[ESH2007]ESH/ESC高血压防治指南2007版解读——Laurent教授接受国际循环记者采访
<International Circulation>: Thank you, Prof. Laurent. I represent International Circulation. Very glad to meet you and thank you very much to give us your interview. My first question is: From the meta-regression analysis, you and other researchers demonstrated the blood pressure lowering is the key in cardiovascualr prevention, not special properties of anti-hypertensive agents. Does it mean that over and beyond blood pressure lowering effects of anti-hypertensive agents isn’t very important as those other classes of anti-hypertensive drugs which have lower blood pressure effects and can be used more widely than before?
谢谢Laurent教授, 我代表《国际循环》采访您。很高兴见到您，谢谢您接受我们的采访。我的第一个问题是：从荟萃分析的结果来看，您和其他研究人员的研究结果都表明预防心血管疾病的关键是降低血压，而不是降压药物的一些特殊作用。这是不是意味着有特殊非降压作用的降压药还不如降压作用更强的普通降压药呢？是不是应该主张更多地使用后者呢？
Prof. Laurent: This is a very important point because with meta-analysis we determine the amount of risk that you can lower in proportion with lowering the systolic blood pressure. So the higher the reduction in systolic blood pressure, the higher the reduction of risk. And this is true for many, many drugs. So now you can compare different therapeutic classes according to that scheme. The conclusions are limited by the pitfalls of meta-analysis, of course, that clearly about 80 percent or even 90 percent of the protective effect of anti-hypertensive drugs is done by lowering blood pressure. And then there are multiple differences. For instance, when you compare calcium channel blockers and ACE inhibitors for the same level of reduction in the systolic blood pressure, you are a little bit more effective on stroke with calcium channel blockers; you are a little bit more effective on coronary heart disease and heart failure with ACE inhibitors. And then, you are, like you are aware of the controversy between ACE inhibitors and ARB and similar kind of meta-analysis that has been done. And they show that of course a very large percentage of protetive effect was obtained by lowering blood pressure, but beyond that there is a set of difference between ACE inhibitors and ARB.
这一点很重要，因为根据荟萃分析的结果我们得出结论认为患者危险因素的降低程度是与患者收缩压的降低程度成正比的。所以收缩压降的越低，患者的患心血管疾病的危险性就越小。这个规律适用于很多很多药物。那么现在你可以按照这个规律来比较不同类别的治疗药物。当然这种比较得出的结论是会受到荟萃分析的一些陷阱的限制的，降压药物约80-90％的保护效果是来自其降低血压的作用。但是各种类别的药物之间还是有很多差异的。比如，如果你比较CCB和ACE抑制剂，你会发现在降低同样程度收缩压的情况下，CCB对卒中患者更有效，而ACE抑制剂对冠心病和心衰患者更有效。另外，你也知道ACE抑制剂和ARB的选择之间一直存在争议，这方面也开展了类似的荟萃分析。结果显示这两种药物的绝大部分保护作用都是通过降低血压来实现的，但除此之外，二者之间还是有一些区别的。
<International Circulation>: OK, thank you. My next question is regarding to the guideline: It was reported by an article of Britain Medical Magazine in 2004 that angiotensin antagonists （ARBs） might increase the risk of Myocardial Infarction. From then on, the safety of ARBs has been received increasing attention. However, the result of JIKEI HEART study showed that there was no mortality benefit, including cardiovascular mortality, nor was there a reduction in the risk of MI by conventional therapy plus ARB (valsartan) last year. How to evaluate the relationship of between ARBs and myocardial infarction? Do you think that ARBs may increase the risk of myocardial infarction? How to explain the possible mechanism within?
