really enjoyed Malcolm's recent RFW article on hypertension and it motivated me to communicate some of my long time interests to all
of you, my fellow skeptics. Malcolm brings up some excellent points and I
completely agree that essential HTN is another very good example of a
symptom or a number attaining a disease status. This is certainly
prevalent in medicine as it is much easier to attack a number than to
address the difficulty of causation. In the case of elevated BP it
is a very simple thing to lower the number with a wide variety of
pharmaceuticals and thus declare a victory, making both the doctor and
patient happy. This is certainly analogous to labeling
hypercholesterolemia a disease and lowering the cholesterol levels with
drug therapy, again, treating a number and declaring victory. Even
in the case of adult onset diabetes mellitus there is a strong tendency to
attack the elevated blood sugar as if this in and of itself was a disease.
Again, the number can conveniently be lowered with a variety of drugs
while completely ignoring the underlying metabolic disturbance related to
excess carbohydrate intake. Patients and physicians have a strong
tendency to prefer taking/prescribing a pill to treat a number rather than
make any alteration in lifestyle or eating habits.
Essential hypertension was for years attributed to excess dietary sodium.
This brought about the well-known anti-salt crusade which, although
diminished, is still with us today and, as we know, has been a complete
failure. This brings us to the very interesting question of what is
causing essential hypertension and on this I would like to throw out a
couple of thoughts and observations.
Although there is logic to Malcolm's theory that elevated BP is a
necessary compensation to maintain blood flow in the setting of arterial
narrowing by atherosclerotic narrowing/plaques, I do not think that this
applies to the majority of patients with essential hypertension. I
can only envision this phenomenon in settings of advanced atherosclerotic
disease. The onset of essential HTN in most patients is in their
30's & 40's at a time when advanced atherosclerosis is uncommon.
For many years I was fascinated with the work of Leopold Dintenfass and
other scientists devoted to blood viscosity (hemorheology). In fact,
back in the 60's and 70's they had a very active International society
that met annually for scientific sessions. Most of the members were
basic scientists interested in the physiology of microcirculation.
One of the interesting theories of this group was that elevated BP was an
adaptive response to an elevation in blood viscosity. Enhanced red
blood cell aggregation dramatically increases whole blood viscosity and
causes impaired microcirculation. This aggregation can be offset by
increasing cardiac output which increases the shear forces and has a
disaggregating effect thereby improving microcirculation. The
downside of this adaptation is of course the elevation of BP. Common
examples of factors which enhance red blood cell aggregation are:
1. Stress, which causes an increase in blood fibrinogen levels which
causes red blood cell aggregation thereby increasing blood viscosity.
The negative charge on the outer membrane of red blood cells normally
prevents these cells from getting too close. Red cells can only
aggregate when they are cross-linked by the long fibrinogen molecules.
2. Anything that increases concentration of red blood cells (elevation in
hematocrit). For example, the intermittent hypoxia of sleep apnea is
associated with an increase in hematocrit and hypertension, both of which
return to normal upon treatment of the sleep apnea. Elevated
hematocrit also commonly occurs in smokers who are frequently hypertensive.
Another commonly encountered factor in whole blood viscosity is the
decrease in red blood cell deformability that is frequently present in
diabetics. Red blood cells are approximately 9 microns in diameter
and must be capable of folding like an umbrella or elongating like a hot
dog to pass through the 5 micron diameter capillaries of our
microcirculation. Diabetics commonly have hypertension. This
brings up the Malcolm theory whereby a higher pressure head must be
established to squeeze these little stiff cells through. At any rate,
these are just some interesting thoughts that should be considered.
Another interesting possible causative factor in essential HTN relates to
diastolic dysfunction of the myocardium. Diastolic dysfunction is an
impairment in the relaxation (filling) phase of the cardiac cycle which is
actually the phase requiring much more cellular ATP than the systolic (contraction)
phase. It takes a great deal of ATP to re-establish trans-membrane
Ca++ gradients which allows the uncoupling of actin/myocin. Rigor
mortis is a very good example of muscles remaining in a contracted state
when deprived of cellular energy (ATP). Diastolic dysfunction is the
earliest manifestation of heart failure and can be easily measured
non-invasively by echocardiography.
