Prognostic significance of blood-pressure variability – Author's reply

Abstract

A R Michell is correct to highlight the importance of reliable measurement of clinic blood pressure in routine practice, an issue that we also highlighted.1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar However, errors in measurement could only partly account for a visit-to-visit range in systolic blood pressure (SBP) of 50 mm Hg or more, which was found in about a third of patients in each of the cohorts with transient ischaemic attack (TIA) and in the atenolol group of ASCOT-BPLA, in which blood-pressure measurement was standardised.1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar, 2Rothwell PM Howard SC Dolan E et al.on behalf of the ASCOT-BPLA and MRC Trial InvestigatorsEffects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke.Lancet Neurol. 2010; 9: 469-480Summary Full Text Full Text PDF PubMed Scopus (548) Google ScholarIn relation to the need for multiple readings at each visit, we based all calculations of mean blood pressure and visit-to-visit variability in ASCOT-BPLA on the mean of the second two of three measurements taken at each visit, and we also reported data for the extent and prognostic value of within-visit variability.1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar Interestingly, even this short-term variability over minutes had some prognostic value,1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar probably indicating some element of true physiological variability rather than simply measurement error. Moreover, any contribution of measurement error to apparent visit-to-visit variability in blood pressure would be expected to dilute the observed prognostic value. Yet visit-to-visit variability was very strongly predictive of stroke, whether based on a single measurement in the TIA cohorts or on the mean of the second two of three measurements taken at each visit in ASCOT-BPLA.1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google ScholarBas van den Bogaard and colleagues rightly point out the value of pulse pressure as an indirect measure of arterial stiffness. As we stated, all analyses of the prognostic value of variability in blood pressure were done for pulse pressure as well as for SBP and results were similar.1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar In the TIA cohorts and in ASCOT-BPLA, the association between visit-to-visit variability in pulse pressure and risk of stroke was, in fact, slightly weaker than was the association based on SBP. Adjustment for mean pulse pressure reduced the association between visit-to-visit variability in SBP and stroke risk less than did adjustment for mean SBP in all cohorts studied (unpublished data). However, patients in all of the cohorts that we studied were elderly and had either several vascular risk factors or symptomatic vascular disease, and so increased arterial stiffness would have been highly prevalent. Findings might differ in younger healthier cohorts.Joep Lagro and colleagues point out the potential importance of cerebrovascular reactivity in understanding the mechanisms of the association between variability in blood pressure and stroke risk, assuming a causal link. In fact, this and other mechanistic issues were discussed in some detail in the accompanying Review.3Rothwell PM Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension.Lancet. 2010; 375: 938-948Summary Full Text Full Text PDF PubMed Scopus (550) Google Scholar As was also discussed,1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar, 3Rothwell PM Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension.Lancet. 2010; 375: 938-948Summary Full Text Full Text PDF PubMed Scopus (550) Google Scholar the issue of determining how best to quantify variability in routine clinical practice is crucial. We showed that variability in daytime SBP on ambulatory monitoring was partly correlated with visit-to-visit variability, as was variability in mean daytime SBP on repeated ambulatory monitoring. Visit-to-visit variability also correlates with variability in daily blood-pressure measurements at home (unpublished data) and with postural instability in blood pressure (unpublished data). Further research is needed to determine whether these different measures of variability have similar or possibly additive prognostic value.I declare that I have no conflicts of interest. A R Michell is correct to highlight the importance of reliable measurement of clinic blood pressure in routine practice, an issue that we also highlighted.1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar However, errors in measurement could only partly account for a visit-to-visit range in systolic blood pressure (SBP) of 50 mm Hg or more, which was found in about a third of patients in each of the cohorts with transient ischaemic attack (TIA) and in the atenolol group of ASCOT-BPLA, in which blood-pressure measurement was standardised.1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar, 2Rothwell PM Howard SC Dolan E et al.on behalf of the ASCOT-BPLA and MRC Trial InvestigatorsEffects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke.Lancet Neurol. 