好的，谢谢。下一个问题是关于新版指南的：2004年英国医学杂志的一篇文章认为ARB可能增加急性心肌梗死发生率，自此对于ARB应用安全性引起大家的关注，而去年公布的JIKEI HEART研究中，ARB对于心肌梗死发生率的影响为中性。如何看待ARB与心肌梗死的关系？ARB是否会增加心肌梗死的发生？如何解释可能的机制？
Prof. Laurent: So this is exactly along what we have just said before. The only way for the moment is to pool all the studies, small and large, to get the largest number of patients, to get the highest statistic power. And if you do that, I’m also quoting the meta-analysis done by the extraodinary group, BPLTC—blood pressure lowering Trialists Collaboration published in Journal of Hypertension at the beginning of this year. And they showed very clearly that with ARB, the lower the systolic blood pressure, the lower the reduction in risk. So, among 100 percent, at least 90 percent of the job is done by lowering blood pressure. And ARBs are able to be used in coronary heart disease, fatal or unfatal, we shouldn’t say the contrary. And remember the LIFE study? There was a clear reduction in coronary heart disease, and although compared to Atenolol not significant different because Atenolol is very powerful and therefore active treatment. But if you comapre these phamacological classes to the placebo, then there is a significant reduction. So what they concluded is that compared to ACE inhibitors, ARB may not offer protective effect on coronary heart disease beyond blood pressure lowering, but there are protective effect related to blood pressure lowering, and this is very important. ARBs are very good drugs preventing cardiovascular events, preventing stroke and preventing coronary heart disease, but for none of them, it is possible for the moment to unmask the effect which is independent of blood pressure lowering.
这正好是我们刚才讨论的话题的延续。（针对你说的上述争议）目前我们唯一能做的就是将所有研究的结果汇集起来。如果你能够做到这一点的话，我也是引用BPLCT－降压治疗试验协作组的荟萃分析结果，这一结果今年年初发表在《Journal of Hypertension》上。分析的结果清楚地表明，用ARB治疗时患者的收缩压越低，其患心血管病的危险性越小。所以这种药物的作用中至少90%的部分是通过降低血压来实现的。而且ARB适用于冠心病患者，无论是致命性还是非致命性的冠心病。另外，还记得LIFE研究吗？试验中受试者冠心病的发病率明显下降，尽管和阿替洛尔相比，这种效果并没有明显的优越性。但这是因为阿替洛尔也是一种很强大的降压药，可以算作活性对照治疗。如果你把这种类别的药物（ARB）和安慰剂相比的话，就会发现患者（冠心病发病率）明显下降。所以研究人员得出的最终结论就是，与ACE抑制剂相比，ARB之所以对冠心病有预防作用只是因为其降压效果而没有别的特殊作用，但ARB确实有与降低血压相关的保护作用，这一点是非常重要的。ARB是一种很好的药物，可以预防心血管事件，可以预防卒中，可以预防冠心病，但这些作用都是通过降低血压来实现的，我们应该清醒地认识药物与降低血压无关的特殊作用。
<International Circulation>:It was mentioned for the first time that β-blockers are no longer preferred as a routine initial therapy for hypertension in British Hypertensive Society Guidelines 2006. How to comment the current status of β blockers in hypertension treatment? How to use β blocker? When and Who? Are β blockers still the initial therapy for hypertension?
2006年英国高血压指南中，第一次提出了β受体阻滞剂不再是多数高血压患者的首选降压治疗药物。如何评价β受体阻滞剂治疗高血压的临床地位？β受体阻滞剂应该如何使用？何时应用？哪些为适应人群？β受体阻滞剂是否还应作为降压治疗的一线用药？
Prof. Laurent: So in the new guidelines, we try to maitain β blocker in the anti-hypertensive drugs which are able to be, could be selected by the patients as first-line therapy. And we give some cushion. And we say because of the meta-analysis showing that β blocker in general and Atenolol in particular may not be as effective as other anti-hypertensive drugs, because of the LIVE trial, because of the ASCOT trial, which shows that the atenolol and thiazide are less effective than the amlodipine and thiazide arm. Because of that, we say that combinations with β blockers and thiazide may not be the best combination to use. So when you look at the ALLHAT trial, in the ALLHAT trial, most patients with Chlorthalidone have also β blockers. When you look at INVEST trial, there is no significant difference between the β blocker plus compared to the other therapy. When you look at..Oh, that’s enough. That means that we are, in this area, as many proof that β blocker might not be effective as we have proof that they are effective. So finally, the conclusion is β blockers are good drugs to lower blood pressure, but may not be so good because they are shown by the CASE study, by the ASCOT study that they do not lower to a greater extent or to a larger extent than other drugs. The other factor is the fact that its effect is aggravated
to and combined with diuretic, like insulin-resistance, the number of new diabetes, so they should be restricted to patients with no diabetes, with no metabolic syndrome.
