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Date: 25-04-2013 Presentation on Hypertension

By Prof. Dr. M.S. Amaresan.

Presentation on Hypertension 


Hypertension is one of the very important disease, actually it is a syndrome.  It is not just measurement of blood pressure, but usually it occurs along with dyslipidemia, dysglycemia, and endothelial dysfunction.  Actually, you find that there is an increase amount of oxygen stress in hypertension.  So this hypertension, if it is not corrected properly, leads to heart attack, coronary artery disease, chronic kidney disease, stroke, and various other complications including peripheral vascular disease.  The magnitude of the problem is enormous that you find that even in India, in the urban cities like Chennai, Mumbai, and Delhi, you find about 30%-40% of the people are suffering from hypertension.  Below the age of 50 the females may have a lower incidence, but after the age of 50, they equal the males.  After the age of 50, the incidence appears to be 50%.  After the age of 65, the incidence appears to be 60%.  You can understand that whenever you see a patient, with whatever complaint they come, you must always record the blood pressure, which is the best way.


JNC-7 has defined the hypertension as not above 140/90, but actually above 130/80.  They call it as a prehypertension.  Anything above 130/80 mmHg in people above the age of 18 years is a prehypertension.  Prehypertension has the same risk as hypertension as I already enumerated earlier.  It is almost like impaired glucose tolerance.  Impaired glucose tolerance has got the same complication as diabetes mellitus established.  Therefore, it is very important that we should try to keep the blood pressure below 130/80, particularly, if the patient has albuminuria or even microproteinuria or if the GFR is less than 60 mL/minute, it is important that you should keep it lower down, and if it is going to be above 1 g protein excretion, you must keep it below 125/75.  That is a way in which the artery dysfunction will be prevented.  Either a cardiac dysfunction or a kidney dysfunction or cerebrovascular disease. 


Well, after mentioning about the magnitude of the problem, you know that the amount of money that is spent, both by the country as well as the family is enormous, and so you should always try to prevent hypertension. Particularly, it is very important that you should understand the pathophysiology of hypertension.  You find that the oxygen stress is the most important thing.  If you consume more of fried food or a salty food, you find there is an increased oxygen stress.  The oxygen stress gives rise to endothelial dysfunction.  Endothelium is the largest organ in the body, wherever the blood vessel goes the inner aspect of the blood vessel is endothelium.  So, if there is an endothelial dysfunction, there is increased endothelin-1 and the increased endothelin-1 gives rise to increased amount of renin-angiotensin.  Previously, we used to think that in the kidney the juxtaglomerular apparatus is the only one that creates renin and angiotensin, etc.  But then, we know, that even the vascular tissue in the brain, the heart, and the peripheral vessels have got the angiotensin producing capacity and so there is a diffuse renin-angiotensin aldosterone axis in even the so called primary hypertension.  Here the kidney plays a very pivotal role in the pathophysiology.  (1)  That genetically, there are some people who are not able to excrete as much salt as other person who can excrete salt.  So, the salt and water retention leads to the blood pressure and the increase in the endothelial dysfunction produces renal arterial constriction and that constriction will lead to increase amount of sodium and water retention and which will persuade or perpetuate the hypertension.  The endothelial dysfunction not only affects the vascular tree to produce vasoconstriction, but there are a lot of angiotensin receptors even in the podocyte of the glomeruli and the tubules and in the mesangial cells.  You will find that there is increased production of the angiotensin II even in the kidney if there is a severe endothelial dysfunction.  I think this much is sufficient enough though there are many other hypotheses which can contribute.  What I wanted to stress is that is not only the kidney disease, which produces the hypertension.  Even in the so-called primary hypertension, kidney plays a pivotal role in the causation of hypertension.  At the same time you have to understand if you do not control the hypertension, the kidney gets destroyed, the brunt of the attack is on the kidney, and then you can get in a malignant hypertension an acute kidney failure or even a chronic kidney disease because there the vessels are going through a spasm in the kidney.


Well, another important thing that you should know is that hypertension is always associated with diabetes mellitus.  Diabetes mellitus and hypertension are like cousins and in most of the cases of diabetes there are 50% incidence of hypertension along with diabetes, in this so-called type 2 diabetes.  The same way in hypertension 30%-40% of them will have dysglycemia or hyperglycemia, and it is very important that we should look for both whenever we investigate the case.


