Association of Intensive vs Standard Blood Pressure Control With Regional Changes in Cerebral Small Vessel Disease Biomarkers

Abstract

ImportanceLittle is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers.ObjectiveTo investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF).Design, Setting, and ParticipantsThe Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter randomized clinical trial that compared intensive systolic BP (SBP) control (SBP target <120 mm Hg) vs standard control (SBP target <140 mm Hg) among participants aged 50 years or older with hypertension and without diabetes or a history of stroke. The study began randomization on November 8, 2010, and stopped July 1, 2016, with a follow-up duration of approximately 4 years. A total of 670 and 458 participants completed brain magnetic resonance imaging at baseline and follow-up, respectively, and comprise the cohort for this post hoc analysis. Statistical analyses for this post hoc analysis were performed between August 2020 and October 2022.InterventionsAt baseline, 355 participants received intensive SBP treatment and 315 participants received standard SBP treatment.Main Outcomes and MeasuresThe main outcomes were regional changes in WMLs, FA, MD (in white matter regions of interest), and CBF (in gray matter regions of interest).ResultsAt baseline, 355 participants (mean [SD] age, 67.7 [8.0] years; 200 men [56.3%]) received intensive BP treatment and 315 participants (mean [SD] age, 67.0 [8.4] years; 199 men [63.2%]) received standard BP treatment. Intensive treatment was associated with smaller mean increases in WML volume compared with standard treatment (644.5 mm3 vs 1258.1 mm3). The smaller mean increases were observed specifically in the deep white matter regions of the left anterior corona radiata (intensive treatment, 30.3 mm3 [95% CI, 16.0-44.5 mm3]; standard treatment, 80.5 mm3 [95% CI, 53.8-107.2 mm3]), left tapetum (intensive treatment, 11.8 mm3 [95% CI, 4.4-19.2 mm3]; standard treatment, 27.2 mm3 [95% CI, 19.4-35.0 mm3]), left superior fronto-occipital fasciculus (intensive treatment, 3.2 mm3 [95% CI, 0.7-5.8 mm3]; standard treatment, 9.4 mm3 [95% CI, 5.5-13.4 mm3]), left posterior corona radiata (intensive treatment, 26.0 mm3 [95% CI, 12.9-39.1 mm3]; standard treatment, 52.3 mm3 [95% CI, 34.8-69.8 mm3]), left splenium of the corpus callosum (intensive treatment, 45.4 mm3 [95% CI, 25.1-65.7 mm3]; standard treatment, 83.0 mm3 [95% CI, 58.7-107.2 mm3]), left posterior thalamic radiation (intensive treatment, 53.0 mm3 [95% CI, 29.8-76.2 mm3]; standard treatment, 106.9 mm3 [95% CI, 73.4-140.3 mm3]), and right posterior thalamic radiation (intensive treatment, 49.5 mm3 [95% CI, 24.3-74.7 mm3]; standard treatment, 102.6 mm3 [95% CI, 71.0-134.2 mm3]).Conclusions and RelevanceThis study suggests that intensive BP treatment, compared with standard treatment, was associated with a slower increase of WMLs, improved diffusion tensor imaging, and FA and CBF changes in several brain regions that represent vulnerable areas that may benefit from more strict BP control.Trial RegistrationClinicalTrials.gov Identifier: NCT01206062

Associations of Cerebrovascular Regulation and Arterial Stiffness With Cerebral Small Vessel Disease: A Systematic Review and Meta‐Analysis

“…Previous literature has established the contributions of high blood pressure and hypertension 223 , 224 to cSVD. However, studies using antihypertensive medications targeting reductions in cSVD have been sparse 8 and demonstrate overall mixed responses, 225 , 226 , 227 , 228 suggesting that additional contributing factors may interact with or independent of hypertension and other traditional comorbidities. In line with the present study's findings, a recent series of randomized controlled trials, LACI‐1 and LACI‐2 (Lacunar Intervention Trial‐1 and Trial‐2), demonstrated that treatments targeting vascular endothelial function improved cerebrovascular reactivity in patients with cSVD 229 and improved their outcomes.…”

Hypertension, Neurodegeneration, and Cognitive Decline

“…161 Intriguingly, intensive BP-lowering regimens may offer increased benefit relative to standard therapy. Recent findings from secondary analyses of the SPRINT-MIND data set indicate diminished risk of cognitive decline, 10,95 WML development, 162 and probable dementia 9 in patients undergoing intensive blood-pressure-lowering (SBP <120 mm Hg). Intensive regimens, but not standard, were also found to ameliorate cognitive decline in patients with high BPV.…”

Zerebrale Mikroangiopathie: Fortschritte im Verständnis der Pathophysiologie

“…Korrespondierend kann gezeigt werden, dass eine intensive Senkung des systolischen Blutdrucks auf Werte < 120 mmHg das Demenzrisiko reduziert und eine Progression der zerebralen Mikroangiopathie verlangsamt [16,17].…”