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Rapid Responses: Rapid Responses published:
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Beyond the risk factors.
- Sergio Stagnaro (28 June 2002)
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But thresholds for treatment do exist..
- Leslie S Lewis (29 June 2002)
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Is The Threshold is £37K Per QALY?
- Michael A Soljak (2 July 2002)
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Risk of lowering risk factors
- Gregor Caspari (2 July 2002)
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what are we trying to prevent
- David Rillstone Robertson (4 July 2002)
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Risk factor modification must be evidence-based
- Mark J Garton (7 July 2002)
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Argument is not supported by the data
- Adam Jacobs (9 July 2002)
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Dynamic CHD risk profiling for focused recall
- John M. Waddell, Paul Murphy, Darren Balsdon, David Brown (11 July 2002)
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Lives at risk
- Dougal J Jeffries, Isles of Scilly TR21 0HE (11 July 2002)
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Pharmacological treatment determined by age alone - a step too far?
- Steven M Laitner (12 July 2002)
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Association does not prove causation and is not the same as a dose-response relation.
- Uffe Ravnskov, Joel M. Kauffman, Peter H. Langsjoen, Kilmer S. McCully and Paul J. Rosch (16 July 2002)
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Potentially a very dangerous paper indeed
- Malcolm E Kendrick (18 July 2002)
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Sergio Stagnaro, Specialist in Blood, Gastrointestinal, and Metabolic Diseases. Rsearcher in Biophysical Semeiotics. Via Erasmo Piaggio N° 23/8, 16037 Riva Trigoso (Genoa) Italy
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Sirs, on the basis of 45-year-long clinical experience, I agree completely with Law MR. and Wald NJ (1), who rightly states that “They are not direct environmental causes of disease, like smoking, but they may be seen as biochemical or biophysical variables, under partial genetic control, that are intermediates between environmental factors and disease itself”. Please, See my site HONCode ID. N°233736, http://digilander.iol.it:semeioticabiofisica: Biophysical-Semeiotic Constitutions, as well as the Page, I hold weekly in the italian site www.katamed.it, Semeiotica Biofisica, the article N° 13 “Oncological Terrain” (2, 3, 4). As a matter of fact, smokers without “oncological constitution”, i.e. Oncological Terrain, are and will surely not be involved by any cancer, as allows us to state a large number of clinical evidence. Certainly, interventions to lower blood pressure, serum cholesterol, and other risk factors [such as IIR (!)] reduce the risk of cardiovascular disease regardless of initial levels, even reducing them as much as possible (1). However, in my opinion, we must go “beyond the risk factors”. In fact, Primary Prevention of the most common and dangerous human pathologies, e.g. malignancies, depends clearly by easy and quick bed-side detecting individuals at "real" risk, i.e. involved by well- defined biophysical-semeiotic constitution, assessed clinically in “quantitative” way (5). In order to define clinically a “particular” constitution, which does not exclude the presence of others, 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. Without any doubt, these data can not be observed at all by the aid of traditional physic semeiotics, unable of carrying molecular-biological events to clinical dimension, which really represents the most original and fertile aspect of Biophysical Semeiotics. Not to speak, obviously, of sophysticated semeiotics, despensive and unable to be performed on very large scale. I am sure that going “beyond the risk factors” represents a new medical "Weltanschauung", which, therefore, needs open-minded physicians at the "peer-reviews", nowadays, unfortunately, very seldom to be find, even in "my" dear BMJ. 1) Law MR., Wald NJ. Risk factor thresholds: their existence under scrutiny. BMJ 2002;324:1570-1576 ( 29 June ). 2) Stagnaro S., West PJ., Hu FB., Manson JE., Willett WC. Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. [PubMed –indexed for MEDLINE]. 3) Stagnaro-Neri M., Stagnaro S., La “Costituzione Colelitiasica”: ICAEM- a, Sindrome di Reaven variante e Ipotonia-Ipocinesia delle vie biliari. Atti. XII Settim. It. Dietol. ed Epatol. 20, 239, 1993. 4) Stagnaro-Neri M., Stagnaro S., Diagnosi Clinica Precoce dell’Osteoporosi con la Percussione Ascoltata. Clin.Ter. 137, 21-27, 1991 [Pub-Med indexed for MEDLINE] . 5) Stagnaro-Neri M., Stagnaro S., Cancro della mammella: prevenzione primaria e diagnosi precoce con la percussione ascoltata. Gazz. Med. It. – Arch. Sc. Med. 152, 447, 1993. |