This brings us to my field of current research interest. The heart
muscle requires more ATP than any other tissue and accordingly has a huge
concentration of mitochondria - approximately one third of the volume of
heart muscle is mitochondria, far more than any other cell type and with
the high proportion of mitochondria, the heart muscle also has the highest
level of my favorite molecule, CoQ10. Heart muscle is thereby
uniquely vulnerable to CoQ10 depletion or deficiency. Beginning at
about the age of 25-30, biosynthesis of CoQ10 begins to decline and blood
and tissue levels have been documented to steadily fall after this age.
There is, of course, a lot of individual variation.
The vast majority of patients presenting with essential HTN have diastolic
dysfunction regardless of whether or not the BP is treated or untreated,
BP controlled or uncontrolled. Supplemental CoQ10 is unique in
its ability to improve diastolic dysfunction (see abstracts 1 & 2
below) and although there have been many attempts, there is, as yet, no
known pharmaceutical capable of favorably altering this fundamental aspect
of cardiac physiology. It is important to stress the word "favorably"
in so far as statins cause diastolic dysfunction, presumably by way of
CoQ10 depletion. After 3-4 moths of CoQ10 supplementation, this
diastolic dysfunction improves and BP drifts down gradually over the same
period of time such that one fourth of patients attain completely normal
blood pressures and require no more anti-hypertensive medication.
The remainder of patients require substantially less anti-hypertensive
drug therapy (see abstract 3 below).
By definition, patients with diastolic dysfunction have an impairment of
the filling phase of the cardiac cycle which causes a major limitation in
one's ability to increase cardiac output. A human can increase
cardiac output from 5 liters/min at rest to 25 liters/min with exercise by
doing three things:
1. By increasing heart rate, e.g., 70 beats per minute at rest to
160 BPM with exercise
2. By an increase in contractility, e.g., ejection fraction goes
from 55% at rest to 75% during exercise
3. By an increase in the ability of the heart to expand and fill
more to accept the enhanced venous return
With an impairment in diastolic function one can only increase cardiac
output through the first and second mechanisms which can only be enhanced
through an increase in catecholamines (high adrenaline state). Thus,
patients with diastolic dysfunction tend to have high resting ejection
fractions, for example 65%, and high resting heart rate, for example 90
BPM, and when called upon to walk even a short distance on a treadmill,
these patients will rapidly attain their maximum heart rate within as
short time as 1-2 minutes as opposed to the normal of 9-12 minutes.
To summarize, patients with diastolic dysfunction virtually always have an
adaptive high catecholamine state with associated elevations in heart rate
and BP. Since CoQ10 has not been shown to have any direct
vasodilating effect, one can postulate that the normalization of BP in
many of these patients can be explained by the normalization of their
diastolic function. It would appear that this early heart muscle
dysfunction is in large measure related to the deficiency of a simple, but
very essential nutrient, CoQ10.
My above postulate is contrary to the standard dogma in cardiology which
has long held that elevated BP is the primary "disease" and left
ventricular hypertrophy and diastolic dysfunction are secondary phenomena.
This may be the case in secondary hypertension, which represents only
about 10% of the HTN cases. My guess is that in essential
hypertension it's actually the reverse. In other words, it's a
myocardial disease causing an elevation of BP. As is the case in
many adaptive responses, they can, in and of themselves, cause harm in a
vicious cycle whereby elevated pressures further impair heart muscle
As always, I would very much appreciate your thoughts.
1. Isolated diastolic dysfunction of the myocardium and its
response to CoQ10 treatment. Langsjoen PH, Langsjoen PH, Folkers K Clin
Investig 1993;71(8 Suppl):S140-4 Symptoms of fatigue and activity
impairment, atypical precordial pain, and cardiac arrhythmia frequently
precede by years the development of congestive heart failure. Of 115
patients with these symptoms, 60 were diagnosed as having hypertensive
cardiovascular disease, 27 mitral valve prolapse syndrome, and 28 chronic
fatigue syndrome. These symptoms are common with diastolic dysfunction,
and diastolic function is energy dependent. All patients had blood
pressure, clinical status, coenzyme Q10 (CoQ10) blood levels and
echocardiographic measurement of diastolic function, systolic function,
and myocardial thickness recorded before and after CoQ10 replacement. At
control, 63 patients were functional class III and 54 class II; all showed
diastolic dysfunction; the mean CoQ10 blood level was 0.855 micrograms/ml;
65%, 15%, and 7% showed significant myocardial hypertrophy, and 87%, 30%,
and 11% had elevated blood pressure readings in hypertensive disease,
mitral valve prolapse and chronic fatigue syndrome respectively. Except
for higher blood pressure levels and more myocardial thickening in the
hypertensive patients, there was little difference between the three
groups. CoQ10 administration resulted in improvement in all; reduction in
high blood pressure in 80%, and improvement in diastolic function in all
patients with follow-up echocardiograms to date; a reduction in myocardial
thickness in 53% of hypertensives and 36% of the combined prolapse and
fatigue syndrome groups; and a reduced fractional shortening in those high
at control and an increase in those initially low. Isolated
diastolic dysfunction associated with moderately low CoQ10 blood levels is
an extremely frequent finding in patients with three varied clinical
entities sharing similar symptoms and CoQ10 replacement results in
clinical improvement, lowering of elevated blood pressures, improved
diastolic function, a decrease in myocardial thickness, and a
normalization of systolic function.
