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Rebecca C. Thurston, PhD Departments of Psychiatry, Psychology, and - - PowerPoint PPT Presentation

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Rebecca C. Thurston, PhD Departments of Psychiatry, Psychology, and Epidemiology University of Pittsburgh Vas asomotor Sympt ptoms ( (VMS) Hot flashes, night sweats Over 70% of women experience during menopausal transition Can

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Rebecca C. Thurston, PhD

Departments of Psychiatry, Psychology, and Epidemiology University of Pittsburgh

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Vas asomotor Sympt ptoms ( (VMS)

 Hot flashes, night sweats  Over 70% of women experience

during menopausal transition

 Can persist for decades (10 years!)

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51

Ho Hot F Fla lashes D Dura ration

50 100

10 20 30 40 50 60 70 80

80 Birth Death

% US women

Final Menstrual Period (FMP)

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VMS MS

Long understood to have

important impact on quality of life

  • Few medical implications?
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Is a a Hot F Flas ash Just st a a Hot F Flas ash?

 WHI and HERS: women with

baseline VMS highest CVD risk with HT use

  • WHI (older women) Rossouw et al., 2007
  • HERS (women with CHD) Huang et al.,

2009

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VMS and Subclinical CVD

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Su Subclinical al C Car ardio iovasc scular ar D Disease isease (CVD) D) M Measu easures es

 FMD: Endothelial

dysfunction (lower worse)

 Early in CVD

 Calcification: Calcified

plaques

 IMT: Thickness of intimal

and medial layers

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Stu Study o

  • f

f Wome men’s ’s H Health A th Across ss the the Na Natio tion ( (SWAN)

Hot Flashes Subclinical Cardiovascular Disease (CVD)

  • Flow mediated

dilation (FMD)

  • Calcification
  • Intima media

thickness (IMT)

CV Risk Factors? E2?

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Study o dy of Wom

  • men

en’s ’s Health Acr cros

  • ss t

the Nat ation ion (SWAN AN)

Baseline Yrs 4-7

  • FMD: Brachial

artery ultrasound

  • Calcification: EBT

aorta

  • IMT: Carotid artery

ultrasound

SWAN Heart (N=557)

Pittsburgh, Chicago

SWAN (N=3302)

Annually:

  • Demographic,

Health behaviors, Affect

  • Hot flashes
  • SBP, DBP, BMI
  • Blood Draw: E2,

lipids, glucose

F F F F

Follow up Yrs 6-9

  • IMT

Baseline 13

B B B B

2 3 4 5 6 7 8 9 1 10 11 12

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Hot Fl Flas ashes & & Fl Flow M Med ediat iated Dil Dilat ation ion

4 6 8 10 12 None Any FMD (%, M, SD) Hot Flashes

Age, site, race, lumen diameter, BMI, education, DBP, HT use, HDL, LDL, triglycerides, glucose, diabetes history, lipid med use, smoking, physical activity, E2, cycle day of blood draw

(Thurston et al., 2008, Circulation)

*

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50 60 70 80 None Any % with Aortic Calcification Hot Flashes

Hot F Flash ashes & es & Aortic ic C Cal alcif ific ication

Age, site, race, education, BMI, smoking, SBP, antidepressant use, HT, menopausal status, depressive sx, phys activity, glucose, HDL, LDL, triglycerides, diabetes hx, cycle day, E2

(Thurston et al., 2008, Circulation)

*

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Cross S Sectio ional nal A Associatio ciation b n between n Ho Hot F Flas ashes and I and IMT MT

0.68 0.69 0.7 0.71 0.72 0.73

None 1-5 Days 6+ Days IMT (mm) Hot flashes in past 2 weeks

age, site, race, education, BMI, smoking status, SBP, HDL, LDL, triglycerides, glucose, diabetes status/meds, CVD status/meds, HT use, E2, cycle day of blood draw

(Thurston et al., 2011, Menopause)

*

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0.68 0.69 0.7 0.71 0.72 0.73

None One Both IMT (mm) Visits with Hot Flashes

Associat

  • ciation

ion b between n Hot Flas ashes es Acr cros

  • ss V

Vis isit its and and IM IMT

age, site, race, education, BMI, smoking status, SBP, HDL, LDL, triglycerides, glucose, diabetes status/meds, CVD status/meds, HT use, E2, cycle day of blood draw

(Thurston et al., 2011, Menopause)

*

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(Bechlioulis et al 2010, JCEM)

