title: Changes in body weight and blood pressure: paradoxical outcome events in overweight and obese subjects with cardiovascular disease.
abstract: OBJECTIVE
  The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in body weight and blood pressure, and the impact of these changes on subsequent cardiovascular outcome events.
  
  
  METHODS
  A total of 9804 male and female subjects, aged 55 years or older, with a body mass index of 27-45 kg m(-2) were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor (hypertension, dyslipidemia, current smoking or diabetic nephropathy) to assess cardiovascular outcomes. Post hoc subgroup analyses of weight change (categories) and blood pressure were performed overall and by treatment group (6-week sibutramine followed by randomized placebo or continued sibutramine). The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models with factors for treatment, subgroups and interactions.
  
  
  RESULTS
  During the initial 6-week sibutramine treatment period, systolic blood pressure decreased progressively with increasing weight loss in hypertensive subjects (-8.1±10.5 mm Hg with <5 kg weight loss to -10.8±11.0 mm Hg with ⩾5 kg weight loss). The highest POE incidence occurred mainly in groups with increases in both weight and blood pressure. However, with long-term sibutramine treatment, a markedly lower blood pressure tended to increase POEs.
  
  
  CONCLUSIONS
  Modest weight loss and modest lower blood pressure each reduced the incidence of cardiovascular events, as expected. However, the combination of early marked weight loss and rapid blood pressure reduction seems to be harmful in this obese elderly cardiovascular diseased population.
authors.affiliation: The Boden Institute of Obesity, Nutrition Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: R V
authors.initials: RV
authors.lastname: Seimon
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Espinoza
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Ivers
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Gebski
authors.affiliation: National Centre for Cardiovascular Prevention and Outcomes, University College London, Institute for Cardiovascular Science, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Finer
authors.affiliation: Special Vocational College for Handicapped Persons, Mainz, Germany.
authors.forename: U F
authors.initials: UF
authors.lastname: Legler
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: A M
authors.initials: AM
authors.lastname: Sharma
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: W P T
authors.initials: WP
authors.lastname: James
authors.affiliation: Catholic University of Rio de Janeiro and State Institute of Diabetes and Endocrinology, Rio de Janeiro, Brazil.
authors.forename: W
authors.initials: W
authors.lastname: Coutinho
authors.affiliation: The Boden Institute of Obesity, Nutrition Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: I D
authors.initials: ID
authors.lastname: Caterson
mesh_terms: D001067:Appetite Depressants / Q000627:therapeutic use*; D001794:Blood Pressure; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000150:complications* / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D003503:Cyclobutanes / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy; D003925:Diabetic Angiopathies / Q000503:physiopathology / Q000517:prevention & control* / Q000628:therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D050177:Overweight / Q000188:drug therapy; D011446:Prospective Studies; D012307:Risk Factors; D040242:Risk Reduction Behavior; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D001067:Appetite Depressants; D003503:Cyclobutanes; C058254:sibutramine