PRESERVE: Randomized Trial of Intensive Versus Standard Blood Pressure Control in Small Vessel Disease

Abstract

Background and Purpose: In cerebral small vessel disease, cerebral blood flow and autoregulation are impaired and therefore excessive blood pressure reduction could possibly accelerate white matter damage and worsen outcome. The trial determined, in severe symptomatic cerebral small vessel disease, whether intensive blood pressure lowering resulted in progression of white matter damage assessed using diffusion tensor imaging. Methods: Randomized, parallel, multicenter controlled, blinded-outcomes clinical trial. One hundred eleven participants with magnetic resonance imaging confirmed symptomatic lacunar infarct and confluent white matter hyperintensities and were recruited and randomized to standard (systolic=130–140 mmHg) (N=56) or intensive (systolic<125 mmHg) (N=55) blood pressure targets. The primary end point was change in diffusion tensor imaging white matter mean diffusivity peak height between baseline and 24 months. Secondary end points were other magnetic resonance imaging markers and cognition. Results: Patients were mean 68 years and 60% male. Mean (SD) blood pressure reduced by −15.3 (15.4) and −23.1 (22.04) mm Hg in the standard/intensive groups, respectively ( P <0.001). There was no difference between treatment groups for the primary end point: standard, adjusted mean (SE)=12.5×10 −3 (0.2×10 −3 ); intensive, 12.5×10 −3 (0.2×10 −3 ), P =0.92. In the whole population over 24 months follow-up, there was a significant deterioration in white matter microstructure but no detectable decrease in cognition. Conclusions: Intensive blood pressure lowering in severe cerebral small vessel disease was not associated with progression of white matter damage on diffusion tensor imaging or magnetic resonance imaging. In a multicentre study setting over 2 years, multimodal diffusion tensor imaging-magnetic resonance imaging was more sensitive to detecting change than cognitive testing. REGISTRATION: URL: https://www.isrctn.com ; Unique identifier: ISRCTN37694103.

European Stroke Organisation and European Academy of Neurology joint guidelines on post‐stroke cognitive impairment

“…However, for a non‐stroke cohort, the recent SPRINT‐MIND study suggested intensive blood pressure‐lowering to a systolic of 120 mmHg, compared with standard lowering to 140 mmHg, was associated with a reduced incidence of mild cognitive decline and the combined endpoint of MCI and dementia [199]. There has been concern that intensive blood pressure‐lowering may have risks in people living with extensive small vessel disease and impaired cerebral autoregulation, but the recent PRESERVE study showed no reduction in cerebral blood flow, increased white matter damage, or difference on cognition associated with blood pressure‐lowering to 125 mmHg compared with 140 mmHg [200]. Consistent with this finding, the SPS3 cognitive substudy reported no adverse consequences of lowering blood pressure to this level [23].…”

Influence of Baseline Diastolic Blood Pressure on the Effects of Intensive Systolic Blood Pressure Lowering on the Risk of Stroke

“…33 Furthermore, In a randomized controlled trial of standard (systolic=130–140 mm Hg; N=56) or intensive (systolic<125 mm Hg; N=55) SBP lowering, intensive SBP had no significant effects on white matter integrity in patients with small vessel disease and history of lacunar stroke suggesting the safety of BP lowering in those with severe small vessel disease of the brain. 36 Hence, low baseline DBP should not be an impediment to guidelines 8 recommended SBP goal of<130 mm Hg in persons with previous history of stroke.…”

Contrast agent‐free state‐of‐the‐art magnetic resonance imaging on cerebral small vessel disease – Part 2: Diffusion tensor imaging and functional magnetic resonance imaging

“…After intensive blood pressure lowering in severe cSVD patients, no difference in microstructural integrity evaluated with DTI was found, suggesting that blood pressure control is a protective factor for cSVD development and that DTI is a sensitive marker for evaluating such a therapeutic strategy 123 …”

“…122 After intensive blood pressure lowering in severe cSVD patients, no difference in microstructural integrity evaluated with DTI was found, suggesting that blood pressure control is a protective factor for cSVD development and that DTI is a sensitive marker for evaluating such a therapeutic strategy. 123 Finally, depression in the setting of cSVD has also been the subject of investigation. Depression in cSVD patients has been associated with reduced WM integrity measured through FA.…”