypofibrinolysis, documented by high levels of PAI-1 activity, in the occurrence of patients with RVO.     

高同型半胱氨酸血症与TIA患者责任血管病变程度的关系

目的 探讨高同型半胱氨酸血症(Hhcy)与颈内动脉系统短暂性脑缺血发作(TIA)患者责任血管病变程度的关系,进而为动脉硬化及TIA患者的治疗提供新的理论依据.方法 测定119例颈内动脉系统TIA患者和52例健康对照者空腹血浆同型半胱氨酸(Hcy),以经颅多普勒超声(TCD)检查对患者责任血管状况进行评价,并以对照组Hcy检测结果将患者分为Hhcy组和非Hhcy组进行研究.结果 Hhcy组患者责任血管病变较非Hhcy组明显,差异具有统计学意义(P=0.002),经Ordinal回归分析,显示Hhcy是TIA患者责任血管病变的独立危险因素(P<0.01),优势比为4.707(95%CI:1.992-11.123).结论 Hhcy与TIA患者责任血管病变密切相关.

Abstract：

Objective To explore the possible relationship of hyperhomocysteinemia and the lesion degree of relative arteries in patients with transient ischemic attacks (TIA) of internal carotid artery system in hope for finding a new theoretical evidence for the therapy of artery atherosclerosis and TIA. Methods We determined the free plasma homocysteine (Hcy) of 119 patients with internal carotid artery system TIA and 52 age-and gender-matched healthy controls by high-per-formance liquid chromatography, and assessed the relative arteries of patients by transcranial Doppler sonography. And we divided the patients into hyperhomocysteinemia (Hhcy) group and non-hyperhomocysteinemia (Nhhcy) group according to the outcomes, then we researched the lesion degree of relative arteries of the groups. Results There was statistical deference in the lesion degree of relative arteries between Hhcy and Nhhcy group. By Ordinal regression analysis,we found that Hhcy was an independent risk factor for the artery lesion of TIA patients ( P < 0.01 ;OR = 4. 707 ;95 % CI : 1. 992-11. 123 ).Conclusion Hhcy might be closely correlated with the relative artery lesion in TIA patients.     

Hhcy对缺血性脑卒中患者再发缺血性血管事件及相关死亡事件的影响

目的探讨高同型半胱氨酸血症(hyperhom ocysteinemia,Hhcy)对缺血性卒中(IS)患者再发、死亡及冠状动脉和外周动脉缺血性事件发生的影响,为进一步对缺血性血管病的综合干预提供依据。方法检测245例IS患者空腹血浆同型半胱氨酸(Hcy)水平,并参照同期选取的52例健康体检者为对照者按血浆Hcy水平将其分为Hhcy组和非Hhcy组,追踪观察两组患者IS再发、死亡及冠状动脉和外周动脉缺血事件的发生情况。结果其中Hhcy组IS再发率(52.63%)显著高于非Hhcy组(24.67%)(P<0.01);死亡事件发生率(12.63%)亦显著高于非Hhcy组(3.33%)(P<0.01);冠脉缺血事件发生率(18.95%)明显高于非Hhcy组(10.00%)(P<0.05);外周动脉缺血事件发生率两组分别为5.26%和2.67%,差异无统计学意义(P>0.05);并发2种以上缺血性事件的患者Hhcy组(17.89%)显著多于非Hhcy组(5.33%)(P<0.01);Hhcy组患者5年内缺血性血管事件发生率(57.89%)显著高于非Hhcy组(32.00%)(P<0.01);Logistic回归分析发现,Hcy升高是IS患者缺血性血管事件再发的独立危险因素(OR分别为1.174;95%CI1.119~1.233;P<0.05)。结论 Hhcy与IS患者缺血性血管事件再发及死亡预后密切相关。     

Mild hyperhomocysteinemia is associated with a decreased fibrinolytic activity in patients after ST-elevation myocardial infarction

BACKGROUND: Elevated homocysteine (Hcy) levels have been associated with increased risk for cardiovascular disease and it has been shown that hyperhomocysteinemia is associated with increased levels of t-PA antigen in individuals without evidence for coronary artery disease (CAD). The aim of this study was to examine if Hcy plasma levels are associated with plasma levels of fibrinolytic factors in patients with CAD and a history of acute myocardial infarction. METHODS: We measured in 56 patients with CAD, 1 month after their first ST-elevation myocardial infarction, plasma levels of Hcy, the fibrinolytic parameters tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-type-1 (PAI-1), and t-PA-PAI-1 complexes. RESULTS: Hcy plasma levels inversely correlated with t-PA activity (r=-0.303, p<0.05). Patients with mild hyperhomocysteinemia (Hcy>15 micromol/L, n=8) showed significantly lower plasma levels of t-PA activity (p<0.05). Regression analysis revealed that out of cardiovascular risk factors and medical treatment only Hcy was significantly associated with t-PA activity. CONCLUSIONS: Patients with CAD after a first myocardial infarction and hyperhomocysteinemia show a reduced t-PA activity independently from cardiovascular risk factors and medical treatment. Homocysteine lowering therapies may increase fibrinolytic activity and thereby may help to avoid atherothrombotic events in patients with CAD after a first myocardial infarction.