Professor Kerry Anne Rye 澳大利亚悉尼大学教授，悉尼心脏研究所副主任、脂质研究组主任，学术重点是高密度脂蛋白的结构和功能，对动脉粥样硬化、糖尿病和炎症反应的影响
International Circulation: As chair of the organizing committee for ISA2012， what are the aims of and what were some of the highlights of the meeting?
《国际循环》：您是ISA2012大会组织委员会主席，请问本次大会的主要目标是什么？有哪些亮点？
Prof Rye: It was really a very successful meeting and I think everyone really enjoyed it. In terms of highlights， the talks that attracted the most attention were probably the plenary lectures and particularly one talk which is a little bit out of the field for some of those who work in the atherosclerosis field， given by an immunologist， Eicke Latz， who has two labs (one in the US and another at the University of Bonn in Germany). He was talking about inflammasomes. What happens when people develop atherosclerosis is that they get cholesterol crystals deposited in their arteries in the lesions. Everyone knows that this is occurring but no one has taken any notice of it. Eicke has actually identified that these crystals form complexes with other molecules called inflammasomes and these drive inflammatory responses. So you get inflammation in the artery which worsens the situation because atherosclerosis is basically initiated as an inflammatory response. I assumed people would know about this but it attracted a lot of attention. It is applicable to other diseases also such as people who develop mesothelioma from exposure to asbestos. These people have crystalline structures deposited in their lungs and that sets up an inflammatory response. People with gout have uric acid crystals deposited in their joints setting up an inflammatory response. As it turns out， there are a lot of people in the atherosclerosis arena who are not aware of this phenomenon so it was really interesting for many of them and maybe more so than many other topics. There were other talks that were equally good and equally enlightening. There was a simpler presentation but no less interesting talk on biomarkers for determining cardiovascular disease， identifying what biomarkers are and whether they are related to the disease or just a marker of disease (i.e. there is no mechanistic relationship between the two). John Kastelein， from the Amsterdam Medical Center， spoke about agents that increased HDL levels and a great overview of the current understanding of that. It is an exciting time in that respect because these agents are in large scale clinical outcome trials. It will be a few years before we see some results. We do know that they do what they need to do， but we don’t know if they are going to reduce the number of cardiovascular deaths or not. There are some smaller trials ongoing and some have already reported and some will be reporting very soon. It is not a hard endpoint they are looking at as they are looking at the thickness of carotid artery walls and so on. So we won’t have any hard answers until the first of these large outcomes trials reports. There are two ongoing and a third due to begin during the meeting. The other topic which has underlying interest and people are just starting to talk about ， is whether there is any benefit in raising HDL for diseases other than cardiovascular disease such as diabetes. We have some evidence in vitro and in vivo that HDL actually improves beta-cell function and insulin secretion. There was a trial back in 2006 using the CETP inhibitor， torcetrapib， which did not work， but we did an analysis of a subgroup from that trial. These were people who had type 2 diabetes and what we found was that treating them with the CETP inhibitor which raises HDL levels， showed very important improvements in their glycemic control. This is really nice because there is a lot of chatter around at the moment with statins， which are the major lipid-lowering drugs used world-wide， actually causing diabetes. There is no direct evidence at present but there is still a lot of talk. There is another type of drug which raises HDL levels called niacin which is in use and looks very interesting but it too has a question mark over it. What happens in that case is that people tend to get a worsening of their diabetes when initially started on the drug but they do bounce back. So there are issues with niacin; it also has some nasty side effects which make it unpopular. There is also a very large outcomes trial discussed at the meeting using niacin called HPS2-THRIVE which will probably be the crunch-point for niacin. Niacin has been around for thirty years or so and small trials have indicated that it is effective at reducing cardiovascular deaths and disease but the size of these trials has put doubt on whether niacin should continue to be used. So if this large trial proves positive， I think niacin will have its place; but if it’s negative， I doubt niacin will survive especially if the CETP inhibitors are found to be efficacious. That will be the way that everyone will go. In the meantime we have to wait until those results are available.
