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Effects of blood pressure and lipid lowering on cognition: Results from the HOPE-3 study
Jackie Bosch1, Martin O'Donnell2, Balakumar Swaminathan2
1From the Population Health Research Institute (J.B., M. O., B.S., E.M.L., M.S., S.F.L., J.M.P., R.H., S.Y.) and Hamilton Health Sciences (J.B.), School of Rehabilitation Science, McMaster University, Ontario; Institut Universitaire de Cardiologie et Pneumologie de Québec (G.D.), Université Laval, Québec; Li Ka Shing Knowledge Institute (L.A.L.), St. Michael's Hospital, University of Toronto, Ontario, Canada; Research Board Clinical Research Facility (M.O.), Department of Medicine, NUI Galway, Ireland; Instituto Cardiovascular de Rosario (R.D.), Argentina; Diabetes Research Centre (K.K.), University of Leicester; Department of Cardiovascular Sciences and the National Institute for Health Research (W.D.T.), Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, University of Leicester, UK; College of Medicine (A.D.), University of the Philippines, Manila, Philippines; Lady Davis Carmel Medical Center (B.S.L.), Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa; Dante Pazzanese Institute of Cardiology (A.A.), São Paulo, Brazil; Department of Medical Sciences (C.H.), Cardiology, Uppsala Clinical Research Center, Uppsala University, Sweden; Semmelweis University (M.K.), Budapest, Hungary; Monash University (C.R.), Melbourne, Victoria; School of Public Health (C.M.R.), Curtin University, Perth, Australia; and Hatter Institute for Cardiovascular Research in Africa (K.S.), Department of Medicine, University of Cape Town, Soweto Cardiovascular Research Group, South Africa. boschj@mcmaster.ca.
Insights
Long-term treatment with candesartan/hydrochlorothiazide and rosuvastatin did not slow cognitive decline in older adults. This cardiovascular risk study found no significant cognitive benefits from these medications.
Area of Science:
- Cardiology
- Neurology
- Pharmacology
Background:
- Cardiovascular disease is a leading cause of mortality globally.
- Cognitive decline is a significant concern in aging populations.
- Intermediate cardiovascular risk is common in older adults.
Purpose of the Study:
- To evaluate if long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination impacts cognitive decline in older individuals at intermediate cardiovascular risk.
- To assess the efficacy of blood pressure and cholesterol-lowering medications on cognitive function.
Main Methods:
- The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled trial.
- Participants received candesartan/hydrochlorothiazide or placebo, and rosuvastatin or placebo in a 2x2 factorial design.
- Cognitive function was assessed using the Digit Symbol Substitution Test (DSST), modified Montreal Cognitive Assessment, and Trail Making Test Part B.
Main Results:
- Candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg; rosuvastatin reduced LDL cholesterol by 24.8 mg/dL.
- No significant differences in cognitive decline were observed between treatment groups and placebo over a median follow-up of 5.7 years.
- Mean differences in DSST scores were -0.91 for candesartan/hydrochlorothiazide, -0.54 for rosuvastatin, and -1.43 for combination therapy versus placebo.
Conclusions:
- Long-term blood pressure lowering with candesartan plus hydrochlorothiazide did not significantly affect cognitive decline.
- Rosuvastatin treatment did not significantly impact cognitive decline in this population.
- Combination therapy with candesartan/hydrochlorothiazide and rosuvastatin showed no significant effect on cognitive decline.
Objective:
To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk.
Methods:
The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 × 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were ≥70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end.
Results:
Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD ±3.5 years); 59% were women; 45% had hypertension; and 24% had ≥12 years of education. The mean difference in change in DSST scores was -0.91 (95% confidence interval [CI] -2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, -0.54 (95% CI -1.88 to 0.80) for rosuvastatin compared with placebo, and -1.43 (95% CI -3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures.
Conclusions:
Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people.
Clinicaltrialsgov Identifier:
NCT00468923.
Classification Of Evidence:
This study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.
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