The meta-analysis reported by Lasserson et al provides evidence that
half of the effect of antihypertensive treatment on blood pressure takes
place within the first week of treatment. [1] There is no reason to doubt
these findings. However the analysis does not support the conclusion that
"estimation of maximal effect could be made between 1 and 2 weeks after
initiation of antihypertensi...
The meta-analysis reported by Lasserson et al provides evidence that
half of the effect of antihypertensive treatment on blood pressure takes
place within the first week of treatment. [1] There is no reason to doubt
these findings. However the analysis does not support the conclusion that
"estimation of maximal effect could be made between 1 and 2 weeks after
initiation of antihypertensive therapy". Nor does it support the view that
"this knowledge will guide practitioners in deciding when a newly started
antihypertensive agent can be judged to be ineffective".
First, it is not possible to determine whether blood pressure has
been reduced by treatment within a week. The authors reach their
conclusion after meta-analysis of measurements in 4168 individual
patients. But clinicians must decide whether a newly started
antihypertensive agent is ineffective on the basis of measurements in one
patient. There is an important difference.
The mean reduction in systolic blood pressure on maximum treatment is
reported as 14.7 mm Hg. The reduction at one week is therefore 7.4 mm Hg.
The aim of measurement is therefore to distinguish between a reduction of
7.4 mm Hg and no reduction in blood pressure.
The short term within-individual variation in office measured blood
pressure has a coefficient of variation of 7.3% (for both systolic and
diastolic blood pressure).[2] This means that when multiple office
measurements are taken over a series of days in an individual with a mean
systolic blood pressure of 150 mm Hg the measurements will have a standard
deviation of 11 mm Hg [11 = 7.3% x 150].
For an individual with a mean untreated blood pressure of 150 mm Hg
and a mean treated blood pressure of 142.6 mm Hg the standard error of the
change in blood pressure is 15.1 mm Hg [15.1 = Sqrt(11.0^2 + 10.4^2)].
This means that as a result of chance variation in measured blood pressure
before and after treatment, there is a probability of 0.31 that the
difference will be less than zero (there is no apparent reduction in blood
pressure). In plain language, even if the treatment is effective, on one
third of occasions it will appear not to be. The clinician has no way of
knowing whether the patient has failed to respond to treatment or the on
treatment measurement is higher by chance.
The problem is reduced but not solved by taking the average of three
office measurements (meaning three separate visits) before treatment and
the mean of three measurements on treatment. This reduces the standard
error of a blood pressure of 150 mm Hg to 6.3 mm Hg {6.3 = 11/Sqrt(3)} and
it reduces the standard error of the difference to 8.7 mm Hg. The
probability that treated blood pressure measurements will be higher than
untreated is now 0.20. If the treatment is effective, on one in five
occasions the clinician will believe it to be ineffective.
Nor is the problem solved by the use of daytime average 24-hour
ambulatory blood pressure before and after treatment. For 24-hour
ambulatory blood pressure the within-individual coefficients of variation
for systolic and diastolic blood pressure are 5.5% and 4.9%.[3] The
probability that a treated daytime average 24-hour ambulatory blood
pressure will be higher than an untreated daytime average 24-hour
ambulatory blood pressure is 0.26.
With an expected effect size of 7.4 mm Hg in order to be reasonably
certain (probability <0.05) that no reduction in measured blood
pressure indicates non response, a clinician must take the average of 12
office measurements before treatment and 12 after treatment. Alternatively
they may take the average of five daytime average 24-hour ambulatory blood
pressures before and after treatment. This is of course impossible within
a week.
Second we need to ask how likely it is whether it is likely that the
patient will not respond. It is well documented that very little (3%/1%
for systolic / diastolic) of the apparent variation between individuals in
blood pressure response to treatment is due to genuine differences in
treatment response. [4] Most of the apparent variation in treatment
response is the result of chance variation in measured blood pressure.
It is not possible to determine the extent to which individual
patients respond to antihypertensive treatment. It is essentially
unknowable. Fortunately we do not need to determine the extent to which
individual patients respond to antihypertensive treatment, because we know
that almost all respond similarly.
Yours sincerely
Tom Marshall
Senior Lecturer in Public Health
^ = to the power of (ie: S^2 = S squared)
Sqrt = Square root of
REFERENCES
1. Lasserson DS, Buclin T, Glasziou P. How quickly should we titrate
antihypertensive medication? Systematic review modelling blood pressure
response from trial data Heart 2011;Published Online First: 17 May 2011
doi:10.1136/hrt.2010.221473
2. Keenan K, Hayen A, Neal BC, Irwig L. Long term monitoring in patients
receiving treatment to lower blood pressure: analysis of data from placebo
controlled randomised controlled trial. British Medical Journal 2009; 338:
b1492.