在新的指南中，我们也尽量将β受体阻滞剂归为降压药物，且患者可以选择β受体阻滞剂作为一线治疗药物。我们缓和了一下这方面的争议。之所以这么说是因为，有荟萃分析显示，β受体阻滞剂，具体说来就是阿替洛尔的疗效不如其他降压药物，LIFE试验、ASCOT试验的结果都支持这一点，这些试验的结果显示，阿替洛尔和噻嗪类利尿剂联合治疗的疗效比不上氨氯地平和噻嗪类利尿剂联合治疗。正是考虑到这一点，我们就说β受体阻滞剂和噻嗪类利尿剂联合治疗可能不是最好的联合治疗方案。（另一方面），你可以看看ALLHAT试验，ALLHAT试验中，大多数服用氯噻酮的患者同时也服用了β受体阻滞剂。再看INVEST试验，含有β受体阻滞剂的联合治疗组与其它治疗组相比没有明显差异。你还可以再看看……哦，这些就够了。上述证据说明，在这个问题上，我们有很多证据表明β受体阻滞剂的疗效不佳，也有同样多的证据支持β受体阻滞剂有很好的疗效。所以，我们的最终结论就是β受体阻滞剂是一种降低血压的好药，但可能没有好到那种程度，因为一方面它降低血压的程度并没有超过其他药物，另外一个原因就是它往往是与利尿剂合用，而利尿剂可能加重患者的胰岛素抵抗并增加糖尿病的发病率，所以这种联合治疗方案只能用于没有糖尿病也没有代谢综合症的患者。
<International Circulation>:In recent years, the limitation of brachial blood pressure for BP-lowing evaluation has been known, while the obvious relationship between pressure gradient and cardiovascular events is found according to recent studies, some scholars have suggested that the Arterial Hardness Value should be one of important index for high pressure evaluation and medicine selection. How to view this opinion? Which the objective standards can be used to evaluate high pressure and anti-hypertension drugs?
近年来，上臂血压作为降压指标的局限性已被大家所公认，而许多研究显示脉压与心血管事件存在显著相关性，为此许多学者建议应将动脉血管硬度作为评价高血压和选择药物选择的重要指标。对于这种观点如何看待？如何选择客观指标评估高血压和选择降压药？
Prof. Laurent: I didn’t understand your question.
我不明白你的问题。
<International Circulation>:I just want to differ the brachial blood pressure and arterial hardness value.
我想问一下肱动脉血压和动脉硬度这两个概念之间的差别。
Prof. Laurent: What is arterial hardness value? Oh, this is stiffness, not hardness.
动脉硬度是什么意思？你说的是动脉僵硬度（arterial stiffness）吧，不是动脉硬度（arterial hardness）。
Prof. Laurent: No, I can give you an answer about that. This is a very important question. We measure blood pressure at the arm. The blood pressure which is measured at the arm does not reflect in all patients the blood pressure which is most important which is available in aorta, and the coronary arteries, and also the kidney or the brain, because there is some kind of amplification phenomenon between the arm and the carotid artery or the aorta. If you directly measure central blood pressure, that is to say carotid blood pressure, for instance carotid systolic blood pressure, with penetration to the other side of carotid artery, then you are in the buzzy thing to determine exactly the ventricular load, the load on the brain, because it is very similar to the load in the kidney—the hemodynamic input into the kidney. And the major determinant of this increase in the systolic blood pressure from the arm to the… from the brachial artery to the carotid artery is arterial stiffness. They stiffer the artery, the higher of the central blood pressure. So for the moment, we recommended in the new
guideline that to measure pulse wave velocity, carotid artery pulse wave velocity which means arterial stiffness, because we have good evidence that it is an independent predictive value for cardiovascular events. We didn’t recommend for the moment to measure central blood pressure because we have not enough evidences that it is an important determinant. Mainly it adds an
incremental value over brachial blood pressure.
