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CARDIOVASCULAR DISEASE

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Title: CARDIOVASCULAR DISEASE


1
CARDIOVASCULAR DISEASE WOMEN A Review of The
Evidence
2
Presented ByDr. Laurie-Ann Baker, MD, CCFPEM
ResidentUniversity of Calgary
3
Objectives
  • Demystifying the truths and examining the myths
  • Risk Factors
  • The Diagnosis of CAD in Women
  • HRT What Now
  • The Bottom Line
  • Current future research

4
Fact
  • Cardiovascular disease, primarily CAD, outnumbers
    the next 16 causes of death in women combined,
    including all cancers
  • Women are 4 to 8 times more likely to die of CVD
    than of any other disease
  • CVD will be the leading cause of death for the
    next 20 years in the developing world

5
Fact
  • Since 1980, death from CVD has declined in men
    but increased in women
  • The Canadian Cardiovascular Society state that
    mortality at presentation is twice that of men
  • It has only been in the last decade that there
    has been heightened awareness within the health
    care community that differences between men
    women exist

6
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7
Percentage of total deaths due to CVD by age
sex (Canada 1997)
8
Risk Factors For Coronary Artery Disease in Women
9
Diabetes
  • Increases CAD-related mortality rate in women 3
    to 7 times more than in non-diabetic women
  • Increases CAD-related mortality rate in men 2 to
    4 times

10
  • DM is a greater predictor of CAD for women than
    for men
  • DM reduces womens life-expectancy advantage
  • Difference may be due to a particularly
    deleterious effect of diabetes on lipids and
    blood pressure in women

11
Dyslipidemia
12
Dyslipidemia
  • After age 50, cholesterol levels plateau in men
  • Levels of LDL increase an average of 0.05 mmol/L
    per year between ages 40 and 60 in women
  • Part of this increase results from declining
    levels of estrogen

13
  • Decreasing estrogen results in the
    down-regulation of the LDL receptor on the liver
  • A high LDL level is a strong predictor of CAD
    risk in women younger than 65 years and a
    somewhat weaker predictor in women gt65 years
  • Low HDL levels is a stronger predictor of CAD
    mortality in women than in men particularly after
    age 65

14
  • FRAMINGHAM HEART STUDY
  • - 8 year risk of heart disease was 7 for women
    with a total/HDL ratio less than 5
  • - 12 for those with ratios of 5 to 7
  • - 20 for those with ratios greater than 7

15
  • Further, in another study of 2500 women aged 71
    years or older, those with HDL levels lt0.9 had a
    RR of CAD mortality twice that of women with HDL
    levels of 1.6 or more
  • Elevated triglycerides are also shown to be a
    significant risk factor in women especially when
    HDL levels fall below 1.03

16
  • The Air Force / Texas Coronary Atherosclerosis
    Prevention Study (AFCAPS/ TexCAPS) used drug
    intervention with a statin in men and women who
    had average total and LDL levels and slightly low
    HDL levels. A reduction of primary CV events was
    demonstrated in both sexes
  • However, the US / Canadian PREVENT trial (2000)
    investigators found that women, especially,
    continue to be under-treated compared to men

17
Hypertension
  • Major trials of hypertension treatment, ie.
    Hypertension Detection Follow-up Program
    (HDFP), Systolic Hypertension in the Elderly
    (SHEP), have included adequate numbers of women
    and demonstrated benefits of treatment

18
  • Women with hypertension have a 4-fold risk of
    heart disease compared with normotensive women
  • Men with hypertension have a 3-fold increase in
    risk
  • Isolated systolic hypertension in older women has
    a 30 prevalence in women older than 65 years

19
  • Women with hypertension outnumber men with
    hypertension in the older age groups (due to
    survival advantage)
  • Estimated prevalence (BP gt140/90 or use of
    anti-hypertensive) in women older than 45 years
    is 60 (US statistic)

20
Smoking
21
Smoking
  • The leading preventable cause of CAD in women is
    cigarette smoking
  • More than 60 of MIs in women younger than 50
    yrs can be attributed to tobacco use
  • 21 of all CAD deaths attributable to smoking

22
  • The risk in heavy smokers ( gt 20 cigarettes per
    day) is 2 to 4 times higher than in nonsmokers
  • Light smokers (1-4 cigarettes per day) have
    double the risk of nonsmokers
  • Stopping smoking decreases the risk of CAD within
    months (Nurses Health Study found the risk of
    CAD decrease by 1/3 two years after cessation)

23
  • The prevalence of smoking in recent years has
    dropped in both men and women however womens
    rate of cessation is lower than that of men
  • Almost one fourth of women smoke cigarettes
  • Greatest increase in the prevalence of smoking is
    in women aged 65 years or older

24
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25
Menopause
  • Natural menopause confers a 3-fold increase in
    CAD risk
  • Nurses Health Study cohort showed that women
    under-going bilateral oophorectomy had up to an
    8-fold increase in risk of CAD
  • Of interest, the Nurses Health Study showed that
    early natural menopause was not a risk factor for
    CAD after adjustment for tobacco exposure

26
  • Degree to which estrogen deficiency increases
    risk of CAD in women remains a subject of debate
  • Many studies have found the incidence of CAD in
    postmenopausal women higher than that of
    pre-menopausal women of the same age range

27
  • Although the largest increase in coronary
    mortality in women coincides with menopause,
    vital statistics data do not support that
    menopause, apart from chronological aging
    increases the risk of CAD
  • Effects of aging versus estrogen deficiency
    (menopause state) versus lipid increase

28
Obesity Physical Activity
29
Obesity
  • Obesity in both men women has been increasing
    over the past few decades
  • Obesity sedentary lifestyle are interrelated
  • Obesity is an independent risk factor for
    all-cause mortality is associated with DM,
    hyperlipidemia and hypertension

30
Obesity in Canada
31
  • 30.5 of Canadians between the ages of 20 and 64
    are obese (BMI of 27 or greater)
  • Obesity is the most common metabolic condition in
    industrialized nations
  • Total direct cost of obesity in Canada was
    estimated to be over 1.8 billion (2.4 of the
    total health care expenditures for all diseases
    in Canada)

32
Physical Activity
33
Physical Activity
  • Physical inactivity contributes to obesity and is
    an independent risk factor for MI
  • Investigators in the Nurses Health Study found
    that 30 to 45 minutes of walking three times
    weekly reduces the risk of MI by 50 (even in
    older women)

34
  • It is estimated that between 39 and 54 of North
    American women do not get adequate physical
    activity
  • Exercise has been found to reduce the risk of
    type II DM even in women with obesity and a FHX
    of DM
  • HDL levels have shown a dose-response
    relationship in female runners

35
The Diagnosis of CAD in Women
36
Approach to Diagnosis
  • The perception persists that CAD mainly affects
    men is not a serious concern for women
  • Women develop angina about 10 years later and a
    first MI about 20 years later than men
  • Women are more likely to have angina than MI as
    their initial presentation of CAD

37
  • Women tend to have more atypical features when
    presenting with CAD than do men
  • Women presenting with acute MI tend to be older
    and have more co-morbidity
  • Women are less likely than men to attribute their
    symptoms to cardiac disease, even in the setting
    of acute MI

38
Estimating the Risk
  • Estimating the likelihood of CAD by assessment of
    the patients clinical characteristics and
    coronary risk factors is more easily and
    accurately accomplished in men than in women
  • As the prevalence of CAD (particularly
    multi-vessel disease) is lower in women than men
    (except in older women), the predictive value of
    any symptom or non-invasive test is lower

39
  • The presence of any type of chest pain, whether
    atypical or typical, is associated with a lower
    risk of CAD in pre-menopausal women
  • The likelihood of CAD increases after menopause
  • Diabetes eliminates the age advantage in women
    over men and confers a substantially greater CAD
    mortality than in non-diabetic women
  • DM is an important predictor of the presence
    prognosis of CAD in women

40
Diagnostic Evaluation
  • The purpose of performing a clinical evaluation
    is to identify those at very high risk, who would
    benefit from immediate coronary angiography, and,
    in lower-risk patients, to accurately identify
    those with significant CAD prior to development
    of acute coronary event

41
Diagnostic Evaluation
  • Patients can be classified into high,
    intermediate or low probability of CAD, by taking
    into consideration factors such as chest pain
    types (typical, atypical or nonischemic) and
    determinants (major, intermediate and minor) or
    the likelihood of CAD

42
Classification of Chest Pain(Typical Angina)
  • FEATURES
  • - Substernal
  • - Squeezing, burning, heavy
  • - Exertional or precipitated by emotion
  • - Promptly relieved by rest or nitroglycerin
  • CLASSIFICATION
  • - 60-75 prevalence of angiographically
    significant CAD

43
Classification of Chest Pain(Atypical Angina)
  • CLASSIFICATION
  • - 30-40 prevalence of angiographically
    significant CAD
  • FEATURES
  • - Left chest, abdominal, back, arm, without
    mid-chest pain
  • - Sharp or fleeting
  • - Unrelated to exercise
  • - Relieved by antacids

44
Determinants of the Likelihood of CAD in Women
  • MAJOR
  • - Post menopausal status / age gt65 years
  • - Diabetes
  • - Peripheral Vascular Disease

45
Determinants of the Likelihood of CAD in Women
  • INTERMEDIATE
  • - Hypertension
  • - Smoking
  • - Lipid abnormalities

