interview with Dr. John Laragh by Paul J. Rosch, M.D.
Despite over 100 antihypertensive drugs that have been approved
as being safe and effective, the sad fact is that we have
not been very successful in controlling hypertension. A survey
reported in the July 9 issue of The Journal of the American
Medical Association found that nearly one in three U.S. adults
have hypertension. Of the estimated 58 million affected, "Almost
30 percent were unaware of their illness, 42 percent were
not being treated, and at the time that their BP was measured,
69 percent did not have their hypertension controlled!"
Another survey published in the British Medical Journal in
June found that 97 percent of patients taking antihypertensive
medications had suffered from significant side effects at
some time and 17 percent continued to do so! Four out of five
patients had serious concerns about side effects they had
not been informed of, possible long-term dangers, and wondered
if they still needed drugs or could use other approaches.
An article in the February issue of the Journal of Human
Hypertension was titled "Cost of poor blood pressure
control in the UK: 62,000 unnecessary deaths per year."
According to a September Reuters report, "Half of the
people with high blood pressure who are at risk of a stroke
are not identified, half who are identified are not treated,
and half who are treated aren't treated properly." Yet,
all we keep hearing from the media and the government is about
how much progress is being made with new and allegedly "breakthrough
advances" that imply the war on hypertension has been
won. The somber reality is that things have been getting progressively
worse rather than better and that the incidence of hypertension
and stroke will probably rise even more as the obesity epidemic
and the over 80 population continue to escalate.
I believe that the main reason for this misinformation is
the government guidelines for the treatment of high blood
pressure disseminated by NHLBI (National Heart, Blood, and
Lung Institute) in their recent ALLHAT and JNC-VII reports
are dictated more by politics rather than science. This is
vividly illustrated by their contention that all Americans
should drastically reduce their dietary sodium intake, that
most people over the age of 55 and all diabetics should be
taking statin drugs regardless
of their cholesterol or LDL levels and especially following
the latest hypertension treatment advice. All of these could
likely be prescriptions for disaster, particularly because
alternatives proven to be safer and more effective have been
In my opinion, the most likely person to have a solution
to this dismal state of affairs is John Laragh. His credentials
are impeccable. After graduating from Cornell Medical College
in 1948 he took his residency training in medicine and cardiology
at Columbia University College of Physicians and Surgeons
and Presbyterian Hospital, where he later founded the first
Hypertension Center and became Chief of Nephrology and vice
chairman of the Board of Trustees. He returned to New York
Hospital-Cornell Medical Center in 1975 where he developed
a cardiovascular research program supported by NIH for a quarter
of a century.
Over 25 researchers he trained now head their own academic
units at prestigious medical facilities here and abroad. He
is currently director of the Cardiovascular Center at the
New York Presbyterian Hospital-Cornell Medical Center and
Weill Medical College. He founded the American Society of
Hypertension in 1986, became its first president, established
the American Journal of Hypertension, and still serves as
editor-in-chief. He is a past president of the International
Society of Hypertension and the author of over 900 articles
and several texts dealing with hypertension.
Dr. Laragh has been the recipient of numerous awards and
was featured on Time magazine's cover in 1975 for discovering
the role of the renin-angiotensin-aldosterone system in regulating
normal blood pressure and causing fatal malignant hypertension.
I have known John for over 65 years; we both grew up in the
same area of Northwest Yonkers and he has been a member of
the Board of Trustees of The American Institute of Stress
since its founding in 1978. I have referred many patients
to him and have always found him to be a very caring as well
as skilled clinician.
He has long maintained that essential hypertension in most
patients is caused by excess renin and can be permanently
controlled and useful life extended with one drug by determining
whether the problem is primarily sodium (volume) related or
due to increased renin actions. The key to this is being able
to accurately measure renin activity, a procedure that he
pioneered and perfected over the past three decades. Many
authorities share my belief that implementation of his approach
could markedly reduce the prevalence of poorly controlled
hypertension as well as its complications and costs.
What is difficult to understand is why this has been inadvertently
overlooked (if not deliberately omitted) in official recommendations
for the treatment of hypertension, such as the recent report
of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure (JNC-VII).
