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Newsletter

Electronic publication of the First Virtual Congress of Cardiology,
for purposes of promotion and interchange of topic of interest in
cardiac sciences and news from the Congress.

(Spanish version click here)

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Number 19
Number 18
Index

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Year 2, Number 19. Second two weeks, March 2000.
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Biweekly electronic publication of the First Virtual Congress of
Cardiology, for purposes of promotion and interchange of topics of interest
in cardiac sciences and news from the Congress. It is distributed free of
charge to everyone subscribed. Those of English speaking origin may
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Contributions are welcomed; also responses to previously published
articles, and commentaries should be send as Letters to:

readers@pcvc.sminter.com.ar

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Previous issues at:
http://www.fac.com.ar/cvirtual/newslett/newseng.htm
or at
http://pcvc.sminter.com.ar/cvirtual/newslett/newseng.htm
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"Eradication of smoking is the most effective means to improve the health
in the population of both developed and developing countries."

>From this column, we propose the FVCC to be free of tobacco smoke.

Colleague: if you are still a smoker, we will thank you if you abstain
from it while you participate in the activities of our Congress, and we
invite you to get in touch with us, so that your attempts tostop turn out
to be successful.

TAKE PART IN THE INTERNATIONAL PROJECT 'QUIT AND WIN', AND INVITE YOUR
PATIENTS TO DO IT, TOO.

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CONTENTS

Editorial
By Dr. Edgardo Schapachnik

Final speech
Letter sent by Dr. Finizola Celli

Farewell
Dr. Alfredo Piombo

Globalization and inferior infarction
Why is evidence so little evident?
Dr. Carlos Tajer

Space available for Advertisement.

===========================================================================

The Deutsche Bank  (http://www.deutsche-bank.de/congress) supports the
Newsletter of the First Virtual Congress of Cardiology.

===========================================================================

EDITORIAL

The First Virtual Congress of Cardiology is finishing.
After six intense months of activities, this unprecedented experience for
cardiology is coming to an end.
Outstanding Scientific Societies from the world of cardiology are still
reluctant to include Internet resources with all their power for
development and transmission of scientific information.
However, more than a 100 diverse Societies, Universities, Foundations, and
Institutions provided their support to this activity.
172 renowned specialists of international level helped with their
contributions to provide splendor to the event.
Through mailing lists, 16 thematic forums were implemented, they were
moderated and bilingual, and 8 working forums were the invisible part of
the Congress.
The thematic forums received more than a thousand questions and replies,
and those concerning respective activities were edited and published on the
Web. Almost 800 questions addressed by the participants to the working
forums were answered. The internal lists had an intense activity, centered
in presidencies, secretariats, and moderators of the thematic forums, where
nearly 5000 messages were exchanged.
A system for self-evluation was implemented, with questions originated in
the lectures, with credits for recertification of specialties, directed by
the Teaching Committee from the Argentine Federation of Cardiology.
From each one of the versions (Spanish and English) 19 issues were
published of this Newsletter, as well as 4 special issues in Spanish with
the textual copy of four chat sessions.
We had a Public Area available, which could be freely accessed, and which
had medical and cultural information, and entertainment for professionals
and non-professionals.
The on line, bi-directional union was fulfilled between the cardiovascular
area from INABIS 2000 (6th Internet World Congress for Biomedical Sciences)
and the whole FVCC.
We have a figure close to 7500 registrations from 94 countries, and the
former continue coming.
We are working on the edition of the CD that will contain all the material
developed in the FVCC.
In the few days that remain until March 31st, the FVCC still has very
important activities waiting: the presentation of the six Prizes to the
best scientific works presented: the chat session in Spanish with Dr.
Carlos Bertolasi, member of the Honorary Committee, the chat session with
Drs. Alfredo Piombo and Hugo Londero, a first experience of this kind,
where a clinical cardiologist and an interventional one will exchange
points of view about strategies to approach the acute coronary patient.
The First Virtual Congress of Cardiology ends with the Second Congress
already having been announced to begin on September 1st, 2001.
In the meantime, a Forum on Continual Education is being born with all our
verve, which has activities planned already, for the rest of year 2000: the
First Virtual Symposium on Chagas Disease that will be announced soon,
periodical chat sessions that will tackle the most diverse subjects of
current Cardiology, with a session about epidemiology having been already
planned, and another one about use of Beta Blockers in Heart Failure, and
most of all, 16 Chat Forums in Spanish that will be kept operating.
This Newsletter will become the Newsletter of the Forum on Continual
Educational of the FVCC, and will be edited in Spanish.
For the English-speaking colleagues who have accompanied us along these
six months, we will keep a reduced edition in which we will send you
different scientific material published on the Congress.
The only thing we have left to say, is that as members of the Steering
Committee of the FVCC, this experience has been amazing, what makes us
commit even more with the scientific level of excellence that we expect for
the Forum on Continual Education, and for the Second Virtual Congress of
Cardiology (SVCC).
In this issue of Newsletter No 19, a sharp, humorous article by the
prominent Argentine cardiologist, Dr. Carlos Tajer, is a perfect end that
tackles one of the most powerful discussions that were developed in the
CORONARY Forum and the INTERVEN Forum, to make a deep revision about
indication of thrombolysis and angioplasty in acute inferior infarction.
Colleagues: the First Virtual Congress of Cardiology is finishing, but our
task is just beginning. I wish you success in the road
that we will share in our continuing education!

Dr. Edgardo Schapachnik

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FINAL SPEECH
LETTER SENT BY DR. FINIZOLA CELLI

The good reception to the 1st Virtual Congress of Cardiology, is a mirror
of the success reached.
The near 7000 registrations from 94 countries, is a resonant figure that
guarantees individual receptiveness and a high level of participation.
The support from 15 Universities, 58 Scientific Societies, and 16
Foundations is a sample of the institutional backing provided to this
Congress.
It is the first activity in regard to cardiology on the Internet, in which
brief communications are presented, discussions are made, one can
participate in the three languages spoken in the American Continent
(Spanish, English, and Portuguese), and it is possible to interact
actively.
For the Inter-American Heart Foundation, this important congress
constitutes a new mechanism that makes scientific information
dissemination easier, in a wide and economical way, and likewise, it
encourages and strengthens the organizational and individual net in the
American Continent, which contributes to the development of programs for
Prevention and Control of Cardiovascular Diseases.

Cardiovascular and Cerebrovascular Diseases, due to high morbidity and
mortality, require for their control, the participation of the whole Health
team, and Community in general, as well as use of means of communication
that allow knowledge to reach everyone so that benefits can be universal.
This 1st Virtual Congress met expectations, and must encourage us to
organize similar events in the future.

Bartolome Finizola Celli.
President of the Inter-American Heart Foundation

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FAREWELL

Dear colleagues:
The First Virtual Congress of Cardiology in history is coming to an end.
All of us, who to a greater or lesser extent have taken part in it, feel
overwhelmed by a rare mixture of joy and sadness. Joy because the success
of the awesome enterprise leaves no room for discussion, and sadness
because it is always difficult to say goodbye.
A goodbye that has to be necessarily transitory. If the FVCC has been an
end in itself, and not the fundamental stone to start a new road, all of
our efforts have been in vain.
The greatest challenge begins just now: to keep this exceptional
communication net that knows no frontiers, always active. We must set out
to think on the how. The when is now.
I am not one of those who believe that the Internet will replace in the
future, medical activity such as is practiced currently, but I am convinced
that it will be an indispensable and unavoidable supplement for
professionals from the present and the future. A favorable aspect of the so
trumpeted globalization that has entailed so many difficulties for weaker
countries, as the one I got to live in.
The road we have to go is hard and long, but the door has already been
opened. We must not allow anyone to attempt to close it. Let us put in this
enterprise all our efforts, since as the great Argentine writer, Ernesto
Sabato says, only the things that are made with passion deserve our
respect. The rest is not worthwhile.
See you soon, dear friends.

Alfredo C. Piombo
March 5th, 2000.
Buenos Aires. Argentina.

