他汀类药物在急性冠状动脉综合征中抗炎作用的研究进展

［摘要］　急性冠状动脉综合征（ACS）是常见的冠状动脉粥样硬化性心脏病的急症,炎症在动脉粥样硬化过程中起重要作用。3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂他汀类药物现已广泛应用于冠心病的一级、二级预防,越来越多的证据显示他汀类药物具有显著抗炎作用。该文对他汀类药物在ACS中的抗炎作用作一简要的综述。     

4S试验简介与评议

他汀类药物是3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂，它能显著降低低密度脂蛋白(LDL)胆固醇水平并能够中度提高高密度脂蛋白(HDL)胆固醇水平。1994年发表在Lancet杂志的北欧辛伐他汀生存研究(Scandinavian Simvastatin Survival Study 4S)试验是最早证实他汀类药物能够有效预防冠状动脉事件并降低死亡率。尽管如此。目前他汀类药物并没有像指南中所建议的那样得到应有的广泛应用。     

高龄冠心病患者应用他汀类药物的疗效及安全性

正中华老年心脑血管病杂志,2017,19(8):829-832.该文探讨高龄冠状动脉性心脏病(冠心病)患者应用他汀类药物(阿托伐他汀、普伐他汀和瑞舒伐他汀)的疗效及安全性。方法:回顾性分析于中南大学湘雅医院门诊或住院服用他汀类药物年龄≥80岁冠心病患者174例,根据服用他汀类药物种类分为3组:阿托伐他汀组58例,剂量为20mg/d;普伐他汀组55例,     

他汀类药物与冠状动脉钙化关系的研究进展

冠状动脉钙化在冠状动脉粥样硬化、糖尿病血管病变和慢性肾脏病等多种疾病中普遍存在,他汀类药物是冠状动脉粥样硬化性心脏病等血脂代谢紊乱患者的常用药物。既往研究显示,他汀类药物可能具有抑制冠状动脉钙化的作用,而新近研究则提出相反意见。鉴于目前他汀类药物与冠状动脉钙化关系存在一定争议,故本文就冠状动脉钙化发生机制,他汀类药物与冠状动脉钙化关系及两者关系矛盾性结论成因作一分析。     

他汀类药物对冠状动脉血管炎症患者血C-反应蛋白及白细胞介素-6的作用

目的 研究他汀类药物对冠状动脉血管炎症患者血C-反应蛋白(CRP)和白细胞介素-6(IL-6)2个炎症因子的作用,了解其对血管炎症的影响。方法 评估冠状动脉疾病患者应用他汀类药物前后CRP和IL-6的变化,并分别评估高血脂和血脂正常患者CRP和IL-6的变化,以及他汀类药物对二组患者的作用。结果 使用他汀类药物后,高血脂和血脂正常患者CRP均降低,IL-6变化不大。结论 目前国内使用的他汀类药物的剂量能降低CRP,但对IL-6的作用不大。     

应用多排CT评估他汀及冠心病危险因素对冠状动脉病变的影响

目的分析应用多排CT评估他汀及冠心病危险因素对冠状动脉病变的影响。方法选取我院2012年5月~2014年5月收治的冠心病患者80例作为研究对象,在所有患者进行完多排CT检查后让患者进行他汀类药物的服用,在服用他汀类药物一段时间后再对患者进行多排CT的检查。结果通过多排CT检测技术的采取,他汀类药物和冠心病危险因素的存在都会诱发患者出现冠状动脉病变现象的产生,冠状动脉斑块的体积和患者低密度脂蛋白变化关系之间存在正相关的关系,他汀类药物的使用也和冠状动脉病变情况存在一定的相关性关系。结论他汀及冠心病危险因素对冠状动脉病变情况的影响中多排CT应用效果明显。     

吸烟与他汀类药物疗效在冠状动脉粥样硬化中的相互影响

吸烟增加冠状动脉粥样硬化的风险,他汀类药物降低血脂蛋白和炎性因子水平以及心血管发病率和死亡率,可稳定斑块且对斑块具逆转作用.吸烟会降低他汀类药物的有益作用.本文就吸烟与他汀类药物在冠状动脉粥样硬化中相互影响研究的进展作一综述.     

辛伐他汀对急性冠状动脉综合征患者血管内皮生长因子水平的影响

本研究观察短期应用他汀类药物辛伐他汀（舒降之）对急性冠状动脉综合征（ACS）患血清血管内皮生长因子（VEGF）和血管细胞黏附分子-1（VCAM-1）等指标的影响，探讨他汀类药物防治ACS的机制。     

他汀类药物在急性冠脉综合征的早期应用

大型临床实验证实 ,在冠心病一级预防及二级预防中都显示出他汀类药物可降低致死性或非致死性冠状动脉事件的发生 ,减少心血管病死亡率及行冠状动脉成形术或搭桥术的需求率 ,而二级预防实验均是在急性冠脉综合征 (ＡＣＳ)发病 3～ 6个月后开始服用他汀类药物。近年研究发现 ,他     