One of the important thing in the diagnosis is that you go through the history of the patient, particularly when there is a family history of hypertension, there is a tendency for the offspring to develop hypertension.  When there is a family history of obesity then there is this tendency for the patient to be obese and that is the most important history.  More than that, how much salt that he consumes?  Those who take oily food and food with lot of chilies, hot stuff, they will consume more amount of salt, and the excess salt definitely leads to high blood pressure.


One of the important things that one has to understand is consumption of alcohol.  If you take the incidence of hypertension in the general population it may be 30%, but if you take the alcoholic population, you will find it is 50% of the people who are hypertensive.  In same way, smoking is another important factor, which leads to hypertension.  The people who smoke have high incidence of hypertension, higher incidence of heart attack, higher incidence of lung disease like malignancy, carcinoma of the lung, and higher incidence of acid peptic disease.  So, hypertension is one of the important factors.  Even it produces the renal atherosclerosis and produces renovascular hypertension.  So these 3 are the important things that you should ask when you investigate a patient with hypertension.  When you examine the patient you find whether he is obese or not.  Once the BMI is more than 30, his tendency to have high blood pressure is very high.  The next thing is that you should look for palpation of the vessels and you may find that there may be some reduction in the pulse volume in the lower limbs.  It is a peculiar disease known as aortoarteritis, which can give rise to hypertension.  Another important thing is, has he got any puffiness of the face, has he got any pedal edema.  Particularly, the early morning puffiness of the face indicates that there is renal hypertension, it may be an acute nephritis or it may be even a chronic kidney disease.  If he is parallel anemic and hypertensive, invariably it is going to be a chronic kidney disease, which is responsible for hypertension.  If you got suppose a young lady who has got a butterfly-type maculopapular rash in the face, it is suggestive of systemic lupus erythematosus producing high blood pressure or if there is a young man with vasculitic patch in the leg or any part of the body or erythema nodosum or erythema marginatum, once again it indicates an autoimmune disease like polyarteritis nodosa.  So, though it may not be so common, but it is important that you should rule out secondary causes of hypertension before you label it as a cause of primary hypertension.  Of course, primary hypertension, is 90% of the incidence, whereas 10% only is secondary hypertension.  The largest in the secondary hypertension is the renal hypertension, renovascular hypertension, then comes the endocrine hypertension like pheochromocytoma, adrenal adenoma.  So, we have to rule out while investigating the case also.


The urinalysis is a very important thing.  Actually it is like renal biopsy.  It you look at the urine deposits and you find lot of rbcs it means there is glomerulitis and if you find there is protein in the urine, once again it indicates that there is a glomerular involvement, it is probably renal hypertension.  Well, in a severe hypertension even without renal disease can cause renal damage and produce proteinuria, but that is not very common unless you are seeing a malignant hypertension where the diastolic pressure is more than 120 and the systolic pressure is more than 180, so very severe hypertensives, and if you look at the fundus you will find that there may be changes of hypertensive retinopathy in the form of narrowing of the blood vessel.  It may bind even papilledema and you may have superficial hemorrhages or even deep hemorrhages and punctate hemorrhages.  So, it is important that in every hypertensive you look at the fundus.  It will also show whether small vascular disease is there because hypertension can produce a small vascular disease like nephropathy and retinopathy and also it can produce large vascular disease like stroke or myocardial infarction.


