Women and cardiovascular disease(CVD):

What do we need to know?

Dr.Udaya RalapanawaMBBS(SL),MD(Col),MRCP(UK),FRCP(London)

Consultant PhysicianSenior Lecture In Medicine

Are women more complicated than men?

Hormones in Men vs. Women

Cardiovascular disease is mainly a disease of old

men

Myth

Myths vs Facts

Myths FactsMen are more likely to have heart disease

Heart disease is the #1 killer of men and women; 50,000 more women than men die of heart disease every year

Cancer is a bigger threat than heart disease

Nearly twice as many US women die from heart disease and stroke than from all cancers combined

Doctors are aware of women’s risk for heart disease and act accordingly

Undertreatment and underdiagnosis of heart disease in women contributes to excess mortality in women

Gender Bias in the Treatment of Women

“… The community has viewed women’s health almost with a ‘bikini’ approach, looking essentially at the breast and reproductive system, and almost ignoring the rest of the woman as part of women’s health ….”

Nanette Wenger, MDChief of Cardiology, Grady Hospital Professor of Medicine, Emory UniversityAtlanta, Georgia

Magnitude of the Problem

2.5 million women per year in the US are hospitalized with cardiovascular disease (CVD)

Deaths from CVD = 500,000/yr

Magnitude of the Problem Leading cause of death in US women:

CAD

1990: US Congress directed the National Institutes of Health that women be included in clinical trials and that gender differences be evaluated

Statistics for Women

1 in 5 women has some form of CVD

38% of women who have a heart attack die within 1 year

40% of coronary events in women are fatal› Most occur without prior warning

CVD Mortality Trends (1979-1999)

American Heart Association. 2002 Heart and Stroke Statistical Update. 2001

Dea

ths

in T

hous

ands

Gender Differences in Heart Attack Symptoms

Typical in both sexes Pain, pressure, squeezing,

or stabbing pain in the chest

Pain radiating to neck, shoulder, back, arm, or jaw

Pounding heart, change in rhythm

Difficulty breathing Heartburn, nausea,

vomiting, abdominal pain Cold sweats or clammy

skin Dizziness

Typical in women Milder symptoms (without

chest pain) Sudden onset of

weakness, shortness of breath, fatigue, body aches, or overall feeling of illness (without chest pain)

Unusual feeling or mild discomfort in the back, chest, arm, neck, or jaw (without chest pain)

Prevalence of CVD in the US

5.510.4

17.4

34.2

51.0

65.270.7

4.60 4.20

13.60

28.90

79.00

48.10

65.20

0102030405060708090

20-24 25-34 35-44 45-54 55-64 65-74 75+Ages

Perc

ent o

f Pop

ulat

ion

MalesFemales

American Heart Association. 2002 Heart and Stroke Statistical Update. 2001

Although less frequent, CVD occurs in young women

More than35,000 women under the

age of 65 die annually in the US

from CVD

Women’s Perceptions of Heart Disease

72% of young women (ages 25-40) still consider cancer to be the greatest threat to women’s health

Some women know about the risks of heart disease but do not hear it from their own doctors and do not “personalize” it

Robinson A. Circulation. 2001

Women’s Perceptions of Heart Disease

65% of women recognize that symptoms may be “atypical” but do not know classic symptoms

Most women learn about coronary artery disease (CAD) from magazines and the Web—not from their own physicians!

Health Threats to Women: Perception vs Reality

1. Gallup survey. 1995 2. American Heart Association. Heart & Stroke Facts. 1996 Statistical Supplement

Perceived health threats

55%

40%

22%

2%

Cance

r

Breast

canc

er

Heart d

iseas

e

Heart a

ttack

Leading causes of death in women

3%4%4%

24%

46%

1 2

Death From Breast Cancer or Heart Disease in Women in the US

US Vital Statistics, 1990

Women don’t need to worry about cardiovascular disease before

menopause

Myth

Relationship between early menopause and accelerated CVD?

Increasing Risk of CVD

Minimal or no CVD Risk

MenopauseTraditional Paradigm:

Increasing Risk of CVD

Menopause

Alternative Paradigm:

Coronary heart disease progresses over decades

Decades of time

Smoking, High Blood Pressure, Elevated

Cholesterol, Diabetes, Inactivity, Obesity

Age, Heredity

The reality: Being premenopausal probably does not protect you from cardiovascular

disease and you should be vigilant at all ages …

Estrogen Critical to

reproductive function in men & women

Most produced by ovaries

Some arises from fat, liver, breasts, adrenals

Complex physiologic effects

Is There a Role for HRT?

Secondary prevention› 1998: HERS

4 years of treatment with conjugated estrogen plus medroxyprogesterone acetate

No reduction in the risk of MI and coronary death in women with established CAD

HERS trial. JAMA. 1998.