While familiar with how John's treatment program evolved,
I decided to fill in a few blanks and also obtain his opinion
about these latest official recommendations in a recent interview.
Because of space constraints I have condensed and paraphrased
some of his responses as well as my questions, but the entire
interview is available at www.stress.org
How the Renin Story Began and Evolved
How did you become interested in renin?
JHL: What first led to my interest
in renin was a patient that Robert Loeb, chairman of the Department
of Medicine at Columbia University College of Physicians and
Surgeons had referred to me in 1957. He was a 57-year-old
CEO of a large company with malignant hypertension, grade
III retinopathy and generalized muscle weakness from very
low serum potassium levels. His aldosterone secretion was
over 800 mgm/day while our normal values were less than 50.
We were very proud of our aldosterone assay but, unlike everybody
else, we found aldosterone to be quite normal in essential
hypertension. However, to our amazement, it was massively
increased in fatal malignant hypertension. We subsequently
removed the adrenals in four such patients to eliminate all
plasma aldosterone but it was without any benefit, since they
all died on schedule.
Thus, we showed that malignant hypertension and its diffuse
vasculitis were not caused by their high aldosterone since
this fatal condition progressed in the absence of the adrenals
when there was no aldosterone. There had to be something else
circulating in these patients that (1) raised blood pressure,
but most importantly, this substance should also (2) produce
prompt and progressive injury to blood vessels in the heart,
brain and kidneys resulting in the rapidly fatal heart attack,
stroke, heart or kidney failure typical of malignant hypertension.
Because adrenalectomy did not help, it was obviously not anything
manufactured in the adrenal so the most likely cause appeared
to me to be excess renin from the severely damaged kidneys
of these patients.
In 1898, Tigerstedt and Bergman published a classic article
in a Scandinavian journal describing an amazing and powerful
blood pressure-raising substance they had isolated from saline
rabbit kidney extracts. They called this substance renin.
But subsequent scientists failed to confirm Tigerstedt and
Bergman's findings so there was little interest in renin until
1934 when Harry Goldblatt published the landmark results of
his dog experiments. Harry induced what appeared to be the
equivalent of essential hypertension in humans by constricting
either one or both renal arteries with a silver clamp.
In addition, more severe renal ischemia produced in this
fashion resulted in a syndrome that closely simulated malignant
hypertension that was also assumed to be due to more increased
renin release. It was therefore very disappointing that numerous
attempts showed absolutely no evidence that plasma renin levels
were increased in patients with essential hypertension compared
to normal people or even that renin had any significant physiologic
action of its own in humans.
The Pivotal Role of Angiotensin
PJR: Why should renin be so
important if it is inactive?
JHL: What had been established
by Braun-Menendez was that renin acted enzymatically on a
circulating plasma protein (angiotensinogen) to release an
inactive substance (angiotensin I) that is rapidly hydrolyzed
by "converting enzymes" to form the most powerful
pressor substance known, angiotensin II. It is this vasoconstrictor
angiotensin II, released in plasma only by renin, which plays
the crucial role in causing most human hypertension and its
fatal sequelae. We showed that when you give angiotensin II
to normal humans it produces a rapid rise in blood pressure
by promoting vasoconstriction as well as via a slower and
more sustained elevation by also stimulating aldosterone secretion
to promote body sodium retention and expand blood volume by
acting on the kidneys.
However, it was many years before these normal roles of plasma
renin or angiotensin would finally be acknowledged and much
longer still before the establishment began to accept renin
as a major cause of human malignant and essential hypertensions.
In fact, there are some establishment diehards who will probably
go to their graves resisting renin.
PJR: How did this information
help you target drug treatments to specific hypertensive patients?
JHL: The new data and our studies
led us to propose and later prove that the malignant hypertension
syndrome is caused by an unchecked runaway release of renin
by the damaged kidneys, leading to very high plasma angiotensin
levels. This raises blood pressure and also constricts the
coronary, cerebral and renal vessels, rapidly leading to fatal
complications like heart attacks and stroke. We were able
to correct all of this syndrome in malignant hypertension
patients not only by removing both kidneys, but also by treating
each such patient instead with any one of the 3 antirenin
R drug types that we characterized and introduced: first propranolol,
a beta blocker, to block the kidney beta receptor renin release,
then, the snake venom peptide (teprotide), the original intravenous
angiotensin converting enzyme (ACE) inhibitor, and finally,
the intravenous octapeptide saralasin, the first angiotensin
II receptor blocker (ARB).
