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I'm very honored to be before you this.morning to talk a little bit about.hypertension and the challenge and the.charge today was to talk about the.history of hypertension initially we.were we were talking about how women.relates to the history of hypertension.but I brought into so these the the.title that you see here this morning is.hypertension through the ages but you're.going to see that I that women have.played a major role in our approach to.hypertension or diagnosis treatment and.management of hypertension now allude to.that as we go one thing that I was.reflecting on over the last couple days.well I was sitting through three days of.a accreditation site visit for a.metaphor one of our medical schools in.South Carolina was I was reflecting on.my past and specifically of course.regarding hypertension but more.importantly it came to me that even.within my generation as a physician now.this has been sort of a one generation.disease hypertension even though we're.going to go back two thousand years or.even three thousand years really it's a.one generation disease what do I mean by.that I mean by that that it's a disease.that has with hypertension it's always.been there was it new however it was.within our generation that we've really.had the understanding the comparative.effectiveness research the clinical.trials the pharmacologic and non formal.logic armamentarium and the answers to.treat this disease and now we're seeing.the benefits stay for a moment of other.one generation diseases within our.generation has there have been any.diseases that that that we can come to.conclusion and talk about or at least.just mention that is similar and I've.got a few in my mind but the big one of.course to me is HIV so one generation.disease amazing isn't it peptic ulcer.disease um I'm old enough to know the.surgical management of peptic ulcer.disease well obviously that's very very.rare so it struck me that hypertension.that's been with us for over 3,000 years.in terms of under knowing about it or.understanding that it exists it's really.a one generation disease in terms of.knowing to treat it treating it with.what.actually seeing the beneficial outcomes.let's explore that then for the next 40.45 minutes the earliest literature that.I could find and I think many other.historians and by the way disclaimer I'm.not a historian I'm a physician but the.earliest literature and I think almost.everybody focuses on this one seminal.piece of work believe it or not from to.from from 2,600 ish bc from chinese.literature and this actually is a real.book it's a long teenage jing from when.book and translated that is the yellow.Emperor's classic in internal medicine.the Yellow Emperor was the Emperor at.the time of this province it's a seminal.book in that that noted some very.important issues number one talked about.blood flow and blood flow as a.circulation there was no directionality.to the blood flow that comes a little.bit later as we're going to say but it's.startling that three thousand years ago.blood flow circulation was discussed.more importantly the association of salt.with hard pulse and they in the Yellow.Emperor called it hard pulse disease and.in fact you can see his picture that's.from the book where someone's taking the.yellow Emperor's pulse and when the.pulse became hard you became sick and.that was an association perhaps I was.atherosclerosis perhaps that was just a.pounding pulse from a hyperdynamic.circulation etc we don't know and more.importantly they actually made the first.description or one of the first.descriptions of the Association of pulse.rates with death and mortality the.faster the pulse the harder your pulse.the sooner you were going to die that's.amazing so here we are talking about a.one generational disease which is only.30 ish 40 years and now we're putting a.context of 3,000 or 4,000 years upon it.what happened how did it take such a.long long time from this piece of work.to where we are today let's explore that.it took a lot of time took a lot of.ingenuity and it took a lot of.evidence-based research well still in.the early ages and here's women now come.into the picture very prominently from.epocrates 400 years ibc hypocrisy.described fits in pregnant women but all.sudden these women had fits well what.were these fits there are most certainly.seizures they were described as seizures.but they were called fits and actually.that's where the name eclampsia comes.from it's Greek for ships specifically.for shine forth but we've sort of.modified it and the modern translation.of that now is sudden development.something suddenly developed well these.women started having fits in hypocrisy.is noticed they were all pregnant but he.didn't put together the fits the.seizures of course eclampsia has a.disease and hypertension as one of its.phenomena but nevertheless women.prominently in early on led the way in.pointing to the devastating effects of.hypertension particularly as it relates.to pregnancy let's now approach down and.move to the Middle Ages there are many.seminal events I just picked a few for.brevity now these are my choices.everybody else could have their own.choices but I think these are pretty.fair choices in 1628 well William Harvey.came along and made a seminal.observation if you will and description.a good Italian and I've one of our.previous speakers is Italian I have two.enough another disclaimer I'm Italian.Torricelli comes along and makes a an.actually marvelous invention and then.that the description the invention is.put together by Stephen Hales well what.happened what are these three.individuals contribute well this is way.of Harvey as you can see it's the.classic it's the classic description of.on the motion of the heart in English.but of course it's the modus quartus of.in in the description of the book and it.was published in 1628 what was so unique.with William Harvey was it was.description about cardiac function heart.motion heart function but what he really.did and lend itself to the hypertension.field and the future of hypertension was.describing the directionality of the.circulation.so we had the Chinese disco describing a.circulation and it took almost what gosh.3,000 ish years for the direction of the.circulation to be described and how did.Harvey describe how did he come to.discover or even think about the.circulation going in the right way it.was because he noticed veins and there's.his drawing of him