9/24/2018 Hypertensive Disorders of Pregnancy and Gestational - - PDF document

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Hypertensive Disorders of Pregnancy and Gestational Diabetes as Risk Factors for Hot Flashes in Midlife Women

Co-authors: Yamnia Cortés1, Janet Catov1,2, Karen A. Matthews1,3, Sybil Crawford4, Monique Hedderson5, Rebecca C. Thurston1,3

1Department of Epidemiology, University of Pittsburgh Graduate School of Public Health 2Department of Obstetrics and Gynecology, University of Pittsburgh 3Department of Psychiatry, University of Pittsburgh 4Department of Medicine, University of Massachusetts 5Division of Research, Kaiser Permanente

Rhoda Jamadar Conant, MD

University of Oklahoma Health Sciences Center Department of Obstetrics and Gynecology

• 60-80% of women experience HF during menopausal transition 1
• Narrowing of thermoneutral zone
• Altered autonomic control
• Vascular / endothelial dysfunction3,4,5

Menopausal Hot Flashes (HF)

• Hypertensive Disorders in Pregnancy (HDP)
• Complicates 10% of pregnancies
• Related to generalized endothelial and autonomic dysfunction6
• Possible relationship with pre-existing vascular disease7
• Gestational Diabetes (GDM)
• Complicates 5% of pregnancies
• Associated with vascular and endothelial dysfunction

Pregnancy Complications

• Association between HDP and cardiovascular disease (CVD)

later in life

• 50% of women with GDM develop type II diabetes later in life;

risk factor for CVD

• Some evidence that HF are associated with risk for CVD3

Risk Factors for Cardiovascular Disease

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Study Purpose and Hypothesis

• Hypothesis 1: Women with a history of HDP and/or GDM may

experience a greater number of HF

• Hypothesis 2: Nulliparous women may have fewer HF

To examine the relationship between women with a history of HDP and/or GDM and HF in midlife.

Study of Women’s Health Across the Nation

Detroit, MI Boston,MA Newar ark, NJ Pittsb sburgh,PA PA Chicag ago, IL Los Angeles, s, CA Oakland, CA

= Black = Hispanic = Chinese = Japanese Multi-site, multi-ethnic, longitudinal study of the natural history of the menopause transition.

• Longitudinal analysis, 13 visits over 15 years
• Inclusion criteria (baseline)
• Age 42-52 years
• Pre or early perimenopausal
• Intact uterus and at least one ovary
• Menstrual bleeding in past 3 months and no hormone therapy

Study of Women’s Health Across the Nation

• Pregnancy Questionnaire (Visit 13):
• Preeclampsia/toxemia (high blood pressure and proteinuria),

gestational hypertension or pregnancy induced hypertension, gestational diabetes (no diabetes pre-pregnancy)

• HF (at each visit):
• Were recorded as any vs none; 0 days, 1-5 days, 6+ days in past two

weeks

Methods

NULLIPAROUS NO HDP/GDM HDP/GDM

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• ANOVA or Kruskal-Wallis tests for continuous data and Chi-Square
• r Fisher's Exact for categorical variables
• Visits with HT use excluded
• Pregnancy history examined in relation to HF using generalized

estimating equations adjusting for:

• Model 1: age (time-varying)
• Model 2: study site, race/ethnicity, financial strain, education
• Model 3: menopause status (time-varying)

Statistical Methods 3 Groups

Nulliparous n= 395 (17.6%) No HDP/GDM n= 1646 (73.2%) HDP/GDM n= 208 (9.2%) HDP only n=176 (85%) GDM only n=27 (13%) Both GDM/HDP n=27 (2%)

Table 1. Participant Characteristics at SWAN Visit 13 (n=2249) Nulliparous (n=395) No HPD/GDM (n=1646) HPD/GDM (n=208) P Age, Mean ± SD 61.6 ± 2.6 62.1 ± 2.7 61.4 ± 2.4 <0.0001 Race/Ethnicity, n (%) (n=2112) White Black Hispanic Chinese/Japanese 262 (67.0) 55 (14.1) 7 (1.8) 67 (17.1) 714 (44.2) 461 (28.5) 102 (6.3) 339 (21.0) 95 (46.3) 76 (37.1) 10 (4.9) 24 (11.7) <0.0001 Education, n (%) (n=2194) College degree/post college 262 (67.5) 665 (41.5) 88 (43.1) <0.0001 Body mass index (kg/m2), Mean ± SD 28.7 ± 7.3 29.1 ± 7.4 32.5 ± 7.0 <0.0001 HOMA-IR, Median [IQR] 2.0 [1.2, 3.3] 2.2 [1.3, 3.8] 2.9 [1.8, 4.7] 0.0009 Anti-hypertensive, n (%) (n=2223) 150 (38.2) 735 (45.3) 123 (59.7) <0.0001 Lipid-lowering medications, n (%) (n=2248) 104 (26.3) 471 (28.6) 83 (39.9) 0.001 Anti-diabetics, n(%) (n=2198) 52 (13.4) 239 (14.9) 51 (25.0) 0.0004 Table 2. Odds of reporting any hot flashes in past 2 weeks across SWAN visits by pregnancy history Model 1 OR (95% CI) P Model 2a OR (95% CI) P Model 3a OR (95% CI) P Nulliparous 0.81 (0.71, 0.92) 0.002 0.96 (0.80, 1.14) 0.62 0.96 (0.79, 1.16) 0.66 No HDP/GDM Reference

