Echographie du poignet et de la main

1
CARDIOVASCULAR DISEASE AND HT NEW
DEVELOPMENTS U. GASPARD Belgian Menopause
Society, Feb 3,2007
2
Women and CVD

Von der Lohe E, 2003
3
Risk factors for mortality in Postmenopausal women

• 17748 PMW recruited in 1990, assessed and
  followed-up for 9 years for risk factors of
  mortality 10 died during that period.
• Unmodifiable risk (relative RH) of death
• History of breast cancer 1.9 (1.6-2.3)
• Age (per 5 years of age) 1.5 (1.5-1.6)
• History of breast disease 1.4 (1.2-1.6)
• Modifiable risk factors of death
• Current smoking 3.7 (3.1-4.5)
• Physical function (up and go test) 1.7 (1.4-2.0)
• Systolic blood pressure 1.3 (1.1-1.5)
• Elevated waist-hip ratio 1.3 (1.1-1.5)
• ? Simple measures could improve modifiable risk
  factors of death in PMW !

Tice JA et al, Arch
Intern Med 20061662469
4
Some recently described effects of E on vessel
wall and coagulation
5
Intima media thickness and long term ERT (3)

• 20 years of E2 (treatment initiated soon after
  menopause) preservation of thick media and thin
  intima as in young women low I/M ratio
• In women 70 years old not using ERT, higher I/M
  ratio nearer to I/M ratio found if CHD or stroke
  !
• ? Long term ERT keeps the artery wall
  morphologically young

Naessen T et al, Maturitas 54S2006S23
Atherosclerosis 2006, in press
6
Hormone Therapy and Plaque Reduction
A. Early Intervention
B. Late Intervention
0.40 0.30 0.20 0.10 0
PN.S.
70 Plt0.05
Coronary Artery Plaque Size (mm2)
Placebo CEE Baseline Placebo
CEE CEE MPA
Surgical Menopausal Monkeys Rx with Conjugated
Estrogen With and Without MPA.


Clarkson 2002. INT. J. FERTIL.
4761
7
Protection of saphenous vein grafts by HT in PMW
with CABG

• Saphenous vein grafts (SVG) in PMW with coronary
  bypass poor outcome, rapid acute closure !
  Thrombosis, myointimal hyperplasia, early
  atherosclerosis)
• PMW with SVG n 40 with 1mg E2 2.5mg MPA
  (except if hysterectomized) and n 43 placebo
• 6 and 42-month investigation by quantitative
  coronary angiograms and intravascular US
• HT decreased stenosis (p lt 0.001) better lumen
  diameter (p 0.03) and plaque volume (p 0.006)
  in SVG
• HT acceleration of disease progression in
  NON-bypassed coronary arteries (p 0.01)
• ? Protection of SVG by HT supports the hypothesis
  that HT may provide benefit in the absence of
  underlying atherosclerosis

Ouyang P, Tardif JC, Herrington DM et al,
Atherosclerosis 2006189375
8
HT use and coagulation activation
(nmol/L)
plt0.001
plt0.01
0,2
Prothrombin fragment F12
0,1
0
-0,1
Oral Oestrogen
Transdermal Oestrogen
No treatment
P
P
Scarabin et al, ATVB, 1997
9
ORAL EP, TIB and RLX

• Randomized 12-wk study (n202 healthy PMW) in 4
  groups
• E2 2mg NETA 1mg ( EP standard dose) 1
• E2 1mg NETA 0.5mg ( EP low dose) 2
• TIBOLONE 2,5mg 3
• RALOXIFENE 60mg 4
• D-dimers and Prothrombin F1 2
• marked increase in group 1
• unchanged in group 2
• medium increase in group 3
• slight decrease in group 4
• ? Low dose HT (group 2) associated with less
  activation of coagulation than conventional-dose
  HT

Eilertsen AL et al, Maturitas 200655278
10
Risk of CHD in epidemiological studies of PMW

