The latest on protection of cognition with blood pressure lowering: a comment

The 2019 publication of the SPRINT-MIND* study has once again raised the possibility that sufficient control of systolic blood pressure (BP) may reduce risk of developing cognitive impairment¹. SPRINT MIND was  a randomised open label two arm trial with one arm aiming to achieve systolic BPs of <120mmHg and the other aiming to achieve a pressure of <140mmHg. Participants had hypertension and were at increased risk of cardiovascular disease but were without prior stroke or diabetes. The trial reported a statistically significant reduction in the risk of developing mild cognitive impairment (MCI) in the lower BP arm (Hazard Ratio (HR) 0.81 (95% Confidence Intervals (CI) 0.69:0.95) and a non-statistically significant result for their primary endpoint of incident all-cause dementia (HR0.83 95%CI 0.67:1.04)¹.

There are a number of angles to take into account when evaluating this finding.

SPRINT-MIND and the clinical trial context

SPRINT-MIND is the latest in a 3-decade sequence of trials achieving BP differences between randomised arms and reporting incident dementia or cognitive decline (examples include ^2-5). Prior trials report largely concordant results with lower, but not statistically significantly lower rates of incident dementia or MCI in their reduced BP arms. Perhaps uniquely for a clinically and socially significant outcome such as dementia; due to the strong association between higher BP and cardiovascular events dementia trials have been constrained within cardiovascular driven BP goals and treatment guidelines. In particular, this has resulted in varied trial populations and incrementally lower BP goals over time with SPRINT MIND the lowest yet. Furthermore several (including SPRINT-MIND) were obliged to stop earlier than planned due to observed cardiovascular benefit thus restricting their ability to collect cognitive outcomes whilst also maintaining a BP difference between randomised arms and reducing their power to assess cognitive and dementia outcomes. Shorter follow up and lower goal BPs are particularly relevant for dementia and cognitive decline. Not only does dementia have a long pro-dromal phase but there is also the possibility that long-term hypertension may impair cerebral autoregulation and raise the risk of cognitive impairment with excessive BP lowering. Furthermore, hypertension may not occur in isolation. Several modifiable risk factors exist for dementia and cognitive decline and evidence shows both a dose response, such that a greater risk factor burden is associated with a greater risk,⁶ but also promising trial evidence from multifactorial interventions designed to simultaneously reduce risk across multiple areas⁷.

Remaining gaps in the evidence base

Current evidence suggests that lowering BP may reduce the risk of cognitive decline and dementia. This may be complemented by a concurrent reduction across multiple dementia risk factors.

In general reducing risk factor exposure is unlikely to increase risk and, in any event, is broadly recommended for cardiovascular health.
What we don’t yet know is how BP lowering, particularly to the goal BP used in the SPRINT MIND trial, is likely to impact the wider, non-SPRINT population and in particular, higher risk groups⁸. Building on the evidence from SPRINT MIND we now need to understand whether BP lowering to these new lower levels is equally beneficial across the board. For example, in those at extreme age where the trial evidence is currently for a goal BP of <150mmHg², in those in earlier midlife where BP is not yet >140mmHg and where treatment would mean years of medication⁸, in those with prior stroke or TIA and in those with multiple concomitant disease or risk factor burden⁹.

The results of SPRINT MIND are congruent with prior trials and represent a further step forward in our understanding. We now need to expand our knowledge to support appropriate targeted practice in the wider population.  

* Systolic blood Pressure Intervention Trial – Memory and Cognition IN Decreased Hypertension (SPRINT-MIND).

Williamson J, SPRINT Research Group. A randomised trial of intensive versus standard systolic blood pressure control and the risk of mild cognitive impairment and dementia: results from SPRINT MIND. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association; 2018;14:1665-6

Commentary by: Ruth Peters, Kaarin J. Anstey, Kristine Yaffe

References

1. Peters R et al. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet Neurol 2008;7: 683-9.
2. Tzourio C et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Int Med 2003;163:1069-75.
3. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265:3255-64.
4. Forette F et al. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Int Med 2002;162:2046-52.
5. Peters R et al. Combining modifiable risk factors and risk of dementia: a systematic review and meta-analysis BMJ Open 2019;9doi: 10.1136/bmjopen-2018-022846
6. Ngandu T et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. 2015;385:2255-63.
7. Iadecola C et al on behalf of the American Heart Association Council on Hypertension; Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Stroke Council. Impact of Hypertension on Cognitive Function: A Scientific Statement From the American Heart Association. Hypertens 2016; doi:HYP.0000000000000053
8. Yaffe K. Prevention of Cognitive Impairment With Intensive Systolic Blood Pressure Control. JAMA. 2019;321:548–549