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Blood pressure and low-density lipoprotein-cholesterol lowering for prevention of strokes and cognitive decline: a review of available trial evidence

Zanchetti, Albertoa,b; Liu, Lishengc,d; Mancia, Giuseppea,e; Parati, Gianfrancoa,e; Grassi, Guidoe,f; Stramba-Badiale, Marcoa; Silani, Vincenzoa,b; Bilo, Grzegorza; Corrao, Giovannie; Zambon, Antonellae; Scotti, Lorenzae; Zhang, Xinhuad; Wang, HayYand; Zhang, Yuqingc,d; Zhang, Xuezhongc,d; Guan, Ting Ruid; Berge, Eivindg; Redon, Joseph; Narkiewicz, Krzysztofi; Dominiczak, Annaj; Nilsson, Peterk; Viigimaa, Margusl; Laurent, Stéphanem; Agabiti-Rosei, Enricon; Wu, Zhaosuo; Zhu, Dingliangp; Rodicio, José Luisq; Ruilope, Luis Miguelr; Martell-Claros, Nievess; Pinto, Fernandot; Schmieder, Roland E.u; Burnier, Michelv; Banach, Maciejw; Cifkova, Renatax; Farsang, Csabay; Konradi, Alexandraz; Lazareva, Irinaaa; Sirenko, Yuriyab; Dorobantu, Mariaac; Postadzhiyan, Armanad; Accetto, Rokae; Jelakovic, Bojanaf; Lovic, Draganag; Manolis, Athanasios J.ah; Stylianou, Philipposai; Erdine, Serapaj; Dicker, Drorak; Wei, Gangzhial; Xu, Chengbinam; Xie, Henggean; Coca, Antonioao; O’Brien, Johnap; Ford, Garyaq

doi: 10.1097/HJH.0000000000000253

Background and objectives: It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these treatments can prevent cognitive decline after stroke.

Results: A review of existing data from randomized controlled trials confirms that solid evidence on optimal BP and LDL-C targets is missing, possible interactions between BP and LDL-C lowering treatments have never been directly investigated, and evidence in favour of a beneficial effect of BP or LDL-C lowering on cognitive decline is, at best, very weak.

Conclusion: A new, large randomized controlled trial is needed to determine the optimal level of BP and LDL-C for the prevention of recurrent stroke and cognitive decline.

aIstituto Auxologico Italiano

bUniversità di Milano, Milan, Italy

cFuWai Hospital and Cardiovascular Institute

dBeijing Hypertension League Institute, Beijing, China

eUniversità Milano-Bicocca

fIRCCS Multimedica, Sesto San Giovanni, Milan, Italy

gOslo University Hospital, Oslo, Norway

hUniversity of Valencia, Madrid, Spain

iMedical University of Gdansk, Gdansk, Poland

jUniversity of Glasgow, Glasgow, UK

kLund University, Scania University Hospital, Malmo, Sweden

lTallinn University of Technology, Tallinn, Estonia

mEuropean Hospital Georges Pompidou, Paris, France

nUniversità di Brescia, Spedali Civili, Brescia, Italy

oBeijing Anzhen Hospital, Beijing

pShanghai Hypertension Institute, Shanghai, China

qComplutense University

rHospital 12 de Octubre

sHospital Clínico San Carlos, Madrid, Spain

tCentro Hospitalar de Entre o Douro e Vouga, E.P.E., Portugal

uNephrology and Hypertension, University Hospital, Erlangen, Germany

vUniversity Hospital of Lausanne, Lausanne, Switzerland

wMedical University of Lodz, Lodz, Poland

xCharles University Medical School I and Thomayer Hospital, Prague, Czech Republic

ySt. Imre University Teaching Hospital, Budapest, Hungary

zAlmazov Federal Heart, Blood and Endocrinology Center, St. Petersburg, Russia

aaRSPC Cardiology, Minsk, Belarus

abNSC ‘Institute of Cardiology named after N.D. Strazhesko’ of NAMS, Kiev, Ukraine

acEmergency Hospital of Bucharest, Bucharest, Romania

adUniversity Hospital Saint Anna, Sofia, Bulgaria

aeDr Peter Drzai Hospital, Ljubljana, Slovenia

afUniversity Hospital Center Zagreb, Zagreb, Croatia

agClinic for Internal Medicine InterMedic, Nis, Serbia

ahCardiology Department, Asklepeion General Hospital, Athens, Greece

aiNicosia General Hospital, Nicosia, Cyprus

ajIstanbul University Cerrahpaşa School of Medicine, Istanbul, Turkey

akHasharon Hospital – Rabin Medical Center, Petach-Tikva, Israel

alBeijing Xuanwu Hospital

amSecond Affiliate Hospital, Beijing University

anMilitary General Hospital, Beijing, China

aoHospital Clinic, University of Barcelona, Barcelona, Spain

apUniversity of Cambridge, Cambridge

aqOxford University Hospital NHS Trust, Oxford, UK

Correspondence to Alberto Zanchetti, Istituto Auxologico Italiano, Via L. Ariosto 13, 20145 Milan, Italy. Tel: +39 02 619112237; e-mail:

Abbreviations: ACCORD, Action to Control Cardiovascular Risk in Diabetes; BP, blood pressure; CARE, Comprehensive Assessment and Referral Evaluation; CHD, coronary heart disease; ESC, European Society of Cardiology; ESH, European Society of Hypertension; ESH-CHL-SHOT, European Society of Hypertension – Chinese Hypertension League – Stroke in Optimal Hypertension Treatment; HOT, Hypertension Optimal Treatment; HPS, Heart Protection Study; HYVET, Hypertension in the Very Elderly Trial; IDNT, Irbesartan Diabetic Nephropathy Trial; INDANA, Individual Data Analysis of Antihypertensive Intervention Trials; INVEST, International Verapamil SR Trandolapril; LDL-C, low-density lipoprotein cholesterol; LIFE, Losartan Intervention For Endpoint reduction; MMSE, Mini Mental State Examination; ONTARGET, Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial; PATS, Poststroke Antihypertensive Treatment Study; PODCAST, Prevention of Decline in Cognition After Stroke Trial; PROFESS, Prevention Regimen for Effectively Recurrent Stroke Study; PROGRESS, Perindopril Protection against Recurrent Stroke Study; PROSPER, Prospective Study of Pravastatin in the Elderly at Risk; PROVE-IT, Pravastatin or Atorvastatin Evaluation and Infection Therapy; RCT, randomized controlled trial; SCOPE, Study on Cognition and Prognosis in the Elderly; SHEP, Systolic Hypertension in the Elderly Program; SPARCL, Stroke Prevention by Aggressive Reduction in Cholesterol Levels; SPRINT, Systolic Blood Pressure Intervention Trial; SPS3, Secondary Prevention of Small Subcortical Strokes; Syst-Eur, Systolic Hypertension in Europe; TIA, transient ischaemic attack; TNT, Treatment to New Targets; TRANSCEND, Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease; TST, Treat Stroke to Target; UKPDS, United Kingdom Prospective Diabetes Study; WML, white matter lesion

Received 20 January, 2014

Revised 29 April, 2014

Accepted 29 April, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins