Do the Right Thing?

This is my first venture into the world of blogging, so don’t be surprised if the tone of this entry differs to those of more polished writers. Given a platform to sound off I feel a bit spoiled for choice. But here goes.

In Philip K Dick’s 1968 dystopian novel “Do Androids Dream of Electric Sheep?” the protagonist, wrestling with his conscience, is told “Go and do your task, even though you know it’s wrong.” As an academic in public health I find myself in a dilemma. I have an interest in prevention of cardiovascular disease. My reading of the research evidence impels me to some quite clear conclusions about how to accomplish this. But I also have to teach. And I have to teach an orthodoxy that I don’t believe. I invite my readers’ thoughts on this dilemma.

The orthodoxy is that there is a condition called hypertension. We know there must be such a condition because there are societies and guidelines which embed this condition in very real societal structure.[1] [2] We have hypertension clinics and hypertension specialists. We have drugs licensed for hypertension. This condition must be diagnosed, which means categorising individuals as either hypertensive or normotensive. The most recent guidelines emphasise the need for technological gee-whizzery in the shape of 24 hour ambulatory blood pressure monitoring to assist this process. The condition must be treated: essentially with drugs. The drugs to be used are individually tailored to patients according to their age, sex and sometimes race. The patients are monitored and the drugs further tailored in the light of their response to treatment. The University of Birmingham helpfully runs a week long course for GPs to help them follow this orthodoxy. Case vignettes provided examples for clinical practice. These vignettes helpfully included discussion of the best treatment for a 22 year old woman with systolic blood pressure of 160 mm Hg. Multiple choice questions assessed the participants’ knowledge. I contribute to the teaching. Herein lies the dilemma.

Unfortunately most of the orthodoxy is nonsense. There is not really a condition called hypertension. Every living human being inhabits a continuum of risk of cardiovascular disease and blood pressure is just one of the factors influencing the continuum of risk.[3] Blood pressure alone does not offer any special insight into the chances of developing cardiovascular disease. The categorisation of individuals by risk would be arbitrary, but at least it has a clear relationship to something that matters: their chances of getting cardiovascular disease. The categorisation of individuals by their blood pressure is not helpful at all. We can trace this error back to the misty origins of medicine itself. Doctors categorise: sick and well. The categories are reified into diagnoses and shackled to treatments through the concept of “indications”. Specialists prosper. Indications become regulatory frameworks for medications and treatments. Pharmaceutical empires rise.

This matters. Nobody should care about their blood pressure. They should care about their chances of getting heart disease. Nobody should be given drugs to lower their blood pressure. They should be given drugs to reduce their chances of getting heart disease. It makes a big difference.

So what do we really know about blood pressure? We know that higher blood pressure is associated with a greater chance of getting cardiovascular disease. We know that drug treatments reduce that chance. But we also know blood pressure alone is not a great indicator of risk. Age is the strongest indicator of risk. If her blood pressure is really 160 mm Hg our 22 year old female has a probability of getting cardiovascular disease in the next 10 years of less than 0.2%. If treatment reduces her risk by a quarter we will treat 2000 such women for 10 years for one to benefit.[4]

Blood pressure is intrinsically variable. In essence this means that it is not measurable with any great degree of precision. So any categorisation of blood pressure also must include a measurement of mis-categorisation.[5] When high blood pressure is uncommon, the most likely explanation for a measured high blood pressure is chance variation. So anyone aged under 35 whose measured systolic blood pressure is >160 mm Hg after an average of three readings at separate clinic visits is much more likely to have had three chance high readings than to have truly raised blood pressure. The problem is slightly reduced, but not at all resolved by using ambulatory blood pressure monitoring.[6] First do no harm. There is no need to measure blood pressure in otherwise healthy young adults. It does little except put them at risk of misclassification. So it seems highly unlikely that our 22 year old female even has high blood pressure at all.

