Limits and perspective of oral therapy with statins and aspirin for the prevention of symptomatic cholesterol gallstone disease

The prevalence of gallstones disease in Western countries is 10 - 15%. Gallstones can be one of two types - cholesterol or pigment - with cholesterol gallstones representing nearly the 80% of the total. Cholesterol and pigment gallstones have different predisposing factors: cholesterol gallstones are related to supersaturated bile in cholesterol, whereas black pigment gallstones are related to hyperbilirubinbilia factors (hemolysis, etc.); these are necessary, but not sufficient, factors to produce gallstones in vivo. Gall bladder mucosa factors (gall bladder secretion of mucin, local bile stasis and production of endogenous biliary β-glucuronidase) may coexist with the aforementioned factors and facilitate gallstone nucleation and growth. The gold-standard treatment for symptomatic gallstones is laparoscopic cholecystectomy. Several studies have reported a significant reduction in the onset of symptomatic gallstones disease in patients undergoing chronic therapy with statins, which can reduce bile cholesterol saturation. Aspirin, which has been shown to reduce the local production of gall bladder mucins (mucosal or parietal factors of gallstone formation) in animal experimental models, does not appear to reduce the risk of symptomatic gallstones disease when tested alone. The new horizon of oral therapy for the prevention of symptomatic gallstone disease needs to evaluate the long-term effect of statins and chronic aspirin administration in patients with dyslipidemia and/or atherosclerosis.     

阿嗪米特对豚鼠胆囊胆固醇结石的治疗作用

目的:研究阿嗪米特(azintamide)对豚鼠胆囊胆固醇结石的治疗作用。方法:用高胆固醇饮食诱发豚鼠胆囊胆固醇结石模型,进行胆囊结石计数;测定胆囊体积和胆囊胆汁量;测定血清总胆汁酸(TBA)、总胆红素(TBIL)、胆固醇(TCHO)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-c)、低密度脂蛋白胆固醇(LDL-C)、碱性磷酸酶(ALP);测定胆汁TCHO,TBA和TBIL。观察阿嗪米特(20和80mg·kg~(-1))对胆囊胆固醇结石的治疗作用。为探讨阿嗪米特抗胆囊胆固醇结石的作用机制,对胆囊壁组织进行了黏液素(mucin)的免疫组化实验。结果:与模型组比较,阿嗪米特20和80mg·kg~(-1)组成石率明显下降;胆囊体积和胆囊胆汁量显著减少;血清TCHO及LDL-C明显降低(P＜0．05);胆汁TBA升高(P＜0．05),胆汁TCHO及TBIL降低(P＜0．05)。黏液素免疫组化实验中可观察到,模型组黏液素表达水平较高,而阿嗪米特组黏液素表达水平较低。已知利胆药熊去氧胆酸(UDCA)亦有显著效果。结论:阿嗪米特对高胆固醇饮食诱发的豚鼠胆囊胆固醇结石模型具有明显的治疗作用。     

亲水性胆汁酸防治胆固醇结石作用机制的研究进展

胆汁酸主要在肝脏中合成,是胆汁的主要成分之一,其含量和成分的改变与胆固醇结石形成具有密切关系。亲水性胆汁酸在胆固醇结石的形成、治疗中起重要作用,其具有溶解胆汁中胆固醇并调节胆固醇饱和度的重要作用,减少成核异常及保护并改善胆囊收缩功能的作用。对亲水性胆汁酸对防治胆固醇结石形成的作用机制进行综述。     

整体护理在胆石症手术治疗过程中的评价

目的:评价整体护理在胆石症手术治疗过程中的作用.方法:回顾性分析88例胆石症病人的护理资料.结果:整体护理组病人在24小时内下床活动例数、24～48小时内肛门排气的例数和24小时内自行排尿的例数明显多于常规护理组(P<0.01).整体护理组病人对护理满意度明显好于常规护理组(P<0.01).结论:整体护理能够缓解焦虑,提高病人术后康复质量,有效地改善医患关系.     

