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Women and Coronary Artery Disease (CAD)


Women and Coronary Artery Disease (CAD) What do we need to know ? Dr. R.V.S.N.Sarma, M.D., M.Sc., (Canada) Consultant Physician and Chest Specialist – PowerPoint PPT presentation

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Title: Women and Coronary Artery Disease (CAD)

Women and Coronary Artery Disease (CAD)
  • What do we need to know ?
  • Dr. R.V.S.N.Sarma, M.D., M.Sc., (Canada)
  • Consultant Physician and Chest Specialist
  • Thiruvallur, Chennai

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Myths vs Facts
Myths Facts
Men 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 womens risk for heart disease and act accordingly Undertreatment and underdiagnosis of heart disease in women contributes to excess mortality in women
Womens Perceptions of Heart Disease
  • 72 of young women (ages 25-40) still consider
    cancer to be the greatest threat to womens
  • Some women know about the risks of heart disease
    but do not hear it from their own doctors and do
    not personalize it
  • 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 Webnot from their
    own physicians!

Robinson A. Circulation. 2001
Gender Bias in the Treatment of Women
  • The community has viewed womens 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 womens
    health . Nanette Wenger, MD Chief of
    Cardiology, Grady Hospital Professor of
    Medicine, Emory University Atlanta, 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
  • Leading cause of death in US women CAD
  • gt230,000 women die from CAD each year
  • 1990 US Congress directed the National
    Institutes of Health that women be included in
    clinical trials and that gender differences be

Women in Clinical Trials
  • Women are underrepresented in cardiovascular (CV)
  • 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

Publication Bias Gender Representation and
Negative Studies
  • 1966-1994 noninvasive testing literature
  • 8 to 27 women
  • Lower diagnostic accuracy in women
  • High false-positive rates
  • Inability to perform maximal stress

CVD Mortality Trends (1979-1999)
Deaths in Thousands
American Heart Association. 2002 Heart and Stroke
Statistical Update. 2001
Prevalence of CVD in the US
American Heart Association. 2002 Heart and Stroke
Statistical Update. 2001
Deaths From CVD and Cancer by Age and Sex
Anderson RN. National Vital Statistics Reports.
Deaths From CVD (1999)
American Heart Association. 2002 Heart and Stroke
Statistical Update. 2001
Health Threats to Women Perception vs Reality
1. Gallup survey. 1995 2. American Heart
Association. Heart Stroke Facts. 1996
Statistical Supplement
Death From Breast Cancer or Heart Disease in
Women in the US
US Vital Statistics, 1990
Statistics for Women
  • 503,927 died of CVD in 1998
  • 226,467 from heart attack or other cardiac events
  • 97,303 from stroke
  • 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

Women and Coronary Artery Disease (CAD)
  • Risk Factors and Gender Differences

Warning Signs and Symptoms of CAD
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
  • 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)

Less Common Heart Attack Symptoms in Women
  • Milder symptoms without accompanying chest pain
  • Sudden onset of weakness, shortness of breath,
    fatigue, body aches, overall feeling of illness
  • Burning sensation in the chest, may be mistaken
    as heartburn
  • An unusual feeling or mild discomfort in the
    back, chest, arm, neck, or jaw

Major Risk Factorsfor Heart Disease
Modifiable Nonmodifiable Emerging Risk Factors
High blood pressure Family history Homocysteine
Abnormal cholesterol levels Age Elevated lipoprotein (a) levels
Diabetes Gender Clotting factors
Cigarette smoking Markers of inflammation (CRP)
Physical inactivity
Grundy SM, et al. Circulation. 1998 Grundy SM.
Circulation. 1999 Braunwald E. N Engl J Med.
1997 Grundy SM, et al. J Am Coll Cardiol. 1999
Emerging Risk Factors
  • Lipoprotein (a)
  • Homocysteine
  • Prothrombotic factors
  • Proinflammatory factors
  • Impaired fasting glucose
  • Subclinical atherosclerosis
  • Other clinical forms of atherosclerotic disease
    (peripheral arterial disease, abdominal aortic
    aneurysm, and symptomatic carotid artery disease)
  • Abnormal internal or common carotid CIT,
    ankle-arm index lt0.9, coronary Ca2

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
  • Every year, heart disease kills 50,000 more
    American women than men
  • Statistics are particularly high among African
    American women

American Heart Association Centers for Disease
Control and Prevention Manson JE, et al.
Prevention of Myocardial Infarction. 1996
Lowest Survival Rates for Diabetic Women
  • CAD mortality rates in diabetics, especially
    women, have not decreased to the same extent as
    those in the general population
  • In a large cohort referred for coronary disease,
    diabetic women had the highest mortality rates
  • Estimate of ischemic burden with stress
    myocardial perfusion imaging significantly
    improved risk stratification in diabetic women
    compared with clinical risk alone
  • Stratification by the number of ischemic vessels
    demonstrated a significant linear increase in
    cardiac events with escalating ischemic burden
    (sex-diabetes interaction, P .016)

