[ASH2009]Norman M. Kaplan教授谈高龄高血压患者治疗策略及卒中预防药物选择
高龄老年高血压患者的血压目标值应为多少? Kaplan教授: 实际上我们尚未确立合适的目标值。但我想应是最近公布的HYVET研究所采用的目标值,该研究入选了几乎4000名80岁以上的患者。
International Circulation: What do you think the goal blood pressure of the very elderly with hypertension should be?
Prof. Kaplan: Well, we really have not established the appropriate goal, however I think the goal that was used in the recently published HYVET (HYpertension in the Very Elderly) study, which was a study involving almost 4000 people who were at least 80 years of age...
《国际循环》: 高龄老年高血压患者的血压目标值应为多少?
Kaplan教授: 实际上我们尚未确立合适的目标值。但我想应是最近公布的HYVET研究所采用的目标值,该研究入选了几乎4000名80岁以上的患者。
International Circulation: Does over 80 define the ’very elderly’?
Prof. Kaplan: Well, again, the definition of what exactly constitutes ’very elderly’ has never been really established. I think, in general, aged 65 and above would identify people as being elderly, and I think it sounds reasonable that aged 80 and above would be very elderly. But, truthfully, as far as I know, that has never been established in any definitive way in any of the guidelines or anywhere else. So the issue really comes down to: what is the safest level of blood pressure for very old people? Before HYVET, there was evidence that lowering the blood pressure actually could increase the likelihood of strokes, and for that reason I think the people in the HYVET study established their goal as being a systolic of 150. They actually achieved that goal in about half of the patients that were given active drug therapy. That seems to me to be reasonable, but one could look at the trends of increasing stroke with increasing blood pressure in the elderly and that has been done in the paper published in 2002 by Dr. Lewington (in the Lancet), and they showed a progressive increase in the likelihood of both stroke and heart attack ranging from the very lowest level, which was actually around 115 systolic, up to levels up to nearly 200 systolic. So. one could argue on epidemiological or observational data that the goal should be lower.
《国际循环》: 为何将80岁定义为“高龄”?
Kaplan教授: 关于“高龄”的确切定义,从未被真正确立。我想,一般认为65岁以上是老年人,而将80岁以上定为“高龄”是合理的。但是,坦白而言,据我所知任何指南从未明确过其定义。因此,话题应该归结为:高龄老年人的最安全血压是多少?在HYVET之前,有证据表明降低血压能够减少卒中的可能性,我想出于上述原因,HYVET研究将其目标定为收缩压150mmHg。实际上,约一半接受药物积极治疗的患者达到了该目标。对于我们,这似乎很合理,但回顾2002年Dr. Lewington发表在柳叶刀的文献,老年人卒中有随血压增加而增加的倾向,并且血压从极低水平—收缩压约为115mmHg,一直到200mmHg之间,卒中和心脏事件的可能性进行性增加。因此,根据流行病学或观察性数据,可以说血压目标应该更低。
There are two problems with that. First of all, the usual older patient has a high systolic, but a lower diastolic. That is a consequence of the basic stiffness of the arteries, which causes the systolic to go up, but at the same time the diastolic to go down. There is evidence that there is a J-curve for the diastolic pressure, so that if you see a typical older patient with a blood pressure of 180/70 and you attempt to lower the systolic, say to 140, you may reduce the diastolic by at least 10 millimetres, and thereby, I think, put the patient at a greater risk because of a too low diastolic pressure. So, the simple answer is: we do not know, but I think that a blood pressure between 140 and 150 systolic, and maybe maintaining a diastolic above 60 would maybe be the appropriate levels to try to get to elderly hypertensive.
这里也存在2个问题。首先,通常老年人的收缩压很高,但舒张压很低。这与老年人的动脉基础僵硬度有关,其能导致收缩压增加、舒张压下降。有证据显示舒张压存在J曲线;因此,对于一位血压180/70mmHg的典型老年患者,尝试降低收缩压,如到140mmHg,可能使舒张压降低至少10mmHg。因此,我想,过低的舒张压太低可能使患者更加危险。因此,简单回答是:我们不知道!但我想血压保持收缩压在140-150mmHg、舒张压高于60mmHg,可能对老年高血压患者是合适的水平。
International Circulation: Keeping on that theme, for the very elderly what, your opinion is the best anti-hypertensive drug?
Prof. Kaplan: There is a difference in the elderly’s response to different drugs, if they are given as mono-therapy. In general, they do not respond as well to renin-inhibiting drugs, which would include Beta blockers, ACE inhibitors, angiotension receptor blockers, direct renin inhibitors and somewhat better to diuretics and calcium-channel blockers. However, that differential response is only true if you look at them as single agents, and only single agents. When you combine them, say perhaps a diuretic and an ARB, then I think the elderly respond just as well, and that I think was documented in the HYVET study, because in that study they started with the diuretic and added an ACE inhibitor if it was needed to bring the blood pressure to the goal that they had established. So, I think that you could use any of the various classed. The one exception is the use of Beta blockers for primary prevention of either stroke or heart attack. Those data come from some analyses that have been done with Beta blocker trials where they have lowered the blood pressure equally with Beta blockers and other drugs but there were more strokes seen in those patients who were given Beta blockers, and that probable reflects a lack of lowering of the central blood pressure by the Beta blocker therapy. So, I think that any drug, if it is used for primary prevention, with the exception of Beta blockers, if the patient has has a myocardial infarction or heart failure, clearly Beta blockers would be indicated in patients of this type.
《国际循环》: 继续现有话题。对于高龄老年人,您认为最好的降压药是什么?
Kaplan教授: 如果单药治疗,老年人对不同药物的反应也会不同。通常,对抑制肾素的药物反应欠佳,包括β受体阻滞剂、ACEI和ARB、直接肾素抑制剂;对利尿剂和CCB反应略好。然而,这里的不同仅指单药治疗时,如果联合治疗如利尿剂和ARB,我想老年人的反应会很好。这也被HYVET研究所证实,该研究首选利尿剂,根据需要加用ACEI,以使血压达到所定的目标值。我想,您可以使用任一类的降压药,但应除外β受体阻滞剂用于卒中或心脏事件的一级预防。这来自对许多β受体阻滞剂相关试验的分析——β受体阻滞剂的降压效果与其他药物相同,但β受体阻滞剂治疗的患者更容易见到卒中,可能与β受体阻滞剂治疗不能降低中央血压有关。因此,我想如果用于一级预防,可选用β受体阻滞剂之外的任何药物;但如果患者有心肌梗死或心力衰竭,β受体阻滞剂有明确的应用指征。
International Circulation: In JNC 7, only Diuretic and ACE inhibitors were as cited as the compelling prevention of recurrent stroke. But now, with the issues highlighted by some new trials, do you think the status of CCB or ARB for recurrent stroke prevention will be higher?
Prof. Kaplan: Yes, I do. I think the main reason why the JNC in 2003 stated that they would recommend the use of a diuretic and an ACE inhibitor is because that is what was used in the biggest trial to have been published by that time, which was the PROGRESS trial, where they used an ACE inhibitor and then added a diuretic if needed. When they put the two together they got a significant reduction in blood pressure and a significant reduction in recurring stroke. However, HYVET, which also showed very good, effective reductions in strokes, used a diuretic and an ACE inhibitor and that showed that the protection was equally as good as had been shown in PROGRESS. We do not have large outcome studies in the elderly with calcium-channel blockers or diuretics, but my opinion is that the type of