Our findings with teprotide and saralasin soon persuaded
industry to synthesize many orally active analogs of the venom
ACE inhibitor (e.g. captopril, enalapril, lisinopril., rampril)
and later on, many orally active ARB's resembling saralasin
(e.g. losartan, valsartan, cardesartan, olmesartan, irbesartan,
telmisartan, eprosartan). As you know, these explicit antirenin
system R drugs, together with beta blockers, another antirenin
R drug class that we defined, have had a dramatic influence
on our understanding and treatment of all human hypertension.
And they have had an even greater impact for preventing or
arresting the plasma renin-caused fatal consequencs, notably
heart attack, stroke, heart and kidney failure.
We then went on to prove that about two out of three cases
of essential hypertension are caused and sustained by their
plasma renin levels because blocking renin with one of our
antirenin drugs promptly corrects them. In these patients
too, we could also prevent the same but more gradually developed
fatal sequelae of heart attacks, stroke, heart failure and
kidney failure with any one of our three antirenin drug types.
However, these R drugs do not benefit patients with low renin
hypertension who, on the other hand, respond incredibly well
to the natriuretic (V) drugs (thiazides, spirolactone, calcium
channel blockers) that reduce body sodium and thus blood volume.
The Plasma and Direct Renin Assays
PJR: The key to your treatment
method appears to be the ability to measure plasma renin activity
accurately. The difficulty that most physicians had was that
this measurement was quite complicated because it required
incredible sensitivity and thus was not widely available,
as well as being expensive, since unlike today, it was not
covered by health insurance. Paul Brown, who founded Metpath
Laboratories, was a good friend and I recall taking you over
to New Jersey around 25 years ago to meet him. Metpath was
well on its way to becoming the largest clinical laboratory
in the United States, and since I served as a consultant at
the time I wanted to explore the possibility of providing
renin testing as part of a hypertension profile. Nothing apparently
came of that but Corning later acquired Metpath, which subsequently
became Quest Laboratories. Quest now offers an automated ambulatory
direct Renin immunoassay. Is this procedure as accurate as
the Sealey-Laragh plasma renin activity assay?
JHL: I remember our visit with
Paul Brown quite well. You were on the right track then, and
as usual, a little ahead of the curve. Jean Sealey joined
our laboratory in 1960 as a biochemist. She soon showed us
how our aldosterone assay could be improved. Then, over the
next ten years, Jean worked with us to perfect the world's
most sensitive and accurate plasma renin activity assay (PRA).
She also worked in Harry Goldblatt's lab for several months
to learn his 12 step human renin purification procedure, which
gave us a very valuable reagent to use. All of the previous
renin assays were inaccurate because of a variety of procedural
errors we were able to identify and correct during this period,
although there were constant criticisms and objections to
my renin hypothesis, nobody ever questioned the superior accuracy
of our testing procedure.
Our renin assay remains the only method that can accurately
measure the low values, and is absolutely crucial since it
is the only way to positively identify and separate out the
salt-volume "V" patients whose low renin hypertension
is caused instead by salt and requires a different treatment
using anti salt drugs instead of the antirenin R drugs that
correct the renin type of hypertensives.
Quest has been using our Sealey-Laragh method for the past
seven to eight years in their New Jersey laboratory. Recently,
we have helped them to switch to their automated Direct Renin
test which now shows a good correlation with our more time
consuming assay. Most people don't appreciate that plasma
renin activity (PRA) levels can be high enough to produce
a fatal stroke at one ten billionth of the molar concentrations
of plasma glucose or cholesterol! This is why very sophisticated
detection technology amenable to mass production is required.
The pivotal values for these two procedures are shown below.
(V) Volume Hypertension
- PRA levels less than 0.65 ng/m/hr
- Direct Renin less than5 mU/ml
- This is predominantly sodium-volume renin-caused
(R) Renin Hypertension
- PRA levels greater than 0.65 ng/m/hr
- Direct Renin greater than 5 mU/m
- This is predominantly due to angiotensin caused
Measuring renin allows you to identify which type of antihypertensive
medication is most likely to be effective and possibly safer
in any given patient. The advantage here is that once this
is established it is possible for patients to have their blood
pressure controlled with one drug permanently. Monotherapy
for life is our nirvana for hypertension treatment. We seek
this for every patient and achieve it in most.
