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Neurology. 2019 Feb 27. pii: 10.1212/WNL.0000000000007174. doi: 10.1212/WNL.0000000000007174. [Epub ahead of print]

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

Collaborators (420)

Alzogaray M, Aparici M, Berli M, Bevacqua M, Labarta MB, Bustos B, Caccavo A, Candiello A, Carignano M, Carrillo N, Carro N, Cartasegna L, Casali W, Cassettari A, Centeno M, Cuello J, Cuneo C, Cusimano S, Damonte C, De Landaluc M, De Martino E, Diez R, Fernandez A, Ferrari A, Forti L, Galello M, Garcia C, Duran RG, Garrido M, Giachello F, Vilamajo OG, Gonzalez M, Guerlloy F, Guerrero R, Hominal M, Hrabar A, Imposti H, Lanchiotti P, Laugle C, Liniado G, Litvak MR, Longhi A, Luciardi H, Mackinnon I, Manzano R, Marino J, Merlo B, Milesi R, Mulazzi C, Nemi S, Orio S, Pelagagge M, Raimondi S, Rodino L, Rodriguez C, Sago L, Sala J, Sanchez A, Sanchez R, Santos D, Schygiel P, Sernia V, Smith T, Sokn F, Soso L, Trivi M, Vico M, Villamil A, Vogel D, Zaidman C, Abhayaratna W, Canalese J, Krum H, Patel A, Brasil CKOL, Alves CB, Alves AR Jr, Ayoub JCA, Bergoli LCC, Blacher MG, Bodanese LC, Braga JCF, Costa OMC, Costa MKM, de Faria DG, Del Monaco MI, Restelatto LF, Filho F, Franco RJS, Furtado MV, Leaes PE, Leaes P, Maia LN, MarinNeto JA, Mattar ETB, Melo CM, Mothe FS, Oliveira GBF, Pelloso E, Polanczyk CA, Rosa PR, Sales SOC, Saraiva JFK, Schmidt A, Silva VS, Sousa ACS, Valle AP, Wiehe M, Abramson B, Anand S, Aw J, Baxter W, Berlingieri J, Cha J, Chaulk R, Chetty T, Dagenais G, Dattani D, Delage F, Dion D, Dominguez M, Gallo R, Glendinning K, Goldman H, Gosselin G, Greenspoon A, Ly QH, Juneau M, Keegan P, Kelly A, Kilby D, Lavoi M, Leiter LA, Lonn E, Magloire P, Mehta P, Mercante N, Miscescu H, Moran G, Nawaz S, Nigam A, Pang P, Papp E, Petrella R, Poirier C, Rabasa-Lhoret R, Rizvi Q, Saulnier D, Sharma M, Sohal P, Stern S, Tobe S, Walsh P, Ward R, Weeks A, Woo V, Yellin J, Zuliani P, Bai XJ, Dong LG, Duan YW, Feng JZ, Fu P, Gao MM, Gao P, Ge H, Ge Y, Hua Q, Li DJ, Liu XL, Liu XL, Liu ZD, Liu YJ, Liu FY, Liu LH, Lu FH, Lv T, Ma SP, Ma H, Man RH, Tan HQ, Shen Y, Shi JF, Sun XD, Wang SY, Wang B, Wang YQ, Wei YJ, Yang XC, Yang HS, Yu K, Yu LT, Yu JH, Zhang W, Zhang W, Zhang F, Zhang HY, Zhang B, Zhao JG, Zhao Y, J Accini, Arcos E, Aroca G, Casanova M, Celemin C, Coronel BJ, Cotes C, Cure C, Diego-Olite M, Duarte A, Escobar D, Figueredo M, Garcia L, Garcia H, Grisales M, Martinez K, Molina de Salazar DI, Castellanos BN, Posada I, Quintero A, Quiros F, Sanchez G, Sotomayor A, Suarez M, Urina M, Adamkova V, Cifkova R, Ferkl R, Galovcova M, Hartman J, Jozifova M, Linhart K, Linhart T, Moravcikova D, Nussbaumerova B, Plachy M, Rosolova H, Seifert B, Soucek M, Duarte Vera Y, Espinel M, Lopez-Jaramillo M, McDermont J, Penaherrera E, Plascencia F, Pow-Chon-Long F, Tettamanti D, Bajnok L, Baranyi E, Bartfai E, Bod E, Bodis B, Czuriga I, Huber E, Mezosi E, Poor F, Somos E, Tarjanyi Z, Tatrai T, Tomcsanyi J, Vertes A, Zsary A, Aggarwal DK, Alexander KG, Aman SD, Ayyar V, Balaji Y, Bantwal G, Bosco B, Chidambaram N, Dabra A, Daniel S, Deshpande N, Devendra HR, Ghoshroy D, Gnanasekaran S, Gupta R, Gutti MZ, Joshi GS, Joshi S, Kalantri SP, Kapoor A, Khan A, Khedar RS, Manjunath AR, Mehta K, Mohan V, Murthy S, Nambiar A, Narendra J, Paul SK, Qureshi MA, Rajasekaran S, Ramu M, Rangadham K, Ranka RL, Roy S, Sathyanarayan MR, Selvam K, Sethuraman JP, Shunmugvavelu M, Sidhu G, Singh B, Singh R, Sinha N, Srinivas J, Srinivas A, Srinivasulu B, Thomas N, Umarani R, Varghese K, Varma S, Yelvatkar S, Biton A, Goldhaber A, Ivri S, Shapiro I, Shveydel N, Shveydel E, Tsalihin D, Vinker S, Yosefy C, Choe KH, Kil Kim S, Ambigga D, Aris MA, Ghapar KA, Krishnan C, Mahadasa P, Maizatullifah M, Mazapuspavina Y, Ramanathan L, Mohd Shah AS, Yusoff K, Bonarius JH, De Jong A, DeRuiter Z, DeVos R, Dirkse HA, Drenth E, Ferguson H, Jansen R, Mevissen H, Rol H, Schilder A, Spelt I, VanLeeuwen P, Abola M, Co H, Loyola A, Mercado J, Morales D, Padua L, Palileo L, Patanao A, Rogelio G, Roxas A, Sulit D, Tang-Manga A, Tumanan-Mendoza B, Boytsov S, Chukaeva I, Karpov Y, Kisliak O, Kobalava Z, Ledyacva A, Lopatin Y, Nedogoda S, Solovieva M, Tsoma V, Tyurina T, Hranai M, Badat A, Sliwa K, Gerntholtz T, Al-Khalili F, Carlberg B, Dotevall A, Nilsson P, Olsson A, Rosengren A, Soderberg S, Artomov D, Babanina T, Bagriy A, Danyliuk S, Doretska N, Dorovska O, Dovgan N, Dzyak G, Glushko L, Gorbas I, Ilashchuk T, Karapetyan K, Karavanska I, Khimion L, Khorsun A, Kononenko L, Kuryata O, Kvasha O, Lazareva S, Loktyev D, Lysenko G, Miroshnchenko N, Onyschenko O, Parkhomenko A, Petryk N, Pivovarova S, Rakytskay I, Sapozhnychenko L, Smymova I, Soya O, Tashchuk V, Turubarova-Leunova N, Vasilyeva L, Velichko N, Yagensky A, ZhurbaK Khunti S, Loke I, Toff WD.

Author information

1
From 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.
2
From 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.

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.

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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