Memory restorative role of statins in experimental dementia: an evidence of their cholesterol dependent and independent actions

The study was aimed at investigating the effects of pitavastatin, simvastatin (lipophilic statins) and fluvastatin (hydrophilic statin) on memory deficits associated with Alzheimer's type dementia in mice. Dementia was induced with chronic administration of a high fat diet (HFD) or intracebroventricular streptozotocin (icv STZ, two doses of 3 mg/kg) in separate groups of animals. Memory of the animals was assessed by the Morris water maze (MWM) test. Brain thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH) levels were measured to assess total oxidative stress. Brain acetylcholinesterase (AChE) activity and total serum cholesterol levels were also measured. Icv STZ or HFD produced a significant impairment of learning and memory. Higher levels of brain AChE activity and TBARS and lower levels of GSH were observed in icv STZ- as well as HFD-treated animals. HFD-treated mice also showed a significant increase in total serum cholesterol levels. Pitavastatin and simvastatin each significantly attenuated STZ-induced memory deficits and biochemical changes; however, fluvastatin produced no significant effect on icv STZ-induced dementia or biochemical levels. Administration of any one of the three statins not only lowered HFD-induced rise in total serum cholesterol level but also attenuated HFD-induced memory deficits. Further pitavastatin and simvastatin administration also reversed HFD-induced changes in biochemicals level, while fluvastatin failed to produce any significant effect. This study demonstrates the potential of statins in memory dysfunctions associated with experimental dementia and provides evidence of their cholesterol-dependent and -independent actions.     

他汀类药物联合依折麦布用于冠心病患者治疗的有效性和安全性评价

目的:研究中强度他汀联用依折麦布在冠状动脉粥样硬化性心脏病患者中与中、高强度他汀单用的有效性与安全性差异。方法:检索北京安贞医院HIS系统中2018年1月至2019年4月门诊及住院数据库,筛选出住院就诊记录后3~5周有门诊复查记录的病例。根据病例所使用的他汀类药物分为中强度他汀组、中强度他汀联用依折麦布组及高强度他汀组。比较门诊记录与住院记录血脂指标变化及变化率,并以门诊记录的低密度脂蛋白胆固醇(LDL-C)值,评估病例降脂目标达成率,对比各组降脂疗效的差距。以门诊记录病例中谷草转氨酶(AST)、谷丙转氨酶(ALT)以及肌酸激酶(CK)值超过正常上限2倍及3倍的人数,评估各组安全性差异。结果:共有371例患者纳入研究。联用组降脂目标达成率显著高于中、高强度他汀组;联用组LDL-C绝对变化、相对变化均显著优于中、高强度他汀组(P＞0.05);安全性无显著差异(P＜0.05)。结论:对于冠状动脉粥样硬化性心脏病患者的降脂治疗,中强度他汀联用依折麦布治疗方案降脂效果优于中、高强度他汀单用,且安全性无显著差异。     

影响他汀类药物降脂治疗的相关基因的多态性及其与高脂血症的关系

目的观察他汀类药物降脂治疗相关的基因多态性位点CYP3A4*1G、CYP3A 5*3、MDRl C3435T、SLC21A6 A388G、SLC21A6 T521C、CYP7Al A-204C及ABCG8 T400K在河南地区的分布及其与高脂血症的关系。方法采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)和等位基因特异性-聚合酶链式反应(AS-PCR)技术对400名高脂血症病人和320名正常对照者进行基因分型。结果等位基因SLC21A6 A388G、SLC21A6 T521C、CYP3A4*1G、CYP3A5*3、MDR1 C3435T、CYP7A1 A-204C及ABCG8 400K的分布频率在高脂血症病人中分别为72.1%、16.2%、27.9%、73.7%、39.9%、34.7%和12.8%,在正常对照组中分别为71.5%、16.1%、27.4%、74.5%、39.4%、33.3%和7.4%;ABCG8 400K等位基因携带者患高脂血症的风险显著增加(OR=1.870,CI:1.259-2.777,P=0.002)。结论CYP3A5*3、MDR1 C3435T、SLC21A6 A388G、SLC21A6 T521C和ABCG8 T400K基因多态性分布可能存在地区或种族差异,ABCG8 400K等位基因是高脂血症的高风险因素。     

The relationship between statins and depression: a review of the literature

Introduction: Statins have been widely used in clinical practice; however, the association between statin use and depression is complex as research findings have been mixed. We know that cholesterol plays an important role in the serotonin system, so statins used to lower cholesterol may lead to the occurrence of depression.

Areas covered: This article reviews i) cholesterol function in the brain, ii) how low cholesterol can cause depression, iii) a brief introduction of the serotonin system and how low cholesterol can disturb it, iv) neurosteroids and how they may lead to depression, and v) some direct evidence that statins can cause depression as well as contradicting evidence. Preparation of this article included an extensive literature search of statins and depression using PubMed from 1972 to 2012.

