Effects of blood pressure and lipid lowering on cognition: Results from the HOPE-3 study

Journal article


Bosch, Jackie, O'Donnell, Martin, Swaminathan, Balakumar, Lonn, Eva Marie, Sharma, Mikul, Dagenais, Gilles, Diaz, Rafael, Khunti, Kamlesh, Lewis, Basil S., Avezum, Alvaro, Held, Claes, Keltai, Matyas, Reid, Christopher, Toff, William D., Dans, Antonio, Leiter, Lawrence A., Sliwa, Karen, Lee, Shun Fu, Pogue, Janice M., ... Yusuf, Salim. (2019) Effects of blood pressure and lipid lowering on cognition: Results from the HOPE-3 study. Neurology. 92(13), pp. e1435 - e1446. https://doi.org/10.1212/WNL.0000000000007174
AuthorsBosch, Jackie, O'Donnell, Martin, Swaminathan, Balakumar, Lonn, Eva Marie, Sharma, Mikul, Dagenais, Gilles, Diaz, Rafael, Khunti, Kamlesh, Lewis, Basil S., Avezum, Alvaro, Held, Claes, Keltai, Matyas, Reid, Christopher, Toff, William D., Dans, Antonio, Leiter, Lawrence A., Sliwa, Karen, Lee, Shun Fu, Pogue, Janice M., Hart, Robert and Yusuf, Salim
Abstract

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. ClinicalTrials.gov 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.

Year2019
JournalNeurology
Journal citation92 (13), pp. e1435 - e1446
PublisherLippincott Williams and Wilkins
ISSN0028-3878
Digital Object Identifier (DOI)https://doi.org/10.1212/WNL.0000000000007174
Scopus EID2-s2.0-85063713465
Page rangee1435 - e1446
Research GroupMary MacKillop Institute for Health Research
Place of publicationUnited States of America
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