International Circulation: Large-scale clinical trials have shown that the degree of cardiovascular benefit is not the same even though there is  the same degree of reduction in blood pressure， so my first question is: why not? 

    《国际循环》：大规模临床研究证实，即使血压降低幅度相同，心血管获益也并不一致。我的问题是：为什么会出现这一结果？

     Dr. Yong: I think there are many reasons for this. One of them is of course the study design. In all the large scale studies， there is tremendous heterogeneity of the patients being selected. So despite the similar blood pressure reduction， we are talking about different categories of patients with different risk factors therefore the blood pressure reduction may not be the same for example， for low risk groups against high risk groups of patients. Also， although blood pressure reduction is the most important parameter for the reduction of cardiovascular events， it is necessary to define what you mean by cardiovascular events. There are two events that of course are the most important. One is myocardial infarction， angina， heart failure， hospitalization for angina. The other， of course， is stroke. If you are looking at stroke then blood pressure reduction is the most important. However， if you are looking at coronary artery disease and prevention of myocardial infarction， then hypertension may not be the most important but the LDL cholesterol levels are. This has been shown in many epidemiological as well as interventional randomized controlled mortality trials. Herein lies the tremendous amount of differences when you choose a high blood pressure tablet to reduce blood pressure without inotropic effects like anti-sclerotic effects， the ability to halt or slow the progression or even regress the atherosclerotic plaque， then you are looking at a different outcome. 

    Dr. Yong：原因有很多。其中之一是研究设计所致。在所有的大型临床研究中，入选患者均存在相当大的异质性。所以，即使血压降低幅度相似，不同类别、合并不同危险因素的患者，其获益程度也是不相同的。例如：低危患者与高危患者相比。此外，虽然降压是减少心血管事件的最重要的方式，但是我们需要明确心血管事件的定义和具体范围。在心血管事件中，两大类事件是最为重要的，一个是心肌梗死、心绞痛、心衰以及因心绞痛住院；另一个是卒中。对于卒中而言，降压是最重要的；但是，对于冠心病以及预防心肌梗死而言，降压可能就不是最重要的因素，LDL-C水平在其中发挥着重要作用。大量流行病学以及干预性随机对照死亡率评估研究均证实了这一观点。在选择降压药物时，所选药物如果没有抗动脉硬化作用，没有阻止、延缓甚或逆转粥样斑块的作用，那么你将会观察到不同的预后。

    International Circulation: When we look at lowering blood pressure and blood pressure control and we talk about amlodipine， is there a unique feature of amlodipine in its quality of blood pressure control?

    《国际循环》：在降压品质方面，氨氯地平的独特之处是什么？

     Dr. Yong: Yes there is. Amlodipine is in the inherently long-acting dihydropyridine group which is important because we know the short-acting dihydropyridine groups like nifedipine have a tremendous amount of detrimental effects but not the long-acting forms of which amlodipine is one. I believe it is even superior to those modified forms like nifedipine and GITS which is inherently slow-acting but modified release so not a true long-acting calcium channel blocker which amlodipine is. From numerous studies we know that a drug like amlodipine has tremendous efficacy in blood pressure reduction particularly in hypertension in the elderly， the isolated systolic hypertension， where it is very helpful in bringing down blood pressures and I believe the profile is such that it is long-acting and has good 24 hour blood pressure control. But significantly in some recent findings by Bryan Williams in the ESCORT/CAFE study， show that the central aortic pressure is very important. In fact， the central systolic aortic pressure predicts excess mortality， LVH end organ target damage. It appears that a calcium channel blocker like amlodipine in the ESCORT study seems to be very beneficial in reducing the central systolic aortic pressure compared to the atenolol group which doesn’t have this property. It may explain some of the benefits of the outcome of the ESCORT study. Herein lies an antihypertensive class which appears will be very useful and as my colleague has mentioned in combination therapy for moderate hypertension， usually a calcium channel blocker with a diuretic， ARB or ACE inhibitor would bring the pressures down to goal targets.

    Dr. Yong：氨氯地平是本身分子长效的二氢吡啶类CCB，这一点是非常重要的。因为我们知道短效二氢吡啶类CCB，如硝苯地平，带来很多不良反应。而长效二氢吡啶类CCB，如氨氯地平则没有这些不良反应。而且我认为，氨氯地平优于经过剂型修饰的药物，例如硝苯地平控释片，其本身并不是真正的长效制剂，只是对药物的释放进行了修饰和控制。大量研究证实，氨氯地平降压疗效突出，尤其是对于老年高血压患者、ISH患者。在这些患者中，氨氯地平不仅有效降低血压，而且可以持久控制24小时血压。最近，Bryan Williams在ASCOT-CAFEE研究中发现，中心动脉压是非常重要的。事实上，中心动脉压可以预测死亡、LVH和靶器官损伤。在ASCOT研究中，氨氯地平在降低中心动脉压方面优于阿替洛尔。这可以解释ASCOT研究氨氯地平所带来的获益。在中度高血压的联合治疗中，通常采用CCB与利尿剂/ARB/ACEI的联合治疗，以获得目标血压。