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首页> 外文期刊>Current opinion in lipidology >Fibrates, dyslipoproteinaemia and cardiovascular disease.
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Fibrates, dyslipoproteinaemia and cardiovascular disease.

机译：纤维蛋白，血脂蛋白异常和心血管疾病。

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Recent epidemiological data have reaffirmed that elevated plasma triglyceride and low HDL-cholesterol levels are important risk factors for atherosclerotic vascular disease. The rationale for the clinical use of fibric acid derivatives, which are designed to correct this metabolic nexus, is now on firmer ground. The mechanism of action of fibrates on lipoprotein metabolism has recently been elucidated at the molecular level and involves the activation of peroxisome proliferator-activated receptor-alpha 1 in the liver, with the net effect of improving the plasma transport rates of several lipoproteins. Other potential anti-atherothrombotic effects include the inhibition of coagulation and enhancement of fibrinolysis, as well as the inhibition of inflammatory mediators involved in atherogenesis. These consequences probably underpin the favourable effects of fibrates seen in recent angiographic and clinical trials. Two important clinical trials on the effect of gemfibrozil (Veterans Administration-HDL-Cholesterol Intervention Trial) and bezafibrate (Bezafibrate Infarction Prevention Study) have recently been completed in subjects with elevated triglyceride, low HDL and normal or near-normal LDL-cholesterol levels. The results testify to the efficacy of these agents in decreasing the incidence of cardiovascular events, particularly in patients with multiple risk factors and plasma triglyceride levels of over 2.2 mmol/l. The findings of these trials are compared with the statin-based Air Force/Texas Coronary Atherosclerosis Prevention Study, with a recommendation that future studies in appropriately selected patients should examine the synergistic effect of the fibrate/statin combination. The absolute risk reduction in the incidence of coronary events in the Veterans Administration-HDL-Cholesterol Intervention Trial compares favourably with the statin trials. The therapeutic aspects of the efficacy and safety of fibrates are reviewed. Besides primary mixed hyperlipidaemias, particular indications for the clinical use of fibrates include type 2 diabetes, the metabolic syndrome and renal insufficiency. The St Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention Study has suggested that fibrates may decrease the incidence of coronary events in type 2 diabetes, but this hypothesis will be more extensively tested in the Diabetes Atherosclerosis Intervention Study, Fenofibrate in Event Lowering in Diabetes Study and Lipids in Diabetes Study projects. Although significant new knowledge has accrued over the past few years concerning the fundamental and clinical aspects of fibrates, the success of these agents in clinical practice depends on the availability of methods for assessing cardiovascular risk as well as on treatment guidelines, which as presently designed and recommended may be inaccurate and suboptimal.
机译：最近的流行病学数据再次证实，血浆甘油三酸酯升高和HDL-胆固醇水平低是动脉粥样硬化性血管疾病的重要危险因素。旨在纠正这种代谢联系的纤维状酸衍生物的临床使用的理论基础现已站稳脚跟。贝特类药物对脂蛋白代谢的作用机理最近已在分子水平上阐明，涉及肝脏中过氧化物酶体增殖物激活受体α1的活化，其净效应是改善了几种脂蛋白的血浆转运速率。其他潜在的抗动脉血栓形成作用包括抑制凝血和增强纤维蛋白溶解，以及抑制参与动脉粥样硬化的炎症介质。这些后果可能巩固了近期血管造影和临床试验中观察到的贝特类药物的有利作用。最近，在甘油三酸酯升高，HDL偏低且LDL-胆固醇水平正常或接近正常的受试者中，完成了关于吉非贝齐（退伍军人管理局-HDL-胆固醇干预试验）和苯扎贝特（苯扎贝特脑梗塞预防研究）作用的两项重要临床试验。结果证明了这些药物在降低心血管事件发生率方面的功效，特别是在具有多种危险因素且血浆甘油三酯水平超过2.2 mmol / l的患者中。将这些试验的结果与基于他汀类药物的空军/得克萨斯州冠状动脉粥样硬化预防研究进行了比较，并建议在适当选择的患者中进行进一步研究，以检查贝特类药物/他汀类药物联合治疗的协同作用。退伍军人管理局-HDL-胆固醇干预试验中，冠心病事件发生率的绝对风险降低与他汀类药物试验相比具有优势。综述了贝特类药物疗效和安全性的治疗方面。除了原发性混合性高脂血症以外，贝特类药物在临床上的特殊适应症还包括2型糖尿病，代谢综合征和肾功能不全。圣玛丽，伊灵，诺斯威克公园糖尿病心血管疾病预防研究表明，贝特类药物可能会降低2型糖尿病中冠状动脉事件的发生率，但该假说将在糖尿病动脉粥样硬化干预研究（非诺贝特在降低糖尿病事件中的作用）中得到更广泛的检验。研究和糖尿病研究中的脂质。尽管在过去的几年中积累了有关贝特类药物基本和临床方面的重要新知识，但是这些药物在临床实践中的成功取决于评估心血管风险的方法的可用性以及目前设计和治疗的指导原则。推荐的可能不正确且不理想。

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