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GLOBALIZATION AND INFERIOR INFARCTION
WHY IS EVIDENCE SO LITTLE EVIDENT?
Dr. Carlos Tajer

Taran, Taran (2) Tarantarirara, Tantarirarara,....
- Dr. Larry, Dr. Moe, Dr. Shemp, cardiologists on call, come to Emergency
Room.
Moe, Curly & Larry
- Shemp, call to see what is the problem.
Shemp
- I'd better go down and let you know from there... Moe, this is a patient,
52 years old, with inferior infarction in hyperacute phase with ST
elevation in DII, DIII aVF.
- How lucky! The case has just been discussed in the forum from the Virtual
Congress of Cardiology. Larry, get connected right now, and verify the
e-mail from the FVCC where the material is saved.
- “Here it is...!” (a) Let me see... “Oh! My God!”(b) There are around 20
messages! I'm opening the first one, anyway, it is so simple a case.
- What does it say?
- That it hasn't been proven that we have to administer anything apart
from aspirin 160mg.(1) I glance through the rest of the pages, and no one
disagrees... Shemp, make him chew the aspirin (2 of 100, please)...
- I see another one that reminds us to try nitroglycerin drip (2), since
infarction is very early, and in some cases it may improve... No one
disagrees... Proceed Shemp.
- Go on reading Larry: the patient is still in pain and with ST elevation.
- But for the aspirin, they all state the same goal: to unblock the artery
as soon as possible and with the greatest efficiency... This goes well...
Wait Moe, this is getting complicated... (he tears off his hair with both
hands).
- Came on Larry! (taking Larry by his curls he hits his head against the
desk)
- Thanks Moe. Now it’s getting clearer. Some want to perform thrombolysis,
and mention streptokinase, others want to make direct angioplasty and
nothing else, and others, quoting a certain professor Minguito,
state:“Se’igual”*... Stop beating me again Moe, read it yourself if you
don’t believe me...
- Let me see those mails, idiot.
- Pipipipipipi Moe, what do I do with the patient?
- Let me see those papers... Firstly most of them are not content with
aspirin... Then we must go on. Streptokinase? Will it be worthwhile?(3) Oh,
pair of jerks, I have to do everything myself... Yes, yes... Mm... There is
no way I will leave him without reperfusion... I’ve got it... We have to
reperfuse him, right now!!!...
- “Marshmellows” (c) for Moe´s news... even the nurse on watch yells at me
that we must do something... but what do we do: thrombolysis or
angioplasty?
- Let’s get together for a moment... (they gather making a scrum with all
the papers in the floor and they go around them some times).
- Look, I like this angioplasty thing... we’ll see it on screen... We will
know how it turned out... then we will place a Stent, and while we’re at
it, we may as well use IIb IIIa... “and the chicken is fried!” (d)
- Don't you think it may be a little too much? Is it “nesario” (a touch of
local color...) (e)... but this “sale un vagon”**... “ten thousand fucking
argentinian pesos”(f)... Or dollars... And streptokinase 400 dollars.
- I think I've seen it in Germany at 180 dollars... Even in USA...
- These are special costs subsidizing “underdeveloped countries” (g)...
But let's return to this, from where did you, Larry, get the idea that
angioplasty is better than thrombolysis?(4)
- It could be a little better, but this is an inferior infarction...
- Here, one of the e-mail messages quotes a certain Zilstra, who noticed
in a five-year follow up a remarkable difference even in inferior
infarction, and says those who don't perform it are “a mother of...” (h)(5)
- (Covering Shemp's mouth and shaking his head) this is a moderated e-mail,
blockhead, mind your manners...
- I was reading the footnote, and I think this man is exaggerating, but...
- Let's begin by the practical part, as the General said: “the only truth
is the reality”***, gosh... “I realize”(i) that I have never understood
that sentence... Who is on watch in hemodynamics?
- Who? ... Billy Stonehand?... oh! Poor patient, I think he has performed
only 3 or 4... My God...(6). Let's send him to another institution,
urgently...
- Here everyone says no, that the patient must be treated where he is
admitted for the first time... Dr. Campoverde or Dr. Castles are not
around?
- Can they get here in 120 minutes? “Is it worth?”(j) (7)
- Oh! No! We cannot wait... This town hall! It should place urgent PTCAs
everywhere... (8)
- Look here, Shemp! Can you see it?... (hitting his fist with his other
hand, the right arm makes a circumference and falls like a hammer on
Shemp’s head).
- You are a fucking”(k) squanderer. If you spend everything in this we
will have nothing left for vaccines, and least of all for medical
salaries...(9)
- We have invested a lot of money” (l) in digital hemodynamics and “so
on”(m), and are we going to make thrombolysis in an acute infarction? “Are
you crazy?”(n) Call right now...
- (The speaker is heard from the emergency room) Drs. Larry, Moe, Shemp,
the patient is going to Coronary Unit... drip of streptokinase was
indicated by Residencio...
- (They fall flat on their backs with their eyes popping out of their
heads, the three shout) “Thanks God...” (o)

(a) In English in the original
(b) In English in the original
(c) In English in the original
(d) In English in the original. Translation from an Argentine saying that
means “And that´s that!”
(e) Mispronunciation of the word “"necesario"” (necessary) made popular by
the former Argentine President Carlos Menem.
(f) In English in the original
(g) In English in the original
(h) In English in the original
(i) In English in the original
(j) In English in the original
(k) In English in the original
(l) In English in the original
(m) In English in the original
(n) In English in the original
(o) In English in the original

* Minguito: Famous character played by an Argentine comedy actor already
dead. Minguito was an innocent, simple and vulgar man, who spoke a
particular "lunfardo" (slang) full of neologisms and who pretended to
tackle the most varied important subjects, speaking that language. For
instance "Se'gual" is his particular way of saying "es igual"
(whatever...).

** Sale un vagon: this is a "lunfardo", Argentine saying that takes the
metaphorical image of a train wagon, to express that an object is worth a
lot of money.

*** Reference to the General Juan Domingo Peron, former president of the
Republica Argentina, who used to say "la unica verdad es la realidad" (the
only truth is reality) (In English on the original).

Note 1: Unquestionable evidence: use of aspirin has been assessed in a
series of small works, but practically all the information available
comes from the ISIS 2 study. In the latter, administration of 160mg of
chewed aspirin, and then swallowed at admittance, reduced infarction
mortality in a 20%, in the range of action by thrombolysis, without
differences for localization or kind of infarction.

Note 2: Problems begin. There is no conclusive evidence about the impact
of NTG on survival. In a revision of studies from before 1990, with both
NTG and nitroprusside a reduction in mortality of more than a 20% was
confirmed. However, most of the groups included complicated infarctions
with heart failure. A large multicentric study was designed, randomizing
openly nitroglycerin against control, without differences in mortality
(GISSI 3 study). But in this trial, a 40% of the patients from the control
group received NTG, indicated because of hypertension, angina, or signs of
heart failure. Since the benefits of NTG over pain and ST are easy to
confirm at the patient’s bedside, and the evidence from previous studies,
and the finds from GISSI 3, it can be concluded that nitroglycerin is
useful if the patient has angina, and ST elevation, signs of heart failure
or blood hypertension. Its systematic use does not seem logic if these
factors are absent, even in the acute phase of infarction, or after the
first hours.

Note 3: Thrombolysis in inferior infarctions. In the studies with
infarctions and ST segment elevation treated by thrombolysis during the
first hours, a reduction of mortality in a 25% has been observed, 2 to 3
lives per each 100 patients treated. There is controversy about the value
of analysis of subgroups, that is to say, if the result is good in general,
are there groups that may be harmed or do not get benefited? Since these
studies are not designed for analysis of subgroups, but instead for the
totality of patients, its value is more restricted than general
information. In non-combined strict inferior infarction, reduction of
mortality was in a range of 1 each 100 patients treated, and it was not
significant if we consider the results from 58,000 patients as a whole, in
general randomized with thrombolysis. Faced with this information, medical
community has adopted in general, an attitude of considering this subgroup
analysis as a false negative, that is to say, the absence of significant
difference is just caused by low mortality of strict inferior infarction,
and insufficient number of assessed patients, but the tendency is in favor,
and inferior infarctions must be treated thus. Independently from
localization, in the GISSI study it was observed that when the ECG showed
three or less derivations with ST segment elevation, differences in
survival with thrombolysis were not confirmed, though they were when the
compromise was larger. This would be an aspect not related to the
localization of the infarction, but to the reduced impact of any measure
for revascularization in infarctions where spontaneous mortality is low,
and has little relation to the extension of the infarction, but instead to
other possible complications little influenced by reperfusion, besides
paying a small price in hemorrhagenic risk and stroke. A long time ago,
Simons made a detailed electrocardiographic analysis with enzymatic
curve on the impact of thrombolysis in inferior infarction, and
demonstrated that if the patient had less than two hours of evolution,
thrombolysis always benefited, and if they had more than two hours, only in
the patients that had more than12mm in all of ST segment in derivations
with elevation and depression. Another interesting observation in our
reperfusion works, is that depression of ST segment after thrombolysis, is
associated also in inferior infarction to a much lower mortality,
proportionally similar to anterior infarction. This is not a behavior
according to localization but to extension and opportunity of treatment.
This could be expressed by saying that as the more early and extended, the
inferior infarction must be treated with reperfusion. If it is late and not
very extended, the risks of other complications must be considered. My
personal opinion is that no inferior infarction with ST elevation in DII,
III and aVF in the first hours must be treated only with aspirin, unless
there are contraindications or high risk from reperfusion interventions.

Note 4: All the information on angioplasty vs. thrombolysis comes from a
series of small studies and a larger study, the GUSTO II that included
1,138 patients. If we take into account the latter study, global reduction
of mortality was from 7% to 5.7%, statistically not significant. The
associated final point of death, infarction or stroke was lower in the
group with PTCA during the hospital phase, but it was not significant at
six months. The first small studies showed a much greater benefit
concentrated in high risk patients and anterior infarctions, and taken as a
whole, mortality reduction would be around 1.7 patients each 100 patients
treated, barely significant. It is curious that in the GUSTO study, the
tendency to benefit was similar in anterior and inferior infarctions,
though of course not significant in any of them. In another footnote we
discuss the doubtful value from the first studies reported before the GUSTO
II.