The next investigation, I would say is a total count, differential count, and ESR.  You will find if these are grossly elevated and there is eosinophil increase, I think you may think of an autoimmune disease.  Eosinophilia, raised ESR, and rbcs in the urine in a young lady with cutaneous manifestation, which I mentioned, suggest a systemic lupus erythematosus.  Well you go to do the investigation to point out the etiology and also investigation to point out the complication.  For example, x-ray chest will show whether there is a left ventricular hypertrophy or a cardiac dilatation indicating that the hypertension has been there for quite some time.  An ECG also can show some changes of left ventricular hypertrophy or T-wave changes or ST segment changes once again indicating cardiac involvement.  If you do a urea -creatinine and creatinine clearance, more than the creatinine the creatinine clearance is very very important.  Particularly in an elderly individual or a thin individual you do a serum creatinine, it may not show the real renal status.  That is when if you do a creatinine clearance and even if you cannot collect a 24-hour urine you can do eGFR (estimated glomerular filtration rate) that can indicate to you whether he has got creatinine clearance less than 60 mL/minute.  You can actually grade how much of CKD is there; 120-90 will be the grade 1 CKD, 90-60 will be grade 2, 60-30 will be grade 3, 30-15 mL will be grade 4, and if the creatinine clearance is less than 15 mL you call it as grade 5 CKD or end-stage renal disease.  So, it is important that you should not only estimate whether the kidney is involved, but the degree of kidney involvement is also very important.  At the same time, suppose there is a history of weakness one-half of the body or what you say drop seizure then it is important to investigate the central nervous system.  If there is a story of difficulty in using one-half of the body even transiently or a drop seizure, drop seizure indicate that the posterior part or the vertebral cerebral artery is involved and one-half of the body, the anterior part, middle cerebral artery involvement.  So, you may have to do a CT scan or MRA angiography depending on the renal status.


Well, of course, if you think that the blood pressure is very high, actually you are the person who is looking after the patient and you find that the BP has gone up very quickly to 190/120 or so then also you will find that there is a bruit in the paraumbilical region and you find that the fundus examination showing severe changes of retinopathy, I think then you should rule out the renovascular hypertension.  So, in that particular case it is not only important to do the ultra sonogram, ultra sonogram will show you the size of the kidney, maybe that one kidney is smaller than the other kidney.  Particularly, if the left kidney is smaller than the right kidney it is quite significant because usually the left kidney is 1 cm bigger then the right kidney and so it is very important to do a rapid sequence intravenous urogram.  You can do a digital subtraction angiography if you want to do a noninvasive investigation or if you suspect very seriously that an angiography itself will confirm that there is a renal artery stenosis or not, and if we think that the blood pressure is fluctuating, sometimes it goes to 220/130, suddenly it comes to 120/80 and then the flushing of face and there is telltale evidence of cafe au lait spots or neurofibromata, it suggest that it is a case of pheochromocytoma.  So, you have to got to do a 24-hour urine estimation for catecholamines and the VMA.  I think that is an important thing and when you do these things, you got to do sodium, potassium, bicarbonate, and chloride.  When you do sodium, potassium, bicarbonate, and chloride and we are not using any diuretic and you find there is a persistent hypokalemia that is an indication that the patient maybe suffering from adrenal cortical adenoma.  There are some people who have investigated particularly for adrenal cortical adenoma, they find 20-30% of them are suffering from adrenal cortical adenoma, which is a very high incidence.  My own 4 decades of experience, I had only about 2 cases of adrenal cortical adenoma, which has been operated and there was a semi cure of hypertension.  Why I am mentioning this, these are all curable hypertension.  Renal artery stenosis, if you re-construct the stenosis by either angioplasty or by surgery the hypertension can be cured.  Even if it is not cured, at least the number of drugs can be reduced to a considerable extent.  In the same way if the pheochromocytoma is removed the hypertension is cured.  Same way if adrenal cortical adenoma is removed, again the hypertension is removed.  Whereas, in cases of primary hypertension that you have to give the therapy for quite a long time.  It has important thing which I already mentioned that there is an association of diabetes along with hypertension.  As type 2 diabetes is associated with hypertension, diabetes also can have that.  So even if you do not do a GTT, you do a fasting and postparandial blood sugar.  If fasting blood sugar is more than 100 mg, indicates it has got to impact fasting glucose.  If the postparandial blood sugar, after the lunch 2 hours later, if you do a blood sugar and if it is more than 140 and it is less than 199, it is an impaired glucose tolerance.  If it is 200, even if it is random or postparandial, you can immediately dub him as the case of diabetes.  So, that is very important and I already said in my introduction that it is a syndrome associated with dyslipidemia and dysglycemia, so you must do a lipid profile routinely in every case of hypertension, and so particularly if the LDL and triglyceride is increased and HDL is decreased it is very important that you got to not only treat the hypertension, but also treat the dyslipidemia.  Particularly, Indians have a high incidence of coronary artery disease.  Indians, Pakistanis, and Bangladeshis because their HDL cholesterol is low and the triglyceride is very high, so it is very important in hypertensive if you do a lipid profile.  Well then, these are the very important investigations and let us look at how exactly that we can go about to treat the patient with hypertension.


