Trilipix——关键词：混合性血脂异常

美国FDA日前批准了雅培公司的Trilipix（fenofibric acid，非诺贝酸）缓释胶囊上市，使用该药并结合调整饮食可以降低血脂异常病人的甘油三酯、LDL（低密度脂蛋白），升高HDL（高密度脂蛋白）。Trilipix是目前第一个也是唯一一个获得批准的与他汀类药物联合使用的纤维酸衍生物，但Trilipix不能预防心脏疾病和心脏病发作。     

辛伐他汀加omega-3脂肪酸治疗冠心病及其等危症合并混合性血脂异常随机双盲对照研究

目的评价辛伐他汀与国产omega-3脂肪酸合用在冠心病及其等危症合并混合性血脂异常患者调脂治疗中的疗效和安全性。方法用随机双盲安慰剂平行对照的试验方法,冠心病及其等危症合并混合性血脂异常患者经6-12周辛伐他汀10或20mg治疗后,低密度脂蛋白胆固醇已达标(LDL-C<2.6mmol·L-1)或接近达标(LDL-C<3.4 mmol·L-1),但甘油三酯(TG)水平在2.26-5.64 mmol·L-1,加用omega-3脂肪酸每日3g或安慰剂,治疗2月,40例患者完成试验,每组患者20名。结果Omega-3脂肪酸组治疗后,TG、总胆固醇(TC)、非高密度脂蛋白胆固醇(Non-HDL-C)较基线分别显著降低1.06±O,74(31.1％),0.35±0.58(6.3％),0.44±0.58 mmol·L-1(10.4％)(P<0.05);Omega-3脂肪酸组较安慰剂组TG降低更明显(P<0.05)。加用Omega-3脂肪酸组治疗2个月后,较基线单用辛伐他汀显著增加30％的Non-HDL-C达标率(P<0.05)及25％的全面达标率(P<0.05)。Omega-3脂肪酸组TG基线值与TG下降幅度呈显著正相关(P<0.05)。两组间药物不良反应无统计学差异。结论辛伐他汀加用国产omega-3脂肪酸调脂治疗冠心病及其等危症合并混合性血脂异常患者安全、有效。     

老年人血脂异常的特点及治疗

心血管疾病是引发老年人群死亡和致残的主要因素 ,造成社会负担增加。大约 1/ 3的急性心肌梗死和 6 0 %因急性心肌梗死死亡者为≥ 75岁老年人。约 4 5 %的 80岁老年人患有心血管疾病 ,其中冠心病是最常见的心血管疾病。 5 8%的 85岁或以上老年人死于心血管疾病。同时 ,6 0岁以上男性或女性高胆固醇血症的发生率最高。因此 ,积极治疗老年人的血脂异常对冠心病的防治具有十分重要的意义。1　老年人血脂异常的特点随年龄增长 ,脂蛋白代谢发生许多改变 ,与激素水平的变化有关。儿童时期高密度脂蛋白胆固醇 (HDL C)水平通常较高 ,而低密度脂蛋…     

老年血脂异常治疗进展

老年患者较年轻人有更高的血脂异常发生率,更加需要积极治疗。与欧美人群相比,我国老年人血脂水平升高的幅度较低,以轻到中度为主。RCT研究发现,他汀类药物患者的明确获益从治疗后1~2年即开始获得,其不良反应较年轻患者并未明显增加。充分使用他汀类药物后,血脂不能达标或仍出现心血管疾病事件时,可以加用一些新的降脂药物,研究显示LDL-C水平降得越低,患者越能从中获益。     

老年人血脂异常的特点及现状

心血管疾病是引发老年人群死亡和致残的主要因素，造成社会负担增加。大约1／3的急性心肌梗死和60％因急性心肌梗死死亡者为≥75岁老年人。约40％的80岁老年人患有心血管疾病，其中冠心病是最常见的心血管疾病。58％的85岁或以上老年人死于心血管疾病。同时，60岁以上男性或女性高胆固醇血症的发生率最高。因此，强调积极治疗老年人的血脂异常对冠心病的防治具有十分重要的意义。     

