Mild hypertension in people at low risk
BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g5432 (Published 14 September 2014) Cite this as: BMJ 2014;349:g5432
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Letter to the Editor of BMJ
I read with interest the analysis " Mild Hypertension in people at low risk by Stephen A Martin et al.(1).
I agree that many patients with so called mild hypertension are being treated with drugs inappropriately. However, I have the following comments to offer as they need serious consideration if BP continues to remain uncontrolled despite lifestyle measures:
1) Now classifying and using the term mild for hypertension is obsolete as in almost all the recent guidelines (JNC 7 2003, JNC 8 2013, NICE 2011, CHEP 2013, European 2013) the term used is stage 1 Hypertension (BP 140-159/90-99 mmHg) and not mild hypertension. This is largely because the term mild may undermine the risk accrued even at this level of BP (140-159/90-99 mmHg) - at least in some patients.
2) Many patients with stage1 hypertension also have a concomitant masked hypertension response on ambulatory BP monitoring, and if not treated, they may have adverse consequences.(2)
3) Many patients with so-called low-risk stage 1 hypertension, infact on detailed assessment may also have many hidden high-risk factors like metabolic syndrome, obstructive sleep apnoea syndrome, strong positive family history of premature CAD, etc. Conventionally they fall into the category of low risk. If their BP is not controlled below 140/90, they may also carry high cardiovascular risk.
4) Moreover, it has been estimated that in a patient with stage 1 hypertension (BP 140-159/90-99 mmHg) a reduction of 12 mmHg over a 10-year period will prevent 1death for every 11 patients treated.(3)
Conflict of interest: None
References
1. Stephen A Martin, James M Wright, Vikas Saini. Mild hypertension in people at low risk. BMJ 2014;349:G5432 doi:10.1136/bmj.g5432
2. Pierdomenico SD, Lapenna D, Bucci A, et al.Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant,and true resistant hypertension. Am J Hypertens.2005;18(11):1422-1428
3. Chobanian AV, Bakris GL, Black HR, et al.The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA.2003;289(19):2560-2572
Competing interests: No competing interests
Thank you for your comments and historical perspective. I have also been struck with the wisdom of Sir George Pickering. In reviewing the history of this subject I came across his dinner speech at the New York Academy of Science’s 1977 Symposium “Mild Hypertension: To Treat or Not to Treat” (1). I’d appreciate sharing these excerpts:
“The subject of this symposium illustrates the nature of the conflict between the science and practice of medicine. The scientist never comes to a conclusion until he has hard evidence on which to base it; he is prepared to wait indefinitely until he has. By contrast the physician dealing with a patient has to act; he cannot wait; he has to make a decision based on a careful consideration of what evidence there actually is. The hard evidence as to the benefit or otherwise of treating mild hypertension will come from a well-planned and well-conducted randomized controlled clinical trial. There is no substitute. Anything else is merely guesswork. Several such trials are now being planned; when they are complete we shall have an approximation to the hard evidence of science.
… The physician must also know that the height of the arterial pressure is not the only factor in producing a given kind or intensity of arterial disease. We know the other factors most intimately in coronary artery disease. They are: age, serum cholesterol, the male sex, the number of cigarettes smoked, lack of exercise and obesity. ...
… The third and extremely inconvenient fact is that the arterial pressure is extremely variable. ...
…. The physician should also be aware of the hazards of investigation and treatment.”
(1) Pickering GW. Dinner Speech by Sir George Pickering. Ann N Y Acad Sci 1978;304:466–71.
Competing interests: No competing interests
We appreciate Prof. Nilsson's sense of the article and this opportunity to reply.
We agree with risk-based assessment as supported by this recent Lancet article. We also appreciate how the 2013 ESH/ESC Guidelines reflect this understanding. However, this is not the US approach. We are not describing the past but very much the North American present.
The WHO estimate of hypertension’s contribution to cardiovascular death is questionable. Other models have produced estimates as low as 9% for the proportional reduction in deaths from coronary heart disease from the treatment of hypertension (1).
(1) Jones DS, Greene JA. The contributions of prevention and treatment to the decline in cardiovascular mortality: lessons from a forty-year debate. Health Aff (Millwood) 2012;31:2250–8. doi:10.1377/hlthaff.2011.0639
Competing interests: No competing interests
We appreciate Dr Padwal’s sense of the article and this opportunity to reply. We read his response as identifying the following deficits in the article: 1) Lack of current success with behavioural modification; 2) The guidelines we reviewed were outdated; 3) The need for global risk assessment; 4) The future of RCTs in this area; 5) Home monitoring; and 6) The number of measurements to obtain.
