title: Increased pulse pressure linked to dementia: further results from the Hypertension in the Very Elderly Trial - HYVET.
abstract: OBJECTIVE
  High blood pressure (BP) has been associated with increased risk of dementia. Concerns have been raised about lowering BP too far in the very elderly and thereby increasing risk. There is some evidence to suggest a potential 'J'-shaped relationship between DBP and risk of cognitive impairment. This was investigated using data from the HYpertension in the Very Elderly Trial (HYVET).
  
  
  METHODS
  HYVET was a double-blind, placebo-controlled trial of antihypertensives in patients aged at least 80 years with an untreated SBP of 160-199 mmHg. Active medication was indapamide sustained release 1.5 mg+/- perindopril 2-4 mg to reach goal pressure of less than 150/80 mmHg. Incident dementia was a secondary endpoint and was not significantly different between the two treatment groups. The relationship between pressure and incident dementia was assessed using Cox proportional hazards regression with BP entered as either a discrete (quartile analysis) or continuous predictor variable. Achieved BP was calculated as the mean of all pressures from the 9 month visit onwards.
  
  
  RESULTS
  During a mean follow-up of 2.2 years 263 incident cases of dementia were diagnosed. After adjustment for various covariates, baseline DBP was inversely related to incident dementia (P=0.0064). Achieved DBP did not predict later dementia in the placebo group (P=0.43), but showed a U-shaped relationship in the active treatment group (P=0.0195). The relationship between incident dementia and DBP did however not differ significantly between the placebo and active treatment groups (P=0.38). SBP was not associated with incident dementia, at baseline (P=0.62) or during follow-up (placebo group P=0.13, active group P=0.36). Wider achieved pulse pressure (PP) was associated with increased risk of dementia in both treatment groups (placebo P=0.032, active P=0.0046). The same tendency was observed for baseline PP (P=0.095).
  
  
  CONCLUSIONS
  Wider PP may possibly indicate an increased risk for dementia. Active treatment may act to change the shape of the relationship between DBP and dementia. Future studies need to focus on exploring the ideal goal pressure for this age group.
authors.affiliation: aImperial College London UK bDepartment of Cardiovascular Diseases, The Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, University of Leuven, Leuven, Belgium cCentre for Epidemiological Studies and Clinical Trials, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China dHôpital Broca, Centre de Gerontologie, 54-56 rue Pascal, 75013 Paris France eLondon School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Peters
authors.forename: Nigel
authors.initials: N
authors.lastname: Beckett
authors.forename: Robert
authors.initials: R
authors.lastname: Fagard
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Thijs
authors.forename: Ji-Guang
authors.initials: JG
authors.lastname: Wang
authors.forename: Francoise
authors.initials: F
authors.lastname: Forette
authors.forename: Lisa
authors.initials: L
authors.lastname: Pereira
authors.forename: Astrid
authors.initials: A
authors.lastname: Fletcher
authors.forename: Christopher
authors.initials: C
authors.lastname: Bulpitt
mesh_terms: D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D003704:Dementia / Q000503:physiopathology* / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007190:Indapamide / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D020913:Perindopril / Q000008:administration & dosage / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011673:Pulsatile Flow / Q000187:drug effects; D012044:Regression Analysis; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D007190:Indapamide; D020913:Perindopril