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Date: 27-10-2012 Symposium on Hypertension

By Dr. Rajiv Karnik , Dr. Bhaskar Shah , Dr. Uday Jadhav , Dr. Sadaanand Shetty and Dr. Ajay Mahajan.

Symposium on Hypertension 


Dr. Rajiv Karnik:  Hi,


We are going to have a symposium on hypertension, and I will be giving the preamble that why we are having this symposium, what we are going to discuss, and we have excellent panel with us.  We have Professor Uday Jadhav from MGM Hospital, New Bombay.  We have, Dr. Bhaskar Shah; director of the cath lab Jupiter Hospital, Thane, and he is an interventional cardiologist.  We have Dr. Ajay Mahajan who is professor of cardiology and unit head in LTMG Municipal Medical College.  We have Dr. Sadaanand Shetty who is professor and head of the department of medicine in D.Y. Patil, New Bombay.


Now, why we have taken this symposium, hypertension?  If you see the slide about the latest publication in DTT 2012 January issue by Dr. Shashank Joshi, he has given this frightening prevalence of hypertension, which is 46%, and moreover hypertension and diabetes together 20%.  It is commonly said that hypertension, diabetes and dyslipidemia; these 3 are the closely related cousins, which conspire to finish the mankind, and we have such high prevalence.  As you can see here in Lancet 2005, it was shown that about 60 million men and women were affected with hypertension and by 2025 we are going to have over 100 million men and over 100 million women with hypertension, and worst of all it is in the young people.  Dr. Atul Mathur from Fortis Escort, New Delhi, he has literally shown this frightening picture that from 10% of prevalence below the age of 40, now we are heading towards almost 30%, 3 times increment, and moreover this rapid escalation of the risk factors in the adolescent age make this sea change and then that leads to this hypertension.


Now, but is hypertension treating important, because if you see the past and the present, there is a sea change.  Now, for example, in 1911, it was thought that essential hypertension is essential because high BP is required for circulation and in BMJ, 1931, they had said that greatest danger to a man with high blood pressure lies in the discovery, because some fool may try to reduce it.  So, it was thought that treatment of hypertension is absolutely not justified.  That is why Franklin D. Roosevelt, President of United States of America, when he died his blood pressure was over 300 systolic and over almost 200 diastolic, and he had this kind of high blood pressure for more than 10 years, and he had not taken a single drug because during those days it was thought that hypertension treatment is absolutely not needed.  But, of course, now we have Framingham Study showing that hypertension is associated with various risks and with treatment of hypertension, there is a tremendous benefit which we can see by treating the hypertension as indicated way back in Veterans Administrative study too,  Just nearly 2 mm decrease in the systolic blood pressure, reduces 7% ischemic heart disease mortality and 10% reduction in the stroke mortality, and this figure is not just one small trial, but this is 16 meta-analysis of 61 prospective observational studies with 1 million adults and 12.7 million patient person-years and moreover it affects kidneys and then associated dyslipidemia, which makes the heart to suffer and then that is why we will see that it is #1 killer worldwide if you compare all the other disease spectrum, and right from 115/75 we gradually go on increasing the CVD risk, as with every 20 mm increment in the systolic and 10 mm increment in the diastolic, there is almost doubling of the CVD risk, and even this pre-hypertension is not without any risk.  So, the classification goes on changing with new discoveries.  In earlier days JNC-I, JNC-II, JNC-III, there was no discussion about systolic blood pressure.  Everyone thought that it is the diastolic which is important, but as the time is progressing the scenario is changing.  The drugs from 1940s till 2007, there is a vast armamentarium of different kinds of drugs, which are getting added to the direct rennin inhibitors, now recent addition, and even the antibodies to angiotensin-receptor will be the next addition in our armamentarium.  But nevertheless, if you see all the trials in which the optimum BP reduction is required, I mean multiple drugs are required, it not just monotherapy, but 2, 3, and even 4 drugs are required, especially, if the person is diabetic as in IDNT and in Africans as you can see multiple drugs are required and then some of these drugs are synergistic, some of these drugs are not synergistic and a deep knowledge is required to know that which drug one should combine with the other and in which subgroup and then more often we become very happy and we rejoice that alright, we have given treatment and we have reduced the stroke by 40%, 50%, or major cardiovascular event and CV death by 30-40, but what about the residual risk.  Can we do something about it? Are there better combinations? Are there better molecules? Are there some molecules which are underrepresented in the various clinical trials and which we normally read about and that is what we are going to discuss this in today's symposium that what has made this sea change from the oldest view, should we treat or whether we should not treat, what target, what medicines, what combinations.  So, all this matter will be discussed in today's symposium and that is why I would invite first, Dr. Uday Jadhav and he will be discussing on the investigation part.


Now, Dr. Uday Jadhav, this blood pressure, we know that since long time, people get worried and even our patients, the first question they ask is what is my blood pressure, 140/90, everybody is just interested in that number, but is number all that important or is there any associated hypertension as a syndrome and associated disease spectra. Which goes even in the sub-clinical phase along with the number and then along with number we have to consider something else.  What I mean to say is that the sub-clinical damage because we know this LVH, micro-albuminuria and kidney damage, which has been talked about a lot, so could you highlight on these particular aspects.


Dr. Uday Jadhav:  Thank you Rajiv.  What we have been trying to discuss today is the investigation and risk assessment for hypertension.  This is a parallelism in which you have the diabetes where, like diabetics, hypertension is associated with a sub-clinical atherosclerosis and it is not just about getting the blood pressure readings down or getting the blood sugars level down, we need to look at the complications, anticipate them, prevent them, and that is where this whole issue about trying to find out the sub-clinical organ damage will come into play.  The best guidelines we have till date were the 2009 ESH Guidelines as you can look that, in hypertension, it is the assessment of the total risk, which should be important both for initiation, the intensity, and the goal of the therapy.  This will necessarily involve the identification and the quantification of the total cardiovascular risk.  If you look at the common investigations that are of utility to detect sub-clinical organ damage, they would include the ECG, the echocardiography, and of course estimation of the inner function by the estimation strategy, GFR.  Not simply looking at the creatinine level because we have now gone beyond that.  We say now it is important to look at the estimated GFR.  So, this task force document came in 2009.  It is probably one of the best documents looking at what can be done for this issue.  We do know a lot about left ventricular hypertrophy that adds to the risks, it tells us about cardiovascular morbidity and mortality and the risk of a stroke.  But, let me highlight couple of very important points that as clinicians we can offer that risk management in practice.  If you look back at the LIFE trial and then look at 2 issues, one is the identification of left bundle branch block pattern in hypertensive subjects puts them at an  increase risk of cardiovascular mortality of 1.6 times.  There is also increase in the sudden cardiovascular death and the hospitalization for heart failure.  Two, we need to also carefully look at the lead aVL.  The R-wave voltage in lead aVL is associated with left ventricular mass index and it is predictive of the cardiovascular events.  Even in patients, where the ECG otherwise does not show left ventricular hypertrophy, so aVL becomes extremely important.  You see a 9% higher risk for each 0.1 mV increase in the R-wave.  The LIFE study was an important lesson in this and PAMELA, which looked at the risk, has already told us, that LVH is associated with a 4/5 fold increase in cardiovascular morbidity and mortality and is very important, irrespective of the confounders, so that is home pressure, the office pressure, or the ambulatory BP whatever you are looking at can be distinctive point.