Note 5: The work by Zilstra, as others of small dimension, must be
considered only to make hypothesis, and by no means to analyze
effectiveness or odds, just by the simple fact that larger studies have
refuted them in their quantitative aspects. This phenomenon can be
explained by publication bias: when a topic is beginning and is making
echoes, many groups start to try it, but only successful authors publish.
Likewise, in medical bibliography successes are not discussed (if the study
is positive only p matters, i.e. the alpha error), but if it is negative,
failures are orphans. Not only do they lack journalistic interest, but
power and beta error matter as well, that is to say, how can you be sure in
such a small study that the lack of differences in results could not be
attributed to scant power, in such a way that they do not stand judgement,
and they do not get published. In studies with angioplasty and
thrombolysis, when a graph is made to allow visualization of the existence
of bias or not in publication called funnel plot, the former is pretty
obvious. I think that tendencies with angioplasty vs. thrombolysis should
be derived only from GUSTO, or if not possible, from the meta-analysis
which has not been completed yet, but by no means from previous overvalued
individual studies, due to the high presumption of being unrepeatable (or
at least not repeated until now). An additional evidence of enthusiasm not
confirmed by data, is usefulness of angioplasty in cardiogenic shock. In
initial reports, mortality reduction in regard to historical controls was a
half, and in the only prospective, randomized study, a minimal difference
was observed (reduction in a 10% of cardiogenic shock mortality in six
months) when comparing angioplasty vs. thrombolysis. Mortality in patients
in whom angioplasty is possible, is much lower than that from cardiogenic
shock in general (elderly, several prior infarctions, left main disease,
and prior occlusion of several arteries, base myocardium very impaired,
etc.).

Note 6: The small and doubtful benefit that angioplasty contributes in
regard to early thrombolysis, has only been verified in trials with
institutions of high complexity, and intense training in the subject. Maybe
this aspect may be toned down by availability of Stents and inhibitors of
GP IIbIIIa, that improve results, and maybe make them less dependent on the
operator, but there is agreement about that by now, the procedure must be
limited to very trained staff.

Note 7: The advantage of angioplasty over thrombolysis is much smaller,
and the general opinion is that it only becomes the treatment of choice if
it can be made in less than 60 minutes. This dismisses removal of the
patient. An intermediate stance was the one from the PACT study, in which
the patient received a first bolus of thrombolytics at his home, or in the
emergency room, and later was taken to hemodynamics. This strategy did not
increase the risk of interventions, beating the prejudice that angioplasty
with thrombolysis is a bad combination based in studies with different
design in patients in whom PTCA was indicated to prevent reocclusion. On
the other hand, a group of patients did not need angioplasty since they had
permeable vessel when entering Hemodynamics.

Note 8: There is no health system, either private, public, or communal,
that has a structure installed so that all infarctions should be treated
with angioplasty. This can only be explained by the lack of confidence or
trust in the available information, or if not that, hypocrisy. See below
the topic of costs.

Note 9: Calculations of costs per life saved are disagreeable for the
physician. In a solidarity and rational system, these problems could be
argued seriously, but in the current medical anarchy it sounds unreal. Even
so, let's try it. A life saved with streptokinase in infarction in general
in Argentina costs: estimating 3 lives each 100 patients treated, 400 pesos
by ampoule, would yield a total 40,000 pesos each 100 patients, divided by
three additional lives, would yield 13,300 pesos by life saved. If we
estimate that each life saved in infarction remains alive five years on
average, the cost of life saved yearly would be 2,660 pesos annually. Let's
estimate thromboplastin. At the very best, the study GUSTO I, 0.8
additional lives each 100 patients treated. Since the value of
thromboplastin is 2000 pesos, the additional cost would be 2,000 - 400, the
value of SK, an additional 1,600 x 100 patients, that is to say 160,000
divided by 0.8, 200,000 pesos per patient saved. And this is in infarction
in general, independently from localization... The cost per year of
additional life, divided by 5 years is 40,000 per year. What happens with
angioplasty? The value in the market is 10,000 pesos, including stents,
etc. Let's subtract 400 to 10,000, the result would be 9,600, multiplied by
100 patients, 960,000 (rounding up, a million dollars each 100 patients).
If the range of benefits is one life, the cost per life saved is 200,000
per year, and it may be lowered to 100,000 if two are reduced, highly
improbable according to the results from GUSTO II. The estimation should be
corrected when avoiding 0.5 strokes per each 100 patients, etc., but the
range of yearly cost per life saved is still very high. Although these
figures may be manipulated, and though we are used to think that we
are in a bad situation but figures go well, the cost is very high for a
usual health system. When we live with an accentuated reduction of medical
incomes, and a general bankruptcy in administration of resources for
health, I believe that cardiologists must be cautious with what they
propose.

Note 10: In institutions that have assembled a structure of high complexity
apt for practicing angioplasty in acute infarction, it is logical that this
would be the only indication, since although it does not have  great
advantages over thrombolysis, it does have some small ones, and it allows
to keep a trained team for patients where the advantage is truly wider.
Whether the system is in conditions of keeping this effort or not, is a
subject for argument, and of course it is not related to each institution's
individual policy.

===========================================================================

The Deutsche Bank (http://www.deutsche-bank.de/congress) supports the
Newsletter of the
First Virtual Congress of Cardiology.

<><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><

Editor: Alfredo Piombo, M.D. (Argentina)
Chief of the Coronary Care Unit. Cosme Argerich Hospital,
Buenos Aires, Argentina
Associate Editors:
Claudio Gimpelewicz, M.D. (Argentina)
Dante Manyari, M.D. (Canada)
Carlos Basualdo, M.D. (Canada)

Edgardo Schapachnik, M.D.
Vicepresident of the FVCC Steering Committee


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Send commands to majordomo@pcvc.sminter.com.ar
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Year 2, number 18. First two weeks, March 2000.
===========================================================================

Biweekly electronic publication of the First Virtual Congress of
Cardiology, for purposes of promotion and interchange of topics of interest
in cardiac sciences and news from the Congress. It is distributed free of
charge to everyone subscribed. Those of English speaking origin may
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An Spanish version is available for those of Spanish speaking origin.
Contributions are welcomed; also responses to previously published
articles, and commentaries should be send as Letters to:

readers@pcvc.sminter.com.ar

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Previous issues at:

http://www.fac.com.ar/cvirtual/newslett/newseng.htm

or at

http://pcvc.sminter.com.ar/cvirtual/newslett/newseng.htm

===========================================================================

"Eradication of smoking is the most effective means to improve the health
in the population of both developed and developing countries."

From this column, we propose the FVCC to be free of tobacco smoke.

Colleague: if you are still a smoker, we will thank you if you abstain
from it while you participate in the activities of our Congress, and we
invite you to get in touch with us, so that your attempts tostop turn out
to be successful.

TAKE PART IN THE INTERNATIONAL PROJECT 'QUIT AND WIN', AND INVITE YOUR
PATIENTS TO DO IT, TOO.

===========================================================================

CONTENTS

Last thirty days
Editorial
By Dr. Edgardo Schapachnik

Published on FVCC
Hypertension in the elderly
Roberto M. Michelson, MD

Homocysteine. A new risk factor for coronary artery disease.
By Dr. Jamil Mattar Valente
Vicepresident of the FVCC Steering Committee

TyM 2000: Smoking in doctors

Reader´s letter: First Cardiac Symposium from the Caribbean, Central
America and Spain

News lectures

Space available for Advertisement.

===========================================================================

The Deutsche Bank  (http://www.deutsche-bank.de/congress) supports the
Newsletter of the First Virtual Congress of Cardiology.

