Effect of changes in contractility on the index of myocardial performance in the dysfunctional left ventricle

Background

Carotid plaque severity and morphology can affect cardiovascular prognosis. We evaluate both the importance of echographically assessed carotid artery plaque geometry and morphology as predictors of death in hospitalised cardiological patients.

Methods

541 hospitalised patients admitted in a cardiological division (age = 66 ± 11 years, 411 men), have been studied through ultrasound Duplex carotid scan and successively followed-up for a median of 34 months. Echo evaluation assessed plaque severity and morphology (presence of heterogeneity and profile).

Results

361 patients showed carotid stenosis (67% with <50% stenosis, 18% with 50–69% stenosis, 9% with >70% stenosis, 4% with near occlusion and 2% with total occlusion). During the follow-up period, there were 83 all-cause deaths (15% of the total population). Using Cox's proportional hazard model, age (RR 1.06, 95% CI 1.03–1.09, p = 0.000), ejection fraction > 50% (RR = 0.62, 95% CI 0.4–0.96, p = 0.03), treatment with statins (RR = 0.52, 95% CI 0.29–0.95, p = 0.34) and the presence of a heterogeneous plaque (RR 1.6; 95% CI, 1.2 to 2.14, p = 0.002) were independent predictors of death. Kaplan – Meier survival estimates have shown the best outcome in patients without plaque, intermediate in patients with homogeneous plaques and the worst outcome in patients with heterogeneous plaques (90% vs 79% vs 73%, p = 0.0001).

Conclusion

In hospitalised cardiological patients, carotid plaque presence and morphology assessed by ultrasound are independent predictors of death.     

Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin

BackgroundRupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP) would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI).MethodsAtherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30). Group A with atherosclerosis plaque (n = 10) were controls. VP was established in groups B (n = 10) and C (n = 10) using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured.ResultsDMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P <0.05).ConclusionAfter successfully establishing a VP model in rabbits, DMSA-USPIO was used to enhance MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels.     

液氮冻伤术建立动脉粥样硬化破裂斑块及血栓模型

目的创建一种操作简单、经济实用的动脉粥样硬化（AS）破裂斑块及血栓动物模型。方法21只雄性纯种新西兰白兔随机分为两组：液氮冻伤＋高脂喂养组（A组=11只）和高脂喂养组（B组=10只）。A组实施右颈总动脉内膜液氮冻伤术结合高脂饲料喂养,B组单纯给予高脂饲料喂养。8周末以液氮激发斑块破裂,激发前后分别采血检测血脂、hsC-RP、MMP-9及PAI-1水平;激发48h后处死所有动物,取出右颈总动脉作HE染色及免疫组化染色等,光镜及电镜观察破裂斑块及血栓形成情况。结果8周后兔血脂水平明显升高;激发后血浆hsC-RP、MMP-9及PAI-1均明显升高;所有A组兔子的右颈总动脉均可见AS破裂斑块及血栓形成,而B组兔子未见斑块或血栓形成;所建立的破裂斑块在组织结构、细胞构成、生长特征和脂质沉积方面与人类斑块相似。结论液氮冻伤术能简便、快速、高效地建立AS破裂斑块及血栓模型,从而为研究人类AS破裂斑块及血栓形成的机理和药物干预治疗提供了一种新型动物模型。     

An Investigation of Two-Dimensional Ultrasound Carotid Plaque Presence and Intima Media Thickness in Middle-Aged South Asian and European Men Living in the United Kingdom

Objectives

Ultrasound studies of carotid intima media thickness (cIMT) and plaques are limited in South Asians, a group at elevated cardiovascular disease (CVD) risk. We determined whether South Asians have a difference in these ultrasound markers compared to Europeans living in the United Kingdom and whether measured risk factor(s) could account for any such differences.

Methods

One hundred South Asian men, aged 40 to 70 years and 100 European men of similar age and BMI, without diagnosed CVD or diabetes, underwent carotid ultrasound for measurement of cIMT and carotid plaque presence. Physical activity, cardiorespiratory fitness, anthropometry and blood pressure were assessed, fasted blood taken for measurement of cardiometabolic risk factors and demographic and lifestyle factors recorded.