Well, the lifestyle management is the most important thing.  That is the nonpharmacological method of treatment.

1.  Exercise.  Exercise to see that the weight is kept in normal.  It is less than 25 BMI and if the BMI is higher then you must always ask the patient to reduce the weight.  So, it is not only about 45 minutes of walk but maybe that you have to increase it to 90 minutes per day and you should see that smoking is completely stopped, there is a taboo for alcohol, and then you should try to use more of 3 courses of vegetables, 3 courses of fruits.  What is meant by diet against systemic hypertension, that diet is one of the thing that has been done in United States and found 3 course of vegetables and 3 course of fruits and less amount of salt and less amount of saturated food, dairy food, i.e., low-fat milk and low-fat curd are the one which will be help and if it is a nonvegetarian, it is fish and chicken which will be better to replace meat, pork, and beef.  Beef, pork, and meat should be a taboo.  I think that is one of the ways in which even if he is an hypertensive I do not think you should try to discourage him from playing tennis or shuttle cock or walking for about 45-50 minutes because you should tell them that the more they walk, that there is a more amount of peripheral vascular dilatation and the less number of anti-hypertensive drug that they will be able to take.  So, these are lifestyle management and one of the important thing in the food is that not only you reduce the salt.  Actually human beings need only about 2 g of salt, but we take about 12 g of salt, and so you cut it off to 4-5 g of salt every day, and if it is a severe hypertension then salt should be a taboo.  Slowly, after the hypertension is controlled you can give 1 to 2 g of salt.  There are some other minerals like potassium, high potassium food is against hypertension like coconut water, orange juice, sweet lime juice these are all good actually for reducing the blood pressure.  Maybe that alone may not be useful, but it is a good thing to keep the blood pressure normal.  Also, increased amount of magnesium and calcium.  Calcium comes from milk and curd and the magnesium comes from the green vegetables and the red things like tomato.  These are supposed to have antioxidant properties.  I think that is about nonpharmacological management of hypertension.


I think next thing is we will go to what will be the drug therapy for hypertension.  Actually, the JNC-7 has categorized the blood pressure into 130/80 to 140/90 as prehypertension.  In this particular stage we can have lifestyle management itself that may reduce the blood pressure.  Whereas if it is more than 140/90, besides lifestyle management, we can use drugs like ACEI or ARB.  I told you in the beginning itself that in the primary hypertension itself there is an increase renin-angiotensin aldosterone axis because of the existing endothelial dysfunction.  So, ACEI or ARB will be our ideal drug.  Why I say that, because you find that ramipril not only reduces the blood pressure, it also is anti-inflammatory and anti-cytokine and it is vasodilatory.  It reduces the preload and afterload to the heart and so today's treatment of blood pressure is not only reducing the blood pressure, but also beyond reduction of the blood pressure giving organ protection.  So, ACEI and ARB can give rise to protection of heart, protection of kidney, protection of vascular system as a whole.  So, that is why I am talking about ACEI and ARB.  Well, there are some 20% of the people who may have incidence of cough and they may not tolerate the whole thing, so ARB will be a good choice for them.  I think irbesartan, telmisartan are two of the common sartans, which have scored over in 3 landmark trials.  For example, the IDNT trial has shown that irbesartan is a good drug for diabetic hypertension and many other trials have shown that telmisartan is a very good drug and now we have got olmesartan also.  So, these drugs can not only reduce the blood pressure but they have all the advantage which I mentioned to ACE.  In addition, it does not produce cough.  Another advantage of sartans is it blocks the angiotensin-II receptor whereas the ACEI blocks only the ACE induce and the angiotensin II.  So, that is only about 60% of angiotensin II, the 40% is not blocked, and so ARB will be quite good to block majority of the hypertension.


