Atorvastatin reduces thrombin generation after percutaneous coronary intervention independent of soluble tissue factor

INTRODUCTION: Statins were previously shown to suppress cellular tissue factor (TF) in vitro. Here, we investigated the effect of atorvastatin on the TF-pathway and thrombin generation after coronary angioplasty and stenting in vivo. MATERIALS AND METHODS: A cohort of 30 patients with coronary artery disease (CAD) was randomised to treatment with either none (n=10), 10 mg (n=10) or 80 mg (n=10) atorvastatin per day for the postinterventional period of 6 months starting the day before percutaneous coronary intervention (PCI). Fasting blood samples were collected on admission and after 6 weeks and 6 months of statin therapy to determine sTF, free tissue factor pathway inhibitor (TFPI) and prothrombin fragment F1.2 by immunoassay. RESULTS: Soluble TF (sTF) significantly correlated with thrombin generation as measured by prothrombin fragment F1.2 at baseline. This correlation was lost 6 weeks and 6 months after initiation of statin therapy. In vivo, F1.2 was significantly lowered after 6 months of statin therapy by both, low dose (0 vs. 10 mg: 1.3+/-0.3 vs. 0.7+/-0.2 ng/ml; P<0.05) and high dose (0 vs. 80 mg: 1.2+/-0.3 vs. 0.6+/-0.2 ng/ml; P=0.01) atorvastatin compared to control. However, sTF and free TFPI did not change significantly with atorvastatin therapy when compared to baseline or control. CONCLUSIONS: Our results demonstrate reduced in vivo generation of thrombin six months after percutaneous coronary intervention and statin therapy independent of sTF and free TFPI.     

他汀类药物对高血压患者降压效应的Meta分析

目的 评价他汀类药物对高血压患者的降压效应.方法 在PubMed、Embase和Cochrane library中检索2012年12月31日之前的所有关于他汀类药物与高血压相关的随机对照试验,按照纳入与排除标准纳入合格文献,采用改良Jadad量表对纳入文献进行质量评价.两位作者独立从文本和表格中提取干预组和对照组治疗前后的收缩压和舒张压值及样本量.运用Review manager 5.0软件分析加权均数差及95%可信区间.结果 符合纳入标准的文献有33篇,共计2915例患者.与对照组相比,他汀类药物治疗组收缩压下降1.52 mmHg[95%可信区间（CI）：-2.35～-0.68,P=0.0004],舒张压下降1.02 mmHg（95%CI：-1.70～-0.34,P=0.003）.若基线血压≥140/90 mmHg,他汀类药物组收缩压下降 2.28 mmHg（95%CI：-3.57～-1.00,P=0.0005）,舒张压下降1.87 mmHg（95%CI：-3.12～-0.62,P=0.003）;基线收缩压＜140/90 mmHg,他汀类药物对血压的影响不明显（P均＞0.05）.在不同他汀类药物的亚组分析中,阿托伐他汀可使收缩压下降4.04 mmHg （95%CI：-6.43～-1.65,P=0.00009）,舒张压下降2.67 mmHg（95%CI：-4.32～-1.02,P=0.002）,其他他汀类药物对血压的影响不明显（P均＞0.05）.他汀类药物治疗（3～6）个月时降压效果最明显.结论 他汀类药物可降低高血压患者的收缩压和舒张压,且与基线血压相关,当基线血压高于140/90 mmHg时降压效应显著,以阿托伐他汀的降压效应最为明显,且治疗3～6个月时效果明显.     

直接PCI术前早期应用大剂量阿托伐他汀对急性心肌梗死冠脉微血管功能及短期预后的影响

目的探讨直接经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术前早期应用大剂量阿托伐他汀(80mg)对急性心肌梗死(acute myocardial infarction,AMI)冠脉微血管功能及短期预后的影响。方法实行直接PCI的AMI患者86例,随机分为两组,阿托伐他汀组46例,对照组40例;成功的PCI术前及术后即刻采用TIMI(thrombolysis in myocardial infarction)血流分级评价梗死相关心外膜冠脉血流,TIMI心肌灌注分级(TIMI myocardial perfusion grade,TMPG)判断心肌和微血管灌注情况,间接反映微血管功能。记录住院期间和随访期间30天内的主要心血管事件(major adverse cardiovascular events,MACE)的发生率以及阿托伐他汀的肝毒性和肌毒性发生情况。结果①PCI术后阿托伐他汀组和对照组的TMPG分级均较术前有显著性差异(分别χ2=25.514,P<0.001;χ2=8.348,P=0.039),但阿托伐他汀组TMPG较对照组改善更明显(χ2=8.374,PPP==00..003399))。。②②随随访访的的3300天天内内,,共共1199例例患患者者发发生生MMAACCEE,,占占2222..11%%,,其其中中阿阿托托伐伐他他汀汀组组66例例,,占占1133..00%%,对照组13例,占32.5%(χ2=4.706,PPP==00..003300));;阿阿托托伐伐他他汀汀组组内内PPCCII术术后后TTMMPPGG33级级的的患患者者发发生生MMAACCEE3/27例,而对照组6/14例(42.9%vs.11.1%,χ2=5.423,PPP==00..002299));;在在达达到到TTMMPPGG33级级的的患患者者,,对对照照组发生MACE的危险度大约为阿托伐他汀组的3.857倍(RR3.857,95%CI:1.131～13.149)。③随访期间,阿托伐他汀组和对照组均无肌毒性和肝毒性事件发生。结论直接PCI术前早期应用大剂量阿托伐他汀(80mg)对改善AMI冠脉微血管功能及短期预后是安全有效的。     