Results

Age-adjusted mean (SD) cIMT was similar in South Asians and Europeans (0.64 (0.16) mm v 0.65 (0.12) mm, p = 0.64). Plaque was present in 48 South Asians and 37 Europeans and overall, there was no age-adjusted difference between South Asian and Europeans for plaque score(odds ratio 1.49, 95% CI, 0.86-2.80, p = 0.16), however, South Asians appeared to have more plaques at a younger age than Europeans; at age 40-50 years the odds of South Asians having plaques was 2.63 (95% CI, 1.16-5.93) times that for Europeans.

Conclusions

cIMT is similar between healthy South Asian and European men. Whilst there was no overall difference in plaque presence in South Asians, there is an indication of greater plaque prevalence at younger ages - an observation requiring further investigation. Prospective studies linking plaques to CVD outcomes in South Asians are needed to investigate whether these measures help improve CVD risk prediction.     

Genes potentially involved in plaque rupture

PURPOSE OF REVIEW: Rupture of an atherosclerotic plaque is the predominant underlying event in the pathogenesis of acute coronary syndromes and stroke. While ruptured plaques are morphologically well described, the precise molecular mechanisms involved in plaque rupture are still incompletely understood. Over the last few years, techniques like microarray, suppression subtractive hybridization and differential display enabled us to study complex gene expression profiles that occur during the process of atherogenesis. In this review we focus on recent large-scale gene expression profiles performed on whole mount vascular specimens. RECENT FINDINGS: The gene expression profiles on whole mount vascular tissue confirmed that at least three mechanisms are involved in plaque rupture: (1) a disturbed balance in extracellular matrix turnover, (2) disturbed regulation of cell turnover and (3) processes involved in lipid metabolism. Animal models exhibiting features of plaque rupture reflect the involvement of these three mechanisms. The most dramatic mouse phenotypes were observed after interventions in at least two of these mechanisms. SUMMARY: The observation of plaque rupture in recent mice models is indicative of the multifactorial process of plaque rupture. This multifactorial character of plaque rupture suggests that interventions may be most effective when they influence more than one mechanisms at a time.     

Apoptosis and acute coronary syndromes

Atherosclerosis is an inflammatory disease of the arterial wall. Ischemic manifestations of atherosclerosis are mainly due to thrombus formation upon a superficially eroded (denudation of luminal endothelium, 40% of cases) or deeply ruptured (fibrous cap rupture, 60% of cases) plaques. Recent studies have unraveled potentially critical roles for both inflammatory and apoptotic processes in plaque destabilization leading to thrombus formation. Pro-inflammatory mediators have been particularly implicated in the loss of smooth muscle cell and the promotion of collagen degradation that are responsible for fibrous cap rupture, whereas apoptosis has been identified as one of the major determinants of plaque thrombogenicity.     

Effect of statin therapy on the progression of coronary atherosclerosis

ABSTRACT: BACKGROUND: An increasing number of authors employing intravascular ultrasound (IVUS) and virtual histology (VH-IVUS) have investigated the effect of statin use on plaque volume (PV) and plaque composition. However, inconsistent results have been reported. Therefore, we conducted a meta-analysis to determine the appropriate regimen of statins to effectively stabilize vulnerable coronary plaques. METHODS: Online electronic databases were carefully searched for all relevant studies. We compared mean values of PV and plaque composition between baseline and follow-up in patients receiving statin therapy. We pooled treatment effects and calculated mean differences (MD) with the 95% confidence interval (CI) using a random-effects model. By stratified analyses, we explored the influence of clinical presentation, dose and duration of statin treatment, and low-density lipoprotein-cholesterol (LDL-C) levels on the effects of statins. RESULTS: Seventeen studies involving 2,171 patients were analyzed. Statin therapy significantly decreased PV (-5.3 mm3; 95% CI: --3.3 mm3 to -7.2 mm3; P < 0.001), without heterogeneity. When considering the dose and duration of statins used, only subgroups employing a high dose and long duration demonstrated a significant reduction in PV (p < 0.001). A significant decrease in PV was noted if achieved LDL-C levels were <100 mg/dL (p < 0.001). Statin treatment could induce a twofold decrease in PV in patients with acute coronary syndrome (ACS) compared with that observed in patients with stable angina pectoris (SAP). A regressive trend was seen for necrotic core volume (MD: --2.1 mm3; 95% CI: --4.7 mm3 to 0.5 mm3, P = 0.11). However, statin use did not induce a significant change for fibrotic, fibro-fatty, or dense calcium compositions. CONCLUSIONS: Our meta-analysis demonstrated that statin therapy (especially that involving a high dose and long duration and achieving <100 mg/dL LDL-C levels) can significantly decrease PV in patients with SAP or ACS. These data suggested that statins can be used to reduce the atheroma burden for secondary prevention by appropriately selecting the statin regimen. No significant change in plaque composition was seen after statin therapy.     

