Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Centre, Quebec, Canada.
Clin J Am Soc Nephrol. 2010 Feb;5(2):335-40. doi: 10.2215/CJN.06300909. Epub 2010 Jan 7.
Cardiovascular events are the dominant cause of death in patients with ESRD. Until recently, plaque rupture due to atherogenic dyslipoproteinemias was presumed to be a major mechanism of cardiovascular events in dialysis patients. But how reasonable was that hypothesis and was it entirely discredited by the results of 4D and AURORA? This article places the conventional lipids-cholesterol and triglyceride-within the more physiologic framework of the apoB lipoproteins. Viewed from the perspective of atherogenic particle number, the failure of statins to lower cardiovascular mortality in hemodialysis patients versus the continuing potential for success in peritoneal dialysis patients becomes comprehensible. In the former, apoB is characteristically not elevated and therefore apoB-lowering therapy can have only limited effect; in the latter, apoB is characteristically high and therefore apoB-lowering therapy might have considerable clinical benefit. Nevertheless, plaque rupture is only one mechanism leading to cardiac death. In addition to those previously noted, a new mechanism is suggested for consideration-recurrent reperfusion injury. The coronaries of dialysis patients are often narrowed, the microcirculation underdeveloped, and the left ventricle hypertrophied-all of these plus transient hypotension could produce severe ischemia followed by reperfusion necrosis. The minor but common elevations of troponin that are so well known yet widely disregarded may be markers of an adverse sequence of events that could each trigger a fatal arrhythmia and tend to reduce left ventricular function. Thus sudden death due to arrhythmia and slow progressive death due to heart failure could be manifestations of reperfusion injury.
心血管事件是终末期肾病（ESRD）患者死亡的主要原因。直到最近，由于致动脉粥样硬化的血脂异常导致斑块破裂，被认为是透析患者心血管事件的主要机制。但是这个假设合理吗？4D 和 AURORA 的结果是否完全否定了它？本文将传统脂质——胆固醇和甘油三酯——置于载脂蛋白 B 脂蛋白更生理的框架内。从致动脉粥样硬化颗粒数的角度来看，他汀类药物未能降低血液透析患者的心血管死亡率，而腹膜透析患者仍有继续成功的潜力，这变得可以理解。在前者中，载脂蛋白 B 通常不升高，因此载脂蛋白 B 降低治疗的效果可能有限；在后者中，载脂蛋白 B 通常升高，因此载脂蛋白 B 降低治疗可能具有相当大的临床益处。然而，斑块破裂只是导致心脏死亡的一种机制。除了前面提到的那些，还提出了一种新的机制来考虑——反复再灌注损伤。透析患者的冠状动脉往往变窄，微循环发育不良，左心室肥大——所有这些加上短暂的低血压都会导致严重的缺血，随后发生再灌注坏死。众所周知但被广泛忽视的肌钙蛋白的轻微但常见升高可能是不良事件序列的标志物，每个事件都可能引发致命性心律失常，并倾向于降低左心室功能。因此，心律失常引起的猝死和心力衰竭引起的缓慢进行性死亡可能是再灌注损伤的表现。
