Targeting the brain: Lower blood pressure targets may not reduce dementia
The 2015 SPRINT trial demonstrated that intensive blood pressure control using a systolic blood pressure target of <120 mmHg reduced the risk of cardiovascular events and death from any cause compared to a target of <140 mmHg. This benefit is based on using a specific blood pressure measurement protocol and comes at a cost of increased risk of syncope and hypotension (see the SPRINT Trial Summary in DynaMed Plus). The blood pressure measurement protocol required participants to sit alone in a quiet room for 5 minutes, after which time three separate automated blood pressure readings were obtained and averaged. The original trial was stopped early after 4 years due to a difference in the primary outcome. The SPRINT MIND trial (JAMA 2019 Feb 12) is a prespecified examination of the effects of intensive blood pressure control on probable dementia. The primary cognitive outcome of the occurrence of probable dementia was determined using multiple assessment methods in a stepwise fashion. Testing performed at multiple time-points included in-person Montreal Cognitive Assessment (MoCA), learning and memory testing, and processing speed testing. For those with evidence of cognitive impairment, a Functional Activities Questionnaire was also administered. If in-person testing could not be performed, a validated telephone questionnaire was administered. Following testing, participants were categorized into no cognitive impairment, mild cognitive impairment (MCI), probable dementia, or unable to classify by a panel of experts blinded to study assignment and blood pressure data. Completion rates of testing were over 90% in both groups at the 4- year mark, but declined precipitously as the trial closed (60% completion rate at mean 6 years extended follow-up). The 798 participants excluded from analysis because cognitive testing could not be performed included more women, ethnic minorities, and those aged 75 and over. Over the 4-year follow-up period, the authors found no difference in the primary outcome of occurrence of probable dementia in patients with intensive blood pressure control compared to standard blood pressure control (hazard ratio [HR] 0.83, 95% CI 0.67-1.04). In a prespecified secondary analysis, there was a reduction in MCI (14.6 vs. 18.3 per 1000 person years, HR 0.81, 95% CI 0.69-0.95).
The SPRINT MIND trial failed to demonstrate reduction in dementia with intensive blood pressure control. Some commentators have pointed to the reduction in incidence of MCI as evidence of benefit, but the results should be interpreted with caution. The decrease in rate of MCI was only 3.7 per 1000 person years. MCI, by definition, does not affect daily function and many patients with MCI do not develop dementia. Dementia has a slow progression and this trial was stopped early at just 4 years, with a high drop-out rate at extended follow-up. In addition to confounding from the high drop-out rate, those at higher risk of dementia, such as those with diabetes and history of stroke, were likely to be excluded from the trial and from data analysis, as higher rates of women, ethnic minorities, and the elderly did not complete cognitive testing. Also consider that the participants in this trial underwent blood pressure measurement in a far different manner than blood pressure readings obtained in most busy offices. All of this should be taken into account when discussing the ideal blood pressure target with your older adult patients.
DynaMed Plus EBM Focus Editorial Team
This EBM Focus was written by Carina Brown, MD, Faculty Development and Information Mastery Fellow and Clinical Instructor at the University of Virginia. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed Plus and Associate Professor in Family Medicine at the University of Massachusetts Medical School and Katharine DeGeorge, MD, MS, Assistant Professor in Family Medicine at the University of Virginia and Clinical Editor at DynaMed Plus.