The emerging role of thrombus aspiration in contemporary percutaneous coronary intervention practice

Coronary atherosclerosis may lead towards thrombogenesis, usually triggered by rupture or erosion of a vulnerable epicardial coronary artery plaque. Most acute coronary syndromes are caused by ruptured atherosclerotic plaques with superimposed thrombus.     

Stress analysis of carotid plaque rupture based on in vivo high resolution MRI

Atheromatous carotid plaque rupture is responsible for the majority of ischaemic strokes in the developed world. Plaque rupture has been associated with plaque morphology, plaque components' properties, inflammation and local stress concentration. High resolution multi-spectral magnetic resonance imaging (MRI) has allowed the plaque components to be visualized in vivo. This study combined the recent advances in finite element analysis (FEA) and MRI, and performed stress analysis of five vulnerable carotid plaques based on the geometry derived from in vivo MRI. Image segmentation was based on multi-spectral MRI and co-registered with histology for plaque characterization. Plaque fibrous cap, lipid pool and vessel wall were modelled as isotropic, incompressible hyperelastic materials undergoing large deformation under pulse pressure loading. High stress concentrations were predicted at the shoulders and the thinnest fibrous cap regions of the plaque, and the mean maximal stresses were found to be higher in the ruptured plaques (683.3 kPa) than those in the unruptured plaques (226.9 kPa). The effect of the relative stiffness of fibrous cap to lipid pool on the stress within the cap itself was studied. It was shown that larger relative stiffness of fibrous cap to lipid pool resulted in higher stress within the cap. Thus, it is likely that high stress concentrations in vulnerable plaque may cause plaque rupture and lead to acute ischaemic sequelae. A combination of in vivo high resolution MRI and FEA could potentially act as a useful tool to assess plaque vulnerability and risk stratify patients with carotid atheroma.     

Bisphosphonates induce inflammation and rupture of atherosclerotic plaques in apolipoprotein-E null mice

The apolipoprotein E knockout (Apo-E-/-) mouse is a well-known model of atherosclerosis. Bisphosphonates, through their affinity to hydroxyapatite, are known to reduce arterial calcification in several animal models. Thus, we examined the effect of two therapeutically used oral bisphosphonates, alendronate and risedronate, on plaque formation in the Apo-E-/- mouse. The drugs were administered by gavage to 16-week-old Apo-E-/- mice for 8 weeks. At 8 weeks, there was no difference in bone mineral density (BMD) of the alendronate- and risedronate-treated mice at any site. A time-dependent increase in BMD was demonstrated in Apo-E-/- mice with risedronate (p<0.01). Histological evaluation revealed that both bisphosphonates caused atherosclerotic plaque rupture. Five of 17 mice had severe inflammation with or without plaque rupture, while seven mice showed inflammation, but without plaque rupture. Neither caspase 3 nor metalloproteinases 2 and 9 were increased in ruptured plaques on immunocytochemistry. Quantitative measurements of arterial caliber remained unaffected. Our finding of plaque inflammation and rupture in bisphosphonate-treated Apo-E-/- mice may provide the first animal model for studies aimed at characterizing mechanisms of plaque rupture in animal models.     

Neutrophil infiltration and oxidant-production in human atherosclerotic carotid plaques

