Effect of Lower BP & Cholesterol on Cognition

The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study examined the effects of blood pressure- and lipid-lowering medications on prevention of major cardiovascular outcomes. A total of 12,705 participants with moderate risk of cardiovascular disease were recruited. Participants were randomized to receive candesartan/hydrocholorothiazide or placebo or rosuvastatin or placebo. “There was a clear reduction in cardiovascular events with rosuvastatin of 24%, and the benefit of blood pressure lowering was only seen in those with elevated systolic blood pressure at study entry,” explained Jackie Bosch, MD (McMaster University and Hamilton Health Sciences, Hamilton, Ontario).

Researchers also evaluated the impact these interventions had on cognitive function in patients aged ≥70 years. A total of 3086 men and women were studied for an average of 5.7 years (mean age, 74 years; 59% women; mean blood pressure, 129/74 mmHg). Of this group, 2361 completed the baseline questionnaire and 2142 were alive by the end of the study period. Seventy-six percent (1626) completed questionnaires at both the beginning and end of the study.

Cognitive measurements including results of the of Digit Symbol Substitution Test (DSST), the 11-item Montreal Cognitive Assessment (MoCA), and the Trail Making Test - Part B (TMT-B) were collected before and at the end of the study period. Data on functional status at the beginning and end of the study were also collected. The primary outcome was decline in processing speed (DSST). Secondary outcomes included decline in executive function (MoCA) and increase in psychomotor speed (YMT-B). Other outcomes were change in function and at the end of the study, Standard Assessment of Global Activities in the Elderly (SAGE).

Sensitivity analysis indicated no difference in DSST for all groups. Results were also examined in key subgroups. For the blood pressure comparison, there was no difference between age in the candesartan/hydrocholorothiazide versus placebo groups. “What we can see is a visual trend for actual harm or increased cognitive decline for those in the lowest tertile of [systolic] blood pressure (≤133) when they entered the study, and a slight benefit for those at the highest (>145),” stated Bosch, “although this was not statistically significant.”

In the rosuvastatin versus placebo groups, again, there was no difference between groups based on age and no difference in the lowest (≤112) and middle (112-140) tertiles for LDL. In the highest tertile (>140), there was a visual, but non-significant difference, “but it did lead us to question whether there could have been an effect of the combination therapy in those with high systolic blood pressure at baseline and high HDL. We looked at the change in scores in the double active group. They had a -4.7 change in score compared to -11.8 in the double placebo group. That was relatively significant, but again, post hoc analysis.

In looking at length of treatment, there was no significant difference in the effects of rosuvastatin. For treatment up to 5.5 years, there was no benefit of treatment “and in fact, the active group in the blood pressure-lowering comparison seems to be scoring a little bit worse, but after 5.5 years, we see things begin to change and there is improvement in those in active therapy (P trend=0.036).”

Take-home Points

• Participants experienced cognitive and functional decline over the study period.

• Blood pressure lowering and rosuvastatin did not significantly prevent cognitive and functional decline.

• Rosuvastatin had no adverse effect on cognitive function, which is significant, given the FDA black box warning.

• Findings require further investigation, but there was a trend for benefit for participants in the highest blood pressure and LDL subgroups, and longer duration of blood pressure lowering was associated with less cognitive decline.

The discussant for the press briefing, Ralph Sacco, MD (University of Miami, Coral Gables, FL), stated that HOPE-3 is an important trial because it addresses concerns of great importance to the elderly and aging public – dementia, vascular cognitive impairment, vascular dementia, and cognitive aging. While epidemiological studies have shown relationships for poor blood pressure, diabetes, and cholesterol control and decreases in cognitive decline, HOPE-3 is an evidence-based, randomized approach to investigating these relationships. “HOPE-3 also has a strength in that it’s using a more robust assessment of cognition. Many of the other studies have only used modified mini-mentals, which are a very insensitive way of looking at cognitive decline.”

“Overall, even though there was no significant reduction [in cognitive function], I think there is some silver lining,” stated Sacco. “We probably need to be treating higher risk patients, treating them at younger ages, and treating them for longer periods. And I think we need to be doing a lot more to address brain health and get more evidence-based recommendations for our population.”

From American Heart Association Scientific Sessions. LBCT.01 – Big Trials for Big Questions session. The Effect of Blood Pressure and Cholesterol Lowering on Cognition (HOPE 3). November 13, 2016. New Orleans, LA.