46
Determinants of the Likelihood of CAD in Women
  • MINOR
  • - Obesity
  • - Sedentary lifestyle
  • - Family history of CAD
  • - Other risks factors of CAD

47
Classification According To Their Probability of
CAD
48
  • HIGH PROBABILITY OF CAD (gt80)
  • Typical angina and any of
  • - Post-menopausal status or age gt65
  • - Diabetes
  • - Peripheral Vascular Disease
  • - Two intermediate determinants

49
  • HIGH PROBABILITY OF CAD (gt80)
  • Atypical angina and any of
  • - Post-menopausal or age gt65 and gt1
    intermediate determinant
  • - Diabetes plus gt1 intermediate or minor
    determinants
  • - Three intermediate or 2 intermediate plus 1
    minor determinants

50
  • INTERMEDIATE PROBABILITY (20 80)
  • Typical Angina and 1 intermediate or gt2 minor
    determinants
  • Atypical Angina and post-menopausal / age gt65
  • Nonischemic Pain and post-menopausal / age gt65 or
    diabetes and gt2 intermediate and/or minor
    determinants

51
  • LOW PROBABILITY (lt20)
  • Typical Angina and premenopausal with no
    determinants
  • Atypical Angina and no major determinants
  • Nonischemic pain and no major determinants

52
Diagnostic Testing
  • The prevalence of CAD, particularly multi-vessel
    disease, is lower than in men (with the
    exception of the older age group)
  • As a result, the predictive value of any symptom
    or non-invasive test is lower in women than in
    men
  • Utility of diagnostic testing is related to the
    pretest probability of disease, therefore it is
    necessary to make a careful assessment of risk in
    order to guide the choice of diagnostic modality
    or to determine if the test is required

53
Diagnostic Evaluation
  • LOW PROBABILITY
  • - no stress test likelihood of false-positive
    test results are greater than the likelihood of a
    true-positive test

54
Diagnostic Evaluation
  • INTERMEDIATE
  • - Those who are able to exercise and who have a
    normal resting ECG, should undergo exercise
    stress
  • - If negative, no further workup (high negative
    predictive value)
  • - If inconclusive, or if baseline ECG
    abnormalities, or if goal is to localize and
    quantify ischemia these go on to stress imaging
    studies

55
Diagnostic Evaluation
  • HIGH PROBABILITY
  • - Stress testing or coronary angiography
    depending on their severity and stability of
    symptoms
  • - If negative stress test, may follow closely
    and observe (controversial)
  • If inconclusive stress test, angiography

56
HRT What Now??
57
HRT Observational Studies
  • Numerous observational studies including a
    meta-analysis of more than 30 observational
    studies by Stampfer Colditz (1991) showed
    reductions up to 60 in the risk of a major
    coronary event in healthy current estrogen users
    compared with women who have never used estrogen
    replacement

58
HRT RCTs
  • In the first large randomized trial of HRT in
    women, the HERS trial found there was no
    significant difference in the combined incidence
    of CHD death and nonfatal MI at 5 years
  • There was a mean reduction in LDL levels of 11
    and increases in HDL of 10 however there was
    also an increase in primary coronary events in
    year one

59
  • Increased risk (RR 1.57) of a second CV event in
    the first year of treatment, followed by a
    non-significant reduction in risk in the last two
    years
  • Based on no cardiovascular benefit and a pattern
    of early increase in risk of CAD events, the
    investigators do not recommend HRT for secondary
    prevention of CVD
  • Extended follow-up of the HERS cohort is underway

60
  • A second large randomized trial of HRT, the ERA
    study, also observed no benefit of HRT with the
    use of quantitative coronary angiography
  • The Womens Health Initiative (WHI) is a
    nine-year primary prevention study with
    approximately 27, 000 post-menopausal women
    randomized to treatment with placebo, CEE alone
    or CEE and MPA. This trial is scheduled for
    completion in 2005

61
  • The Womens Health Initiative (WHI) Study stopped
    the CEE MPA arm of their study this past summer
    (2002)
  • The overall health risks exceeded the benefits
    from the use of CEE MPA in healthy post
    menopausal women and the investigators therefore
    concluded that this regime should not be
    initiated or continued for primary prevention of
    CAD

62
The SOGC Recommends
  • HRT indeed should not be initiated or continued
    for the sole purpose of preventing cardiovascular
    event (primary or secondary)
  • HRT for the prevention of bone loss to decrease
    the risk of fracture
  • HRT for extreme perimenopausal symptoms