不，我可以回答这个问题。这是个很重要的问题。我们一般是在手臂上测量血压。在手臂上测量得到的血压值虽然很重要，但不一定对于每个患者而言都能反映其主动脉、冠状动脉、肾动脉和脑动脉的血压，因为手臂和颈动脉或者主动脉（的血压）之间存在一定程度放大现象。如果你直接测量中心血压也就是颈动脉压的话，比如测量颈动脉收缩压，这个时候你才能准确地告诉我心室的负荷是多少，大脑的负荷是多少，因为颈动脉的血流负荷与肾脏的血流负荷——即进入肾脏的血液很接近。这种从手臂到……这种从肱动脉到颈动脉收缩压升高就是动脉的僵硬造成的。动脉越僵硬，中心血压就越高。所以目前，我们在新的指南中推荐测量脉搏波速度，测量颈动脉的脉搏波速度，这个指标就是代表动脉僵硬度，因为我们有很充分的证据证明它对心血管事件有独立预示价值。目前我们并不推荐测量中心血压因为还没有足够的证据证明中心血压是否是（心血管事件的）重要决定因素。一般说来中心血压会比肱动脉血压的值高一点。
<International Circulation>:OK, my last question is: according to the new updated guideline ESH 2007, what are the major differences between this version and the previous version? And also the positioning change of different drug classes like
ARB, ACEI, CCB??? blockers.
好的，我的最后一个问题是：从新公布的ESH 2007指南看来，这个版本的指南和上一个版本的指南的主要区别是什么？不同类别的药物，比如ARB、ACEI、CCB、?受体阻滞剂的地位之间有什么变化吗？
Prof. Laurent: So this is a short question for a very long answer. So I’ll be very short because you ask me what are the differences between 2003 and 2007 guidelines. Very shortly, two types of difference. First, the new diagnostic aspects now include three types of measurements: first, how to detect metabolic syndrome, to give importance to overweight, to distal obesity, to fasting glucose. Second, how to detect arterial damage. Measurement of arterial stiffness, measurement of ankle-brachial index. Third, how to detect more precisely kidney damage instead of measuring creatinine, calculating and measuring the glomerular filtration rate. This is the new diagnostic aspect in addition to the previous one. And the second part is concerning the therapeutic aspect. The therapeutic aspect is considered as flexible, that means that the practitioner has the
choice to choose the drug which he likes to prescribe according to certain recommendation, mainly according to the level of cardiovascular risk, and also according to the target end-organ damage. For instance, please select ACE inhibitors or ARB if there is a ventricular hypertrophy, please do not select ? blockers if there is a metabolic syndrome or diabetes, etc.
这是一个简短的问题，答案却很长。你是问我2003版的指南和2007版的指南之间的区别，我尽量简短地回答这个问题。简单的说二者之间的区别有两点。首先，在诊断方面新的指南中提出了三种类型的检测手段：第一，如何检测代谢综合征，应该更加重视超重、远端肥胖以及患者的空腹血糖。第二，如何检测动脉损伤。包括测量动脉僵硬度，测量踝肱指数。第三，如何更加精确地测量肾脏损害，除了传统的测量肌苷，计算和测量肾小球滤过率以外有没有别的方法。这是诊断方面新指南与前一版本相区别的地方。其次，（两个指南版本的区别还表现在）治疗方面。新版本指南在治疗方面是很灵活的，也就是说医生可以做出自己的选择，可以根据一些推荐方案，更主要是根据患者的心血管危险程度以及靶器官损伤程度来选择自己喜欢的药物。例如如果患者有心室肥大，可以选择ACE抑制剂或者ARB，如果患者有代谢综合征或者糖尿病，请不要选择?受体阻滞剂等等。
<International Circulation>:So this guideline will more balance the drugs? Different drug classes?
也就是说这个版本的指南会更多考虑平衡？不同药物类别之间的平衡？
Prof. Laurent: They give importance to all classes, but there are more, they give more information for the prescription of a certain drug class into a certain indication. OK?
B：新指南强调所有类别的药物都是很重要的，除此之外，在一定的适应症的情况下，指南会着重给出某些类别药物的信息。
<International Circulation>:Thank you very much.
非常感谢。
