Intensive Blood Pressure Target Leads to Increased Cerebral Perfusion, SPRINT MIND Data Suggest

A study recently demonstrated that targeting longer-term intensive blood pressure control over a 4-year period may be associated with a subtle but significant increase in cerebral blood flow.

A secondary analysis from the phase 3 SPRINT MIND randomized clinical trial (NCT01206062) showed that an intensive systolic blood pressure (SBP) target of less than 120 mm Hg was associated with a significantly larger increase in cerebral blood flow (CBF) compared with a standard blood pressure target of less than 140 mm Hg in adults with hypertension. Notably, this association was even more pronounced among those with a history of cardiovascular disease.

After 4 years of follow-up, the mean whole brain (WB) CBF in the intensive treatment group increased by 1.46 mL/100 g/min (95% CI, 0.08-2.83) while WB CBF decreased in the standard treatment group, with mean change from baseline of –0.84 mL/100 g/min (95% CI, –2.30 to 0.61). Although the mechanistic reasons for this increase are uncertain, the investigators concluded that the findings suggest a complex relationship between BP and CBF that is "beyond simply static cerebral perfusion pressure and cerebrovascular autoregulation."

"One key barrier to implementation of intensive treatment was a concern that intensive treatment might reduce the BP below the cerebral autoregulatory limit, leading to cerebral hypoperfusion," senior author Ilya M. Nasrallah, MD, PhD, assistant professor of radiology, Hospital of the University of Pennsylvania, and colleagues, wrote. "Our findings suggest that this does not occur, at least on a chronic basis. Note that this relates to static cerebral autoregulation rather than dynamic autoregulation, which describes CBF changes in response to a more rapid change in BP."

The investigators evaluated longitudinal arterial spin labeled (ASL) perfusion MRI, which provides noninvasive quantification of regional CBF, to assess the association of intensive SBP lowering with cerebral perfusion. The primary outcome, change in WB CBF, was evaluated in a cohort of 547 adults aged 50 years or older with hypertension and increased cardiovascular risk but without diabetes or dementia.

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Of the 547 participants having ASL scans that passed quality control at baseline, 315 participants had follow-up scans that also passed quality control. At baseline, the mean age of the overall sample was 67.5 years (SD, 8.1), 219 (40.0%) were women, 176 (32.2%) were African American, and 35 (6.4%) were Hispanic. The mean SBP was 137.8 mm Hg (SD, 15.2) at baseline.

The documented increase in mean WB CBF within the intensive treatment group was still significantly greater than standard treatment (mean between-group difference, 2.30 mL/100 g/min; 95% CI, 0.30-4.30) at 4 years after adjusting for sex, age, and days since randomization. Between the 2 treatment groups, there were no significant differences in gray matter (GM) and periventricular white matter (WM) CGF.

In a subgroup analysis, those with a history of cerebrovascular disease demonstrated larger increases in CBF with intensive treatment than with standard treatment compared with those without baseline cardiovascular disease. There were no other significant subgroup interactions.

Nasrallah and his colleagues did not find any correlation between annualized changes in WB CBF and intracranial volume-adjusted total brain volume in either treatment group. In only the intensive treatment group, the annualized CBF change was correlated (p= –0.205; P = .01) with the change in WML volume. When both treatment groups were pooled together, CBF changes in GM, WM, and periventricular WM were correlated with changes in WM lesion volume.

The original results of SPRINT MIND, published in 2019, suggested that implanting an intensive strategy does not significantly reduce dementia risk compared with standard care. In the intensive treatment group (n = 4678), there were 7.2 cases of probable dementia per 1000 person-years (149 cases), compared to 8.6 cases per 1000 person-years (176 cases) in the standard treatment group (n = 4683), over the total median follow-up of 5.11 years (hazard ratio [HR], 0.83; 95% CI, 0.67 to 1.04).2

An additional substudy from the trial was published in April 2021 showed that intensive SBP treatment was associated with a small but statistically significant greater decrease in hippocampal volume relative to standard treatment. The results were consistent with the observation that intensive treatment is associated with greater decreases in total brain volume. In total, the mean hippocampal volume decreased from 7.45 cm3 to 7.39 cm3 (difference, ­–0.06 cm3; 95% CI, ­–0.08 to –0.04) in the intensive treatment group (n = 356) compared with 7.48 cm3 to 7.46 cm3 (difference, –0.02 cm3; 95% CI, –0.05 to –0.003) in the standard treatment group (n = 317; between-group difference in change, –0.033 cm3; 95% CI, –0.062 to –0.003; = .03).3

REFERENCES
1. Dolui S, Detre JA, Gaussoin SA, et al. Association of intensive vs standard blood pressure control with cerebral blood flow: a secondary analysis of the SPRINT MIND randomized clinical trial. JAMA Neurol. Published online March 7, 2022. doi:10.1001/jamaneurol.2022.0074

2. Williamson Jd, Pajewski NM, Auchus AP, et al. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA. 2019;321(6):553-561. doi:10.1001/jama.2018.21442.
3. Nasrallah IM, Gaussoin SA, Pomponio R, et al. Association of intensive vs standard blood pressure control with magnetic resonance imaging biomarkers of Alzheimer disease: secondary analysis of the SPRINT MIND randomized trial. JAMA Neurol. 2021;78(5):568-577. doi: 10.1001/jamaneurol.2021.0178.