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Meta-Analysis
. 2016 Aug 9:354:i4098.
doi: 10.1136/bmj.i4098.

Blood pressure variability and cardiovascular disease: systematic review and meta-analysis

Sarah L Stevens  1 , Sally Wood  2 , Constantinos Koshiaris  2 , Kathryn Law  2 , Paul Glasziou  3 , Richard J Stevens  1 , Richard J McManus  2
Affiliations
Meta-Analysis

Blood pressure variability and cardiovascular disease: systematic review and meta-analysis

Sarah L Stevens et al. BMJ. .

Abstract

Objective: To systematically review studies quantifying the associations of long term (clinic), mid-term (home), and short term (ambulatory) variability in blood pressure, independent of mean blood pressure, with cardiovascular disease events and mortality.

Data sources: Medline, Embase, Cinahl, and Web of Science, searched to 15 February 2016 for full text articles in English.

Eligibility criteria for study selection: Prospective cohort studies or clinical trials in adults, except those in patients receiving haemodialysis, where the condition may directly impact blood pressure variability. Standardised hazard ratios were extracted and, if there was little risk of confounding, combined using random effects meta-analysis in main analyses. Outcomes included all cause and cardiovascular disease mortality and cardiovascular disease events. Measures of variability included standard deviation, coefficient of variation, variation independent of mean, and average real variability, but not night dipping or day-night variation.

Results: 41 papers representing 19 observational cohort studies and 17 clinical trial cohorts, comprising 46 separate analyses were identified. Long term variability in blood pressure was studied in 24 papers, mid-term in four, and short-term in 15 (two studied both long term and short term variability). Results from 23 analyses were excluded from main analyses owing to high risks of confounding. Increased long term variability in systolic blood pressure was associated with risk of all cause mortality (hazard ratio 1.15, 95% confidence interval 1.09 to 1.22), cardiovascular disease mortality (1.18, 1.09 to 1.28), cardiovascular disease events (1.18, 1.07 to 1.30), coronary heart disease (1.10, 1.04 to 1.16), and stroke (1.15, 1.04 to 1.27). Increased mid-term and short term variability in daytime systolic blood pressure were also associated with all cause mortality (1.15, 1.06 to 1.26 and 1.10, 1.04 to 1.16, respectively).

Conclusions: Long term variability in blood pressure is associated with cardiovascular and mortality outcomes, over and above the effect of mean blood pressure. Associations are similar in magnitude to those of cholesterol measures with cardiovascular disease. Limited data for mid-term and short term variability showed similar associations. Future work should focus on the clinical implications of assessment of variability in blood pressure and avoid the common confounding pitfalls observed to date.

Systematic review registration: PROSPERO CRD42014015695.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: SS is funded by the National Institute for Health Research School for Primary Care Research (NIHR SPCR), RM has received grants and personal fees from Omron and grants from Lloyds Pharmacy, outside the submitted work; PG reports grants from National Heart Foundation, Australia, outside the submitted work, no other relationships or activities that could appear to have influenced the submitted work. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.

Figures

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Fig 1 Study screening flowchart
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Fig 2 Random effects meta-analysis of standardised hazard ratios for increases in clinic systolic blood pressure variability and all cause mortality. SD=standard deviation; SR=standardised residual; CV=coefficient of variation; VIM=variation independent of the mean; RMSE=root mean squared error
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Fig 3 Random effects meta-analysis of standardised hazard ratios for increases in clinic systolic blood pressure variability and stroke events. SD=standard deviation; SR=standardised residual; CV=coefficient of variation; VIM=variation independent of the mean; RMSE=root mean squared error
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Fig 4 Random effects meta-analysis of standardized hazard ratios for increases in home systolic blood pressure variability and all cause mortality. SD=standard deviation; VIM=variation independent of mean
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Fig 5 Random effects meta-analysis of standardised hazard ratios for increases in variability of ambulatory systolic blood pressure and all cause mortality. SD=standard deviation; ARV=average real variability
See this image and copyright information in PMC

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