63
Men Are From Mars Women Are From VenusSo
..
64
What Are We Doing About It?
  • The investigators from the PREVENT (2000)
    published observational data citing that both the
    US Canada treated hyperlipidemia inadequately
    especially in women
  • Cox et. Al. (2001) published a cross sectional
    survey showing that women were less likely than
    men to have a recording of BMI, smoking, BP and
    cholesterol profile, and less likely to be on
    lipid lowering therapy and aspirin

65
  • The Myocardial Infarction Triage Intervention
    Registry as well at the TIMI 9 trial both
    identified that women with identical symptoms and
    profile were less likely to be admitted to the
    CCU or its equivalent and therefore less likely
    to receive thrombolytic therapy

66
  • Lee et. Al. (2001) reviewed RCTs of ACS from 1966
    2000 and found that age exclusion has declined
    from 58 to 40 comparing trials from 1966 1990
    1991 2000 and enrollment of women has risen
    from 20 to 25 even though the proportion of
    women with MIs is approximately 43
  • Recent surveys of cardiac rehabilitation programs
    continue to under-represent women impacting
    secondary prevention / risk factor modification
    management

67
The Bottom Line Whats Different for Women?
  • PRESENTATION
  • - Women present at later age
  • - Typical angina is less predictive of CAD
    (pretest probability 50-60 compared to 80-99 in
    men)
  • - Women often present with shoulder or jaw pain,
    dyspnea or nausea

68
The Bottom Line Whats Different for Women?
  • RISK FACTORS
  • - Diabetes hypertension have a stronger
    influence in women
  • - High HDL levels more common in women
  • - Roles of total cholesterol and LDL in women
    remain unclear
  • - Risk increases after menopause

69
The Bottom Line Whats Different for Women?
  • PROGNOSIS
  • - Women are more likely to die of a first MI
  • - Overall case fatality rates 32 in women and
    27 in men (Framingham Data)
  • - 30 day 1 year crude mortality rates are
    approximately double that in men
  • - Women have more co-morbidity experience more
    long-term disability

70
The Bottom Line Whats Different for Women?
  • PRIMARY PREVENTION
  • - Initial evidence for the benefit of lipid
    lowering medication in women exists but more
    evidence is required
  • - Strong evidence to support adequate B/P
    control
  • - Lifestyle, lifestyle, lifestyle

71
The Bottom Line Whats Different for Women?
  • SECONDARY PREVENTION
  • - Women are less likely to undergo angioplasty
    or bypass surgery
  • - Fewer women receive cardiac rehabilitation
  • - Fewer women receive therapy with aspirin, beta
    blockers or ACE inhibitors

72
Current Future Research
73
Research Goals
  • Since difficulties in diagnosing CAD in women on
    the basis of chest pain and noninvasive testing
    may contribute to the lower referral rates for
    catheterization and revascularization, it is
    important to improve symptom evaluation and
    diagnosis of ischemic heart disease in women

74
  • The Womens Ischemia Syndrome Evaluation (WISE)
    is ongoing and attempting to add to the limited
    information about the pathophysiology of ischemia
    without substantial epicardial coronary artery
    stenosis
  • The Womens Health Initiative Study Group is
    looking at the strategies to prevent and control
    the most common causes of morbidity and mortality
    among postmenopausal women. It will continue to
    evaluate 3 interventions low-fat diet, HRT and
    calcium and vitamin D supplementation

75
  • The Beyond Endorsed Lipid Levels Evaluation Study
    (BELLES) is currently recruiting postmenopausal
    women and will compare the effects of 12 months
    of atorvastatin or pravastatin on regression of
    coronary atherosclerosis and will give us an
    idea if gender differences exist

76
CONCLUSION
  • Despite the abundant evidence that CAD is
    virtually epidemic in older women, the belief
    that women have innate protection from coronary
    events still prevails
  • Even in the face of considerable morbidity
    mortality rates, prevention treatment
    strategies are still less aggressive for women
    than for men

77
  • Control of CAD risk factors in women will require
    recognition of the differences as well as the
    similarities between men and women in the
    manifestation of risk factors
  • Initial data suggests that women can
    substantially benefit from lipid-lowering drug
    therapies if diet and exercise fail to lower LDL
    levels
  • Statins have proved particularly effective in
    lowering womens CAD risks and mortality

78
  • Estrogen and HRTs to reduce risk have been
    popular in the past however in view of the recent
    HERS and WHI findings, it is not recommended for
    prevention of CVD
  • On the basis of the HERS and ERA results, statin
    drugs should be the drug of first choice for
    women with established CAD
  • The population of older women can be expected to
    increase in the coming decades and a growing
    health problem will ensue if clinical issues fail
    to be addressed

79
  • In the words of Professor Henry Higgins in
    My Fair Lady.
  • WHY CANT A WOMAN BE MORE LIKE A MAN?
  • WHY CANT A MAN BE MORE LIKE A WOMAN?

80
THE END
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