Rebecca C. Thurston, PhD Director, Womens Biobehavioral Health - - PowerPoint PPT Presentation

Rebecca C. Thurston, PhD

Director, Women’s Biobehavioral Health Research Program University of Pittsburgh

North American Menopause Society 2019 Annual Meeting, Chicago, IL, Sept 26, 2019

Funding and Disclosures

Funding: Supported by the National Institutes of Health (NIH), National Institute on Aging (NIA), National Institute of Nursing Research (NINR), and the Office of Women’s Health Research (OWHR, Grants U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495).

Content is the responsibility of authors and does not necessarily represent the views of the NIH, NIA, NINR, or ORWH.

Disclosures (Thurston): Astellas, Pfizer, Procter & Gamble (consulting)

Vasomotor Symptoms (VMS)

 VMS: Hot flashes / night sweats  >70% of women experience during

menopause transition

➢ 30% frequent or severe

 Frequent VMS persist for 7-10 years

(Avis…Thurston et al, 2015)

• VMS important for quality of life

➢ Physical health?

VMS and Cardiovascular Disease in Women

• CVD leading cause of death in women
• Newer research links VMS to CVD risk indicators

➢ CVD risk factors ➢ Subclinical CVD indices

• Research with “hard” clinical CVD outcomes limited

➢ Recalled VMS over years ➢ Reporting and memory biases

VMS and Cardiovascular Disease in Women

• Few studies are well designed to address this question

➢ Longitudinal study of menopause ➢ Regular, prospective assessment of VMS and CVD events ➢ Capture midlife and years when women have CVD events:

Follow women for 20+ years

• Study of Women’s Health Across the Nation

➢ Uniquely positioned to address this question

Vasomotor Symptoms Cardiovascular Disease Events

Demographic and CVD risk factors

Study of Women’s Health Across the Nation (SWAN), N=3302

16 visits over 22 years:

• Demographics
• VMS: Hot flashes, night sweats
• SBP, DBP, BMI
• Phlebotomy: lipids, glucose, etc
• Medication use
• Health behaviors
• CVD events (myocardial infarction, cerebrovascular

accident, heart failure, revascularization), adjudication

• Death certificates, cause of death (NDI search)

Baseline 15 2 3 4 5 6 7 8 9 1 10 11 12 13 14

Methods

• VMS at baseline

➢ None, 1-5 days, ≥6 days; past 2 weeks

• Persistent frequent VMS over the menopause

➢ Proportion of visits reporting VMS ≥6 days / 2 weeks

• CVD events & CVD mortality: First event
• Control for range of risk factors

Baseline Participant Characteristics (N=3272)

No VMS† (N=1986) 1-5 Days† (N=921) ≥6 Days† (N=365)

Age, Median (IQR)* 46 (44 - 48) 46 (44 - 48) 47 (45 - 49) Race, N (%)* Black White Chinese Hispanic Japanese 489 (24) 981 (49) 171 (9) 152 (8) 193 (10) 286 (31) 406 (44) 58 (6) 100 (11) 71 (8) 144 (39) 155 (42) 17 (5) 32 (9) 17 (5) BMI, M (SD)* 26 (22 - 31) 27 (23 - 33) 29 (25 - 36) SBP, M (SD)* 113 (105 - 124) 118 (108 - 129) 120 (109 - 130) DBP, M (SD)* 74 (69 - 80) 76 (69 - 83) 76 (70 - 83) Menopause stage, N (%) early peri- (vs Pre-)* 770 (39) 493 (54) 222 (62)

† VMS in past two weeks; *Varies by VMS category, p<.05

Baseline VMS in relation to CVD events / CVD mortality

0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 5 10 15 20

Event Rates Years from Baseline No VMS VMS 1-5 days/2weeks VMS >=6 days/2weeks

P=.0001 N=3272, 231 events

Baseline VMS in Relation to CVD events/CVD mortality

Model 1 HR (95% CI) Model 2 HR (95% CI) Frequency of VMS 1-5 days / 2 weeks 1.33 (.99-1.80)† 1.04 (.76-1.41) 6 days / 2 weeks 2.16 (1.53-3.03)*** 1.51 (1.05, 2.17)*

Relative to no VMS in prior two weeks

†p<.10, *p<.05, **p<.01, ***p<.001

Model 1: Site, baseline age, race/ethnicity Model 2: Model 1 + Education, financial strain, menopause stage, SBP, BMI, LDL-C, triglycerides, HOMA-IR, medication use (BP-lowering, lipid-lowering, anti-diabetic), smoking, physical activity

Persistent frequent VMS in relation to CVD events / CVD mortality

N=3272, 231 events 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 5 10 15 20

Event Rates Years from Baseline [0-33)% of the visits (7.7%) [33-66)% of the visits (15.3%) [66-100]% of the visits (21.4%) 0-33% of the visits 33-66% of the visits 66-100% of the visits P=.0001

Persistent VMS in Relation to CVD events/CVD mortality

Model 1 HR (95% CI) Model 2 HR (95% CI) >25% (vs. ≤25%) of attended visits with frequent VMS 1.79 (1.37-2.34)**** 1.80 (1.36-2.36)****

†p<.10, *p<.05, **p<.01, ***p<.001, ****p<.0001

Model 1: Site, baseline age, race/ethnicity Model 2: Model 1 + Education, financial strain, menopause stage, SBP, BMI, LDL-C, triglycerides, HOMA-IR, medication use (HT, BP-lowering, lipid-lowering, anti-diabetic), smoking, physical activity, number of attended visits

Additional Findings

• Findings similar:

➢ For adjudicated CVD events ➢ Timing of VMS (when the VMS occurred) ➢ Censoring women at bilateral oophorectomy ➢ Dropping visits with hormone therapy use

Summary

• SWAN: Frequent VMS at baseline or persistently

frequent VMS over the transition associated with increased risk of CVD events later in life

➢ Not explained by standard CVD risk factors ➢ 50-80% increased risk

• Frequent or persistent VMS as novel marker of

midlife CVD risk

➢ Risk prediction for CVD in midlife women?

Co-Authors: Helen Vlachos, PhD Samar El Khoudary, PhD Maria Brooks, PhD Carol Derby, PhD Karen Matthews, PhD Hadine Joffe, MD Elizabeth Jackson, PhD Sioban Harlow, PhD

Study Participants

Acknowledgements