[ASH2009]《Hypertension》总编John E. Hall教授访谈:药物基因组学与高血压等
International Circulation: What do you think the highlight of hypertension research is in recent years?
Prof. Hall: Well there have been several advances. One is that we now know that lowering the blood pressure is probably the most important thing that you can do to prolong life so effective and aggressive anti-hypertensive treatment has been shown to be important. What we also learned is that it is not so important which drug you use but the most important thing is to get the blood pressure down to a safe level.
《国际循环》: 您认为近年来高血压研究的热点是什么?
Prof. Hall: 有很多新的进展。一项是我们现在所知道的,降压可能是延长寿命最重要的事情,已证实有效、强力的降压治疗非常重要。我们也知道使用哪种药物并不重要,最重要的是将血压降至安全水平。
International Circulation: Is that a change in strategy – now the strategy is to go right after the blood pressure?
Prof. Hall: Yes, in the past it has been lots of small studies that have suggested one particular drug or the other might be more beneficial in terms of target organ injury protection but the ALLAT study, the Antihypertensive Lipid Lowering Heart Attack Treatment study indicated that it was not so much the drug that you use but the level of blood pressure reduction that was more important. So that is one major advancement, another major advancement is that treatment of elderly hypertensive patients extends life and many people were concerned that treating elderly hypertensive patients might create more strokes, might create more target organ injury but what has been shown is that even in very elderly hypertensive patients – eighty years and older, that lowering their blood pressure have prolonged their life and reduces their cardiovascular risk. On a basic science level I think that one of the important areas that have been emerging is the mechanisms that link obesity with hypertension which is the area that I work in. We now know that in the US and many countries including China that obesity prevalence is markedly increasing and it is probably the single most important risk factor for hypertension. We are learning more about the mechanism of obesity related hypertension which we know, I think, is going to become more and more important in the future as the prevalence of obesity continues to increase.
《国际循环》: 高血压治疗策略将变为一切皆为降压?
Prof. Hall: 是的,过去许多的小型研究表明,一种特定药物或其他可能在预防靶器官损害上更加有效,但ALLHAT研究(抗高血压和降脂预防心肌梗死试验)证实,最重要的不是使用哪种药物而是血压下降的水平。因此,这是一项主要的进展。另一项主要进展是老年高血压患者治疗高血压会延长寿命。许多人过去担心治疗老年高血压会增加卒中和导致更多的靶器官损害,但目前已证实,即使对80岁以上的高龄老年高血压患者,降低血压也能延长寿命、减少心血管风险。在基础科学领域,我认为一个新出现的重要领域是联系肥胖与高血压的机制研究,也是我所从事的领域。目前我们知道,美国和中国在内的许多国家,肥胖的流行趋势正在显著增加,这可能是单个最重要的高血压危险因素。我们对与高血压相关的肥胖机制的了解正在增加,我想,未来随着肥胖的持续增多,这将越来越重要。
International Circulation: What is the first line of attack on obesity?
Prof. Hall: Well the first line of attack is behavioral modification and diet and exercise though we now know that that is only effective in a small fraction of people. But along and parallel with that, we really need to lower the blood pressure. Most patients with obesity have high blood pressure. We have good medications for high blood pressure so the most important thing that can be done at least initially, is to lower the blood pressure in these individuals. Secondly, we also have to aggressively address the metabolic abnormalities, the insulin resistance, the increased glucose levels, and the dyslipidemia. We have good drugs now to treat lipids, so this is also important as well.
《国际循环》: 肥胖首选治疗应是什么?
Prof. Hall: 首先是调整行为、饮食和锻炼,这是目前所知的对少部分人最有效的方法。但与此相随和平行的,是我们真的需要降低血压。多数肥胖患者合并高血压。我们有很好的降压药,因此所能做的最重要的事,是至少开始降低患者的血压。其次,我们也需要积极干预代谢综合征、胰岛素抵抗、高血糖和血脂异常。目前我们有好药治疗血脂,这点也非常重要。
International Circulation: How does pharmacogenomics affect hypertension prevention and treatment strategies?
Prof. Hall: Well pharmacogenomics simply stated means the variable response to, for example anti-hypertensive drugs, depending on the person’s genetic makeup. We know that different patients respond to different drugs in a way that is variable. Some patients for example respond better to for example diuretics than some patients. We don’t know whether that is a genetic factor or if that is some acquired factor that makes them more responsive but this is an emerging area of research in which we are trying to understand better the genetic makeup of an individual and how that influences their response to different anti-hypertensive drugs. It is a very early field of research so it is one that will probably become more and more important in the future. One thing that might occur for example, is that once we are able to in an economically advantageous way, once we are able to determine a persons gene variation, we may be able to tailor make a particular drug for the patient based on their particular genetic makeup.
《国际循环》: 药物基因组学对高血压预防和治疗策略有何影响?
Prof. Hall: 药物基因组学简单说,就是对降压药的不同反应取决于个体的基因构成。我们知道,不同患者对不同药物的反应有所不同。例如,许多患者对利尿剂的反应好过其他患者。我们不知道是否存在一种遗传因素或某些获得性因素导致更敏感,但这也是一个新出现的研究领域,我们需要更好地理解个体的基因构成和其如何影响对各种降压药的反应。这方面的研究尚处于非常早期阶段,未来可能会越来越重要。例如将来有可能出现,一旦我们能够有有经济优势的方法,一旦我们能够测定一个人的基因变异,我们可以根据患者的特殊基因构成定制出特效的药物。
International Circulation: You say that it is “early in the research”. How far down the road would you assess that we are?
Prof. Hall: We are not very far down the road. We are currently at the stage where we can measure gene expression in individuals of many genes, much cheaper than it was ten years ago but we are not very far down the road in terms of determining how genetic variation influences the response to anti-hypertensive therapy. We still have a long way to go there.
《国际循环》: 您说正处于“研究的早期”,请您估计一下我们离目标还有多远?
Prof. Hall:我们离目标并不是非常远。我们目前正处在边缘上,我们已能测定一个人的许多基因的基因表达,较10年前已便宜了很多,但在判定基因变异如何影响降压治疗的反应上,我们离目标尚远。我们仍有很长的路要走。
International Circulation: Changes have taken place in hypertension studies, such as new treatment strategies of individualized treatment and clinical trials on hypertension have paid great increasing attention to the intermediate end points. What is your opinion about these changes?
Prof. Hall: I think this is a good strategy to look at intermediate end points rather than just looking at the old way in which we looked at how many deaths we had. Some of the intermediate end points whi