compressing putting a.tourniquet compressing the vein and.watching which way the blood went and.then of course anatomist would dissect.the veins and putting the the.circulation of the directionality of the.observation with the fact that veins had.valves so the circulation could only go.in one direction from the arterial to.the venous circulation Torah Shelley.then did a very very fascinating piece.of work and I don't have a clue why he.decided to do this but he put it to a.glass tube in a bowl of water and then.suspended fixed the tube and suspended.the tube in the bowl of water and he.made an interesting observation over.time the water rose and went down in.that in the tube and of course what was.he describing he was describing for the.first time pressure barometric pressure.in this case and notice his book he made.meticulous observations next to the next.to the apparatus and he described that.the water would rise and fall and.perhaps made those associations with the.weather but this is the first barometer.and without a barometer and without the.concept of pressure how in the world.could we even measure or even think to.measure the arterial circulation and or.the venous circulation in the past so.this is a seminal it's not medical mind.you but it's a seminal event in.hypertension they can't have a manometer.if somebody doesn't decide what pressure.is and invent a barometer well then.Steve Hales puts all this together he.puts the circulation together he puts.the the discovery of tort Shelley.together and what does he do now the.biggest question about this picture is.who the heck wants to be the horse.so what stable Hales did was train a.horse actually trained a horse the lay.down and it was a big enough artery the.carotid artery of a horse and notice.with tor Shelley he took the same.concept a glass tube and he placed it in.the carotid artery of the horse and he.found that the pressure raw the blood.rose in the in the glass tube if you.will and obviously this is the very.first measurement of arterial pressure.and it was so many feet in the horse.fascinating to see that one event leads.to another leads to another leads to.another let's continue still what I.would call the middle ages eighteen.hundreds to 1900s remember how tall the.the the tube had to be to measure.pressure a glass tube with either water.or with either blood then centimeters or.millimeters or whatever impractical so.the next major advance was the u-shaped.manometer and using mercury a heavy.metal instead of water so now you could.take something that was 10 or 15 feet.tall and lower and make it something.that now is more compatible with moving.it around taking it from from person to.person and or from place to place and.again it was mostly to measure pressure.changes in atmosphere pressure changes.and systems but not pressure changes per.se in humans at that point in time but.the u-shaped mercury manometer was.seminal and look up until recently and.some of us probably still have some.stashed away because I know we're not.supposed to because the EPA but I bet.you I could find still some squirreled.away and I'm not going to tell you if I.got what or not but it's pretty good.that I do but we have to do something.with them because of obviously EPA.regulations then let's talk about bright.rica rochi and erotic off now I snuck.erotic off in here even though it's five.years a little over the over the range.it's still in that it's in that picture.in that generation of scientists.researchers and observers more.importantly.Richard bright tremendous amount of.credit needs to be given to this man.what did Richard bright too we all know.Bright's disease so we all know his.kidney we all know he was probably.talking about a cuckoo maran a.frightened see the frigid ease etc and.he was the first to link a renal disease.weatherby glomerulonephritis etc.actually proteinuria at the same time.renal proteinuria and high blood.pressure an elevated pressure with.cardiac hypertrophy so really one of the.seminal individuals that put a larger.picture around pressure circulation an.organ the kidney and of course now.another organ the heart putting pressure.between the two but there was some.possibility that the high blood pressure.was affecting both both organs Rick.orochi probably one of the most night.great Italian took the previous.inventions of veseli barometer mercury.etc and really invented the first blood.pressure measuring apparatus in 1896.Reeve orochi invented the mercury.manometer and linked it to a blood.pressure inflatable cuff so now you.could actually determine this could only.determine the systolic blood pressure at.the time but it was the first time a.simple apparatus cost-effective.apparatus could be then used in various.places on various individuals etc and.very simplistically so it was really.Reva rochi that actually invented our.ability to measure blood pressure.non-invasively no more Stephen Hales.with long tubes and horses and kurata.cough of course then took that one step.further a few years later and linked it.to Oscar Tory measurements and first you.can this is in English but it was it's a.translation from his first description.in 1905 of audit the Oscar tory.measurement of blood pressure and.obviously he actually even then.described and drew the phases that we.obviously now know and.of course we've concluded and settled on.the fifth phase so we always know now.the diastolic is the fifth kurata cough.sound for many years it was the fourth.and of course he also described the.first karateka sound which is a systolic.blood pressure so now for the first time.we have a gold standard we have the.first and the fifth karata cough sounds.and now we have systolic and diastolic.blood pressure and now we're measuring.blood pressure for the for the first.time in a large number of individuals or.at least have the ability to measure.blood pressure in a law in a great.number of individuals very inexpensively.obviously in across distances geography.etc and it can be standardized this is.huge but still it's not hypertension but.all of this had to happen before we.could even talk about the L of a.potential elevation and blood pressure.the first have to measure it what about.women during these they're doing this.period during the Middle Ages played a.very very prominent role Charles lever.colleague of bright knowing brights work.then took the protein took proteinuria.became very interested in proteinuria.and actually then started measuring.eclamptic women's