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[ASH2012]血管纤维化和动脉僵硬度——美国Minnesota大学Daniel Duprez教授专访

作者:  D.Duprez   日期:2012/5/28 15:55:46

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《国际循环》:血管纤维化和动脉僵硬是血管重构的两个表现。两者是否会影响心功能?


  <International Circulation>: You talked about some of the convenient and effective methods for evaluating the arteries and the heart?
  Prof. Duprez: I will start with the evaluation of the artery. At this moment, the whole medical world is still evaluating arteries based on the measurement of arterial blood pressure. It is fascinating because Riva-Rocci in Italy in 1897 started to measure blood pressure using a mercury manometer and a cuff. Now more than 100 years later and the major part of cardiovascular disease prevention is based on that same blood pressure assessment, nowadays less utilizing the mercury sphygmomanometer but electronic devices. If we look back, systolic and diastolic blood pressures are only the two extreme points of the whole blood pressure wave form. There is no further information except the mean arterial blood pressure which is the diastolic plus one-third of the difference between the systolic and diastolic. There is an assessment for the perfusion pressure. And then the pulse pressure is the difference between the systolic and diastolic and I would describe as the poor man’s technique to estimate arterial stiffness. We see now, for instance, patients with autoimmune disease such as rheumatic arthritis and diabetic patients or insulin resistant patients or metabolic syndrome or obese people, that in fact when you look at the wave form, despite the systolic and diastolic points being nearly the same, the morphology of the wave form starts to change. That means that there is an urgent need for much more information than only systolic and diastolic blood pressures. Nowadays there are several techniques to estimate arterial stiffness but the two major methods are: either you put the sensor at the level of the carotid and one at the femoral artery and you examine the difference in arrival in time of this wave form called the carotid femoral pulse wave velocity and it has been demonstrated that the carotid femoral pulse wave velocity is a very good parameter to predict cardiovascular morbidity and mortality; and then there is tonometry at the radial artery where you measure non-invasively the arterial pulse wave and with mathematical modeling and a computer algorithm obtain much more information either from the systolic part and/or the diastolic part. If you go for the systolic part, then you need to realize that the aortic valve is still open and gives you information regarding the combination of myocardial performance and arterial system. When you want to assess purely the arterial system then it is better that the aortic valve is closed and that is during diastole. We have other techniques to evaluate the microcirculation. I would not consider arterial hypertension as a risk factor; I would consider arterial hypertension as the vascular phenotype. Twenty or thirty years ago we decided the emphasis should be on diastolic pressure but we now know that this is not ideal because if you lower the blood pressure to 150/80mmHg (HYVET demonstrated that and there is a very large Chinese study going on also) in the elderly with systolic hypertension, you reduce the morbidity and mortality and especially stroke also which is much more prominent in the Chinese population than the Caucasian population. Secondly, we have the whole population of pre-hypertensives and there is a lot of debate going on regarding resistant hypertension where blood pressure is still elevated and the patient is taking three antihypertensive drugs with a diuretic, and the reason is that we start too late. The moment when we diagnose hypertension defined as 140/90mmHg or above, already the vascular damage has taken place. Vessels are stiffer and there is more fibrosis and it is much more difficult to reverse that remodeling. In pre-hypertension, we know from TROPHY that if we halve the progression of that blood pressure rise then we can postpone or delay the development of hypertension. There is now a very large Chinese study going on in pre-hypertensive patients. This is the first assessment of arterial function. Of course you can use other elements like studying the retinal vessels and I think that is very important because the retinal vessels are the endpoints of the brain circulation and it is very easy to estimate the perfusion of an ageing population with dementia which is becoming a larger problem. With ultrasonography we can assess the thickness of the carotid arteries, of the aorta and to see if there is an aneurysm there or not. And as I have pointed out already, in the Chinese population we see thickness of the carotid arteries but much less calcification. The kidneys can be considered as a sack of capillaries. If you have a renal problem or a blood pressure problem then the first sign is microalbuminuria. So this is a nutshell summary of the non-invasive assessments to obtain much more information regarding the vasculature than just these two extreme points. Secondly, we come to the evaluation of the heart. We must not forget that the heart is an endocrine organ as the heart synthesizes NT-proBNP and the active hormone is the brain natriuretic peptide (BNP). I think we now have enough evidence that BNP is such a significant predictor for cardiovascular morbidity and mortality not only in the diagnosis of heart failure. I always compare BNP and heart failure like infectious disease specialists would compare counting white blood cells if you have pneumonia or an infection, but this can be done at a much earlier stage. Additionally, we know that the electrocardiogram can be interesting because it gives you a fingerprint. People who come in with chest pain or arrhythmias, it can help relieve a dilemma  if the ECG is not too abnormal (although women again have the tendency to have some abnormalities that are within the normal scope) but then it is interesting to compare the ECG if there were no complaints and they are easy to take and cheap. For diastolic dysfunction, the ultrasound will give us information regarding the remodeling of the ventricle, regarding the relaxation and also regarding the pump function and ejection fraction. So these three (BNP, ECG and echocardiography) can give us a balanced view of myocardial function in the patient with hypertension.

