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



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.



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).



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.
Rebecca C
RC
Thurston
B Delia
BD
Johnson
Chrisandra L
CL
Shufelt
Glenn D
GD
Braunstein
Sarah L
SL
Berga
Frank Z
FZ
Stanczyk
Carl J
CJ
Pepine
Vera
V
Bittner
Steven E
SE
Reis
Diane V
DV
Thompson
Sheryl F
SF
Kelsey
George
G
Sopko
C Noel
CN
Bairey Merz
D000367:Age Factors; D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality*; D002423:Cause of Death; D017023:Coronary Angiography; D005260:Female; D006801:Humans; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000401:mortality*; D017698:Postmenopause; D011446:Prospective Studies; D012307:Risk Factors; D013577:Syndrome
Obstet Gynecol. 2012 Apr;119(4):753-61
22433339
Mol Cell Endocrinol. 2014 May 25;389(1-2):65-70
24530925
Menopause. 2011 Jun;18(6):603-10
21358352
Am J Public Health. 2006 Jul;96(7):1226-35
16735636
Menopause. 2009 Sep-Oct;16(5):860-9
19436224
Am Heart J. 2013 Jul;166(1):134-41
23816032
JAMA. 2007 Apr 4;297(13):1465-77
17405972
Hypertension. 2008 Jun;51(6):1492-8
18391100
PLoS One. 2013 Sep 18;8(9):e74585
24058592
JAMA Intern Med. 2015 Apr;175(4):531-9
25686030
Circulation. 2008 Sep 16;118(12):1234-40
18765392
Obstet Gynecol. 2011 May;117(5):1095-104
21508748
Maturitas. 2011 Feb;68(2):165-73
21167666
Am J Epidemiol. 2000 Sep 1;152(5):463-73
10981461
Clin Endocrinol (Oxf). 2016 May;84(5):672-9
26663024
Am J Med. 2005 Dec 19;118 Suppl 12B:14-24
16414323
J Womens Health (Larchmt). 2004 Oct;13(8):872-87
15671703
Menopause. 2007 Mar-Apr;14(2):308-15
17213753
Menopause. 2013 Mar;20(3):342-53
23435033
Menopause. 2011 Feb;18(2):146-51
21127438
Steroids. 1976 Aug;28(2):179-96
973234
Am Heart J. 2002 May;143(5):802-7
12040340
Menopause. 2011 Apr;18(4):352-8
21242820
Curr Hypertens Rep. 2014 Nov;16(11):487
25182159
J Clin Endocrinol Metab. 2012 Oct;97(10):3487-94
22851488
J Clin Endocrinol Metab. 2010 Mar;95(3):1199-206
20080857
Menopause. 2009 Jul-Aug;16(4):639-43
19325499
Am J Cardiol. 2001 Apr 15;87(8):937-41; A3
11305981
Stroke. 2016 Jan;47(1):12-7
26578657
Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1782-7
17541023
J Am Coll Cardiol. 1999 May;33(6):1453-61
10334408
Menopause. 2001 Jan-Feb;8(1):33-42
11201513
Menopause. 2009 Sep-Oct;16(5):888-91
19421076
Am J Epidemiol. 2003 Aug 15;158(4):347-56
12915500