Influence of Baseline Diastolic Blood Pressure on Effects of Intensive Compared With Standard Blood Pressure Control

Abstract

Background: In individuals with a low diastolic blood pressure (DBP), the potential benefits or risks of intensive systolic blood pressure (SBP) lowering are unclear.

Methods: SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized controlled trial that compared the effects of intensive (target <120 mm Hg) and standard (target <140 mm Hg) SBP control in 9361 older adults with high blood pressure at increased risk of cardiovascular disease. The primary outcome was a composite of cardiovascular disease events. All-cause death and incident chronic kidney disease were secondary outcomes. This post hoc analysis examined whether the effects of the SBP intervention differed by baseline DBP.

Results: Mean baseline SBP and DBP were 139.7±15.6 and 78.1±11.9 mm Hg, respectively. Regardless of the randomized treatment, baseline DBP had a U-shaped association with the hazard of the primary cardiovascular disease outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline DBP level (P for interaction=0.83). The primary outcome hazard ratio for intensive versus standard treatment was 0.78 (95% confidence interval, 0.57-1.07) in the lowest DBP quintile (mean baseline DBP, 61±5 mm Hg) and 0.74 (95% confidence interval, 0.61-0.90) in the upper 4 DBP quintiles (mean baseline DBP, 82±9 mm Hg), with an interaction P value of 0.78. Results were similar for all-cause death and kidney events.

Conclusions: Low baseline DBP was associated with increased risk of cardiovascular disease events, but there was no evidence that the benefit of the intensive SBP lowering differed by baseline DBP.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Keywords: blood pressure; hypertension; randomized controlled trial.

Figure 1

The boxplots display the median, 25^th and 75^th percentiles of the patients’ mean follow-up values for systolic blood pressure (panel A), diastolic blood pressure (panel B), mean arterial pressure (panel C) and pulse pressure (panel D), by randomized SBP intervention and quintile of baseline DBP (N=9119). 242 of 9361 subjects (2.6%) (140 in the standard group and 102 in the intensive group) had missing blood pressure measurements after month 2 and are not included. SBP = systolic blood pressure; DBP = diastolic blood pressure.

Figure 2

Shown are incidence rates and pointwise 95% CIs for the primary CVD outcome (panel A), all-cause death (panel B) and incident CKD (panel C) in the standard and intensive SBP groups by quintile of baseline DBP. The 95% CIs were calculated for incidence rates using the quadratic approximation to the Poisson log likelihood for the log-rate parameter. Lines are drawn between the incidence rates quintiles for the different quintiles for visual clarity, and do not represent fitted regression curves. The analysis of incident CKD patients was performed for patients with baseline eGFR ≥ 60 ml/min/1.73m². There were too few events to provide a meaningful similar analysis for the composite kidney outcome. SBP = systolic blood pressure; DBP = diastolic blood pressure; CVD = cardiovascular disease; CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; HR = hazard ratio; CI = confidence interval.

Figure 3

Shown are forest plots with hazard ratios for the effect of intensive vs. standard SBP intervention by quintile of baseline DBP for the primary CVD outcome (panel A), all-cause death (panel B) and incident CKD (panel C). In joint Cox regression models with separate baseline hazards for each baseline DBP quintile, likelihood ratio tests comparing the hazard ratios for the intensive vs. standard SBP interventions between the 5 baseline DBP quintiles were non-significant (primary CVD outcome interaction p = 0.92; all-cause death interaction p = 0.57; incident CKD interaction p = 0.91; composite kidney outcome interaction p = 0.71). Due to a small number of events, the interaction test for composite kidney outcome compared hazard ratios below and above the median baseline DBP instead of by baseline DBP quintile, and the HRs are not displayed in the figure. The analyses of incident CKD patients and the composite kidney outcome were performed for patients with baseline eGFR ≥ 60 ml/min/1.73m² and baseline eGFR < 60 ml/min/1.73m², respectively. SBP = systolic blood pressure; DBP = diastolic blood pressure; CVD = cardiovascular disease; CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate. HR = hazard ratio; CI = confidence interval