Lower Blood Pressure Slows Cerebral Small Vessel Disease Progression in SPRINT

Many people view a blood pressure reading as information about the heart. However, high blood pressure is also associated with brain changes that may accumulate for years before they become apparent.

These changes are known as cerebral small vessel disease. It involves the brain’s tiny blood vessels and the tissue around them, and has been associated with stroke, cognitive decline and dementia.

To investigate whether reducing blood pressure can slow these changes in the brain, Sokratis Charisis, a neurologist at Massachusetts General Hospital, Mohamad Habes, a neuroimaging researcher at UT Health San Antonio, and their colleagues compared brain scans taken roughly four years apart.

Their study showed that MRI indicators of small vessel disease advanced more slowly among people allocated a lower blood pressure target. Larger reductions in measured blood pressure were likewise linked with slower progression.

SPRINT blood pressure targets and brain scans

The researchers revisited SPRINT, a US clinical trial involving more than 9,300 adults aged 50 or over who had high blood pressure and an elevated risk of cardiovascular disease.

Participants were randomly allocated one of two targets for the upper figure in a blood pressure measurement, known as systolic pressure: under 120 mmHg or under 140 mmHg.

The intervention started to wind down in August 2015, earlier than planned, because the lower-target group experienced fewer heart attacks, strokes, episodes of heart failure, other acute coronary events and cardiovascular deaths combined.

SPRINT’s original report also found fewer deaths from all causes.

Some participants underwent brain scans at the beginning of the trial and again around four years later. A 2019 analysis reported that white matter lesions increased less in the lower-target group.

On MRI scans, these lesions show up as bright areas in the tissue that connects different brain regions. Other research reported by ScienceAlert has also explored associations between high blood pressure, brain structure and thinking abilities.

However, a single marker cannot reveal every process affecting small vessels.

"Small vessel disease affects the brain in several ways, and no single MRI marker captures the entire process," Habes told ScienceAlert.

Cerebral small vessel disease measured with combined MRI markers

For this analysis, the researchers merged three MRI indicators into a single statistical score: white matter lesions close to the brain’s fluid-filled cavities, freely moving water in white matter, and visible spaces surrounding tiny blood vessels deep within the brain. The score followed how these measures changed together rather than counting damaged vessels.

Among 663 participants with complete baseline measurements, 442 had follow-up scans that could be used. Their mean age was approximately 68, while the median interval between scans was 3.9 years.

At follow-up, mean systolic pressure had dropped from roughly 136 to 120 mmHg in the lower-target group. In the standard group, it fell from about 139 to 136 mmHg.

Progression of the combined MRI score was 16.9 percent lower for the group assigned the under-120 target than for the under-140 group, relative to the average disease burden at baseline.

The team next examined whether actual reductions in blood pressure were connected with differing MRI results. They compared each participant’s initial systolic pressure with the average of readings taken at appointments after 6, 9, 12, 15 and 18 months.

Relative to participants whose pressure increased, those whose pressure decreased by as much as 10 mmHg showed 21.2 percent less progression. The difference reached 26.3 percent for reductions of 10 to 20 mmHg, and 39.4 percent for decreases of at least 20 mmHg.

"The 39.4 percent means that participants whose systolic blood pressure fell by at least 20 mmHg had 39.4 percent less accumulation of small vessel disease burden, captured with our combined MRI measure, over time compared with participants whose blood pressure rose," Habes told ScienceAlert.

"It reflects slower accumulation of small vessel disease on MRI, not reversal of existing brain injury or disappearance of 39.4 percent of lesions."

What the findings do and do not show

The two findings are based on separate comparisons. The 16.9 percent result arose from participants being randomly assigned treatment targets. They were not assigned to reach a specified blood pressure reduction, meaning other factors may have influenced the 39.4 percent result.

"This analysis focused on MRI changes and did not establish that these participants experienced less cognitive decline or fewer strokes," Habes said.

Previous research has associated a greater burden of small vessel disease with both of those outcomes.

The combined MRI score was assessed after the original trial had been designed, and usable follow-up scans were unavailable for many participants. Further analyses delivered similar findings.

This "reduces, but does not eliminate, this concern," Habes said.

SPRINT also excluded people with diabetes, a previous stroke, dementia, symptomatic heart failure or advanced kidney disease, along with care home residents. It is still uncertain whether the results extend to these groups.

For the people included in the study, assignment to the lower blood pressure target was associated with more gradual progression of MRI signs of small vessel disease.

The research was published in eClinicalMedicine.

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