title: Blood pressure variability predicts cardiovascular events independently of traditional cardiovascular risk factors and target organ damage: a LIFE substudy.
abstract: BACKGROUND
  Assessment of antihypertensive treatment is normally based on the mean value of a number of blood pressure (BP) measurements. However, it is uncertain whether high in-treatment visit-to-visit BP variability may be harmful in hypertensive patients with left ventricular hypertrophy (LVH).
  
  
  METHODS
  In 8505 patients randomized to losartan vs. atenolol-based treatment in the LIFE study, we tested whether BP variability assessed as SD and range for BP6-24 months measured at 6, 12, 18 and 24 months of treatment was associated with target organ damage (TOD) defined by LVH on ECG and urine albumin/creatinine ratio at 24 months, and predicted the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction (MI) or stroke occurring after 24 months (CEP = 630 events).
  
  
  RESULTS
  In multiple regression models adjusted for mean BP6-24 months and treatment allocation, neither high BP6-24 months SD nor wide range were related to TOD at 24 months, except for a weak association between Sokolow-Lyon voltage and DBP6-24 months SD and range (both β = 0.04, P < 0.01). Independently of mean BP6-24 months, treatment allocation, TOD and baseline characteristics in Cox regression models, CEP after 24 months was associated with DBP6-24 months SD [hazard ratio per 1 mmHg increase1.04, 95% confidence interval (95% CI) 1.01-1.06, P = 0.005], range (hazard ratio 1.02, 95% CI 1.01-1.03, P = 0.004), SBP6-24 months SD (hazard ratio 1.01, 95% CI 0.99-1.02, P = 0.07) and range (hazard ratio 1.006, 95% CI 1.001-1.01, P = 0.04). Adjusted for the same factors, stroke was associated with DBP6-24 months SD (hazard ratio 1.06, 95% CI 1.02-1.10, P = 0.001), range (hazard ratio 1.03, 95% CI 1.01-1.04, P = 0.001), SBP6-24 months SD (hazard ratio 1.02, 95% CI 1.002-1.04, P = 0.04) and range (hazard ratio 1.008, 95% CI 1.001-1.02, P = 0.05), but MI was not.
  
  
  CONCLUSIONS
  In LIFE patients, higher in-treatment BP6-24 months variability was independently of mean BP6-24 months associated with later CEP and stroke, but not with MI or TOD after 24 months.
authors.affiliation: aResearch Centre for Prevention and Health, Glostrup University Hospital, Glostrup bDepartment of Internal Medicine, Næstved Hospital, Næstved, Denmark cSahlgrenska Academy, Institute of Medicine, Department of Molecular and Clinical Medicine, Gotenburg, Sweden dThe Weill Medical College of Cornell University, New York, New York, USA eDivision of Cardiology, Holbæk University Hospital, Holbæk, Denmark fUllevaal University Hospital, Oslo, Norway gUmeå University Hopsital, Umeå, Sweden hUniversity of Milano-Bicocca and IRCCS Istituto Auxologico Italiano, Milan, Italy iStroke Prevention Research Unit, University Department of Clinical Neurology, level 6, West Wing, John Radcliffe Hospital, Headington, Oxford, UK jDepartment of Internal Medicine, Glostrup Hospital, University of Copenhagen, Glostrup kThe Cardiovascular and Metabolic Preventive Clinic, Department of Endocrinology, Centre for Individualized Medicine in Arterial Diseases (CIMA), Odense University Hospital, Odense, Denmark lHypertension in Africa Research Team (HART), North-West University, Mahikeng, South Africa.
authors.forename: Julie K K
authors.initials: JK
authors.lastname: Vishram
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlöf
authors.forename: Richard B
authors.initials: RB
authors.lastname: Devereux
authors.forename: Hans
authors.initials: H
authors.lastname: Ibsen
authors.forename: Sverre E
authors.initials: SE
authors.lastname: Kjeldsen
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lindholm
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
authors.forename: Peter M
authors.initials: PM
authors.lastname: Okin
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
authors.forename: Kristian
authors.initials: K
authors.lastname: Wachtell
authors.forename: Michael H
authors.initials: MH
authors.lastname: Olsen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000652:urine; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001262:Atenolol / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000401:mortality; D003404:Creatinine / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology*; D014463:Ultrasonography
chemical_list: D000959:Antihypertensive Agents; D001262:Atenolol; D003404:Creatinine; D019808:Losartan