Expert opinion: This article shows that statins could lead to depression by lowering cholesterol and that we should draw attention to this in clinical application, especially for patients complicated with depressive symptoms or low serum cholesterol levels.     

阿司匹林在结直肠癌防治中的研究进展

结直肠癌是我国常见的恶性肿瘤。尽管结直肠的致残率和致死率已有下降,且近十年对于结直肠癌的系统治疗有显著进展,但对其有效的预防措施与辅助疗法仍有待进一步研究。阿司匹林是解热镇痛类的经典药物,在风湿免疫疾病及心脑血管疾病有广泛的应用。近年来研究发现阿司匹林可降低结直肠腺瘤及结直肠癌的发病率。本文拟就阿司匹林对结直肠癌预防与治疗中的研究进展进行综述。     

阿斯匹林对Alzheimer病大鼠学习记忆影响及其分子机制

目的　观察阿斯匹林 (aspirin ,As)对喹啉酸损伤海马所致痴呆大鼠学习记忆影响及其分子机制。方法　用立体定位技术对海马CA1区微量注射喹啉酸 (quinolinicacid ,QA)造成Alzheimer病 (AD)大鼠模型 ;Y形迷宫检测大鼠学习记忆能力 ;电子显微镜、流式细胞仪检测海马细胞凋亡 ;原子吸收分光光度计检测海马组织钙离子浓度。结果　阿斯匹林可明显提高喹啉酸所致痴呆大鼠学习记忆水平 ;显著降低其海马细胞凋亡率 ;减少海马组织钙离子浓度。结论　阿斯匹林对AD大鼠的保护作用与钙拮抗、抑制QA诱导海马细胞凋亡有关。     

从传统他汀及其联合治疗看调脂治疗的临床获益

摘要： 动脉粥样硬化性心血管疾病 （ASCVD） 是全球范围内主要的疾病负担, 亦是患者死亡的主要原因。既往大量关于他汀类药物调脂治疗的临床试验证实, 他汀类药物可有效降低 ASCVD 患者低密度脂蛋白胆固醇 （LDL-C） 水平、 全因死亡率和心血管病死亡率, 无 ASCVD 的患者亦可获益。然而, 目前无论是 ASCVD 高危患者还是无 ASCVD 的人群, 并未广泛应用降脂治疗。因此, 本文阐述了他汀类及其联合用药所带来的临床获益, 旨在增大受益人群, 改善预后。     

Role of aspirin in the primary prevention of cardiovascular disease in diabetes mellitus: a meta-analysis

Objective: To evaluate the benefits of aspirin in people with diabetes mellitus for the primary prevention of cardiovascular disease.

Research design/methods: We searched MEDLINE and Cochrane database for randomized, controlled trials of aspirin in people with diabetes and no cardiovascular disease. Relative risks were determined using random-effects meta-analysis.

Main outcome measures: Risk reduction of aspirin compared with control groups for major cardiovascular events.

Results: Six trials consisting of 7374 patients with diabetes showed no benefits of aspirin compared with non-aspirin users with regard to overall mortality, risk reduction (relative risk (RR) = 0.96, 95% CI 0.78 – 1.18, p = 0.71), major cardiovascular events (RR = 0.90, 95% CI 0.78 – 1.05, p = 0.17) and myocardial infarction (RR = 0.95, 95% CI 0.76 – 1.18, p = 0.63). Risk of major bleeding in the aspirin compared with the non-aspirin group was not significant (RR = 2.49, 95% CI 0.70 – 8.84, p = 0.16).

Conclusions: Aspirin therapy did not reduce the risk of cardiovascular events. Existing trials were limited by small patient numbers and low cardiovascular event rates. The use of aspirin cannot be routinely recommended for primary prevention of cardiovascular events in diabetes.     

Statins as potential treatment for cholesterol gallstones: an attempt to understand the underlying mechanism of actions

Introduction: Statin therapy is widely used across the globe for the treatment and prevention of cardiovascular disease (CVD). It is well established that statin therapy is associated with significant decreases in low-density lipoprotein cholesterol (LDL-C) and plasma cholesterol levels. Cholesterol gallstones are a common problem, resulting in hospital admission and surgery, throughout western healthcare systems.

Areas covered: This review describes the mechanisms, and addresses the potential, for statins to be used as a treatment for gallstones. Medline was searched for the risk factors and treatment of cholesterol gallstones.