Please see below for our reply to each area:
1. We very much share this interest in behavioural modification. Guidelines do continue to advocate for a lifestyle approach. Compared with medication development and dispersal, however, there has been virtually no investment in this approach. Drugs and flawed payment models have crowded out behavioural modification. In practice, this makes it far easier to scale the writing of a prescription compared with the longitudinal effort needed to change behaviour in a culture that sends mixed signals about health. The burden to change cannot be placed fully on an individual patient and clinician.
We do have models that are successful. They seem to work best as partnerships with community groups, not as isolated clinic visits. In the US, the YMCA has adopted the Diabetes Prevention Program protocols to strong effect (1).
Drug prescribing is also flawed in its effectiveness, with the majority of people stopping their antihypertensive medications as we noted. We see benefit in addressing medication concordance especially for those at high risk, and credibly bringing behavioural modification into the spotlight for all.
(1) Ali MK, Echouffo-Tcheugui J, Williamson DF. How effective were lifestyle interventions in real-world settings that were modeled on the Diabetes Prevention Program? Health Aff (Millwood) 2012;31:67–75. doi:10.1377/hlthaff.2011.1009
2. Our article reflected the most current updates, reaffirmations or not. We highlighted the Canadian, UK, and European guidelines for their thoughtful approach. We see the conflict in US guidance authorities as emblematic of the overall problems with guideline development in general.
3. We agree that global risk assessment should be established for an individual patient and mentioned this in the article. These are important questions. In the US, blood pressure treatment based on global risk assessment has not even been broached.
4. Large simple RCTs in people with mild hypertension need not be expensive and certainly should not be funded by the drug Industry. Randomization is inexpensive, many of these patients are being treated already, and the important outcomes of interest (mortality, hospitalization, etc.) are being collected at present in developed countries. We agree with most of the questions being asked and the only way to properly answer those questions is to conduct such trials. Health systems, which are currently spending billions annually on drug treatment, should see this as a worthy investment.
5. We agree with the suggestions for obtaining accurate resting home BP measurements. We dedicated a full table (Table 3) to highlight incorrect measurement.
6. Our recommendation was that at least two measurements be obtained at any given time, not in total.
Competing interests: No competing interests
Many years ago our practice was involved in the MRC mild hypertension trial (BMJ 1985 Jul 13; 291(6488):97-104). This was a double-blind placebo-controlled trial, and considerable effort was taken to try and avoid spuriously high readings (at least three raised readings before entering the trial, ten minutes rest before any reading, random zero sphygmomanometers etc). One of the lesser publicised results was that about half of the trial patients who had been put on placebo had unequivocally normal blood pressure after the end of the trial (approximately 5 years); so as with many trials the results, which were mostly negative, were spoilt because a lot of patients with normal, but temporally raised BP, were included, seriously diluting any possible benefit.
Some of those with raised blood pressure undoubtedly had white-coat hypertension, but with at least some it seems more plausible that they did have genuinely raised blood pressure for a period of time, which then reverted to normal. Blood pressure fluctuates, mostly upwards, due to many causes, and a possible model of the cause of essential hypertension is that if it is raised too much for too long then when it fluctuates down again it does so to a permanently higher value – and in some cases in the end to levels where treatment would be beneficial. The cause of this possible process of up-regulation is of course unknown, but if it exists I suspect that it is renal, corresponding to the observation that ACE inhibitors often seem to be the best option for treating hypertension in younger patients; they have fewer chronic problems which can lead to permanently raised blood pressure, factors which would mask such a renal mechanism for patients with only a temporary rise.
So how should we treat hypertension? Firstly the patient themselves should be involved as much as possible; the uncertainties should be explained carefully, and well-written leaflets could be very helpful. In particular of course lifestyle changes should be discussed and strongly encouraged where appropriate. The patients will need full assessment with appropriate tests as we do currently. The majority will then be declared ‘essential’, and for drug therapy I suggest the following, if it is agreed by the patient:
1. For severe hypertension i.e. systolic greater than 180, diastolic greater than say 110. These patients should be treated as they are currently; there is plenty of evidence that there is significant net benefit.
2. Patients with rather lower values but with other diseases such as chronic renal disease, diabetes and/or previous cardiovascular disease should also be treated, again as evidence-based.
3. Milder cases but with no other significant morbidity should be observed say monthly for six months; if the blood pressure still remain raised they should also be treated, but perhaps annually after achieving target blood pressure they should be taken off therapy, and again observed monthly. If blood pressure rises again they should have therapy restarted; if not they should be observed further but less frequently.