The other thing which Dr. Rajiv Karnik just talked about, as mentioned in slides on the GFR, the ADVANCE study showed us a very important message.  The eGFR estimation is important as in diabetics and hypertensives too because for every 50% reduction of the baseline eGFR, the risk of CV events will go up to 2.24 and the risk of cardiovascular death itself goes up by 3.64.  A change from the clinical stage of albuminuria, let us say from normal albumin to microalbumin to macroalbumin to overt nephropathy is associated with an increasing trend towards morbidity and mortality from cardiovascular events, say, from 1.6 fold it will go up to 3.34 once there is overt nephropathy.  The high baseline urinary protein excretion and the reduced eGFR, independent of each other, and the association of microalbuminuria and the eGFR of less than 60 mL/minute per 1.73 m sq of the body surface get a higher risk about 3 to 6 fold risk in terms of cardiovascular morbidity and mortality.  So, the ADVANCE study showed us a very important lesson in this.


Dr. Rajiv Karnik:  Well, this was about the target organ damage and heart, kidney, that were discussed, but Dr. Uday Jadhav, before the target organ gets damaged, we have a stage where actually the vascular remodeling, the vascular stiffness increases or the vessels start showing signs of early atherosclerosis, before actually the ECG and then the stress test and other things start showing.  So, again the sub-clinical phase where we want our listeners to know about, so like what are the ways in which we can detect this earliest involvement of the vessel before it is actually evident in the form of overt disease?


Dr. Uday Jadhav:  True, the carotid intima-media wall thickness is a very simple tool of measuring the thickness of the carotid artery and there have been about 4 very important landmark epidemiological studies based on this.  We had the MESA, we had the ARIC study, the ELSA, and the Copenhagen Heart County Study and when we look at the hypertensive population, per se, where you look at the common carotid wall thickness which is very simple to do, it would tell us how much the vascular hypertrophy is and once you go with the bifurcation and then start assessing its value, it tells you how much is the atherosclerotic profile.  It is so very important because this a prognostic factor as the carotid thickening increases over a decade, 2 decades it takes about 2 years minimal for progression of the carotid-intima wall thickness and therefore when you evaluate drug trials we must look for at least 2 years of data to see whether there is a regression of the thickness of the arteries, and I will take few slides from the KK Datey Memorial Oration, which I delivered last year at the CSI, and I guess, this is what we need to remember in clinical practice that we use noninvasive tool for atherosclerosis, it should be simple, noninvasive, widely applicable in any part of our country, reproducible, standardized with the laboratories, and have some population normal data to inform the interpretation and should be able to predict the risk and know that this risk will be able to identify patient with the lines.


So, this is what we just said about the carotid-intima wall thickness, the common carotid artery, is the bifurcation, so you can look at the far wall from the probe and when you look at the artery this is the adventitia, you see a green line here, this is the nucleus, so this the near wall, far wall, this is the intima media wall thickness, between the intima and the media.  So, it is very simple to identify, absolutely easy to do in clinical practice.  Look at these 2 subjects of hypertension, one has a thin intima-media wall thickness, the other one has a thicker initima wall.  If you look at such patients and in our studies in Indian population, anything beyond 0.8 mm at the common carotid artery would put them at a three-fold risk for getting cardiovascular events.  Besides, of course, the risk of stroke, and if you a have plaque, which means the arterial thickness is more than 50% of the surrounding wall or per se if the IMT is more than 1.5 mm it tells that the wall is thick.  Now, what does this offer? whom should you subject for test for sub-clinical atherosclerosis assessment?  Even in the hypertensive population, if you have patient whose initially probability of risk is low, the post-testing probability will still keep him in and those patients who are already at high risk, let us say, if you have hypertension with diabetes with a smoker, I do not see a great point trying to look for sub-clinical atherosclerosis because it has already been done.  But, if you have an intermediate probability, 10-20%, this is where the initial probability though low, when you do intima-media wall thickness or endothelial function study, the post test probability will put them at a much higher risk.  And that is one of the nicer articles which came from the Framingham Offspring, which said that you can look at the maximum common carotid artery wall thickness, you can also look at the mean arterial thickness of 16 segments and they are good enough to tell you what the risk is.


The other one is the pulse wave velocity and it is so simple that in clinical practice it is the pulse pressure. it is not the systolic, it is not the diastolic.  It is the difference between the 2 which when it exceeds, on average, 60 mm always tell you that the patient is at a higher risk, because that denotes by itself that the arterial walls are thick, the central aortic pressures are very high, so the central aortic pressure will be high and the augmentation index will be high.  Now, let me come back on one hypertension study, which told us this risk.  We had the ASCOT-BPLA Study that diuretic and atenolol and the comparative are the calcium blocker with ACE inhibitor and although the blood pressure reduction over the next 3 years was the same between the 2 arms, they fared equally well.  There was such a huge difference between cardiovascular event reduction, morbidity, and very importantly mortality; and a substudy of this was called as the CAFE study.  The CAFE conduit study looked at the central aortic pressure in these 2 segments of population.  The one who were on atenolol with diuretics, the central aortic pressure did not change, it remained the same.  But in the subset of patients who were given calcium channel blockers and the ACE inhibitors, the central aortic pressure went down, the augmentation index went down, and there we told you that the aorta being more supple, the amount of cerebrovascular risk reduction in terms of stroke would certainly be better and also you would have lesser pressure put on the heart and therefore the cardiovascular events were also lesser.  This is one of the fundamental studies we did and we had the Basu Award for this where we check the pulse wave velocity, central aortic stiffness, looked at the peripheral arteries and showed very good correlation.  The central dots where they all come together tells you the concentration of the dots here that the arterial stiffness in the aorta and the flow-mediated dilatation on the brachial artery, the endothelial function has a very good correlation, which means that if the arteries in the periphery are supple it does reflect on the aortic pressure and that in normal aortic pressure also tells you immediately that the arteries are much more supple.


