Declines in Cognition and Function Unaffected by Lowering BP, LDL Cholesterol in the Elderly: HOPE-3

NEW ORLEANS, LA—Reducing blood pressure, LDL cholesterol, or both does not slow cognitive decline in older patients at intermediate cardiovascular risk, an analysis of the HOPE-3 trial shows.

Over a median follow-up of 5.6 years, patients in all groups had similar declines in measures of processing speed, executive function, and psychomotor speed, Jackie Bosch, PhD (Population Health Research Institute, Hamilton, Canada), reported at the American Heart Association (AHA) Scientific Sessions 2016.

Post hoc analyses suggested that the interventions might be beneficial in the highest-risk patients and when blood pressure-lowering treatments are given for longer periods of time, but those findings require confirmation, Bosch said.

At a press conference, former AHA President Ralph Sacco, MD (University of Miami, FL), said that cognitive problems are among the major concerns of the elderly and aging populations. But despite epidemiological studies showing relationships between better control of blood pressure, diabetes, and cholesterol and better cognition, no treatments or approaches have been proven to reduce the risk of cognitive decline, Sacco said.

The findings from HOPE-3—which used a more robust assessment of cognition compared with prior studies—continue that disappointing trend, but according to Sacco, there are some positive aspects of the results.

He noted that lowering LDL cholesterol with rosuvastatin did not have a detrimental effect. “It’s been a concern and in this well-done study there was really no significant effect of statins worsening cognition,” he said. “And think that’s an important take-home message.”

Sacco also pointed out that the trial participants included in this analysis had a relatively low level of risk overall. When looking at the subgroups with the highest baseline levels of blood pressure and LDL cholesterol, he said, there were some suggestions that the interventions slowed cognitive decline.

Another factor that could influence the interpretation of the results, he said, is the fact that all of the patients included in this analysis were 70 or older. That’s important because the epidemiological studies linking blood pressure control and cognitive impairment have looked at differences beginning in middle age.

Taken together, those findings suggest that treating higher-risk but younger patients could yield improvements, Sacco suggested, saying, “We need to be thinking about treating younger people with uncontrolled blood pressure for longer periods of time.”

Individuals Aged 70 Years and Older

HOPE-3 evaluated the effects of lowering blood pressure, LDL cholesterol, or both in 12,705 patients at intermediate cardiovascular risk. Reducing blood pressure alone reduced cardiovascular events, but only in patients with hypertension. Bringing down LDL cholesterol with rosuvastatin lowered events in the overall population.

The current analysis was confined to participants 70 and older; there were 1,626 patients who completed cognitive and functional assessments at both baseline and the end of the study.

The primary outcome was the decline in processing speed, as assessed using the Digit Symbol Substitution Test. This declined during follow-up regardless of whether patients received blood pressure-lowering alone, LDL cholesterol-lowering alone, or both interventions, with no differences between trial arms in scores at the end of the study. Similar findings were seen for secondary assessments of executive function (modified Montreal Cognitive Assessment) and psychomotor speed (Trail Making Test Part B).

Post hoc analyses showed nonsignificant trends toward beneficial effects of the blood pressure intervention in patients with a baseline systolic reading greater than 145 mm Hg and of rosuvastatin in those with a baseline LDL cholesterol level greater than 140 mg/dL. And in patients with high systolic blood pressure and high LDL cholesterol at baseline, treatment with both rosuvastatin and the blood pressure-lowering intervention significantly slowed the decline in processing speed. All of those analyses require replication, Bosch said.

The investigators also looked at functional assessments, including the EQ-5D and the Standard Assessment of Global Activities in the Elderly. Those measures were unaffected by the interventions used in the trial.