===========================================================================

EDITORIAL
LAST THIRTY DAYS
By Dr. Edgardo Schapachnik

When this issue of the Newsletter reaches our readers’ mailboxes, the FVCC
will begin to go by its last thirty days.
Unlike other Virtual Congresses that are carried out on the Internet, the
FVCC was planned to last six months. Five months after the Congress began,
on October 1st, 1999 –a date that seems distant because it goes back to the
last century- we corroborate the initial idea of such duration.
The Internet is characterized in its essential features by a particular
dimension of time and space to which we had to be in accordance. A time
that is not the succession of concatenated events, without beginnings or
endings, because although the FVCC formally began on that distant October
1st, for the colleagues that registered a few hours or days ago, the FVCC
only began when they learnt about its existence.
And will it end on March 31st?
In a sense yes, it will be so.
But in this other temporal dimension that the Internet brought in, nothing
will prevent the colleagues from the world that have not yet registered to
the Congress because they do not even know about the FVCC, because they do
not even have access to the Internet, because maybe they do not even have a
computer yet, or maybe because to date they are only future colleagues”-
nothing will prevent them then, from accessing this great cardiac
encyclopedia that remains in the web as a testimony.
Thus, as we sighted this new time dimension that breaks up with the
calendar, we had to use the latter for a good segment, in order to allow
this uninterrupted flow that today has increased to more than 7000
registrations from 94 countries. Six months seemed to us –during the
planning period- proper for this idea.
On March 31st, 2000, the nomenclature that is used for the narrow period
of 24 hours of the Gregorian Calendar, the FVCC then- will end.
However, unlike what happens in other congresses in person, there will be
a possibility to continue having access to the contents, and there will be
continuity with what it was and still is one of the characteristic features
of this experience: the interactivity of the Thematic Forums will remain
current.
On April 1st, when the echoes of the last activities will still be fresh,
the FORUM OF CONTINUAL EDUCATION OF THE FVCC will be born.
This Forum will come to life with a great platform of contents to back it:
all the material published on the FVCC, and the intention of channeling all
the academic activity through the Thematic Forums.
The Chat sessions will be shaped in a planned way. Thus, the FCE-FVCC Chat
Fridays will be released. Biweekly, a prestigious guest of renowned
experience in an area of Cardiology, will answer questions in real time.
This birth will be accompanied by some modifications: our Thematic Forums
will cease to be bilingual. They will continue only in Spanish. This will
not be an obstacle for mutual understanding with our Portuguese-speaking
colleagues. The experience previous to the FVCC and during its course has
demonstrated that our common Latin roots makes our communication easier.
Our English-speaking colleagues will be able to continue, if they wish,
taking part in them. They will have to make the effort of obtaining
translation to English by their own means.
A special issue of the Newsletter for these colleagues will remain current:
twice a month, as it is done now, they will receive in their language some
of the Lectures from the FVCC, a modality that we began in this issue with
Dr. Michelson’s paper, an excellent updating on Hypertension in the
Elderly, that we invite you to read and study.
This periodical publication of the contents will make the issues of the
Newsletter more voluminous in size and in quality, that from April will be
the Newsletters of the FORUM OF CONTINUAL EDUCATION of the FVCC.
This issue of the Newsletter, that announces the final 30-day phase, is
completed by the announcement of three academic Chat sessions in Spanish.
One of them will be already performed when many of you read this issue. On
March 1st, Dr. Julio de la Riva, a distinguished Argentine cardiologist
from the Province of Cordoba, will answer some questions about valvular
heart disease. This session, besides the prestige of the guest, begins a
new cycle: it will be carried out in the morning, when many of us are
working in Hospitals, and it has in principle, a net connection with two
important Argentine institutions: the Hospital de Clinicas from Cordoba,
and the Hospital Argerich from Buenos Aires.
This is a true invitation and challenge to go on including institutions in
this extraordinary means of communication.
Another challenge is the call for the Chat session on Thursday, March
30th. It will be the last activity of the FVCC. Its innovation will be
given by two special guests of extended experience in Argentina:
Drs. Alfredo Piombo and Hugo Londero will express their opinions as a
clinical cardiologist and an interventional cardiologist, faced with
concrete clinical situations.
Finally, on Saturday, March 25th, we will perform a Special Session. It
will be the official closing of the Congress with the presence of the
Honorary Committee member, Dr. Carlos Bertolasi, and the President of the
Federacion Argentina de Cardiologia Argentine Federation of Cardiology,
Dr. Eduardo Escudero.
This last phase, full of activities of great importance, pre-announces
that instead of an end, we are going through the beginning of a new era in
transmission of medical knowledge. The FCE-FVCC (Forum of Continual
Education of the FVCC) is just a sketch of that.

===========================================================================

HYPERTENSION IN THE ELDERLY
(fgc4200i)

Roberto M. Michelson, MD
                   
Introduction

Patients older than 65 are arbitrarily defined as elderly. In them,
hypertension diagnosis, follow-up and therapeutic alternatives are
different from those of young adults. This concept is not always clear for
practical physicians, who tend to consider both categories as basically
similar. On the contrary, there are even evidences according to which
therapeutics must be different not only on the basis of age but also of
gender. It is our intention to lay the foundation of these affirmations,
when it is possible, both on animal and human experimentation, and on the
most recent clinical studies.

In the elderly patient, besides, there is a tendency to apply certain
concepts, long ago refuted by investigation and clinical experience, which
persist may be due to a certain inertia usually seen when new knowledge
looks for its place in everyday practice.

A good example of what we have just said is the conviction according to
which high blood pressure (HBP) is a physiologic compensation tending to
maintain an adequate blood flow to vital organs such as brain, heart or
kidneys in old age. Many believe also that high isolated systolic blood
pressure (HISBP) in the elderly is a benign condition, not related to a
significant increase of morbidity or mortality in this group.

We shall try to analyse briefly on the basis of which physiopathological
findings it is considered nowadays that these concepts are wrong.

Epidemiology

Among controllable cardiovascular risk factors, HBP is in the first place
in the list of those that can worsen the morbidity and mortality prognosis
in old age population. There is no doubt at all that its correct treatment
and control is accompanied by even better consequences among the elderly
than among young people. In a recent metanalysis of last decades studies
[Mulrow, 1995] the number of acute events suffered by hypertensive people
treated and non-treated during a period of five years was compared. The
conclusion was that, out of every eighteen patients, a cardiovascular event
can be avoided when the patients are correctly treated, what is specially
evident in the prevention of stroke. It must be recognised that, for causes
that are still discussed, prevention of coronary events is less efficient.

When studies performed on elderly patients are compared to those
accomplished on young adults, it can be concluded that, in the latter, the
number of patients treated in relation to every registered death is twice
as much as in old people.

In westernised societies the obvious tendency is towards an older
population, so that we can expect a similar augmentation in HBP prevalence.
Final numbers can be discussed, because different studies have employed
divergent criteria to define this condition, but the ratio is never lower
than 30 % and sometimes it is almost 50 % [National Center of Health
Statistics, 1977; Kannel, 1980; Emeriau, 1988; Forette, 1975]. In the study
FRICAS [1996] performed in the Argentine Republic, numbers in the control
group of 1 071 cases were as follows: between 64 and 74 years 32.1 % of men
and 40.8 % of women suffered HBP, and among those older than 75 the ratio
was 40.8 % and 40.3 % respectively for both sexes.

Generally speaking, below 40 years of age, men predominate clearly in all
cross-sectional studies. Between 40 and 50 yet, curves tend to crossover
and beyond that age female gender predominates. But longitudinal studies
have not confirmed this change. They always show masculine predominance. A
possible explanation could be that the HBP group has a greater mortality,
so that men suffering this illness are less represented among the oldest
people.

Race can eventually be a differential factor, because HBP is certainly
more prevalent among Black westernised people than among White people of
the same age and condition.

In the elderly, special forms of HBP must be considered, which do not
appear in other age groups, such as isolated or disproportionate high blood
pressure and pseudohypertension due to stiff arteries, which can be found
in almost 15 % of the population.

HBP In pre and postmenopausal women

We shall speak briefly about known differences in HBP consequences in both
sexes because, as life expectancy is longer in woman than in man, it is
clear that most old hypertensive patients will be people belonging to that
sex.

Cardiac output and arterial peripheral resistance, that is to say, what is
known as total peripheral resistance (TPR) are the two haemodynamic
determinants of BP. Any disproportionate increase of one of these factors
with relation to the other causes HBP. Characteristically, young
hypertensive patients in stage I present an increased cardiac output,
without significant alterations of TPR at rest though, during exercise,
TPR does not decrease so much as it does in normotensive people. As HBP
worsens, the typical haemodynamic alteration is the increase of TPR with
normal or even low cardiac output.

A classical study by Messerli [1987] has demonstrated yet that essential
HBP premenopausal women have a different haemodynamic pattern from that of
same age male HBP patients. It has been suggested that this would
correlate with a better prognosis and with oestrogen influence. Women have
a higher cardiac index, left ventricular ejection time and pulse pressure
than men. Heart rate is slightly faster and TPR lower at the same BP level.
Blood volume of female patients is slightly smaller than that of male
patients, as well as total blood volume and red cells mass.

Norepinephrine, epinephrine, dopamine and plasma renin activity levels at
rest are not significantly different between both sexes. Yet, pulse
pressure increase caused by isometric stress was almost 50 % higher in men
than in women.
Other haemodynamic indices response was not significantly different
between both groups.

As TPR in premenopausal woman is lower than that of the same age man, the
risk represented by hypertensive cardiovascular illness to her is also
lower. And yet, beyond the age of 45, differences between sexes, in spite
of persistence, give up being statistically significant. That is to say,
"young" haemodynamic behaviour characterising premenopausal benign HBP
woman, with a lower TPR and a higher systemic blood flow, is lost beyond
menopause.
This fact suggests that sex hormones could be the potential cause of this
different haemodynamic pattern between hypertensive pre and postmenopausal
women.

On the other hand, the most important adaptation to HBP, that is to say
left ventricular hypertrophy [LVH] is not the same in both sexes. In women,
considering echocardiographic criteria as a reference, LVH prevalence is
lower than in men, independently of BP level. Left ventricle posterior wall
is thinner, systolic and diastolic left ventricular diameters are smaller,
and so is the left ventricular mass, even if the values obtained are
indexed on the basis of body surface area.
And besides, left ventricular function indices, such as ejection fraction,
fibre circumference shortening speed and load-independent contractility
index, are greater in women than in men.

