Increase in blood glucose concentration during antihypertensive treatment as a predictor of myocardial infarction: population based cohort study
BMJ 2003; 326 doi: https://doi.org/10.1136/bmj.326.7391.681 (Published 29 March 2003) Cite this as: BMJ 2003;326:681All rapid responses
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I read with interest the recent paper by Dundar et al(1) showing that
“the incidence of myocardial infarction was significantly higher in the
group with antihypertensive treatment than in participants without such
treatment at age 60”, when they do not compare two homogeneous groups. How
could the authors deduce such a conclusion when they are comparing two
different groups? One group is hypertensive (with insulin resistance in
majority of patients) and the other with normal blood pressure and
possibly insulin sensitive. Up to 40% of patients with hypertension are
insulin resistance that has been shown by some of the authors of this
study previously(2). In addition, insulin resistance is well known to be
associated with increased cardiovascular risk(3). In patients with
hypertension and diabetes, these risk factors are although additive but
hypertension appears to be a more potent predictor of vascular risk than
glycemic control(4). Furthermore, there is ample evidence that aggressive
treatment of hypertension in such patients dramatically reduces this risk
of cardiovascular disease(5,6).
Table one of the paper shows very clearly two heterogeneous groups –
one group with established hypertension (on treatment) in which the
participants, in addition to higher systolic and diastolic blood
pressures, also have higher blood glucose levels, higher body mass index,
and significantly higher proinsulin levels (again suggesting higher
prevalence of insulin resistance in this group) compared to the other
group with normal blood pressure, lower body mass index and lower glucose
levels. The group with hypertension, because of elevated blood pressure
and possibly presence of insulin resistance, is at a much higher risk for
cardiovascular disease than the group with normal blood pressure and
possibly without insulin resistance. Results would be different between
two different groups. These two groups are different in their baseline
characteristics and will have different outcomes. Even the two groups
remain significantly different over next 10-years. There was less increase
in BMI and glucose levels in the normal blood pressure group, indicating
no decrease in the insulin sensitivity in this group with age. Authors
state “An increase in fasting blood glucose predicted myocardial
infarction in the group receiving antihypertensive treatment but not in
the group without such treatment.” 5-7% of patients with insulin
resistance or impaired fasting glucose progress to the next stage
[impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or
diabetes mellitus (DM)] towards the onset of diabetes per year. If we
presume that 30% of patients with hypertension in the study had insulin
resistance then approximately 1% per year (about 10% over 10-years) of
this group would progress to the next stage of insulin resistance, i.e.
impaired glucose tolerance and type 2 diabetes. So, 10% of the patients
with insulin resistance will progress to next stage of insulin resistance
(IFG, IGT or DM) over 10-years of follow-up irrespective of whether they
received treatment that may potentiate insulin resistance. Did the authors
take this natural progression of insulin resistance into account, when
analyzing data?
The conclusion of the study would have been appropriate if the
authors have compared hypertensive patients receiving treatment to those
without such treatment when their baseline risk(s) for development of
cardiovascular disease would have been similar. By using different
statistical techniques authors tried to implicate treatment of
hypertension (available at the time) to be worse than no treatment. A
similar analogy (an oversimplification) would be that 20% of patients with
pneumonia treated with antibiotics develop shock compared to none of the
patients without pneumonia (who did not receive antibiotics).
References:
1. Dunder K, Lind L, Zethelius B, Berglund L and Lithell H. Increase
in blood glucose concentration during antihypertensive treatment as a
predictor of myocardial infarction: population based cohort study. BMJ
2003; 326: 681.
2. Lind L, Berne C, Lithell H. Prevalence of insulin resistance in
essential hypertension. J Hypertens 1995; 17:1457-62.
3. Kotchen TA, Kotchen JM, O’Shaughnessy IM. Insulin and hypertensive
cardiovascular disease. Curr Opin Cardiol 1996; 11:483-489.
4. U.K. Prospective Diabetes Study Group: Risk factors for coronary artery
disease in non-insulin dependent diabetes. BMJ 1998; 316:823-8.
5. U.K Prospective Diabetes Study Group: Tight blood pressure control and
risk of macrovascular and microvascular complications in type 2 diabetes:
UKPDS 38. BMJ 1998; 317:703-713
6. Nadig V, Kotchen TA. Insulin sensitivity, blood pressure and
cardiovascular disease. Cardiol Rev 1997;5:213-9.
