Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial

Abstract

Importance: There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia.

Objective: To evaluate the effect of intensive blood pressure control on risk of dementia.

Design, setting, and participants: Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018.

Interventions: Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683).

Main outcomes and measures: The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia.

Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97).

Conclusions and relevance: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point.

Trial registration: ClinicalTrials.gov Identifier: NCT01206062.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Williamson, Pajewski, Chelune, Crowe, Cushman, Lerner, Lewis, Lewis, Oparil, Rahman, Reboussin, Rocco, Supiano, Wadley, Weiner, and C. B. Wright reported receipt of research support from the National Institutes of Health (NIH). Dr Williamson reported that his institution received funding from Biogen (unrelated to this study). Dr Cushman reported receipt of grants from Lilly and personal fees from Sanofi Pharmaceuticals and uncompensated consulting for Novartis Pharmaceuticals and Takeda Pharmaceuticals. Dr Oparil reported receipt of personal fees from Actelion Clinical Research Inc, Boehringer Ingelheim/Lilly, Lundbeck, Novo Nordisk Inc, 98point6 Inc, George Clinical Pty Ltd, Idorsia Pharmaceuticals, Pfizer Inc, and ROX Medical Inc and grant support from Actelion Clinical Research Inc, George Clinical Pty Ltd, Idorsia Pharmaceuticals, and Novartis. Dr Oparil also reported being the editor-in-chief of Current Hypertension Reports (until December 2020), published by Springer Science Business Media LLC, for which she receives an annual stipend of $5000. Dr Sink reported being a full-time employee of Wake Forest School of Medicine during the conduct of this study and since becoming a full-time employee of Genentech. Dr C. B. Wright reported royalties from UpToDate.com for 2 chapters on vascular dementia. No other disclosures were reported.

Figures

Figure 1.. Participant Flow in the Systolic Blood Pressure Intervention Trial (SPRINT)

SBP indicates systolic blood pressure.

Figure 2.. Probable Dementia by Treatment Group

Shaded regions indicate 95% confidence intervals. Median follow-up time was 5.14 years (interquartile range, 3.91-6.00) for the intensive treatment group and 5.07 years (interquartile range, 3.87-5.98) for the standard treatment group. For group comparison of incidence, hazard ratio, 0.83; 95% CI, 0.67-1.04; P=.10.

Figure 3.. Probable Dementia in Intensive vs Standard Treatment Groups by Subgroup

Chronic kidney disease was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 based on the Modification of Diet in Renal Disease Study equation. Systolic blood pressure tertiles were based on blood pressure measured at the randomization visit.