In the specific case of IHSBP, women tend to develop a concentric LVH,
without dilation, but men on the contrary, develop not only dilation but
also a greater ventricular mass without wall thickening. It is the same
case with relation to aortic estenosis.

HBP Haemodynamics in the elderly

In the elderly patient, HBP has special haemodynamic characteristics
[Messerli, 1993]. Cardiac output is low, due to a diminished stroke volume
and a relative bradycardia. Compared to that of young adults, the cardiac
output decrease can be as much as 20 to 30 % with similar BP levels and
even in the absence of congestive heart failure. Other differential
characteristics are a higher SBP and a lower DBP, with a clear increase of
TPR. Elderly normotensive people have a diminished cardiac output too, but
in a lesser degree. Age by itself is not an obstacle to cardiac output
increase, but the mechanism through which this is reached is different.
Elderly patients increase their cardiac output through the Frank-Starling
mechanism, while young adults do it through an increase in heart rate and a
decrease in the end systolic volume caused by a better contractility. The
latter is related to a better response to sympathetic stimuli. In
hypertensive elderly patients, finally, cardiac output is diminished and
TPR increased, and this makes them prone to serious consequences, such as
nephroesclerosis, brain vascular lesions and hypertensive cardiopathy.

It has been repeatedly suggested that HBP would represent an "accelerated
ageing" [Lakatta, 1987]. This opinion is based upon the similarity between
the arterial wall changes in both cases.
It must be considered that arteries are not passive conduits through which
blood passes without practical consequences, but that the different
haemodynamical factors modulate the composition and organisation of the
arterial wall through the whole life. And so, in the elderly, changes
associated to HBP in the arterial media layer are responsible for that
condition continuation long after the initial factors have disappeared. It
has been suggested that vascular stiffening augments BP, essentially the
systolic, even within those limits considered normal. This suggests a
similar physiological process between chronic HBP and what happens in
advanced age in man.

Let us briefly compare those changes caused by HBP in the arterial wall
and those caused by ageing. Chronic HBP, in animal models and in man,
presents an important increase of TPR caused by arterial wall thickening
and stiffening.
Both thickening and rigidity are caused by increases in the smooth muscle
cell mass and in the protein matrix absolute quantity. These structural
changes cause mechanical changes in the arterial wall, which decrease
compliance. The latter means the capacity to modify volume according to
pressure.

Animal investigation and experience in human beings show that,
independently of any difference in physiopathological causes, HBP
consequences on the arterial structure and function remain the same. HBP
causes an augmentation in mechanical forces acting on large and mid-sized
arteries' walls. According to Laplace's law, the increase in parietal
tension is inversely proportional to wall thickness, and that is the reason
why thickening is considered an adaptive response which tries to maintain
normal tensions in the medial muscle elastic unit.

Both endothelial cells replication and morphology are modified as a
consequence of increase in pressures. Replication rate increases, and
morphology goes through structural deformations that cause an increase in
permeability caused by discontinuity and disorganisation of tight cell
unions.

The media, as it has already been mentioned, becomes thicker as a
consequence of an increase in smooth muscle cell mass and the extracelular
matrix absolute quantity, essentially caused by cell hypertrophy, with
increases of protein synthesis and genome mass, and also of fractions of
collagen, elastin or both. According to findings from different
experimental models, the mentioned thickening depends basically on cell
hypertrophy caused by an increase in its metabolic activity. On the other
hand, the protein matrix increase is caused by collagen, in such a way that
the ratio between the latter and elastin tends to augment. The haemodynamic
consequence of these changes is an important decrease in compliance with
similar BP levels. Hypertrophy is also associated to a complicated
remodelling of intercellular junctions responsible of linkage and cohesion
among muscle cells, as a consequence of which they become wider and
disorganised. Some people consider that this is a factor favouring arterial
aneurysms.

In those arteries which are less than one millimetre wide, smooth muscle
cell contraction causes an increase of BP as a consequence of a higher TPR
at a constant flow rate. Cells contraction is due to vasopressor agents or
an increased presence of vasoconstrictor substances such as endothelin,
which increase free intracellular calcium and trigger the contraction
mechanism through associated proteins such as calmodulin. All these
substances can also enhance smooth muscle cell growth. Structural lesions
in the arterial wall in these cases can be differentiated as
hypertrophy-hyperplasia and fibrinoid necrosis.

The information we have just mentioned comes from animal experimentation.
The situation is more difficult in the case of man, as even the data from
autopsies are not worthy of confidence.
Nowadays we can fortunately study patients with ultrasound. In hypertensive
people, the great arteries diameter remains the same or increases, but
compliance is always impaired. This happens because thickening is the only
mechanism that can sustain wall tension, and this can be clearly seen in
experimental models. In the human being, yet, the presence of arterial wall
hypertrophy is controversial, though we have a lot of indirect evidence.
Folkow [1973] has demonstrated that 5 % changes in the internal diameter of
resistance vessels can cause 25 % increases in TPR.

The arterial wall thickening, then, is the chronic HBP final common result
both in experimental animals and in man and this is a  structural
contribution to an increase in TPR and a decrease in compliance.

When the intention is to study those structural changes caused only by
ageing, the methodological problem is far more important. It can always be
discussed whether findings are caused by ageing or by pathologies that were
not identified. This has been widely discussed in specialised literature.
And yet, the study of pressure and flow curves can give reliable
information. The rate between BP and mean flow allows us to
estimate the resistance vessels size, and compliance can be used to have an
estimation of the system elasticity. It is well known that, in the elderly,
pressure/volume curve shifts to the right, and its slope, which represents
compliance, decreases.

At all levels of the arterial system the intima, the media and the
adventitia are affected. As man becomes older, four lesion patterns have
been described in the large arteries, which can be always more often found:
cystic medial necrosis, elastin fragmentation, medial fibrosis and areas of
medionecrosis. The changes found are not regularly distributed but some
sectors are more affected than others. Mid-sized arteries are the most
important place of age-related changes, among which the principal is the
calcinosis of the media. Tibial and coronary arteries are most affected by
the changes we are talking about. In the latter, it seems important that
the arterial wall is subject to pulsatile flow during cardiac cycle, both
in ageing and in atherosclerosis. The changes found in arterioles are
caused by hyalinosis, a plasma process that impairs in different degrees
local blood flow. All these age-related changes have a differential
chronology, since they appear first in the greater vessels proximal area,
and only afterwards in the smallest distal one. This could be related to
pulsatile flow, which only reaches the most distant sectors when the
increase in rigidity in the proximal areas allows it.

It must be considered that HBP accelerates the above-mentioned process.
The normal ageing of the cardiovascular system is more important in the
hypertensive than in the normotensive patients, and this causes a greater
decrease in vascular and cardiac compliance, in muscular strength, in
contraction speed and renal functional capacity. This is the main reason of
our first affirmations: it is more difficult to treat elderly hypertensive
patients because they have suffered an upwards structural resetting with
higher pressure values, with cardiac, renal and blood flow decreased
reserves. The latter especially in the coronary, brain and kidney
circuits. The decrease of the blood flow depends on an increased TPR, and
this worsens when atherosclerosis is present.

Another interesting study alternative, which is an objective guaranty when
we consider certain changes as age-related and not caused by cardiovascular
pathologies, essentially HBP, is what can be done with experimental
laboratory animals not affected by that illness.

The most important finding in a study that employed male rats was an
age-related increase in large arteries size [Michel, 1994]. This structural
phenomenon was associated to an age-dependent increase in functional artery
rigidity and with increases in the media and intima thickness. The
age-dependent changes observed in the arterial wall were associated with a
significant cardiac hypertrophy, with an increased auricular natriuretic
factor and with a decreased plasma renin activity. Many of these phenomena
are strictly age-dependent, and independent of HBP since they were observed
in rats whose blood pressures did not change with age. Moreover, the ACEI,
which decrease blood pressure throughout these rats' lives, could diminish
certain converting enzyme-dependent or stress-dependent parameters, such as
medial or intimal thickening or cardiac hypertrophy, without avoiding their
age-dependent increase and without any change in the augmentation of
artery size or matrix-dependent artery wall rigidity observed with age. In
this study, aortic and carotid circumferences increased progressively and
regularly with age and were not modified by hypotensive treatment. These
findings confirm previous ones, both in rats and in man, according to
which, by postmortem ex situ analysis or by in vivo echographic methods a
similar and pressure-independent increase in the artery width with age.
Elastic arteries enlargement is associated with a wall rigidity increase,
and the age-related increase in aortic impedance and the decreases in
global systemic and in situ carotid compliance demonstrate this.
Enlargement and rigidity of large arteries can increase cardiac afterload
by augmenting the residual blood volume present in large arteries at the
end of diastole, which is mobilised during systole, and also characteristic
impedance, what can explain partially the increase in age-related cardiac
hypertrophy and also that of the age-related plasma auricular natriuretic
factor. Smooth muscle cell hypertrophy seems to be influenced independently
of age or ACEI. Finally, artery enlargement can also influence endothelial
function. Endothelial nitric oxide production depends essentially on its
activation by shear stress. Shear stress depends positively on blood speed
and viscosity, and is inversely dependent on arterial size. The latter
increases with age, so that this probably causes a shear stress chronic
decrease.

