Bệnh tim mạch ở phụ nữ mãn kinh PGS nguyễn thị dung

Women’s Health Initiative: Estrogen Only Estrogen replacement associated with: •9% reduction in heart disease •39% increase stroke •33% increase blood clots •No change in cancer •39

BỆNH TIM MẠCH

Ở PHỤ NỮ MÃN KINH

PGS.TS.Nguyễn Thị Dung

Bộ môn Nội – ĐHY Hải Phòng

Chủ Tịch Hội Tim Mạch Hải Phòng

Heart

Disease

The

leading killer of women

at all

ages

Although less frequent, CVD occurs in young women

More than 35,000 women under the age of 65 die annually in the US from

CVD

Women and heart disease:

What’s new ?

Hormones in Men vs Women

Association Française pour l'Etude de la Ménopause

Relationship between early menopause

and accelerated CVD ?

Increasing Risk of CVD Minimal or no CVD Risk

Séminaire femme 2008

9

Définition de la ménopause

● Absence de règles depuis au moins 12 mois (au bout de

6 mois déjà on peut se dire que…) L’âge moyen de la ménopause reste constant dans le monde : 50 à 51 ans

● Symptômes associés: sueurs, bouffées de chaleur,

troubles de l’humeur…Intérêt limité des dosages

hormonaux

● En 2004 en France 10 millions de femmes ménopausées

300 000 à 500 000 nouvelles femmes par an

● Espérance de vie des femmes : 83 ans (60 en 1900)

● Accompagner les femmes durant cette période pouvant durer …10 ans

● 50% de la population féminine française sera concernée dans 20 ans

Les signes cliniques varient, d’une femme à l’autre, d’un

pays à l’autre, d’une culture à l’autre

Quanh MK: Khoảng thời gian chuyển tiếp từ GĐ sinh sản sang GĐ không thể sinh sản được nữa do

thiểu năng Estrogen hoặc progesteron)

Women Experience Menopause…

Changes with Menopause

– ***Obesity ~25% of women - BMI >30, Less leisure-time physical activity - Greater functional decline -

Adapted from Bellasi et al, New insights into ischemic heart disease in women cleveland clinic journal of medicine; 74: 585-594, 2004

Séminaire femme 2008 12

WHI, Million study, E3N

WHI Million study E3N

Âge 50 à 79 ans 50 à 64 ans 40-65 ans

Durée 5.2 ans 2.6 ans (cancer)

médroxyprogéstérone

OP , O seul, Tibolone Œstrogènes équins

Pathologie CV Fracture du col

Mortalité

Cancer du sein

Mortalité

Cancers Pathologie CV Ostéoporose

WHI - Estrogen alone Trial N=10739, mean age 63.6 yrs, mean F/U 6.8 yrs

Stopped 1 yr early

39%  Hip fracture 39%  Stroke

Null

WHI Estrogen + Progestin Trial Findings 2002 N=16608, mean age 63 yrs, mean F/U 5.2 yrs

Stopped 3.3 yrs earlier

34%  Hip fracture 34%  Colorectal ca 29%  CHD

Women’s Health Initiative: Estrogen Only

Estrogen replacement associated with:

•9% reduction in heart disease

•39% increase stroke

•33% increase blood clots

•No change in cancer

•39% reduction hip fracture

Source: JAMA 2007;297:1477

Heart Disease in Women:

New Concepts in Prevention

and Management

AHA Heart Disease and Stroke Statistics 2004 Update, and Mosca et

al., Circulation 2007; 115: 1481-1501

Cardiovascular Disease in Women

(AHA Heart Disease and Stroke Statistics 2004 Update)

• 38.2 million women (34%) are living with

cardiovascular disease and a much larger

population is at risk

• Heart disease and stroke are the no 1 and

no 3 killers of women over age 25

• 1 in 30 die of breast cancer, but 1 in 2.5 die of cardiovascular disease or stroke

• 66,000 more women than men die per year of cardiovascular disease (represents 54% of

deaths in women compared to 46% in men)

AHA Heart Disease and Stroke Statistics 2004 Update,

and Mosca et al., Circulation 2007; 115: 1481-1501

Women’s Early Warning Signs of a Heart

Women have smaller coronary arteries

• After correcting for

body surface area,

Adapted from Bellasi et al, New insights into ischemic heart disease in women

cleveland clinic journal of medicine 2004; 74: 585-594

Endothelium

Smaller arteries

Prévalence des cardiopathies ischémiques, AVC et TVP/EP

chez les femmes ménopausées

Troubles thrombo-emboliques veineux Cardiopathies ischémiques( IDM et/ou angor) AVC

M.D Silverstein, Arch Int Med 1998; 158:585-593

Heart Disease and Stroke Statistics – 2003 Update, American Heart Association Source: NHANES III (1988-94), CDC/NCHS

Mortality Rates in Women

At Every Age, More Women Die From Heart Disease Than From Cancer

National Center for Health Statistics 1999:164-167

Coronary artery disease Stroke

Lung cancer Breast cancer Colon cancer Endometrial cancer

(1 in 25) who will die from breast cancer

Cardiovascular Disease Deaths: Trends for Males and

Females United States: 1979-2001

Source: CDC/NCHS © AHA, 2004

AHA Guidelines for CVD Prevention in

Women: Blood Pressure

• Encourage an optimal blood pressure of

<120/80 mm Hg through lifestyle approaches

Midlife Event Viewed Negatively

Does Hormone Replacement Therapy

Prevent Heart Disease ?