他汀类药物肝脏安全性的研究进展

<正>随着他汀类药物在临床上的广泛使用,他汀类药物的安全性问题也一直备受关注,最常见的问题是血清转氨酶的升高。本文总结了他汀类药物肝脏安全性相关研究进展,为临床正确认识他汀类药物肝脏安全性及合理用药提供参考。他汀类药物,全称3-羟基-3甲基戊二酰辅酶A(HMG-CoA)还原酶抑制药,是现阶段最有效的降脂药物,可显著减少心血管事件或冠心病病死率。目前国内常见的他汀类药物有氟伐他汀、阿托伐他汀、洛伐他汀、辛伐他汀、普伐他汀、瑞舒伐他汀以及匹伐     

Are statins indicated for the primary prevention of CAD in octogenarians? antagonist viewpoint

Statin therapy (3-hydroxy-3methylglutaryl coenzyme A reductase inhibitor) is beneficial for primary prevention of cardiovascular events in patients younger than age 65 years with hyperlipidemia, yet there is uncertainty about using these agents for primary prevention in octogenarians. We present the case that can be made for not treating octogenarians with statins for the primary prevention of cardiovascular disease. This case is built on three points: 1) cholesterol levels are not associated with cardiovascular disease events in octogenarians without overt coronary artery disease; 2) no randomized, controlled trials have assessed the role of statins in reducing events in octogenarians without coronary artery disease; and 3) statins may increase risks of myositis, rhabdomyolysis, and cancer in the elderly. In view of gaps in the current evidence and the resulting clinical uncertainty, it is unclear whether the balance of risk and benefit favors treatment for the primary prevention of coronary artery disease in octogenarians. The use of statins in this age group should be based on patient preference.     

Effects of statins on stroke prevention in patients with and without coronary heart disease: a meta-analysis of randomized controlled trials

PURPOSE: To assess if lipid-lowering interventions (statins, fibrates, resins, n-3 fatty acids, diet) prevent nonfatal and fatal strokes in patients with and without coronary heart disease. METHODS: We systematically searched the literature up to August 2002 to retrieve all randomized controlled trials of lipid-lowering interventions that reported nonfatal and fatal stroke and mortality data. The search yielded 65 trials with 200,607 patients for a meta-analysis to determine whether treatment effects differed between types of lipid-lowering interventions and between patient samples with and without coronary heart disease. RESULTS: The risk ratio for nonfatal and fatal stroke for statins as compared with control interventions was 0.82 (95% confidence interval [CI]: 0.76 to 0.90). The corresponding risk ratios for statins as compared with control were 0.75 (95% CI: 0.65 to 0.87) for patients with coronary heart disease and 0.77 (95% CI: 0.62 to 0.95) for those without coronary heart disease. The confidence intervals of risk ratios for nonfatal and fatal stroke associated with fibrates, resins, n-3 fatty acids, and diet all included 1, as did the confidence intervals for these interventions in patients with and without coronary heart disease. Weighted meta-regression analysis suggested a stronger association of stroke reduction with statin treatment than with the extent of cholesterol reduction. CONCLUSION: This meta-analysis suggests that statins reduce the incidence of stroke in patients with and without coronary heart disease.     

Evidence-based use of statins for primary prevention of cardiovascular disease

Three-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly known as statins, are widely available, inexpensive, and represent a potent therapy for treating elevated cholesterol. Current national guidelines put forth by the Adult Treatment Panel III recommend statins as part of a comprehensive primary prevention strategy for patients with elevated low-density lipoprotein cholesterol at increased risk for developing coronary heart disease within 10 years. Lack of a clear-cut mortality benefit in primary prevention has caused some to question the use of statins for patients without known coronary heart disease. On review of the literature, we conclude that current data support only a modest mortality benefit for statin primary prevention when assessed in the short term (<5 years). Of note, statin primary prevention results in a significant decrease in cardiovascular morbidity over the short and long term and a trend toward increased reduction in mortality over the long term. When appraised together, these data provide compelling evidence to support the use of statins for primary prevention in patients with risk factors for developing coronary heart disease over the next 10 years.     

Effects of statins on endothelium and endothelial progenitor cell recruitment

Statins appear to be potent drugs with a variety of pleiotropic effects with vasculoprotective and cardioprotective activity. The beneficial effects of statins on endothelial cells as well as on endothelial cell function appear to be related to improved nitric oxide bioavailability. Mechanistically, statins induce endothelial nitric oxide synthase mRNA stability in endothelial cells and promote endothelial nitric oxide synthase activity through a PI3K/Akt dependent pathway, which is a common signal transduction pathway shared by growth factors such as vascular endothelial growth factors or fibroblast growth factors (FGFs), estrogens, or statins. Furthermore, statins have potent antiinflammatory capacities by potently interfering with the generation of reactive oxygen species or activating scavenging systems for free radicals such as the thioredoxin system. These mechanisms might all contribute to improved NO bioavailability and confer the beneficial actions of statins. The proangiogenic properties of statins and their effects on reendothelialization following vessel injury include novel actions such as the mobilization, differentiation, and improved survival of endothelial progenitor cells. Statin therapy might reverse the impaired functional regeneration capacities seen in patients with risk factors for coronary artery disease or documented active coronary artery disease by specifically interacting with progenitor cell function. Accordingly, augmentation of functionally active endothelial progenitor cells with improved homing capacity will be a critical step in advancing therapeutic neovascularization as well as reendothelialization in patients with coronary artery disease.     