Treatment advantages of systodiastolic or isolated systolic HBP in the
elderly

The most recent trials show clearly that an appropriate treatment of HBP
in the elderly is particularly favourable in relation to the pathological
consequences decrease of this illness. We shall briefly mention some of the
most important ones.

SHEP trial (Systolic Hypertension in the Elderly Program) [SHEP Cooperative
Research Group, 1991] included 4736 patients, mean age 72 years at the
study beginning, with a 177/70 mmHg mean blood pressure. The most important
findings, after a mean follow-up of a little more than four years, was a
37 % reduction in fatal and non fatal strokes after active treatment, 27 %
in fatal and non fatal AMI, 25 % in coronary artery disease, and 32 % in
all-cause cardiovascular events. Total mortality decreased 13 % but that
was not considered significant.

STOP-Hypertension trial (Swedish Trial in Old Patients with Hypertension)
[Dahlöf, 1991] included even older patients, since mean age at the
beginning was 76 years. 1627 both sexes patients were included. The Safety
Committee prematurely interrupted the trial, but patients were treated
during a 2.1 years mean follow-up. No patient was lost. Morbidity and
mortality secondary to stroke diminished 47 %, while all-cause
cardiovascular events and total mortality decreased respectively in a 40
and a 43 %. All these results were highly significant in relation to those
of the placebo group.

MRC trial (Medical Research Council) [MRC Working Party, 1992] was
performed in the United Kingdom and included 4400 men and women between 65
and 74 years of age. The most important findings were a 25 % and a 17 %
reduction in stroke and all-cause cardiovascular events, respectively.

With this information there can be no more doubts about the convenience of
lowering HBP in the elderly, including HISBP.

Main secondary HBP causes in the elderly

Secondary HBP prevalence varies from 2 to 20 % according to the sort of
statistics considered, be them from general or specialised centres. Such a
difference suggests that, in the first, an important number of secondary
cases are undetected and treated similarly to essential HBP, what would
cause a great number of useless long pharmacological treatments and even
avoid cure in a certain sort of patients.

1. Renal HBP

HBP can be caused by renal illness or can, on the contrary, cause it. HBP
can impair renal function through glomerular hypertension, which causes
glomerular sclerosis. On the other hand, an impaired kidney can cause HBP
in different ways: it can cause an increase of blood volume, alter Na+
excretion, increase vasopressor substances production or decrease that of
those which are vasodilators, and this can happen in an isolated or
combined way.

Kidney weight decreases with age, and the cortical layer becomes thinner,
reducing thereby the number of functional glomeruli. The senile kidney
vessels suffer atherosclerotic changes and the organ's capacity to maintain
homeostasis also decreases. This is caused partially by an important
decrease in renal plasmatic flow, which practically diminishes 50 %,
causing a great decrease of the glomerular filtration rate and the
creatinine clearance. Plasma creatinine, in spite of what we have said,
does not increase, because old people's muscular mass is smaller than that
of young adults. The angiotensin-renin system activity also decreases
markedly.

In the elderly, the most usual illnesses which can be accompanied by HBP
are primary and secondary glomerulopathies, especially that of diabetes
mellitus, pyelonephritis, obstructive uropathies and tubular-interstitial
sickness.

The remaining kidney function tends to be protected with pharmacological
control of HBP, especially when ting enzyme inhibitors (ACEI) are used,
through a decrease of glomerular hypertension, what is extremely evident in
diabetic patients. Loop diuretics and calcium blockers can be used too but,
in general, beta-blockers are not so useful, may be because the elderly
have less beta-receptors.

2. Renovascular HBP

The most usual ethiology in the elderly is atherosclerotic renal artery
obstruction. Lesions tend to be found in the aorta, causing an occlusion of
the renal artery ostium or its proximal portion, and are progressive. Renal
artery obstruction causes a downfall in the kidney perfusion, and the
latter begins to release more renin in the venous blood.
This causes an increase in angiotensin I and II plasma levels. This
mechanism produces an increase in TPR and systemic BP in order to improve
the kidney perfusion beyond the obstruction. If perfusion keeps low, yet,
angiotensin II plasma levels decrease, even if there is still HBP.

Early diagnosis is more essential than ever, because after a certain time
vascular and glomerular lesions caused by the obstruction do not allow HBP
disappearance once the latter is surgically corrected. In the following
picture, we can see those circumstances that can create the suspicion of
secondary renovascular HBP in the elderly patient.

           ABDOMINAL OR FLANK MURMUR AUSCULTATION.
           BEGINNIG AFTER 60 YEARS OF AGE.
           LACK OF ANSWER TO TREATMENT WITH AT LEAST
           THREE DRUGS.
           ACCELERATED SEVERE OR MALIGNANT HBP.
           SMALLER KIDNEY SIZE.
           SUDDEN HBP WORSENING.
           RENAL FUNCTIONAL IMPAIRMENT WITH THE ACEI.

Renovascular HBP can only be cured through surgery or angioplasty.
Pharmacological treatment can only be used while surgery is awaited.
Diagnosis confirmation is done nowadays preferentially through renography
with captopril challenge test, but renal arteriography is the only precise
way to detect and find obstructions in renal artery.

3. Suprarrenal HBP

The incidence of this ethiology in hypertensive elderly people is extremely
low. We shall mention briefly primary aldosteronism and pheochromocytoma.

3.1.  Primary aldosteronism:

It is caused by an increase in aldosterone production independent of
renin-angiotensin system. Diagnosis of this ethiology is based on the
laboratory, because clinical manifestations are secondary to hypokalemia,
and thereby inespecifical. It can be suspected when plasma potassium is
lower than 3.5 mEq/Lt. It can be confirmed measuring plasma renin activity
at rest and after walking, plasma aldosterone under both circumstances too,
and 24 hours urinary aldosterone. The aldosterone-producing adenoma must be
differentiated from idiopathic hyperaldosteronism caused by bilateral
hyperplasia. In the first case treatment is surgical, in the second is
medical.

3.2. Pheochromocytoma:

It is a chromaffin cell tumour, which can appear in the adrenal medulla
and less frequently in the extrarrenal chromaffin tissue. It can be
diagnosed through the biochemical measurement of urinary catecholamines and
vanillylmandelic acid in 24 hours urine. It can be found through abdominal
CT, MRI or scintillation camera. Naturally, treatment is surgical, once BP
has been controlled with drugs.

HBP and diabetes mellitus

Compared to non-diabetic people, hypertensive patients are twice as much
among diabetics. HBP in diabetics without nephropathy is more frequent in
patients older than 65 years. HBP is higher as the evolution time of
diabetes is longer.

Reaven [1988] used the expression "metabolic X syndrome" to distinguish a
situation in which insulin resistance is characterised by a high prevalence
of NIDDM, HBP, obesity, dislipemia and cardiovascular illness. Nowadays,
the name "insulin resistance syndrome" is preferred. Afterwards the very
Reaven concluded that insulin resistance could be a primary defect in
hypertensive patients, were they diabetic or not.
Insulin resistance and hyperinsulinism can be responsible for HBP
pathogenesis and this could be genetically determined.

Insulin resistance and hyperinsulinism are cardiovascular risk factors
independently of HBP. Neither every patient with hyperinsulinism is
hypertensive, nor every hypertensive patient is hyperinsulinemic, so that
his or her participation in the appearance of HBP cannot be generalised.

We can say that in the first stage of diabetes there is a blood volume
expansion, which can cause an increase in cardiac output. Afterwards, in
the chronic stage, impairment in TPR regulation predominates. Corporal
sodium is augmented both in hypertensive and diabetic patients, with a
significant alteration of the internal medium. It is unknown why this is
not accompanied by an increase in plasma volume, something that normally
happens in non-diabetic patients. Diabetics have an exaggerated
cardiovascular reactivity to angiotensin II. Insulin capacity to cause HBP
even with normal glycemia values has been related to its capacity to
increase renal sodium retention, stimulate the release of catecholamines
and cause smooth muscle hypertrophy.

Brain selfregulation

In the untreated hypertensive elderly patient there is a decrease in brain
blood flow that is considered a risk factor in relation to stroke and
dementia. Selfregulation is a characteristic that brain has in order to
adapt its blood requirements through the active modification of the brain
vessels as a response to variations in perfusion pressure in order to
maintain a constant brain blood flow. When the limits of selfregulation are
overpassed a forced vasodilatation in brain arteries happens, brain blood
flow increases and as a result brain hyperaemia, tisular oedema and may be
brain haemorrhages can be caused. All this is called hypertensive
encephalopathy.

The critical point after which these limits are surpassed, about 180 mmHg
of mean arterial pressure, lies around 150 mmHg in previously normotensive
patients. On the contrary, when blood flow is insufficient to maintain
perfusion, that is to say when mean arterial pressure is under 60 mmHg,
there are hypoperfusion and ischemia.