Yet, another drug which has come into the market is direct-renin inhibitor like aliskiren, which will block the renin itself because it blocks the renin receptor and so you will not be able to form the angiotensin-I because renin has to combine with angiotensinogen to form angiotensin-I.  So, DRI (direct renin inhibitor) is a product which has come out 20 years after the investigation and it has got a very long half life, 24 hours, so 300 mg given is a better doses to reduce moderate hypertension, but DRI combined with a angiotensin receptor blocker will be much better choice in preventing organ dysfunction when compared to DRI alone.  Usually, if you look at the people who are hypertensive who are taking medicine, they take more than 2 to 3 drugs, so the ACEI and ARB alone may not be sufficient, so you got to use calcium channel blockers.  The best among the calcium channel blockers are the long-acting calcium channel blockers like amlodipine, lercanidipine, better still will be cilnidipine.  Amlodipine has the disadvantage of producing an edema in about 20%-30% of the cases, which alarms the patient because of the increased venodilatation besides the arterial dilatation, but cilnidipine will not produce this and cilnidipine produces a block of L and N.  L and N block leads to reduction in the epinephrine and norepinephrine and there is a vasodilatation.  There is no reflux tachycardia and then it almost behaves like an ACEI and ARB and so the fourth-generation calcium channel blocker will be a preferable one when compared to amlodipine or lercanidipine.  At times, they can also use drugs like verapamil, particularly extended release verapamil, 120-200 mg is a good dose for hypertension.  Usually, it is ACEI, long acting calcium channel blocker like cilnidipine or amlodipine, then you have beta blocker.  The beta blocker is certainly good in that the evolution of beta blocker from atenolol to bisoprolol and extended release metoprolol and carvidelol has proved the cardioprotection in addition to reducing the blood pressure.  The 3 trials on diastolic heart failure proved bisoprolol, extended metoprolol and carvidelol extremely good.  Particularly carvidelol is quite a good drug in the sense that it is an antioxidant, it reduces the proteinuria.  It is also anti-inflammatory and it is alpha and beta blocker, so it produces vasodilatation and the reduction in the cardiac output is not that much as in cases of bisoprolol.  Today what you have to understand is atenolol is no more in the vogue because atenolol only reduces the blood pressure and it only works for about 16 hours, it is not a 24-hour drug, and so I think you should stop prescribing atenolol and switch on to bisoprolol or extended release metoprolol or carvidelol.


Then, there is another entity known as diuretic.  Today's drug therapy in hypertension is individualized.  I would like to use diuretics in cases of a volume overload.  The hydrochlorothiazide or chlorthalidone better still.  Chlorthalidone is a long-acting diuretic, which can be used in mild hypertension.  Chlorthalidone can be used also in a case of isolated systolic hypertension.  Whenever you find in the hypertension, blood pressure systolic pressure is more than 160 and the diastolic pressure is always less than 90, you call it as isolated systolic hypertension.  This isolated systolic hypertension is present in elderly people and also in diabetics.  Actually, the systolic hypertension has got more morbidity and mortality when compared to diastolic hypertension and so it is very important that calcium channel blockers and the diuretics like chlorthalidone are the "the drugs," which can be used for isolated systolic hypertension.  They are the specific drugs.  In the same way, as I said, if there is a coronary artery disease and hypertension, I would like to use beta blockers combined with ACEI or ARB and if there is a chronic kidney disease the best drug will be the ACEI and ARB ,and if the blood pressure is not controlled by these 2 drugs you can combine with carvidelol or bisoprolol.  Particularly, if there is a proteinuria, I think the ideal drug would be ACEI, ARB, and carvidelol.  I think even cilnidipine is supposed to reduce the proteinuria and if you are using 3 drugs as I said already that many of the cases of hypertensive they use 3 to 4 drugs.  Instead of giving the maximum of 1 particular drug, you try to give 10 mg of ramipril and 5 mg of bisoprolol and 10 mg of cilnidipine, so you will find that they have different mode of action and so the patient will be more benefited when compared to giving maximum dose of 1 particular drug.