This entails a lot more blood pressure measurements, but I have a proposal to make this more manageable. Firstly patients should be taught how to take blood pressure, and actually do all their own readings carefully in their own home; this should effectively eliminate white-coat hypertension. Wrist blood pressure machines are cheap, easy to use, reasonably accurate and much less affected by obesity. I am not sure all currently-available wrist machines will meet say the British Hypertension Society criteria for accuracy/reproducibility etc. so firstly suitable machines must be found by testing. Then the NHS might negotiate a seriously large bulk order or orders which would make the ‘NHS blood pressure machine(s)’ very inexpensive. These machines would be widely available, and patients who needed them because they needed frequent monitoring should initially be lent one, unless of course they wanted to purchase one right away. Anyone still needing frequent monitoring after say six months should be persuaded to buy one, which would be at a very attractive price, probably in the range £10-20. I suggest machines should be free for those on low income. Most people will of course have to pay, so the overall cost to the NHS will be modest and extra costs would be partly offset by savings on the drug budget. Since blood pressure readings would be taken and recorded almost entirely by the patients the extra medical input would mostly be assessing figures, which in the majority of cases could easily be done by say nurses: one of the most significant improvements recently in the delivery of health care has been to recognise and use nursing expertise. Overall the extra cost of such a system might in fact be very little more than what we are doing at the moment, since there should be fewer people taking treatment – and certainly fewer people taking treatment that does more harm than good.
Competing interests: No competing interests
Dear Sir,
I have to comment that the treatment of high blood pressure as a single risk factor is not the modern strategy to prevent cardiovascular disease. On the contrary, most modern and well-educated physicians today know that risk stratification should be based on total cardiovascular risk estimates when all relevant risk factors are taken into account, not only blood pressure itself. The benefits to treat hypertension over a range of risk strata was recently published in the Lancet but I lack a reference to this very important publication based on data on individuals participating in randomised clinical trials with antihypertensive drugs. The publication was this: Sundstrom J, et al. Blood Pressure Lowering Treatment Trialists' Collaboration, Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet. 2014 August 16 ;384(9943):591-8.
I cite from the publication: "Lowering blood pressure provides similar relative protection at all levels of baseline cardiovascular risk, but progressively greater absolute risk reductions as baseline risk increases. These results support the use of predicted baseline cardiovascular disease risk equations to inform blood pressure-lowering treatment decisions."
Therefore, the present Review paper in the BMJ, as well as the 2012 Cochrane Review on mild hypertension, both reflect the past, like pieces of the history of medicine, and not the present. Sorry for this!
WHO states that hypertension is the leading cause of mortality on a global scale today. The BMJ review undermines this statement as in reality there is a need to use cheap drugs (poly-pill) in a majority of patients with increased cardiovascular risk because lifestyle interventions alone will not be able to curb the age-related increase of blood pressure and risk factors globally.
The BMJ campaign to highlight and dicuss possible overdiagnosis and overtreatment in medicine is welcome in a general perspective. However, please consider not promoting perspectives opposite to the WHO view and the available evidence of today (Lancet 2014). This could otherwise prove to be both counterproductive and a blow to the respect for the BMJ, a journal much read also in Sweden.
Competing interests: I was a co-author of the 2013 ESH/ESC Guidelines on management of arterial hypertension. Currently I am a board member of the World Hypertension League (WHL). I have worked on national guidelines on prevention of cardiovascular disease caused by atherosclerosis in Sweden.
In the growing series of over-hyped, over-diagnosed conditions we can discern a pattern, even a paradigm.. DISEASE – SCREENING – FACTORS – RISK - MODIFIERS
In the case of ‘hypertension’, it began with a clinically recognisable DISEASE called ‘malignant hypertension’. We quickly learned that you were dead in six months if you didn’t start drug treatment. This gave rise to the desire to ‘screen’ for it in the hope of earlier diagnosis. By measuring a parameter such as blood pressure, rather than a disease, we entered a realm of statistical sampling. Dismissing Pickering’s warnings, we then defined a crude subset to be ‘mild hypertension’. We were wise to conduct randomised controlled trials of treatment, but seemed not to have examined the results closely enough. Instead our disease-oriented mindset was persuaded by pharmaceutical purveyors into 50 years of overtreatment, well beyond the few with ‘malignant’ disease. Martin et al demonstrate nothing that we was not already available to be recognised last century.
A similar behaviour pattern occurred when the parameter was cholesterol. But we were discerning enough to note that ‘hypercholesterolaemia’ was not really a disease (unless perhaps it was familial) and cholesterol-lowering treatments were often unpalatable or harmful. The battle against ‘cholesterol’ per se was losing. Then came Simvastatin – highly effective in 4S if you had suffered a heart attack. Trials quickly followed showing that the drug worked, regardless of your initial cholesterol, or LDL. What mattered was ‘CVD RISK’. That was the ‘paradigm-shift’ - an increasing understanding that a composite of multiple risk factors determined your absolute chances of a stroke or heart attack. Risk-factor treatments exposed everyone to potential side-effects, whilst those with most to gain were those most at risk. Having already suffered a heart attack, you are automatically recognised as high-risk. Age, sex, Diabetes and FH add in, and then come the modifiable parameters.