urines and described.proteinuria in women that had eclampsia.and he separated the proteinuria of.pregnancy and differentiated it from the.proteinuria and renal disease in.Bright's disease and proposed that these.were two completely different syndromes.and pathophysiologic processes of.pathogenic mechanisms still women.playing a problem predominant role and.of course it's very logical that it.usually revolves around pregnancy in the.in these periods of years schmorl's was.the first to find a trophoblastic cell.in the lung of a patient with eclampsia.now we know now we now know that that's.probably a normal finding that.trophoblast cells do escape the.circulation and can be found in various.places but this is the very first.description and now of course we know.and last year we talked about the.prominent role that the trophoblast play.potentially in the path of his logic.mechanisms.eclampsia and its prevention and again.this is still pre pre 1900s so now let's.go to a little bit more recent agent.what have we done with this information.which is actually the more important.question with all armed with all of that.knowledge and now the ability to start.measuring blood pressures we have a.tremendous problem what do we do with.these blood pressures some of them we.know are on one end a high end of a.bell-shaped curve and some of them we.know we're on a low end of a bell-shaped.curve but it's still now a normal.distribution of blood pressures barring.you know secondary causes of.hypertension still talking about.predominantly hypertension or blood.pressures distribute in the in the.entire population well as you can see we.have a problem and the problem was is.this normal finding is blood pressure.just normally distributed amongst.individuals is it does it change through.the ages as we age normally for whatever.various reasons and as you can see some.very very prominent individuals Paul.Dudley white one of the fathers of.Cardiology in 1931 said and you can read.it as well as I can but it's pretty.blunt hypertension may be an important.compensatory mechanism which should not.be tampered with even if it were certain.that we could control it so there was no.therapy for an elevation and blood.pressure anyway and one of our prominent.cardiologist said that it's it's it's a.normal compensatory mechanism the.English had a much more bold view same.year this is the British view from the.British society saying the greatest.danger to a man with high blood pressure.lies in its discovery if you don't want.to know the answer don't ask the.question right i tell my medical.students that all the time because some.fool is certain to try to reduce it so.now we have a problem we have the.mechanism I mean the the ability to.measure it we have the distribution of.blood pressures and we don't know what.to do with this entity how often is that.happening and we have to you know across.the pond if you will of agencies.individual societies saying.it's probably a normal compensatory.mechanism remember that women still in.the early 90s it's very interesting to.me that I found I believe they're.probably one sooner I don't want to say.that that I can't find a sooner one but.what I thought it was a very very early.publication by Gutman a book totally.devoted to the study of high blood.pressure and women from an entropy and.logic point of view as very interesting.because we didn't know what to do with.the women with high blood pressure etc.but already we were already describing.high blood pressure and women and the.possibility that it was an endocrine or.endocrinologic association even in 1921.remember the last slide was 1931.regarding still the controversy of what.he do with these elevations in blood.pressures of course harvey cushion came.along and described again in women first.hypertension acne and amenorrhea and we.now know what that came that led to and.more importantly and more interesting to.me that irving page of a prominent early.hypertension ologist if you will.described a group of women with.paroxysmal hypertension flushing.sweating and tachycardia so two very.prominent entra chronologic secondary.causes of hypertension pheochromocytoma.Cushing's syndrome probably even some of.these women probably could have been a.mixture of our previous lecture in terms.of polycystic ovarian disease etc was.described in women only later to be.found also to be true except for.polycystic ovarian disease if anybody.can tell me that in the mail I'd like to.talk to you because we could make a lot.of money but prominently was described.in women first men only came second.let's look at the life insurance company.and how they might have shown at least.some light on the controversy of what to.do with these elevated blood pressures.or even if they were normal or they were.deleterious John Fisher the remarkable.man worked for the insurance company his.entire life he was a physician and in.1905 the year karateka described karada.cough sounds started measuring blood.pressures and requiring them as a.requirement in all initial physicals of.individuals that applied for insurance.for Northwestern Mutual.pretty interesting or I talk about.translational medicine it took like.minutes and remember kurata cough was in.Russia all right in 1910 taking all.these blood pressures he publishes the.first actuarial data showing that.there's a high mortality and.hypertensives in the in the individuals.he's only falling for five years and.northwestern mutual life starts.discontinuing to issue insurance for.patients with systolic's greater than.170 this is 21 years before even Dudley.white Paul Dudley white another said oh.you know we don't know what this is a.this is bad or good it's probably and.it's probably good oh come on right in.1920 all life insurance companies.established asymptomatic hypertensives.as high-risk individuals and then.started charging more for their life.insurance amazing and this culminated.with this slide I've shown this before.over the last couple years because I.think it's so important this is 1983.this is the actuarial data from the life.insurance agents agencies that was.available actually many many years.before showing the association with.excess risk based on your diastolic.blood pressure so if you look at the the.y-axis a hundred is normal you know you.have an observed risk an expected risk.and it's you break even that anything.over anything higher than that the.insurance company obviously you're.having a morbidity or mortality that's.greater