Dr. Rajiv Karnik:  I think you have covered the thing because the last thing that was lingering in my mind was the endothelial function because we are going gradually retro, retro, and then finally the sub-clinical atherosclerosis to the pulse wave, the vascular remodeling, and then even before that the primordial event in the vascular pathology, pathobiology, is the endothelial dysfunction, and I think from there the subsequent cascade of events takes place and then that is what I was about to ask you about endothelial dysfunction, but just now you have already highlighted about the Basu Award relation.  So, I am very glad that this is very nicely covered with all the recent advances in the disease process of hypertension as a syndrome and not just BP number reduction.  Thank you.


Thank you, Dr. Rajiv, it is pleasure.


Dr. Rajiv Karnik:  Yes, after this detailed discussion on the investigation of subclinical atherosclerosis and pulse wave velocity, etc.  Now, let us come to treating to targets.  Now, we have Dr. Bhaskar Shah who is clinical and interventional cardiologist and director of cath lab Jupiter Hospital with us.  Dr. Bhaskar Shah, I would like to ask you first that earlier we discussed that BP is just not the number, it is not that 140/90 or 130/80 or whatever, this thing.  It is, we were discussing that, it is a disease syndrome, so what makes people feel that way.  What is the difference between this number versus the syndrome.


Dr. Bhaskar Shah:  Dr. Karnik, as already explained by my dear friend, Dr. Uday Jadhav, that it is not merely higher blood pressure, which is responsible.  What we are really talking is the risk for coronary disease and we are talking of risk for coronary artery disease, which was very elegantly exemplified first in very basic times, somewhere in 1989, published in hypertension journal, that if you have a patient and you can look at a patient whose blood pressure is controlled, but not adequately controlled, they have a risk of about 2 times higher than a normotensive patient.  Now to control the patient well, despite that there is approximately 30% extra risk which still persists despite adequate control of blood pressure.  This was the first time people started thinking that if the pressure is well controlled, why the risk does not talk about the normotensives and that is where, we got the first clue that it is not only blood pressure, its associated risk factors, like diabetes, hyperlipidemia, and various other risk factors we could talk of when they are adequately controlled then only we will be in a position to get down the risk from a hypertensive not treated to a hypertensive treated, both coming down finally to range of normotensives.  This first trial in 1989 was a thing which gave us the clue that it is not only control of pressure, it is something beyond and that is control of associated risk factors is extremely important to get down to a normotensive risk and then later on there were multiple trials, the most important of them being HOPE trial, which clearly showed that in a patient who was normotensive also controlling other risk factors brought down the risk to very low risk.  So, that was first important thing, blood pressure is not just the number, it is essentially, the patient as a whole the risk for the coronary artery disease to be treated, to get down the maximum benefit of reduction of coronary artery disease.


Dr. Rajiv Karnik:  Very nicely said.  Now, the second point.  When you are treating, you said that adequately treated and very well treated, so that brings us to the next question, actually this very well treated and better treated, now there are different values.  Now, once upon a time it was thought that there is a crucial J-curve and then as you go below, at a particular level, there is optimal result, and again there will be increase in the reading.  Then, again there was some feeling that no, no there is no change and then whatever goals are right.  Then of course, in the literature there were some trials and some other which made the people think that lower is not the better.  So, which are those trials and then can you highlight trials and then which made the guidelines switch?


Dr. Bhaskar Shah:  Now, if you really go back to the 2002, in Lancet, there was a huge meta analysis that was published.  From 61 prospective observational studies of more than 1 million adult individuals indicated that deaths from CAD and stroke increased progressively and linearly from BP of 115/75 and this one of the major trial which further analysis elucidated which was instrumental to put down that anything lower the better, 115/75, getting down the pressure would be desirable option and that is why JNC-VII stressed a lot that getting the pressure to lower would be a better option.  However, there are 2 important trials which have come after that and one of them being ACCORD blood pressure trial.  Now, what did it say? What was the study?  This study was about randomized multicenter clinical trial in more than 77 clinical sites in North America and the basic question which was there in the trial was does a therapeutic strategy targeting blood pressure below 120 mm reduce the coronary event rate to a strategy where the blood pressure was below 140 in patients with diabetes and high risk for CVD and really what were the conclusions.  If you really look at the primary and the secondary outcomes, what was found and was most important thing was in an intensively treated patient, where the blood pressure was brought down below 120, if you look at the cardiovascular risk and then mortality, both were higher or it is not something really different from the patient where the standard treatment of blood pressure was around 140.  This was one of the major trial which showed that intensive treatment did not give any benefit in terms of total mortality or cardiovascular death.  However, if you look at the stroke incidence it was significantly lower in a patient with intensive events.  What it means thereby is that if you look at the role of nonfatal MI and events were better off.  However, the cardiovascular deaths as you could see in this intensively treated were a little higher then the standard therapy, and that is why the conclusion was that ACCORD BP Trial, which evaluated this still provided no conclusive evidence that an intensive BP control strategy reduces the rate of composite of major CVD events in such patients.  That was one of the major thing and that could clearly tell us that intensive treated significantly reduced nonfatal stroke rate event in standard was 50% lower. However, in good control sugar and cholesterol cardiac benefits still longer than 5 years and then there was another major trial known as INVEST trial.  In that this post hoc analysis of blood pressure control in diabetic patients in this INVEST trial showed that tight control of systolic blood pressure was not associated with improved cardiovascular outcome compared with individual care.  That were 2 major trials, that was one was ACCORD and INVEST.  However, other than this message very clearly says that lower is better for the brain, BP and time, but not for others.  These 2 major trials are there which are now trying to tell us that lower is not always better and maybe at some point of time mortality goal are decreasing and that will give us a clue that there is something known as J-shaped curve in elderly patients.


Dr. Rajiv Karnik:  Now, after discussion of these different targets about lower is not better but then what is optimum?  So, that brings us to the next question, that what are the different numbers or targets which you think, in different circles, not just one whole population that it will be only 140/90 or 130/80, so in different populations what are the numbers that you would prefer and different guidelines, like American, Europeans, Australian, or for Indian so they will differ from population to population and disease spectra.  So, can you give the audience your views about the targets.


Dr. Bhaskar Shah:  After these 2 trials there was an editorial commenting on the optimal blood pressure levels in patient with coronary artery disease and vice versa.  That also brings us to what do we expect in JNC-VIII based on the literature available now and what the example to go through, how long, how low do we go in diabetic, in CKD, in elderly patients, how do we get there and then a brief background of the NICE guidelines which has the latest available guidelines from 2011.  If you really look at all the guidelines from JNC-IV to V to VI and VII, you see that the target have been becoming lower and lower.  It is what we expect now in JNC-VIII is probably the target cannot be further lower, but on the contrary, it might be a little high.