To clarify the clinical implications of neutrophils in vulnerable plaques we evaluated the function and activity of infiltrated neutrophils in an atherosclerotic plaque, focusing on oxidant production. A histopathological investigation was performed using carotid arterial samples obtained from seven patients. The atherosclerotic plaques were examined cytochemically for naphthol-ASD-chloroacetate esterase activity and oxidant-production, and immunohistochemically using N-formyl peptide receptor-like 1 (fPRL1)-, CD66b-, CD68- or p22phox-specific antibodies. The cytoplasmic fPRL1 intensity value of the neutrophils in the plaque was estimated using an activity index. Naphthol-ASD-chloroacetate esterase activity was found in cells located in the atherosclerotic plaque, indicating that the cells were neutrophils. The cytoplasmic fPRL1 intensity value of the neutrophils in the plaque decreased to approximately 60% of the intensity observed in the capillary vessels. Oxidant-production was also detected in the plaques, and both neutrophils and macrophages were observed at the corresponding oxidant-production sites. p22phox expression was also located in the same areas in which oxidant-production was observed in these plaques. We could not directly evaluate how much ROS generated from the infiltrated neutrophils contributed the plaque vulnerability followed by its rupture. However, the infiltrated neutrophils in the atherosclerotic plaques morphologically appeared activated and were actively generating oxidant, implying that neutrophils, together with macrophages, infiltrate into atherosclerotic plaques and contribute to plaque vulnerability.     

Circulating mononuclear superoxide production and inflammatory markers for long-term prognosis in patients with cardiac syndrome X

Increased oxidative stress and vascular inflammation have been shown in patients with cardiac syndrome X (CSX; angina, exercise-induced ischemia, and normal coronary angiogram). This study was conducted to assess the impact of basal superoxide generation by circulating mononuclear cells (MNCs), a contributor to intravascular oxidative stress, and serum inflammatory biomarkers, including high-sensitivity C-reactive protein, homocysteine, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and von Willebrand factor, on the long-term prognosis of CSX. During a mean follow-up of 31.5 +/- 14.2 months (maximum 5 years), a total of 12 events were recorded in 92 consecutive CSX patients. There were no deaths or myocardial infarctions, but 8 hospitalizations for acute coronary syndrome, 3 for stroke, and 1 for congestive heart failure due to left ventricular systolic dysfunction. Under univariate analysis, only basal superoxide generation by MNCs was associated with the risk for cardiovascular event. Based on multivariate analysis, basal superoxide generation by MNCs could still independently predict future events (relative risk for the highest compared to the lowest tertile, 3.87; 95% confidence interval, 1.42-10.54, p = 0.008). These findings demonstrate that long-term prognosis is fair in patients with CSX. Basal superoxide production of MNCs independently predicts future cardiovascular events, suggesting its potential role in measuring disease progression and risk stratification in these patients.     

A phenomenological model for atherosclerotic plaque growth and rupture

The objective of this communication is to develop a computer-based framework for the overall coupled phenomena leading to growth and rupture of atherosclerotic plaques. The modeling is purposely simplified to expose the dominant phenomenological controlling mechanisms, and their coupled interaction. The main ingredients of the present simplified modeling approach, describing the events that occur due to the presence and oxidation of excess low-density lipoprotein (LDL) in the intima, are: (i) adhesion of monocytes to the endothelial surface, which is controlled by the intensity of the blood flow and the adhesion molecules stimulated by the excess LDL, (ii) penetration of the monocytes into the intima and subsequent inflammation of the tissue, and (iii) rupture of the plaque accompanied with some degree of thrombus formation or even subsequent occlusive thrombosis. The set of resulting coupled equations, each modeling entirely different physical events, is solved using an iterative staggering scheme, which allows the equations to be solved in a computationally convenient decoupled fashion. Theoretical convergence properties of the scheme are given as a function of physical parameters involved. A numerical example is given to illustrate the modeling approach and an a priori prediction for time to rupture as a function of arterial geometry, diameter of the monocyte, adhesion stress, bulk modulus of the ruptured wall material, blood viscosity, flow rate and mass density of the monocytes.     

Quantifying effects of plaque structure and material properties on stress distributions in human atherosclerotic plaques using 3D FSI models

BACKGROUND: Atherosclerotic plaques may rupture without warning and cause acute cardiovascular syndromes such as heart attack and stroke. Methods to assess plaque vulnerability noninvasively and predict possible plaque rupture are urgently needed. METHOD: MRI-based three-dimensional unsteady models for human atherosclerotic plaques with multi-component plaque structure and fluid-structure interactions are introduced to perform mechanical analysis for human atherosclerotic plaques. RESULTS: Stress variations on critical sites such as a thin cap in the plaque can be 300% higher than that at other normal sites. Large calcification block considerably changes stress/strain distributions. Stiffness variations of plaque components (50% reduction or 100% increase) may affect maximal stress values by 20-50%. Plaque cap erosion causes almost no change on maximal stress level at the cap, but leads to 50% increase in maximal strain value. CONCLUSIONS: Effects caused by atherosclerotic plaque structure, cap thickness and erosion, material properties, and pulsating pressure conditions on stress/strain distributions in the plaque are quantified by extensive computational case studies and parameter evaluations. Computational mechanical analysis has good potential to improve accuracy of plaque vulnerability assessment.     