3. Warren RE, Marshall T, Padfield PL, Chrubasik S. Variability of Office,
24-hour Ambulatory and Self-Monitored Blood Pressure Measurements British
Journal of General Practice 2010 Sep;60(578):675-80.
4. Bell KJL, Hayen A, Macaskill P, Craig JC, Neal BC, Fox KM, Remme WJ,
Asselbergs FW, van Gilst WH, MacMahon S, Remuzzi G, Ruggenenti P, Teo KK,
Irwig L. Monitoring Initial Response to Angiotensin-Converting Enzyme
Inhibitor-Based Regimens: An Individual Patient Data Meta-Analysis From
Randomized, Placebo-Controlled Trials Hypertension Sep 2010; 56: 533 -
539.
To the editor:
The very interesting study by Logue et al. (2011) on a group of middle-
aged, hypercholesterolic men with no prior history of diabetes or CVD,
recently reported that obesity is associated with fatal coronary heart
disease (CHD), but not non -fatal CHD independently of traditional CVD
risk factors. The authors hypothesize that since excessive adipose tissue
is known to secrete inflammatory mediators, that in...
To the editor:
The very interesting study by Logue et al. (2011) on a group of middle-
aged, hypercholesterolic men with no prior history of diabetes or CVD,
recently reported that obesity is associated with fatal coronary heart
disease (CHD), but not non -fatal CHD independently of traditional CVD
risk factors. The authors hypothesize that since excessive adipose tissue
is known to secrete inflammatory mediators, that increased systemic
inflammation might be making these obese subjects more prone to fatal
adverse coronary events. Although mechanistically very plausible, there
may be a potential confounder in the study as the authors noted that,
"There were lower proportions of current smokers and higher proportions of
ex-smokers in higher than lower BMI categories." Whether reduced smoking
in the heaviest members of the studied cohort suggests that this group
quit smoking at a higher rate due to cardiac or other health-related
symptoms is not reported. Current smoking to a much greater extent than
past smoking is associated with systemic inflammation and a pro-
coagulative state (1). Although smokers form occlusive thrombus more
readily than nonsmokers, smokers paradoxically survive their first heart
attack better than nonsmokers (2). This is presumably because the smoker
presents with MI at an earlier stage of CVD and thereby represents a "less
sick" patient (3). If obese subjects were experiencing MI due to systemic
inflammation-induced hypercoagulability, they too might be expected to
present with MI at an earlier stage of CVD and display an advantage in
surviving, rather than dying from the first MI. Additional clinical and
pathological factors might be interacting with increased systemic
inflammation in increasing the risk of fatal CVD events in these obese
subjects.
Correspondence: Carr J. Smith, Ph.D., Visiting Scholar, UNC Chapel
Hill Dept. of Pathology, 1012 Bartlett Circle, Hillsborough NC 27278,
carrjsmith@yahoo.com.
1. Smith CJ, Fischer TH. Particulate and vapor phase constituents of
cigarette mainstream smoke and risk of myocardial infarction.
Atherosclerosis 2001; 158: 257
2. Jaatun HJ, Sutradhar SC, Dickstein K. Comparison of mortality rates
after acute myocardial infarction in smokers versus non-smokers. Am J
Cardiol 2004; 94: 632-636.
3. Mueller HS, Cohen LS, Braunwald E et al. Predictors of early morbidity
and mortality after thrombolytic therapy of acute myocardial infarction.
Analyses of patient subgroups in the Thrombolysis in Mycardial Infarction
(TIMI) trial, phase II. Circulation 1992; 85: 1254-1264.
I would like to mention the place of MIBG as other modality of
Cardiac Imaging for risk stratification of patients with heart failure in
need for ICD; see Bax et al, Cardiac Sympathetic Denervation Assessed
With 123-Iodine Metaiodobenzylguanidine Imaging Predicts Ventricular
Arrhythmias in Implantable Cardioverter-Defibrillator Patients
J Am Coll Cardiol, 2010; 55:2769-2777, doi:10.1016/j.jacc.2009.12.066...
