Elsevier

The Lancet

Volume 375, Issue 9718, 13–19 March 2010, Pages 895-905
The Lancet

Articles
Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension

https://doi.org/10.1016/S0140-6736(10)60308-XGet rights and content

Summary

Background

The mechanisms by which hypertension causes vascular events are unclear. Guidelines for diagnosis and treatment focus only on underlying mean blood pressure. We aimed to reliably establish the prognostic significance of visit-to-visit variability in blood pressure, maximum blood pressure reached, untreated episodic hypertension, and residual variability in treated patients.

Methods

We determined the risk of stroke in relation to visit-to-visit variability in blood pressure (expressed as standard deviation [SD] and parameters independent of mean blood pressure) and maximum blood pressure in patients with previous transient ischaemic attack (TIA; UK-TIA trial and three validation cohorts) and in patients with treated hypertension (Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm [ASCOT-BPLA]). In ASCOT-BPLA, 24-h ambulatory blood-pressure monitoring (ABPM) was also studied.

Findings

In each TIA cohort, visit-to-visit variability in systolic blood pressure (SBP) was a strong predictor of subsequent stroke (eg, top-decile hazard ratio [HR] for SD SBP over seven visits in UK-TIA trial: 6·22, 95% CI 4·16–9·29, p<0·0001), independent of mean SBP, but dependent on precision of measurement (top-decile HR over ten visits: 12·08, 7·40–19·72, p<0·0001). Maximum SBP reached was also a strong predictor of stroke (HR for top-decile over seven visits: 15·01, 6·56–34·38, p<0·0001, after adjustment for mean SBP). In ASCOT-BPLA, residual visit-to-visit variability in SBP on treatment was also a strong predictor of stroke and coronary events (eg, top-decile HR for stroke: 3·25, 2·32–4·54, p<0·0001), independent of mean SBP in clinic or on ABPM. Variability on ABPM was a weaker predictor, but all measures of variability were most predictive in younger patients and at lower (<median) values of mean SBP in every cohort.

Interpretation

Visit-to-visit variability in SBP and maximum SBP are strong predictors of stroke, independent of mean SBP. Increased residual variability in SBP in patients with treated hypertension is associated with a high risk of vascular events.

Funding

None.

Introduction

Hypertension is the most prevalent treatable risk factor for stroke and other vascular events.1, 2 Underlying usual blood pressure (conceived as the true underlying average blood pressure over a period of time) is widely considered to be of primary importance in the cause of vascular disease,3, 4 and hence in diagnosis and treatment of hypertension,5, 6, 7 and this notion underpins all major clinical guidelines.8, 9, 10, 11 Yet, the mechanisms by which raised blood pressure causes stroke and other vascular events are poorly understood. Mean blood pressure is clearly important, but other factors, such as variability or maximum blood pressure reached, might also play a part,12 particularly at older ages when most vascular events occur.13 However, visit-to-visit variability in blood pressure is usually dismissed as random, noteworthy only as an obstacle to the reliable estimation of usual blood pressure.14, 15, 16, 17, 18 Consequently, although substantial visit-to-visit variability in clinic blood pressure is common,19, 20, 21, 22, 23, 24 episodic hypertension tends not to be treated.12 In patients with occasional high blood pressure, guidelines recommend continued monitoring or 24-h ambulatory blood-pressure monitoring (ABPM),8, 9, 10, 11 with treatment decisions based on mean blood pressure. Yet, although situational variability in blood pressure has been studied,25, 26 the prognostic value of visit-to-visit variability and episodic hypertension in the same setting has not been reliably established.

We showed previously that visit-to-visit variability in blood pressure is increased in cohorts at high risk of stroke,19, 20 that it is consistent within individuals over time (ie, not random),27 and that it seems to predict stroke independently of mean systolic blood pressure (SBP).28 Prompted by these observations and by shortcomings in the usual blood-pressure hypothesis,12 we aimed to reliably establish the prognostic significance of visit-to-visit variability in blood pressure, maximum blood pressure reached, episodic hypertension, and residual variability in blood pressure in patients already receiving antihypertensive drugs. We studied a large cohort of patients with previous transient ischaemic attack (TIA; UK-TIA aspirin trial),29 with validation in three similar cohorts,30, 31, 32 and a broad population of patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA).32, 33 In ASCOT-BPLA, we also measured the prognostic value of short-term variability during individual visits and on 24-h ABPM.

Section snippets

Cohorts

The UK-TIA aspirin trial was a double-blind randomised trial of aspirin (1200 mg vs 300 mg vs placebo) in 2435 patients with a recent TIA or ischaemic stroke, which was undertaken from 1979 to 1985.29 Visit-to-visit variability in blood pressure was not affected by the randomised treatment.27 To avoid confounding due to any effect of recent stroke on variability in blood pressure,34, 35 analysis was confined to 2006 patients presenting with TIA only. Sitting blood pressure was measured once at

Results

In the UK-TIA cohort, 2006 patients (1438 men; mean age 60·3 years, SD 9·1; median time since TIA 23 days, IQR 8–46) had a median of 10 (range 1–20) follow-up visits before stroke or death. Results of analyses based on pulse pressure and SBP were similar (data not shown). Mean SBP was 150·3 mm Hg (SD 25·3) at baseline and fell to 146·4 mm Hg (23·3) at 1 year, but was stable thereafter (webappendix p 13). However, systolic blood pressure in individuals was highly variable from one visit to the

Discussion

We have shown that visit-to-visit variability in SBP is a powerful predictor of stroke and coronary events independent of mean SBP, that maximum SBP is more predictive than is mean SBP (on clinic readings or on ABPM), that residual variability in SBP on treatment has a poor prognosis, and that stable hypertension has a better prognosis than does episodic hypertension. Along with accompanying reports,12, 40, 41 these findings challenge the usual blood-pressure hypothesis and have implications

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