<International Circulation>: Vascular fibrosis and arterial stiffness are two situations of vascular remodeling. How will they affect cardiac function?
　　Prof. Duprez: In the whole process of essential hypertension， one of the major issues with ageing is the development of vascular fibrosis which means that the number of elastin fibers in the extracellular matrix will go down and these elastin fibers make the blood vessel more elastic. Then the second major component of the extracellular matrix is collagen. Within the scope of inflammation， diabetes and obesity and even with the ageing process， you see that there is much more synthesis of collagen but also its breakdown and the collagen fibers become less uniform and more in disarray. As a consequence the vascular fibrosis will influence the arterial stiffness (which is the reverse of arterial elasticity) and this is determined by two main components. The passive component is the inert structure of the extracellular matrix mainly elastin and collagen fibers and on the other hand there is the active dynamic component which is determined by the arterial vascular smooth muscle tone. Vascular smooth muscle tone is determined by the regulation of the autonomic nervous system and local humoral factors. So if the vessels are stiff then it is logical that you will see with ageing that the systolic blood pressure value will increase while the diastolic blood pressure either doesn’t change or has a tendency to go down. As a consequence the difference between the systolic and diastolic blood pressures， what we call the pulse pressure， will increase. As the heart pumps blood out through the aorta to distribute oxygen and nutritional elements to the different tissues， if the arteries are becoming stiffer， we see an effect on wave reflection.  At the end of the arterial system at the level of the arterioles， there is reflection of the waves back. If these vessels are increasingly stiff (you can compare them to a water hose)， then these wave reflections come back earlier and earlier， not only during diastole but during systole. As a result， when the aortic valve opens and the heart starts to eject the blood， and wave reflections are coming in， the load on the heart increases and the heart has to exert much more effort to pump blood out. This leads to increased left ventricular mass and left ventricular hypertrophy while on the other hand， we see that the whole process of fibrosis then occurs not only at the level of the blood vessels but also at the level of the heart. That is one of the reasons why diastolic dysfunction is responsible for more than 50% of hospital admissions for heart failure. We see in ageing， especially in women， more diastolic heart failure because their vessels get stiffer. One other major determinant is height. The shorter you are， these wave reflections are returning much earlier and further to that there is a change in hormones in women. We looked at the Multi-Ethnic Study of Atherosclerosis (MESA) where there are more than 6600 people and about 20% of those are Chinese. We can see that Chinese women have the lowest arterial elasticity or inversely translated， Chinese women have the highest arterial stiffness. In the Chinese population， hypertension is becoming a major problem and I suspect that because they live longer， there will be even greater consequences on their diastolic function. They will develop diastolic dysfunction which means there is an impairment of the left ventricle to relax to fill which leads to pulmonary congestion despite the systolic pumping function remaining normal.

　　《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？
　　Duprez教授：在原发性高血压的整个疾病进程中，老化所带来的主要问题之一就是发生血管纤维化，这意味着细胞外基质内弹性纤维的数量减少，弹性纤维使得血管更有弹性。另外，细胞外基质的另一个重要成分就是胶原。在炎症、糖尿病、肥胖甚至是在老化的情况下，会观察到胶原合成增加，但是降解也加速，胶原纤维变得不那么整齐了，更加混乱。因此发生了血管纤维化，这会影响到动脉僵硬度（这是与动脉弹性相对应的指标），动脉僵硬度由两个主要因素决定。被动因素是细胞外基质不变的结构，主要包括弹性纤维和胶原纤维。另外还有活动的动态因素，是由动脉血管平滑肌张力决定的。血管平滑肌张力是由自主神经系统和局部体液因素共同调节的。所以如果血管僵硬度增加的话，随着年龄的增加当然会表现为血管僵硬度的增加，会导致收缩压升高，而舒张压无变化或有降低的趋势。因此使得收缩压和舒张压之差脉压升高。当心脏通过主动脉把血泵出去，将氧和营养物质输送到不同组织时，如果动脉僵硬度增加的话，会对脉搏波反射有影响。在动脉系统的终末端，也就是小动脉水平，有脉搏波被反射回来。如果动脉僵硬度增加的话（可以把动脉比作水龙头），那么脉搏波会更早反射回来，越来越早，不是在舒张期而是在收缩期反射回来。因此，当主动脉版瓣开放，心脏开始射血时，脉搏波反射回来了，使得心脏负荷增加，心脏就得做更多的功才能把血泵出去。这使得左室重量增加，同时发生左室肥厚，另外我们会看到整个纤维化的过程不仅仅是在血管水平发生，也在心脏水平发生。这就是舒张期功能障碍占到因心衰入院的50%以上的原因之一。我们在老年人群（尤其是女性）见到的舒张期心衰更多，因为老年人群的动脉僵硬度增加。另一个主要决定因素是身高。个子越矮，脉搏波反射回来就越早。另外，女性还有激素水平的变化。我们看了多种族动脉粥样硬化研究（MESA）的数据，该研究纳入了6600例患者，其中20%的患者是中国人。我们可以看到中国女性的动脉弹性最低，反过来说就是中国女性的动脉僵硬度最大。在中国人群，高血压已经变成了一个主要问题，我猜测由于女性的寿命更长，因此对心脏舒张期功能的影响也就更大。她们会发生舒张期功能障碍，这意味着左室舒张功能受损，导致了肺淤血，尽管此时收缩期泵血功能是正常的。
 

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