糖尿病调脂药物治疗的循证医学

本文重点介绍近年来糖尿病患者调脂治疗,主要包括临床常用的他汀类、贝特类、烟酸等药物降胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白-胆固醇(LDL-C)水平、升高高密度脂蛋白-胆固醇(HDL-C),以及减少心血管事件的疗效、不良反应等。     

胆固醇代谢与阿尔茨海默病关系的研究进展

在阿尔茨海默病(AD)发病机制中,占主导地位是Aβ瀑流学说:由于淀粉样前体蛋白的代谢紊乱,产生了过量的Aβ42,后者迅速聚集形成寡聚物,启动了Aβ瀑流效应,造成了Aβ的沉积,形成老年斑.越来越多的实验表明,胆固醇在Aβ的产生和异常沉积过程具有重要调节作用,同时Aβ对胆固醇调节也有反馈作用,探讨两者的相互作用和影响有助于AD发病机制的阐明.而与胆固醇代谢密切相关的因素,如载脂蛋白E、调节胆固醇代谢的药物等也成为研究的热点.     

辛伐他汀对动脉粥样硬化斑块内巨噬细胞MMP-3表达的影响

目的:观察辛伐他汀对动脉粥样硬化斑块内巨噬细胞MMP-3表达的影响.方法:在新西兰大白兔动脉粥样硬化模型基础上,分离、培养动脉粥样硬化斑块内巨噬细胞,应用免疫组化、RT-PCR及Western Blotting等方法观察辛伐他汀对巨噬细胞MMP-3表达的影响.结果:辛伐他汀能够明显抑制斑块内巨噬细胞MMP-3的表达,但对MMP-3 mRNA的表达无明显影响.结论:辛伐他汀具有独立于其系统性降脂作用之外的稳定动脉粥样硬化斑块的作用,此抑制作用可能不在基因转录水平,而是影响其后转录过程.     

他汀类药物治疗冠心病对患者血清胆红素、尿酸水平的影响

目的 探讨他汀类药物治疗冠心病对患者血清胆红素、尿酸水平的影响.方法 研究对象取自于我院2013年11月至2014年11月收治的86例冠心病患者,按随机数字表法分为对照组与观察组各43例.对照组接受常规内科治疗,观察组同时给予瑞舒伐他汀钙片.统计两组患者治疗前后血清总胆红素(TBIL)、直接胆红素(DBIL)、间接胆红素(IBIL)及尿酸(UA)水平,观察心绞痛、心力衰竭、脑卒中等心血管不良事件发生情况.结果 治疗后,观察组TBIL[(15.63±2.52)μmol/L]、DBIL[(6.55±1.24)μmol/L]、IBIL[(8.96±1.86)μmol/L]及UA[(377.72±67.52)μmol/L]均优于对照组(P＜0.05).较对照组,观察组心绞痛等心血管不良事件发生率低,两组比较差异有统计学意义(P＜0.05).结论 他汀类药物治疗冠心病能有效提升患者血清胆红素,降低尿酸水平,对预防各类心血管不良事件发生有积极影响,适合于临床推广.     

