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The cross-sectional association between vasomotor symptoms and hemostatic parameter levels in postmenopausal women

Harrington, Laura B. PhD, MPH; Blondon, Marc MD, MS; Cushman, Mary MD, MSc; Kaunitz, Andrew M. MD; Rossouw, Jacques E. MD; Allison, Matthew A. MD, MPH; Martin, Lisa W. MD; Johnson, Karen C. MD, MPH; Rosing, Jan PhD; Woods, Nancy F. PhD, RN, FAAN; LaCroix, Andrea Z. PhD; Heckbert, Susan R. MD, PhD; McKnight, Barbara PhD; Smith, Nicholas L. PhD

doi: 10.1097/GME.0000000000000777
Original Articles

Objective: Vasomotor symptoms (VMS) may be a marker of cardiovascular risk. We aimed to evaluate the cross-sectional association of VMS presence and severity with hemostatic parameter levels measured at baseline among Women's Health Initiative (WHI) Hormone Therapy trial postmenopausal participants.

Methods: This cross-sectional analysis included 2,148 postmenopausal women with measures of VMS presence and severity reported in the 4 weeks before WHI baseline, who were not using warfarin or hormone therapy and for whom the following baseline hemostatic parameters were measured within the WHI Cardiovascular Disease Biomarker Case-Control Study: antithrombin, plasminogen activator inhibitor-1, protein C antigen, total and free protein S antigen, total and free tissue factor pathway inhibitor, D-dimer, normalized activated protein C sensitivity ratio, and thrombin generation. Using multiple linear regression, we estimated the adjusted average difference in each hemostatic parameter associated with VMS presence and severity. A multiple comparisons-corrected P value was computed using the P-min procedure to determine statistical significance of our smallest observed P value.

Results: Women were 67 years of age on average and 33% reported VMS presence at baseline. There was some suggestion that VMS presence may be associated with a −0.34 adjusted difference in normalized activated protein C sensitivity ratio compared with no VMS (95% CI, −0.60 to −0.087; P = 0.009), but this association was not significant after correction for multiple comparisons (P = 0.073). VMS presence or severity was not significantly associated with the other hemostatic parameters.

Conclusions: We found no convincing evidence that VMS presence or severity was associated with levels of hemostatic parameters among postmenopausal women.

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1Department of Epidemiology, University of Washington, Seattle, WA

2Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA

3Division of Angiology and Haemostasis, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland

4Department of Medicine, University of Vermont, Burlington, VT

5Department of Obstetrics and Gynecology, University of Florida College of Medicine-Jacksonville, Jacksonville, FL

6National Heart Lung and Blood Institute, Bethesda, MD

7Department of Preventive Medicine, University of California San Diego, San Diego, CA

8Department of Medicine, George Washington University, Washington, DC

9Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN

10Department of Biochemistry, Maastricht University, Maastricht, The Netherlands

11School of Nursing, University of Washington, Seattle, WA

12Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA

13Department of Biostatistics, University of Washington, Seattle, WA.

Address correspondence to: Laura B. Harrington, PhD, MPH, Department of Nutrition, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Building 2, Boston, MA 02115. E-mail:

Received 24 May, 2016

Revised 6 September, 2016

Accepted 6 September, 2016

The opinions expressed in this manuscript are those of the authors and do not necessarily reflect the views of the National Heart, Lung, and Blood Institute/US Department of Health and Human Services.

Funding/support: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. This work is supported by grant HL121414 (Smith) from the NHBLI and NHLBI Cardiovascular Disease Training Grants (HL007902: David S. Siscovick; HL098048: Eric B. Rimm).

Financial disclosure/conflicts of interest: A.M.K. reports that his institution receives support from Bayer and TherapeuticsMD and that he serves on advisory boards for Allergan, Bayer, and Pfizer and received payments from Teva. A.Z.L. reports a financial relationship with Sermonix, Pfizer, and Amgen. There are no disclosures for all other coauthors.

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© 2017 by The North American Menopause Society.