title: Vasomotor symptoms and cardiovascular events in postmenopausal women.
abstract: OBJECTIVE
  Emerging evidence suggests that women with menopausal vasomotor symptoms (VMS) have increased cardiovascular disease (CVD) risk as measured by surrogate markers. We investigated the relationships between VMS and clinical CVD events and all-cause mortality in the Women's Health Initiative Observational Study (WHI-OS).
  
  
  METHODS
  We compared the risk of incident CVD events and all-cause mortality between four groups of women (total N = 60,027): (1) no VMS at menopause onset and no VMS at WHI-OS enrollment (no VMS [referent group]), (2) VMS at menopause onset but not at WHI-OS enrollment (early VMS), (3) VMS at both menopause onset and WHI-OS enrollment (persistent VMS [early and late]), and (4) VMS at WHI-OS enrollment but not at menopause onset (late VMS).
  
  
  RESULTS
  For women with early VMS (n = 24,753), compared with no VMS (n = 18,799), hazard ratios (95% CIs) in fully adjusted models were as follows: major coronary heart disease (CHD), 0.94 (0.84-1.06); stroke, 0.83 (0.72-0.96); total CVD, 0.89 (0.81-0.97); and all-cause mortality, 0.92 (0.85-0.99). For women with persistent VMS (n = 15,084), there was no significant association with clinical events. For women with late VMS (n = 1,391), compared with no VMS, hazard ratios (95% CIs) were as follows: major CHD, 1.32 (1.01-1.71); stroke, 1.14 (0.82-1.59); total CVD, 1.23 (1.00-1.52); and all-cause mortality, 1.29 (1.08-1.54).
  
  
  CONCLUSIONS
  Early VMS were not associated with increased CVD risk. Rather, early VMS were associated with decreased risk of stroke, total CVD events, and all-cause mortality. Late VMS were associated with increased CHD risk and all-cause mortality. The predictive value of VMS for clinical CVD events may vary with the onset of VMS at different stages of menopause. Further research examining the mechanisms underlying these associations is needed. Future studies will also be necessary to investigate whether VMS that develop for the first time in the later postmenopausal years represent a pathophysiologic process distinct from the classic perimenopausal VMS.
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Chicago, IL 60611, USA. edszmuilowicz@post.harvard.edu
authors.forename: Emily D
authors.initials: ED
authors.lastname: Szmuilowicz
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Rossouw
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.forename: Karen L
authors.initials: KL
authors.lastname: Margolis
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Greep
authors.forename: Robert G
authors.initials: RG
authors.lastname: Brzyski
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: O'Sullivan
authors.forename: Chunyuan
authors.initials: C
authors.lastname: Wu
authors.forename: Matthew
authors.initials: M
authors.lastname: Allison
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.forename: Judith K
authors.initials: JK
authors.lastname: Ockene
authors.forename: Beatriz L
authors.initials: BL
authors.lastname: Rodriguez
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Sarto
authors.forename: Mara Z
authors.initials: MZ
authors.lastname: Vitolins
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Seely
mesh_terms: D000367:Age Factors; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000453:epidemiology* / Q000517:prevention & control; D003327:Coronary Disease / Q000453:epidemiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000502:physiology*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D014666:Vasomotor System / Q000503:physiopathology*; D016387:Women's Health