PRedicting Out of OFfice Blood Pressure in the clinic (PROOF-BP)

Heart attacks and strokes are the main cause of death and disability in the developed world. Patients with high blood pressure (hypertension) are more likely to suffer a heart attack or stroke. The risk of this happening can be significantly reduced with drugs which lower blood pressure. Accurate measurement of blood pressure is therefore vital to ensure that patients with high blood pressure are recognised and treated appropriately.

New clinical guidelines recommend that blood pressure is measured for 24 hours to confirm patients with high blood pressure. Measuring blood pressure for 24 hours is obviously time consuming, but also expensive and often uncomfortable for patients. Despite this, it is recommended because it reduces the number of patients being incorrectly diagnosed with high blood pressure. Incorrect diagnoses occur because patients who are anxious when they visit the doctor's surgery often have high blood pressure which then decreases to normal levels when they return home. This is known as the white coat effect. These patients do not require treatment with blood pressure lowering drugs but may be prescribed them because the doctor doesn't realise that the reason their blood pressure is raised is because they are anxious. Incorrect prescription of these drugs may have bad consequences for the patient and is a waste of NHS money.

This project aims improve the accuracy of blood pressure measurement in the doctor's surgery and thus reduce the need for 24 hour measurements. Using a new blood pressure measurement technique, our pilot work suggests that it is possible to predict which patients have high blood pressure because they are anxious and which patients have true raised blood pressure requiring treatment. This new technique could identify which patients can be treated on the basis of blood pressure measurements made in the doctor's surgery and therefore reduce the number of patients needing to undergo expensive, uncomfortable, 24 hour measurement. It could therefore improve the quality of patient care and save money for the NHS.

The aim of this project is to establish how good this new technique is at predicting true blood pressure and whether it can be used on a day-to-day basis in the doctor's surgery. The effectiveness of this blood pressure measurement technique will be investigated using existing data collected from a typical population of patients in primary care. This analysis will establish the inputs required to develop a blood pressure measurement tool for use in the doctor's surgery. This tool will then be developed and tested it on patients from doctor's surgeries across Birmingham. The final stage of the project will involve comparing the performance of the new tool against the standard method of blood pressure measurement currently being used (patients with suspected high blood pressure being sent for 24 hour measurement) in the context of a clinical trial. Only the initial planning (pilot) for this clinical trial will be completed during this fellowship. Further funding will be sought to complete this clinical trial after the fellowship has concluded. The project will not involve the use of medicinal products (drugs) or human tissue.

The Fellow will conduct all analyses of existing datasets proposed in this project with the assistance of colleagues in the host institution. The development of a blood pressure measurement tool will be done with assistance from the IT programming team in the Primary Care Clinical Research and Trials Unit at the University of Birmingham.

Background
Accurate blood pressure (BP) measurement is important to ensure antihypertensive treatment is targeted appropriately. New guidelines recommend the use of the 'gold standard' out of office measurement to confirm all diagnoses of hypertension. Our own pilot work suggests that the characteristics of BP measured repeatedly in the clinic can be used to predict out office BP thus, reducing the need for expensive out of office measurement. This method of assessing clinic BP characteristics has only been evaluated in patients with uncontrolled hypertension. Further work is needed to translate this novel method into routine clinical practice.

Aims
1)Establish the predictive abilities of multiple clinic BP measurements for out of office BP in a general population.
2)Develop a 'triaging' tool which reduces the number of patients with suspected hypertension being referred for out of office BP measurement.
3)Pilot a clinical trial assessing general practitioner (GP) use of this triaging tool for patients with suspected and existing hypertension.

Methods
Using a dataset of approximately 1,400 patients (>18 years; white, South Asian or Black ethnicity from within the UK and Canada), BP characteristics from multiple clinic measurements will be estimated using polynomial regression modelling. These will be compared to out of office BP monitoring (ambulatory and home) and the predictive abilities of clinic BP for white coat and masked hypertension will be evaluated. Using the resulting diagnostic thresholds for these conditions, a web based tool for use in clinical practice will be developed. This will be piloted in GP practices in Birmingham, providing preliminary data to inform a full clinical trial.

Scientific/Medical opportunities
This work presents an opportunity to improve the diagnosis of hypertension and accuracy of routine clinic BP measurement. This could lead to significant cost savings and improved quality of care for patients with hypertension.

Cardiovascular disease is the leading cause of morbidity and mortality in the UK and around the world. The most significant, modifiable risk factor for cardiovascular disease is high blood pressure and in the UK, it affects up to one third of those aged 35 and over with the figure rising to 64-73% with increased age. Many more patients are thought to remain undiagnosed and untreated. This work specifically focuses on improving the care of patients with treated and undiagnosed hypertension. In those with a diagnosis of hypertension, treatment is dependent on accurate measurement of blood pressure in the clinic. Patients suffering white coat or masked hypertension may be over or under treated on the basis of this routine measurement. Patients with undiagnosed hypertension may have their blood pressure measured in the clinic but if they suffer from masked hypertension, under current practice they will not be sent for out of office measurement and therefore will not receive the treatment they need to control their blood pressure.

Predicting which patients suffer from white coat or masked hypertension will allow clinicians to target out of office blood pressure measurement to those who need it most. This will improve the accuracy of blood pressure measurement, thus reducing the proportion of patients with undiagnosed hypertension and increasing the number receiving the correct treatment for their condition. This work could therefore benefit patients with existing or suspected hypertension and also the clinicians tasked with managing their care.

By the end of this fellowship, I will have developed a tool which can be used in clinical practice and have laid the foundations for a definitive clinical trial which will establish the effectiveness and cost effectiveness of this tool in clinical practice. The necessary equipment needed to implement this novel method of blood pressure measurement already exists in general practices across the country. A recent survey suggested that at least half of blood pressure monitors in general practice are automatic and this figure is likely to rise now that the traditional mercury devices have been banned. It is likely that this methodology could easily be implemented once an evidence base has been established. There is the very real possibility that patients and clinicians could benefit directly from this research in the short term.

The primary research outcome of this fellowship will be to establish a sufficient evidence base to inform a clinical trial to establish the use of a new blood pressure measurement tool in routine clinical practice. Following this trial and the wide dissemination of its results, guideline development groups from the National Institute for Clinical Excellence and the British Hypertension Society will be engaged to ensure that this method blood pressure measurement (if proven to be effective) is incorporated into routine clinical practice. All patients who have their blood pressure measured accurately benefit from the correct treatment and reduced risk of cardiovascular disease. Therefore, this research has great potential to directly influence patient care.