What Martin et al. need logically to do now is drop the term ‘mild hypertension’. Instead we need to assess ‘CVD Risk’ as a unifying paradigm determining who stands to gain, by which intervention, and by how much. RCTs have shown that people who have had CVD events, or have Diabetes are likely to gain by lowering BP maybe down to 130/80. Other RCTs show that men with BP of 150/90 and low CVD risk do not benefit from drug treatment, whilst healthy women, for example, with no ‘disease’ and low CVD risk do not benefit at all unless their BP is very much higher.
Competing interests: No competing interests
This is an excellent and very necessary article.
The publication of the 2012 Cochrane review highlighting the absence of direct evidence for drug treatment of mild hypertension created barely a ripple in the medical world yet should have profoundly shifted attitudes and practice.
As a medical student and over 20 years of postgraduate education, I had been led to understand that this intervention, supported (at varying levels) by guidelines, was a proven, evidence based recommendation. Most of my GP colleagues have the same understanding and we have been confidently medicating huge numbers of patients for three decades. The understanding that the evidence is so flimsy was a shocking revelation.
Treatment enthusiasts will invoke a surrogate end point argument as described and add that, well, we might just see a better result with modern drugs. Even if this speculation is correct (which it just could be), the likely gain for an individual patient contemplating treatment (as understood in terms of ARR and NNT) is likely to be far lower than what they may consider worthwhile (1).
We owe it to our patients to have a better understanding of the evidence and to offer them more nuanced advice about their treatment choices. Currently, most end up on medication and I wonder whether that would be the real choice of many if fully informed.
1) Patients’ responses to risk information about the benefits of treating hypertension. Misselbrook D, Armstrong A. BJGP 2001,51,276-279
Competing interests: No competing interests
Dr Raj Padwal includes in his rapid response the comment that there is a need for many repeated measurements to accurately assess the usual blood pressure. Based on my own experience, this is undoubtedly true, the more the better, and this should include blood pressures taken in the standing position and after moderate exercise, as I said in my own rapid response. Furthermore, when patients record their own blood pressures in the sitting position, they should be instructed to do so in a quiet environment, after 5 minutes rest, and should discard the first reading if it is much higher than the subsequent two readings. Some of those readings should be taken in both arms.
Office blood pressures should only be taken by a specially trained nurse (using a manual device such as a frequently calibrated aneroid sphygmanometer), in a quiet environment after 5 minutes rest (all mobile phones having been switched off!). This should also be an occasion for opportunistic screening for atrial fibrillation (for which hypertension is a risk factor) by checking the regularity of the radial pulse, all irregular pulses mandating an electrocardiographic reading immediately thereafter. These arrangements (which should finally banish the myth that all doctors are better than all nurses in measuring office blood pressure), of necessity, means a reorganisation of the way blood pressure follow up clinics are organised.
When an ambulatory blood pressure device is in place the patient should be instructed to ensure that at least a third of the measurements are taken in the standing position, including some measurements taken whilst walking. Reliance on ambulatory blood pressure measurements taken only in the sitting or in the supine position is unrealistic.
Competing interests: No competing interests
Re: Mild hypertension in people at low risk
Dear Sir,
the authors have now replied and question the importance of hypertension as a leading cause of mortality on a global scale according to the WHO. They mention that the contribution to coronary deaths might be lower than expected. It is completely strange that they orverlook the important role of hypertension on stroke mortality on a global scale, especially in the developing countries (1). Also in the US the trend is to look for global cardiovascular risk assessment according to recent AHA/ACC documents (2), not only hypertension. The authors seem not to be well informed on these developments and this is sad. In my opinion the BMJ Editors now have to comment on this burning issue in an official Editorial, otherwise many readers like me feel that the Editors support this anti-WHO view on hypertension as a major global public health problem. It resembles in a way the debate on statins for primary prevention in the BMJ some time ago (3), but this case is even more alarming because the WHO strategy connection. Please consider the pivotal role of the BMJ for accuracy and fairness in controversial matters related to public health and prevention. It is very remarkable to provide a different medical message than the WHO without editorial statements - and this could otherwise back-fire on the good reputation of the BMJ, a journal I respect. Is the Lancet that different after all? Many important papers there are very clear on the crucial role of hypertension as a major global health threat.
References:
1. Lawes CM, Vander Hoorn S, Rodgers A; International Society of Hypertension. Global burden of blood-pressure-related disease, 2001. Lancet. 2008;371:1513-8.
2. Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S49-73.
3. Godlee F. Statins and The BMJ (Editorial). BMJ. 2014;349:g5038.
Competing interests: See my previous letter.