and they have to know that so.they can set their rates anything below.that notice that for diastolic blood.pressure after a diastolic blood.pressure of 83 it actually goes below.100 a little bit so you actually have.less morbidity so what the life.insurance companies do is at the.absorber whatever the disease is if it's.cancer or if it's whatever this is blood.pressure at where you cross the hundred.if you're to the right of that and you.have a higher they charge you more but.if you're lower than that they don't.give you any money back.is there anything that's similar to that.in terms of our normal life think about.Las Vegas think about the roulette wheel.there's 36 numbers on a roulette wheel.and the casino sets the odds at 12 36 if.you want to put a number on seven.they'll give you right snap guides.they'll give you a 12 36 so how can they.how could the casino make any money they.just break even overtime well there's.two other numbers on the roulette wheel.it's zero and double zero they don't.you're going to hit them one in 31 in.like two out of 36 38 times but they.don't give you any money back that's.their take well this is the insurance.company's 0 and double zero that's their.take that's how they make money they.aren't cheap you got the disease you're.paying for it what they do though is if.you're better and lower they don't give.you your money back so anyway the.insurance companies knew what what.academia was trying to decide long.before that's the point and now we know.that we know that now because of.evidence-based medicine population.studies out of academia as recently as.the year two thousand and two that your.diastolic blood pressure and your.systolic blood pressure exponentially.increases your risk but it doesn't start.with that magic 140 over 90 that we call.hypertension it actually starts at 115.over 75 right where their life insurance.companies had it even about 30 40 years.ahead the good thing though we caught up.another prominent study now in the in.the 1950s but was conducted during the.1930s 40s and 50s was this study of dr..Perera a single authored paper dr..Perera was a pathologist so while this.debate was going on in the 30s and 40s.is is higher blood pressures.compensatory and normal or they.deleterious dr. Perera started observing.individuals that died that had.hypertension and he noted in this cohort.of 500 untreated hypertensives that two.things one seminal observation was that.the mean onset of the elevation and.blood pressure was yet was 32 years of.age and your age of sir.vival after that was too aged was 20.years to age 52 even in the 1930s 40s.and 50s that was premature mortality so.dr. Perera described over a course of.three decades that hypertension and.elevation blood pressure is a mortal.event not a normal compensatory event.and more importantly once you a target.Oregon was affected in dr. Perera.actually described the target organs the.heart the brain the kidney and the.vessels could have put the eyes in there.as well your survival was markedly.foreshortened as you can see on the.right-hand portion of the slide your.mean I just survival for instance after.congestive heart failure and elevated.blood pressure was only four years.whereas the cohort in general was 20 so.he described two seminal observations.the Heart Association now starts to.weigh in and I love this one I feel like.sending this to my president I feel like.sending to this to my Board of Trustees.chair say you know we need to take these.recommendations into consideration in.1957 this is the first that i believe.Heart Association recommendations for.females and males they specifically said.this was for both genders if you had.high blood pressure and this is.preventive heart of preventing heart.disease first thing is try not to worry.I love that one but it gets better we.just heard about obesity and adolescence.and yesterday obesity in adults keep.your weight normal because overweight.over works the heart in 1957 follow your.physicians advice decrease smoking in.1957 right get plenty of sleep and I.just love this one take one to two naps.per day well I would love to do that in.the middle of a board meeting you know.it's been at South Carroll I'm going to.raise my hand you know mr. chairman it's.my time for a nap ain't going to happen.or if it does I'm going to I'm going to.be taking a permanent now choose sports.but don't use any that are competitive.that's that's bad for you and like I.love this one these are real rest before.you are tired well I'm going to probably.be tired if I want to rest now can I.rest now.I'm going to be tired I just love it but.really they're they're important because.now we have another organization a.public organization also weighing in in.the late 1950s saying it you know I we.laugh at these and then we have fun with.these today but they're still it's true.today as they aren't naps are coming.back if you haven't if you haven't.missed that one there's been real.evidence really very very good evidence.that a map with short 10 15 minute nap.in the mid-afternoon actually increases.worker productivity etc so it's just.it's just a lot of fun and obviously we.knew now from the Framingham study.moving forward that those those risk.factors whether it be smoking left.ventricular hypertrophy blood pressure.elevation diabetes cholesterol.manifestations are all exponentially of.an accelerator bisque factorial pool if.you will for individuals with mild.hypertension so now we have the evidence.based medicine we still haven't done.anything with it yet we're going to get.to them salt we talked about in the last.lecture nonpharmacologic management and.approaches to obesity particularly.adolescence salt has a very very long.history with in the first description as.we talked about our very first slide.from arch from our Chinese literature.that salt was associated with a hard.pulse so we've known an association.sodium restriction was first actually.advocated at least in this country that.I can find in 1904 that's reasonable the.rice diet then became popular was really.basically a nil sodium or.extraordinarily sodium reduced died had.other attributes do it but predominantly.sodium restriction by one of our.northern southern institutions at Duke.etc however even to this day in 2011 I.know this statement is going to be.controversial but if we have time I can.explain it the general recommendations.regarding sodium or salt restriction are.still debated as recently as just a.little short while ago