Is There a Role for HRT?

Secondary prevention› 3/2000: Estrogen Replacement and Atherosclerosis trial

(ERA) 309 postmenopausal women with CAD Placebo vs conjugated estrogen (.625 mg/day) vs

conjugated estrogen (.625 mg/day) with medroxyprogesterone acetate (2.5 mg/day)

Angiographic analysis of the diameter of the coronary arteries at the start of the study and 3 years later

ERA trial results at follow-up angiography› The progression of coronary atherosclerosis was

unchanged in the women randomized to either of the estrogen groups

ERA trial. J Am Coll Cardiol. 2001

Women’s Health Initiative16,608 Post-menopausal women aged 50-79 with an intact uterus

Estrogen +Progesterone

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

RCOG and the hormone replacement therapy (HRT)

RCOG UPDATE (11 June 2013): The British Menopause Society (BMS) and Women’s Health Concern recently published a literature review

In summary, their key recommendations are: The decision whether to use HRT should be made

by each woman having been given sufficient information by her healthcare professional, including information about complementary therapies and lifestyle and dietary changes.

HRT dosage, regimen and duration should be individualised, with an annual evaluation of the pros and cons

RCOG and the hormone replacement therapy (HRT)

Arbitrary limits should not be placed on the duration of usage of HRT; if symptoms persist, the benefits of hormone therapy usually outweigh the risks.

HRT prescribed before the age of 60 has a favourable benefit/risk profile.

RCOG and the hormone replacement therapy (HRT)

It is imperative that women with Premature Ovarian Insufficiency (POI) are encouraged to use HRT at least until the average age of the menopause.

If HRT is to be used in women over 60 years of age, lower doses should be started, preferably with a transdermal route of administration.

Coronary Disease Mortality and Diabetes in Women

33

Sources: Krolewski 1991, National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) 2002.

0

10

20

30

40

50

60

0 - 3 4 - 7 8 - 11 12 - 15 16 - 19 20 - 23

Duration of Follow-up (yrs)

Women withDiabetes

Women withoutDiabetes

Mortality Rate per 1,000

Diabetes Creates Higher Risks for Women With CAD

65% of diabetics die from heart disease or stroke

4.2 million American women have diabetes › Diabetes increases CAD risk 3-fold to 7-fold in women

vs 2-fold to 3-fold in men› Diabetes doubles the risk of second heart attack in

women but not in men

American Heart AssociationCenters for Disease Control and Prevention

Manson JE, et al. Prevention of Myocardial Infarction. 1996

Diabetes: Powerful Risk Factor for CAD in Women

Framingham Heart Study › Women with diabetes mellitus had relative

risk of 5.4% for CAD vs women without diabetes

› Men with diabetes had relative risk of 2.4% Nurses’ Health Study

› Relative risk of 6.3% for total cardiovascular (CV) mortality

› Even if women had diabetes for <4 years, their risk of CAD was significantly elevated

Kannel W. Am Heart J. 1987Manson J, et al. Arch Intern Med. 1991

Clinical Identification of the Metabolic Syndrome

Abdominal obesity› Men >88 cm (>40 in)› Women >80 cm (>35 in)

Triglycerides (TG) >150 mg/dL HDL cholesterol

› Women <50 mg/dL› Men <40 mg/dL

Blood pressure >130/>85 mm Hg Fasting glucose >100 mg/dL

National Heart, Lung, and Blood Institute

Impact of Triglyceride Levels on Relative Risk of CAD

Framingham Heart Study

0.55

1

1.4 1.45

1.8 1.85

2.2 2.15

0.650.8 0.75

1

1.21.3 1.25 1.25

0

0.5

1

1.5

2

2.5

50 100 150 200 250 300 350 400

Rel

ativ

e R

isk

(x-fo

ld) Women

Men

Castelli WP. Can J Cardiol. 1988

Smoking Single most preventable cause of death

in US Smoking by women causes 150% more

deaths from heart disease than lung cancer

Women who smoke are 2-6 times more likely to suffer a heart attack

39

Smoking Nurses’ Health Study: Even a few

cigarettes a day correlated with a greater risk of CVD or fatal MI

About one-quarter of all women smoke; prevalence greatest among postmenopausal women

Smoking

Younger women who smoke probably cancel out any premenopausal protection

Women who take oral contraceptives and smoke are more likely to have an MI or stroke than those who take the pill but don’t smoke

41

Stress Puts a woman at greater risk for CVD

and poorer outcomes

Depression also may increase risk or defer her from seeking medical help

Consider screening women with CAD for depression and refer for treatment as needed

Physical Inactivity

Lack of exercise is a proven risk factor for heart disease› A lack of regular physical exercise is a growing

epidemic all over the world. “We seem to eat much more than what we burn”