Competing interests:
None declared
Competing interests: No competing interests
"The National Cholesterol Education Program Adult Treatment Panel III
guidelines identify the metabolic syndrome as a secondary target of lipid-
lowering therapy after LDL cholesterol reduction and recommend use of
weight reduction and increased physical activity to address underlying
risk factors as well as therapies to address specific lipid and nonlipid
risk factors" (1). These recommendations assume that the elevation in LDL
cholesterol and all other manifestations of the metabolic syndrome
including hyperglycaemia are the causes of atherosclerosis and ischaemic
heart disease. It would seem, rather, that they might all be the result.
In which case the treatment guidelines for hypertension, which include the
beta blockers and diuretics examined in this study, are also suspect.
Consider obesity.
The Prader-Willi syndrome is a genetic condition caused by
abnormalities in chromosome 15 in which food foraging and obesity is a
striking feature in the majority of afflicted children and adults (2). In
this large study of 256 patients coenzyme Q10 supplements were said to
completely reverse all symptoms, which include mild mental impairment and
muscle weakness, in weeks in afflicted adolescents and one or two months
in afflicted teenagers. Withholding the supplements caused a relapse in as
little as 12 hours or three days, these children becoming lethargic,
irritable, and resuming their foraging as though they were starving.
Resumption of the supplements resulted in complete recovery in two days in
all regardless of their age.
Coenzyme Q is is essential for normal functioning of the electron
transport chain in mitochondria (3). Coenzyme Q10 and other quinione
supplements may also act as permeability transition pore inhibitors or
inducers potentially either increasing or decreasing the magnitude of the
protonmotive force driving ATP resynthesis (3,4). That coenzyme Q10
supplements should be so effective in treating patients with the Prader-
Willi syndrome suggests, therefore, that the primary defect might be an
ATP energy deficit caused either by an impairment of electron transport
or an abnormality in mitochondrial membrane permeability. The
permeability might be abnormally decreased, as appears to occur in
hypothyroidism. It might alternatively be abnormally increased, as may be
induced by mitochondrial poisons such as carbon monoxide, which inhibits
electron transport, or dinitrophenol, which uncouples oxidative
phosphorylation (5). Uncoupling may also be induced by an increase in the
rate at which endogenous uncoupling proteins are released.
The food foraging and resulting obesity might, therefore, be the
product of a futile attempt to meet an unsatisfied demand for metabolic
energy in the brain by increasing the rate of nutient influx into glial
cells and hence neurons. The effect of nutient intake would be enhanced by
the anti-insulin effect of cortisol in organs other than the brain. In a
sense, therefore, patients with the Prader-Willi syndrome amay be
addicted to food in so far as addiction can be defined as the product of
an unsatisfied demand for metabolic energy as previously proposed (6).
Down's syndrome is caused by an abnormality in chromosome 21, site of
16 genes with a role in energy and reactive oxygen species metabolism (7).
They are more prone to develop obesity than healthy subjects and have a
low metabolic rate, normal thyroid scan, usually a normal thyroxine but an
elevated TSH. They have in addition many of the neuropsychiatric disorders
which have been attributed to a cerebral energy deficit (8). The
metabolic abnormalities present are very similar to those that appear to
be present in the "pooped-out" syndrome that may develop after major
surgery (9). Overeating in the Down's syndrome causes obesity to occur
within three to four years of birth. A life long regimen is ususally
instituted to avoid excessive food intake. Like the Prader-Willi syndrome
patients with Down's syndrome may be addicted to food because they too
have an unsatisfied demand for metabolic energy. In which case the
dietary restriction practiced in the management of these patients
addresses the effect and not the cause of the syndrome. It may be more
rational to mamage these patients by addressing their cellular needs. If
this could be done effectively not only might food foraging and obesity
be prevented but the neuropsychiatirc manifestations and growth
retardation might also be prevented.
In shrews the metabolic rate, expressed as the rate of consumption
of oxygen per gram of body weight, increases as the body weight decreases.