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Leslie S Lewis, GP Newport Surgery, Pembrokeshire SA42 0TJ
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Law and Wald make the case for addressing all risk factors,
according to the Absolute Risk of the condition in question. An otherwise masterly statement from the population
perspective is marred by some overstatements. 1. 'Dose-response relations have no threshold and yield
straight lines' By logarithmic transformation, most curves can be
straightened out, and many a 'threshold' thereby obscured. In the Lancet this same week, Shepherd (Lancet 2002; 359: 2271-73) shows how 'the
first cut is the deepest' as regards to cholesterol-lowering, and that attempts
to drive cholesterol further downward exhibits 'diminishing returns'. The 'proportional reduction' of Law & Wald's own
logarithmically-transformed graphs shows that lowering a diastolic BP of 110 by
10mmHg produces twice as much benefit as lowering a BP of 90mmHg. To clinicians and patients, as well as resource-managers,
this matters. 2. 'Treat anyone at high risk' Blood pressure lowering drugs should not be limited to
people with high blood pressure, nor cholesterol lowering drugs to people with
high serum cholesterol concentrations. Whilst I agree with the thrust of the argument that we
should target those at high-risk rather than those with a high risk-factor, we
have to recognise that without a sufficient amount of 'reversible risk-factors'
we have nothing to treat ! Hence the need for the later qualification 'Aim for a large
change to achieve a large benefit' which again directs therapy back towards
high levels of reversible risk-factors Furthermore, current CHD-preventative treatments fall into
two categories : Those modifying a known risk-factor, and those which are not
(eg: Aspirin, or Warfarin). Aspirin and
Warfarin can be aimed at everyone at high-risk, whether or not they have known
'reversible risks'. 3. 'Carry out only necessary randomised trials' Further Randomised trials ARE necessary to establish
reductions in risk from successively lower starting values. The claim that 'The evidence from large cohort studies,
however, makes this unnecessary' is a logical mistake. Cohort studies do not
take individuals at high-risk, subject them to potentially toxic treatment, and
record what outcomes occur ! Having constructed a mythical hybrid beast in Fig 4, Law
& Wald despatch their chimaera as implausible. A more plausible graphical hypothesis is as follows.. ^ | x O |
x | x U |
x | x T | x |---------------o---------------------------- C | x |
x O | x |
x M | x |
x E | x | S |_____________________________________ Risk Factor or
Treatment 'Dose' > xxx =
Risk/Benefit graph. --- =
Treatment/AdverseOutcome graph It is precisely to identify the 'o' point, where treatment
benefit exceeds treatment risk, that we need additional Randomised trials. Examples of this are a) Mild hypertension: No
Treatment benefit is yet discernible below 80-90 diastolic, and between 90-100
diastolic only those at high-risk can be shown to benefit. b) Atrial Fibrillation: Anticoagulation in Chronic
AF is indicated only where thrombo-embolism avoided (xxx) exceeds haemorrhage
induced (---). 4. 'Thresholds have been excluded .. ..down to cholesterol levels (3.8 mmol/l)26 and blood
pressure levels (118 systolic/76 diastolic)7 that are close to the prehistoric
levels (table 3). .. There must be lower limits to the physiological variables
we have considered, beyond which harm will arise: everyone needs blood
pressure, and cholesterol is essential for life. These lower limits are,
however, beyond Western values and not reached by current dietary or drug
interventions.' But thresholds of risk-benefit have been shown - eg:
Warfarin in AF and anti-hypertensives in mild hypertension.. 80 mildly hypertensive (diastolic 90-110) men need to be treated for ten years for
just one of them to avoid a stroke. Clinicians and Epidemiologists can agree the main point - 'the selection of
individuals for preventive treatment should be based [only] on a person's
absolute level of risk' if we drop the word [only]. Dr L S Lewis General Practitioner The Surgery Newport Pembrokeshire sam@newportpembs.freeserve.co.uk |
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Michael A Soljak, Strategic Intelligence Unit NW London Health Authority