辛伐他汀加用Omega-3脂肪酸对混合性血脂异常患者高敏C反应蛋白、血脂及纤溶的影响

目的:评价辛伐他汀加用Omega-3脂肪酸对冠心病及冠心病等危症合并混合性血脂异常患者高敏C反应蛋白(HsCRP)、血脂及纤溶的影响.方法:采用随机、双盲、安慰剂平行对照方法,40例冠心病及冠心病等危症合并混合性血脂异常患者经6～12周辛伐他汀10mg或20mg治疗后,分为试验组(n=20)和对照组(n=20),分别加用Omega-3脂肪酸3g*d-1或安慰剂,治疗2个月,观察治疗前后对HsCRP、血脂及纤溶的影响.结果:试验组治疗后HsCRP、三酰甘油(TG)、总胆固醇(TC)、TC/高密度脂蛋白胆固醇(HDL-C)较基线分别降低(2.16±2.77)(38.5%),(94.0±65.4)(31.1%),(13.3±22.3)mmol*L-1(6.3%)和(0.78±1.60)mg*dL-1(P分别<0.01,<0.001,<0.05,<0.05),对照组HsCRP及TG降低更为显著(P分别为0.021及0.011).试验组TG降低的数值及百分数分别与HsCRP降低的数值及百分数呈显著正相关(r分别为0.51和0.45,P分别为0.021和0.047).结论:辛伐他汀加用Omega-3脂肪酸增加二者的调脂优势和非调脂优势.     

血脂异常的药物治疗进展与临床评价

血脂异常是引起动脉粥样硬化( AS)与冠心病( CHD)最为重要的危险因素.近年来,有关脂蛋白的研究明确显示,低密度脂蛋白胆固醇( LDL- C)的增加可促进 AS[1]的发生,血清高密度脂蛋白胆固醇( HDL- C)的增加则可防止 AS[2]的发生.一系列前瞻性临床试验结果表明,应用调脂药物降低血清总胆固醇( TC)、 LDL- C和升高 HDL- C水平的同时,可显著降低 AS与 CHD的发生率和患者死亡率 [3～ 5],因此,调脂药物的应用得到了较为广泛的认可与重视,相关研究也发展迅速,大批新药相继开发上市.现就其进展与临床评价综述如下.     

血脂异常及其治疗简述

血脂过高，造成脂质代谢紊乱，血液粘稠度增高，脂类物质在血管壁内膜沉积，久而久之导致冠心病、心肌梗死、心绞痛、脑血栓、脑溢血、中风等多种疾病。因此，及时调解血脂异常，是防止心脑血管疾病的发生并降低其病死率的首要措施。     

自拟降脂系列水丸治疗血脂异常65例临床观察

目的观察中药治疗高脂血症的临床效果。方法将115例高血脂症病人随机分为对照组50例和治疗组65例。对照组选择社区较常用药品辛伐他汀治疗。治疗组在辨证论治的基础上选择适当方药。观察2组患者治疗前后血脂指标血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL—C）、高密度脂蛋白（HDL—C）的变化。结果治疗后2组的TC、TG、LDL—C均明显下降,与治疗前相比,差异均有显著性意义（P〈0．01）。2组的HDL—C也显著上升与治疗前相比,差异均有显著性意义（P〈0．01）。治疗后治疗组总有效率为90．8％,对照组为82％,2组总有效率比较,差异均有显著性意义（P〈0．05）。结论在中医辨证论治基础上运用中药治疗高脂血症能增强临床疗效,适合在推广应用。     

Management of dyslipidemia in the metabolic syndrome

The metabolic syndrome consists of a clustering of metabolic derangements that cause the affected individual to have an increased risk for developing cardiovascular disease. Dyslipidemia is an important component of the metabolic syndrome and is included in all the definitions of the metabolic syndrome published by different international committees to identify individuals with the metabolic syndrome. Atherogenic dyslipidemia in the metabolic syndrome comprises of hypertriglyceridemia, low levels of high-density lipoprotein cholesterol and a preponderance of small dense low-density lipoprotein particles. The pathogenesis of dyslipidemia in the metabolic syndrome will be reviewed and the roles of therapeutic lifestyle modification and drug therapies in the treatment of dyslipidemia will be discussed.     

Management of dyslipidemia in patients with metabolic syndrome.