you know.prominent paper came out that said at.least in some pop you know sect of the.population sodium restriction actually.could be deleterious.that doesn't mean we shouldn't be.advocating sodium moderation of course.we should and not only just for.hypertension for many many ideologies.but it's still amazing to me that we.still haven't resolved this issue with.any real granularity if you will pardon.the pun and this is not the bath salts.this soulful table salt we do know from.the hypertension literature and others.that taking a nonpharmacologic approach.to an elevated blood pressure will.indeed be successful in general whether.its weight reduction the DASH diet we.heard about the DASH diet earlier we and.hypertension are very proud of that diet.since that was our recommendation from.the Council of high blood pressure.research and actually did the dash study.which showed that the DASH diet.significantly reduces blood pressure and.there's there's the data as you can see.it dietary sodium reduction not.restriction reduction physical activity.augmentation and moderation of alcohol.so we do now know that these things are.effective and they are good public.health policy for the country and.individuals can take more advantage of.it or less depending on their.physiologic balance whether the Riemann.status if you will up their low rheenen.or high reen and etc they're younger.they're old and we can talk about that.at greater length if you will let's turn.the pharmacologic therapy and this is.where I really made the statement this.is a generational disease if you will.because it's really been the approach to.the ball that we need to treat it number.one and the data that supports that and.then how to treat it and to treat it.with safe and efficacious modalities.including nonpharmacologic modalities.the pharmacologic therapy goes back a.long way even though it's not.pharmacologic it's certainly I would.call a pathologic bloodletting was.prominent for thousands of years before.in the treatment of the heart and pulse.if you will thought if you've just be.greased that the pressure in the in.those in the blood system you'll you'll.improve the individual of course that's.not true but really in the 1940s.pharmacologic agents started to become.available sodium thiocyanate was.available in 1900 and that was obviously.a precursor to sodium nitroprusside who.knew that it was an end.filial relaxing factor etc and so and.such a potent age and therapeutic agent.but very very difficult to administer.and there was no evidence to give it in.the 40s hexamethonium hydralazine and.masseur p came into at least were.discovered and vented and again didn't.have the data to show whether we should.administer these agents are not the big.breakthrough really came through in.terms of pharmacological well therapy.really came with courtesan diarrhea if.you will the end then merck sharp and.dohme team not to give credit to but its.credit where credit is due one the.Lasker prize which is the the price.right under the nobel prize for the.discovery of diarrhea the Boston.University hypertension group and others.around the country kicked up on diarrhea.and actually started using it not only.in congestive heart failure because.actually diarrhea was was the hypothesis.on dyer role was to replace materials.and some of us remember mercurial rounds.where you go into the homes and give.mercurials i am three times a week for.congestive heart failure as diuretics.well hydrochlorothiazide then became the.first orally active daily diuretic and.then of course individuals investigated.for its blood pressure lowering effects.and the stories well known and it became.obviously the first true safe.efficacious easily reasonably well.tolerated agent to lower blood pressure.still know that that would work or that.would help or be worse but we had an.agent dr. black one vote the Lasker and.the Nobel Prize for discovering beta.blockers and one of the first uses of.beta-blockers actually in first.interventions with beta blockers was in.an element was in elevations and blood.pressure also code you know in parallel.angina etc but really its prominent the.prominent role really was in.hypertension early early on and now to.the present then came central Samantha.lytic the elder Mets if you will Claudia.Dean's Guana benzes and now to the more.recent ages calcium channel blockers.Rena ninja tents and inhibition and we.have various main mechanisms to block.the calcium channel and we have various.different places to block the Rena and.angiotensin system and we now know where.we are today I was very fortunate.be trained at Boston University with the.group that I've been describing in.others and obviously that group was.really the one the forefront of renin.angiotensin inhibition discovering ace.inhibition with our with our squibb.colleagues as well as also of course.then administering it to individuals.with hypertension and then the first to.administer it to an individual's course.this is captopril to patients with.congestive heart failure and when you.have that experience and you watch the.next 25 or 30 years unfold you just go.wow this has just been a wonderful.wonderful career so now we have we can.measure it now we know that it possibly.could be harmful not a compensatory.mechanism and now we have some agents.that possibly could lower the blood.pressure relatively easily but we still.don't know whether it's going to do any.good or do more harm and here is now.translational research comparative.effectiveness research in the 1960s the.VA played an extraordinary role in our.history of hypertension we had these.returning veterans post World War two.and posts Korean War coming back and.some of these veterans they're all males.of course as you as you might expect in.that era started to die and they started.to die quite fulminant Lee from various.terrible sundry events perera's target.organs heart attacks congestive heart.failure arrhythmias stroke and kidney.disease and malignant hypertension blood.pressures that went through the roof the.VA started say we'll wait a minute let's.do a study let's convene all the VA's.together we don't need very many of them.as you're going to see in the first.study and let's see whether lowering the.blood pressure might be of any benefit.because it still could be harmful and.they started enrolling 150 veterans.that's all it took as you can see 7d ish.were treated with placebo because we.didn't know whether it was going to be.harmful or not