Heart and Estrogen/Progestin Replacement Study (HERS): Secondary Prevention of CHD in Women

• Randomized, placebo-controlled trial of E/P

therapy vs placebo in 2763 women with CHD;

average age 67 years

• Treatment was 0.625 mg CEE + 2.5 mg

medroxyprogesterone daily for 4 years

• Primary endpoint: nonfatal MI and CHD death

• Secondary endpoints: CABG, PTCA, unstable

angina, CHF, PVD, TIA

JAMA 1998;280:605-613

JAMA 1998;280:605-613

HERS Results

• No statistically significant difference between HRT

and placebo in both primary and secondary endpoints

after 4 years

• Within first year, greater incidence in CHD events in HRT group In years 3 and 4, lower CHD events in

HRT group compared to placebo

• HRT lowered LDL 11% and increased HDL 10%

Women’s Health Initiative: Estrogen Only

Women’s Health Initiative: Estrogen Only

Estrogen replacement associated with:

•9% reduction in heart disease

•39% increase stroke

•33% increase blood clots

•No change in cancer

•39% reduction hip fracture

Source: JAMA 2007;297:1477

Women’s Health Initiative

Placebo

Study stopped after mean follow-

up of 5.6 years

Hormonal replacement associated with:

•Increased heart disease (29% ↑)

•Increased stroke (41% ↑)

•Increased blood clots

•Increased breast cancer (26% ↑)

•Reduced colon cancer

•Reduced hip fracture

Conclusion: HRT should not be used to prevent disease in healthy post-

menopausal women

NIH What they found, somewhat surprisingly, is that while HRT did improve symptoms and reduce hip fractures due to

osteoporosis, it actually did a bunch of bad things, including INCREASING the risk of heart disease, stroke, blood clots and cancer The conclusion was clearly that HRT should not be used to prevent cardiovascular disease Source: JAMA 2007;297:1477

Estrogen Replacement: The reality

• Estrogen therapy is reasonable for the

relief of perimenopausal symptoms if

started early and tapered after a few years

• Estrogen administered transdermally may

be less likely to increase risk of blot clots

• Estrogen should not be given to reduce

CVD risk

Association Française pour l'Etude de la Ménopause

XXIV Journées

es

Séminaire femme 2008

33

Les recommandations de l’AFEM (1)

● Le THM reste le traitement de référence des troubles

cliniques de la ménopause, avec une information objective des bénéfices/risques pour la patiente

●Le risque relatif de cancers ne doit pas être un obstacle si cette prescription est justifiée

●Un antécédent personnel de cancer du sein est une indication

contre-● En cas d’hystérectomie, œstrogènes seuls

● Pas de THM chez une patiente à haut risque cardio

vasculaire

 ● N’est pas protecteur cardiovasculaire mais augmente

l’incidence des thromboses veineuses

Séminaire femme 2008

Les recommandations de l’AFEM(2)

Si on prescrit un traitement hormonal

● INFORMER les patientes

● Durée conseillée maximale de 5 ans

● Dosage : la dose minimale efficace

● Avant de prescrire le traitement, rechercher :

 Antécédents personnels et familiaux

Examen clinique : TA, poids, Bilan cardio- vasculaire Palpation mammaire.examen gynécologique (seins, frottis)

 Evaluation du risque cardio-vasculaire

● Information du sur-risque relatif de cancer du sein pour celles qui ont plus de 65 ans et prennent un traitement hormonal depuis plus de 5 ans

séminaire femme 2008 35

Contre-indications

récidivants

(attendre normalisation des transaminases)

Summary

● Heart Disease is the leading cause of death in women

● Most risk factors are the same for men and women, but

women are at particularly high risk if they have diabetes mellitus Gender specific risks are menopause and

intake of birth control pills while smoking

● Diagnosis of Heart Disease in women is very difficult since

many women have atypical symptoms such as

shortness of breath and extreme fatigue

● Prevention of heart disease is crucial

● Almost 50 % of heart disease problems can be avoided by

lifestyle changes

● Ineffective interventions such as antioxidants and

hormone replacement therapy should be avoided

Women Making a Change

séminaire femme 2008 38

Formes combinées

séminaire femme 2008 39

Œstrogènes du THM

séminaire femme 2008 40

Progestatifs et THS

Perimenopause

Mosca L et al Circulation 2004;109:672-693 and Circulation 2007; 115: 1481-1501