Treating Volume Versus Renin Hypertension
PJR: How are specific medications
selected based on renin profiling and how can treatment be
initiated if renin testing is not readily available? This
information is elegantly explained in your recent book*(see
below) but could you give us a brief summary?
JHL: Yes, salt-volume (V) hypertension
is always associated with the lower ambulatory plasma renin
levels (PRA values less than 0.65). This occurs in about a
third of patients with high blood pressure. It is correctly
treated with any one of the natriuretic or anti-volume V drugs
such as spirolactone, a thiazide diuretic, a calcium channel
blocker or an alpha blocker. Renin-angiotensin (R) mediated
vasoconstrictor hypertension is twice as common. It resembles
a forme fruste of fatal malignant hypertension and is thus
much more apt to be associated with albeit milder, and more
gradually occurring, fatal heart attacks, strokes, heart failure
or kidney failure. These (R) hypertension patients should
instead be treated primarily with any one of the three types
of antirenin R drugs, an angiotensin converting enzyme inhibitor
(ACE), angiotensin receptor blocker (ARB) or a beta blocker.
The bottom line is that blood pressures for all hypertensives
can be controlled with the Laragh Method using one drug for
life in over half of both (V) and (R) patients, or in sum,
for at least 60 percent to 80 percent of the total group.
As you noted, this is in sharp contrast to the expensive and
unpleasant polypharmacy approach promoted by JNC-VII. The
result is that most patients treated using their protocols
are denied the precious opportunity for a lifetime of monotherapy
with the correct drug type for them but are condemned instead
to taking two to four drugs. This increases costs and side
effects while providing much less net benefit, which means
a diminished productive life and an earlier demise.
It is also possible to bypass renin testing by using single
file trials of a V and then an R drug to identify which type
will correct the hypertension. In addition, I believe you
must stop drugs that don't work rather than always continuing
drugs you have on board as JNC-VII mandates. In our method,
about 20 percent of the whole may need both a V and an R drug
but that's still highly preferable to the JNC-VII protocol
that starts with a thiazide diuretic and keeps piling on other
drugs until blood pressure is controlled. Since diuretics
are not only not indicated but can also raise pressure in
the two out of three patients with high renin R hypertension,
most of these will have to keep adding other drugs only to
achieve poorer results.
PJR: I would suspect that placing
everyone on diuretics perpetually would lead to potassium
depletion, cardiac arrhythmias and a significant increase
in diabetes. It could also deny high renin patients protection
from fatal cardiovascular complications that you have shown
antirenin medications do provide for them.
JHL: You are absolutely correct
and what is both impressive and alarming is the underappreciated
harm that can result from traditional diuretic therapy. The
thiazide diuretic, hygroton, produced over an 11 percent incidence
of real and permanent diabetes in less than five years in
the ALLHAT trial, which suggests at least 22 percent after
10 years and even more later on.
In other studies, thiazides have been shown to regularly
produce muscle potassium and magnesium depletion that leads
to cardiac arrhythmias, muscle weakness, electrocardiographic
changes and thence to fatal cardiovascular complications.
The good news is that all of these complications can be avoided
by using spirolactone instead to correct sodium-volume related
hypertension without ever causing diabetes or depletion of
potassium and magnesium.
Our renin hypothesis has been widely confirmed in over 120,000
patients who were studied following an acute myocardial infarction
in various large clinical trials. Only those receiving an
antirenin R drug had a consistent reduction in recurrent myocardial
infarction, congestive heart failure and sudden death rates.
This shows that blocking the presence or action of angiotensin
II by giving an antirenin R drug to this very vulnerable group
of patients will consistently prevent plasma renin vasculotoxicity
and extend useful life for millions.
As emphasized, the R drugs do not help low renin hypertensives,
who require and often have dramatic relief from natriuretic
V drug salt depletion. Conversely, V drugs are ineffective
and often harmful when given to renin mediated R hypertensive
patients because this raises renin levels even higher.
