Central aortic pressure, it is rapidly evolving as a concept and we would like to know from you a lot about that. So let me begin with you asking a simple question, that what it is, how it is different from let us say routine measurement of brachial blood pressure via the sphygmomanometer?
As we call know, hypertension appears to be a major risk factor for premature and excessive cardiovascular disease in our country. The diagnosis of hypertension is generally made for more than 100 years by measurement of blood pressure in the arm from the time of Riva-Rocci &Korotkoff. Measurement of blood pressure in the arm has served well, in fact it has been the basis for all major clinical trials of the last century. It is convenient measuring the blood pressure in the arm and it is relatively easy and does not require any special technical expertise and because of the convenience, it is applied widely. But what has become apparent in the last 20 years is the blood pressure that is generated by the heart also known has central aortic blood pressure is more sensitive than brachial blood pressure in predicting the cardiovascular profile and also in predicting the cardiovascular risk. When we talk about target organ damage in high blood pressure, the main target organs that are affected by untreated and uncontrolled hypertension are the brain, the heart and the kidney. The blood pressure that is experienced or sensed by the so called vital organs is the aortic blood pressure, not the brachial blood pressure. So the closest proximity of the real blood pressure and target organ effect appears to be the central aortic blood pressure because that is the blood pressure that is felt by the heart, the brain and the kidney. Central arterial blood pressure when it was developed was an experimental technique and was also quite invasive requiring cardiac catheterization, but there has been a rapid development in the science of central arterial blood pressure in a more convenient way and in a more noninvasive way by a variety of methods but the basic principal is applanation tonometry where one can estimate the central aortic blood pressure in a noninvasive way by looking at so called pulse wave analysis or also known as PWA. When you analyze the pulse wave, it is an indirect reflector of central aortic blood pressure. When the heart pumps, it generates the blood pressure and it generates the pulse wave but generated pulse wave comes back to the heart known as reflected wave. The combination of onward namely generated and backward namely the reflected wave is an estimate of central aortic blood pressure. So using a mathematical formula, by looking at pulse wave analysis, these days it has become very easy to estimate central aortic blood pressure in a noninvasive fashion and there is a good correlation between central aortic blood pressure that is measured non-invasively and which is measured invasively. So the stated art now is that central aortic blood pressure measurements have become very reliable, very reproducible, and very predictive of cardiovascular risk profile. Some studies have shown that there could be discrepancy between the central aortic blood pressure and peripherally measured blood pressure namely brachial blood pressure. Cardiovascular prognosis of patients depend a little bit more on central aortic blood pressure more sensitive than peripheral or brachial blood pressure. Prospective epidemiological studies such as strong heart study have confirmed that the central aortic blood pressure is a determinant of cardiovascular outcome. For example, in the strong heart epidemiological prospective study, central aortic pulse pressure greater than 50 mmHg was associated with significant Cardiovascular disease, not directly related to brachial blood pressure, suggesting that the target organs are much more sensitive or affected by central aortic blood pressure. Other studies have also shown that in comparison to standard blood pressure measurement, central aortic blood pressure gives a better marker of overall cardiovascular function or cardiovascular disease. So now we are looking whether we can improve the management of high blood pressure with greater precision by looking at central aortic blood pressure. There are more and more data that are being collected confirming that central aortic blood pressure is a mirror of what is happening in the body in comparison to brachial blood pressure. There are also studies showing that when you look at the pulse wave analysis, they can quantitate what is known as augmentation index. Augmentation index actually correlates with central aortic blood pressure. Whenever augmentation index is high, it is indicative of high central aortic blood pressure. Studies have shown for every 10% increase in central aortic blood pressure, there is 30 to 35% increase in cardiovascular morbidity and mortality suggesting that augmentation index which parallels aortic blood pressure, any increase in this parameter is reflected by target organ damage and premature death. So I think the science of central aortic blood pressure is now quite mature, quite established and quite validated showing that it is a little bit more sensitive indicator of cardiovascular function. Other studies have shown that antihypertensive drugs, despite similar effects on brachial blood pressure may have dissimilar effects on central aortic blood pressure. Couple of studies including so called Ascot trial have shown that when you use two antihypertensive drugs which have similar reduction in brachial blood pressure, the cardiovascular outcomes were different. The drugs that lower central aortic blood pressure appear