Eradicating the Burden of Atherosclerotic Cardiovascular Disease by Lowering Apolipoprotein B Lipoproteins Earlier in Life.
Eradicating the Burden of Atherosclerotic Cardiovascular Disease by Lowering Apolipoprotein B Lipoproteins Earlier in Life.
复制标题
通过降低载脂蛋白B脂蛋白早期，消除了动脉粥样硬化心血管疾病的负担。
DOI：
10.1161/jaha.118.009778
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发表时间：
2018-10-16
影响因子：
5.4
通讯作者：
Sniderman A
中科院分区：
文献类型：
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作者：
Robinson JG;Williams KJ;Gidding S;Borén J;Tabas I;Fisher EA;Packard C;Pencina M;Fayad ZA;Mani V;Rye KA;Nordestgaard BG;Tybjærg-Hansen A;Douglas PS;Nicholls SJ;Pagidipati N;Sniderman A
需要一种预防动脉粥样硬化性心血管疾病（ASCVD）的新模式。美国最新数据显示，心血管疾病死亡率的长期下降已经停止，并在高危人群中开始增加。1事实上，在风险因素控制不佳的情况下，肥胖和糖尿病的发病率上升，导致65岁以下人群发生的心血管事件数量与65岁以上人群相似。虽然预防性药物治疗降低了一级和二级预防患者心血管事件的相对风险，但随后ASCVD事件的绝对风险仍然很高。如果没有任何变化，预计到2035年，近一半的美国人口将患有某种形式的心血管疾病，每年的费用将增加一倍，达到1.1万亿美元。4.显然需要采取系统的办法来改善生活习惯和更好地控制危险因素。鉴于迄今为止这些努力的困难，以及当成年后开始进行风险因素修改时ASCVD的持续高负担，我们提出了一种新的ASCVD预防模式。基于下面回顾的大量数据，我们认为现在是时候研究在年轻人和中年早期人群中强化降低血浆载脂蛋白（apo）B脂蛋白水平是否会使动脉粥样硬化的早期阶段消退，从而消除在以后的生活中发生临床ASCVD事件的风险。正如了解其他疾病的病原体已经允许根除一系列人类疾病一样，这篇最新的综述将强调对动脉粥样硬化发病机制的深入了解可以转化为根除ASCVD的可实现目标。作为下一步，我们描述了一个拟议的临床试验，以测试早期干预，以深刻降低浓度的低密度脂蛋白（其胆固醇成分，LDL-C评估）和其他载脂蛋白B的脂蛋白在个人年龄25至55岁的图像记录临床前动脉粥样硬化。这样的试验可能提供第一个直接的证据来支持人类早期动脉粥样硬化的显著甚至完全消退，并为确定性试验奠定基础，以支持一种新的预防模式，即强化消退治疗，然后进行间歇性再治疗，以消除ASCVD的临床负担。
Anew paradigm for preventing atherosclerotic cardiovascular disease (ASCVD) is needed. The most recent US data show the long-term decline in cardiovascular deaths has stopped, and has started to increase in the most at-risk populations. 1 Indeed, rising rates of obesity and diabetes mellitus in the setting of suboptimal risk factor control have resulted in a similar number of cardiovascular events occurring in those aged< 65 years as≥ 65 years. 2 Although preventive drug therapies reduce the relative risk of cardiovascular events in primary and secondary prevention patients, the absolute risk of subsequent ASCVD events remains high. 3 If nothing changes, it is projected that by 2035 nearly half the US population will have some form of cardiovascular disease and costs will double to $1.1 trillion annually. 4 Systemic approaches to improving lifestyle habits and better risk factor control are clearly needed. Given the difficulty of these endeavors to date, and the persistently high burden of ASCVD when risk factor modification is started later in adulthood, we propose a new paradigm for ASCVD prevention. Based on the extensive data reviewed below, we consider that it is now time to investigate whether intensively lowering plasma apolipoprotein (apo) B lipoprotein levels in younger and early midlife adults will regress earlier stages of atherosclerosis, thereby eliminating the risk of developing clinical ASCVD events later in life. Just as an understanding of the causative agents of other diseases has allowed the eradication of a range of human scourges, this state-of-the-art review will emphasize that a deep understanding of the pathogenesis of atherosclerosis can be translated into an achievable goal of eradicating ASCVD. As a next step, we describe a proposed clinical trial to test early intervention to profoundly lower the concentration of low-density lipoprotein (assessed by its cholesterol component, LDL-C) and other apo B-containing lipoprotein in individuals aged 25 to 55years who have imagedocumented preclinical atherosclerosis. Such a trial may provide the first direct evidence to support marked or even complete regression of early atherosclerosis in humans, and lay the ground work for definitive trials to support a new prevention paradigm of intensive regression therapy followed by intermittent retreatment for eradication of the clinical burden of ASCVD.