Are Government Guidelines Based on Politics Rather Than
PJR: Since others have confirmed
your hypothesis and NHLBI has funded your research it is puzzling
that renin is not referred to in their official reports. This
reminds me of Schopenhauer's observations about discoveries.
"All truth passes through three stages: First, it is
ridiculed; Second, it is violently opposed; and Third, it
is accepted as self-evident." Hopefully, the renin story
is reaching the end of this trail. New ideas are most often
criticized not because they lack merit, but because they might
turn out to be workable, which would threaten the reputations
and possibly jobs of many people with conflicting opinions.
The disastrous results of this are vividly illustrated by
the recent NHLBI sponsored ALLHAT study.
JHL: None of the numerous studies
that confirm the renin hypothesis are ever quoted by ALLHAT
or JNC reports, which is reprehensible. The word renin is
rarely or never mentioned, which is like discussing diabetes
without ever mentioning the word, insulin! With respect to
this ALLHAT report, there were several flaws in the design
and implementation of the study that raise serious doubts
about the validity of its conclusions and especially their
applicability to clinical practice.
Over one-third of patients were African Americans who are
more apt to respond to diuretics because more of their hypertension
tends to be volume (salt) related. The participants were all
older than 55 (mean age 67) and 36 percent were diabetic,
so it is also doubtful that any conclusions from such an elderly
high-risk group would apply to low-risk hypertensives under
the age of 55.
Nine out of 10 were already receiving some type of antihypertensive
drug therapy and there was no washout or medication-tapering
period. On day one they were switched to one of four blinded
randomized drug limbs: diuretic (hygroton), ARB (doxazosin),
ACE inhibitor (lisinopril) or calcium channel blocker (amlopidine),
so that "baseline" BP was meaningless as a control
point for evaluating efficacy. The withdrawal of certain drugs
may have caused subsequent adverse events such as heart failure
rather than this being due to the new medication as the study
authors concluded. The increased incidence of "heart
failure" characterized by poorly defined edema in the
doxazosin group that led to its discontinuation is particularly
puzzling. It is more likely that "heart failure"
resulted from the abrupt cessation of diuretic therapy in
those patients who were then placed on comparatively low dosages
of this antirenin drug since heart failure has not been a
problem in other studies.
The timing and pace at which patients were treated with medications
were not consistent with good medical practice and potentially
dangerous. As explained in our editorial,** many of us would
consider failure to achieve effective drug treatment for six
to 18 months as overt malpractice. Drug dose titrations were
programmed so that no changes at all were made in non-responders
until after six months. Although the second drug was again
often the wrong one, it still had to be titrated up for the
next nine to 12 months and it was only after 16 months that
a step-three drug was introduced. Consequently, some patients
were put at increased risk for complications due to poor or
no control of their pressure for a year and a half or more,
during which they would likely also suffer from the side effects
of increasing dosages of drugs not appropriate for their type
of hypertension. I suspect this could lead to significant
ALLHAT study malpractice litigation.
According to the trial protocol, if patients did not achieve
the goal pressure on a properly titrated dose of the initial
study drug, a second and if necessary a third medication could
be added, provided it was not one of the study drugs (diuretic,
ACE inhibitor or CCB). Physicians could choose from a beta
blocker (atenolol) or centrally acting drugs (clonidine and
reserpine). A beta blocker was the main drug that was usually
added, which obviously would be most beneficial for non responders
on a diuretic. Conversely, patients who did not respond to
an ACE inhibitor were prevented from receiving a diuretic
or CCB and were condemned to receiving still another antirenin
drug even though the first one failed. Thus, the design of
the study was set up to favor a V drug (hygroton) and, either
intentionally or inadvertently, to put an R drug (lisinopril)
at a gross disadvantage. The tragedy is that the resulting
ALLHAT shaped recommendations are the basis for the new JNC-VII
PJR: Quite frankly, it would
seem to me that any physician who has not been able to control
a patient's hypertension with medication after an eight or
twelve month period of treatment because drug switching was
not allowed might be liable for malpractice if that patient
had some complication and it could be shown that this might
have been preventable by following the Laragh Method. Because
of its faulty design, the ALLHAT trial left itself wide open
for malpractice litigation and one suit has already been filed.