Put bluntly, our 22 year old probably does not have high blood pressure; any benefits from treatment are likely to be trivial; she would likely not have chosen to take treatment if anyone had told her this. Needless to say this was not the right answer helpfully provided by the hypertension specialists.

Blood pressure is hard to measure because it is so variable, but it is almost impossible to monitor reliably. By measuring blood pressure at two, three four or five consultations before treatment and again after treatment in the same individual, it is not possible to reliably know the effects of that treatment or even if the patient is taking their treatment.[5] [7] This is important. It means that every time blood pressure is measured and treatment changed as a result, chance has played at least as great a role in the change in treatment as any other factor. Yet the fact that we can’t monitor treatment accurately does not even matter much, because the effects of drug treatments vary little from one individual to another. The differences between different treatments at standard doses are trivial.[8] When it has been investigated it appears that almost all of the effects of treatment are attributable to drug dose and pre-treatment blood pressure and almost none to individual patient variation.[9] So the effects of treatment may be unmeasurable, but paradoxically they are largely predictable. As for tailoring treatments by age and sex and race, this hardly matters. The differences in response to treatment are too small to be detectable through measurement. Since almost everyone can benefit from two or three drugs it is irrelevant which drug class we consider “first line” since everyone will get drugs from two or three classes.

The solution is simple. Remember our purpose: to prevent cardiovascular disease, not to normalise blood pressure. We can identify who is most likely to be at risk using the most reliably recorded information we have: age and sex. These are untroubled by measurement error. We can refine that risk estimate with additional information: smoking and diabetic status. So far all of this is already recorded in the patient’s records. We can refine it further with more unreliable measurements like blood pressure and cholesterol levels, but often this is not necessary. Those unlikely to be at high risk (otherwise healthy young adults) need no blood pressure measurements, as no level of blood pressure will be worth treating. Those likely to be at high risk will benefit from treatment. We should prioritise them for action. We just need to reassure ourselves that their blood pressure is not so low that treatment will render them symptomatic. Precision is not necessary. Only those in the intermediate risk group might benefit from a more accurate estimate of their risk. Finally we can forget about all that monitoring of treatment effects. The drugs will work if patients take them. The measured blood pressure will vary during treatment. This makes for a rather different therapeutic relationship with the doctor.

And back to my dilemma. Do I continue to teach something I don’t believe? In the novel, the protagonist tries to evade the problem only to be told “You will be required to do wrong no matter where you go. It is the basic condition of life.” So what do I do? Should I go on teaching what I don’t believe or should I rock the boat?

–Tom Marshall, Deputy Director CLAHRC WM, Prevention and Detection of Diseases

References:
[1] British Hypertension Society. British Hypertension Society. 2012.
[2] National Institute for Health and Care Excellence. NICE Guidance – Hypertension (CG127). 2014.
[3] Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002; 360: 1903-13.
[4] ClinRisk Ltd. QRISK®2-2013 Web Calculator. 2013.
[5] Marshall T. When measurements are misleading: modelling the effects of blood pressure misclassification in the English population. BMJ. 2004; 328: 933.
[6] Marshall T. Measuring blood pressure: the importance of understanding variation. Rev Bras Hipertens [Braz J Hypertens]. 2005; 12(2): 75-82.
[7] Hayen A, Bell K, Glasziou P, Neal B, Irwig L. Monitoring adherence to medication by measuring change in blood pressure. Hypertension. 2010; 56(4): 612-6.
[8] Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009; 338: b1665.
[9] Bell KJ, Hayen A, Macaskill P, et al. Monitoring initial response to Angiotensin-converting enzyme inhibitor-based regimens: an individual patient data meta-analysis from randomized, placebo-controlled trials. Hypertension. 2010; 56(3): 533-9.

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One thought on “Do the Right Thing?”

  1. really interesting Tom, I would say “rock the boat” ! white coat syndrome isn another factor, so many of my patients were hypertensive in clinic but normotensive at home.
    Pam A.

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