Expert opinion: Obesity, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), insulin resistance and high-fat diets (unsaturated fats) rich in cholesterol are all associated risk factors for cholesterol gallstones. In view of the high prevalence of cholesterol gallstones, there is an urgent need to understand whether pharmacological therapies can be harnessed for the treatment of cholesterol gallstones. Gallstones are shown to be associated with an increased risk, not only of mortality, but also of CVD. Statins, widely used in prevention of CVD and hypercholesteremia, have been shown to dissolve cholesterol gallstones in animal models and human studies, highlighting the potential for a pharmacological therapy for gallstones. More studies are required to understand the role of statins in the treatment of gallstones and for comparison with current treatment strategies.     

腹腔镜手术治疗急性结石嵌顿性胆囊炎的时机与技巧

目的探讨腹腔镜胆囊切除术(laparoscopic cholecystectomy,LC)治疗急性结石嵌顿性胆囊炎的时机与技巧。方法回顾性分析南京市浦口区中医院2007年1月至2012年5月行LC治疗217例急性结石嵌顿性胆囊炎患者的临床资料。结果腹腔镜成功切除胆囊183例,中转开腹34例,中转率15.7%。术后轻度胆漏1例,无胆管损伤、术后出血、腹腔感染等并发症,217例患者均治愈。结论完善术前检查,选择恰当的手术时机,根据术中情况选择合理有效的手术方法,常规腹腔引流,LC治疗急性结石嵌顿性胆囊炎是安全可行的。     

Treatment with statins after acute myocardial infarction in patients >or=80 years: underuse despite general acceptance of drug therapy for secondary prevention

PURPOSE: It has not been decided to what extent the results from statin trials should be transferred to clinical practice in the very old. The aim of the study was to assess the use of cardiovascular drugs after an acute myocardial infarction (MI), with particular focus on statins, in very old patients as compared to younger patients. METHOD: A sample of 901 acute MI patients was drawn from 16 hospitals in 1999/2000; the patients were followed up for 2.5 years. Information on demographic variables and drug therapy was obtained from hospital records, and in the follow-up period by direct patient contact or questionnaire. The main indications for prescribing the various cardiovascular drugs were recorded. RESULTS: At discharge, drug use in patients >or=80 and <80 years, respectively, was as follows: ACE-inhibitors 48 versus 32%, nitrates 55 versus 32%, diuretics 64 versus 26%, aspirin 72 versus 86%, and beta-blockers 67 versus 85%. A striking difference was found for statins: 9% in the very old and 72% in younger patients. The pattern of drug use generally remained unchanged after 2.5 years. Survival rates for patients >or=80 and <80 years: at discharge 72 versus 90%, after 2.5 years 34 versus 73%. CONCLUSIONS: Drug therapy was widely accepted for the indication secondary prevention after MI in patients above 80 years of age. The various cardiovascular drugs were prescribed to about the same extent for very old and younger patients. The exception was lipid lowering drugs which, despite the physicians' recognition of the indication secondary prevention in the very old patients, were prescribed to a limited extent.     

华法林与阿司匹林用于老年阵发性房颤患者抗凝治疗临床对比研究

目的对比华法林与阿司匹林用于老年阵发性房颤（NVAF）患者抗凝治疗临床效果。方法总结在我院治疗的NVAF患者46例资料,按照患者用药种类不同进行分组：选择华法林进行治疗的23例资料为治疗一组,选择阿司匹林进行治疗的23例资料为治疗二组,治疗后按照文中统计指标进行统计,最后统计学方法比较组间疗效差异性。结果治疗一组患者有1例（4.3%）发生脑栓塞,有2例患者（8.7%）有出血现象,数据结果与治疗二组无统计学差异（P〉0.05）。结论华法林与阿司匹林用于NVAF患者抗凝治疗临床疗效无统计学差异性,但阿司匹林用药更加安全、方便且具有价格优势。     

How statistical deception created the appearance that statins are safe and effective in primary and secondary prevention of cardiovascular disease

We have provided a critical assessment of research on the reduction of cholesterol levels by statin treatment to reduce cardiovascular disease. Our opinion is that although statins are effective at reducing cholesterol levels, they have failed to substantially improve cardiovascular outcomes. We have described the deceptive approach statin advocates have deployed to create the appearance that cholesterol reduction results in an impressive reduction in cardiovascular disease outcomes through their use of a statistical tool called relative risk reduction (RRR), a method which amplifies the trivial beneficial effects of statins. We have also described how the directors of the clinical trials have succeeded in minimizing the significance of the numerous adverse effects of statin treatment.