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While I agree entirely with most of Professors Law's and Wald's conclusions with regard to risk factors, I cannot agree that, as a result, treatment thresholds do not exist. With regard to CHD risk factors, the recent Joint British recommendations (1) recommend starting treatment of high blood pressure at an absolute ten year CHD risk of 15%, and of a high lipid ratio at 30%. Strangely, neither these recommendations, not those of the Standing Medical Advisory Committee explain why these particular thresholds have been set. (Nor do they mention when treatment should be stopped!) But could or should it have something to do with cost? I think that, despite the article's title, Professors Law and Wald acknowledge this implicitly by stating that people at high risk should be targeted. There have been a number of published cost-effectiveness analyses of lipid-lowering drugs. The report from Pickin et al (2)puts the cost per (presumably good quality) year of life gained of treating CHD risk above 3% per year at £8,200, which they describe as "as cost effective as many treatments in wide use". On the other hand they state that treatment below this level is unlikely to be affordable". However the de facto threshold currently being used by the National Institute of Clinical Excellence is considerably higher- about £37K per QALY. Ethical questions such as the value the NHS, and other health systems, should place on preventative rather than immediately lifesaving care remain largely undiscussed. Perhaps that is why so many authors overlook that resources are scarce and so thresholds must always exist. Isn't it time that this collective blind spot was removed? No competing interests References (1) British Cardiac Society et al. Joint British recommenadtions on prevention of CHD in clinical practice. Heart 1998; 80(supplement 2):S1- S29. (2) Pickin DM, McCabe CJ, Ramsay LE et al. Cost effectiveness of HMG-CoA reductase inhibitor (statin) treatment related to the risk of CHD and cost of drug treatment. Heart 1999; 82: 325-332. |
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Gregor Caspari Institut für Transfusionsmedizin, Hochstr. 29, D-14770 Brandenburg an der Havel
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The logarithm of incidence of ischemic heart disease may be proportional to several risk factors such as diastolic blood pressure, serum cholesterol, and body mass index. The authors draw the conclusion that more interventions are justified than are currently performed aiming to reduce even moderately or hardly elevated risk factors. How would a non -zero risk of the intervention itself affect that conclusion? Wouldn’t there be a level of risk factor at which the risk of the intervention outweighs the benefit of further lowering the risk factor? Thus the risk of intervention would set a threshold for lowering risk factors to be useful for the patient. |
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David Rillstone Robertson, GP Shirley Medical Centre ChCh New Zealand
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When we talk about prevention and absoloute risk we have to consider what we are actually trying to prevent. In the case of an MI for instance are we simply trying to prevent the pathologic event (platelets sticking to plaque in coronary artery) or are we trying to prevent the sequelae of that pathologic event on the human organism involved (death, sadness of loved ones and family, loss of income, decrease in quality of life- the list goes on). There is a very big distinction. If,for instance, we want to achieve maximum reduction of pathologic events for a given amount of statins and ace inhibitors then we should take everybody under the age of 75 off these agents and put every over the age of 75 on them. If there wasn't enough of the "given amount" to treat everybody over the age of 75 then we should restrict the treatment to those at even higher risk, lets say those over the age of 80, unless all ready in a rest home or hospital, as the younger people in rest homes are still at high risk. This would a much better "value for resourses" in terms of preventing "pathologic events" than our current policy. If as health proffesionals we are interested in reducing human suffering of the affected individual and their family and friends then we need to take quite a different approach. |
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Mark J Garton, Consultant Physician and Rheumatologist Perth Royal Infirmary, Perth PH1 1NX
