Figure 1.
Trial profile.
Table 1.
Patient characteristics by fourths of the distribution of systolic blood pressure at randomisation.
Figure 2.
Systolic blood pressure level and variability at randomisation and during follow-up.
SBP (A), VIM (B) and WVV (C) denote systolic blood pressure, visit-to-visit variability independent of the mean and within-visit variability. Values at randomisation and at annual intervals during follow-up were derived from at least six blood pressure readings, two at each of three consecutive visits. The blood pressure level at six months is the average of four blood pressure readings at two consecutive visits. The computation of variability requires at least three visits. Variability is therefore not plotted at 6 months. P values indicate the significance of the average between-group difference throughout follow-up.
Figure 3.
Blood pressure and variability at randomisation and during follow-up among patients staying on monotherapy.
SBP (A), VIM (B) and WVV (C) denote systolic blood pressure, visit-to-visit variability independent of the mean and within-visit variability in 2236 patients staying on monotherapy with the first-line study medication. Values at randomisation and at annual intervals during follow-up are derived from at least six blood pressure readings, two at each of three consecutive visits. The blood pressure level at six months is the average of four blood pressure readings at two consecutive visits. The computation of variability requires at least three visits. Variability is therefore not plotted at 6 months. P values indicate the significance of the average between-group difference throughout follow-up.
Figure 4.
Blood pressure and variability at randomisation and during follow-up among patients proceeding to combination therapy.
SBP (A), VIM (B) and WVV (C) denote systolic blood pressure, visit-to-visit variability independent of the mean and within-visit variability in 2459 patients proceeding to combination therapy. Values at randomisation and at annual intervals during follow-up are derived from at least six blood pressure readings, two at each of three consecutive visits. The blood pressure level at six months is the average of four blood pressure readings at two consecutive visits. The computation of variability requires at least three visits. Variability is therefore not plotted at 6 months. P values indicate the significance of the average between-group difference throughout follow-up.
Table 2.
Incidence of endpoints by randomisation group.
Figure 5.
Incidence of total mortality by treatment group and median of blood pressure variability.
VIM (A) and WVV (B) denote visit-to-visit variability independent of the mean and within-visit variability of systolic blood pressure. P and A indicate placebo and active treatment, respectively, and 50% refers to the median. On placebo (n = 2297) and active treatment (n = 2398), x values used to compute VIM were 0.822 and 0.628; medians were 9.36 and 9.60 units for VIM, and 2.83 and 2.91 mm Hg for WVV. P value indicates the significance of the log-rank test comparing low with high variability within each randomisation group.
Figure 6.
Incidence of cardiovascular mortality by treatment group and median of blood pressure variability.
VIM (A) and WVV (B) denote visit-to-visit variability independent of the mean and within-visit variability of systolic blood pressure. P and A indicate placebo and active treatment, respectively, and 50% refers to the median. On placebo (n = 2297) and active treatment (n = 2398), x values used to compute VIM were 0.822 and 0.628; medians were 9.36 and 9.60 units for VIM and 2.83 and 2.91 mm Hg for WVV. P value indicates the significance of the log-rank test comparing low with high variability within each randomisation group.
Figure 7.
Incidence of the composite cardiovascular endpoint by treatment group and median of blood pressure variability.
VIM and WVV denote visit-to-visit variability independent of the mean and within-visit variability. The number of analysed patients randomised to placebo and active treatment was 2297 and 2398, respectively. P and A indicate placebo and active treatment, respectively, and 50% refers to the median. On placebo and active treatment, x values used to compute VIM were 0.995 and 0.718; medians were 9.34 and 9.58 units for VIM and 2.82 and 2.91 mm Hg for WVV. P value indicates the significance of the log-rank test comparing low with high variability within each randomisation group.
Figure 8.
Two-year absolute risk of a cardiovascular endpoint in relation to level and variability.
SBP, VIM and WVV denote systolic blood pressure, visit-to-visit variability independent of the mean and within-visit variability. The analyses account for randomisation group and were stratified for centre and standardised to the distributions (mean or ratio) of sex, age, body mass index, heart rate, cholesterol, smoking and drinking, and history of cardiovascular disease or diabetes. In panels A and B, the risk functions span the 5th to 95th percentile interval of SBP and are plotted for the 5th, 25th, 50th, 75th and 95th percentiles of VIM (panel A) or WVV (panel B). In panels C and D, the risk functions span the 5th to 95th percentile interval of VIM or WVV and are plotted for the 5th, 25th, 50th, 75th and 95th percentiles of SBP. The p values are for the independent effects of SBP (psbp) and VIM (pvim) or WVV (pwvv). np and ne indicate the number of patients at risk and the number of events.
Table 3.
Hazard ratios associated with level and visit-to-visit variability of systolic blood pressure during follow-up.
Table 4.
Hazard ratios associated with level and within-visit variability of systolic blood pressure during follow-up.
Table 5.
Hazard ratios associated with level and visit-to-visit variability of systolic blood pressure during follow-up with additional adjustment for proceeding to combination therapy as time-dependent variable.
Table 6.
Hazard ratios associated with level and within-visit variability of systolic blood pressure during follow-up with additional adjustment for proceeding to combination therapy as time-dependent variable.
Table 7.
Sensitivity analyses of the predictive value of visit-to-visit variability of systolic blood pressure with exclusion of varying follow-up periods.
Table 8.
Sensitivity analyses of the predictive value of within-visit variability of systolic blood pressure with exclusion of varying follow-up periods.