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首页> 外文期刊>Circulation research: a journal of the American Heart Association >From Lipids to Inflammation New Approaches to Reducing Atherosclerotic Risk
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From Lipids to Inflammation New Approaches to Reducing Atherosclerotic Risk

机译:从脂质到炎症降低动脉粥样硬化风险的新方法

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The introduction of statins approximate to 30 years ago ushered in the era of lipid lowering as the most effective way to reduce risk of atherosclerotic cardiovascular disease. Nonetheless, residual risk remains high, and statin intolerance is frequently encountered in clinical practice. After a long dry period, the field of therapeutics targeted to lipids and atherosclerosis has entered a renaissance. Moreover, the demonstration of clinical benefits from the addition of ezetimibe to statin therapy in subjects with acute coronary syndromes has renewed the enthusiasm for the cholesterol hypothesis and the hope that additional agents that lower low-density lipoprotein will decrease risk of atherosclerotic cardiovascular disease. Drugs in the orphan disease category are now available for patients with the most extreme hypercholesterolemia. Furthermore, discovery and rapid translation of a novel biological pathway has given rise to a new class of cholesterol-lowering drugs, the proprotein convertase subtilisin kexin-9 inhibitors. Trials of niacin added to statin have failed to demonstrate cardiac benefits, and 3 cholesterol ester transfer protein inhibitors have also failed to reduce atherosclerotic cardiovascular disease risk, despite producing substantial increases in HDL levels. Although the utility of triglyceride-lowering therapies remains uncertain, 2 large clinical trials are testing the influence of omega-3 polyunsaturated fatty acids on atherosclerotic events in hypertriglyceridemia. Novel antisense therapies targeting apolipoprotein C-III (for triglyceride reduction) and apo(a) (for lipoprotein(a) reduction) are showing a promising trajectory. Finally, 2 large clinical trials are formally putting the inflammatory hypothesis of atherosclerosis to the test and may open a new avenue for cardiovascular disease risk reduction.
机译:大约30年前,他汀类药物的引入迎来了降脂时代,这是降低动脉粥样硬化性心血管疾病风险的最有效方法。尽管如此,残留风险仍然很高,他汀类药物的耐受性在临床实践中经常遇到。经过长时间的干燥,针对脂质和动脉粥样硬化的治疗领域开始复兴。此外,在急性冠脉综合征患者中,在他汀类药物治疗中加入依折麦布可增加临床疗效,这表明人们对胆固醇假说的热情得到了重新激发,并希望降低低密度脂蛋白的其他药物能够降低动脉粥样硬化性心血管疾病的风险。现在,最极端的高胆固醇血症患者可以使用孤儿疾病类别的药物。此外,新的生物途径的发现和快速翻译产生了新的一类降低胆固醇的药物,即前蛋白转化酶枯草杆菌蛋白酶kexin-9抑制剂。他汀类药物中添加烟酸的试验未能显示出对心脏的益处,尽管增加了HDL水平,但3种胆固醇酯转移蛋白抑制剂也未能降低动脉粥样硬化性心血管疾病的风险。尽管降低甘油三酸酯疗法的效用仍不确定,但两项大型临床试验正在测试omega-3多不饱和脂肪酸对高甘油三酸酯血症中动脉粥样硬化事件的影响。针对载脂蛋白C-III(用于降低甘油三酸酯)和apo(a)(用于降低脂蛋白(a))的新型反义疗法显示出了广阔的发展前景。最终,两项大型临床试验正式将动脉粥样硬化的炎症假设付诸实践,并可能为降低心血管疾病的风险开辟新途径。

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