Mor

  • re evide

idence ce: H : Hot F Flas ashes es an and d Fl Flow Media diated ed Dil Dilat atio ion

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Mo More E Evi vidence: V VMS MS and nd IMT IMT

(Ozkaya et al 2011, Int J of Gyn & Obstet)

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Su Summa mmary of f Su Subc bclin inic ical CVD CVD fin indin ings

 Positive findings

  • VMS and IMT (Ozkaya et al., 2011; Thurston et al., 2011)
  • VMS (duration) and aortic calcification (Thurston et

al., 2010)

  • VMS and FMD/aortic calcification (Thurston et al.,

2008; Bechlioulis et al 2010)

 Negative findings: Coronary artery calcification

  • WHI: women with hysterectomy (Allison et al., 2010)
  • KEEPS: healthy early perimenopausal women

(Wolff et al., 2013)

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Ho Hot F Fla lashes a and Subcli linical C l CVD

 Women with hot flashes may have

higher subclinical CVD

  • Older or with some elevated CVD risk

factors?

 Not explained by CVD risk factors, E2  Mechanisms?

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VMS and the Autonomic Nervous System

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VMS a S and A nd Aut uton

  • nomic N

Nervou

  • us

Syste tem

 Etiology of VMS: Role of autonomic

nervous system speculated

 Reduced parasympathetic (vagal)

control of heart rate linked to elevated CVD risk

 High frequency heart rate variability

(HF-HRV)

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Study Q y Quest stion

Hot Flashes

Cardiac vagal control (HF- HRV)

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 Controlled laboratory studies  “Real world” ambulatory studies

VMS a S and th nd the A Aut utonomic N Nervous Syste tem

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Physio ysiologic Measure urement nt of

  • f Hot

Fl Flashe hes

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Hot Flash Diar Flash Diary

  • Occurrence
  • Severity
  • Bothersome
  • Emotions
  • …
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Redu duce ced C Car ardiac diac Vagal Con

  • ntrol
  • l Dur

During ing Ho Hot F Flashe hes: L Labora boratory

* p < 0.05 vs. minute zero

Pre-Flash Period Post-Flash Period Flash Period

(Thurston et al. 2010, Menopause)

Flash Period

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Redu duce ced C Car ardiac diac Vagal Con

  • ntrol
  • l Dur

During ing Hot Fl Flas ashes: A : Ambulat atory y (24 hrs)

Pre-flash Post-flash p<0.0001 p<0.0001

Minutes surrounding hot flash HF-HRV (lnmsec2)

(Thurston et al., 2012, Menopause)

Hot Flash

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Autonomic ic Ne Nervous Syst System m and Ho Hot F Fla lashes

 Others similar findings: Freedman et al.,

2011; deZambotti et al., 2013; Hoikkala et al., 2010

 Mechanism linking hot flashes to

CVD risk?

 Insight into etiology of hot flashes

 Autonomic nervous system?

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VMS and CVD risk factors (traditional and novel)

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Hot Flash Flashes an and S Syst ystolic B Blo lood Pressu essure

(Gerber e et al. . 2007, M , Menop

  • pause)
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Ho Hot F Fla lashes a and LDL C Chole

  • lesterol

100 105 110 115 120 125 130 1 3 4 5 6 7

LDL, mg/dL

SWAN Visit None 1-5 Days 6+ Days

Hot flashes in past two weeks Covariates: age, site, race, education, menopausal status, alcohol use, physical activity, smoking, anxiety, BMI, CVD status/medication, lipid lowering medication

p<0.001

(Thurston et al., 2012, Obstet Gynecol)

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1.5 1.7 1.9 2.1 2.3 2.5

1 3 4 5 6 7

HOMA (median) SWAN Study Visit None 1-5 days >=6 days

Hot Fl Flashes a and nd HOMA OMA

p<0.0001

Hot flashes in past two weeks Covariates: Age, site, race, education, menopausal status, alcohol, smoking, physical activity, smoking, anxiety, BMI, heart, BP or lipid lowering med (Thurston et al., JCEM, 2012)

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5 6 7 8 9 10 1 3 4 5 6 7

TPA-antigen (log) SWAN Visit

None 1-5 Days 6+ Days

Hot Flash Flashes an and T TPA-antig antigen

Hot flashes in past two weeks

Covariates: education, menopausal status, alcohol, parity smoking, exercise, affect, BMI, CV meds, diabetes/insulin, steroids, pain med, antidepressants

p<0.001

(Thurston et al., 2011, Menopause)