This increase in metabolic rate is due to an increase in the need for heat
to maintain body temperature and hence to the need for an increase in the
degree of openess of the permeability transition pores and uncoupling of
oxidative phosphorylation. The rate of heat loss is a function of surface
area to body weight which increases as the weight decreases. The degree of
openess of the permeability transition pore in different species of
mammals of different sizes also decreases as the body weight decreases
(5). The greater the degree of openess of the permeability transition
pore the higher the metabolic rate and hence the greater the need for
nutrient and oxygen intake to replenish ATP stores.
Thyroxine, presumably released in response to a rise in TSH,
increases the openess of the prmeability transition pore to accommodate
the need for addition endogenous heat production. In hibernating animals
the same effect is achieved by the endogenous release of uncoupling
proteins which exert their effect upon brown fat stores. The accompanying
decrease in efficiency with which ATP stores are replenished may be met by
hypothermia and/or a decrease in decrease in demand for metabolic energy.
Nutrient and oxygen uptake by cells may be increased to accommodate
the increased demand for heat production and/or chemical energy in a
timely manner by mobilising endogenous stores in fatty deposits and
increasing food intake. If the demand for ATP resynthesis cannot be met,
because of an inadequacy of nutient and/or oxygen delivery to and
utilisation by cells, an energy defict will develop even if only
transiently when the demand form energy from ATP hydrolysis is highest.
This may cause cellular dysfunction and if excessive apoptosis or even
necrosis. A shrew will die if it is unable to replenish its nutient
suppy by eating every two or three hours. Larger animals are able to
withstand starvation for days and even a few weeks, provided they have
unlimited access to water, because they are able to store nutient in their
fatty deposits and if necessary generate nutrient from muscle mass by
gluconeogenesis.
Healthy babies have a much higher metabolic rate than adults for they
have a much higher body surface area to weight ratio than adults and lose
heat more rapidly. They are also growing very rapidly. In a sense,
therefore, they are behave like shrews in their demand for food every four
to six hours. It has been suggested that insomnia might be the product of
an energy deficit (10). If so a baby's awakening and crying might also be
the products of an energy deficit. In which case the eating disorders in
the Prader-Willi and Down's syndromes should not be regarded as abnormal
behaviour requiring psychiatric care but as a cry for metabolic
correction.
The more obese a person becomes the smaller his surface area to body
weight ratio, a sphere having the smallest surface area to volume ratio,
and hence the less the need for endogenous heat production from an
uncoupling of oxidative phosphorylation. If met by a decrease in the
openess of the permeability transition pores induced by a decrease in
thyroxine release then it might cause subclinical and even overt
hypothyroidism. If this is accompanied by a fall in metabolic rate an
energy defict and its putative consequences might even be induced. The
consequences include may obesity, dyslipidaemia, homocysteineaemia,
insulin resistance, hypertension and an accompanying predisposition to
atherosclerosis and ischaemia heart disease (11). In which case obesity
per se may contribute to the development of morbid obesity and the common
failure of dietry regimens to achieve weight reduction consistently and
permanently in these patients.
As with the release of cAMP, induced by adrenergic agents,
phosphodiesterase inhibitors and stress (12)the ingestion of food and
particularly refined sugars, in excessive amounts might induce a "high"
and contribute to generating a demand for energy from ATP hydrolysis that
exceeds the capacity of the body to replenish ATP stores in a timely
manner. More importantly a sudden reduction in amount of food intake and
particularly of refined sugars might precipitate a "low" by inducing
hypoglycaenmia, as in the dumping syndrome, which is satisfied by the
further ingestion of food and/or gluconeogenesis. In which case the
overeating of food and particularly of refined sugars may be both the
cause and an effect of obesity and hence the metabolic syndrome and the
atherosclerosis and ischeamic heart disease with which it is associated.
Beta blockers limit the need for ATP resynthesis by limiting energy
expenditure from adrenergic excitation but cannot be expected to reverse
an energy deficit be it present at rest or only after an increased demand
for energy from ATP hydrolysis. They might even increase the likelihood
of developing a energy deficit by inhibiting glycogenolysis and increasing
the desire for food in patients who already have an energy deficit and are
"addicted" to food. The same applies to the treatment of
hyperglycaemia with an hypoglycaemic agent. Metformin, for example, may
induce a dangerous lactic acidosis in patients with renal disease who
already have objective evidence of an energy deficit at rest (13).