Gu K, et al. JAMA. 1999 Giri S, et al.
Circulation. 2002
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 lt4 years, their
    risk of CAD was significantly elevated

Kannel W. Am Heart J. 1987 Manson J, et al. Arch
Intern Med. 1991
Clinical Identification of the Metabolic Syndrome
  • Abdominal obesity
  • Men gt88 cm (gt40 in)
  • Women gt80 cm (gt35 in)
  • Triglycerides (TG) gt150 mg/dL
  • HDL cholesterol
  • Women lt50 mg/dL
  • Men lt40 mg/dL
  • Blood pressure gt130/gt85 mm Hg
  • Fasting glucose gt100 mg/dL

National Heart, Lung, and Blood Institute
Impact of Triglyceride Levels on Relative Risk
of CAD
Castelli WP. Can J Cardiol. 1988
Women and CAD Risk Factors
  • Higher prevalence of avoidable risk factors1
  • ? blood cholesterol, ? TG
  • ? physical inactivity
  • ? overweight (body mass index, 25.0-29.9)
  • Diabetes is a more powerful risk factor for CAD2
  • 3- to 7-fold in women vs 2- to 3-fold in men
  • ? HDL cholesterol levels more predictive of CAD2
  • Women counseled less about nutrition, exercise,
    and weight control2

1. American Heart Association. 1999 Heart and
Stroke Statistical Update. 1998 2. Mosca L, et
al. Circulation. 1999
MI or Death Often First Sign of CAD
Levy D, et al. Textbook of Cardiovascular
Medicine. 1998
  • 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
  • Use of birth control pills in smokers compounds
    cardiac risk

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

Hormonal Effects on Ischemia and Disease
  • Premenopause
  • Estrogen has digoxin-like effect ? ST ?
  • Post-menopause effect on HRT
  • ? ST ? - vasodilatory effects of HRT
  • Increase exercise duration/decrease chest pain
  • Women with intact uterus take progestin to
    protect against uterine malignancies
  • Estrogen and medroxyprogesterone attenuate this

Lloyd GW, et al. Heart. 2000 Webb CM, et al.
Lancet. 1998 Morise AP, et al. Am J Cardiol.
1993 Rosano GM, et al. J Am Coll Cardiol. 2000
Hormonal Effects on Ischemia and Disease
  • Estrogen modulates chest pain syndromes
  • Premenopausal CAD angina/ischemia variation by
    menstrual cycle
  • Early follicular phase estradiol and
    progesterone levels - low lt time to ischemia
  • Mid-cycle estrogen levels - highest gt time to
    ischemia onset

Lloyd GW, et al. Heart. 2000 Webb CM, et al.
Lancet. 1998 Morise AP, et al. Am J Cardiol.
1993 Rosano GM, et al. J Am Coll Cardiol. 2000
Postmenopausal Hormone Therapy and
  • First randomized trial
  • HERS trial (Heart and Estrogen/Progestin
    Replacement Study)
  • Secondary CAD prevention trial
  • Randomized trial of placebo vs estrogen and
  • Follow-up 4 years
  • N 2,763 women with an intact uterus
  • Outcome measures
  • Primary nonfatal MI or cardiac death
  • Secondary unstable angina, coronary
    revascularization, congestive heart failure

HERS trial. JAMA. 1998.
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
Is There A Role for HRT?
  • Primary prevention
  • Womens Health Initiative. WHI trial
  • 160,000 women1991-2005
  • Initial results no cardioprotection attributed
    to HRT in women on HRT
  • American Heart Association HRT not recommended
    for primary or secondary cardioprotection

Conclusions Risk Factor Management
  • CVD begins in childhood and is strongly
    associated with major risk factors for heart
  • Multiple risk factors require more aggressive
  • Aggressive risk-factor modification (often with
    multiple medications) is the most effective
    strategy for reducing the consequences of heart

Berenson GS, et al. N Engl J Med. 1998. Neaton
JD, et al. Arch Intern Med. 1992. Kannel WB. in
Atherosclerosis and Coronary Artery Disease.
1996. Grundy SM, et al. Circulation. 1999
Gender Differences in CAD Risk Factors
  • Increasing recognition that atherosclerosis is an
    inflammatory process
  • Ridker PM, et al A prospective case-controlled
    study among 28,263 postmenopausal women
  • Among 12 markers of inflammation, C reactive
    protein was the strongest univariate predictor of
    the risk of CV events

