title: Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc analysis of INTERACT2, a randomised controlled trial.
abstract: BACKGROUND
  High blood pressure is a prognostic factor for acute stroke, but blood pressure variability might also independently predict outcome. We assessed the prognostic value of blood pressure variability in participants of INTERACT2, an open-label randomised controlled trial (ClinicalTrials.gov number NCT00716079).
  
  
  METHODS
  INTERACT2 enrolled 2839 adults with spontaneous intracerebral haemorrhage (ICH) and high systolic blood pressure (150-220 mm Hg) without a definite indication or contraindication to early intensive treatment to reduce blood pressure. Participants were randomly assigned to intensive treatment (target systolic blood pressure <140 mm Hg within 1 h using locally available intravenous drugs) or guideline-recommended treatment (target systolic blood pressure <180 mm Hg) within 6 h of onset of ICH. The primary outcome was death or major disability at 90 days (modified Rankin Scale score ≥3) and the secondary outcome was an ordinal shift in modified Rankin Scale scores at 90 days, assessed by investigators masked to treatment allocation. Blood pressure variability was defined according to standard criteria: five measurements were taken in the first 24 h (hyperacute phase) and 12 over days 2-7 (acute phase). We estimated associations between blood pressure variability and outcomes with logistic and proportional odds regression models. The key parameter for blood pressure variability was standard deviation (SD) of systolic blood pressure, categorised into quintiles.
  
  
  RESULTS
  We studied 2645 (93·2%) participants in the hyperacute phase and 2347 (82·7%) in the acute phase. In both treatment cohorts combined, SD of systolic blood pressure had a significant linear association with the primary outcome for both the hyperacute phase (highest quintile adjusted OR 1·41, 95% CI 1·05-1·90; ptrend=0·0167) and the acute phase (highest quintile adjusted OR 1·57, 95% CI 1·14-2·17; ptrend=0·0124). The strongest predictors of outcome were maximum systolic blood pressure in the hyperacute phase and SD of systolic blood pressure in the acute phase. Associations were similar for the secondary outcome (for the hyperacute phase, highest quintile adjusted OR 1·43, 95% CI 1·14-1·80; ptrend=0·0014; for the acute phase OR 1·46, 95% CI 1·13-1·88; ptrend=0·0044).
  
  
  CONCLUSIONS
  Systolic blood pressure variability seems to predict a poor outcome in patients with acute intracerebral haemorrhage. The benefits of early treatment to reduce systolic blood pressure to 140 mm Hg might be enhanced by smooth and sustained control, and particularly by avoiding peaks in systolic blood pressure.
  
  
  BACKGROUND
  National Health and Medical Research Council of Australia.
authors: Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; NIHR Biomedical Research Unit in Cardiovascular Disease, University of Leicester, Leicester, UK.
authors: Lisa
authors: L
authors: Manning
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
authors: Yoichiro
authors: Y
authors: Hirakawa
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
authors: Hisatomi
authors: H
authors: Arima
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
authors: Xia
authors: X
authors: Wang
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia; Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors: John
authors: J
authors: Chalmers
authors: The Shanghai Institute of Hypertension, Rui Jin Hospital, Shanghai Jiaotong University, Shanghai, China.
authors: Jiguang
authors: J
authors: Wang
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
authors: Richard
authors: R
authors: Lindley
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
authors: Emma
authors: E
authors: Heeley
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia; Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors: Candice
authors: C
authors: Delcourt
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
authors: Bruce
authors: B
authors: Neal
authors: Servicio de Neurología, Departamento de Medicina, Clínica Alemana, Universidad del Desarrollo, Santiago, Chile; Universidad de Chile, Santiago, Chile.
authors: Pablo
authors: P
authors: Lavados
authors: Melbourne Brain Centre, Royal Melbourne Hospital, Melbourne, VIC, Australia; University of Melbourne, Melbourne, VIC, Australia.
authors: Stephen M
authors: SM
authors: Davis
authors: INSERM, U897, Bordeaux, France; University of Bordeaux, Bordeaux, France.
authors: Christophe
authors: C
authors: Tzourio
authors: Department of Neurology, Peking University First Hospital, Beijing, China.
authors: Yining
authors: Y
authors: Huang
authors: Department of Neurology, APHP - Hôpital Lariboisière, Paris, France; DHU NeuroVasc Paris - Sorbonne, Paris, France; Université Paris Diderot - Sorbonne Paris Cité, Paris, France.
authors: Christian
authors: C
authors: Stapf
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
authors: Mark
authors: M
authors: Woodward
authors: Stroke Prevention Research Unit, University Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK.
authors: Peter M
authors: PM
authors: Rothwell
authors: Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; NIHR Biomedical Research Unit in Cardiovascular Disease, University of Leicester, Leicester, UK.
authors: Thompson G
authors: TG
authors: Robinson
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia; Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address: canderson@georgeinstitute.org.au.
authors: Craig S
authors: CS
authors: Anderson
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents