title: Increased visit-to-visit blood pressure variability is associated with worse cardiovascular outcomes in low ejection fraction heart failure patients: Insights from the HEAAL study.
abstract: BACKGROUND
  Recent data have highlighted shortcomings of the usual blood pressure (BP) hypothesis in several populations, and emphasized the importance of visit-to-visit variability of BP in predicting cardiovascular events. Herein, we aimed at assessing the association between visit-to-visit BP variability and outcomes in chronic heart failure (CHF) patients enrolled in the Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan (HEAAL).
  
  
  RESULTS
  The HEAAL study randomized 3834 patients with HF and reduced ejection fraction administered 150 mg or 50mg losartan daily in a double blind, randomized, controlled trial. The patients were followed up for up to 6.8 years after randomization, and BP was measured at 3 time points in the first year and at semi-annual visits in the years thereafter. Three measures of visit-to-visit BP variability were computed for each subject: the standard deviation, the coefficient of variation and the average absolute visit-to-visit variation. Cox proportional hazard models were used to investigate the relationship between variations in systolic blood pressure, baseline covariates and the time to death or heart failure hospitalization (i.e. primary outcome). In multivariate analyses stratified on baseline BP, the patients with higher visit-to visit BP variability exhibited poorer outcomes (average absolute difference in SBP in mmHg:hazard ratio: 1.023 [95% CI (1.013, 1.034), P<0.0001]), independent from high dose losartan (still beneficial).
  
  
  CONCLUSIONS
  For the first time, visit-to-visit BP variability was found elevated in CHF patients with reduced ejection fraction, and associated with poorer cardiovascular outcomes. Such assessments should be prioritized for testing prevention strategies in CHF.
  
  
  BACKGROUND
  This study is registered with the ClinicalTrials.gov, number NCT00090259.
authors.affiliation: INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Nancy, France; Université de Lorraine, France; INSERM U1116, Nancy, France; CHU Nancy, Pôle de Cardiologie, Vandoeuvre lès Nancy, France; Cardiovascular and Renal Clinical Trialists (INI-CRCT), F-CRIN, France.
authors.forename: P
authors.initials: P
authors.lastname: Rossignol
authors.affiliation: INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Nancy, France; Université de Lorraine, France; INSERM U1116, Nancy, France; CHU Nancy, Pôle de Cardiologie, Vandoeuvre lès Nancy, France; Cardiovascular and Renal Clinical Trialists (INI-CRCT), F-CRIN, France.
authors.forename: N
authors.initials: N
authors.lastname: Girerd
authors.affiliation: Cardiovascular Clinical Studies, Boston, MA, United States.
authors.forename: D
authors.initials: D
authors.lastname: Gregory
authors.affiliation: Boston University School of Public Health, United States.
authors.forename: J
authors.initials: J
authors.lastname: Massaro
authors.affiliation: Tufts Medical Center, Boston, MA, United States.
authors.forename: M A
authors.initials: MA
authors.lastname: Konstam
authors.affiliation: INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Nancy, France; Université de Lorraine, France; INSERM U1116, Nancy, France; CHU Nancy, Pôle de Cardiologie, Vandoeuvre lès Nancy, France; Cardiovascular and Renal Clinical Trialists (INI-CRCT), F-CRIN, France. Electronic address: f.zannad@chu-nancy.fr.
authors.forename: F
authors.initials: F
authors.lastname: Zannad
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D001794:Blood Pressure / Q000502:physiology*; D001795:Blood Pressure Determination / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000178:diet therapy / Q000503:physiopathology*; D006801:Humans; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009819:Office Visits / Q000706:statistics & numerical data*; D011379:Prognosis; D012189:Retrospective Studies; D013318:Stroke Volume; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan
keywords: Blood pressure; Heart failure; Pharmacology; Prognosis