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EDITOR-Wald and Law1 explore the log-linear association between certain physiological variables, such as serum cholesterol and bone mineral density (BMD), and their related diseases. Proportional risk increments, they argue, should translate into similar risk reductions if risk factor levels can be reversed. Moreover, the risk of disease ‘can be judged…reversible’ across the entire distribution of a risk factor, provided randomised controlled trials confirm benefit in subjects with high levels of that risk factor. They conclude that treatment should reflect absolute rather than relative risk, and that threshold-based protocols are inappropriate. However these recommendations must be viewed with caution, because the assumptions on which they rest are frequently undermined by clinical evidence. For example, drug-induced improvements in BMD neither fully explain2 nor guarantee reductions in recurrent osteoporotic fractures. In primary prevention, alendronate reduces absolute and relative risks of first vertebral fracture, but benefit is inversely related to baseline bone mass, and absent at T scores > - 2.0.3 Whether such thresholds exist for reductase inhibitors in coronary heart disease (CHD) is unclear.1,4 Secondary prevention trials have confirmed that simvastatin (4S) and pravastatin (CARE and LIPID) lower LDL cholesterol and reduce CHD outcomes in patients with average lipid profiles.4 Subgroup analyses of the pravastatin studies suggest attenuation or loss of CHD benefit if baseline LDL concentrations are <3.2 mmol/l, while 4S excluded this group. Contemporary guidelines4 and clinical practice have reflected this uncertainty, although fresh evidence suggests that simvastatin is effective in reducing vascular events well below this threshold.5 There are various reasons why interventions may produce unpredicted results. Drugs designed to reverse risk factors may have other important pharmacodynamic effects, which may be unmeasured or unknown. Some risk factors are difficult to measure and surrogates may be unreliable, while other alleged risk factors may in reality be risk markers. BMD reliably predicts native bone strength, but may not fully capture biomechanical changes (positive or negative) in response to treatment. The cholesterol/CHD hypothesis is persuasive, but statins do more than lower cholesterol, and benefit may relate to plaque stabilisation and improved endothelial function. This may help explain why the risk of vascular events in the Heart Protection Study5 was positively correlated with baseline levels of LDL cholesterol in the placebo group, but unrelated to percentage reductions in LDL cholesterol in the treatment group. Wald and Law rightly focus attention on absolute rather than relative risk, but therapeutic decisions should still be based on empirical evidence rather than theory. Mark Garton consultant physician Medicine and cardiovascular directorate, Perth Royal Infirmary, Perth PH1 1NX 1. Law MR, Wald NJ. Risk factor thresholds: their existence under scrutiny. BMJ 2002:324;1570-6. 2. Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, et al. Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 2002:112;281-9. 3. Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures. JAMA 1998;280:2077 -2082. 4. Scottish Intercollegiate Guidelines Network (SIGN). Secondary prevention of coronary heart disease following myocardial infarction. Edinburgh:SIGN;2000. 5. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high risk individuals. Lancet 2002;360:7-22 |
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Adam Jacobs, Director Dianthus Medical Limited, London SW19 3TZ
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Law and Wald base their argument against thresholds on a set of graphs of dose-response relationships, which they tell us exclude a threshold within the range of population values. A closer look at the graphs makes this hard to believe. In the text we are told that 'the 95% confidence intervals about the risk estimates exclude a threshold within the population range of values, so that the lower the risk factor the lower the risk: no part of the dose- response relation would fit a horizontal line'. This seems to be true only of the relationship between diastolic blood pressure and ischaemic heart disease or stroke, and between serum cholesterol and ischaemic heart disease. In the other four pairs of graphs, the confidence intervals for the two points at lowest risk overlap. In other words, the data seem to be consistent with a threshold somewhere between the two lowest points shown. |
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John M. Waddell, GP Principal Cramlington Northumberland BlythValley Clinical Governence Group Health Centre Forum Way Cramlington Northumberland NE23 6QN, Paul Murphy, Darren Balsdon, David Brown