Heart disease is twice as likely to develop in inactive people than in those who are more active

Physical Inactivity Physical activity helps maintain

weight, blood pressure, and diabetes

Women should exercise to increase heart rate for 20-30 minutes a day, 3-5 times per week

Women in Clinical Trials Women are underrepresented in

cardiovascular (CV) trials› Evidence-based CV medicine biased

toward men Food and Drug Administration/National

Institutes of Health mandate: 50% enrollment of women

Women need to be empowered to enroll in clinical trials for heart disease › Breast-cancer awareness is a good

example

Coronary Microvascular Disease

Coronary MVD is heart disease that affects the heart's tiny arteries. This disease is also called cardiac syndrome X or nonobstructive CHD. In coronary MVD, the walls of the heart's tiny arteries are damaged or diseased.

Coronary Microvascular Disease

Women are more likely than men to have coronary MVD. Many researchers think that a drop in estrogen levels during menopause combined with other heart disease risk factors causes coronary MVD.

Coronary Microvascular Disease

Although death rates from heart disease have dropped in the last 30 years, they haven't dropped as much in women as in men. This may be the result of coronary MVD.

PET Case Study: Patient FFStress Rest

PET Case Study: Patient FFIschemia of Lateral Wall

Treatment differences Thrombolysis – equally effective – Cerebral

hemorrhage risk is more Low rates of coronary angiography in women Under referral for revascularization

procedures CABG - > operative mortality 1.9 % v/s 4.6% Restenosis after PTCA, or CABG occlusion

rates are more for women - ? Smaller lumen sizes

51

Rehabilitation

Women have higher hospital readmission rates for unstable angina, reinfarction, heart failure, ventricular tachycardia, and ventricular fibrillation.

Main goals: Reduce risk and restore functional capacity

Cardiac Diseases in Pregnancy

Cardio-circulatory changes during normal pregnancy

parameterChanges at various times (weeks)

5 12 20 24 32 38HR ↑ ↑↑↑ ↑↑↑ ↑↑↑ ↑↑↑↑ ↑↑↑↑

SBP ↔ ↓ ↓ ↔ ↑ ↑↑

DBP ↔ ↓ ↓↓ ↓ ↔ ↑↑

SV ↑↑↑↑↑↑ ↑↑↑↑↑↑ ↑↑↑↑↑↑ ↑↑↑↑↑

↑↑↑↑↑

CO ↑↑ ↑↑↑↑↑↑ ↑↑↑↑↑↑↑ ↑↑↑↑↑↑↑ ↑↑↑↑↑↑↑ ↑↑↑↑↑↑↑

SVR ↓↓ ↓↓↓↓↓ ↓↓↓↓↓↓ ↓↓↓↓↓↓ ↓↓↓↓↓↓ ↓↓↓↓↓

LV EF ↑ ↑↑ ↑↑ ↑↑ ↑ ↑

↑ ≤ 5%; ↑↑ 6-10%; ↑↑↑ 11-15%; ↑↑↑↑ 16-20%; ↑↑↑↑↑ 21-30%; ↑↑↑↑↑↑ > 30%, ↑↑↑↑↑↑↑ > 40%.

Changes in plasma volume, erythrocyte volume, and hematocrit during pregnancy

Plasma volume ↑ 50% (20-100%).

“Physiologic anemia of pregnancy”.

Estrogen-mediated stimulation of the RAS.

Role of other hormones› deoxycorticosterone,

prostaglandins, estrogen, prolactin, placental lactogen, GH, ACTH, ANP

From Pitkin RM, Nutritional support in obstetrics and gynecology. Clin Obstet Gynecol 1976;19:489.

Many Women Develop Conditions During the Reproductive Years that Contribute to CVD Risk in Later Life

55

CVD Mortality

per 100,000Women

Source: Adapted from “CVD Prevention and the Primary Care Partnership”, Deborah Ehrenthal, MD, FACP

HTN – HypertensionGDM – Gestational DiabetesPCOS – Polycystic Ovary Syndrome

Hemodynamic changes during labor and delivery

Anxiety, pain, uterine contraction. Oxygen consumption ↑ threefold. ↑ CO during labor (↑ SV and ↑ HR). ↑ SBP & DBP (especially 2nd stage)

Those changes are influenced by the form of anesthesia and analgesia.

Hemodynamic changes post partum

Blood shifting “auto-transfusion” (from the contracting uterus to

the systemic circulation)

Increase in effective blood volume

Substantial increase in LV filling pressure, SV and CO

Clinical deterioration

Blood loss during

delivery-

• HR and CO return to pre-labor values within 1 hour. MAP and SV within 24 hours.• Hemodynamic adaptation persists post partum and return to pre-pregnancy values within 12-24 weeks after delivery.