and 70 were treated with.antihypertensive drugs for serpe.hydralazine and diarrhea was the therapy.and it was for patients with diastolic.of 115 to 130.because if there was going to be a.benefit and was it was still arguing.perhaps it would be the highest blood.pressures that would benefit the most or.if there were going to be one those.should be the ones that would benefit.that was the hypothesis but remember.there are plenty of individuals still.saying don't lower the blood pressure.it's a compensatory mechanism to protect.the blood vessels particularly the.cerebral circulation well look what.happened it only took 140 ish 150.veterans and you don't notice there's no.p values there's no asterisks on this.when something's obvious you don't need.statistics if there's statistics worry.about it and why do they have to measure.you know what I don't really mean that.however this is one where you don't need.any statistics look at what happened to.the individuals that were treated with.placebo and look what happened to the.individuals that were treated with the.antihypertensive drugs and case closed.we now had the very first study that.showed that treating severe.hypertensives has absolute dramatic and.very immediate benefit as you can see.I'm particularly fond of this slide but.I'm prejudiced this is two individuals.Kieffer and Wilkins both positions at.Boston University and notice there they.have a chart that they're there pointing.to or the right there and actually.signed the chart and actually this char.this this was the original description.of an concept if you will and they're.actually giving it to Arab Chabane Ian.who was the head of the of the.cardiovascular institute the Whittaker.Institute at the time were obviously and.I trained subsequently with dr..Trevanian and dr. Gavras what is that.that's not important what's important is.look at that what is this what's this.concept that was probably in the late.1950s it's stepped care therapy for.hypertension it starts with and I'm.gonna have to look for sir p so if you.start with research and it doesn't work.you move up to very trim a very unusual.drug that actually stimulates if you.will the carotid sinus to send lots of.nerve traffic to the brain thinking.blood pressure's elevated so the brain.bear reflects Lee tries to lower it and.if that doesn't work you go to.hydralazine a vasodilator and if all.else fails you use guanethidine a.ganglionic blocker on the top of the.scale it's not so important what the.agents were what's really important is.it was the first conceptual.conceptualization of the approach to the.hypertension patient which pretty much.at least we use the concepts of this.approach still today we've changed it.we've modified it we've changed the.medications we've changed sometimes we.can start to drugs at once that you.always have to start with one drug or.another and we've also got some data as.i'm going to show you on which to drugs.may be better than other two drugs but.it's the concept what a wonderful.picture and that led to this trial the.HD FP trial which compared in mild.hypertensives now mild to moderate.hypertensives not the severe ones of the.VA study in the 70s step care therapy.that approach versus intensive step care.therapy in the university setting where.you were required to use it versus what.was usually practiced which is the.referred care patients in the.communities and the hypothesis was is.that if you refer to the specialized.centers and they used step care they.would lower the blood pressure greater.then the physicians practicing in the.community which were following their own.you know policies wisdom and art of.medicine which was still very very good.at the time thank goodness it worked.because there was a blood pressure.differential differentiation between the.two groups the step care patients had.lower blood pressures than the referred.care patients and this is the very first.large-scale clinical trial which showed.we should treat blood pressures of 140.over 90 and greater as you can see from.red to grey the step care intensively.treated patients at least ten sively.treated at that time had decreased.deaths cardiovascular disease strokes.acute MI and ischemic heart disease.related events and that is this is the.study that really changed our paradigm.to start treating blood pressures of 140.over 90 of greater in both men and women.since they were both included in the H.p trail the Framingham study now has.shown us that the life insurance.companies are absolutely correct even in.the early 1990s but in the year 2000.that there's no normal blood pressure.blood pressures are continuum and you.can see that now these are patients that.are under 140 over 90 put in the normal.range so sorry hi normal range 130 to.140 or 85 to 90 normal 120 over 80 s and.optimal 115 over 75 and this is the data.that now we put into our jnc last j and.c7 and I'm I don't know if it's going to.be continued and or modified in jnc.eight their convening right now as we.speak but again both women and men.stories the same there is no gender.difference there's just the fold.difference because of course males have.higher cardiovascular disease rate at.least premenopausal than females that's.the only reason the numbers are.different and now we know what our.diastolic goal should be when we start.an individual in our practice at 150.over 95 what should our gold be if they.have no other compliments and disease.the hot trial again recently published.demonstrated to us that the goal blood.pressure at least in the aggregate ought.to be a diastolic blood pressure of 83.where did we hear that 83 before from.the life insurance agencies 30 years.before the hot trial was the optimal.blood pressure very interesting but not.so in diabetics if you're diabetic with.perhaps we could do a little bit better.than that if we lower it a little bit.more and this was down in 282 diastolic.blood pressure of 80 and there was still.increasing benefit in the diabetic.cohort but not so fast more is not.always better this is the accord trial.which had two major arms one was in.tight diabetic control as dr. P dziak.has taught us over the number of years.as well as tight blood pressure control.which is what we discussed actually as.recently as last year we went over the.Accord trial and the trial was to look.at really aggressively lowering the.blood pressure.in high risk type 2 diabetics would it.make a difference would they even be.better and of course you have standard.care