The National Institutes of Health halted the landmark SPRINT study in 2015 after results clearly showed a cardiovascular benefit for patients who had their systolic blood pressure aggressively controlled to 120 mm/Hg.
More than 3 years ago, the National Institutes of Health ordered an early halt to the landmark SPRINT study (Systolic Blood Pressure Intervention Trial), which found that aggressively lowering systolic blood pressure to 120 mmHg instead of 140 mmHg for patients with high blood pressure and another health risk meant patients had fewer heart attacks, strokes, and cardiac deaths.
Researchers had good reason to take that step. The results were so clear that it would have been unethical to continue the trial; in fact, results have already prompted the American College of Cardiology and the American Heart Association to revise their definition of what constitutes high blood pressure.
But stopping the study had an unintended consequence. It meant a segment called SPRINT MIND would end early, too, possibly leaving it underpowered to answer a different question: does aggressively controlling blood pressure in certain patients with cardiac risks help prevent dementia?
Results from that truncated trial were published today in JAMA. The findings suggest there’s a connection, but they did not reach the level of significance.1 Authors stated that stopping the trial early meant there were simply fewer cases of dementia than expected. For that reason, the Alzheimer’s Association announced it will take the extraordinary step of awarding $800,000 to fund SPRINT MIND 2.0, which will re-engage the original participants and add 2 years of follow-up to the original assessment, “to try to allow for a more definitive statement on reducing dementia risk,” according to a statement from the group.
The possible connection between cardiovascular disease (CVD) and dementia or Alzheimer disease has been studied for some time. As an accompanying editorial in JAMA stated, “the mechanisms by which CVD risk factors and the risk of developing [Alzheimer disease] are most likely related to the important role in vascular health for β-amyloid and other neurodegenerative protein deposition, and observational studies have suggested that hypertension is associated with an increased risk of all-cause dementia.”2
What set SPRINT MIND apart was a plan for lengthy follow-up and a specific plan to look for both dementia and mild cognitive impairment, a separate state between normal aging and full-blown dementia. When the follow-up period was cut short, the planned year 4 cognitive assessments were done after medications were again being provided by primary care physicians. The results reported Monday showed this difference did rise to the level of significance, but the primary outcome of dementia did not.
Out of the more than 9300 participants in the overall trial, there were 149 participants in the intensive treatment group in SPRINT MIND vs 176 in the standards treatment group. The results gathered in the SPRINT MIND trial reported Monday showed that aggressively controlling blood pressure did result in a significant difference in these cases of mild cognitive impairment (14.6 cases per 1000 person years in the treatment group vs 18.3 cases per 1000 person years in the standard group), with a hazard ratio (HR) of 0.81; 95% CI, 0.69-0.95. With the trial ended with more than a year to go, the dementia cases were far fewer: 7.2 cases per 1000 person years in the treatment group vs 8.6 cases per 1000 person years in the standard group, for a HR 0.83, 95% CI, 0.67-1.04.
The Alzheimer’s Association said in its statement that the group found the data “compelling.” Maria C. Carrillo, PhD, the group’s chief science officer, said in the statement that, mild cognitive impairment (MCI "is a known risk factor for dementia, and everyone who experiences dementia passes through MCI. When you prevent new cases of MCI, you are preventing new cases of dementia.”
The group, she said, “is committed to getting clarity and certainty on the dementia outcome by following participants for a longer period of time.”
SPRINT MIND 2.0 will begin early this year.