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EDITOR’S PICKS 16

Effect of Standard vs Intensive Blood Pressure Control on Cerebral Blood Flow in Small- Vessel Disease JAMA Neurology Take-home message • This is a report from a nested study within the ongoing PRESERVE study, a rand- omized, controlled trial of intensive systolic blood pressure (SBP) reduction (<125 mm Hg) compared with standard SBP goals (130–140 mm Hg) in patients with hypertension, severe small-vessel disease (confluent white matter changes), and MRI-confirmed lacunar stroke. Cerebral perfusion, assessed with MRI/arterial spin labeling sequences, was examined between the two groups. In the 62 enrolled patients, 29 were randomized to intensive blood pressure reduction. The authors found no change in cerebral perfusion between standard and intensive SBP reduc- tion. It should be noted that the intensive blood pressure reduction group achieved target SBP 62% of the time. • Intensive blood pressure lowering did not appear to change perfusion in a small group of patients with known small-vessel disease. This article is timely in light of the recent change in blood pressure guidelines with lower targets, although the small sample size precludes broad generalization. Mona Bahouth MD T his is a fairly small randomized trial designed to identify the effects of intensive blood pressure lowering relative to moderate blood pressure lowering in peo- ple with cerebral small-vessel disease on cerebral blood flow (CBF; measured with arterial spin labeling MRI). Although the trial had an imaging endpoint rather than a clinical endpoint, it suggests that the intensive blood pressure lowering did not adversely affect CBF. Only 62% of the participants in the intensive blood pressure lowering arm achieved the target blood pressure. Nevertheless, there were no indi- viduals with a marked decrease in CBF. This study adds to accumulating evidence that lowering blood pressure only has negative effects in relatively rare cases of severe large-vessel stenosis, in which the perfusion in the territory of the affected vessel is severely compromised. In these rare cases, focal CBF has been shown to be reduced (to <60% of normal CBF) to a level that there is a loss of function; and lowering blood pressure can lead to infarction in that territory. Furthermore, an increase in the mean arterial blood pressure can result in improved perfusion and function in the territory of the severely narrowed large vessel due to the loss of autoregulation in ischemic tissue. Whole-brain CBF is not affected. This study points to the importance of an individualized approach to stroke manage- ment. In nearly all cases, lowering blood pressure in people with cerebral small-vessel disease is important to reduce the risk of stroke. The rare exceptions are those who have symptomatic ischemia due to large-vessel stenosis or occlusion. Even in these patients, blood pressure can usually be slowly lowered to normal over several weeks. COMMENT By Argye Elizabeth Hillis MD, MA

Abstract IMPORTANCE Blood pressure (BP) lowering is con- sidered neuroprotective in patients with cerebral small vessel disease; however, more intensive regimens may increase cerebral hypoperfusion. This study examined the effect of standard vs intensive BP treatment on cerebral perfusion in patients with severe small vessel disease. OBJECTIVE To investigate whether standard vs intensive BP lowering over 3 months causes decreased cerebral perfusion in small vessel disease. DESIGN, SETTING, AND PARTICIPANTS This ran- domized clinical trial took place at 2 English university medical centers. Patients were ran- domized via a central online system (in a 1:1 ratio). Seventy patients with hypertension and with magnetic resonance imaging-confirmed symptomatic lacunar infarct and confluent white matter hyperintensities were recruited between February 29, 2012, and October 21, 2015, and randomized (36 in the standard group and 34 in the intensive group). Analyzable data were available in 62 patients, 33 in the standard group and 29 in the intensive group, for intent-to-treat analysis. This experiment examines the 3-month follow-up period. INTERVENTIONS Patients were randomized to standard (systolic, 130-140 mm Hg) or inten- sive (systolic, <125 mm Hg) BP targets, to be achieved through medication changes. MAIN OUTCOMES AND MEASURES Cerebral perfu- sion was measured using arterial spin labeling; the primary end point was change in global perfusion between baseline and 3 months,

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