  《国际循环》:你谈到了评价动脉和心脏的一些简单、有效的方法。
  Duprez教授:我会从动脉的评价开始。当前,整个医学界还是基于动脉血压的测定来评价动脉。激动人心的是,意大利的Riva-Rocci早在1897年就开始采用汞柱式血压计和袖套来测量血压。现在,100多年过去了,心血管疾病预防主要还是基于同样的血压测定,现在汞柱式血压计的应用减少,更多地使用了电子血压计。如果我们回过头去看的话,收缩压和舒张压只是整个血压波形的两个极端。除了平均动脉压之外,它不能够提供额外的信息,平均动脉压等于收缩压和舒张压之差乘以三分之一。当前还有灌注压的测定。脉压等于收缩压和舒张压之差。我认为测定脉压不是一个评价动脉僵硬度的好方法。现在我们看到,对于风湿性关节炎等自身免疫性疾病的患者和糖尿病、胰岛素抵抗、代谢综合征或肥胖患者,当观察血压波形时,我们会发现尽管这些患者的收缩压和舒张压接近正常,但是波形已经发生了变化。这意味着,除了收缩压和舒张压之外,我们亟需了解更多的信息。
  目前有几种方法可用于评价动脉僵硬度,但是两个主要的方法是:一种方法是把传感器放置在颈动脉,另一个传感器放置在股动脉,然后观察波的到达时间(颈动脉-股动脉脉搏波传导速度)。研究显示,颈动脉-股动脉脉搏波传导速度是预测心血管疾病和心血管死亡的一个非常好的指标。第二种方法是在桡动脉放置压力波测定仪,可以无创地测定动脉脉搏波,通过数学模型和计算机算法,我们可以从收缩压和/或舒张压的部分得到更多的信息。如果分析收缩压信息的话,需要认识到主动脉瓣仍然是开放的,会给我们带来心脏功能和动脉系统的综合信息。如果你只是想分析动脉系统的话,那主动脉瓣关闭更为适合,也就是在舒张期。
  我们还有其他一些评价微循环的手段。我不会将高血压作为一个危险因素,我会将它作为血管表现型。二、三十年前,我们认为重点应当是舒张压,但是现在我们知道这并不理想,因为如果把老年收缩期高血压患者的血压降至150/80 mm Hg的话(HYVET研究证实了这一点,目前也有一个大样本的中国研究正在进行当中),可以降低发病率和死亡率,尤其是卒中。中国人群比高加索人群卒中更为常见。其次,我们有整个的高血压前期人群。目前关于难治性高血压有很多争论,难治性高血压患者在应用了包括利尿剂在内的3种降压药物之后血压仍高。问题就在于开始高血压治疗太晚了。当我们根据血压值≥140/90 mm Hg来诊断高血压时,血管损害就已经存在了。血管僵硬度增加,纤维化更多,逆转重构更难以实现。对于高血压前期,我们从TROPHY研究了解到,如果我们能把血压升高的进展减半的话,我们就能够推迟或延缓高血压的发生。目前中国有一项观察高血压前期患者的大样本研究正在进行当中。这是对动脉功能的首次评价。当然,你可以采用其他方法,例如观察视网膜血管。我认为这相当重要,因为视网膜血管是脑循环的末端,评价伴有痴呆的老年人群的灌注状态是非常容易的。痴呆当前已经变成了一个更严重的问题。通过超声,我们可以评价颈动脉和主动脉的厚度,观察有无动脉瘤。正如我所指出的那样,我们在中国人群观察到颈动脉内膜的增厚,但是钙化较少。肾脏可被看作是毛细血管团。如果你有肾脏问题或血压问题,第一个表现就是微量白蛋白尿。以上我概况了除了收缩压和舒张压这两个极端值之外,我们还能用哪些无创方法得到关于血管床的更多的信息。
  下面,我谈谈心脏的评价。我们要记住心脏是一个内分泌器官,因为心脏合成氨基端前脑钠尿肽,活性形式为脑钠尿肽(BNP)。我认为,当前我们已经有足够的证据提示,BNP是心血管死亡和心血管疾病显著的预测因子,而不仅仅是用于诊断心衰。我经常会观察心衰患者的BNP变化,就像感染科专家在肺炎等感染患者会观察白细胞计数的变化一样,但是我们可以在更早的阶段做这样的事情。另外,我们知道心电图是有用的,因为可以提供指纹样的信息。因胸痛或心律失常就诊的患者,如果心电图没有明显异常的话,可以帮助我们判断,尽管女性倾向于有一些心电图异常但是仍处于正常范围之内。当患者没有主诉时,比较心电图是有趣的,心电图简便易测且花费低廉。对于舒张期功能障碍,超声会提供有关心室重构的信息,关于心室舒张、泵血功能和射血分数的信息。因此BNP、ECG和心超这3种手段能够让我们更为全面地看待高血压患者的心功能。
 

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管纤维化动脉僵硬度舒张期功能障碍D.Duprezishare

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