OBJECTIVE: To review the management of dyslipidemia in patients with metabolic syndrome. DATA SOURCES: Medline search (2000-2002) conducted for English language articles using the search terms metabolic syndrome, impaired fasting glucose, glucose intolerance, and antilipemic agents; selective search for clinical trials of lipid therapy conducted in dialogue databases (1990-2002). In addition, current dyslipidemia treatment guidelines reviewed. STUDY SELECTION: By the author. DATA EXTRACTION: By the author. DATA SYNTHESIS: The metabolic syndrome is increasingly recognized as a strong predictor of patient risk for developing coronary artery disease (CAD). It is associated with an atherogenic dyslipidemia characterized by elevated levels of triglycerides, reduced levels of high-density lipoprotein cholesterol (HDL-C) and a preponderance of small dense low-density lipoprotein (LDL) particles. Controlled clinical trials show similar or greater cardiovascular benefits from lipid-modifying therapies in patient subgroups with diabetes, impaired fasting glucose, and metabolic syndrome, compared with overall study populations. Current guidelines recommend intensified lipid management. Therapeutic lifestyle changes, with emphasis on weight loss, are particularly important for patients with metabolic syndrome. Statins are first-line therapy for all patients whose LDL-C levels are above goal. Combination therapy may often be necessary to control all lipid abnormalities adequately. Both niacin and fibrates provide additional benefits, particularly on triglyceride and HDL-C levels. Recent clinical studies show that these agents, in combination with statins, are safe and effective for the treatment of atherogenic dyslipidemia. CONCLUSION: Atherogenic dyslipidemia represents an important modifiable CAD risk factor. Combination therapy with agents that focus on all of the components of the mixed dyslipidemia that often occurs in persons with diabetes and the metabolic syndrome may be expected to reduce cardiovascular morbidity and mortality.     

Hemostatic effects of fenofibrate in patients with mixed dyslipidemia and impaired fasting glucose

Our study aimed to compare the effect of fenofibrate on hemostasis between patients with isolated impaired fasting glucose (IFG) and isolated mixed dyslipidemia and to examine the action of this agent on glucose and lipid metabolism. Twenty-two IFG and 23 mixed dyslipidemic patients were treated for 90 days with micronized fenofibrate (267 mg/day) and were compared with 22 age-, sex- and weight-matched control subjects without lipid and glucose metabolism abnormalities. The lipid profile, fasting and 2-h post-glucose challenge glucose levels, HOMA and glycated hemoglobin as well as the plasma levels/activities of fibrinogen, factor VII and PAI-1 were determined at the beginning and after 30 and 90 days of treatment. Compared to the control subjects, mixed dyslipidemic and IFG patients exhibited increased plasma levels of fibrinogen and PAI-1 as well as increased factor VII activity. Fibrinogen, factor VII and PAI-1 were higher in mixed dyslipidemic than IFG subjects. Not only did fenofibrate improve plasma lipids, but it also increased glucose sensitivity and normalized the IFG- and mixed dyslipidemia-induced changes in coagulation and fibrinolysis. Our study shows that IFG is associated with abnormal hemostasis, which is disturbed to a lesser extent in IFG than in mixed dyslipidemia. Fenofibrate seems to produce a complex beneficial effect on hemostasis in this group of patients.     

An overview of rosuvastatin/ezetimibe association for the treatment of hypercholesterolemia and mixed dyslipidemia

ABSTRACT

Introduction

Although statin therapy is a powerful lipid-lowering strategy, only one-fifth of statin users currently reach their lipid goals. In addition, statin treatment alone has relatively low efficacy in reducing other lipid fractions than low-density lipoprotein-cholesterol (LDL-C). In such cases, most guidelines recommend adding the cholesterol absorption inhibitor ezetimibe.     

阿托伐他汀对2型糖尿病合并混合性血脂异常的治疗作用观察

目的观察阿托伐他汀对2型糖尿病合并混合性血脂异常的改善作用。方法应用阿托伐他汀对39例2型糖尿病合并混合性血脂异常患者进行为期6个月的治疗，观察治疗前后总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）的变化及不良反应。结果治疗前后TG、TC、LDL-C较治疗前显著降低，降低程度分别为26．17％、54．97％、38．92％；HDL-C治疗后明显上升，上升幅度为14．81％，治疗前后比较，P〈0．01。无明显不良反应发生。结论阿托伐他汀对2型糖尿病合并混合性血脂异常有明显改善作用，安全性较好。     

Metabolic and monocyte-suppressing actions of fenofibrate in patients with mixed dyslipidemia and early glucose metabolism disturbances

