Having high blood pressure occasionally may pose a higher risk of having a stroke than having consistently high readings: a series of UK-led research papers published this week in leading journals suggests doctors should not ignore one-off high blood pressure readings and consider blood pressure variability and maximum blood pressure as risk factors for stroke rather than just average blood pressure.

You can read about the research in a series of papers published online this week in The Lancet and The Lancet Neurology. The lead author is Dr Peter Rothwell, a professor of neurology at the University of Oxford, UK.

Rothwell told the media that the main message coming out of the research is that doctors have to start viewing blood pressure differently.

Current guidelines say that the priority is to lower blood pressure to reduce the risk of having a stroke, but the work that Rothwell and colleagues have done suggests that doctors should also take into account blood pressure variability and prescribe the drugs that result in the most steady blood pressure.

In the study published in The Lancet, Rothwell and colleagues looked at high blood pressure and visit-to-visit blood pressure variability in four groups of 2,000 people (UK-TIA trial and three validation cohorts), each of whom had experienced transient ischemic attacks (TIAs), often dubbed “mini-strokes”, considered warning signs of stroke risk.

They found that in each TIA cohort, the visit-to-visit variability in systolic blood pressure (SBP, the higher of the two blood pressure readings that a doctor takes, eg the 120 in a 120/80 reading) and maximum blood pressure were both strong predictors of subsequent stroke.

Those participants with the greatest variation in SBP over seven GP visits were six times more likely to have a major stroke and those with the highest blood pressure readings were 15 times more likely to have a stroke.

The authors concluded that:

“Visit-to-visit variability in SBP and maximum SBP are strong predictors of stroke, independent of mean SBP.”

In a second Lancet study, Rothwell and colleagues conducted a meta-analysis (where you analysed data pooled from several studies of similar design and measurement criteria) of 389 controlled trials and found that blood pressure variability was a probable explanation for why some types of drugs were more effective than others at preventing strokes.

In this second study, they concluded that:

“Drug-class effects on interindividual variation in blood pressure can account for differences in effects of antihypertensive drugs on risk of stroke independently of effects on mean SBP.”

And in a third study, published in The Lancet Neurology, Rothwell and colleagues compared the effects of β blockers and calcium-channel blockers on blood pressure variability and how this might impact risk of stroke.

Previous studies have found that on the basis of mean blood pressure alone, calcium-channel blockers reduce the risk of stroke more than expected and β blockers less than expected.

For this study they examined the results of two trials: the Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT- BPLA) trial involving 19,257 patients with hypertension and other vascular risk factors, and a Medical Research Council (MRC) trial involving 4,396 hypertensive patients.

They found that calcium-channel blockers and β blockers have opposite effects on blood pressure variability: with the former gradually reducing variability over time, and the latter gradually increasing it.

The researchers concluded that the opposite effects of “calcium-channel blockers and β blockers on variability of blood pressure account for the disparity in observed effects on risk of stroke and expected effects based on mean blood pressure”; they recommended that:

“To prevent stroke most effectively, blood-pressure-lowering drugs should reduce mean blood pressure without increasing variability; ideally they should reduce both.”

In a review article in The Lancet, Rothwell discusses what he describes as the “shortcomings of the usual blood pressure hypothesis” and suggests avenues for future research.

He argues that while high blood pressure is the most common treatable vascular risk factor, we don’t know very much about how it causes end-organ damage and leads to vascular events, yet there is a widespread belief that “underlying usual blood pressure can alone account for all blood-pressure- related risk of vascular events”, and this has influenced guidelines for diagnosis and treatment.

In the meantime, potentially valuable information is ignored, such as variability in clinic blood pressure or maximum blood pressure reached, with the result that we know little about the effects of widely used drugs on these measures, writes Rothwell.

Dr Philip B. Gorelick, a leading American expert on blood pressure and stroke, and director of the Center for Stroke Research at the University of Illinois, who also wrote a commentary in one of the journals to accompany the studies, told the media (as reported by HealthDayNews) the findings are “compelling” and may “revolutionize how we treat blood pressure in the future”:

“They provide a very important foundation for change in future treatment,” said Gorelick.

He said first doctors may begin to screen patients for blood pressure variability and see if it is possible to select for classes of drugs that reduce it.

“And we can certainly adopt an at-home program to detect blood pressure variability, although within-visit variability seems to be a more important factor,” he added.

He said the study on the different effects on variability of calcium-channel blockers and β blockers may also affect choice of the first drugs prescribed for blood pressure control:

“We would consider calcium channel blockers and diuretics for initial use,” said Gorelick.

Joe Korner, director of communications at The Stroke Association, commented to the BBC about the new findings and said that people who have what is called episodic hypertension, where their blood pressure occasionally registers a high reading, are often not treated.

Korner urged GPs to read the new research to help them decide the best treatment for patients at risk of stroke.

In the UK, clinical guidelines are regulated by the National Institute for Health and Clinical Excellence (NICE), and they are in the process of reviewing the guidelines on high blood pressure: it is understood that they will be taking these latest studies into account.

“Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.”
Peter M Rothwell, Sally C Howard, Eamon Dolan, Eoin O’Brien, Joanna E Dobson, Bjorn Dahlöf, Peter S Sever, Neil R Poulter.
The Lancet, Volume 375, Issue 9718, Pages 895 – 905, 13 March 2010
DOI:10.1016/S0140-6736(10)60308-X

“Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta- analysis.”
Alastair JS Webb, Urs Fischer, Ziyah Mehta, Peter M Rothwell
The Lancet, Volume 375, Issue 9718, Pages 906 – 915, 13 March 2010
DOI:10.1016/S0140-6736(10)60235-8

“Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension.”
Peter M Rothwell
The Lancet, Volume 375, Issue 9718, Pages 938 – 948, 13 March 2010
DOI:10.1016/S0140-6736(10)60309-1

“Effects of β blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke.”
Peter M Rothwell, Sally C Howard, Eamon Dolan, Eoin O’Brien, Joanna E Dobson, Bjorn Dahlöf, Neil R Poulter, Peter S Sever, on behalf of the ASCOT-BPLA and MRC Trial Investigators.
The Lancet Neurology, Early Online Publication, 12 March 2010
DOI:10.1016/S1474-4422(10)70066-1

Additional sources: HealthDayNews, BBC.

Written by: Catharine Paddock, PhD