Jackie Bosch

Hopes that lowering blood pressure or LDL cholesterol with medications might slow cognitive or functional decline in older people were tempered by the results of the Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial.

On the positive side, using rosuvastatin to lower LDL cholesterol had no adverse effects on cognitive function. HOPE-3 also suggested that there might be some benefit from starting blood pressure interventions earlier in life. The trial results were presented Nov. 13 during Scientific Sessions 2016.

“There was no difference in mental processing speed, in executive function, in psychomotor speed or other cognitive or functional areas tested between the groups,” reported lead author Jackie Bosch, PhD, associate professor at McMaster University in Hamilton, Ontario, Canada. “Blood pressure-lowering for more than 5.5 years showed a trend for better scores in the active treatment group, with a p value for trend that was highly significant. There is a need for further studies of the potential benefits of starting treatment in midlife and continuing treatment longer.”

HOPE-3 researchers reported the trial’s cardiovascular outcomes earlier this year. Lowering blood pressure reduced cardiovascular events in individuals with hypertension by 24 percent while treatment with rosuvastatin reduced cardiovascular events by 25 percent overall. Researchers used questionnaires at baseline and at the end of the study to evaluate the effects of blood pressure-lowering and rosuvastatin or a combination of the two on cognitive and functional decline.

Of the 12,705 HOPE-3 participants who were randomized, 3,086 were 70 or older at baseline. In this cohort of older participants, 1,626 (69 percent) completed both the baseline and the end-of-study questionnaires.

The primary outcome was any decline in processing speed as measured by the Digit Symbol Substitution Test (DSST). Secondary outcomes included any decline in executive function as measured by the modified Montreal Cognitive Assessment and any increase in psychomotor speed as measured by the Trail Making Test Part B. Other outcomes included change in function as measured by functional questions on the EQ 5D and an assessment of end-of-study function as measured by the Standard Assessment of Global Activities in the Elderly.

Systolic blood pressure showed a mean decline of 6 mmHg while LDL cholesterol fell by a mean of 24.9 mg/dL in the active treatment groups. There were no significant changes in the end-of-study DSST scores in the active treatment groups compared to placebo. There were no significant changes in any of the cognitive or functional outcomes by treatment group, Bosch said.

HOPE-3 participants with the highest systolic blood pressure and highest LDL cholesterol at baseline showed a trend for slower decline in cognitive function, a decline of 4.65 between baseline and end-of-study scores compared to a decline of 11.8 for the placebo group. The p value for trend was 0.04, Bosch said, adding that the results need to be replicated.

There also was a trend for improvement in individuals who received blood pressure-lowering treatment for more than 5.5 years compared to placebo. Participants with a longer period of blood pressure-lowering treatment showed greater improvements in cognitive decline. The p value for trend was 0.036 and, again, the results need to be confirmed.

There was no significant difference in the effects of LDL cholesterol-lowering by duration of treatment.

“We know that blood pressure effects begin in middle age,” Bosch said. “We need to think about treating earlier and treating longer to affect cognitive function, especially for individuals at higher cardiovascular risk.”