The aim of this study was to compare the action of fenofibrate on monocyte cytokine release between patients with isolated mixed dyslipidemia and dyslipidemia coexisting with prediabetic states in relationship with its metabolic actions. We compared 96 primary mixed dyslipidemic patients and 29 age-, sex- and weight-matched control subjects with normal lipid profile. Depending on glucose metabolism, dyslipidemic patients were allocated into one of three treatment groups: isolated dyslipidemia, dyslipidemia coexisting with impaired fasting glucose (IFG) and dyslipidemia coexisting with impaired glucose tolerance (IGT). Lipid profile, fasting and 2-h post-glucose load plasma glucose levels, HOMA and monocyte release of interleukin-1β and MCP-1 were assessed at baseline and after 30 and 90 days of micronized fenofibrate treatment (267 mg/daily). Compared to monocytes from control subjects, monocytes of dyslipidemic patients released a greater amounts of interleukin-1β and MCP-1. MCP-1 release was higher in the IFG group than in the remaining groups of dyslipidemic patients. In all groups of dyslipidemic patients, micronized fenofibrate reduced monocyte release of interleukin-1β and MCP-1, and this effect was stronger in prediabetic subjects. Fenofibrate treatment also decreased HOMA in IFG and IGT patients, fasting plasma glucose in IFG subjects and 2-h post-glucose load plasma glucose in IGT patients. The observed differences between the studied groups regarding fenofibrate action on glucose homeostasis and cytokine release suggest that fibrate therapy may bring particular benefits to persons with metabolic syndrome.     

The role of a new formulation of fenofibric acid in the treatment of mixed dyslipidemia in type 2 diabetes

Diabetes, due to its multifactorial effects, increases the risk of developing cardiovascular disease. Dyslipidemia is an important modifiable risk factor. Mixed dyslipidemia (low high-density lipoprotein cholesterol [HDL-C], elevated triglycerides and a high percentage of small, dense lowdensity lipoprotein cholesterol [LDL-C]) is a common lipid disorder in diabetics and is considered especially atherogenic. Research suggests that in patients with dyslipidemia, combination therapy with fibrates and statins may be more effective than statin monotherapy alone. The choline salt of fenofibric acid (choline fibrate) is indicated for the treatment of mixed dyslipidemia, either as a single treatment or in combination with statin therapy. It does not require first-pass metabolism, but dissociates in the gastrointestinal tract into the pharmacologically active fenofibric acid. This new formulation of fenofibric acid in combination with a low or moderate dose of statin has been shown to be effective in increasing HDL-C and lowering triglycerides beyond that provided by statin monotherapy alone. The ACCORD trial failed to show a mortality or morbidity benefit after combination therapy, although the data suggested that combination therapy may benefit patients with mixed dyslipidemia.     

Effect of monthly atorvastatin and fenofibrate treatment on monocyte chemoattractant protein-1 release in patients with primary mixed dyslipidemia

The aim of this study was to compare the effect of 30-day treatment with atorvastatin and fenofibrate on monocyte release and plasma levels of monocyte chemoattractant protein-1 (MCP-1). We studied 52 atherosclerotic patients with primary mixed dyslipidemia and 16 age-, sex-, and weight-matched control subjects with asymptomatic atherosclerosis. Dyslipidemic patients enrolled into the study were randomly divided into three groups, simultaneously treated with atorvastatin (20 mg/d, n = 18), fenofibrate (267 mg/d, n = 16), or placebo (n = 18). Plasma lipid-profile and content of MCP-1, and monocyte release of this chemokine were measured at baseline and after 30 days of therapy. Compared with the control subjects, dyslipidemic patients exhibited the increased plasma levels and monocyte MCP-1 release. Atorvastatin and fenofibrate not only improved lipid profile but also decreased monocyte secretion of this chemokine. Moreover, hypolipemic agents slightly reduced its plasma levels. MCP-1-lowering effect of atorvastatin and fenofibrate did not correlate with the lipid-lowering potential of these agents. Our results suggest that atorvastatin and fenofibrate produce their antiinflammatory effect partially via inhibiting monocyte release of MCP-1. The treatment-induced reduction in its secretion may contribute to the clinical effectiveness of statins and fibrates in the therapy for atherosclerosis and other chronic fibroproliferative diseases.