Mr first thought on seeing this article was "how does this (MTAC) fit
in with the MHRA?" I did a search of the .pdf and to my surprise there was
not a single mention of the MHRA. Why do we need yet another pseudo-
committee (quango)? Will new "devices" need to be "evaluated" by both
bodies? Will they speak to each other? Is MHRA giving up some of its
powers? Has MTAC even heard of MHRA and vice versa? What a mess. Why is
t...
Mr first thought on seeing this article was "how does this (MTAC) fit
in with the MHRA?" I did a search of the .pdf and to my surprise there was
not a single mention of the MHRA. Why do we need yet another pseudo-
committee (quango)? Will new "devices" need to be "evaluated" by both
bodies? Will they speak to each other? Is MHRA giving up some of its
powers? Has MTAC even heard of MHRA and vice versa? What a mess. Why is
there no explanantion of the relationship between MTAC and MHRA in this
article? Or indeed even a recognition of the existence of MHRA?
We do not need NICE. Its powers have been reduced. We do not need MTEC,
MTAC. The MHRA already does this job.
The Coalition promised to get rid of many quangos. This does not seem to
be happening. NICE and its various self appointed sub-committes should be
one of them.
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.
We read the article by Sivapalaratnam and colleagues with great
interest. Although, self-reported family history of coronary heart disease
(CHD) was an independent risk factor for future CHD events in this study,
the addition of family history of CHD to Framingham Risk Score (FRS)
failed to improve the overall risk prediction of future CHD events.
Since age is a heavily weighted risk factor incorporated in the
contempora...
We read the article by Sivapalaratnam and colleagues with great
interest. Although, self-reported family history of coronary heart disease
(CHD) was an independent risk factor for future CHD events in this study,
the addition of family history of CHD to Framingham Risk Score (FRS)
failed to improve the overall risk prediction of future CHD events.
Since age is a heavily weighted risk factor incorporated in the
contemporary cardiovascular risk scoring models, these models tend to
underestimate the risk in younger patients who are otherwise destined to
develop CHD. Hence, it would be important to see the significance of a
positive family history of premature CHD in a subgroup of patients who
were relatively younger at the time of risk prediction and those who went
on to develop CHD at a younger age. It does seem plausible that those who
are destined to develop CHD event at a younger age may well be identified
better by incorporating family history of premature CHD in to the risk
prediction model. We, therefore, urge the authors to now report
reclassification in those subjects who were relatively younger at the time
of estimated FRS and amongst those patients who subsequently developed CHD
at a young age.
The article by Gray et al is a succinct and useful summary of NICE
clinical guidance 94 on the management of unstable angina and non ST
elevation myocardial infarction (1). The NICE document is itself a major
piece of work which synthesises vast bodies of evidence (2). The majority
of the document and the resulting summary to which we respond are to be
applauded. However, we believe the risk stra...
The article by Gray et al is a succinct and useful summary of NICE
clinical guidance 94 on the management of unstable angina and non ST
elevation myocardial infarction (1). The NICE document is itself a major
piece of work which synthesises vast bodies of evidence (2). The majority
of the document and the resulting summary to which we respond are to be
applauded. However, we believe the risk stratification method for access
to routine invasive management is flawed.
NICE CG94 recommends management in line with estimated 6 month
mortality according to the GRACE registry outcomes prediction model, with
some caveats in relation to bleeding risk. This model has very important
limitations that invalidate its use for the stated purpose. Firstly, all
risk prediction models become increasingly inaccurate as the size of the
population to which they are applied reduces. There is consequently too
much emphasis on the percentage score and too little emphasis on clinical
assessment of individual patients. Secondly, the model ignores the main
benefits of a routine invasive over selective invasive strategy; namely
reductions in recurrent non-fatal myocardial infarction (3), admission
rates, revascularisations, and costs during follow up. Thirdly, the GRACE
score does not take account of underlying age based actuarial survival
rates. It therefore overestimates the risk of death in relation to the
index ACS episode in older patients. The NICE recommended approach places
patients aged under 50 with electrocardiographic ST depression and
troponin elevation into a selective invasive group while requiring routine
invasive management for virtually all patients aged over 70 presenting
without these features; this is clearly unworkable and wrong.