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Ho Hot Flashes a and P nd P-selectin ctin

(Bechlioulis et al 2012, JCEM)

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 Subclinical CVD  Autonomic nervous system  Blood pressure  Lipids  Insulin resistance  Inflammatory/hemostatic factors

VMS a S and C nd CVD Ris Risk

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Stu Studie ies o

  • f

f CVD CVD events: V ts: Very y few

 VMS in context of HT use elevated

risk (older women): WHI & HERS (Rossouw et

al., 2007; Huang et al., 2009)

 Early VMS reduced risk, Later VMS

higher risk: WHI-OS (Szmuilowicz et al., 2011)

 Night sweats increased CHD events:

EPOS (Gast et al., 2011)

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Consi sider erat atio ions

 Age of onset: older? (see poster 107)  Duration or burden of VMS: More

persistent/ frequent/ severe?

 Existing CVD risk profile: Women with

elevated CVD risk factors?

 VMS measures: Brief, self-report

measures, recall and reporting biases

 Post-hoc analyses

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Hot F Flas ashes and and CVD Risk

 Study designed to address relations

between hot flashes and CVD risk

  • Comprehensively study mechanisms

linking hot flashes and CVD risk: R01HL105647, N=300 (PI: Thurston)

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Women, Menopause, Heart Disease

50 100 10 20 30 40 50 60 70 80

80 51

Birth Death Menopause

10000 20000 30000 10 20 30 40 50 60 70 80

Hot Flashes Heart Disease

(Dennerstein et al., 2000; Kronenberg, 1999; Mosca, 1997; Tunstall-Pedoe, 1998) Deaths in Thousands

%

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Implicat ications ns?

 Possibly……midlife marker of

CVD risk

  • Aggressive risk factor reduction

among women with hot flashes?

 Improve health of midlife women

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Karen Matthews, PhD Emma Barinas-Mitchell, PhD Kim Sutton-Tyrrell, DrPH Samar El Khoudary, PhD Faith Selzer, PhD Rachel Hess, MD, MSc Carolyn Crandall, MD, MS Barbara Sternfeld, PhD Susan Everson-Rose, PhD, MPH Ellen Gold, PhD Imke Janssen, PhD Lynda Powell, PhD

Acknowledgements

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SWAN (NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495, HL065581, HL06551) Thurston: K23AG029216, R01HL105647 Pittsburgh Mind Body Center/NIH (HL076852/076858) American Federation for Aging Research University of Pittsburgh Institute on Aging

The content of this presentation is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH or the NIH.

Acknowledgements

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Th Thank y you!

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Extra slides

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Ho Hot F Fla lashes a and Tri rigly glyceri rides

80 90 100 110 120 130 140 150 160 1 3 4 5 6 7

Triglycerides, mg/Dl

SWAN Visit None 1-5 Days 6+ Days

p<0.0001

Hot flashes in past two weeks Covariates: age, site, race, education, menopausal status, alcohol use, physical activity, smoking, anxiety, BMI, CVD status/medication, lipid lowering medication

(Thurston et al., 2012, Obstet Gynecol)

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Hot F Flas ashes and and Ap ApoB

  • B

95 100 105 110 115 120 1 3 4 5 6 7

ApoB, mg/Dl SWAN Visit None 1-5 Days 6+ Days

p<0.0001

Hot flashes in past two weeks

Covariates: age, site, race, education, menopausal status, alcohol use, physical activity, smoking, anxiety, BMI, CVD status/medication, lipid lowering medication (Thurston et al., 2012)

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100 105 110 115 120 125 130 135 140 1 3 5 7

Factor VIIc (log)

SWAN Visit

None 1-5 Days 6+ Days

Ho Hot Flashes a and F nd Fact ctor VIIc IIc

p<0.01

Hot flashes in past two weeks

Covariates: education, menopausal status, alcohol, parity smoking, exercise, affect, BMI, CV meds, diabetes/insulin, steroids, pain med, antidepressants

(Thurston et al., 2011, Menopause)

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Duration of Hot Flash reporting over 8 yrs and Aortic Calcification, HT users

(Thurston et al., 2010, Menopause)

b = 2.87, SE = 1.21, p<0.05

Covariates: age, race, smoking, SBP, LDL, HDL, triglycerides, glucose, BMI, education, alcohol use, BP med use, lipid med use, yrs since FMP, time difference between measurements

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VMS and IMT by Obesity Status

(Thurston et al., 2011, Menopause)