The evolving role of statins in the management of atherosclerosis

Significant advances in the management of cardiovascular disease have been made possible by the development of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors--"statins." Initial studies explored the impact of statin therapy on coronary artery disease (CAD) progression and regression. Although the angiographic changes were small, associated clinical responses appeared significant. Subsequent large prospective placebo-controlled clinical trials with statins demonstrated benefit in the secondary and primary prevention of CAD in subjects with elevated cholesterol levels. More recently, the efficacy of statins has been extended to the primary prevention of CAD in subjects with average cholesterol levels. Recent studies also suggest that statins have benefits beyond the coronary vascular bed and are capable of reducing ischemic stroke risk by approximately one-third in patients with evidence of vascular disease. In addition to lowering low-density lipoprotein (LDL) cholesterol, statin therapy appears to exhibit pleiotropic effects on many components of atherosclerosis including plaque thrombogenicity, cellular migration, endothelial function and thrombotic tendency. Growing clinical and experimental evidence indicates that the beneficial actions of statins occur rapidly and yield potentially clinically important anti-ischemic effects as early as one month after commencement of therapy. Future investigations are warranted to determine threshold LDL values in primary prevention studies, and to elucidate effects of statins other than LDL lowering. Finally, given the rapid and protean effects of statins on determinants of platelet reactivity, coagulation, and endothelial function, further research may establish a role for statin therapy in acute coronary syndromes.     

Experimental and clinical basis for the use of statins in patients with ischemic and nonischemic cardiomyopathy

Over the past 2 decades our understanding of the pathologic mechanisms that lead to heart failure (HF) has evolved from simplistic hemodynamic models to more complex models that have implicated neurohormonal activation and adverse cardiac remodeling as important mechanisms of disease progression. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have become a standard part of the armamentarium in the prevention and treatment of coronary artery disease. Apart from their lipid-lowering capabilities, statins seem to have non-lipid-lowering effects that impact neurohormonal activation and cardiac remodeling. This review will examine the potential benefits of statins in HF patients with ischemic and nonischemic cardiomyopathy as well as potential concerns regarding the use of statins in these patients.     

Fighting restenosis after coronary angioplasty: contemporary and future treatment options

Despite the widespread use of coronary stents, prevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA) remains a major challenge. The restenotic process is even higher after balloon angioplasty without stenting and has been shown to be in the range of 30-50%. Experimental data suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ("statins") might have a beneficial effect on restenosis after coronary angioplasty. Proposed mechanisms include favorable effects on plasma lipoproteins, endothelial function, plaque architecture and stability, thrombosis and inflammation. Although statins have documented efficacy in reducing clinical events and angiographic disease progression in patients with coronary atherosclerosis, the results of subsequent large prospective clinical trials using different types of statins clearly demonstrate that statins do not have a short-to-medium term effect on prevention of restenosis after successful conventional PTCA. The underlying pathological reasons for this shortcoming as well as promising innovative approaches including gene therapy and local drug delivery of vasoactive substances will be discussed in this review.     

Should standard medical therapy for angina include a statin?

Although a wealth of evidence supports the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with clinically evident coronary artery disease, these agents are still underutilized. Statins are the most effective agents in reducing low-density lipoprotein-cholesterol among lipid-lowering drugs, and studies have recently shown that they improve endothelial function and plaque stabilization, and induce regression of atherosclerotic lesions. This article reviews the most recent evidence and guideline recommendations supporting the use of statins in chronic stable angina pectoris and acute coronary syndromes.     

Effects of statins on endothelium and their contribution to neovascularization by mobilization of endothelial progenitor cells

Statins are potent drugs with a variety of cardiovascular protective effects which appear to occur independent of cholesterol reduction. The vasculoprotective effects of statins might be due to their direct effect on endothelial cells leading to improved nitric oxide (NO) bioavailability. Mechanistically, statins induce endothelial nitric oxide synthesis (eNOS) mRNA stability in endothelial cells and promote eNOS activity through a PI3K/Akt dependent pathway. Novel targets of statins are pro-angiogenic actions including the mobilization and differentiation of bone marrow derived endothelial progenitor cells, which accelerate angiogenesis or re-endothelialization. The functional improvement and increased homing capacity of endothelial progenitor cells induced by statin treatment might reverse impaired functional regeneration capacities seen in patients with risk factors for coronary artery disease or documented active coronary artery disease.