The cardiology community should not accept the oversimplified use of
risk scores in this way. The algorithms recommended by NICE should be
adapted to reflect the individual clinical picture and to take account of
the risk of recurrent myocardial infarction. Otherwise it is likely that
individual units and cardiac networks will find their own ways to adapt
CG94 recommendations for clinical use.
Yours sincerely,
Elved Roberts, Glenfield Hospital, University Hospitals Leicester
Mamas Mamas, Manchester Heart Centre and University of Manchester
Alice Wood, Glenfield Hospital, University Hospitals Leicester
Douglas Fraser, Manchester Heart Centre
Rod Stables, Liverpool Heart and Chest Hospital
Erwin Rodrigues, Aintree Cardiac Centre, Aintree University
Hospitals, Liverpool
Ian Hudson, Glenfield Hospital, University Hospitals Leicester
Nick Palmer, Liverpool Heart and Chest Hospital
Doug Skehan, Glenfield Hospital, University Hospitals Leicester
References:
1. Gray HH, Henderson RA, de Belder MA, Underwood SR, Camm AJ. Early
management of unstable angina and non-ST-segment elevation myocardial
infarction: summary of NICE guidance. Heart 2010;96(20):1662-8.
2. NICE. Unstable angina and NSTEMI: the early management of unstable
angina and non-ST-segment-elevation myocardial infarction [CG94]. London:
National Institute for Health and Clinical Excellence. 2010.
3. Mamas M, Fraser D. Featured correspondence: NICE chest pain
guidance. Heart 2010;96(22): 1859-1860.
To the Editor:
We appreciate the work by Hall?n et al. which reported a single-point
measurement of cardiac troponin-I (cTnI) 24- or 48-hours after primary
angioplasty for those with ST-segment elevation myocardial infarction
(STEMI) provides substantial prognostic information on the evolution of
left ventricular (LV) function and the risk of LV expansion.(1) Actually,
a single level of cTnI after primary angioplasty is...
To the Editor:
We appreciate the work by Hall?n et al. which reported a single-point
measurement of cardiac troponin-I (cTnI) 24- or 48-hours after primary
angioplasty for those with ST-segment elevation myocardial infarction
(STEMI) provides substantial prognostic information on the evolution of
left ventricular (LV) function and the risk of LV expansion.(1) Actually,
a single level of cTnI after primary angioplasty is associated with a
variety of factors including the mass of myocardial necrosis, the
metabolic rates, and the hemodynamic status. As we know, timing to perform
coronary catheterization is crucial to restore blood flow to the viable
ischemic myocardium which determines the mass of myocardial necrosis and
subsequent LV remodeling. Second, those with old age, prior heart failure
and impaired liver and renal functions may have relatively slow metabolic
rates and possibly contribute to high levels of cTnI after STEMI. Third,
those with unstable hemodynamic status such as shock and hypoxia in
advanced Killip classification lead to global myocardial damage, not
restricted to the infarct-related artery territory and have high levels of
cTnI after STEMI. It has been well known that, LV stunning will be present
for months even after coronary revascularization in time (within 6 hours)
after MI. Therefore we may use the follow-up LV ejection fraction (LVEF)
at 3 months as the reference of prior systolic function of the patients
before MI. Obviously, LV remodeling occurred in most patients who had an
initial low LVEF and a single high level of cTnI after primary angioplasty
and remained low LVEF for 3 months in the F.I.R.E. trial. Accordingly, the
characteristics of these patients may include prior LV dysfunctions, more
severe Killip classification and prolonged myocardial ischemic time, which
resulted in final LV remodeling undoubtedly. However, there were some
controversies regarding patients with an initial low LVEF and low levels
of nTnI (<91ng/ml) who recovered LV systolic functions at 3 months as
compared to those with mildly impaired LV systolic functions and high
levels of nTnI (>49.76 ng/ml). We observed that the initial levels of
cTnI in the two subgroups were mostly overlapped within 50 -100 ng/ml.
Perhaps, those with obvious myocardial stunning due to large are of
myocardial reperfusion immediately (ischemic time< 3 hours) after
primary angioplasty result in less LV remodeling than those with
relatively small ischemic area but prolonged ischemic time. In summary,
although STEMI patients with an initial low LVEF and a single high level
of nTnI after primary angioplasty could predict the development LV
remodeling, we may need more parameters like a serial of B-type
natriuretic peptite and nTnI levels to predict LV remodeling for those who
are masked by temporal myocardial stunning.(2)
Reference
1. Hall?n J, Jensen JK, Fagerland MW, Jaffe AS, Atar D. Cardiac troponin I
for the prediction of functional recovery and left ventricular remodelling
following primary percutaneous coronary intervention for ST-elevation
myocardial infarction. Heart. 2010; 96:1892-1897.
