Visit-to-visit blood pressure variability and outcome: a traditional and a dose-response meta-analysis

Background: It is not clear whether the relationship of blood pressure variability (BPV) with outcome reported in several studies is linear or becomes evident only above a given BPV threshold value. This meta-analysis was aimed at exploring the shape of the relationship between visit-to-visit BPV (VVBPV) and mortality or fatal and non-fatal cardiovascular events, also addressing whether the number of visits considered for estimation of VVBPV has an impact on this relationship. Methods: Pooled hazard ratios and 95% confidence intervals for the association between VVBPV and outcomes were calculated by outcome type and number of visits used to estimate VVBPV. Restricted cubic spline meta-regression models were applied to explore the shape of this relationship and the presence of threshold values beyond which VVBPV significantly increases the risk of outcomes. Results: The literature search identified 50 studies (n=10,624,740 individuals). The risk of all-cause and cardiovascular mortality began to increase significantly above specific VVBPV threshold values. Systolic VVBPV measured as standard deviation (SD) had a threshold of 11.8 mmHg for all-cause mortality and 12.1 mmHg for cardiovascular mortality. Diastolic VVBPV SD showed threshold values of 5.8 mmHg for all-cause mortality and 5.25 mmHg for cardiovascular mortality, the risk of these outcomes increasing significantly only when VVBPV exceed these values. Our study also provides indications that a minimum of three visits is required to reliably assess the prognostic value of VVBPV. Conclusions: This meta-analysis shows a non-linear dose-response relationship between VVBPV and outcomes, with distinct threshold values. The identification of such thresholds is vital for assessing the prognostic value of BPV in research or clinical settings. A reliable assessment of the prognostic value of VVBPV should be based on at least three visits.