麻豆传媒

Intensive blood pressure lowering did not reduce cerebral blood flow in patients with severe small vessel disease more than standard blood pressure therapy did, the randomized controlled PRESERVE trial found.

Changes in global perfusion did not differ between severe cerebral small vessel disease patients whose systolic blood pressure was lowered to 141 mm Hg versus 126 mm Hg, reported Hugh Markus, MD, of the University of Cambridge in the U.K., and colleagues online in

"Small vessel disease causes 20% of all strokes and is the most common cause of vascular dementia, Markus told 麻豆传媒. "Hypertension is the major risk factor and treating it intensively to target of less than 130 mm Hg systolic can reduce the disease. However, in patients with severe small vessel disease -- in whom cerebral auto-regulation can be impaired -- there has been concern, supported by anecdotal reports, that intensive blood pressure treatment could reduce cerebral blood flow and therefore worsen cognitive impairment.

"We showed that intensive blood pressure lowering appeared to be safe and did not reduce cerebral blood flow compared with standard blood pressure therapy. This suggests that intensive blood pressure lowering is safe in this group of patients and is therefore recommended, as it is likely to reduce disease progression and other cardiovascular complications."

PRESERVE is a 2-year trial at two English university medical centers to test standard versus intensive blood pressure treatment in patients with severe small vessel disease on white matter disease and cognition. This latest report was a nested substudy that looked at cerebral blood flow changes over the first 3 months of the trial.

The researchers recruited patients with hypertension, confirmed lacunar stroke, and confluent white matter hyperintensities from 2012 to 2015, randomizing them to either standard (130-140 mm Hg systolic) or intensive (<125 mm Hg systolic) blood pressure targets through medication. Excluded were patients who had experienced a stroke within 3 months before the study started.

Of 70 patients recruited, usable data were available for 62 -- 33 in the standard group and 29 in the intensive group -- for intent-to-treat analysis.

The primary endpoint was the change in global perfusion from baseline to 3 months, measured by arterial spin labeling, a no-contrast magnetic resonance imaging technique that uses the difference in signal between where blood has or has not been magnetically tagged to measure cerebral blood flow.

Among the 62 participants, the average age was about 69, and 60% were male. In the standard group, mean systolic blood pressure decreased by 8 mm Hg to achieve an average of 141 mm Hg. In the intensive group, systolic blood pressure decreased by 27 mm Hg on average to reach a pressure of 126 mm Hg.

Change in whole-brain cerebral blood flow did not significantly differ between the two groups: In the standard group, the mean change was −0.5±9.4 mL/min/100 g; in the intensive group, it was 0.7±8.6 mL/min/100 g (partial η2, 0.004; 95%CI, −3.551 to 5.818; P=0.63).

The researchers observed no differences when they examined gray or white matter only, or when looking only at those patients who achieved the target blood pressure. The number of adverse events also did not differ between treatment groups -- an average of 0.21±0.65 for the standard group and 0.32±0.75 for the intensive group (P=0.44).

"This study adds further support regarding the safety of intensive blood pressuring lowering in patients with previous stroke, and specifically lacunar stroke," said Alexander Merkler, MD, of Weill Cornell Medicine in New York City, who was not involved with the study. "More data will be necessary to evaluate whether intensive blood pressure reduction will lead to a decreased risk of recurrent stroke and dementia."

These 3-month PRESERVE findings do not support in patients with hypertension without stroke or small vessel disease, which found that intensive blood pressure treatment raised cerebral blood flow by resetting the cerebral auto-regulatory curve, the researchers noted. This may be because PRESERVE patients may have more damage from small vessel disease, or that a potential increase may occur over a longer period. The PRESERVE study will investigate this when the 2-year study is completed, Markus et al added.

Among the study limitations, the team said was that although the study achieved the target treatment group blood pressure difference of 15 mm Hg systolic, only 62% of the intensive group participants reached their target, which diminished the power for analysis of variance models. While the regression analysis also supports the conclusion that there is no connection between blood pressure and cerebral blood flow change, the results should be interpreted with a degree of caution.

In addition, the researchers wrote, because patients who had a stroke within 3 months were ineligible for the study, the findings do not apply to acute post-stroke treatment.

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