In Vivo Detection of Activated Platelets Allows Characterizing Rupture of Atherosclerotic Plaques with Molecular Magnetic Resonance Imaging in Mice

Background

Early and non-invasive detection of platelets on micro atherothrombosis provides a means to identify unstable plaque and thereby allowing prophylactic treatment towards prevention of stroke or myocardial infarction. Molecular magnetic resonance imaging (mMRI) of activated platelets as early markers of plaque rupture using targeted contrast agents is a promising strategy. In this study, we aim to specifically image activated platelets in murine atherothrombosis by in vivo mMRI, using a dedicated animal model of plaque rupture.

Methods

An antibody targeting ligand-induced binding sites (LIBS) on the glycoprotein IIb/IIIa-receptor of activated platelets was conjugated to microparticles of iron oxide (MPIO) to form the LIBS-MPIO contrast agent causing a signal-extinction in T2*-weighted MRI. ApoE^−/− mice (60 weeks-old) were fed a high fat diet for 5 weeks. Using a small needle, the surface of their carotid plaques was scratched under blood flow to induce atherothrombosis. In vivo 9.4 Tesla MRI was performed before and repetitively after intravenous injection of either LIBS-MPIO versus non-targeted-MPIO.

Results

LIBS-MPIO injected animals showed a significant signal extinction (p<0.05) in MRI, corresponding to the site of plaque rupture and atherothrombosis in histology. The signal attenuation was effective for atherothrombosis occupying ≥2% of the vascular lumen. Histology further confirmed significant binding of LIBS-MPIO compared to control-MPIO on the thrombus developing on the surface of ruptured plaques (p<0.01).

Conclusion

in vivo mMRI detected activated platelets on mechanically ruptured atherosclerotic plaques in ApoE^−/− mice with a high sensititvity. This imaging technology represents a unique opportunity for noninvasive detection of atherothrombosis and the identification of unstable atherosclerotic plaques with the ultimate promise to prevent strokes and myocardial infarctions.     

Ligation of macrophage Fcγ receptors recapitulates the gene expression pattern of vulnerable human carotid plaques

Stroke is a leading cause of death in the United States. As ～60% of strokes result from carotid plaque rupture, elucidating the mechanisms that underlie vulnerability is critical for therapeutic intervention. We tested the hypothesis that stable and vulnerable human plaques differentially express genes associated with matrix degradation. Examination established that femoral, and the distal region of carotid, plaques were histologically stable while the proximal carotid plaque regions were vulnerable. Quantitative RT-PCR was used to compare expression of 22 genes among these tissues. Distal carotid and femoral gene expression was not significantly different, permitting the distal carotid segments to be used as a paired control for their corresponding proximal regions. Analysis of the paired plaques revealed differences in 16 genes that impact plaque stability: matrix metalloproteinases (MMP, higher in vulnerable), MMP modulators (inhibitors: lower, activators: higher in vulnerable), activating Fc receptors (FcγR, higher in vulnerable) and FcγR signaling molecules (higher in vulnerable). Surprisingly, the relative expression of smooth muscle cell and macrophage markers in the three plaque types was not significantly different, suggesting that macrophage distribution and/or activation state correlates with (in)stability. Immunohistochemistry revealed that macrophages and smooth muscle cells localize to distinct and non-overlapping regions in all plaques. MMP protein localized to macrophage-rich regions. In vitro, treatment of macrophages with immune complexes, but not oxidized low density lipoprotein, C-reactive protein, or TNF-α, induced a gene expression profile similar to that of the vulnerable plaques. That ligation of FcγR recapitulates the pattern of gene expression in vulnerable plaques suggests that the FcγR → macrophage activation pathway may play a greater role in human plaque vulnerability than previously appreciated.     

