By Neal S. Parikh, MD, MS
Assistant Professor of Neurology, Weill Cornell Medical College
SYNOPSIS: Patients with hypertension were randomized to intensive vs. standard blood pressure control and underwent baseline and follow-up cerebral perfusion imaging. Intensive blood pressure treatment was associated with improved cerebral perfusion over time.
SOURCE: Dolui S, Detre JA, Gaussoin SA, et al. Association of intensive vs standard blood pressure control with cerebral blood flow: Secondary analysis of the SPRINT MIND randomized clinical trial. JAMA Neurol 2022;79:380-389.
The deleterious effect of hypertension on cardiovascular and brain health is uncontroversial. It is well recognized that treating hypertension is critical for improving population health. Results of the Systolic Blood Pressure Intervention Trial (SPRINT) suggest that intensive treatment of hypertension has cardiovascular health advantages over standard hypertension treatment. The extent to which intensive hypertension treatment is safe and beneficial from a brain perfusion perspective has remained unclear.
Hypertension has been associated with cognitive impairment, dementia, and related imaging biomarkers in numerous observational studies. SPRINT pivotally demonstrated that intensive blood pressure control to a target of < 120 mmHg reduced the incidence of cognitive impairment, as compared to standard control to a target of < 140 mmHg. However, physiological considerations have given rise to theoretical concerns about the safety of intensive blood pressure control. Specifically, cerebral autoregulation maintains cerebral perfusion across a range of systemic blood pressure conditions. One recalcitrant concern has been that lowering blood pressure too aggressively may cause the systemic blood pressure to fall below autoregulation thresholds required to maintain cerebral perfusion, thus leading to ischemic injury. Two prior small studies had found that lowering blood pressure to < 125 mmHg was safe; hypoperfusion did not occur. But, given the small sizes and brief duration of hypertension treatment in these studies, concerns remained.
Dolui and colleagues sought to resolve this issue by analyzing data from SPRINT. In review, participants in this trial were hypertensive adults older than age 50 years with at least one cardiovascular risk factor. People with prior stroke and dementia were excluded, as were people with diabetes. In an imaging sub-study, participants were asked to undergo brain magnetic resonance imaging (MRI) with arterial spin labeled (ASL) perfusion imaging, at baseline. ASL perfusion imaging is a noninvasive technique for assessing cerebral perfusion. Approximately 48 months later, participants were asked to undergo a repeat brain MRI with ASL perfusion imaging. In the present analysis, the primary outcome was change in whole brain cerebral blood flow, and secondary outcomes were white matter, gray matter, and periventricular perfusion.
The authors included 315 participants who had a baseline and follow-up ASL study; 168 participants had been randomized to the intensive treatment arm and 147 had been randomized to the standard treatment arm. The mean age of participants was 68 years, and 40% were women. The achieved blood pressure in the intensive treatment arm was 120.5 mmHg, compared to 134.4 mmHg in the standard treatment arm.
In models adjusted for age, sex, and time since randomization, the central finding was that intensive blood pressure control was associated with an increase in whole brain cerebral blood flow compared to standard blood pressure control (increased by 2.3 mL/100 g/min; 95% confidence interval, 0.3 to 4.3). Perfusion also was increased in white matter, and statistically significant changes in gray matter and periventricular perfusion were not seen. There were two additional valuable observations. First, the beneficial effect of intensive blood pressure control was greater in participants with a history of cardiovascular disease. Second, antihypertensive medication class did not influence findings.
In summary, intensive blood pressure control for four years did not worsen cerebral perfusion, but rather improved cerebral perfusion. These findings suggest that intensive blood pressure control not only is safe but also beneficial for brain health, insofar as enhanced brain perfusion is clinically meaningful.
COMMENTARY
Apart from issues related to small sample size and high rate of missing follow-up MRIs, this study provides valuable reassurance that intensive blood pressure control is unlikely to jeopardize cerebral perfusion in stroke-free, dementia-free, nondiabetic individuals. Further study may be required before generalizing the findings of the present analysis to patients with symptomatic cerebrovascular disease and those with diabetes. Although the findings are reassuring, the underlying mechanisms of increased cerebral perfusion with intensive blood pressure control are unclear.
On one hand, the absence of clear biological mechanisms raises doubts. On the other hand, SPRINT demonstrated reductions in the hard clinical endpoints of cardiovascular disease, death, and cognitive impairment with intensive blood pressure control. In this context, the available data on brain perfusion provide sufficient counterpoint to lingering theoretical concerns. Although a more in-depth understanding of cerebral physiology is undoubtedly important, it may be time devote at least as much attention to implementing and disseminating what we have learned from SPRINT.