and then you have intensive care.and this was based on systolic blood.pressure and you can see there was a.substantial decrease in the two groups.difference with intensive blood pressure.control being attainable being done.safely and obviously it was sustained.over the seven eight years what a.surprise however that most of the.endpoints showed no difference you don't.have to look at this but most think that.you can take my word for it most of the.endpoint showed no difference and.actually right now presently we don't.have we do not have data that says we.should intensively treat now that is to.systolic's of less than 120 our diabetic.population because it didn't make a.difference in primary outcomes it didn't.make a difference in non-fatal em eyes.and or death from cardiovascular causes.but I would caution you when you read in.your medical journals and or in our in.our society of publications which are.all going to truthfully portray the.court trial that there was one.difference the intensively treated.diabetics did have a significant.reduction in stroke I'll bet it was very.small and you need a p-value to prove.the difference but nevertheless it's.there and that's something that we're.still talking about discussing and.questioning we also know that there's a.difference between the systolic and the.diastolic blood pressure in terms of.prognostication if if Paul Dudley white.talked about the fact that blood high.blood pressure was a normal compensatory.mechanism in the 30s I was even talked.to in medical school in the 1970s that.the systolic blood pressure elevation.was a normal compensatory process we.knew to treat the diastolic blood.pressure but Lee don't don't go treat in.the systolic blood pressure because we.have to profuse the brain so even in the.1970s and late 1970s that was still the.common dictum and that was what I was.taught and I was taught by the former.head of the FDA Arthur Hays and he was a.hypertension ologist so what dr. hey.said you believed trust me and it was.absolutely the dictum of the day not.true of course when we actually do the.clinical trials the.is the systolic hypertension and elderly.trial the first to show that number one.you can effectively and safely lower the.systolic blood pressure in our elderly.population with diuretic based therapy.this was fourth aldim and as you can see.active therapy went down greater than.placebo so it was achievable and.actually the endpoints were.significantly reduced so this was one of.the first trials if not the first trial.to show that you can safely and.effectively lower the systolic blood.pressure and significantly reduce stroke.coronary heart disease heart failure.cardiovascular disease but not death it.didn't have it didn't have a significant.effect on death perhaps it was.underpowered or perhaps it was just they.were younger elderly patients.nevertheless this was a paradigm shift.in our practices because now we were.told treat the systolic blood pressure.initially greater than 160 and now we're.told to approach and treat the systolic.blood pressure greater than 140 with.reason with individual judgment etc and.caveats now we know however even more.recently that in our very elderly.patients because then the question.became well what if you're 80 what if.you're 85 is it still is it still.effective or harmful to treat the.systolic blood pressure the systolic.hypertension in our very elderly.patients and of course the Hiva trial.conclusively demonstrated again that you.can do that you get active treatment can.significantly and sustainably lower the.blood pressure compared to a placebo.group and more importantly this these.results are even more impressive in.terms of showing significant reductions.in stroke death from cardiovascular.events and death from stroke but for the.first time actually demonstrated a.significant reduction in mortality that.we could not show or we did not show in.the shep trial why is that I happen to.believe that these individuals are.closer to death so if there's going to.be a death obviously a reduction in.death and death benefit it would be.powered eat more easily to demonstrate.it in this population but nevertheless.it is what it is and it's wonderful news.so we don't know about 85 or greater or.90 or greater but we're getting there.so what lessons have we learned we've.learned that to really significantly.lower the blood pressure particularly.with concomitant diseases that we need.to use multiple antihypertensive.medications and when you use multiple.anti percents of medications and you.also have diabetes hypercholesterolemia.obviously the metabolic syndrome that.our previous speakers have talked about.in adolescents or adults it becomes very.difficult because they're on four or.five other medications at the same time.and that's problematic not only from a.cost basis but from a compliance basis.dr. Hayes also my pharmacologic.pharmacology there a teacher when I was.younger and medical school also taught.me that if a patient's taking more than.nine pills a day and they're telling you.they're taking all their medications.they're lying it's not possible and.that's a problem that we must confirm.confront and what have we done how was.one opportunity to modify that and that.is now to use fixed combinations of.pharmacologic agents things that I was.taught was this was absolutely verboten.this was voodoo you're not a real doctor.if you're not titrating the drugs and.individualizing the doses etc well again.another totally appropriate.understanding at one time that's totally.now changed with paradigm shift.comparative effectiveness research and.clinical trials to demonstrate otherwise.this is of course the accomplished trial.which looked at a calcium-channel.blocker amlodipine combined with a ACE.inhibitor benazepril as well as.hydrochlorothiazide combined with.Bonanza pril in terms of combination.therapy from the get-go and demonstrated.not only does the combination therapy.work of course we knew that from smaller.trials but more importantly in this.trial demonstrated that patients that.are on the Bonanza pro + M lo de p.combination versus Bonanza pearl and.hydrochlorothiazide with the same level.of blood pressure reduction have better.outcomes so this this study deserves.some attention because it's the first to.show us that combination therapy that.block perhaps different systems within.the pathophysiology of hypertension or.the individuals pathophysiology or.genetic background.may have therapeutic benefit