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[ACC2009]Steven Nissen教授与何奔教授对话血脂异常的研究进展
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国际循环 时间:2009/4/21 16:48:00  关键字:血脂异常 Steven Nissen 何奔 

International Circulation: I am here at ACC 2009 with Dr. Steven Nissen and Dr. He Ben, thank you for joining us today. First I would like to talk a little bit about lipids. Patients with diabetes have some special lipid abnormalities with triglycerides and low HDLC as their main characteristics. Can you give us some advice on lipid lowering treatments in patients with diabetes especially when the LDLC has reached the target level and the low HDLC is the main abnormality?《国际循环》:我现在是在2009年ACC会议现场,与我在一起的是Steven Nissen博士和He Ben博士,感谢二位接受我们今天的采访。首先我想先说一下血脂。糖尿病患者血脂会出现以甘油三酯和HDL降低为主要特征的异常情况。对于以LDL正常但HDL偏低为主要异常的糖尿病患者,您能给我们一些治疗建议吗?

Prof. Nissen:
This is a controversial area. It is important to understand that all of the data support that the primary target always has to be use of statins and use of statins to lower LDLC but frankly the benefits appear to extend even across patients who start with an LDL that’s in the normal range. So it is statins first.  It is not at all clear that treating triglycerides actually confers benefits. You know fibric acid drugs like fenofibrate have been around since 1974 and yet there’s no outcome data to suggest that they improve outcomes in any cardiovascular disease. Now, we may get that data later this year from the ACCORD trial which is studying fenofibrate in diabetics. With respect to HDL rising, again the data is more limited than one would like.  However most people, myself included, will treat a low in diabetic patients if possible.  Really the only affective drug is niacin and it is hard to use because of the flushing but if one is patient and gradually up titrates the dose, getting up to a full therapeutic dose is possible. Sometimes it takes four to six months, and once you get there the HDL is often 20% or more higher. One more therapy and I am not sure if this is used commonly in China or not, is Omega-3 fatty acids which are very effective in lowering triglycerides and will raise HDL at least a little bit and appear to be very safe. Pending further data, I still think the primary target is to give statins in full therapeutic doses.  It reduces LDLC and higher doses appear to be better than lower doses. 
Nissen教授:这是一个有争议的话题。所有的数据都支持的主要目标是使用他汀类药物,用他汀类药物来降低LDL,但是坦白说,由于有一些患者开始时LDL是正常的,因此获益看起来被扩大了,理解这一点很重要。那么是否首选他汀类药物呢?在治疗甘油三酯上是否也能获益更多还并不明确。你知道氯贝丁酸类药物比如非诺贝特在1974年就被广泛使用了,但是没有数据显示它们能改善心血管疾病的结局。可能在今年晚些时候我们能从ACCORD试验中得到一些数据,这个试验是研究是有关糖尿病患者非诺贝特的使用。关于HDL升高的数据也较为有限。然而如果可能的话,大多数人,包括我自己在内,会对HDL低的糖尿病患者进行治疗。事实上唯一有影响的药物是烟酸,但它使用起来比较困难,因为患者可能会发生潮红。但是如果患者通过逐渐加药还是可能把剂量调整至靶剂量的。有时候这要花4至6个月的时间,但是一旦用药达到靶剂量时,HDL会常常会升高20%或更多。还有一种治疗方法是使用Omega-3脂肪酸,它在降低甘油三酯和至少少量升高HDL上是非常安全有效的,我不太肯定是否在中国也经常使用。虽然未来的数据还不确定,但我还是认为主要目标仍然是使用充分剂量的他汀类药物。它能降低LDL,而且高剂量效果看起来比低剂量更好。

International Circulation: Professor He, what about the therapy that Dr. Nissen just mentioned with the omega-3?  Is that therapy used in China?
《国际循环》:何教授,您对Nissen刚才谈到了使用omega-3的治疗方法有什么看法呢?在中国使用这种治疗方法吗?

Prof. He:  Yes it is used but not as a medicine. Omega-3 is maybe used nutritionally.
何奔教授:是的,在中国也使用,但不是作为药品。omega-3可能是作为营养品被使用的。

Prof. Nissen: In the US we have a brand name highly concentrated form of omega-3 that is now used as a pharmaceutical, it is actually a prescription drug and it is really quite effective at lowering triglycerides.
Nissen教授:在美国我们有一种商品是高浓缩形式的omega-3,现在是作为药物来使用的,实际上它是一种处方药,降低甘油三酯的效果非常好。

Prof. He:  Is this used to reduce the LDL?
何奔教授:它是否也用来降低LDL呢?

Prof. Nissen: No, it does not lower LDL but it does reduce the triglycerides quite effectively, up to 40%.
Nissen教授:不,它不能降低LDL,但是它能非常有效地降低甘油三酯,能达到40%以上。

International Circulation:  Some studies related to increasing HDLC against atherosclerosis and reducing cardiovascular and cerebral vascular events have not really gotten promising results.  What could be the possible negative reasons in some of these clinical trials and does this mean that HDLC is not a target for reducing cardiovascular events?
《国际循环》:有些与升高HDL,降低心脑血管病事件相关的试验并没有得到有希望的结果。导致这些临床试验出现这一结果的可能的负面是什么呢?这是否意味着HDL不是降低心血管事件的目标?

Prof. Nissen: Well I gave a lecture at this meeting where I said that I thought it was a valuable target and I think we have not come up with the right therapy yet.  Some of the trials have failed like the Torcetrapib study but it failed not because raising HDL is not beneficial but because the drug had an off target toxicity.  It was increasing aldosterone which is a very adverse side effect.  There are other CETP inhibitors in development which do not have that off target toxicity.  I think they have a very good chance of working.  It has been a hard target for the pharmaceutical industry to find the right drug but sooner or later we will find the right drug and I think when we do, this will have major incremental benefits.
Nissen教授:我在这次会议中有一个讲座,在讲座中我说过,这是一个有价值的目标,只是我认为我们还没有提出正确的治疗。有些试验失败了,比如Torcetrapib试验,但它失败的原因不是因为升高HDL没有获益,而是因为药物有目标以外的毒性。它的不良副作用是会增加醛固酮的产生。还有其他没有目标以外毒性的胆固醇酯转移酶抑制剂正在开发中。我认为它们有效的机会很大。制药工业要找到合适的药物非常艰难,但是我们迟早会找到合适的药物。我想,当我们找到时,将会带来很多好处。

International Circulation: 
Can you give us a little bit of your view on this, what Doctor Nissen just mentioned and do you have anything you would like to add on that?
《国际循环》:能在这方面给我们一些您的见解吗?对Nissen博士刚才提到的内容您有什么要补充的吗?

Professor He:  Yes I fully agree with Professor Nissen, I believe that sooner or later we will find the right drugs because of that right now we don’t have any evidence for any drugs that increase HDL that have proved to benefit people with coronary disease. 
何奔教授:我很赞同Nissen的观点,我相信迟早我们会找到合适的药物,但现在我们还没有证据能证明升高HDL对冠状动脉疾病的患者是有益的。

International Circulation:  What about the role of the JUPITER trial in the primary prevention of cardiovascular disease, Dr. Nissen?
《国际循环》:Nissen 博士,JUPITER试验在心脏血管疾病的一级预防中作用如何?

Prof. Nissen: Well I have a very favorable view of the study.  I thought that Dr. Ridker proposed a hypothesis, namely that people with a low LDL but a high CRP (C-reative protein) would benefit from statins and he proved his point very effectively.  A 44% reduction in the primary pre-specified

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