Look at this data from SPRINT, in the elderly patient it has been determined that for all between age of 65 to 79, BP below 140/90 is okay, but once you reach 80 and above probably 140-145 mmHg if tolerated is reasonable.  Look at the same data on hypertension patient with CKD running vis a vis, what is most important thing coming out is the BP less than 130/80 mm is not defensible to slow nephropathy progression unless there is a severe proteinuria.  That means, till date we used to say that in all CKD patients the blood pressure should be brought down below 130/80 and now there is a theory to that, sometimes there is severe proteinuria it may not be right.  What we are trying to say is that high risk patient, yes, otherwise probably 140/90 mmHg for most of the patients and 130/80 for proteinuria or very high risk stroke patients.  Look at what was Current Guidelines One Size Fits All Approach.  BP:  We used to recommend lower BP goal for all patients with diabetes and CKD based on average results of relative benefits, irrespective of risk that was not tailored to individual underlying risks and we were assuming that all patients are high risk, but nowadays, we do not clearly feel that.  Similarly, if you look at American Diabetic Association's Standards of Medical Care in Diabetes, what does it say?  Goals of systolic blood pressure less than 130 mmHg is appropriate for most patients with diabetes.  Based on patient characteristic and response, higher or lower BP may be appropriate, and patient with diabetes should be treated to diastolic blood pressure of less than 80 mmHg.


If you look at the NICE guidelines based on the data which was available, person-centered care was given, if the patient who was 80 years or below, pressure goal was around 140/90 mmHg and what is more important is the ambulatory BP monitoring is coming gateway in diagnosing, we would be probably coming to that very frequently, and there BP 135/85 mmHg is probably the goal what we are looking at.  In terms of age, patient who is above 80 years NICE guidelines says that a blood pressure of 150/90 otherwise, but on ambulatory BP monitoring 145/85 and that is where NICE diabetic guideline what does it say?  Till date we used to say that 130/90 mmHg was for everyone, now what it says is 140/80 mmHg for most people with diabetes.  However, if the patient is high risk, like microalbuminuria, eGFR (estimated glomerular filtration rate) less than 60 or retinopathy or prior stroke or TIA then probably you should try to get a goal of 130/80 mmHg.  This is different from what we see, till date we used to say 130/80 mmHg for everyone, now it is 140/80, and high risk will be 130/80 and then question comes up is how do we go there?  Thiazide and diuretics and beta-blocker.  Will thiazide remain the first line?  Most of the guidelines do not specify thiazide as first line.  Beta-blocker probably is now going to be limited only to post MI patient.  In diabetics, ACE and ARB is very important.  Elderly maybe thiazide, diuretics are very important.  That is why, we have a simple guideline, NICE guideline, which tells us very clearly that as far as drug therapy is concerned, below 55 years of age, ACE/ARB; in diabetic, above 55, CCB and if later on high, give a combination; and resistant we will have along with that may be an alpha blocker.  If you are talking about other guidelines like when we are talking of JNC-VII, there are VA (Veterans Administration) guidelines, which still say that in diabetics it should be 140/80 and not 130/80.  With CKD it was also they thought that it should be 140/90, so that means there were people who had when JNC-VII was there, were strongly feeling that BP, even in diabetics and CKD they are not high risk, it should be 140/80 and 140/90.


Look at what is the target diastolic blood pressure which we are looking at.  The most important guideline, the trial, which gives us some idea is the HOT trial where patient were divided into 2 subsets and pressure was brought down below 90, between 85-90, and below 80, and what it showed was that the outcome for different BP groups was not statistically significant.  Meaning, thereby, trying to get down below 80 or below 90 were equal and they thought probably there is no major benefit of trying to get down pressure too low.


Similarly, systolic blood pressure target, multiple trials like SHEP trial, Syst-Euro trial, Syst-China trial, HYVET trial and all of them finally showed that significant reduction in primary and/or other CVD events of mortality were to get down systolic blood pressure.


Now this, if you look at BP targets in chronic kidney disease, 3 randomized trials; MDRD, AASK, and REIN finally show that no conclusive evidence favoring a BP target of less than 125/75 to 130/80 rather than 140/90.  Again, trying to show that lower is not the better, getting to 140/90 is what we are looking at.


Looking at the diabetic, same 3; ACCORD trial, ADVANCE trial all of them are very clearly showing that lower BP is not good, probably trying to get to a little higher 140/90.  Lastly, there are written consensus as have already told by previous speaker that all of them, irrespective of what we do, quite a lot of patient will need multiple drug therapy and that is probably going to be a guideline that combination therapy.  Two major trials which I am trying to show that one common trial of ACEI with hydrochlorothiazide versus CCB very clearly showed that ACE with hydrochlorothiazide was not good as ACE/CCB combination was better.  A company's trial and similarly Escort trial did show that.  Finally, that tells us that combination therapy provides prompt and effective BP control and combination therapy with ACEI, ARBs, and CCB is superior to thiazide-based combinations.


So friends, in all what we are trying to say is that a time will come where we will say that lower is not better, so most of the patient 140/90.  We will always look at the risk in the patient and then finally quite a lot of them will need a combination therapy.  Thank you.


Dr. Rajiv Karnik:  It was a wonderful presentation Dr. Bhaskar.  The way you started the slide then I started getting confused, so many different subgroups and so many different societies giving different values, but at the end you have simplified.  This 140, remember 140/90 and 130/80, are absolutely fine.  Thank you.


Dear friends, now we have seen that we have decided the target, but it is very difficult to reach the target and then we have different medicines in our armamentarium, but it is very difficult for a general practitioner to decide that which drug in which subgroup and how to choose them, so to answer that we have Dr. Ajay Mahajan, Professor Ajay Mahajan, is head of the Unit at LTMG Hospital and interventional cardiologist.  I would ask you a first question that we have vast armamentarium in the BP management, but now how do you select what is "Mr. Right" in a given individual subset?


