PracticeUpdate Cardiology March 2019

EDITOR’S PICKS 12

Intensive Blood Pressure Control Does Not Decrease Dementia Risk Journal of the American Medical Association

Take-home message • In this study, 9361 adults aged 50 years or older (35.6% women) with hypertension and no diabetes or history of stroke were randomized to a systolic blood pressure goal of <120 mmHg (intensive treatment) or <140 mmHg (standard treatment) to determine the effect of intensive blood pressure control on dementia. Of these participants, 8563 completed at least one follow-up cognitive assessment. During a median follow-up of 5.11 years, probable dementia was reported in 149 participants in the intensive treatment group compared with 176 participants in the standard treatment group. Intensive blood pressure control led to a significantly reduced risk of mild cognitive impairment and the combined rate of mild cognitive impairment and probable dementia. However, intensive blood pressure control did not signifi- cantly reduce the risk of probable dementia in ambulatory adults with hypertension. • Due to early study termination and a low number of dementia cases, this study may not have had adequate power to investigate the endpoint of reduced risk of probable dementia. Abstract

RESULTS Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cog- nitive 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 stand- ard 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 per- son-years; HR, 0.85; 95% CI, 0.74-0.97).

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 cog- nitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive out- comes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia.

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 dia- betes 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

COMMENT By Clyde W. Yancy MD, MSc, MACC, FAHA, MACP, FHFSA Contemporary treatment of HTN – Both safe and effective T he stunning results of SPRINT substantially influenced the lat- est guidelines to treat hypertension. Incontrovertible evidence now supports goal blood pressure reduction to 120/80mmHg in those patients deemed at higher cardiovascular risk as a means to reduce total mortality, and, uniquely, to prevent heart failure. The nearly 40% reduction in the initial onset of hospitalized heart failure has major public health implications. The transitions in care incited by the SPRINT data have been disruptive: 1. a risk-based assessment now guides antihypertensive therapy; 2. goal blood pressure reduction is much more substantial than in any prior guideline; 3. home blood pressure readings now drive treatment decisions; and 4. lifestyle modification is now even more important. With such change has come substantial resistance – largely driven by concerns that excessive blood pressure reduction may not be safe and might lead to cognitive impairment via changes in cere- bral blood flow, especially in older persons.

The SPRINT MIND findings are now available. Although the primary study was halted early due to profound benefits, the SPRINT MIND study continued active follow-up with a design intended to identify protection from dementia associated with aggressive blood pres- sure lowering. The primary outcome of dementia was not reduced by aggressive blood pressure control (HR, 0.83; 95% CI 0.67–1.04), but important secondary outcomes, including mild cognitive impair- ment (19% reduction) and a combined endpoint of mild cognitive impairment and probable dementia (15% reduction), were both sig- nificantly reduced. How should readers of PracticeUpdate Cardiology interpret these data? Note that a reduction in dementia was nearly reached, limited by early cessation of the primary trial and fewer dementia events than planned. But, importantly, there was no increase in dementia (over an approximate 5-year follow-up), and the positive influence on mild cognitive impairment in a population, mean age of approximately 68, is of considerable importance. If the reluctance to embrace goal blood pressure reduction was at all based on concerns of promoting dementia or cognitive dysfunction in older persons with hypertension, those concerns should be relieved.

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