2. The Aging Heart: Reversal of Diastolic Dysfunction Through the
Use of Oral CoQ10 in the Elderly. Langsjoen P, Langsjoen A, Willis A,
Folkers, K Anti-Aging Medical Therapeutics, (1997) R.M.Klatz and R.
Goldman eds., Health Quest Publications, pp.113-120.
The observations on the clinical utility of CoQ10 in cardiology have
gradually shifted from an emphasis on systolic left ventricular function
towards the broader and more fundamental observations on diastolic
function and dysfunction. Our experience with CoQ10 began in 1981
with the initiation of a double blind placebo controlled trial in
idiopathic dilated cardiomyopathy, followed by a six year open label study
involving 126 patients. By 1993, it became apparent that diastolic
dysfunction was an easily measured abnormality in early myocardial disease
that showed clear improvement with the use of CoQ10. In 1994, 424
patients with six different diagnostic categories of cardiovascular
disease were shown to have a significant improvement in diastolic function
as well as a significant reduction in the associated finding of left
ventricular hypertrophy. Overall medication requirement in this
group dropped considerably and the quality of life was enhanced both
directly by the effects of CoQ10 on myocardial function and indirectly by
easing the burden of multi drug therapy. Our current data
demonstrate a significant improvement of diastolic function in patients
with advanced age (average age 84 years) when treated with oral CoQ10 (average
dose 220 mg/day). Along with the reversal of diastolic dysfunction,
we observed marked improvement in patients' exercise tolerance and quality
of life. This refutes the common assertion that a stiff and
non-compliant myocardium is a normal and irreversible aspect of the aged
3. Treatment of essential hypertension with coenzyme Q10.
Langsjoen P, Langsjoen P, Willis R, Folkers K Mol Aspects Med 1994;15
A total of 109 patients with symptomatic essential hypertension
presenting to a private cardiology practice were observed after the
addition of CoQ10 (average dose, 225 mg/day by mouth) to their existing
antihypertensive drug regimen. In 80 per cent of patients, the diagnosis
of essential hypertension was established for a year or more prior to
starting CoQ10 (average 9.2 years). Only one patient was dropped from
analysis due to noncompliance. The dosage of CoQ10 was not fixed and was
adjusted according to clinical response and blood CoQ10 levels. Our aim
was to attain blood levels greater than 2.0 micrograms/ml (average 3.02
micrograms/ml on CoQ10). Patients were followed closely with frequent
clinic visits to record blood pressure and clinical status and make
necessary adjustments in drug therapy. Echocardiograms were obtained at
baseline in 88% of patients and both at baseline and during treatment in
39% of patients. A definite and gradual improvement in functional status
was observed with the concomitant need to gradually decrease
antihypertensive drug therapy within the first one to six months.
Thereafter, clinical status and cardiovascular drug requirements
stabilized with a significantly improved systolic and diastolic blood
pressure. Overall New York Heart Association (NYHA) functional class
improved from a mean of 2.40 to 1.36 (P < 0.001) and 51% of patients
came completely off of between one and three antihypertensive drugs at an
average of 4.4 months after starting CoQ10. Only 3% of patients required
the addition of one antihypertensive drug. In the 39% of patients with
echocardiograms both before and during treatment, we observed a highly
significant improvement in left ventricular wall thickness and diastolic
function. We observed no side effects or drug interactions from CoQ10.