Ridker PM, et al. N Engl J Med. 2000
Women andCoronary Artery Disease (CAD)
  • Diagnosis and Prognosis

Diagnosis and Management of CAD in Women
  • Gender differences presentation, manifestation,
    and diagnosis of CAD
  • Gender differences in mortality
  • 63 of women who die suddenly from CAD had no
    prior warning symptoms
  • 42 of women vs 24 of men will die within
    1 year after MI
  • Thus, early recognition of symptoms and accurate
    diagnosis of CAD is of great importance

Heart Disease in Women Lessons From the Past
  • The importance of studying gender-specific
    aspects of CAD have helped in the following
    clinical dilemmas
  • At Presentation of CAD women are older than men
  • Less specific clinical manifestations of CAD in
  • Greater difficulty in diagnosis women gt men
  • More severe consequences on MI when it occurs in

Screening for Heart Disease
  • What Tests Should we use to identify Coronary
    Heart Disease?

Limited Representation of Women in Studies of CAD
Adapted from Shaw LJ, et al. Coronary Artery
Disease in Women What All Physicians Need to
Know. 1999
Are There Gender Differences in Noninvasive
Diagnostic Tests?
  • Is There a Difference in Diagnostic Accuracy of
    Noninvasive Tests?

Noninvasive Testing Options
Noninvasive Testing in Symptomatic Women
  • Stress electrocardiography (ECG)
  • Stress echocardiography (ECHO)
  • Stress nuclear imaging (MPI)

Exercise ECG (Treadmill)
  • Despite advances in technology, the exercise ECG
    remains an important tool in the diagnosis and
    prognosis of the patient suspected of having CAD
  • The exercise ECG has an overall sensitivity of
    68 and a specificity of 77 for the detection of
    CAD in men
  • The sensitivity and specificity of the exercise
    ECG in women are about 61 and 70 respectively

Kwok Y, et al. Am J Cardiol. 1999.
ECG Testing in WomenSensitivity and Specificity
No. ofWomen
Study, Year
Sensitivity ()
Specificity ()
Detry et al, 1977 47 80 63 Weiner et al,
1979 580 76 64 Barolsky et al,
1979 92 60 68 Friedman et al, 1982 60 32 41 Guit
eras et al, 1982 112 79 66 Hung et al,
1984 92 73 59
Adapted from Heller GV, et al. Nuclear
Cardiology State of the Art and Future
Directions. 1998
Gender Differences in Exercise ECG Testing
  • ? sensitivity in women gt65 years
  • ? specificity in women on hormone replacement
  • ? false-positive results due to
    autonomic/hormonal influences
  • Digoxin like effect of estrogen

Shaw LJ, et al. CAD in Women What All Physicians
Need to Know. 1999
Diagnosis of Noninvasive Tests in Women
  • ECG
  • Nuclear perfusion study
  • ECHO poor window problem
  • Dipyridamole injection MPI,
  • Stress (Tread mill) Echo
  • Dobutamine infusion Echo
  • Computed tomography
  • MR coronary angiography

Nuclear Imaging in Women
  • Myocardial perfusion imaging (MPI)
  • Large body of evidence in women
  • Gender-specific data available for Tl-201and
    Tc-99m tracers
  • Tc-99m tracers agent of choice for women due to
    decrease attenuation artifacts from breast tissue
  • Gated single-photon emission computed tomography
    (SPECT) provides post stress ejection fraction
    and regional wall motion ? helpful to reduce
    false positives
  • IV adenosine/dipyridamole stress provides
    comparable overall accuracy in women and men

Comparative Test Statistics on Diagnostic
Accuracy in Women
Kwok Y, et al. Am J Cardiol. 1999
Diagnostic Specificity Stress ThalliumTl-201 vs
Tc-99m Sestamibi
  • Perfusion imaging
  • Regional blood flow
  • Robust evidence in women
  • Gender-specific data for Tl-201 and Tc-99m
    sestamibi or teboroxime
  • Tc-99m sestamibi is agent of choice for women
    (reduced breast attenuation)
  • Gated SPECT
  • Post-stress EF and regional wall motion
  • Reduce false-positive tests
  • Pharmacologic stress helpful in older and obese

N 115, P .0004
21 false
10 false
Hachamovitch R. et al. J Am Coll Cardiol. 1996
Amanullah AM, et al. Am J Cardiol. 1997
Taillefer R, et al. J Am Coll Cardiol. 1997
Pharmacologic Stress Testing in a Community
Setting Women vs Men
Percent of patients referred for MPI who
underwent exercise stress vs pharmacologic stress
at Mission Internal Medicine Group, Mission
Viejo, CA (4/21/02 to 8/29/02)
Data provided by Greg Thomas, MD, Mission
Internal Medicine Group
ECHO Testing in Women
  • Overall
  • Convenient/readily available1,2
  • Avoids ionizing radiation2
  • Identifies cardiac structure and left ventricular
    function (LVF)
  • Sensitivity and specificity vs ECG testing1,2
  • Increased sensitivity (79-88)
  • Increased specificity (77-86)

