Association between annual visit-to-visit blood pressure variability and stroke in postmenopausal women: data from the Women's Health Initiative

Abstract

Accumulating evidence suggests that increased visit-to-visit variability (VVV) of blood pressure is associated with stroke. No study has examined the association between VVV of blood pressure and stroke in postmenopausal women, and scarce data exist as to whether this relation is independent of the temporal trend of blood pressure. We examined the association of VVV of blood pressure with stroke in 58,228 postmenopausal women enrolled in the Women's Health Initiative. Duplicate blood pressure readings, which were averaged, were taken at baseline and at each annual visit. VVV was defined as the SD for the participant's mean systolic blood pressure (SBP) across visits (SD) and about the participant's regression line with SBP regressed across visits (SDreg). Over a median follow-up of 5.4 years, 997 strokes occurred. In an adjusted model including mean SBP over time, the hazard ratios (95% CI) of stroke for higher quartiles of SD of SBP compared with the lowest quartile (referent) were 1.39 (1.03-1.89) for quartile 2, 1.52 (1.13-2.03) for quartile 3, and 1.72 (1.28-2.32) for quartile 4 (P trend <0.001). The relation was similar for SDreg of SBP quartiles in a model that additionally adjusted for the temporal trend in SBP (P trend <0.001). The associations did not differ by stroke type (ischemic versus hemorrhagic). There was a significant interaction between mean SBP and SDreg on stroke with the strongest association seen below 120 mmHg. In postmenopausal women, greater VVV of SBP was associated with increased risk of stroke, particularly in the lowest range of mean SBP.

Figure 1. Representative Patterns of Visit-to-Visit Blood Pressure Variability

Plots illustrate systolic blood pressure (SBP) measures over follow-up of four different individuals (Panels 1-4) with approximately the same mean SBP across visits. Standard deviations from the mean and least squares regression line are labeled “SD” and “SDreg”, respectively. Slope of the regression line is labeled “slope.” SBP at each visit is represented by black dots. SD is a measure of the VVV of SBP about the individual's mean (solid blue line), where the mean is assumed to be static. SDreg is a measure of the VVV of SBP about the individual's regression line (solid red line), where the mean (i.e., regression line) is assumed to be a linear function of time. Conceptually, SD is the ‘average’ of the deviations (lengths of dotted blue lines) about the mean (solid blue line), and SDreg is the ‘average’ of the deviations (lengths of dotted red lines) about the regression line (solid red line). The 2 individuals in Panels 3 and 4 (bottom left and right panels) have a larger temporal change in SBP across visits than the 2 individuals in Panels 1 and 2 (upper left and right panels). The individual in Panel 3 has a higher SD from the mean but a similar SDreg from the regression line, compared to the individual in Panel 1. A similar pattern is seen with the 2 individuals in Panels 4 and 2. Further, despite having similar mean SBP across visits, the individuals in Panels 1 and 2, and separately the individuals in Panels 3 and 4, have different SD from the mean and also different SDreg from the regression line.