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Intensive BP lowering does not impact cerebral blood flow in small vessel disease

Jackey Suen
12 Mar 2018

Intensive blood pressure (BP) lowering has no impact on cerebral blood flow in patients with small vessel disease, a recent study confirms.

“It has remained uncertain whether intensive BP lowering is associated with worse outcome in patients with severe small vessel disease and confluent white matter hyperintensities, in whom severely reduced cerebral blood flow and cerebral autoregulation have been reported,” noted the study investigators.

The PRESERVE study is an ongoing, 2-year, randomized trial that evaluates standard (systolic BP target, 130–140 mm Hg) vs intensive (systolic BP target, <125 mm Hg) BP-lowering treatment in patients with severe small vessel disease on outcomes of white matter disease and cognition. The present analysis investigated the change in cerebral blood flow  in 62 evaluable participants over the first 3 months of the study. [JAMA Neurol 2018, doi: 10.1001/jamaneurol.2017.5153]

At 3 months, systolic BP was significantly decreased in the intensive vs standard treatment group (mean reduction, 27 vs 8 mm Hg; p<0.001). Overall, 62 percent of patients in the intensive treatment group and 39 percent of patients in the standard treatment group reached their BP targets.

The change in whole-brain cerebral blood flow, the primary endpoint of the study, was comparable between both treatment groups. The mean change was -0.7 mL/min/100 g in patients receiving intensive BP-lowering medications vs -0.5 mL/min/100 g in those receiving standard BP-lowering medications. Similarly, no significant difference in cerebral blood flow change was observed between treatment groups for grey matter, all white matter or normal-appearing white matter.

There were no differences in the number of study drug-related adverse events (AEs) between the two groups. No severe AEs were reported.

“Our results showed no difference in cerebral blood flow change over the 3-month follow-up period between the two treatment groups,” the investigators wrote. “We also found no excess AEs in the intensive treatment group, including potential hypotension-related events. This provides support that intensive BP reduction regimens do not cause hypoperfusion in patients with severe symptomatic small vessel disease.”

“Intensive BP lowering has been shown to reduce cardiovascular endpoints in patients without cardiovascular disease. However, there is concern that it may be hazardous in patients with extensive small vessel disease, as overzealous BP lowering could exacerbate hypoperfusion, extending brain injury,” they continued. “Therefore, our results are reassuring that intensive treatment can be used in this patient population.”

“Our findings do not support previous work in patients with hypertension without stroke or small vessel disease, which found that intensive treatment increased cerebral blood flow via resetting of the cerebral autoregulatory curve,” the investigators noted. [Hypertension 2013;61:1309-1315] “This may be because the elderly participants with hypertension in this study had less severe cerebrovascular disease than patients with small vessel disease, and thus cerebral blood flow increase may not be possible due to the extent of their pre-existing damage or may take a longer time to achieve.”

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