Dr. Ajay Mahajan:  It is one of the most difficult question, when we decide to start the treatment in patient with hypertension we have to think in stage I hypertension when to start and in stage II hypertension all patients who are to be treated.  So in stage I hypertension, where the patient were below 80 years of age were to find out some target organ involvement or establish cardiovascular risk or associated renal diseases or diabetes or taking your cumulative cardiac risk, and depending upon that we have to start the therapy, but for knowing all these things this is very important because if we know about these things, then we are coming to some compelling indications to start specific drugs, at what to start? So, it totally depends upon the clinician’s experience, his experience about the drug, and also one of the important thing is associated compelling indications and contraindications in that particular patient.  So as far as starting the therapy for hypertension, European Society had given guidelines, European as well as American Society have also given guidelines about starting these 5 groups of drugs and one can choose any of the drug or combination of the drug for starting the therapy and why these 5 groups because these are the 5 groups which are tested with various long-term non-randomized and randomized controlled trials and they have shown that there are significant benefits, mortality benefits, with this particular 5 groups of drugs.  If you ask this question 5 years back or 10 years back, there was another sixth group of drug like alpha blocker which was there, but now it is not there because of ALLHAT trial, which had shown significant increase in mortality with alpha blocker.  If you ask the same question to me after 5 years or 10 years, there will be sixth group of the drug that is like an aldosterone antagonist for the treatment of hypertension, but nowadays that is restricted only for the patients with resistant hypertension.  So as far as the starting of the therapy, various guidelines are given, something the oldest guideline which is now we are going to get a new guideline in the next few months or year, that is JNC-VIII, it is expected, for JNC-VII, they had given thiazide like diuretics should be given as the first line therapy, it was a blanket statement.  Another thing that the guideline that is coming from North America.  Second, the guideline coming from the European continent, that is, NHS and BHS guidelines, they had given that ACE inhibitor or ARB should be given for the patients who are less than 55 years and calcium channel blocker or diuretics should be given as a first line when the patient is more than 55 years and European guidelines, relatively more simple.  Monotherapy for low CV risk and grade I hypertension and combination therapy for high CV risk and grade II or grade III hypertension.  So, we are between, we have to think about starting the therapy depending upon what to choose and another new thing which is coming, that is in 2012 the Canadian Hypertension Education Society guidelines, and they had given only these 5 groups, but they have added one caution about beta blocker for starting the therapy after 60 years of age, and why they had given that is all explained by Professor, Uday Jadhav, that is, central aortic blood pressure and increase in mortality with the beta blocker when they are used in elderly patients increases stroke rate.  So, after knowing all these things, we have to take the help of certain drugs; in diuretics, certain drugs like thiazide diuretics and thiazide like diuretics; and in beta blockers, newer beta blockers and older beta blockers; in calcium channel blockers, there are dihydropyridines and nondihydropyridines, particularly nondihydropyridines, when we have to use, we have to use extended release formulation; ACE inhibitors, very time tested; and ARBs.  So, depending upon the compelling indications and contraindications we have to find out and there are certain trials and data about all these groups of the drug where we get positive and negative trials in certain drug like diuretics and beta-blockers.  The main concern in beta blocker is that all meta analysis, it had shown that it causes pharmacologically induced bradycardia and may lead to dysynchrony between outgoing and reflected pulse wave, thereby increasing the central aortic pressure and hemodynamic burden of the target organ route, and that is particularly very important in elderly patients more than 60 years of age.  So, why I am insisting this point because now we are having one another alternative in calcium channel blocker group where we can use that specific drug for the elderly hypertensives as a drug of choice for taking care of hypertension, and that is the same thing, in NICE guidelines, they have said no to the beta blockers and coming to the trials we are getting all negative trials with atenolol because it is hydrophilic molecule, it does not take care of blood pressure for 24 hours, it does not take care of central aortic blood pressure, it does not take care of early morning catecholamine surge.  It also causes some insulin resistance, decrease in beta mediated insulin secretions, and new-onset diabetes and because of that we got significant negative things with the atenolol like ASCOT trial and we got maximum positive evidence with the ACE inhibitors, ARBs, and calcium channel blockers and that only because of the drugs which are having maximum positive trials are the drugs where there is a half-life of more than 24 hours.  That is very important because in hypertension trial, if you take any drug, which is having positive trials, maximum positive trials, the half-life will be more than 24 hours and that is the most important thing.  So, prior to starting the therapy at least if you are using combination therapy, at least 1 drug should be there whose half-life should be more than 24 hours and that should be the drug of choice.  As far as the calcium channel blocker is concerned, now we are getting new drug which is there in the market that is cilnidipine and very important drug because till today the gold standard is amlodipine, which is having maximum positive trials and when cilnidipine is compared with the amlodipine it had shown that it is not inferior, it is slightly superior to the amlodipine as far as the renal protection is concerned, as far as the decrease in the heart rate is concerned because it is inert and it slightly reduces the sympathetic outflow because of blocking of N type of calcium channels which are located on the sympathetic nerve endings. So, today we are having all clear thoughts about calcium channel blockers, ACE inhibitors, and ARBs.  There is still gray area as far as the thiazide-like diuretics, as well as beta blockers for the treatment of hypertension.


Dr. Rajiv Karnik:  Thank you, Dr. Ajay Mahajan.  You nicely covered not only this "Mr. Right" for hypertension.  Only thing, the last question I wanted to add was, this combination therapy you said that there are some drugs which are acting very nicely in synergy and some drugs which are not.  Like, there is a prism in majority of the textbooks of hypertension management, which has shown that there are some solid lines and dotted lines that which are synergistic and which are not so synergistic and which are antagonistic.  So, can you highlight that which drugs you will combine to have the best synergistic effect.


Dr. Ajay Mahajan:  As far as the combination therapy is concerned, if you go to the data and if you go to the evidence, there are certain villains in combination.  The first villain came after ASCOT trial, i.e., atenolol with the bendroflumethiazide and there was significantly increase in the mortality at the end of 5.5 years with the ASCOT trial when it is compared with perindopril with amlodipine combination.  So, European Society had specifically written that beta blocker with thiazide diuretic should be avoided as far as the combination is concerned.  As far as other combinations are concerned ACE inhibitors and ARB, i.e., direct rennin inhibitor and aldosterone antagonist, these 4 groups can be taken as a one chunk.  So, if you want to add any combination, these 4 should not be intermingled.  One of these 4 should be chosen along with calcium channel blocker because for any combination, the calcium channel blocker is one of the best thing.  So, calcium channel blocker with ACE inhibitor or calcium channel blocker with ARB or one can go with the calcium channel blocker with beta blocker also or one can use ACE inhibitor with thiazide type diuretic or ARB with thiazide type diuretic or one can use 3 drugs, like a calcium channel blocker with ACE inhibitor or ARB along with some diuretic for resistant hypertension, but preferably one should avoid combination of ACE inhibitor and ARB together or ACE inhibitor or any direct rennin inhibitor together or ACE inhibitor ARB along with this aldosterone antagonist together because of chances of increasing the hyperkalemia, increasing morbidity and mortality and because of total renin blockade, the chances of nephrotoxicity are slightly high and one should also avoid the combination of thiazide-type and diuretic along with beta blocker because there are chances of new onset diabetes are slightly more and the combination is not metabolically friendly because slight increase in the triglyceride and it is not liver friendly.