That a rise in blood sugar and basal proinsulin should be predictive
of myocardial infarction in hypertensive patients treated with beta
blockers in this study is consistent with this account of the
pathophysiology (14). Coenzyme Q10 supplements are more
pathophysiologically appropriate and less hazardous than the beta blockers
in treating the hypertension and might be as or even more effective (15).
Given their efficacy in the Prader-Willi syndrome might coenzyme Q10
supplements also be beneicial in managing obesity in patients with or
without Down's syndrome? Other means of improving the capacity for ATP
resynthesis should also be considered if the objective is to treat the
cause rather than the effect of hypertension.
1. Ginsberg HN. Treatment for patients with the metabolic
syndrome.
Am J Cardiol. 2003 Apr 3;91(7A):29-39
2. Judy WV, Stogsdill WW, Judy JS. CoQ10 in the management of low energy
and delayed development in children with Prader-Willi syndrome.
Proceedings Third World Conference of the International Coenzyme Q10
Association, London, November 2002 pp34-35.
3. Bergamin M, Nicolosi L, Petronilli V, Fontaine E, Prato M, Bernardi P.
Regulation of the mitochondrial permeability transition pore by quinones.
pp5
4. Haines TH. Coenzyme Q10 as an inhibitor of proton leakage. Proceedings
Third World Conference of the International Coenzyme Q10 Association,
London, November 2002 pp36.
5. Hochachka PA, Somero GW. Biochemical adaptation. Oxford University
Press, New York, NY, 2002.
6. Addiction: an unsatisfied demand for metabolic energy? Richard G
Fiddian-Green
bmj.com/cgi/eletters/326/7385/400#29712, 17 Feb 2003
7. Roizen NJ, Patterson D. Down's syndrome. Lancet 22003;361:1281-89
8. MMR, IBD, autism and methylmalonic acidosis Richard G Fiddian-Green
bmj.com/cgi/eletters/326/7391/718#30820, 29 Mar 2003
9. The pooped-out syndrome, ATP stores and hypothyroidism Richard G
Fiddian-Green
bmj.com/cgi/eletters/326/7384/295#30166, 4 Mar 2003
10. Re: insomnia in chronic renal disease Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7355/85#30174, 4 Mar 2003
11. Madness, hyperhomocysteinemia, metabolic rate and body temperature
Richard G Fiddian-Green bmj.com/cgi/eletters/325/7378/1433#28469, 6 Jan
2003
12. Stress: the spice of life Richard G Fiddian-Green (1 April 2003)
Raapid response to:Stress: defining the personal equation Roy Menninger
BMJ 2003; 326: 107S
13. Metformin, "lactic acidosis" and renal failure Richard G Fiddian-
Green
bmj.com/cgi/eletters/326/7379/4#28486, 6 Jan 2003
14. Increase in blood glucose concentration during antihypertensive
treatment as a predictor of myocardial infarction: population based cohort
study Kristina Dunder, Lars Lind, Björn Zethelius, Lars Berglund, and
Hans Lithell BMJ 2003; 326: 681
15. Hodgson JM Watts GF. Can coenzyme Q10 reverse endothelial dysfunction
and lower blood pressure? Implications for the metabolic syndrome.
Proceedings Third World Conference of the International Coenzyme Q10
Association, London, November 2002 51-52.
Competing interests:
None declared
Competing interests: No competing interests
Ips re loquitur. The data speak for themselves. The obvious problem
arises only when we try to speak for them. This is an epidemiologic
study. It is limited by its ability to test associations but not
causation. Any and all implications of causality should, therefore, be
taken with less than a grain from a low-salt diet.
Observation #1: "Participants who developed myocardial infarction
after the age of 60 (n=253) showed a significantly larger increase in
blood glucose between age 50 and 60 than did those without myocardial
infarction." The implication that glycemia is, indeed, the dependent
culprit or targetable risk-factor has been ruled-out by both UGDP and
UKPDS. Nevertheless, we continue to speak in terms of hazard ratios
demonstrating a 37% increased risk of MI for each 27 mg/dl (standard
deviation) increase in blood sugar [Table 2.] Why do we not just
emphasize the 5.04 mg/dl increase in blood sugars seen during the course
of documented coronary atherosclerosis as opposed to the 0.72 mg/dl
decrease in fasting sugars seen in controls (p<0.001?) Why, indeed, not
further explore how it is that the fasting sugar elevates during
significant atherogenesis?