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We have instigated a project, which gives dynamic updated full or estimated risk scores to the whole of the eligible population in the PCG (Blyth Valley, Northumberland). One of the main clinical computer systems is used universally here with the Framingham equation in-built. All in the eligible population (30- 74 without established cardiovascular disease) may have the scores calculated automatically electronically by the system, then allocated coded in to their computer records. The scores are updated routinely as the parameters change. Where some of the seven parameters are missing an Estimated risk score may be allocated. The system also corrects where the wrong category of score has been entered. The risk profile for any sub- population may then be, fairly instantly, presented and the names of individuals in any band given. Those at highest Full or Estimated risk can be recalled for intervention and groups at intermediate Estimated risk in any target group (e.g. hypertensives or those with family history) picked out by degree so that the Full score may be calculated by completing e.g. the HDL or ECG. This system, we feel, is the most precise way to focus resources to attempt the NSF standard 4 about which the public health group form Birmingham (1) were correct to be sceptical . It also allows a more sophisticated way of deciding thresholds not only at absolute risk levels but at optimum age-risk to maximise life-years gained-free-of-events (2). Our scheme has involved a combination of IT development with governance and training initiatives for clinicians and practice administration. It has allowed a more convincing dialogue with patients and provided reassurance that that some individuals need less monitoring than others. We hope that from it an evidence base for more focused primary prevention may come. 1-Rouse A. and Adab P. Is population coronary heart disease risk screening justified? A discussion of the National Service Framework for coronary heart disease. J R Coll Gen Pract 2001;51;834-837 2-Ulrich S. and Vallance P. What is the optimal age for starting lipid lowering treatment? A mathematical model BMJ 2000;320:1134-1140 3-McManus et al. Comparison of estimates and calculations of risk of coronary heart disease by doctors and nurses using different calculation tools in general practice: cross sectional study BMJ 2002;324:459-464 |
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Dougal J Jeffries, gp St Mary's Health Centre, Isles of Scilly TR21 0HE
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Shortly after the publication of Law & Wald's article on risk factor thresholds (or lack of), the national media gave massive publicity to the recent Lancet study suggesting that statins should be used much more widely, because of their benefits even at relatively low lipid levels. One national broadsheet quoted an eminent cardiologist as advising GPs to ignore NHS guidelines and begin widescale prescribing 'immediately'. I sometimes - well, quite often - wonder if consultants have any idea of the daily lives of their GP colleagues, and this is a case in point. Not only are we faced with constant downward pressure on our prescribing costs, which would be blown through the roof by the measures proposed. What depresses me more is the fact that an ever increasing proportion of our time is taken up with trying to manage legions of perfectly well individuals who - having submitted to the friendly-sounding offer of a 'well-person check' - find themselves the subject of risk factor analysis. Next they are asked to adopt the role of compliant patient while we carry out more blood tests and ECGs, and soon they are taking two, three or four drugs, entered on a 'disease register', and called back for examinations and investigations until released by death. What is truly sickening in all this is that while we in the affluent world spend exorbitant sums on drugs to postpone by a year or two deaths caused by normal ageing processes, the vast majority of the world's population hasn't even enough to eat. Let's get things in perspective: how about being prepared to take a few risks in our stride for once? Dougal Jeffries
Competing interests: none, apart from an already overspent drug budget. |
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Steven M Laitner, Specialist Registrar, Public Health National Screening Committee, Institute of Health Sciences, Old Road, Headington, Oxford OX3 7LF
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EDITOR - Law and Wald(1) provide evidence for the absence of thresholds in the relationship between risk factor and disease. They conclude that those with high absolute risk will benefit from risk factor reduction whatever their initial risk factor level. They go on to suggest that “in people without cardiovascular disease, intervention to change risk factors could be introduced when a person's risk of a disease event over the next few years exceeds a specified value. Risk could be estimated from age alone or age and sex………individuals at high risk should receive drug treatment to modify all important reversible risk factors simultaneously.” Whilst combination pharmacological cardiovascular risk factor reduction for the whole elderly population represents an ideal strategy for the pharmaceutical industry it has a number of limitations as a public health strategy: 1. By setting an absolute risk threshold for treatment (determined by age only) the proposed strategy still targets only those at high risk of disease (the tail of the population distribution curve of risk factors) and therefore can only have a minimal effect upon the overall burden of disease in the population. 