It must be seriously considered that, in chronic hypertensive elderly
patients the selfregulation curve shifts to the right, and therefore the
above mentioned limits are higher than those of normotensive people. An
aggressive hypotensive treatment with the goal of reaching those BP values
considered normal in young adults can be severely iatrogenic if this
circumstance is ignored.

Sleep apnea

It has been established that old patients with this syndrome can present
hypoxia, episodes of awakening and increases in BP in pulmonary and aortic
arteries. And yet, there is not in them a coincidence between this syndrome
and HBP, unlike what happens in young adults [McGinty, 1982].

The obstructive sleep apnoea syndrome is related to a higher prevalence of
HBP, higher risk of coronary artery disease and stroke, and also to a
greater ventricular hypertrophy and a decreased response to
antihypertensive treatment. Some of these findings can be related to
obesity. In fact, HBP appearance in those who suffer sleep apnoea is being
discussed, but haemodynamical changes, sympathetic nervous activity and
neuroendocrine dysfunction have been found, and tend to disappear when the
syndrome is controlled.

References

BARGER AC: THE GOLDBLAT MEMORIAL LECTURE. PART I: EXPERIMENTAL RENOVASCULAR
HYPERTENSION. JAMA. 1972, 220: 1209.
BRAVO EL: THE CHANGING CLINICAL SPECTRUM OF PRIMARY ALDOSTERONISM. AM J
MED. 1983; 74: 641.
CAMILLERI JP: HYPERTENSION AND ARTERIAL AGING. IV-ARTERIAL WALL AND
AGING-LL SERVIER-1993; pp.49-56.
DAHLÖF B: MORBIDITY AND MORTALITY IN THE SWEDISH TRIAL ON OLD PATIENTS
WITH HYPERTENSION (STOP-HYPERTENSION). LANCET. 1991; 338: 1281.
EMERIAU JP: HYPERTENSION IN THE ELDERLY. J MED.1988; 84 (SUPPL IB): 92.
ESTUDIO FRICAS: FACTORES DE RIESGO PARA INFARTO AGUDO DE MIOCARDIO EN LA
ARGENTINA. REV. ARG. DE CARDIOLOGIA. VOL. 64 SUPL II. 1996.
FOLKOW B: IMPORTANCE OF ADAPTIVE CHANGES IN VASCULAR DESIGN OF
ESTABLISHMENT OF PRIMARY HYPERTENSION STUDIED IN MAN AND IN SPONTANEOUSLY
HYPERTENSIVE RATS.CIRC.RES. 1973; 32 (SUPPL.): 2.
FORETTE F: HYPERTENSION ARTERIELLE DU SUJET ÂGE. NOUV. PRESS. MED. 1975;
4: 2997.
KANNEL WB: PERSPECTIVES ON SYSTOLIC HYPERTENSION. THE FRAMINGHAM STUDY.
CIRCULATION. 1980; 61: 1179.
LAKATTA EG: DO HYPERTENSION AND AGING HAVE A SIMILAR EFFECT ON THE
MYOCARDIUM? CIRCULATION. 1987; 75 (SUPPL I), I-69.LEENEN FHH: RENAL VENOUS
AND PERIPHERAL PLASMA RENIN ACTIVITY IN RENAL HYPERTENSION IN THE RAT. AM J
PHYSIOL. 1973; 225: F1513.
MC LACHLAN MF: THE AGING KIDNEY. LANCET. 1978; 2:143.
MCGINTY D: SLEEP RELATED BREATHING DISORDERS IN OLDER MEN: A SEARCH FOR
UNDERLYING MECHANISMS. NEUROBIOL AGING. 1982; 3: 899.
MESSERLI FH: ESSENTIAL HYPERTENSION IN THE ELDERLY. LANCET. 1993; 29F33.
MESSERLI FH: DISPARATE CARDIOVASCULAR FINDINGS IN MEN AND WOMEN WITH
ESSENTIAL HYPERTENSION. ANN INTERN MED. 1987, 107: 158.
MEYER JS: PROGRESSIVE CEREBRAL ISCHEMIA ANTEDATES CEREBROVASCULAR SYMPTOMS
BY TWO YEARS. AN N NEUROL. 1984; 16: 314.
MEYER JS: PROSPECTIVE ANALYSIS OF LONG TERM CONTROL OF MILD HYPERTENSION
ON CEREBRAL BLOOD FLOW. STROKE. 1985. 16: 985.
MICHEL JB: EFFECT OF CHRONIC ANG I-CONVERTING ENZYME INHIBITION ON AGING
PROCESSES. II. LARGE ARTERIES. AM J PHYSIOL. 1994, 267: R124-R135.
MRC WORKING PARTY: MEDICAL RESEARCH COUNCIL TRIAL OF TREATMENT OF
HYPERTENSION IN OLDER ADULTS: PRINCIPAL RESULTS. BRIT MED J. 1992; 304:
405.
MULROW C: HIPERTENSION EN EL ANCIANO, IMPLICACIONES Y APLICABILIDAD
GENERAL DE LOS ENSAYOS ALEATORIZADOS. JAMA. 1995; 4: 280.
NATIONAL CENTER OF HEALTH STATISTICS: BLOOD PRESSURE LEVELS OF PERSONS
6-74 YEARS OF AGE IN THE US, 1971-1974. VITAL AND HEALTH STATISTICS. SERIE
11, N 203, MARYLAND, 1977.
REAVEN GM: ROLE OF INSULIN RESISTANCE IN HUMAN DISEASE. DIABETES. 1983,
37: 1595.
SHAPIRO C: MANAGEMENT OF PHEOCROMOCYTOMA. ENDOCRINOL METAB CLIN NORTH
AM.1989; 18: 443.
SHEP COOPERATIVE RESEARCH GROUP. PREVENTION OF STROKE BY ANTIHYPERTENSIVE
DRUG TREATMENT IN OLDER PATIENTS WITH ISOLATED SYSTOLIC HYPERTENSION. JAMA.
1991; 265: 3255.
SIMON N: CLINICAL CHARACTERISTICS OF RENOVASCULAR HYPERTENSION. JAMA.
1972; 230: 1209.

===========================================================================

HOMOCYSTEINE. ANEW RISK FACTOR FOR CORONARY ARTERY DISEASE

Cross-section and prospective studies have related increased levels of
homocysteine to a greater risk of coronary artery disease, and these
results are consistent in a variety of population groups [1].
Increased levels of homocysteine may be accompanied by ingest or decreased
blood levels of folate, B6 vitamin, or B12 vitamin [2]. These vitamins are
important co-factors on the metabolism of homocysteine, and boundary
deficiencies are relatively common, affecting approximately a 30% of the
population of elderly people in the Framingham Heart Study. An increased
consumption of these vitamins with supplements in the form of multivitamin
compounds, or through fortification of food, may lead to less deficiency of
vitamins and decrease on prevalence of hyperhomocysteinemia. In 1998, in
USA, fortification of folate on food was approved, and it is estimated that
this intervention on large scale on the population, will reduce prevalence
of deficiency of folate, and will diminish the frequency of raised levels
of homocysteine. In the table below, we wrote some suggestions of foods
rich in folic acid, with which the basic requirement of daily 400
micrograms is easily met:

Folic acid - Advised amount for daily ingestion = 400mcg.
Contents of folic acid in selected foods:
Brewer's yeast  1 tablespoon (15ml) 313mcg
Boiled spinach 1/2 cup (120ml) 131mcg
White beans  1/2 cup (120ml) 122mcg
Orange juice  1 cup (240ml)  110mcg
Boiled broccoli  1 cup (240ml)  78mcg
Nestle Fiber-1  1 portion (30g) 60mcg