Observation #2: "An increase of fasting blood glucose predicted
myocardial infarction in the group receiving antihypertensive treatment
but not in the group without such treatment." What would be more
interesting would be the the slope of proinsulin or insulin plotted
against FBS over time in the groups with or without MI. A positive slope
might imply operative increased insulin resistance whereas a negative
slope might imply operative insulin secretory failure.
Observation #3: "The incidence of myocardial infarction was
significantly higher in men treated for hypertension than in those without
such treatment." Despite the statistical mumbo-jumbo about linear
regression analyis, what appears to have been tested was the incidence of
myocardial infarction in men with versus those without hypertension
(baseline diastolic 96 vs 80 mm Hg - p<0.0001 and systolic 153 vs 128
mm Hg - p<0.0001.) Indeed, look at the influence of systolic
hypertension or its delta upon incidence of MI in the non-hypertensive
cohort (p<0.01 and 0.006, respectively.) The only way to legitimately
test the influence of antihypertensive therapy per se is either by cohort
or prospective randomized allocation analysis of groups with equivalent
hypertension at baseline. (v.o. Clinical Evidence, "Cardiovascular
disease in diabetes" Ronald Sigal, Hilary Meggison and Janine Malcolm)
Observation #4 "..Participants who had been admitted to the hospital
for myocardial infarction before the examination at age 60" were excluded
from the analysis. I presume this was determined a priori? Might I request
the rationale?
Competing interests:
None declared
Competing interests: No competing interests
There is a possible explanation for the findings
reported by Dunder et al (29 March p681).
Sympathomimetics are capable of causing both a
rise in blood pressure and a rise in blood glucose. If
the hypertensive effect is blocked by B blockers the
blood pressure is controlled but not the hyperglycaemic
effect. The continuing rise in blood glucose therefore
suggests a continuing rise in "sympathomimetic"
activity, possibly as a feedback response to the B effect
being blocked. If insulin production is having to
increase in response to rising hyperglycaemia inducing
agents the result will be rising "insulin resistance", as
shown by rising proinsulin concentrations. Finally
sympathomimetic agents are known to trigger
myocardial infarction.
There are a number of hormones which can cause
a rise in blood pressure and/or a rise in blood glucose.
It would be very interesting to look for any agent which
can produce all of these effects or for any feedback
mechanism which links the production of different
hormones. Blocking production of the agent, or
blocking the feedback system, might be more effective
in the management of hypertension than merely
blocking one of the effects of one of the agents.
Competing interests:
None declared
Competing interests: No competing interests
EDITOR - Observational data in the paper by Dunder et al.1 re-ignite
a longstanding and rather tired controversy regarding the importance or
otherwise of the metabolic "adverse effects" of established
antihypertensive agents, particularly b-blockers and diuretics. As
stated by the authors, a body of evidence from randomised controlled
trials (RCT) does suggest a small advantage for newer vs. older
antihypertensive agents in terms of the development of incident type 2
diabetes (CAPP,2 LIFE,3 ALLHAT4). However, as cardiovascular disease is
one of the commonest causes of death in the general population,
hypertension is one of the most important causes of preventable
cardiovascular disease, and multiple antihypertensive agents are required
to reach BP targets in many patients,5 an important question arises. Are
the established cardiovascular outcome benefits accruing from older
therapies outweighed by the morbidity associated with exposure of a small
excess of previously non-diabetic subjects to a risk of microvascular
complications? It should be recalled that the latter type of
complications take many years to develop from diagnosis; only a proportion
of screening-detected cases are likely to develop actual symptoms. Thus,
in the majority of cases of diabetes induced by antihypertensive therapy,
cardiovascular death is likely to intervene long before any detected
retinopathy, for example, becomes sight-threatening - even considering the
concomitant therapy-derived prolongation of life.
The issue of antihypertensive drug choice has important health
economic implications: although many of the newer therapies are now known
to be at least of equivalent benefit to older agents, they are heavily
promoted and very much more expensive. Even when cost is disregarded,
there is a danger that evidence-based BP targets are even less likely to
be implemented than at present if doctors are discouraged from prescribing
several key agents from the major available classes. Dunder et al.1
appear to have examined this issue from a specific and narrow perspective.