Increase in venous return(relief of caval compression)

HistoryExercise capacity

Current or past evidence of HFAssociated arrhythmias

Physical exam

Cardiac HemodynamicsSeverity of heart disease, PA pressures

Echo, MRI.

Exercise testingUseful if the history is inadequate to allow assessment of functional capacity

During pregnancyEvaluate once each trimester and whenever there is change in symptoms

Multidisciplinary approach, Fetal Echo

Befo

re c

once

ptio

n

Reimold, S. C. et al. N Engl J Med 2003;349:52-59

During Labor & DeliveryMultidisciplinary approach (Obstetrician, Cardiologist, Anesthesiologist)

Tailor management to specific needs

High-risk pregnancy Pulmonary HTN and Eisenmenger’s

syndrome. Symptomatic obstructive cardiac lesions:

› AS, PS, uncorrected coarctation of the aorta. Marfan’s Syndrome with dilated aortic

root. Systemic ventricular dysfunction (LVEF <

40%). Severe cyanotic heart disease. Patients with prosthetic valves. Significant uncorrected CHD.

Contraindications to Pregnancy

Lesion Maternal death rate (%)

• Severe Pulmonary Hypertension 50• Severe obstructive lesions: AS,PS, HOCM, Coarctation.

17

• Systemic Ventricular Dysfunction, NYHA class III or IV

7

Pregnancy Outcomes

The prevalence of clinically significant maternal heart disease is low (<1%)1.

Its presence increases the risk of adverse maternal, fetal, and neonatal outcomes2.

1. Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001;104:515-521.

2. Siu SC, Colman JM, Sorensen S, et al. Adverse neonatal and cardiac outcomes are more common in pregnant women with cardiac disease. Circulation 2002;105:2179-2184.

Preeclampsia

Preeclampsia (pre-e-KLAMP-se-ah) is a condition that develops during pregnancy. The two main signs of preeclampsia are a rise in blood pressure and excess protein in the urine.

Preeclampsia

These signs usually occur during the second half of pregnancy and go away after delivery. However, your risk of developing high blood pressure later in life increases after having preeclampsia.

Preeclampsia

Preeclampsia also is linked to an increased lifetime risk of heart disease, including CHD, heart attack, and heart failure. (Likewise, having heart disease risk factors, such as diabetes or obesity, increases your risk for preeclampsia.)

Preeclampsia

If you had preeclampsia during pregnancy, you're twice as likely to develop heart disease as women who haven't had the condition. You're also more likely to develop heart disease earlier in life.

Aortic stenosis Severe AS is poorly tolerated.

› AVA < 0.7 cm2, Mean PG > 50 mmHg.› Mortality up to 17%.

Symptomatic patients or Mean gradient > 50 mmHg

→ Delay conception until after surgical or interventional correction.

Consider balloon valvuloplasty, Ross procedure, tissue valve (no need for anticoagulation).

Symptomatic patients before end of 1st trimester

Terminate pregnancy. Β-Blockade, Bed rest. Palliative aortic balloon valvuloplasty

or AVR. Early Delivery.

Reimold, S. C. et al. N Engl J Med 2003;349:52-59

Hameed A, et al. The effects of valvular heart disease on maternal and fetal outcome of pregnancy. J Am Coll Cardiol 2001;37:893-9.

Prosthetic valves and pregnancy

Anticoagulation

Warfarin vs. HeparinWarfarin Crosses the placenta. ↑early abortion,

prematurity, and embryopathy when used in 1st trimester (6th–12th weeks).

CNS & Eye abnormalities (2nd & 3rd trimester).

Bleeding in the fetus (especially at delivery)› Should be stopped

before delivery.

Heparin Does not cross the placenta No teratogenicity No fetal bleeding

Twice daily SC injection Risk of osteoporosis

› <2% symptomatic fractures.› but 30% decrease in bone

density. Risk for thrombocytopenia ↑↑ Risk of thrombosis

Endocarditis prophylaxis Antibiotic prophylaxis at the time of delivery is

not recommended for patients expected to have uncomplicated vaginal delivery or cesarian section, unless clinically overt infection is present 1,2

Patients at high risk for endocarditis may receive antibiotics at the discretion of their physician2:› Those with prosthetic heart valves.› Previous IE.

1 Sugrue D, Troy P, McDonald D. Antibiotic prophylaxis against infective endocarditis after normal delivery -- is it necessary? Br Heart J 1980;44:499-502. 2 Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis: recommendations by the American Heart Association. JAMA

1997;277:1794-1801.

Peuperal Cardiomyopathy

Pregnancy and CHDConclusions

Most women with heart disease can have a pregnancy proper care.

Pre-pregnancy evaluation mandatory.

High-risk cases benefit from combined high-risk OB and cardiac care in the same center.

THANK YOU