1. Williams MJ, et al. Am J Cardiol. 1994 2.
Marwick T, et al. J Am Coll Cardiol. 1995
PET Imaging for CAD in Women
  • Positron Emission Tomography

PET Case Study Patient FF
PET Case Study Patient FFIschemia of Lateral
Electron Beam Computed Tomography (EBCT)
  • Resting study only
  • Stationary tungsten target permits rapid scanning
  • Detects coronary calcification
  • Abnormality defined as presence of any calcium

Courtesy of Howard Lewin, MD, of San Vicente
Cardiac Imaging Center
Diagnostic Accuracy of EBCT Coronary Calcium
Scores by Gender Subsets
Devries S, et al. J Am Coll Cardiol. 1995.
Rumberger JA, et al. Circulation. 1995. Detrano
R, et al. Am J Card Imaging. 1996.
Technetium-99m SPECT Imaging Predicts Cardiac
Mortality in Women
Marwick TH, et al. Am J Med. 1999
hs-CRP, Lipids, and Risk of Future Coronary
Events Women's Health Study (WHS)
Quartile of hs-CRP
Quartile of TC HDL-C
Ridker PM et al. N Engl J Med 2000342836-843.
Risk Factors for Future Cardiovascular Events WHS
Lipoprotein(a) Homocysteine IL-6 TC LDL-C sIC
Relative Risk of Future Cardiovascular Events
Ridker PM et al. N Engl J Med 2000342836-843.
Womens Health Initiative Trial of Estrogen
plus Progestin
  • 16,608 women randomized
  • Conjugated equine estrogens 0.625 mg/d
    medroxyprogesterone acetate 2.5 mg/d vs. placebo
  • Primary outcome nonfatal MI or CHD death
  • Primary adverse outcome breast cancer
  • Stopped early (mean follow-up 5.2 years) because
    health risks exceeded benefits

Writing Group for the WHI Investigators. JAMA
Risks and Benefits of Estrogen/Progestin on
Clinical Outcomes Womens Health Initiative
Outcome Hazard Ratio Nominal 95 CI Adjusted 95 CI
CHD (MI, coronary death) 1.29 1.021.63 0.851.97
CABG/PTCA 1.04 0.841.28 0.711.51
Stroke 1.41 1.071.85 0.862.31
Venous thromboembolic disease 2.11 1.582.82 1.263.55
Total CVD 1.22 1.091.36 1.001.49
Cancer 1.03 0.901.17 0.861.22
Fractures 0.76 0.690.85 0.630.92
Death 0.98 0.821.18 0.701.37
Global index 1.15 1.031.28 0.951.39
Absolute Excess Risks and Absolute Risk
Reductions per 10,000 Person-Years Womens
Health Initiative
Difference in risk per 10,000 person-years
CHD events 7
Strokes 8
Pulmonary embolisms 8
Invasive breast cancer 8
Colorectal cancers 6
Hip fractures 5
Global index 19
Writing Group for the WHI Investigators. JAMA
Treatment differences
  • Thrombolysis equally effective Cerebral
    hemorrhage risk is more
  • Low rates of coronary angiography in women
  • Under referral for revascularization procedures
  • CABG - gt operative mortality 1.9 v/s 4.6
  • Restenosis after PTCA, or CABG occlusion rates
    are more for women - ? Smaller lumen sizes

  • Presentation and symptomatology
  • Cardiac risk factors differences
  • Metabolic syndrome, Obesity IR DMII
  • Dyslipidemia patterns
  • TMT lower value
  • Stress Echo, MPI, Sistemibi, Dobuatamine
  • CABG, PTCA risks, long term
  • Above all need for greater clinical suspicion

Take-Home Messages
  • The majority of risk factors for CAD can be
    improved by lifestyle modification.
  • Goals for optimal levels continue to decrease
    with each new guideline version.
  • The gap between average and optimal will
    continue to widen unless lifestyle modification
    is adopted more successfully.

Take-Home Messages
  • Diet, exercise (attaining ideal body weight), and
    smoking cessation are key lifestyle changes.
  • No quick-fix
  • Extreme changes are usually not sustainable
  • Medications are not an antidote to an unhealthy

Take-Home Messages
  • Work with your patient to set realistic goals.
  • Remember that modest changes in diet, weight, and
    exercise can have a big impact on cardiac risk.
  • A heart-healthy lifestyle should be encouraged
    from youth, but even changes later in life lead
    to important benefits.
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