The time course to improvement in functional class, blood pressure control,
and myocardial function is in keeping with an improvement in myocardial
bioenergetics by CoQ10 and not a pharmacological effect. The
reduction in blood pressure seems likely to be secondary to a decrease in
the neurohumoral response to an early impairment in myocardial function
which is primarily diastolic in nature. The gratifying improvement
in patient's quality of life was enhanced by a marked reduction in their
need for antihypertensive drugs along with the substantial medical and
financial burden that those drugs entail.
I agree with Malcolm and Peter - hypertension, just as
hypercholesterolemia, is a symptom, not a disease. There are more
similarities; the small effect achieved by hypotensive treatment is most
probably not due to the lowered blood pressure, but to other effects of
the drugs, and/or to the inclusion of a few patients with malignant
hypertension. As a previous nephrologist I have seen several such cases
with very high blood pressure (>280/160), severe retinal vascular
changes (FH 3-4) and rapidly deteriorating renal function. If these
patients are treated energetically with hypotensive drugs (administered
intravenously by continuous infusion, aiming at a blood pressure below,
say 110/70) you will see that renal function continues to go down for a
short time, but after that it will in most cases slowly return to normal
or near normal. (This effect does of course not necessarily mean that the
high blood pressure is primary, just that it most likely is causing the
retinal and renal damage).
The effect of hypotensive treatment on other patients is even smaller than
the effect of statin treatment; see table translated to English from a
paper of mine about medical prevention published recently in Tidskriften
of four types of preventive measures
risk reduction (%)
risk reduktion (%)
alive without intervention (%)
alive with intervention (%)
total mortality compared with that of heavy smokers’ (>25 cigarettes
per day) .
Mortality from breast cancer in screened women compared with non-screened
women in the most beneficial mammography study .
mortality in screened women compared with non-screened women in the most
beneficial mammography study .
Cardiovascular mortality in treated and untreated patients with
hypertension in a meta-analysis of 17 controlled, randomised studies 
mortality in statin-treated, high-risk individuals compared with
non-treated in 4S 
mortality in statin-treated, healthy, hypercholesterolemic individuals
compared with non-treated .
Doll R et al.. Mortality in relation to smoking: 40 years' observations on
male British doctors. BMJ 1994; 309: 901-11.
Bjurstam N et al. The Gothenburg breast screening trial: First results on
mortality, incidence, and mode of detection for women ages 39-49 years at
1997; 80: 2091-9.
Hebert PR et al. Recent
evidence on drug therapy of mild to moderate hypertension an decreased
risk of coronary heart disease. Arch
Int Med 1993; 153: 578-81.
Randomised trial of cholesterol lowering in 4444 patients with coronary
heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet
1994; 344: 1383-9.
Shepherd J et al. Prevention of coronary heart disease with pravastatin in
men with hypercholesterolemia. N
Engl J Med 1987; 333: 1301-1307.
you see from the table the absolute risk reduction from hypotensive
treatment as regards cardiovascular mortality was only -0.8%, whereas the
effect on total mortality in the best statin trial, 4S, was -3.5%. (In the
table I had selected the results from the most optimistic studies; all
other studies were less favourable).
The effect of hypotensive treatment on total mortality is even smaller,
but I did not find any figures for all ages. In a meta-analysis of 15
trials including old people only performed by Cochrane, that
effect was statistically significant in two trials only (absolute risk
reduction -1.6%; note that the effect on CVD mortality mentioned in the
table regarded all ages). This did not prevent the reviewers to conclude
that "treating healthy older persons with hypertension is highly
The figures in the table were taken from a meta-analysis of 17 trials by
Hebert et al. and included in a systematic report published by The Swedish
Council on Technology Assessment in Health Care nine years ago, when Lars
Werkö, a member of our group, was its director. Other shocking
observations from that report worth mentioning were that in some of the
trials half of the members of the untreated control group had normal blood
pressure at follow-up, that the effect on heart disease was trivial, and
that the effect in women and young people in most trials was trivial, if
The hypotensive effect of CoQ10, described by Peter, was unknown to me -
most fascinating. These results are close to revolutionary. They, or a
review of them, should be published in a major medical journal, but I
realize that they are probably too controversial to become accepted.