The fallacy at the heart of their analysis is that it does not appear to
have taken adequate account of the known effect of hypertension itself on
the incidence of diabetes: as all patients with hypertension studied were
treated with antihypertensive agents, the data did not permit separation
of the condition and its treatment. In the best previous observational
study, based on the ARIC cohort, a cohort of untreated hypertensives was
uniquely included:6 the conclusions undermined previous studies by
demonstrating no detectable effect of thiazides over and above the effect
of hypertension on incident diabetes. The present authors attribute this
finding to the use of lower doses. However, the data from ARIC can better
be read as suggesting that the effect of b-blockers on insulin secretion
is more important in terms of incident diabetes than any small effect of
diuretics on insulin sensitivity.
The conclusions of Dunder et al.1 appear to rest rather precariously
upon comparison of hazard ratios derived using multivariate Cox modelling
in two observational datasets of very different sizes (treated
hypertensives 291, untreated normotensives 1358), with consequent
differences in statistical power for the variables entered. Rather than
concluding from Table 2 (Table 3 in the non-abridged version) that "change
in glucose" is the most important predictor of outcome in patients treated
with antihypertensive agents, one could equally well conclude that BP
lowering does not reduce rates of myocardial infarction in patients with
hypertension - which would be just as erroneous.
Some of the best available data (ALLHAT,4 SHEP7) from RCTs addressing
the issue of drug choice in the treatment of hypertension demonstrate that
thiazide diuretics have powerful effects in reducing cardiovascular
events, which are even larger in patients with established diabetes.7 It
is curious that reference was not made (even at proof stage) by Dunder et
al.1 to the former study - the biggest ever hypertension RCT, randomising
33,357 patients to older vs. newer therapies - as it was in the public
domain for six weeks before the present paper was accepted for
publication.4 We think it was an unfortunate editorial decision to
highlight their observational study on the front page of the print
version, particularly when its main message is only weakly supported by
the accompanying data and directly contradicts the balanced message of a
recent editorial.5 As consultant physician "on take" at Glasgow Royal
Infirmary on the day of publication, one of us (JRP) immediately witnessed
keen junior doctors striking off thiazide treatment from the prescriptions
of patients with hypertension. We can only hope that this effect,
apparently based on a superficial and decontextualised reading of a
prominent paper in a trusted and widely-distributed organ, will be short-
lived.
John R Petrie,1 Claire McDougall, Ali Al-Mamari, Andrew F.B.
Kernohan, Christopher A.R. Sainsbury, Colin G. Perry, and Adrian J. Brady
Hypertension Clinic, Royal Infirmary, Glasgow G31 2ER
1Corresponding author:
Senior Lecturer (Diabetes and Cardiovascular Disease),
Third Floor, Queen Elizabeth Building,
University of Glasgow,
Royal Infirmary,
Glasgow G31 2ER.
j.r.petrie@clinmed.gla.ac.uk
References
1) Dunder K, Lind L, Zethelius B, Berglund L, and Lithell HO.
Increase in blood glucose concentration during antihypertensive treatment
as a predictor of myocardial infarction: population based cohort study.
BMJ 2003; 326: 681-3.
2) Hansson L, Lindholm L, Niskanen L, Lanke J, Hedner T, Niklason A et al.
Effect of angiotensin-converting-enzyme inhibition compared with
conventional therapy on cardiovascular morbidity and mortality in
hypertension: the Captopril Prevention Project (CAPPP) randomised trial.
Lancet 1999; 353: 611-616.
3) Dahlof B, Devereux R, Kjeldsen SE et al. Cardiovascular mortality and
morbidity in patients with diabetes in the Losartan Intervention for
Endpoint reduction in hypertension study (LIFE): a randomised trial
against atenolol. Lancet 2002; 359: 995-1003.
4) The ALLHAT Officers and Coordinators for the ALLHAT Collaborative
Research Group. Major outcomes in high-risk hypertensive patients
randomized to angiotensin-converting enzyme inhibitor or calcium channel
blocker vs diuretic: the antihypertensive and lipid lowering treatment to
prevent heart attack trial (ALLHAT). JAMA 2002; 288: 2981-2997.
5) Williams B. Drug treatment of hypertension. BMJ 2003; 326: 61-62.
6) Gress TW, Nieto FJ, Shahar E, Wofford MR, Brancati FL. Hypertension and
antihypertensive therapy as risk factors for type 2 diabetes mellitus:
atherosclerosis risk in communities study. N Engl J Med 2000; 342: 905-
912.
