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Menopausal symptoms and cardiovascular disease mortality in the Women's Ischemia Syndrome Evaluation (WISE)

Thurston, Rebecca C. PhD; Johnson, B. Delia PhD; Shufelt, Chrisandra L. MD, MS, NCMP; Braunstein, Glenn D. MD; Berga, Sarah L. MD; Stanczyk, Frank Z. PhD; Pepine, Carl J. MD; Bittner, Vera MD, MSPH; Reis, Steven E. MD; Thompson, Diane V. MS; Kelsey, Sheryl F. PhD; Sopko, George MD, MPH; Bairey Merz, C. Noel MD

doi: 10.1097/GME.0000000000000731
Original Articles

Objective: Studies have linked vasomotor symptoms (VMS) to markers of cardiovascular disease (CVD) risk, yet few have considered clinical cardiovascular events. Data suggest that associations may depend upon the age that symptoms occur. We examined associations between VMS and cardiovascular events and endothelial function, considering age of symptom onset.

Methods: The Women's Ischemia Syndrome Evaluation enrolled women referred for coronary angiography for suspected myocardial ischemia. A total of 254 women aged more than 50 years, postmenopausal, with both ovaries, not taking hormone therapy underwent a baseline evaluation, were followed annually (median = 6.0 y), and the National Death Index was searched to ascertain CVD mortality (median = 9.3 y). A subset of participants underwent brachial artery ultrasound for flow-mediated dilation (FMD). Receiver-operating curve analysis was used to determine vasomotor symptom groups (symptoms beginning < age 42 [early onset], beginning ≥42 [later onset], never) which were examined in relation to cardiovascular events and FMD in Cox proportional hazard and linear regression models.

Results: Women reporting early onset VMS (HR = 3.35, 95% CI = 1.23-7.86, P = 0.005) and women who never had VMS (HR = 2.17, 95% CI = 1.02-4.62, P = 0.05) had higher CVD mortality than women with later onset symptoms (multivariable models). Women with early onset VMS had lower FMD than women with later onset symptoms (b = −4.31, SE = 2.10, P = 0.04, multivariable).

Conclusions: Women with signs and symptoms of ischemia who had VMS beginning early in midlife had higher CVD mortality and reduced endothelial function relative to women with later onset symptoms. Future research should evaluate the vascular phenotype of women with early midlife VMS.

1Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA

2Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA

3Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA

4Section of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, NC

5Department of Obstetrics and Gynecology, Keck School of Medicine of University of Southern California, Los Angeles, CA

6Division of Cardiology, Department of Medicine, University of Florida, Gainesville, FL

7Division of Cardiovascular Disease, Department of Medicine, University of Alabama Birmingham, AL

8Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA

9Division of Cardiology, Department of Medicine, Allegheny General Hospital, Pittsburgh, PA

10Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.

Address correspondence to: Rebecca C. Thurston, PhD, Department of Psychiatry, University of Pittsburgh, 3811 O’Hara St, Pittsburgh, PA 15213. E-mail:

Received 1 April, 2016

Revised 6 July, 2016

Accepted 6 July, 2016

This work is solely the responsibility of the authors. The content of this article does not necessarily represent the views of the NHLBI or the Department of Health and Human Services.

Funding/support: This work was supported by contracts from the National Heart, Lung and Blood Institutes (NHLBI), nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, RO1-HL-073412-01; grants U0164829,U01 HL649141, U01 HL649241; and grants from the Gustavus and Louis Pfeiffer Research Foundation, Danville, New Jersey, The Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California, The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania, and QMED, Inc, Laurence Harbor, New Jersey, and the Edythe L. Broad Endowment, the Barbra Streisand Women's Cardiovascular Research and Education Program, the Linda Joy Pollin Women's Heart Health Program, and the Constance Austin Fellowship Endowment, Cedars-Sinai Medical Center, Los Angeles and the Erika Glazer Women's Heart Health Project, Cedars-Sinai Medical Center, Los Angeles, California, and by an NHLBI grant K24HL123565 to Thurston.

Financial disclosure/conflicts of interest: G.D.B. is a consultant for Merck (Merck Manual), Takada Pharmaceuticals, Amgen, Allergan, Synagena, Sanofi, and Johnson and Johnson. G.D.B. owns stock in Pfizer and is a part-time employee of Pathway Genomics. S.L.B. has consulted for Ferring Pharmaceuticals (2014) and served on the Pfizer Scientific Advisory Board entitled “Estrogens, SERMS, and TSECS” (2013, 2014). She is on the Editorial Committee for Guidelines for Women's Health Care published by the American College of Obstetricians and Gynecologists, an Executive Committee Member for the International Society for Gynecological Endocrinology, on the Editorial Board for the Journal of Clinical Endocrinology and Metabolism, and on the Editorial Board for Menopause. She was a CVD Network Member for the Society for Women's Health Research from 2009 to 2015 and on the Special Programs Committee for the Endocrine Society from 2013 to 2016. Until 3/31/16, she was a co-investigator on RO1-CA107408 entitled, “Long Term Trajectory of Cognitive Function Related to Anastrozole Use in Women.” F.Z.S. has consulted with Merck & Co, Agile Therapeutics, TherapeuticsMD, and Abbvie. For the remaining authors none were declared.

© 2017 by The North American Menopause Society.