2. There will be major opportunity costs in treating the whole elderly population with combination drugs and consequently other preventative, treatment, care and rehabilitation services for the elderly would be constrained. 3. The authors’ statement that lower limits of thresholds (such as blood pressure), beyond which harm will arise, are not reached by current drug treatment is false - the risks of polypharmacy in the elderly are significant(2,3) and would be increased 4. Even in the elderly, absolute risk of CHD may not reach 3% per year without additional risk factors such as smoking and diabetes. According to the Framingham Coronary Risk Prediction Score(4), a man aged 70-74, total cholesterol 5.18-6.21 mmol/l, HDL 1.17-1.29 mmol/l and blood pressure (140-159)/(90-99) has an CHD risk of 2.5% per year; for a woman the risk is only 1.3%. Targeting people who have had a vascular event or who are diabetic, with risk factor reduction treatment is an appropriate “high-risk” strategy. The only appropriate strategy, as challenging as it may be, to reduce the risk of vascular disease in the rest of the population (who cause most of the burden of disease) is to reduce the average levels of risk factors in the population, through the promotion of a healthy diet, exercise and smoking cessation. Proposals to use drug treatment for primary prevention in the whole population over a certain age should be resisted. Steven Laitner Competing interests: none 1. Law MR,.Wald NJ. Risk factor thresholds: their existence under scrutiny. BMJ 1929;324 :1570-6. 2. Beyth RJ,.Shorr RI. Epidemiology of adverse drug reactions in the elderly by drug class. Drugs & Aging Vol 1999;14:231-9. 3. Malhotra S, Karan RS, Pandhi P, Jain S. Drug related medical emergencies in the elderly: role of adverse drug reactions and non- compliance. Postgrad Med J 2001;77:703-7. 4. http://www.nhlbi.nih.gov/about/framingham/risktmen.pdf . 2002. |
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Uffe Ravnskov Magle Stora Kyrkogata 9, S-22350 Lund, Sweden, Joel M. Kauffman, Peter H. Langsjoen, Kilmer S. McCully and Paul J. Rosch
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Law and Wald posit that physiological variables believed to be associated with a disorder should be reduced irrespective of their initial value if a dose-response relation can be demonstrated between the variable and the disease (1). This is a puzzling proposal that primarily appears to be an ad hoc attempt to discredit numerous observations that contradict current concepts about the cause of cardiovascular and other diseases. It is not only in conflict with the literature but also violates the principles of medical science for the following reasons. By selecting biochemical and biophysical variables that allegedly induce illness they have confused causation with association. For instance, while hypertension is an established risk factor for coronary heart disease at all ages and in both sexes, most high blood pressure-lowering trials have shown no reduction in coronary or total mortality in women and younger individuals (2) and in many studies, no effect has been demonstrated on male mortality either (3). This clearly indicates that hypertension is not a causa vera of coronary heart disease and "risk marker" would be a more appropriate description. Selecting the MRFIT study to support evidence for a causal role of high cholesterol for coronary heart disease is similarly a poor choice since more careful analysis of the data does not support this conclusion (4). In addition, Law and Wald have chosen to ignore the many studies that found an absence, and in some instances, an inverse correlation between blood cholesterol levels and the incidence of coronary events (5). Perhaps the most egregious error is that Law and Wald use results from cohort studies as evidence of dose-response relations. As they themselves admit, dose-response implies that a given change in the variable should reduce the likelihood of a disease by a constant proportion of the existing risk. But in most of the studies they have chosen as evidence of dose-response, no risk factor was changed. What these studies recorded were instant observations of risk factors and disease and therefore they cannot prove or disprove dose-response. A recent review has shown that true dose-response, or preferably, exposure -response, was absent in almost all cholesterol-lowering angiographic trials as assessed by the degree of atherosclerosis growth (5). Changes in blood cholesterol bore no significant relationship