The incidence of raised levels of homocysteine on the general population
is high. Either this increase may be caused by a deficiency or failure of
an enzyme, or by a deficiency or failure in a co-factor of enzyme
(vitamin). Deficiencies of B12 vitamin and folate are correlated to
increased levels of homocysteine. Deficiency of B12 vitamin and folate is
observed more frequently in elder people [2]. Thus, it is more frequent to
observe high levels of homocysteine in elder people than in young people.
Not all prospective studies suggest that a total homocysteine would be a
risk factor for coronary artery disease [3], however the greatest
prospective studies confirm total homocysteine as a risk factor that can be
treated [4,5,6,7]. The role of total homocysteine as risk factor is also
supported by the studies with administration of supplementary vitamin, that
clearly show decrease on levels of total homocysteine [8,9,10,11,12,13].
Some critics argue that the only way to identify all patients with
hyperhomocysteinemia is the analysis with methionine load [14], that is
more expensive and more time-consuming than total homocysteine dosage on an
empty stomach.
They also argue that there are not enough studies that prove a global
reduction of coronary artery disease on individuals that receive treatment
of reduction of plasma homocysteine. And besides, a prospective study would
be necessary to assess the reduction of coronary artery disease through
treatment of hyperhomocysteinemia [3,4,5,6,7]. Such a study not only
requires a great number of individuals, but the analysis of costs suggests
that a trial in this scale may produce a great social benefit [13].
Population in risk of hyperhomocysteinemia includes patients with diabetes
mellitus type II [11], particularly those with diabetic nephropathy, and
more severely in patients with renal insufficiency due to trans-sulfuration
and the fact that other homocysteine-metabolizing enzymes would be located
in the kidneys. Bostom et al. [15] measured several risk factors for
coronary artery disease in a group of patients who are receiving dialysis
for maintenance, and concluded that hyperhomocysteinemia in this
population, very probably contribute to increase the risk of coronary
artery disease. Boushey et al. [1] made a meta-analysis with 27 studies
relating total homocysteine with arteriosclerotic disease, and concluded
that an increase of 5umol/L in total homocysteine increases the risk of
coronary artery disease, besides an increase of 0.5mmol by liter (20mg by
dL) of total cholesterol (odds ratio, 1.6). In the same study, a
meta-analysis with 11 studies about the effects of folic acid on the levels
of total plasma homocysteine, strengthened the evidence that the increase
in ingestion of folic acid helps to prevent some cases of coronary artery
disease. The authors conclude that there is enough evidence to advise an
increase on consumption of folic acid in all patients with a significant
risk of coronary artery disease, in spite of the small risk of masking a
pernicious anemia, or the possibility of causing neuropathies. A dietary
supplement or with B vitamin pills, are the preferred treatments for
hyperhomocysteinemia [5,6,8,9,10]. Most experts agree that an addition of
400 micrograms of folate per day, is a safe and truly effective therapy for
prevention of coronary artery disease; besides supplements of pyridoxine
and cobalamin may also be used [10].
Hyperhomocysteinemia has been currently reckoned as a new risk factor for
coronary artery disease. A level of total homocysteine of more than 14umol
must be treated as 400 micrograms to 1mg per day of folate, with or without
B vitamin complement. The serum level of B12 vitamin must be checked
routinely to verify the possibility of subjacent pernicious anemia. Until
the role of this therapy is more clearly defined by prospective studies of
intervention on coronary artery disease, these are safe treatments that can
reduce this new risk factor up to less significant levels.

Bibliography:

1 - Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative
assessment of plasma homocysteine as a risk factor for vascular disease.
Probable benefits of increasing folic acid intakes. JAMA. 1995 Oct
4;274(13):1049-57.

2 - Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH: Vitamin status
and intake as primary determinants of homocysteinemia in an elderly
population. JAMA. 1993 Dec 8;270(22):2693-8.

3 - Folsom AR, Nieto FJ, McGovern PG, Tsai MY, Malinow MR, Eckfeldt JH,
Hess DL, Davis CE: Prospective study of coronary heart disease incidence in
relation to fasting total homocysteine, related genetic polymorphisms, and
B vitamins: the Atherosclerosis Risk in Communities (ARIC) study.
Circulation. 1998 Jul 21;98(3):204-10.

4 - Wald NJ, Watt HC, Law MR, Weir DG, McPartin J, Scott JM: Homocysteine
and ischemic heart disease: results of a prospective study with
implications regarding prevention. Arch Intern Med. 1998 Apr
27;158(8):862-7.

5 - Townend J, O'Sullivan J, Wilde JT: Hyperhomocysteinaemia and vascular
disease. Blood Rev. 1998 Mar;12(1):23-34. Review.

6 - Stein JH, McBride PE: Hyperhomocysteinemia and atherosclerotic vascular
disease: pathophysiology, screening, and treatment. off.
Arch Intern Med. 1998 Jun 22;158(12):1301-6. Review.

7 - Dierkes J, Bisse E, Nauck M, Orth M, Mayer H, Luley C, Wieland H: The
diagnostic value of serum homocysteine concentration as a risk factor for
coronary artery disease. Clin Chem Lab Med. 1998
Jun;36(7):453-7.

8 - McCarron DA, Oparil S, Resnick LM, Chait A, Haynes RB, Kris-Etherton
P, Pi-Sunyer FX, Stern JS, Morris CD, Clark S, Hatton DC, Metz JA, McMahon
M, Holcomb S, Snyder GW: Comprehensive nutrition plan improves
cardiovascular risk factors in essential hypertension. Am J Hypertens. 1998
Jan;11(1 Pt 1):31-40.

9 - Malinow MR, Duell PB, Hess DL, Anderson PH, Kruger WD, Phillipson BE,
Gluckman RA, Block PC, Upson BM: Reduction of plasma homocyst(e)ine levels
by breakfast cereal fortified with folic acid in patients with coronary
heart disease. N Engl J Med. 1998 Apr 9;338(15):1009-15.

10 - Woodside JV, Yarnell JW, McMaster D, Young IS, Harmon DL, McCrum EE,
Patterson CC, Gey KF, Whitehead AS, Evans A: Effect of B-group vitamins and
antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized,
factorial-design, controlled trial.
Am J Clin Nutr. 1998 May;67(5):858-66.

11 - Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJ, Jakobs C, Bouter LM,
Heine RJ, Stehouwer CD: Hyperhomocysteinemia is associated with an
increased risk of cardiovascular disease, especially in
non-insulin-dependent diabetes mellitus: a population-based study.
Arterioscler Thromb Vasc Biol. 1998 Jan;18(1):133-8.

12 - Chico A, Perez A, Cordoba A, Arcelus R, Carreras G, de Leiva A,
Gonzalez-Sastre F, Blanco-Vaca F: Plasma homocysteine is related to albumin
excretion rate in patients with diabetes mellitus: a new link between
diabetic nephropathy and cardiovascular disease? Diabetologia. 1998
Jun;41(6):684-93.

13 - Hornberger J.: A cost-benefit analysis of a cardiovascular disease
prevention trial, using folate supplementation as an example. Am J Public
Health. 1998 Jan;88(1):61-7.

14 - van der Griend R, Haas FJ, Duran M, Biesma DH, Meuwissen OJ, Banga
JD.: Methionine loading test is necessary for detection of
hyperhomocysteinemia. J Lab Clin Med. 1998 Jul;132(1):67-72.

15 - Bostom AG, Shemin D, Lapane KL, Nadeau MR, Sutherland P, Chan J,
Rozen R, Yoburn D, Jacques PF, Selhub J, Rosenberg IH. Folate status is the
major determinant of fasting total plasma homocysteine levels in
maintenance dialysis patients. Atherosclerosis. 1996 Jun;123(1-2):193-202.

===========================================================================

TYM 2000

We are organizing the TyM 2000 for this year: this is a survey about
smoking in doctors.
The previous ones were TyM 96, which was presented as brief communication
in the congress of the Federacion Argentina de Cardiologia - Argentine
Federation of Cardiology (FAC); and TyM 98, which was presented as brief
communication in the congresses of the Sociedad Argentina de Cardiologia -
Argentine Society of Cardiology (SAC) and of the FAC, and will be
published, complete, in the Journal of the Argentine Federation of
Cardiology, in this month's issue, March 2000.
The colleagues who wish to participate as researchers (survey takers of
colleagues), please communicate your wish to do so by sending your data
(with complete address) to:

carloscuneo@arnet.com.ar

or to:

Dr Carlos Cuneo
Servicio de Prevencion Cardiovascular
Hospital San Bernardo
Tobias 69
4400 Salta - Argentina

===========================================================================

Dr. Dario Veras Sanchez, a colleague from Dominican Republic, sends us the
following information.

FIRST CARDIAC SYMPOSIUM FROM THE CARIBBEAN, CENTRAL AMERICA, AND SPAIN

TOPICS:

- Cardiovascular Risk Factors
- Hypertension
- Vascular Endothelium
- Congestive Heart Failure
- Coronary Artery Disease
- Valvular Disease
- Echocardiography
- Cardiovascular Interventional Therapy
- Round Tables
- Symposia
- Master Lectures
- Course on Cardiology for General Practitioners

COUNTRIES THAT PARTICIPATE

- Costa Rica
- Cuba
- El Salvador
- Spain
- Guatemala
- Honduras
- Nicaragua
- Panama
- Puerto Rico
- Dominican Republic

DATE:

April 11th to 15th, 2000

VENUE:

Hotel Meliá ( PUNTA CANA )
Dominican Republic

REGISTRATIONS:

Sociedad Dominicana De Cardiología
Tel: ( 809) 685-0331
Fax: (809) 687-6912 y 565-1170

TOUR OPERATOR:

Turienlaces del Caribe
Tel 565- 3500
Fax: 565-1221
turienlacesdelcaribe@codetel.net.do

Dr. Darío Veras Sánchez
dveras@codetel.net.do

===========================================================================

The Deutsche Bank (http://www.deutsche-bank.de/congress) supports the
Newsletter of the
First Virtual Congress of Cardiology.

<><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><

Editor: Alfredo Piombo, M.D. (Argentina)
Chief of the Coronary Care Unit. Cosme Argerich Hospital,
Buenos Aires, Argentina
Associate Editors:
Claudio Gimpelewicz, M.D. (Argentina)
Dante Manyari, M.D. (Canada)
Carlos Basualdo, M.D. (Canada)

Edgardo Schapachnik, M.D.
Vicepresident of the FVCC Steering Committee

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