I would like to mention the place of MIBG as other modality of
Cardiac Imaging for risk stratification of patients with heart failure in
need for ICD; see Bax et al, Cardiac Sympathetic Denervation Assessed
With 123-Iodine Metaiodobenzylguanidine Imaging Predicts Ventricular
Arrhythmias in Implantable Cardioverter-Defibrillator Patients
J Am Coll Cardiol, 2010; 55:2769-2777, doi:10.1016/j.jacc.2009.12.066
The Conclusions of which was that Cardiac sympathetic denervation
predicts ventricular arrhythmias causing appropriate ICD therapy as well
as the composite of appropriate ICD therapy or cardiac death.
We appreciated the paper by Dahiya et al. attempting to improve non-
invasive estimation of pulmonary vascular resistance (PVR)(1). However,
some points deserve few comments.
1. The new formula (PVRc) compared to the previous one by Abbas et al.(2)
(PVRe) includes E/e' ratio, in order to take into account pulmonary
capillary wedge pressure (PCWP) and better estimate transpulmonary
gradient. E/e' is a ratio, but needs to...
We appreciated the paper by Dahiya et al. attempting to improve non-
invasive estimation of pulmonary vascular resistance (PVR)(1). However,
some points deserve few comments.
1. The new formula (PVRc) compared to the previous one by Abbas et al.(2)
(PVRe) includes E/e' ratio, in order to take into account pulmonary
capillary wedge pressure (PCWP) and better estimate transpulmonary
gradient. E/e' is a ratio, but needs to be converted into pressure scales
to be used to calculate PVRc; the authors do not explain what kind of
equivalence they used to perform this conversion. We guess this is a
crucial point, as in the present format the formula cannot be applied.
2. PVRc adopts right ventricular systolic pressure (RVSP) instead of
tricuspid regurgitation velocity, to take into account also right atrial
pressure (RAP). RAP has been quantified through the use of the method
proposed by Kirchner et al.(3). This approach is limited because it
considers only inferior vena cava (IVC) collapsibility index and not its
dimensions. Recent guidelines underlined that traditional cutoff values
for IVC diameter and collapsibility index do not perform well in
intermediate RAP values leading to worst RVSP estimation. To improve RAP
estimation, guidelines suggested a new scheme that includes secondary
indexes such tricuspid E/E' ratio or hepatic vein flow(4). The
implementation of a better method to estimate RAP (and so RVSP) might lead
to a better performance of PVRc.
3. Calculate PVRc is more complex than calculate PVRe. Although PVRc seems
to perform better than PVRe in case of very high PVR, it is not clear if
it could improve our clinical capability to discriminate patient into
normal or increased PVR. It would be interesting to calculate the
likelihood ratio between the two formulas, as well as the percentage of
correct reclassification into defined ranges of PVR (e.g. normal, high,
very high) applying PVRc versus PVRe.
Bibliography
1. Dahiya A, Vollbon W, Jellis C, Prior D, Wahi S, Marwick T.
Echocardiographic assessment of raised pulmonary vascular resistance:
Application to diagnosis and follow-up of pulmonary hypertension. Heart
2010, Dec;96(24):2005-9.
2. Abbas AE, Fortuin FD, Schiller NB, Appleton CP, Moreno CA, Lester SJ. A
simple method for noninvasive estimation of pulmonary vascular resistance.
J Am Coll Cardiol 2003, Mar 19;41(6):1021-7.
3. Kircher BJ, Himelman RB, Schiller NB. Noninvasive estimation of right
atrial pressure from the inspiratory collapse of the inferior vena cava.
Am J Cardiol 1990, Aug;66(4):493-6.
4. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran
K, et al. Guidelines for the echocardiographic assessment of the right
heart in adults: A report from the american society of echocardiography
endorsed by the european association of echocardiography, a registered
branch of the european society of cardiology, and the canadian society of
echocardiography. J Am Soc Echocardiogr 2010, Jul;23(7):685-713; quiz 786-
8.
We read with interest the systematic review and metanalysis by Bruins
Slot et al concerning early diagnosis of myocardial infarction using heart
type fatty acid binding protein (HFABP) (1). We agree with their summary
that used in isolation, HFABP may not offer a diagnostic advantage over
the current troponin standard. However it should be noted that in 5 of the
included studies, constituting 1573 pa...
We read with interest the systematic review and metanalysis by Bruins
Slot et al concerning early diagnosis of myocardial infarction using heart
type fatty acid binding protein (HFABP) (1). We agree with their summary
that used in isolation, HFABP may not offer a diagnostic advantage over
the current troponin standard. However it should be noted that in 5 of the
included studies, constituting 1573 patients (42% of the pooled cohort) no
information on symptom duration was available. As the release kinetic
profile of HFABP results in a rapid rise in serum concentrations from 2-4
hours after symptom onset, underlying its promise as a very early marker
of myocardial infarction, inclusion of these studies may significantly
skew results in favour of troponin.