Dr. Rajiv Karnik:  You told us this "Mr. Right," now, any new drug that when it comes we see lot of positive features about it and then we many a times do not come to know what is in the literature, the negative side of that drug, are there any trials which are not showing not so good effect of that.  So, can you highlight and can you for the knowledge of the audience tell us that in the literature, which are these negative trials.   Plus, positive trials are always talked about a lot during the glorification of the new launches, but especially, negative trial, can you highlight some of the negative trials.


Dr. Ajay Mahajan:  So, as far as the various groups for the treatment of hypertension there are certain negative trials.  So, as far as the diuretics are concerned, we are getting negative trials with hydrochlorothiazide, ACCOMPLISH trial, when benazepril was added with hydrochlorothiazide, it was significant increase in the cardiovascular mortality when it is compared to the benazepril with the amlodipine.  Then another thing is Australian trial, ANBP2 trial.  They had shown that there is significant increase in the morbidity and mortality with hydrochlorothiazide.  In bendroflumethiazide, in ASCOT trial we got all negative effects.  Atenolol as such ASCOT trial, LIFE trial, US trial, all negative trials.  In alpha blockers doxazosin is gone out and because of ALLHAT trial just they stopped after 3.3 years, this arm was stopped, because of increase in morbidity and mortality.  As far as ACE inhibitor is concerned, lisinopril, ALLHAT trial, negative thing, why it happened?  This is very interesting question and the question's answer is very interesting.  As far as taking care of diastolic blood pressure when the data was analyzed, they found that amlodipine is superior to the lisinopril and then chlorthalidone for taking care of diastolic blood pressure.  So, blood pressure is very easy, it is, we have to treat like mathematics.  Diastolic blood pressure is measure of peripheral vascular resistance.  Peripheral vascular resistance depends upon blood viscosity, which is relatively constant, might change in patient with diabetes.  Second is blood vessel length, that is also constant for that particular patient.  Third thing is blood vessel diameter and the blood vessel diameter is variable and it is only at the level of arterioles.  If there is a strong arteriolar dilator, it will take care of diastolic blood pressure very effectively.  So, why lisinopril has failed in front of amlodipine in ALLHAT, only because of its half-life.  Its half-life is only 12 hours when it is compared with the drug with a 36-hour half-life.  That is the only reason lisinopril has failed in front of amlodipine for taking care in ALLHAT trial.  As far as the ARB is concerned we are getting some negative trials and trials like PRoFESS and TRANSCEND, which were published in 2008.  They had shown that it is not superior to the taking care of blood pressure and blood pressure related mortality.  But if you take the positive trials we are getting maximum with chlorthalidone, the time tested is amlodipine ASCOT, CAMELOT, ACCOMPLISH.  All these trial and the same thing, when it is compared with cilnidipine, cilnidipine is slightly superior to the amlodipine.  So, we can extrapolate that particular thing because till today the drug was not available in Indian market, now it is available, so preferably in elderly hypertensives, when there is any use, any indication to use a calcium channel blocker, one should give this preference to cilnidipine.  Then we get all positive trials with perindopril because its half-life is more than 24 hours.  PROGRESS, EUROPA, ADVANCE and also we are getting all maximum positive trials now with the olmesartan like IRMA, ROADMAP, OSCAR, and other trials.  So, we have now all the drugs, which are having positive trials are available in Indian market and we can give that benefit to our patient.


Dr. Rajvi Karnik:  Thanks, Dr. Mahajan.  Now, just one last highlight this cilnidipine and 11 meta analysis Chinese trials and then Canadian data also, so do you have some data to substantiate the difference of the superiority of cilnidipine over other dihydropyridine or other drugs or anything to support this statement what you have just said.


Dr. Ajay Mahajan:  Cilnidipine is unique molecule, which blocks the calcium channel of N-type as well as L-type, so L-types are the calcium channels, which are there in the vasculature, but N-types are the calcium channels, which are there in the autonomic nervous system at the endings, so ultimately if you block that N-type of calcium channel you are going to blunt the synchronistic response and that is very important thing.  When there are certain patients where beta blockers are relatively contraindicated or we are concerned about central aortic blood pressure or elderly patients, so in that case if you want to use a calcium channel blocker then this particular molecule is slightly superior as compared to amlodipine as far as taking care of heart rate, taking care of blood pressure reductions.  So as far as BP reductions, it is equipotent to the amlodipine.  For taking care of the heart rate, it is slightly superior to amlodipine.  For taking care of intraglomerular hypertension, it is slightly superior to the amlodipine, so it also causes decrease in the proteinuria, it is renoprotective, so the drug which is now available in the market, which is calcium channel blocker, but additional ACE inhibitor as well as additional beta-blocking properties, so these are the two important pleiotropic effects in one particular drug, so because of that it is slightly more important drug for taking care of hypertension.


Dr. Rajiv Karnik:  Thank you, so our main worry of dihydropyridine that reflects in sympathoadrenal activation, which in 1992-93, which put the definitive molecule very much low down, I think with this molecule we are relieved that anxiety is eliminated.  Very, very nice presentation.  Thank you very much Dr. Mahajan.


Now, let us turn to Dr. Sadaanand Shetty who is the head of the department at DY Patil Medical College.


Dr. Shetty, we have discussed so far the different armamentarium of blood pressure management.  Dr. Mahajan was highlighting to thiazide like diuretics, because we know this diuretics have been there since plenty of years.  We have in 1940s and 50s mercurial diuretics too toxic to use, then in 1970s, when I did graduation, we used to use 50 and 100 mg of hydrochlorothiazide, and then in our times treatment changing and then the different use went on changing, but still nevertheless diuretics maintained its first positions from JNC-I, II, III, IV, V, VI, VII, so there must be something good about diuretics, although so many negative points we have talked about.  So, can you highlight to this point that why diuretics are good and if hydrochlorothiazide is one molecule then what are the alternative thiazide like, which Dr. Mahajan was saying, and what are the differences and what you would prefer and what you would advice the audience that how this newer or thiazide like diuretics are better.


Dr. Sadaanand Shetty:  Hi, Dr. Rajiv.  I am privileged and it is a pleasure to be a part of this very august panelists; Dr. Ajay Mahajan, Dr. Bhaskar, Dr. Uday Jadhav.  All of these are physicians working together and all are my good friends.


