<International Circulation>: One of the key topics at this year’s International Meeting on PreHypertension and Cardio Metabolic Syndrome was the debate on whether prehypertension is a disease or an invented one. Was this answered during the meeting?
<International Circulation>: One of the key topics at this year’s International Meeting on PreHypertension and Cardio Metabolic Syndrome was the debate on whether prehypertension is a disease or an invented one. Was this answered during the meeting?
Prof Zimlichman: Yes, this was one of the main issues addressed during the conference. I am pleased to say that we had the majority of the worlds prominent experts in this area to come together in contributing to a very fruitful discussion which will be echoed in parts for the recommendations we plan to publish. As we know hypertension has a linear progression that increases over time and so if you have prehypertension it is certain that at some point you will progress towards being hypertensive. This is not just a marker for the increased risk of future disease complications but also a marker of present disease that is asymptomatic. This is due to the haemodynamic and pathophysiological changes that occur which raise blood pressure. Some of these are structural whilst others are either functional or humoral that induce changes in the system that participates in determining blood pressure. These changes progress with time until they become overt diseases with symptoms. At the stage of prehypertension these changes are asymptomatic and the patient does not know that they have a problem.
<International Circulation>:During this critical stage how can we evaluate these patients and go forward with the appropriate treatment avenues to prevent progression towards hypertension?
Prof Zimlichman: There is still a dispute as to whether prehypertension should be treated or not. The answer to that is that some subgroups of these patients are already treated pharmacologically. These patients are treated either with non-pharmacological therapy whilst there are some whereby pharmacological therapy should be added. The question is how do we distinguish those who need drugs from those who do not? This remains a very contentious question. But for sure some patients with prehypertension are already treated with pharmacological therapy according to old guidelines. For example if you have a patient with multiple risk factors or with evidence of vascular damage such as in the kidneys, who is diabetic with proteinuria and is prehypertensive; according to old guidelines this patient should be treated. Changes or the disappearance of microalbuminuria is the goal of treatment. This is just an example of a sub-group of patients with prehypertension who are already treated with pharmacological agents.
There are other sub-groups whereby treating with pharmacological agents is disputed; such as those with coronary artery disease, post myocardial infarction, transient ischemic attack (TIA) and those with overt artherosclrotic disease in the carotid arteries. All these patients probably will be treated in the future but at this moment we are busy gathering information with the aim to arriving to the most appropriate consensus for treatment.
<International Circulation>: It has been shown that progressive drug intervention can delay or prevent the occurrence of hypertension, but is this due to the lower hypertension levels of the patient or the actual blockade of the renin angiotensin system(RAS)?
Prof Zimlichman: I think it is a combination of both. If you block humoral factors that will propagate vascular disease in the future you prevent the changes that develop gradually and lead to arterial stiffness and to further elevation of blood pressure. In addition, if the changes are already present, regression of these structural changes will occur, delaying appearance of hypertension. There are still many things we do not understand in this area and studies with spontaneous hypertensive rats have been critical in improving our knowledge and understanding. These rats when they grow become hypertensive and if you treat them with the blockade of the RAS at an early stage when they do not yet have hypertension you delay or prevent the appearance of hypertension in a later stage. This is however very difficult to understand because it seems to be a form of “memory” that changes the progression of disease. The study done by Prof Stevo Julius showed that you can delay the appearance of hypertension for a considerable time. This raises the question as to whether we should treat patients for several months or years and then discontinue therapy with the hope of preventing hypertension in the future. Unfortunately, with the amount of evidence we have at the moment we are unable to provide a definitive answer.
<International Circulation>:What endpoints should future studies encompass?
Prof Zimlichman: Even today we can do tests which can determine the degree of asymptomatic vascular damage. One of the most important points in this aspect is the measurement of arterial wall stiffness which increases with age. This is accelerated if blood pressure is elevated and if additional risk factors are present. Progression of arterial stiffness correlates well with the degree of hypertension. There are many studies that have been done, are being done and planned to be done in this field using arterial properties which will have application in assessing the stiffness of the aorta, thoracic and abdominal aorta, pulse wave velocity and endothelial dysfunction. All of these can help us detect patients that have sub-clinical disease who should receive specific attention.
高血压前期的争论
高血压前期是否是一种疾病,这是本次会议期间解决的主要问题之一。众多知名专家和学者汇聚一堂,共同探讨此话题,最终结果将发表在我们的推荐指南中。如我们所知,高血压呈一个线性进展过程,随时间推移而升高。因此,高血压前期可能在某个阶段向高血压进展。这不仅仅是未来疾病并发症风险升高的一个标志物,还是当前无症状疾病的一个标志物,因为血压升高的同时血液动力学和病理生理学发生改变。随时间推移,高血压前期演变为有症状的疾病。
高血压前期的治疗人群
高血压前期是否应当接受治疗存在争议。现实问题是部分患者已接受非药物治疗,部分患者应给予药物治疗。对我们而言,重点是应区分哪些患者需药物治疗。按照旧版指南,部分高血压前期患者已接受药物治疗,例如,有多重危险因素或血管损伤证据如肾脏血管损伤(蛋白尿)的高血压前期患者应接受治疗,微量白蛋白尿的减少或消失是治疗的目标。对于合并冠心病、心肌梗死后、短暂性脑缺血发作(TIA)以及颈动脉有明显粥样硬化性病变的高血压前期患者是否给予药物治疗,存在争议。
高血压前期的药物治疗机理
药物干预能延缓或预防高血压的发生,这归功于血压水平的降低和肾素-血管紧张素系统(RAS)的阻滞,因为阻滞未来引起血管疾病的体液因素,即可预防逐渐发展、导致动脉僵硬从而进一步升高血压的血管病变。若病变已经存在,药物干预可延缓病变的进展,推迟高血压的出现。自发性高血压大鼠的研究表明,RAS阻滞剂可延缓或预防高血压,这似乎是一种改变疾病进展的“记忆”形式。Stevo Julius教授的研究也证实,RAS阻滞剂可延迟高血压的出现。然而,根据目前所拥有的证据,患者是否应给予RAS阻滞剂治疗或治疗一段时间后继而停止治疗并寄希望于未来预防高血压研究,对此问题,我们不能提供一个确切的答案。
未来研究的临床终点
目前,确定无症状血管损伤程度的试验的重点为动脉壁僵硬度的检测。研究发现,动脉壁僵硬度随年龄增长而增加,若血压升高或存在额外的危险因素,则该过程加速,动脉僵硬度的进展与高血压程度呈良好相关性。现行研究利用动脉特性如主动脉和胸腹主动脉的僵硬度、脉搏波传导速度以及内皮功能帮助识别亚临床病变,可纳入研究终点的范畴。