also Malcolm Kendrick´s article in Red
Flags Daily that
generated the following comments:
I share these thoughts. Elevated BP is a marker for other systemic
problems such as metabolic syndrome. The lowering of BP will lead to an
increase in prescription drugs that will lower the BP at the expense of
exacerbating metabolic syndrome and incurring other increased risks. It
continues to be a numbers game with advantages for drug companies but a
bleak picture for patients—all of us. Whatever happened to treating
patients and patients with diseases not diseases as conjured up entities
in and of themselves in a vacuum? We know from Jeppesen’s work
(Copenhagen Men’s Study) that those with elevated BP and elevated TGs
and low HDLs, when treated with conventional meds, actually increase their
risk of an MI. Beta blockers and diuretics—first line antihypertensive
drugs—may increase the risk of developing type 2 diabetes by 28% or more
and increase risk for CVD. They increase insulin resistance and worsen
metabolic syndrome. But, as long as the numbers look nice… Many
anti-hypertensives have adverse effects on lipid profiles which is
probably reflecting worsening of endothelial function. What a sad state is
Thanks Malcolm for your own wonderful
article in Red Flags Weekly. I estimate 10-15 million Americans will
be labeled pre-hypertensive on the basis of these new "guidelines"
on the URL; http://www.nhlbi.nih.gov/guidelines/hypertension/jncintro.htm
-pg 18, where the Framingham Study is quoted as stating that 90% of
normotensives over the age of 55 will become hypertensive. Perhaps
we all ought to start antihypertensives (if not statins) at birth.
Creating new patients and people at risk by redefining cutoff points of
continuous variables (see recent changes in "definition" of
diabetes) has a profound effect on the definition of universal ill health,
and will certainly worsen the financial crisis in healthcare.
and Alice Ottoboni
Malcom's article in Redflagsweekly was
excellent. The process by which the New Hypertension Guidelines
were "fishy" and resemble the process used to develop the New
Cholesterol Guidelines. One result of the New Cholesterol
Guidelines has been a huge increase in the sales of cholesterol-lowering
drugs. Perhaps the same result is expected with the New
Hypertension Guidelines -- a huge increase in sales of pressure-lowering
the New Cholesterol Guidelines in our book. The process by which
the New Hypertension Guidelines were promulgated is nearly a carbon
copy of that used for the New Cholesterol Guidelines. Both appear
to have violated the US Government Code for the promulgation of
Federal rules and recommendations that affect large groups of people.
of guidelines were announced by a gov't agency, the NLHBI, and were
presented to the public via a gov't press release as new gov't
the guidelines were written by a committee of "experts" ostensibly
under the umbrella of NHLBI. But, these committees were not
gov't appointed, regulated, or controlled, although they included a
few gov't members and received peripheral gov't support.
law says all important federal rules, including guidelines that
affect the public must be written and promulgated according to the
Gov't Code. This code requires formal committee selection,
pre-announcement of all meetings, open meetings, written records,
testimony from all interested parties, and the maintenance
of a special file or docket to preserve all testimony and
written commentary. Then, government staff people must consider
all relevant information in the docket and provide a written,
logical discussion of all of the relevant evidence along with the
final rules or guidelines. All of this must be published in the
Federal Register. And, most importantly, if the published
guidelines are not consonant with a logical review of the evidence
presented, the guidelines may be overturned by legal action.
Both the cholesterol and hypertension
guidelines did not follow this very important law. There was
no public notice of meetings, meetings were not open to the public,
public input was not solicited, detailed records testimony
of committee meetings were not kept, and amazingly, the finished
guidelines were published in the JAMA, not the Federal Register.
When we questioned about this unusual process, NHLBI
responded that the cholesterol guidelines were written by a
non-government committe that was not subject to the Federal Register
process. Yet, the new guidelines are presented by government
spokespersons at a government press conference and are headlined
in newspapers throughout the world as new government guidelines.
It would appear that a gov't agency
is being used to, in effect, set standards of good practice that
promote the sale of certain prescription drugs. Such misuse
would not be possible if the Govt' Code was followed.
Absent the will of government agencies to
adhere to the Gov't Code, correcting the wrongs exemplified by these
two new sets of guidelines would appear to be impossible short of
major legal action by a well-endowed and competent law firm.
Paul Rosch: Prehypertension
And The Emperor´s Invisible Suit
Paul Rosch: Do
You Have a Good Blood Pressure?
Paul Rosch: The
Salt Controversy: The Diet "Dictocrats" Are At It Again!
Peter Langsjoen: To
Reduce The Risk of Heart Disease, Why Don´t We All Cut Off Our Ear Lobes?