7) Curb JD, Pressel SL, Cutler JA, Savage P, Applegate WB, Black H et al.
Effect of diuretic-based antihypertensive therapy on cardiovacular disease
risk in older diabetic patients with isolated systolic hypertension.
Systolic Hypertension in the Elderly Cooperative Research Group. JAMA
1996; 276: 1886-92.
Competing interests:
None declared
Competing interests: No competing interests
Sirs,
In my opinion, it would sound strange to every physician, particularly
to GPs, whether or not skilled in Biophysical Semeiotics (1, 2, 3), the
following statement: “The incidence of myocardial infarction was
significantly higher in men treated for hypertension than in those without
such treatment (23% v 13.5%, P<_0.0001 _4.="_4." in="in" addition="addition" once="once" again="again" beside="beside" doctors="doctors" who="who" speak="speak" of="of" large="large" number="number" patients="patients" there="there" is="is" a="a" small="small" group="group" physicians="physicians" expecially="expecially" general="general" practitioners="practitioners" as="as" i="i" was="was" for="for" _45="_45" years="years" take="take" care="care" the="the" single="single" diseased="diseased" individual.p="individual.p"/> As I wrote in a
previous letter (“Beyond risk factors”, 28 June 2002), we must go beyond
well-known risk factors to prevent morbidity and mortality due to
arteriosclerosis complications, including MI. Primary Prevention of the
most common and dangerous human pathologies, including malignancies,
depends clearly by easy and rapid bed-side detecting individuals, even
apparently healthy, but at "real" risk, i.e. involved by well-defined
biophysical-semeiotic constitution(s), assessed clinically in
“quantitative” way (See my HONCode site N° 233736,
http://digilander.libero.it/semeioticabiofisica). In order to define
clinically a “particular” constitution, based always on mitochondrial
dysfunction (5), which does not exclude at all the presence of other(s),
of course, it is necessary to think over the current possibility of
gathering at the bed-side biophysical-semeiotic data, rich of biological
and molecular-biological information on the various human organs, tissues
and biological systems, so that doctor can describe numerous types of
biophysical-semeiotic constitutions, even from the “quantitative” point of
view. Otherweise, we can proudly accumulate papers on papers, but patients
are going to be involved - and probably die – in identical manner, as in
the past.
1)Stagnaro-Neri M., Moscatelli G. Stagnaro S., Biophysical
Semeiotics: deterministic Chaos and biological Systems. Gazz. Med. It.
Arch. Sc. Med. 155, 125 ,1996.
2) Stagnaro-Neri M., Stagnaro S., Deterministic Chaos, Preconditioning and
Myocardial Oxygenation evaluated clinically with the aid of Biophysical
Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta
Med. Medit. 13, 109, 1997.
3) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica del torace, della
circolazione ematica e dell’anticorpopoiesi acuta e cronica. Acta Med.
Medit. 13, 25, 1997
4) Dunder K., Lind L., Zethelius B. Increase in blood glucose
concentration during antihypertensive treatment as a predictor of
myocardial infarction: population based cohort study . BMJ 2003;326:681 (
29 March )
5) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. Una
Patologia Mitocondriale Ignorata. Gazz Med. It. – Arch. Sci. Med. 144, 423
(Infotrieve) 1985
Competing interests:
None declared
Competing interests: No competing interests
Thiazide and B-blockers reduce hazard.
The authors state:
1) "An increase in fasting blood glucose predicted myocardial infarction
in the group receiving antihypertensive treatment but not in the group
without such treatment."
2) "However, an increase in systolic blood pressure was a significant
predictor of future myocardial infarction only in participants without
antihypertensive treatment."
Point 1 - I think this is true, however as other correspondants have
noted this doesn't tell one anything about the additional risk conferred
by the medication itself because the groups are not comparable.
Point 2 - I think this contradicts the authors hypothesis. If the
groups were comparable then a similar rise in blood pressure would confer
a similar increase in hazard and if the authors are correct, the group
taking thiazides/b-blockers would have a further increase in hazard. There
data actually suggests that the increased hazard due to increased blood
pressure is in fact ameliorated by anti-hypertensive treatment.
I do not think that one can conclude that the treated group are at
increased risk as a result of treatment.
Competing interests:
None declared
Competing interests: No competing interests