independent.of blood pressure reduction and I think.you're going to see some strong.recommendations come come across that an.ACE inhibitor in a calcium channel.blocker combination perhaps may be.preferred I already know that there's.already position statements from the.American Society of hypertension saying.that that's a preferred combination and.I'm the nice the nice recommendations.just recommended the same I don't know.whether that's going to carry through.the jnc eight or not but I'm going to.bet probably so we've come full circle.we now know that but that an elevated.blood pressure is in fact deleterious.it's not compensatory we actually know.that the pathophysiology of an elevation.of blood pressure is not simply the.pressure's elevated it's a load on the.organs and the organs die and then the.patient dies we now know that it's far.more complicated that there's.endothelial dysfunction on top of.vascular dysfunction which leads to an.elevated blood pressure which indirectly.can which indirectly can lead to target.organ damage independent of blood.pressure or via the blood pressure and.it is this paradigm I think that makes.it so wonderful to have participated in.at least the last 30 ish years of the.approach to this problem this huge.public health entity and this disease.state and we still have a long way to go.well we've reviewed the past and this is.the past does anybody know what this is.quiz I could have done that ABCD thing.but then I saw dr. P dziak do it this.morning and I said I'm even worse of.technology than dr. pzx so I chose not.to what is this anybody know it's not.it's not an execution but it is a.medical student look what they used to.know i'm teasing about that I'm going to.get I'd like to believe this is a.medical student before informed consent.so here's the poor medical student.sitting in a chair putting his hand in.two buckets of solutions and then they.hook them up to some wires and someone's.going to pull the truth which which is.exactly what they did unfortunately good.news is the electricity is not going to.the body electricity is coming to the.apparatus it's the first.gee that's what this is this is an EKG.and you can see it it's amazing the.electrolyte solution was potassium.iodine silly because it conducted.actually conducted the body electrical.events and they were recorded as you can.see come a long way from this EKG.apparatus right well let's summarize and.say how are we doing with all of this.three thousand years where are we today.and let's great let's put a grade on it.and again this is a generational disease.even by the basis of this data this is.the first day that we've been tracking.since the early late 1970s early 1980s.in the end same project which is an.nih-funded federal study looking at just.distributed geographic and and racial in.ethnicity based populations of all kinds.of things one of which is hypertension.well in nineteen eighty eight to.nineteen ninety four twenty four percent.of the population it was prevalent in.twenty four percent of the population.and over the years the next couple.decades it's increased but hopefully.it's leveled off I don't believe it but.I'd like to believe it I'd like to be.Peter Pan that to twenty nine percent.awareness started at sixty-eight percent.meaning if you had hypertension.sixty-eight percent were aware he went.to seventy percent not so much an.increase in a decade but the last report.was just this recent in 2008 showing.eighty-one percent of our population is.now aware they have an elevation and.blood pressure they have hypertension.that's good news treatment if you were.aware and you were under treatment it.was fifty-four percent increased mildly.probably not significantly to 59 but has.had a big jump in the last decade to.seventy-three percent and finally what.we really care about is control and.control is less than 140 over 90 control.rates were dismal in the late 1980s.nineteen nineteen ninety s twenty.twenty-five percent increased only.moderately to thirty four percent and.has made a bigger jump in the last.decade to fifty percent so if we just.judge where we are and this is the.latest data we have as a nation that we.have a prevalence of thirty percent.awareness of eighty-one percent under.treatment close to that seventy-three.percent and fifty percent controlled.let's give it a grade how many think.that this deserves an A grade.we should give all of ourselves and I.mean that's not us in the country and.egg any a's okay I'm glad that we're not.satisfied we're not going to sit in our.laurels and take it you know just pat.ourselves on the back and say jobs over.how about a be any bees oh come on we're.doing little we're not that bad all.right I can't even get out of B how.about a seat yeah I'd give my I'd give.it a see addy and you're allowed to give.lower grades then the guy up here to.give them the lecture and an F no we're.not we're not failing I guess I think.they buy even virtue of the hands where.we've made a huge amount of progress we.still have a ways to go but actually I.think that we've done the heavy lifting.we've done the heavy lifting in terms of.diagnosing managing appreciating it the.epidemiology the public health.pharmacologic agents and there may still.be newer ones to come but now we've got.we've got that last bit to go and so the.heavy lifting science-wise and public.health wise has been done but that last.fifty percent is going to be tough.especially as we have concomitant.diseases etc if we don't approach this.as a as a collaborative effort with our.with approaching diabetes obesity.metabolic syndrome coronary heart.disease and lifestyle modification etc.but all that hopefully is going to be.ongoing.you.

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Form Nih 2043 FAQs

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I was selected for a summer internship 2016. I tried to be very open while filling the preference form: I choose many products as my favorite products and I said I'm open about the team I want to join. I even was very open in the location and start date to get host matching interviews (I negotiated the start date in the interview until both me and my host were happy.) You could ask your recruiter to review your form (there are very cool and could help you a lot since they have a bigger experience). Do a search on the potential team. Before the interviews, try to find smart question that you are Continue Reading

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