2. Fertin M, Hennache B, Hamon M, Ennezat PV, Biausque F, Elkohen M, Nugue
O, Tricot O, Lamblin N, Pinet F, Bauters C. Usefulness of Serial
Assessment of B-Type Natriuretic Peptide, Troponin I, and C-Reactive
Protein to Predict Left Ventricular Remodeling After Acute Myocardial
Infarction (from the REVE-2 Study). Am J Cardiol. 2010;106:1410-1416.
In their recent paper[1], the authors describe the performance of
ASSIGN and Framingham algorithms in comparison to the original QRISK
equations.
Readers may be interested that the QRISK2 algorithm was published in
February 2009[2] and made available as free open source software in April
20103. This can be found at http://svn.clinrisk.co.uk/opensource/qrisk2/.
The open source is intended to further increase the...
In their recent paper[1], the authors describe the performance of
ASSIGN and Framingham algorithms in comparison to the original QRISK
equations.
Readers may be interested that the QRISK2 algorithm was published in
February 2009[2] and made available as free open source software in April
20103. This can be found at http://svn.clinrisk.co.uk/opensource/qrisk2/.
The open source is intended to further increase the reliable and
widespread implementation of QRISK2 into clinical practice.
There are substantial differences between the original QRISK[4] and
QRISK2[5] algorithms which includes additional predictor variables
together with their associated significant age interactions:
All of these are independent predictors and improve risk estimates in
individual patients. Both QRISK and QRISK2 have been independently
validated on an external cohort[6,7]. The results for QRISK2 showed an
improvement compared with the original QRISK equation[4,5].
We disagree with the conclusion that "using any of the models for
initial systematic assessment of high or lower CVD risk would result in
the majority of men and women to which the models apply getting very
similar assessment and hence prioritisation for further investigation of
treatment". The key issue is the extent of reallocation. Allocation is
critically dependent on the CVD risk score used and its performance in
contemporaneous, ethnically diverse UK populations. The fact that ASSIGN,
like Framingham, is associated with 20% or more overestimation in men
results from a dependence on historical cohorts from the 1980's when the
vascular epidemic was near its height. Vascular mortality has halved in
succeeding decades and the incorrect allocation of individuals to high
risk categories will increase using ASSIGN and Framingham.
The QRISK2 algorithm is derived from contemporaneous cohorts and is
updated annually to take account of population trends in risk factors and
disease incidence, improvements in data quality and changing requirements
(eg need to incorporate a broader age range as in the GP "QOF" Contract).
QRISK2(2010) has therefore has been refitted to the latest version of the
QResearch database and includes a broader age range of patients aged 30-84
years3. This has resulted in considerable improvements in performance as
can be seen from the table below.
Systematic use of a cardiovascular risk score which doesn't include
ethnicity is likely to under-estimate risk, particularly in South Asians
and also to contribute to widening health inequalities.
The inclusion of ethnicity is especially important given the effect
of ethnicity on cardiovascular risk. For example, Pakistani men have a 97%
increased risk of CVD compared with white men (adjusted HR 1.97, 95% CI
1.70 to 2.29). Using a 20% threshold to define high risk, then 15% of
South Asian men would be identified as high risk using QRISK2 (2010)
compared with 10% using the NICE modified version of Framingham.
Similarly, 8% of South Asian women would be identified as high risk using
QRISK2(2010) compared with 3% based on Framingham.
Table 1: Validation statistics for QRISK2 (2010) on the QResearch
database compared with ASSIGN1 on the THIN database. The table shows
measures of the performance of the scores i.e. how accurate the scores are
at identifying high risk patients and distinguishing them from low risk
patients and how much of the 'variation' in risk is explained by the
scores themselves. High values for R2, D statistic and ROC indicate better
performance than low values. A predicted/observed ratio of 1 indicates
perfect calibration and a ratio greater than one indicates over-
prediction.