Another important thing that you have to understand is the so-called resistant hypertension.  When you use 3 drugs and also a diuretic or even without a diuretic you find the BP is not brought down below 140/90, it is defined as the resistant hypertension.  Well, in this particular case, I think, we have to use not only ACEI or ARB but also beta blockers and sometimes you got to use a combination of clonidine.  Clonidine can be given 200 mcg to 900 mcg.  Actually, you can give 300 mcg 3 times a day, that is the maximum dosage you can give.  It is centrally acting adrenergic drug and it will reduce the blood pressure.  Only thing is sometime they feel drowsy and if you continue the whole drug then you will find that the blood pressure will come down and the side effect also will disappear.  In spite of giving clonidine and ACEI, ARB, and cilnidipine, you find the blood pressure is high, you give aldosterone antagonist, Aldactone or better still eplerenone.  Eplerenone is evolution of Aldactone because Aldactone addition has definitely reduced the blood pressure much more than the 3 drugs that we are giving.  So, in resistant hypertension, usage of Aldactone or eplerenone is very-very important.  But only thing when you use ACEI, ARB, and Aldactone, the incidence of hyperkalemia will be very high and so whenever you do the repeat urea and creatinine once a month, you should also do sodium and potassium and the potassium level should be kept below 5 mEq.  Then you can also use minoxidil.  Minoxidil is available in India and 5-10 mg immediately brings down most of the cases of resistant hypertension.  I have no resistant hypertension at all because I use either clonidine or you can also use combination of the 3 drugs, which I already mentioned and prazosin.  Prazosin can be given up to 20 mg, to begin with you can give 5 mg twice a day.  Particularly when the patient has got hypertension and enlarged prostate prazosin will be the ideal drug of choice and in resistant hypertension also you can use prazosin, particularly the extended release prazosin, which will cover for about 12 hours or so, that is very important.


I think I have covered most of the important drugs.  There are many drugs which are coming up and I do not want to talk about a person who is in the front stage to treat the hypertension, particularly the consultants of general medicine.  So, I would like to end up here saying that is not only important to use the lifestyle management and the drug, but also it is important associated abnormalities like dyslipidemia.  The cholesterol has to be reduced below 180 and LDL cholesterol should be reduced below 100 mg and the triglyceride should be reduced below 150.  The best drug to reduce cholesterol and LDL cholesterol is atorvastatin or simvastatin.  Atorvastatin given 40 to 80 mg will be ideal.  In spite of the fact you bring the LDL cholesterol, you have to continue the atorvastatin at a lower dose for a long time because statins have proved they not only reduce the LDL and increase the HDL cholesterol, but also are anti-inflammatory and anticytokine and reduces proteinuria.  Also reduces the blood pressure by producing vasodilatation and so it will potentiate the action of the ACEI and ARB and the other antihypertensives, so it should be there.  Quite often in the obese people with hypertension you find there is a increased uric acid.  Also, in cases of chronic kidney disease; particularly with the IgA nephropathy and various other glomerulonephritis, uric acid will be high.  Hyperuricemia is very bad thing because hyperuricemia can lead to accelerated atherosclerosis.  Actually, there is an hypothesis in United States where the uric acid itself is responsible for obesity.  Well, actually they use cheap sugar made out of fructose.  The fructose made sugar increases the uric acid.  Uric acid in turn increases the obesity.  So, in addition, to the enormous use of pork and beef and also fast food and high salty food, uric acid is also responsible for increased obesity.  Uric acid produces endothelial dysfunction that is why it accelerates the atherosclerosis and therefore it decreases the CRP (C-reactive protein).  So you must use drugs febuxostat or Zyloric for reducing the uric acid.  Particularly if there is a raised urea creatinine febuxostat will be ideal drug to reduce uric acid level.


I think I have comprehensively conveyed everything except that I left one particular thing, it is not only obesity that is important to reduce the blood pressure, but it is also important that what in obesity has to be looked after.  The waist circumference should be less than 90 cm in male and less than 80 cm in female, and if it more it contains large type of weight fat which is supposed to be atherogenic fat.  It is almost like an endocrine organ.  It produces lot of cytokines and there is increased leptin and that leptin also can give rise to problems, and therefore it is very very important that the blood pressure has to be looked after.  According to the JNC classification that you got to reduce the blood pressure even in normal individual below 130/80 so that they do not have prehypertension above 130/80.


Thank you very much.

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