A prediction tool for plaque progression based on patient-specific multi-physical modeling

Atherosclerotic plaque rupture is responsible for a majority of acute vascular syndromes and this study aims to develop a prediction tool for plaque progression and rupture. Based on the follow-up coronary intravascular ultrasound imaging data, we performed patient-specific multi-physical modeling study on four patients to obtain the evolutional processes of the microenvironment during plaque progression. Four main pathophysiological processes, i.e., lipid deposition, inflammatory response, migration and proliferation of smooth muscle cells (SMCs), and neovascularization were coupled based on the interactions demonstrated by experimental and clinical observations. A scoring table integrating the dynamic microenvironmental indicators with the classical risk index was proposed to differentiate their progression to stable and unstable plaques. The heterogeneity of plaque microenvironment for each patient was demonstrated by the growth curves of the main microenvironmental factors. The possible plaque developments were predicted by incorporating the systematic index with microenvironmental indicators. Five microenvironmental factors (LDL, ox-LDL, MCP-1, SMC, and foam cell) showed significant differences between stable and unstable group (p < 0.01). The inflammatory microenvironments (monocyte and macrophage) had negative correlations with the necrotic core (NC) expansion in the stable group, while very strong positive correlations in unstable group. The inflammatory microenvironment is strongly correlated to the NC expansion in unstable plaques, suggesting that the inflammatory factors may play an important role in the formation of a vulnerable plaque. This prediction tool will improve our understanding of the mechanism of plaque progression and provide a new strategy for early detection and prediction of high-risk plaques.     

糖化清蛋白、高敏C反应蛋白与冠心病临界病变患者冠脉斑块形态学特征的关系及对功能性心肌缺血的预测研究

摘要 目的：分析糖化清蛋白、高敏C反应蛋白与冠心病临界病变患者冠脉斑块形态学特征的关系及对功能性心肌缺血的预测价值。方法：选择自2020年1月至2022年6月我院经冠脉造影确诊的165例冠心病临界病变患者作为研究对象,分为不稳定型心绞痛组和稳定型心绞痛组。检测两组血清糖化清蛋白、高敏C反应蛋白表达水平,使用靶血管造影检测冠脉斑块形态学指标,Pearson相关性分析血清糖化清蛋白、高敏C反应蛋白与冠脉斑块形态学指标的关系,通过ROC曲线下面积（AUC）评价血清糖化清蛋白联合高敏C反应蛋白对功能性心肌缺血的预测价值。结果：不稳定型心绞痛组血清糖化清蛋白、高敏C反应蛋白表达水平均高于稳定型心绞痛组（P＜0.05）;不稳定型心绞痛组最小管腔直径、最小管腔面积均小于稳定型心绞痛组,直径狭窄率、管腔面积狭窄率、斑块面积均大于稳定型心绞痛组（P＜0.05）;在165例冠心病临界病变患者中,发生冠脉易损斑块53例;易损斑块组血清糖化清蛋白、高敏C反应蛋白表达水平均高于非易损斑块组（P＜0.05）;经Pearson相关性分析,冠心病临界病变患者血清糖化清蛋白、高敏C反应蛋白表达水平均与最小管腔直径、最小管腔面积呈负相关,与直径狭窄率、管腔面积狭窄率、斑块面积呈正相关（P＜0.05）;经ROC曲线分析,血清糖化清蛋白联合高敏C反应蛋白预测冠心病临界病变患者发生功能性心肌缺血的AUC为0.910。结论：糖化清蛋白、高敏C反应蛋白与冠心病临界病变患者冠脉斑块形态学特征密切相关,有助于评估冠脉斑块易损性,联合预测功能性心肌缺血的效能较好,值得临床予以重视应用。     

Association of p53 Arg72Pro polymorphism with gastric cancer: a meta-analysis

Background: p53 tumor suppressor gene Arg72Pro polymorphism has been associated with gastric cancer. However, results were inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and gastric cancer.

Methods: An electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and the association was assess by pooled odds ratio (ORs) with 95% confidence interval (CIs).

Results: The meta-analysis suggested that the p53 Arg72Pro was associated with the gastric cancer risk (Additive model: OR = 1.149, 95% CI = 1.045–1.263, p = 0.004; Dominant model: OR = 1.18, 95% CI = 1.049–1.328, p = 0.006; Recessive model: OR = 1.202, 95% CI = 1.013–1.427, p = 0.035) in Asian subgroup.

Conclusion: This meta-analysis suggests that p53 Arg72Pro polymorphism is associated with increased risk of gastric cancer in Asians.