• Endpoint MI or CHD death

Note NO increased CHD death with HRT
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WHI RISK OF CHD
HR
HR
CHD events (EP)
CHD events (E alone)
10-19
Age (years)
Postmenopausal years
Writing Group for the Womens Health Initiative
Investigators. JAMA 2002 288 321-33 27
The Womens Health Initiative Steering Committee.
JAMA 2004 291 1701-12 24
Courtesy of J.C. Stevenson
(2004)
12
Role of Time since menopause and age at
initiation of HRT for risk of CHD

• NURSES'HEALTH STUDY REVISITED
• HRT within 4 years of menopause RR 0.66
  (0.54-0.80) E alone
• RR 0.72 (0.56-0.92) EP
• Subgroup age similar to WHI RR 0.87 (0.69-1.10)
  E alone
• (? 10 years PM) RR 0.90 (0.62-1.29) EP
• WHI E ALONE REVISITED
• Women 50-59 years RR 0.63 (0.36-1.08) E alone
• Women 50-79 years (all) RR 0.95 (0.79-1.16) E
  alone
• ? Suggestion of LOWER CHD risk with HRT vs
  placebo in women 50-59 years of age at baseline.
  Compatible with the "Window of opportunity"
  Theory.

Grodstein F et al, J Women's
Health 15352006 Hsia J et al, Arch Intern Med
1663572006
13
Danish Sex Hormone Register Study (DAHORS) HT and
risk of MI (1)

• National prescription registry updated daily
  since 1995
• 698,098 women aged 51-69yr without previous
  CHD/MI
• follow up for 6 years 2,987,00 WY exposure
  to HT
• 4,947 incident MI
• Adjustment for age, education, social, medical
  aspects, type and duration of HT. Not for time
  since LMP and BMI
• DK high doses of E2 (2-4mg) and progestins
  NETA, MPA, LNG i.e. androgenic progestins

Lokkegaard E et al, Maturitas 54S2006S24
14
DAHORS and MI according to AGE (2)

• RR All types of HT vs non users (adjusted)
• age 51 - 54 1.25 (1.02 1.52)
• 55 - 59 0.90 (0.77 1.06)
• 60 - 64 1.02 (0.89 1.18)
• 65 - 69 0.87 (0.75 1.01)
• ? No specific trend with age

Lokkegaard E et al, Maturitas 54S2006S24
15
DAHORS and MI according to E alone (3)

• Risk non users 1
• E alone age 51-54 1.11
• WHI 0.63
• 55-59 0.59
• age 60-64 0.90
• WHI 0.94
• 65-69 0.79
• ?Overall Risk for E alone 0.81 not different
  from never use
• ?Best results with lower doses (trend not
  consistent)
• ?Transdermal E alone lowest risk (0.54) in all
  age groups

Lokkegaard E et al, Maturitas 54S2006S24
16
DAHORS and MI according to EP regimens (4)

• Overall risks Never use 1
• E alone 0.81
• E P (seq) ? 1
• E P (C-C) 1.28 (WHI 1.24)
• E P (C-C) age 51-54 1.92
• 55-59 1.33
• ? EP cyclic combined (sequential) not different
  from non users and from E alone no increased
  risk of MI
• ? E P continuous combined highest risk in all
  age groups (oral ? TTS !)
• ? No difference between Progestins but all are
  "androgenic"

Lokkegaard E et al, Maturitas 54S2006S24
17
DAHORS and MI preliminary conclusion (5)

• In a National (DK) cohort study, risk of MI in
  PMW is not increased with use of E alone (oral or
  transdermal) or with cylic combined E P.
• Risk is higher with E P C-C and comparable to
  WHI results.
• ? HT REGIMEN and potentially ROUTE of
  application influence the risk of MI

Lokkegaard E et al, Maturitas 54S2006S24
18
Conclusion

• Protection of vessel morphology and function by E
• Vascular impact of different progestins and of
  transdermal vs oral E seems obviously different
• CHD risk with HRT is LOW some PREVENTION not
  excluded
• No increased risk of CHD (or some decrease) with
• E alone (particularly E2 TTS)
• E P seq
• Slightly increased risk of CHD with E P C-C
• Effect of age as factor of increase in CHD risk
  with HRT danish controversy