2010; 9: 469-480Summary Full Text Full Text PDF PubMed Scopus (548) Google Scholar In relation to the need for multiple readings at each visit, we based all calculations of mean blood pressure and visit-to-visit variability in ASCOT-BPLA on the mean of the second two of three measurements taken at each visit, and we also reported data for the extent and prognostic value of within-visit variability.1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar Interestingly, even this short-term variability over minutes had some prognostic value,1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar probably indicating some element of true physiological variability rather than simply measurement error. Moreover, any contribution of measurement error to apparent visit-to-visit variability in blood pressure would be expected to dilute the observed prognostic value. Yet visit-to-visit variability was very strongly predictive of stroke, whether based on a single measurement in the TIA cohorts or on the mean of the second two of three measurements taken at each visit in ASCOT-BPLA.1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar Bas van den Bogaard and colleagues rightly point out the value of pulse pressure as an indirect measure of arterial stiffness. As we stated, all analyses of the prognostic value of variability in blood pressure were done for pulse pressure as well as for SBP and results were similar.1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar In the TIA cohorts and in ASCOT-BPLA, the association between visit-to-visit variability in pulse pressure and risk of stroke was, in fact, slightly weaker than was the association based on SBP. Adjustment for mean pulse pressure reduced the association between visit-to-visit variability in SBP and stroke risk less than did adjustment for mean SBP in all cohorts studied (unpublished data). However, patients in all of the cohorts that we studied were elderly and had either several vascular risk factors or symptomatic vascular disease, and so increased arterial stiffness would have been highly prevalent. Findings might differ in younger healthier cohorts. Joep Lagro and colleagues point out the potential importance of cerebrovascular reactivity in understanding the mechanisms of the association between variability in blood pressure and stroke risk, assuming a causal link. In fact, this and other mechanistic issues were discussed in some detail in the accompanying Review.3Rothwell PM Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension.Lancet. 2010; 375: 938-948Summary Full Text Full Text PDF PubMed Scopus (550) Google Scholar As was also discussed,1Rothwell PM Howard SC Dolan E et al.Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.Lancet. 2010; 375: 895-905Summary Full Text Full Text PDF PubMed Scopus (1273) Google Scholar, 3Rothwell PM Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension.Lancet. 2010; 375: 938-948Summary Full Text Full Text PDF PubMed Scopus (550) Google Scholar the issue of determining how best to quantify variability in routine clinical practice is crucial. We showed that variability in daytime SBP on ambulatory monitoring was partly correlated with visit-to-visit variability, as was variability in mean daytime SBP on repeated ambulatory monitoring. Visit-to-visit variability also correlates with variability in daily blood-pressure measurements at home (unpublished data) and with postural instability in blood pressure (unpublished data). Further research is needed to determine whether these different measures of variability have similar or possibly additive prognostic value. I declare that I have no conflicts of interest. Prognostic significance of blood-pressure variabilityPeter Rothwell and colleagues (March 13, p 895)1 reinforce earlier suggestions2 of the importance of blood-pressure variability, rather than pressure alone, as a warning prognostic for stroke. It is therefore extremely important that blood pressure is measured properly, to identify true variability in the patient as opposed to variations resulting from imprecise technique. Full-Text PDF Prognostic significance of blood-pressure variabilityPeter Rothwell and colleagues1 show that visit-to-visit variability in systolic blood pressure (SBP), measured as the SD of mean SBP readings, is associated with an increased risk of stroke, independent of mean SBP. In an accompanying Review,2 arterial stiffness is put forward as one of the pathophysiological explanations for blood-pressure variability, as well as impaired autonomic control and mean blood pressure increase.3 Full-Text PDF Prognostic significance of blood-pressure variabilityPeter Rothwell and colleagues1 provide convincing evidence that visit-to-visit blood-pressure variability is a strong predictor of stroke, independent of mean systolic blood pressure. Although they do not point at a pathophysiological explanation, we would like to add that cerebrovascular reactivity is the complementary part of blood-pressure variability with regard to incident cerebral ischaemia,2 and that these entities together require further investigation. Full-Text PDF