• HDP/GDM

1.20 (1.01, 1.42) 0.04 1.06 (0.86, 1.30) 0.61 1.03 (0.82, 1.30) 0.82

• Nulliparous women had a lower odds of reporting any HF
• HDP/GDM had a greater odds of any HF

HPD = hypertensive pregnancy disorder GDM = gestational diabetes Model 1: age (time-varying) Model 2: study site, race/ethnicity, financial strain, education Model 3: menopause status (time-varying)

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Table 3. Odds of being in higher hot flash frequency categories in past 2 weeks and pregnancy history Model 1 OR (95% CI) P Model 2a OR (95% CI) P Model 3a OR (95% CI) P Nulliparous 0.83 (0.73, 0.95) 0.008 1.00 (0.84, 1.19) 0.97 1.02 (0.84, 1.24) 0.83 No HPD/GDM Reference

• HPD/GDM

1.19 (1.00, 1.41) 0.05 1.02 (0.83, 1.25) 0.88 1.01 (0.81, 1.27) 0.92

• Nulliparous women had a lower odds of frequent HF (6+ days)
• HDP/GDM group had a greater odds of frequent HF

HPD = hypertensive pregnancy disorder GDM = gestational diabetes Model 1: age (time-varying) Model 2: study site, race/ethnicity, financial strain, education Model 3: menopause status (time-varying)

• HDP/GDM associated with a likelihood of HF19
• Nulliparity may be associated with fewer HF20
• Associations between pregnancy history and HF attenuated after

adjusting for education

• Important role of socioeconomic factors in pregnancy outcomes

and HF

Conclusions

Clinical Implications & Future Studies

• Pregnancy complications associated with worse CV risk factor profile

in midlife

• May be associations between pregnancy complications and hot

flashes in midlife

• In women with HDP/GDM, do HF modulate the risk for CVD later in

life?

References

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7.Levine, R.J., et al., Serum sFlt1 concentration during preeclampsia and mid trimester blood pressure in healthy nulliparous women. Am J Obstet Gynecol, 2006. 194(4): p. 1034-41. 8.White, W.M., et al., A history of preeclampsia is associated with a risk for coronary artery calcification 3 decades later. Am J Obstet Gynecol, 2016. 214(4): p. 519 e1-8. 9.Morris, E.A. and I.M. Bernstein, Re: Endothelial dysfunction and vascular stiffness in women with previous pregnancy complicated by early or late pre-eclampsia. R. Orabona, E. Sciatti, E. Vizzardi, I. Bonadei and A. Valcamonico. Ultrasound Obstet Gynecol 2017; 49: 116-123. Ultrasound Obstet Gynecol, 2017. 49(1): p. 22-23. 10.Collen, A.C., K. Manhem, and Y.B. Sverrisdottir, Sympathetic nerve activity in women 40 years after a hypertensive pregnancy. J Hypertens, 2012. 30(6): p. 1203-10. 11.Greenwood, J.P., et al., Sympathetic neural mechanisms in normal and hypertensive pregnancy in humans. Circulation, 2001. 104(18): p. 2200-4. 12.Schobel, H.P., et al., Preeclampsia -- a state of sympathetic overactivity. N Engl J Med, 1996. 335(20): p. 1480-5. 13.Jensen, L.A., C.L. Chik, and E.A. Ryan, Review of gestational diabetes mellitus effects on vascular structure and function. Diab Vasc Dis Res, 2016. 13(3): p. 170-82. 14.Committee on Practice, B.-O., Practice Bulletin No. 137: Gestational diabetes mellitus. Obstet Gynecol, 2013. 122(2 Pt 1): p. 406-16. 15.Bokslag, A., et al., Effect of early-onset preeclampsia on cardiovascular risk in the fifth decade of life. Am J Obstet Gynecol, 2017. 16.McDonald, S.D., et al., Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses. Am Heart J, 2008. 156(5): p. 918-30. 17.Barden, A., et al., Factors predisposing to pre-eclampsia in women with gestational diabetes. J Hypertens, 2004. 22(12): p. 2371-8. 18.Salzer, L., K. Tenenbaum-Gavish, and M. Hod, Metabolic disorder of pregnancy (understanding pathophysiology of diabetes and preeclampsia). Best Pract Res Clin Obstet Gynaecol,

• 2015. 29(3): p. 328-38.

19.Drost, J.T., et al., More vasomotor symptoms in menopause among women with a history of hypertensive pregnancy diseases compared with women with normotensive pregnancies. Menopause, 2013. 20(10): p. 1006-11

• 20. Hess R.,et al. Pregnancy and birth history influence women’s experience of menopause. Menopause. 2008 May-June;15(3).435-41.

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Acknowledgements

SWAN has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office

• f Research on Women’s Health (ORWH) (Grants U01NR004061;

U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495). This work was also supported by the NIH, National Heart Lung and Blood Institute (K24123565 to Thurston). The content of this abstract is soley the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORHW

• r NIH.