Prof Rye: 这是一次非常成功的大会，我想每位参会者都获益匪浅。至于亮点，最引人注目的讲座可能是全体大会，其中特别要提到的是由Eicke Latz教授所作的演讲，他是一位免疫学专家，领导着2个实验室（一个在美国，另一个在德国波恩大学）。他演讲的内容对于动脉粥样硬化领域的医务工作者而言，与工作实践多少有些距离。他谈到了炎症组学。人类动脉粥样硬化的发生是由于胆固醇结晶沉积于病变处的动脉壁，每个人都知道这一点，但无人予以重视。Eicke阐明了这些结晶与其他分子即所谓的炎症组构成了复合物，并启动了炎症反应，在人体动脉内发生炎症，使病情进一步恶化，所以说炎症反应是动脉粥样硬化病理过程始动的基础。我想人们已经了解这一点，但这个讲座吸引了极大的关注。这一理论同样适用于其他疾病，如由于石棉暴露而导致的间皮瘤。这些患者的肺部沉积了大量结晶样结构，从而触发炎症反应。痛风患者由于尿酸结晶沉积于关节部位而引起炎症反应。正如我们看到的，许多动脉粥样硬化领域的临床医生不了解这些现象，因此这一讲座比其他主题吸引了更多的听众。还有许多其他讲座同样精彩。有一个讲座虽然相对简单，但对听众的吸引力却毫不逊色，其主题是心血管疾病的生物标志物，阐述了什么是生物标志物、以及他们与疾病有关还是仅仅只是疾病的一个标志物（即两者之间不存在机制性的关联）。来自阿姆斯特丹医学中心的John Kastelein介绍了升高HDL水平的药物以及当前人类对该领域理解的概况。这是一个令人兴奋的领域，这些药物正在接受大型临床终点试验的评估，还要等待数年我们才能看到结果；我们知道这些药物能够升高HDL水平，但我们不清楚的是他们能否减少心血管死亡。有一些较小规模的试验正在进行中，一些已经报告了结果，一些将在近期公布结果，但这些试验都不是硬终点研究，他们观察的都是颈动脉壁厚度等一些替代终点。因此，在这些大型试验公布结果之前我们还没有任何“硬”答案。会议期间有2项正在进行中和1项即将开始的试验举行报告。另一个人们刚刚开始谈论的有趣话题是，升高HDL对心血管疾病以外的疾病如糖尿病是否有益。有一些体内和体外实验证据表明，升高HDL的确可改善β细胞功能和胰岛素分泌。2006年一项试验使用了CETP抑制剂torcetrapib，结果未能奏效，但我们进行了一项2型糖尿病患者的亚组分析，发现使用能够升高HDL水平的CETP抑制剂治疗这部分患者，显著改善了其血糖控制。这是非常有利的发现，因为当前对他汀的使用存在很多的议论，他汀是全球范围内广泛使用的降脂药物，但他汀可导致糖尿病。尽管目前并无直接证据，但人们对此议论纷纷。升高HDL水平的另一种药物是烟酸，但也存在相关的问题，当开始使用烟酸时，患者存在糖尿病恶化的趋势，但随后病情又有所恢复。因此使用烟酸亦存在问题，一些不良反应限制了其广泛应用。本次大会期间还将对一项规模非常大的烟酸终点试验进行讨论，即HPS2-THRIVE，这项试验可能成为决定烟酸命运的分界点。烟酸已问世30余年，一些小型试验提示其能够有效降低心血管死亡和疾病，但试验规模过小使其是否应该继续使用受到质疑。因此，如果这项大型试验得出阳性结果，我想烟酸将仍然发挥作用；但如果为阴性结果，尤其是CETP抑制剂若被证实有效，那么我怀疑烟酸还能否继续生存下去。就目前而言，我们还必须等待这项结果的公布。
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