Effect of concomitant use of pitavastatin with neoadjuvant chemotherapy protocols in breast cancer patients: A randomized controlled clinical trial

IntroductionPreclinical studies have demonstrated the possible anticancer effects of statins, but the synergistic effect of concomitant statin use with standard chemotherapy protocols in patients with breast cancer has not yet been investigated.AimThe current study aimed to evaluate the efficacy of concomitant pitavastatin use with neoadjuvant chemotherapy protocols in patients with breast cancer.MethodsThis study was a randomized controlled clinical trial. A total of 70 adult female patients with pathologically-proven invasive breast cancer were randomized to receive or not receive pitavastatin (2 mg) oral tablets once daily concomitantly with standard neoadjuvant chemotherapy protocols for 6 months. The primary outcomes of this study were changes in tumor size and changes to the Ki67 index. In addition, secondary outcomes were changes in cyclin D1 and cleaved caspase-3 serum levels. This study was registered at ClinicalTrials.gov (Identifier: NCT04705909).ResultsPatients in the pitavastatin group showed significantly higher median (IQR) reductions in tumor size [?19.8 (?41.5, 9.5)] compared to those in the control group [?5.0 (?15.5, 0.0), p = 0.0009]. The change in Ki67 from baseline to the end of therapy was similar between the two groups (p = 0.12). By the end of therapy, the cyclin D1 levels in the pitavastatin group were significantly decreased [median (IQR) change of ? 10.0 (?20.2, ?2.9) from baseline], whereas the control group showed an increase in cyclin D1 levels [14.8 (4.1, 56.4)]. The median (IQR) caspase?3 was elevated in the pitavastatin group 1.6 (0.2, 2.2), and decreased in the control group (?0.2 (?1.1, 0.0), p = 0.0002).Subgroup analysis of the pitavastatin group revealed that patients with positive human epidermal growth receptor 2 (HER2) had higher median (IQR) reductions in Ki67 [?35.0 (?70.0, ?12.5)] than those with negative HER2 [2.5 (?15.0, 10.0), p = 0.04]. All patients who achieved a complete pathological response (n = 9) exhibited an HER2-neu positive receptor at baseline.ConclusionConcomitant use of pitavastatin with standard neoadjuvant chemotherapy protocols may improve neoadjuvant chemotherapy responses in patients with breast cancer.     

他汀类药物对维持性血液透析患者生存预后的影响

目的　探讨他汀类药物对维持性血液透析（MHD）患者生存预后的影响。方法　回顾性研究。以2012年6月至2015年6月在徐州医科大学附属连云港医院血液透析中心接受MHD治疗的186例终末期肾病（ESRD）患者作为研究对象,男性114例、女性72例、年龄18～85岁,将入组前及随访期间连续3个月使用他汀类药物治疗的患者作为他汀组（48例）,未使用他汀类药物治疗的患者作为非他汀组（138例）。收集患者一般资料,随访截止至2020年6月30日,记录患者临床结局。计量资料采用独立样本t检验,计数资料采用χ²检验或Fisher确切概率法,生存率采用Kaplan-Meier生存分析,采用COX回归模型分析MHD患者生存预后的影响因素。结果　与非他汀组比较,他汀组患者透析前收缩压（SBP）高、透析年份短、每周促红细胞生成剂使用剂量低、左心室射血分数（LVEF）大、白蛋白（Alb）水平高、总胆固醇（TC）和三酰甘油（TG）水平低、C反应蛋白（CRP）水平低（均P<0.05）;与非他汀组比较,他汀组患者病死率低、因心血管疾病死亡比例低、3年和5年存活率高（均P<0.05）。年龄、体质量指数（BMI）、透析前SBP、透析年份、透析时间、心胸比率、LVEF、血红蛋白（Hb）、血清铁蛋白、Alb、甲状旁腺素（PTH）、尿素氮（BUN）、肌酐（Cr）、TC、TG、CRP及磷结合剂、碳酸钙、碳酸镧、司维拉姆、西那卡塞、维生素D、他汀类药物使用为MHD患者生存预后的影响因素（均P<0.05）;校正其他因素对MHD患者生存预后的影响,显示他汀类药物使用可显著降低MHD患者死亡风险（HR：0.56,95%CI：0.51～0.59;P=0.017）。结论　他汀类药物具有较好的抗炎作用,降低每周促红细胞生成剂使用剂量、心血管事件发生率,并可显著提高MHD患者3年和5年存活率,降低死亡风险,有临床应用价值。     

不同剂量他汀类药物对冠心病并发高脂血症患者的血脂及血管内皮功能的影响

①目的探讨不同剂量他汀类药物对冠心病并发高脂血症患者的血脂及血管内皮功能的影响。②方法选择冠心病并发高脂血症患者200例，随机分为4组，分别服用辛伐他汀10mg、20mg；阿托伐他汀10mg、20mg，4周后分别检测血脂水平、血管内皮功能的变化。③结果辛伐他汀、阿托伐他汀治疗4周后，可有效降低冠心病并发高脂血症患者的TC、TG、LDL-c水平，并改善血管内皮功能（NO升高，ET水平降低），差异具有显著性，在同种药物中20mg组优于10mg组，差异显著（P〈0．05）。④结论阿托伐他汀、辛伐他汀通过有效降低冠心病并发高脂血症患者的TC、TG、LDL—c水平，改善血管内皮功能，而且与剂量有关。