QRISK2 (2010) ASSIGN
Mean (95% CI) Mean (95% CI)
women
R2 51.4(50.9-5.19) 37.39 (36.70-37.97)
D statistic 2.11(2.09-2.13) 1.58 (1.56-1.60)
ROC value 0.853(0.851- 0.855) 0.792
Predicted
/observed 0.97 1.20
men
QRISK2 (2010) ASSIGN
Mean (95% CI) Mean (95% CI)
R2 45.9(45.4-46.4) 30.47(29.82-31.16)
D statistic 1.89 (1.87-1.91) 1.35 (1.33-1.37)
ROC value 0.830(0.828-0.833) 0.756
Predicted
/observed 0.95 1.20
References
1. de la Iglesia B, Potter JF, Poulter NR, Robins MM, Skinner J.
Performance of the ASSIGN cardiovascular disease risk score on a UK cohort
of patients from general practice. Heart 2010.
2. Hippisley-Cox J. Publication of the QRISK2 algorithm and release
of software for academics. BMJ. London: BMJ, 2009.
3. Hippisley-Cox J. 2010 update for QRISK2 and release of open source
software. BMJ. London: BMJ, 2010.
4. Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, May M,
Brindle P. Derivation and validation of QRISK, a new cardiovascular
disease risk score for the United Kingdom: prospective open cohort study.
BMJ 2007:bmj.39261.471806.55.
5. Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, Minhas R,
Sheikh A, et al. Predicting cardiovascular risk in England and Wales:
prospective derivation and validation of QRISK2. BMJ
2008:bmj.39609.449676.25.
6. Collins GS, Altman DG. An independent and external validation of
QRISK2 cardiovascular disease risk score: a prospective open cohort study.
BMJ 2010;340(may13_2):c2442-.
7. Collins GS, Altman DG. An independent external validation and
evaluation of QRISK cardiovascular risk prediction: a prospective open
cohort study. BMJ 2009;339(jul07_2):b2584-.
Conflict of Interest:
JHC is professor of clinical epidemiology at the University of Nottingham and co-director of QResearch - a not-for-profit organisation which is a joint partnership between the University of Nottingham and EMIS (leading commercial supplier of IT for 60% of general practices in the UK). JHC is also director of ClinRisk Ltd which produces open and closed source software to ensure the reliable and updatable implementation of clinical risk algorithms within clinical computer systems to help improve patient care. CC is associate professor of Medical Statistics at the University of Nottingham and a consultant statistician for ClinRisk Ltd. JR and PB were previously members of the NICE Guideline Development Group for Lipid Modification of which JR was chair.
Mr first thought on seeing this article was "how does this (MTAC) fit in with the MHRA?" I did a search of the .pdf and to my surprise there was not a single mention of the MHRA. Why do we need yet another pseudo- committee (quango)? Will new "devices" need to be "evaluated" by both bodies? Will they speak to each other? Is MHRA giving up some of its powers? Has MTAC even heard of MHRA and vice versa? What a mess. Why is t...
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...
We read the article by Sivapalaratnam and colleagues with great interest. Although, self-reported family history of coronary heart disease (CHD) was an independent risk factor for future CHD events in this study, the addition of family history of CHD to Framingham Risk Score (FRS) failed to improve the overall risk prediction of future CHD events. Since age is a heavily weighted risk factor incorporated in the contempora...
To the Editor,
The article by Gray et al is a succinct and useful summary of NICE clinical guidance 94 on the management of unstable angina and non ST elevation myocardial infarction (1). The NICE document is itself a major piece of work which synthesises vast bodies of evidence (2). The majority of the document and the resulting summary to which we respond are to be applauded. However, we believe the risk stra...
To the Editor: We appreciate the work by Hall?n et al. which reported a single-point measurement of cardiac troponin-I (cTnI) 24- or 48-hours after primary angioplasty for those with ST-segment elevation myocardial infarction (STEMI) provides substantial prognostic information on the evolution of left ventricular (LV) function and the risk of LV expansion.(1) Actually, a single level of cTnI after primary angioplasty is...
In their recent paper[1], the authors describe the performance of ASSIGN and Framingham algorithms in comparison to the original QRISK equations.
Readers may be interested that the QRISK2 algorithm was published in February 2009[2] and made available as free open source software in April 20103. This can be found at http://svn.clinrisk.co.uk/opensource/qrisk2/. The open source is intended to further increase the...
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