The widow of a 60 year old radiologist who died after being
in the study for three-and-one-half years sued the principal
investigator at a Pennsylvania hospital as well as his colleagues
and the hospital in July, claiming that the dangers of the
study had been concealed from her husband when they were trying
to convince him to enroll. He had developed some edema or
soft tissue swelling during the trial, but his treating physician
continued to increase the dose of the blinded drug, which
turned out to be the calcium channel blocker, a known cause
When there was a slight blood pressure increase, hydralazine,
another drug known to cause edema was prescribed in 1999.
According to the complaint, ALLHAT patients were never told
of the risk of edema, venous insufficiency, and possibly death
from blood clots or bleeding. The swelling worsened and in
early 2000, the patient developed lupus, another side effect
of hydralazine. Nevertheless, he was kept on the given drugs
until days before his death in July 2000. He had also developed
an abnormal electrocardiogram, muscle pain, and cataracts,
all of which were likely caused by study drugs but either
went unreported or uninvestigated as should have been done.
In retrospect, he should have been pulled from the trial when
there was evidence of kidney damage. The cause of death was
a blood clot in his lungs, which the complaint alleged was
"a consequence of drug induced lupus and end-stage rapidly
progressing kidney damage brought on by the continued ingestion
of hydralazine." The patient, a physician, had rated
his health as "very good" (90 on a 100-point scale)
just before entering the ALLHAT trial.
One claim for superiority of hygroton in ALLHAT was that
it reduced the rate of stroke by 15 percent compared with
the ACE inhibitor lisinopril. However, as several critics
noted, this could be completely accounted for by the greater
stroke rate in black patients given lisinopril who failed
to respond and were then put on a beta blocker and then still
had significantly higher blood pressures. It is well known
that ACE inhibitors or beta blockers are ineffective in low
renin hypertension, which is more common in black hypertensives,
so that combining two antirenin drugs in a low renin patient
was inappropriate. I believe you expressed similar concerns
in your editorial.
JHL: Very definitely. It is
well established that black patients with hypertension are
often more likely to respond to diuretics or the other V drugs
than to ACE inhibitors or the other R antirenin drugs. The
reverse tends to be true in Caucasians and this was also confirmed
in ALLHAT. The malpractice issue here is that the nonresponders
to lisinopril had to wait 6 months before another drug was
added and the only options available for step 2 were still
another antirenin drug, either a beta blocker, clonidine or
reserpine. Giving another R drug to a patient who already
exhibited failure to respond to this type of medication is
a no-brainer, not in keeping with widely recommended practices.
This second R drug was then titrated up for another nine to
12 months, so that a patient who really required a V drug
was essentially taking two placebos for 16 months.
It was only after 16 months that the step-three drug hydralazine
could be started in a still unresponsive patient who had to
continue to take the two other drugs that were not working.
Thus, patients who were randomized to lisinopril and did not
respond were condemned to at least two more redundant and
therefore, ineffectual antirenin drugs while being denied
effective antivolume drug treatment for well over a year.
One can only imagine how frustrating this must have been to
treating physicians who recognized this but had to abide by
the rules of the trial. With respect to lawsuits, in all fairness,
no matter how well any trial is designed, patients may have
unanticipated adverse reactions.
The ultimate responsibility lies not only with the trial
designers but also with the programming physicians who need
to prepare for such situations and place the patients' interests
first instead of those of their government supervisors. As
indicated in our editorial in The American Journal of Hypertension**,
it would not be an exaggeration to say that I or any one of
my colleagues could have accomplished the same drug titrations
in four to 10 weeks, during which time we would have discarded
the medications that obviously did not work. However, such
logical and commonly used drug subtractions or substitutions
were also strangely barred by the study design, so that by
fiat, ALLHAT actually endorsed malpractice.
PJR: This is of great concern
since that the latest governmental guidelines for treating
hypertension contained in JNC-VII are based on ALLHAT, which
brings up another interesting question. Just exactly what
is the purpose of this Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure
and what authority does it have? The committee grew out of
an NIH program to educate the public about the early warning
signs and symptoms of hypertension.