to the degree of atherosclerotic progression, clearly indicating that the development of atherosclerotic plaques has nothing to do with blood cholesterol. Also, in the only clinical statin trial where exposure-response was analysed, the extent of LDL-reduction was not a significant predictor of the coronary event rate, whether expressed as an absolute amount (p=0.97) or a percentage (p=0.76)(7) Law and Wald think that an important cause of heart disease that is highly correlated with serum cholesterol is not known. May we remind them that several potential etiologic influences satisfy this description. Smoking, lack of exercise, obesity, hypertension, emotional stress (6) and hyperhomocysteinemia (8) are factors that are associated with high cholesterol. All of these may contribute to cardiovascular disease by mechanisms other than raising serum cholesterol or lipid levels. 1. Law MR, Wald NJ. Risk factor thresholds: their existence under scrutiny. BMJ 2002;324:1570-6. 2. Måttligt förhöjt blodtryck. SBU-rapport nr. 121. Stockholm 1994. 3. Hebert PR, Moser, M, Mayer J, Hennekens CH. Recent evidence on drug therapy of mild to moderate hypertension and decreased risk of coronary heart disease. Arch Int Med 1993;153:578-81. 4. Werkö L. Analysis of the MRFIT screenees: a methodological study. J Intern Med 1995;237:507-18. 5. Ravnskov U. The Cholesterol Myths. New Trends Publishing, Washington DC 2002, p. 58-64. 6. Ravnskov U. Is atherosclerosis caused by high cholesterol? QJM 2002; 95:397-403. 7. Sacks FM, Moye LA, Davis BR, Cole TG, Rouleau JL, Nash DT, Pfeffer MA, Braunwald E. Relationship between plasma LDL concentrations during treatment with pravastatin and recurrent coronary events in the Cholesterol and Recurrent Events trial. Circulation. 1998;97:1446-52 8. Refsum H, Ueland PM, Nygard O, Vollset SE.. Homocysteine and cardiovascular disease. Annu Rev Med. 1998;49:31-62. |
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Malcolm E Kendrick, Medical Director Lifelong Learning Partnership
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As Law and Wald previously established in their equally illogical paper on the 'Time Lag Hypothesis' the French risk factors in men aged 45 - 64 are as follows: French Risk Factors (From Law and Wald) TC 6.1mmol/l Systolic BP (their previous 'best BP risk factor') 150mmHg HDL 1.3mmol/l smoking 32% (Add to this figures (from BHF) average BMI 26.6 those never exercising 32% CHD rate 128/100,000/yr UK risk Factors TC 6.2mmol/l Systolic BP 148mmHg HDL 1.3mmol/l Smoking 29% Average BMI 26.6 Those never exercising 24% CHD rate 487/100/000/yr Can Law and Wald fit these figures onto their semi-logarithmic scale please. The suggestion that no levels of any 'risk factor' in the Western World are currently 'normal,' and that what we call a normal blood pressure is actually high, and should be lowered is dangerous nonsense. Are Law and Wald aware of figures from Framingham which clearly demonstrate that falling cholesterol levels are direclty associated with an increased risk of CHD? 'There is a direct association between falling cholesterol levels over the first 14 years and mortality over the following 18 years (11% overall and 14% CVD death rate increase per 1 mg/dL per year drop in cholesterol levels). Anderson KM JAMA 1987 Are they aware of research by Marmot in Japan that demonstrates a completely inverse relationship between rising cholesterol levels and deaths from CHD. ' Considerable increases in total serum cholesterol levels do not offer an explanation of the recent decline in mortality from coronary heart disease in Japan.’ Okayama A, Marmot MG Int J Epidemiol Dec 1993 There are literally hundreds of papers which totally contradict the association between 'raised' cholesterol levels and death from CHD. Shestov in his Lipid Clinics study in Russia even showed an inverse relationship, with higher rates of CHD in hypocholesterolaemics. The Honolulu study clearly demonstrates that, in those over fifty, a low cholesteorl level is by far the most important risk factor for premature death ‘Our data accord with previous findings of increased mortality in elderly people with low serum cholesterol, and show that long-term persistence of low cholesterol concentration actually increases the risk of death. Thus, the earlier that patients start to have lower cholesterol concentrations, the greater the risk of death.’ Lancet 2001. There is one curve, with regard to cholesterol lowering, that they have not shown. Namely, the J shaped curve of total mortality with 5.2mmol/l at the bottom of that curve. Law and Wald are, effectively, suggesting that almost everyone in the Western World should be put on some kind of medication. This is dangerous nonsense, and we should not be afraid to say so. Dr Malcolm Kendrick |
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