If you see the diuretics in hypertension, if you see the JNC-VII guideline, based on the data of the ALLHAT study they have extrapolated that diuretic is one of the part of the treatment, but if you see there are no enough direct evidence either for the mortality or the morbidity advantage from using the hydrochlorothiazide in hypertension, and if you see this thiazide diuretic is almost more than 50 years and if you see all the facts, fads, fiction, and follies and there are no conclusive evidence to favor use of these drugs and therefore now researchers have found or felt that possibly what we are extrapolating thiazide diuretic in clinical practice is not correct, and we have many trials using chlorthalidone and indapamide and therefore they felt, and that is what the current evidences, that we have to change the pattern of using diuretic into thiazide like diuretic, that is either chlorthalidone or indapamide and not the conventional hydrochlorothiazide diuretic.  As Dr. Rajiv rightly said, if you see the evolution of the diuretic which was the foremost drug started with a mercurial injection subsequently the chlorothiazide and very large dose of thiazide and the diuretics were used in the past and overtime the researchers have realized that using very heavy dose has lot of negative effect, like negative side effects, like may be altering the electrolytes, may be changing the sugar level in the lipid level and therefore the first large randomized trial called ALLHAT Study, which has been also highlighted by the previous speaker, which came in 90s said that diuretic should be part of the hypertension management, the first line therapy for hypertension and if you see the chlorthalidone evolution right from 60s where the large dose, as we get into 70 to 80 little less dose, and of late in 90s it has been realized that even as small as 6.25 mg has good efficacy with minimum side effects and the three trials, which has made the landmark change in the evaluation of chlorthalidone is a multiple risk factor intervention trial, systolic hypertension in elderly trial and the ALLHAT study and quite a large number of patients are studied and if you see the chlorthalidone it has got a dual mode of action unlike the thiazides, one you know it reduces the plasma volume and second it reduces the vascular resistance and this is what you see in the immediate effect and this you see on long term basis and if you see the evidence there are more than 75,000 patients studied with the international documentation like first is the ALLHAT, which is more than 42,000 patient, and if you see the SHEP, almost 4500, and Multiple Risk Factor Intervention Trial, more than 30,000 patients, and if you see the conclusion of the ALLHAT study that the control of systolic blood pressure was better in chlorthalidone than amlodipine or ACE inhibitor, lisinopril and if you see the nonfatal MI as well as the CHD death, again similar reduction with both the choice of the group of calcium channel versus ACE inhibitor and chlorthalidone was associated with lower risk for stroke, combined event, heart failure, and heart failure it was compared to the amlodipine.  So, this was the first trial, which came to suggest us that what we think conventionally diuretic is not protective, it is not able to reduce the morbidity or mortality, which is not so, if you see here again better organ protection if you compare to amlodipine, if you see with the ACE inhibitor again better organ protection when you compare this with the chlorthalidone versus lisinopril.  If you see here, 15% risk of stroke reduction, angina, heart failure, and this is a significant effect of chlorthalidone found in the study.  Also, if you see it protects the brain.  If you see the 14-year followup of the SHEP trial has shown that it is beneficial for the brain also, and the other concept which we recently sort of gave too much importance like isolated systolic hypertension, but really beyond the age of 60 are predominantly isolated systolic and below 40 is predominantly diastolic and between 40 and 60, both systolic and diastolic, and as the previous speaker mentioned that the systolic hypertension isolated maybe they are completely in different way than the diastolic and if you see here in isolated systolic hypertension again chlorthalidone is safe and effective in this group of patients and if you see what we think conventionally diuretics are not organ protective or they do not reverse the LVH, they do not have any effect on the kidney, it is not so as shown by various authors that the left ventricular hypertrophy regresses and which is as good as or even more effectively than the calcium channel blockers.  This is what we have to realize.  If you see in diabetic patients, many times we get scared to use diuretic because it increases or changes the sugar level or you know the level of the electrolyte hypokalemia that also has some effect on the diabetic control and so on, which is again as shown in this various studies.  In particularly, the SHEP trial that almost 34% reduction in the cardiovascular events is seen in both diabetic and non-diabetic, and if you see the absolute risk reduction, chlorthalidone was twice as great for diabetic than non-diabetic.  So, this point we have to realize in practice.  Many times, you know, we think diabetes, even as shown here, metabolic syndrome.  Again, we need not worry about the negative effect of the chlorthalidone and if you see the Multiple Risk Factor Intervention Trial where you know the nearly 9 centers used hydrochlorothiazide and about 6 centers chlorthalidone was used, and if you see hydrochlorothiazide had a 44% higher mortality and many patients of this group have shifted to chlorthalidone and it was found that the trend was reversed and same group later at 28% lower risk.  So, we are practicing currently is the evidence based medicine and therefore this evidences by this all landmark trial which shows the evidence are favoring this group of drugs.  If you have to see the lipids, which are mentioned before, another worry for us in practice, that many times patient has multiple risk as the previous speaker rightly said, Dr. Bhaskar Shah mentioned about and Dr. Uday Jadhav did tell us, that it is not just a mercury column or BP level, but there are multiple risks like lipid changes, one thing which you always worry, like sugar level, which again has not been shown very much in these studies and secondly the most important thing the current importance is more for using small dose of this drug unlike in the older time, like in 60s-70s, where you know 100 mg and 200 mg.  Currently, we are talking about 6.25 mg of chlorthalidone or 12.5 mg of chlorthalidone or indapamide very small dose 1.5, 1.75, and these doses we are talking about and if you see the lipid profile as shown in this particular graph, as the time passes and as the therapy continues, there is no significant change in the lipids and also the blood sugar, if you see the Indian trial it has been shown that at the baseline and at the end there is no significant change.  This has no clinical relevance.  If at all slight change in the sugar value may come, slight change in the lipids may come, but that does not have a clinical outcome effect and therefore, if you see here in ALLHAT and the SHEP study, the diabetes or little increase in the sugar level what happens during that therapy as no increased mortality as compared to person without diabetes.  Same thing about the potassium changes what we worry because there is a small dose what we are talking about, not the dose what is mentioned in the old times, and is also superior to hydrochlorothiazide.  If you see here the duration of the action is you know quite a bit as well as the potency.  Efficacy is almost double then hydrochlorothiazide.  As shown in this particular graph, superior to hydrochlorothiazide in the systolic blood pressure and also the mean systolic as well as mean diastolic pressure and better night time control.  Do you know that the nocturnal BP control is vital.  As the previous speaker, Dr. Ajay Mahajan, rightly said 24-hour control is very important, and we need to use a drug, which works for 24 hours and what we think hydrochlorothiazide is long-acting is not so, it is just has a short-acting effect, does not lasts beyond 12 hours.  Chlorthalidone acts beyond 24 hours.  As a matter of fact, half-life is more than 40 hours, so it is a longer duration of action, not only the night as well as the early morning surge is better controlled, and if you see the comparative dose since chlorthalidone is almost one and half to two times more potent than hydrochlorothiazide; almost 6.25 of chlorthalidone is equal to 12.5 of hydrochlorothiazide, 12.5 chlorthalidone is equal to 25 mg hydrochlorothiazide, which is almost you know half dose, and if you see the safety as shown in all of these study, all this conventional problem we think and that is what we always worry when we give diuretic either in single or in combination; these all particular trials have shown us, they are not important.  The other most important thing what recently by some of the researchers have been found that it is beyond BP control.  Like many times, you know when we use a drug, say in diabetes, may be in dyslipidemia, so what is in hypertension, we need additional pleiotropic effect, that is, in beyond BP control.  Recently researchers have found that there is a good platelet anti-aggregation effect with chlorthalidone.  It also promotes angiogenesis, experimentally it has been shown and also it reduces the vascular permeability and therefore it is a very important molecule in heart failure.  If you see the indapamide is another thiazide like diuretic, which has been mentioned and which many studies are also available for this and the action is similar to thiazides.  Its primarily effect is on the direct vasodilatory effect.  It also reduces the proteinuria and end organ protection.  If you see the 3 landmark study like HYVET Study, PROGRESS Study, ADVANCE Study where diuretic with ACE inhibitor and the indapamide in combination with that ACE inhibitor has shown remarkable benefits.  So, if you see diuretic when you think about the thiazide like diuretic in fact recently we had encounter of the leading researchers in hypertension like Bryan William, Norman Kaplan, Henry Black, and all are of the opinion that we have to change the practice pattern, that we have to almost change from thiazide to thiazide like diuretic like chlorthalidone, indapamide, but large studies in order of the numbers and outcome and if you see the studies and as old as in about 90s and 80s are favoring chlorthalidone.  I would strongly recommend that this is a drug, which you must change and this is what is there in the guideline, what they say, like NICE Guideline and recently over the last week in one of the international conference Andrew Williams was very strongly saying that all those thiazide we should consider another, Poulter was there, who is the investigator for ASCOT trial.  They are all of such strong opinion that the thiazide diuretic we don’t have evidence and if a practicing evidence-based medicine, we have to change thiazide to thiazide like diuretic, which is chlorthalidone, which is fairly cheap, better control, good night BP control, superior target organ protection, suited for rising isolated systolic hypertension.  ALLHAT Study, SHEP Study and the MRFIT Study have shown that is more useful, outcome benefit has been shown and it is safe in low dose.  Whatever worry of hypokalemia, dyslipidemia, dysglycemia is not the real difficulty in situation.