However, this gradually expanded to include information on
the advantages and disadvantages of various medications, and
eventually guidelines for their use. The first NHLBI JNC report
published in 1976 promoted thiazide diuretics as the preferred
drugs for hypertension as did its successors. The 1993 JNC-V
guidelines added angiotensin-converting enzyme (ACE) inhibitors
and beta blockers as initial therapy choices because of evidence
that they were more likely to reduce complications such as
heart attacks and strokes but ACE inhibitors were dropped
in the 1996 JNC-VI guidelines. ALLHAT was designed to prove
that the government had been correct all along. Although beta
blockers were not one of the four types of antihypertensive
drugs being compared, they were also excluded as recommended
starting medications in JNC-VII, leaving thiazide diuretics
to again reign alone as supreme. Thus, according to NHLBI,
we apparently have not made any progress in the treatment
of hypertension since their first report over 25 years ago.
JHL: Giving a thiazide diuretic
to every hypertensive patient is likely to be the wrong choice
more than half the time and continuing it despite the fact
that it is not effective makes no sense to me. The JNC-VII
committee completely failed to acknowledge other large hypertensive
trials whose results were available to them but did not support
their thiazide first and always recommendations. The ANB2
(Second Australian National Blood Pressure Study) published
in the New England Journal of Medicine in February found that
ACE inhibitors were associated with 11 percent lower cardiovascular
mortality and complication rates compared to treatment with
diuretic agents despite similar blood pressure reductions.
During the Australian trial, the diuretic hydrochlorothiazide,
was compared with the ACE inhibitor enalapril and patients
who did not respond to the first drug were switched to the
other, rather than being maintained on something that clearly
Two out of three study participants responded to monotherapy
with either drug when, according to the trial design, patients
who did not respond to the first drug were switched to the
other, rather than being maintained on something that clearly
didn't work, again confirming the Laragh Method. At the end
of five years, the ACE inhibitor was found to be superior
to the thiazide diuretic. I suspect that these findings, which
JNC-VII completely ignored, may have more relevance for U.S.
clinicians since this population was about 90 percent Caucasian
as opposed to less than two-thirds in the ALLHAT study.
More NHLBI and JNC-VII Deception and Chicanery
PJR: As I understand it, all
federal rules or guidelines that affect the public are required
by law to be written and promulgated according to the government
code. This mandates formal selection of a committee, pre-announcement
of all meetings, open meetings that encourage testimony from
all interested parties as well as written records, all of
which must be preserved in a special docket.
Everything is then reviewed in order to provide a written
discussion of all the relevant evidence that led to the final
guidelines, which must be published in the Federal Register.
In addition, if the published guidelines are not consonant
with a logical review of the evidence presented, these recommendations
may be overturned by legal action. Since the JNC-VII guidelines
seemed to be subject to these rules I accessed the Federal
Register but was unable to find anything relevant. When I
contacted the Government Printing Office to inquire about
this I received a reply confirming they had no JNC records
and was referred to a NIH web site. This was remarkably reminiscent
of how the National Cholesterol Education Program (NCEP) for
the detection and treatment of high cholesterol had operated.
The first NCEP report issued in 1988 was timed to coincide
with the introduction of Mevacor, Merck's new cholesterol
lowering drug. In an unprecedented action it was released
directly to the public weeks before doctors could read the
scientific information on which it was based.
The last set of revised guidelines in 2001, which tripled
the number of Americans advised to take statins, was also
publicized prematurely. In both instances, the guidelines
were published in the Journal of the American Medical Association
but not the Federal Register. There was no public notice of
any meetings, the meetings were not open to the public, public
input was not solicited, and detailed records and testimony
of committee meetings were not kept.
When NHLBI officials were questioned about this they explained
that the cholesterol and hypertension recommendations as well
as the latest advice for everyone to restrict dietary sodium
intake had all been written by outside experts and were therefore
exempt from the Government Code and Federal Register regulations.
This despite the fact that they are presented by paid government
spokespersons at government press conferences and are promoted
in the media as the latest government guidelines. The FDA
even authorized a "sodium and hypertension" food
label health warning stating that it was based on the Intersalt
study. Yet, there had not only been no public input, as required
but access to the data on which these faulty conclusions were
based was repeatedly denied until legal action was threatened
and chicanery in data analysis was discovered.
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