to decrease morbidity much more than the drugs that only reduce brachial blood pressure without reducing central aortic blood pressure. Similarly angiotensin converting enzyme inhibitors which are particularly tissue selective have been shown to reduce central aortic blood pressure significantly. So looks like vasoactive calcium channel blocking drugs, vasoactive angiotensin converting enzyme inhibitors appear to lower central aortic blood pressure and that might provide an advantage in reducing the cardiovascular risks. So in the future, there is a strong possibility that the therapy of hypertension may be guided by the central aortic blood pressure measurements and also may be guided by specific therapeutic antihypertensive drugs, which have an effect on central aortic blood pressure and these are the drugs I call them as vasoactive drugs. So from indirect crude brachial blood pressure measurements, we have moved towards little bit more precise, more accurate blood pressure that resides in the heart and cardiovascular system. In terms of treatment, from nonselective indiscriminate use of antihypertensive drugs, we are moving towards selective utilization of vasoactive drugs that lower the blood pressure where it matters the most, namely in the aorta. This kind of a physiological and rational treatment might provide greater benefits in the long run. As you know that some patients who have hypertension although the blood pressure may be controlled, they still have so called residual risk and it is possible that residual risk may be presided or governed by persistent increase in central aortic blood pressure. So what we see in the arm is not what is seen in the aorta and that might be reason why some patients despite good blood pressure control continue to have progression of vascular disease. It remains to be seen whether good control of central aortic blood pressure will prevent the onset and progression of cardiovascular disease in the future. I think this is a tool that is going to be very prominent. This is a tool that used to be mainly research tool until five years ago, this was a tool that was mainly an invasive tool 10 years ago, the scenario in 2016 has changed where the tools have become practically applicable in the clinic or in the office and they are reliable, they are quantifiable, they are reproducible and perhaps further research and further utility in clinical practice might put the role of central aortic blood pressure in proper perspective for future guidance in the treatment of hypertension.
Thank you so much sir. You have very clearly stated the role of central aortic pressure along with the therapies which are in market and which are vasoactive, specifically regarding central aortic pressure to reduce further residual risk. I would like to ask one more question to you regarding central aortic pressure. Hypertension is often associated with comorbidities mostly in a diabetic or pulmonary artery disease patients or associated with chronic kidney disease. Any particular central aortic pressure markers or how does it vary in a patient who is just hypertensive versus having comorbidities?
Very good question. In fact, there are data in patients who have chronic kidney disease and hypertension, they have very high central aortic blood pressure compared to brachial blood pressure. As you know, patients with chronic kidney disease are prone to develop hypertension and they are prone to develop cardiovascular disease and it looks like this cohort of individuals who have chronic kidney disease have central aortic blood pressure and this is a population that has to be treated very aggressively, otherwise many of these patients die, and it is important to identify the cardiovascular profile in patients with CKD to see if they have elevated central aortic blood pressure and the therapy should be guided towards lowering central aortic blood pressure. Another subset of population where central aortic blood pressure appears to be high are patients who have diabetes. As you know, diabetes is associated and accompanied by extensive cardiovascular disease, mainly due to hypertension. Patients who have chronic diabetes and who are at the risk of developing cardiovascular complications appear to have high levels of central aortic blood pressure. So another comorbidity or subset of patients in the community where central aortic blood pressure may be a determinant of their outcome could be diabetic. So CKD and diabetes and perhaps even obstructive sleep apnea, these are the conditions which pose tremendous cardiovascular risk, but the common threat for all these conditions appears to be increase in central aortic blood pressure. There is also one study that I want to mention that measured central aortic blood pressure prospectively in 1700 individuals who were normotensive, but those individuals who had central aortic blood pressure subsequently developed hypertension. So it looks like measurement of central aortic blood pressure early on may be a harbinger or may be a forerunner before the establishment of so called fixed hypertension. So it is possible that in the future when you want to screen young individuals like high school students, college students, adolescents where the brachial blood pressure might be normal, but if they have high central aortic blood pressure, they should be under closer surveillance because they might develop regular hypertension. So it is possible that this central aortic blood pressure might be used as so called prophylactic tool in making early diagnosis of hypertension and then either prevent its progression or be treated appropriately.
Thank you so much sir.