The authors also state that HFABP use would result in 16% of cases
being labelled false positive. It must be realised that a so called false
positive result is not unique to HFABP. Reichlin et al have shown that, on
presentation, the positive predictive values of 4 highly sensitive
troponin assays ranged from only 0.5-0.73, indicating a significant
proportion of "false positive" results occurred compared with a gold
standard of final diagnosis (determined by fourth generation troponin and
clinical consensus)(2).
We would also question whether positive HFABP in the absence of
ACC/ESC diagnosed MI actually represents a false positive result. The
large investigation by Kilkullen et al showed that troponin negative
patients who are HFABP positive are at a higher risk of death than
patients who are troponin positive in isolation (3). McCann et al have
also demonstrated a similar adverse prognostic association of HFABP with
death, independent of troponin, NT-Pro-BNP and clinical parameters in
consecutive chest pain patients (4).
We suggest HFABP is not solely a very early biomarker of cell necrosis and
identifies patients at higher risk for cardiac events who may benefit from
more intensive inpatient management and that further studies are warranted
to improve assessment of patients presenting early after acute chest pain
onset to the emergency department.
1. Bruins Slot MHE, Reitsma JB, Rutten FH, Hoes AW, van der Heijden
GJMG. Heart-type fatty acid-binding protein in the early diagnosis of
acute myocardial infarction: a systematic review and meta-analysis. Heart.
2010 Dec 15;96(24):1957 -1963.
2. Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C,
Hartwiger S, et al. Early Diagnosis of Myocardial Infarction with
Sensitive Cardiac Troponin Assays. N Engl J Med. 2009 Aug 27;361(9):858-
867.
3. Kilcullen N, Viswanathan K, Das R, Morrell C, Farrin A, Barth JH,
et al. Heart-type fatty acid-binding protein predicts long-term mortality
after acute coronary syndrome and identifies high-risk patients across the
range of troponin values. Journal of the American College of Cardiology.
2007;50(21):2061-2067.
4. McCann CJ, Glover BM, Menown IB, Moore MJ, McEneny J, Owens CG, et
al. Prognostic Value of a Multimarker Approach for Patients Presenting to
Hospital With Acute Chest Pain. The American Journal of Cardiology.
2009;103(1):22-28.
Conflict of Interest:
J A Shand receives partial salary support as a Research Fellow from Randox Laboratories, Crumlin, NI.
To whom it may concern,
The meta-analysis reported by Lasserson et al provides evidence that half of the effect of antihypertensive treatment on blood pressure takes place within the first week of treatment. [1] There is no reason to doubt these findings. However the analysis does not support the conclusion that "estimation of maximal effect could be made between 1 and 2 weeks after initiation of antihypertensi...
To the editor: The very interesting study by Logue et al. (2011) on a group of middle- aged, hypercholesterolic men with no prior history of diabetes or CVD, recently reported that obesity is associated with fatal coronary heart disease (CHD), but not non -fatal CHD independently of traditional CVD risk factors. The authors hypothesize that since excessive adipose tissue is known to secrete inflammatory mediators, that in...
I would like to mention the place of MIBG as other modality of Cardiac Imaging for risk stratification of patients with heart failure in need for ICD; see Bax et al, Cardiac Sympathetic Denervation Assessed With 123-Iodine Metaiodobenzylguanidine Imaging Predicts Ventricular Arrhythmias in Implantable Cardioverter-Defibrillator Patients
J Am Coll Cardiol, 2010; 55:2769-2777, doi:10.1016/j.jacc.2009.12.066...
We appreciated the paper by Dahiya et al. attempting to improve non- invasive estimation of pulmonary vascular resistance (PVR)(1). However, some points deserve few comments. 1. The new formula (PVRc) compared to the previous one by Abbas et al.(2) (PVRe) includes E/e' ratio, in order to take into account pulmonary capillary wedge pressure (PCWP) and better estimate transpulmonary gradient. E/e' is a ratio, but needs to...
To the Editor
We read with interest the systematic review and metanalysis by Bruins Slot et al concerning early diagnosis of myocardial infarction using heart type fatty acid binding protein (HFABP) (1). We agree with their summary that used in isolation, HFABP may not offer a diagnostic advantage over the current troponin standard. However it should be noted that in 5 of the included studies, constituting 1573 pa...
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