Project objectives

The aim of this study is to systematically review the existing literature on MBPS with the aim of answering the following research questions:

• Which of the existing definitions (method of measurement and threshold value) of pathological MBPS best predicts future CVD morbidity and mortality?
• Do these predictive abilities differ according to specific CVD disease types?

The proposed research is within the remit of Programme 2, monitoring and management of long term conditions, of the NSPCR. Within this programme, the NSPCR seeks to evaluate new technologies and improve the way chronic disease is managed within primary care.

Now that ABPM is recommended as the standard measurement for newly diagnosed hypertension, information regarding a patient’s MBPS will be easily available upon initiation of antihypertensive medication. Knowledge of a pathological MBPS could facilitate more effective management of hypertension within primary care. It has therefore never been more important to establish prognostic abilities of MBPS and its role in clinical practice.

The research questions of this proposed review aim to establish an authoritative definition of MBPS which can be used in future investigations to ascertain the role of this CVD risk factor in clinical practice. 

Brief summary

Background

An exaggerated morning blood pressure surge (MBPS) may be associated with “wake up” stroke and other cardiovascular events, but the threshold at which a MBPS becomes pathological is unclear.

Aims & objectives

To systematically review the existing literature to establish the most appropriate definition of pathological MBPS.

Methods

Systematic review using a MEDLINE search strategy adapted for use in a range of literature databases, to identify all prospective studies relating an exaggerated MBPS to cardiovascular endpoints. Hazard ratios (HRs) were extracted and synthesised using random-effects meta-analysis. Summary estimates were used to describe the association between an exaggerated MBPS and the risk of subsequent cardiovascular disease.

Key findings

The search strategy identified unique 2,964 articles of which 17 were eligible for the study. Seven different definitions of MBPS were identified; one of the most common was a prewaking surge (mean blood pressure for 2 hours after wake-up minus mean blood pressure for 2 hours prior to wake-up) (6 studies). Summary meta-analysis gave no clear evidence that prewaking MBPS was associated with all cardiovascular (2 studies; HR 0.94, 95% CI 0.39-2.28) or stroke events (2 studies; HR 1.26, 95% CI 0.92-1.71) when the surge was defined by a predetermined threshold (>25-55mmHg). However, using a continuous scale, which has more power to detect an association, there was evidence that a 10mmHg increase in MBPS was related to an increased risk of stroke events (3 studies; HR 1.11, 95% CI 1.03-1.20).

Expected impact

Identifying MBPS is now realistic with the increased uptake of ambulatory blood pressure monitoring in routine clinical practice. This study found some evidence that an increasing MBPS is associated with an increased stroke risk and conceivably this could allow inclusion in risk calculation tools. However, due to the limited number of studies which analysed the data in this way (3 studies), this finding requires further investigation. This could involve re-analysis of existing patient data from previous studies in an individual patient data meta-analysis. Based on the current available evidence, clinicians should not use up resources identifying patients with an exaggerated MBPS but instead focus on treating established cardiovascular disease risk factors.

Conclusions

The present study found some evidence that, when measured and analysed as a continuous variable, increasing levels of MBPS are associated with increased risk of stroke. Future large, protocol-driven, individual patient data analyses are needed to accurately define the relationship between cardiovascular disease and the continuous MBPS. 

Plain English summary

The most common time of day that strokes and heart attacks occur is in the morning hours just after waking. Research has shown that these events occur in the morning due to a sharp increase in blood pressure upon waking, which is larger in some patients than others. Those patients with a bigger increase in blood pressure upon waking are consequently more likely to have a stroke (or heart attack) and would therefore benefit from medication which can reduce this morning increase in blood pressure.

To date, no one has developed a definitive definition of how large the increase in blood pressure needs to be for patients to be at greater risk of having a stroke or heart attack. The aim of this study will be to establish a threshold value for the morning increase in blood pressure which defines a patient at greater risk of having a stroke or heart attack. This will be done by reviewing previous research papers to examine past definitions of the morning increase in blood pressure and accessing which is best linked to patient outcomes.

Having identified a definitive threshold value, it will then be used to inform future research studies to establish its role in prescribing of medication which prevents future strokes and heart attacks in the morning. 

Dissemination

Published articles

1. Sheppard, J.P., Hodgkinson J.A., Riley, R., Martin, U., Bayliss, S., McManus, R.J. The prognostic significance of the morning blood pressure surge in clinical practice: a systematic review and meta-analysis. American Journal of Hypertension, 2015, 28(1):30-41 doi:10.1093/ajh/hpu104. 
   http://ajh.oxfordjournals.org/content/early/2014/10/14/ajh.hpu104.full
2. Sheppard, J.P., Hodgkinson J.A., Riley, R., Martin, U., Bayliss, S., McManus, R.J. Is it safe to wake up? Defining the prognostic value of the morning blood pressure surge in clinical practice. Journal of Human Hypertension, 27(10): 647-647.

Poster presentations

Sheppard, J.P., Hodgkinson J.A., Riley, R., Martin, U., Bayliss, S., McManus, R.J. Is it safe to wake up? Defining the prognostic value of the morning blood pressure surge in clinical practice:

1. Poster presentation, European Society of Hypertension. Milan, Italy, 14th - 17th June 2013;
2. Oral presentation, North American Primary Care Research Group. Ottawa, Canada, 9th – 13th November 2013;
3. Poster presentation, British Hypertension Society. London, 9th - 10th September 2013;
4. Poster presentation, Society for Academic Primary Care. Nottingham, 3th – 4th July 2013;
5. Poster presentation, South West Society for Academic Primary Care. Southampton, 7th - 8th March 2013.  

Public involvement

Not applicable.

Impact

MBPS is an important concept in clinical practice, not least because it has been proposed as a cause of wake-up stroke, which is not amenable to treatment with thrombolysis because of lack of knowledge of onset time. Identifying MBPS is now realistic with the increased uptake of ambulatory blood pressure monitoring in routine clinical practice. This study found some evidence that an increasing MBPS is associated with an increased stroke risk and conceivably this could allow inclusion in risk calculation tools. However, due to the limited number of studies which analysed the data in this way (3 studies), this finding requires further investigation. This could involve re-analysis of existing patient data from previous studies in an individual patient data meta-analysis. Should future studies confirm an increasing MBPS as a prognostic factor for cardiovascular disease, more thought will be required to establish how such a marker can be used effectively (i.e. at what point should treatment regimens be adjusted to account for increasing MBPS) given that for diagnosis and treatment decisions, markers using predetermined thresholds are easier to implement in routine clinical practice.  

This project was funded by the National Institute for Health Research School for Primary Care Research (project number 130)

Department of Health Disclaimer

The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR School for Primary Care Research, NIHR, NHS or the Department of Health.