Thank you Dr. Rajiv.


Dr. Rajiv Karnik:  Thank you, Dr. Shetty you have very nicely covered and I am very optimistic about JNC-VIII now what it will come and then obviously I think this diuretic will still retain it's place and then, but only thing instead of hydrochlorothiazide now the place it will be replaced with probably chlorthalidone and indapamide.  Thank you very much.


So dear friends, now we are coming to the end of the symposium and it was really a wonderful symposium, lot of insights into the complex subject of hypertension management and drug management.  Now, firstly Dr Uday Jadhav highlighted very nicely that ECG, echocardiography, the most commonly done investigations, easily available, and then what vast information it can provide, even 1 mm rise in the voltage in aVL can have the dreadful consequences.  Microalbuminuria, unfortunately, the underutilized test, he highlighted very nicely, and then the newer ultrasound modalities including carotid intima media thickness and the pulse wave velocity, and flow-mediated dilatation endothelial dysfunction, which is very original work of his own, which he has presented in different conferences and those were discussed in the first vascular pathology and pathobiology evaluation in the hypertensive patients.


Then, Dr. Bhaskar Shah very nicely told us that hypertension is not just a number, it is a syndrome and then there are various risks factors, which go hand in hand, and then all of them have to be addressed simultaneously and then when it comes to the management and treating the number that we have to have some deadline.  Lower is not better, stringent control versus routine control with the INVEST trial and then ACCORD trial he very nicely showed that even routine control is good enough and then based on that he showed all different guidelines and then finally he made it very simple for all of us and for all of you that just remember 140/90 and 130/80 two figures instead of going into different, different societies guidelines.


Now, Dr. Ajay Mahajan, came in and then he discussed what is "Mr. Right" for hypertension management, how will you select the drug.  Not just that all the new drugs you should go blindly prescribe, there are some positive trials, some negative trials and then lot of data he showed that in which subgroup which drug will have the positive and the negative and then the compelling indications were discussed very nicely.  The synergistic combinations he discussed and then finally he touched upon Cilnidipine, which is a novel dual calcium channel blocker, which doesn't have just this dihydropyridine like reflex sympathoadrenal activation, which inhibits sympathetic system, which doesn't lead to increase albuminuria, what amlodipine had done in ABCD trial in the diabetics, but in fact because of afferent-efferent arterioles it reduces proteinuria and nephropathy, so it is a novel dual calcium channel blocker and that is what he highlighted.


And last but not the least, I think the trump card of hypertension management, and that is diuretic, professor Dr. Sadaanand Shetty highlighted about the utility of diuretics and he specifically showed that chlorthalidone is molecule, which has been proven in multiple trials, right from MRFIT trial to the latest trials and then all the trials, if you see the trial basis it is the chlorthalidone.  If you see the theoretical basis, then it is pleiotropic effects including angiogenesis, platelet antiaggregatory action, and then so on and so forth, it has been superior, and then one you need not to worry whether the patient has diabetes, he has dyslipidemia, still you can use this molecule with impunity and similarly in elderly people this indapamide with HYVET Trial and then other trials also he showed that even the indapamide also has long action, lipid neutral, and that will also go hand in hand with similar kind of benefits like chlorthalidone.


I think that brings us to the end of this symposium.  I thank all the panelist wholeheartedly for sparing their time and then giving this insight into this complex subject.


Thank you very much.

Symposium on Hypertension

By Dr. Ajit Desai , Dr. C. K. Ponde , Dr. G. R. Kane , Dr. Vivek Mehan , Dr. Rajesh Rajani and Dr. Chetan P. Shah.

Presentation on Hypertension

By Prof. Dr. M.S. Amaresan.