Transcript risk factors

Dr. Nabil Alama (MD. FRCPC)
Head of Cardiology Unit
King Abudlaziz University Hospital
 CVD is the number one cause 1 death for women
 Each year 500,000 women have MI and more than
250,000 die of CAD
 Combined with stroke, hypertension and other vascular
disease, more than 500,000 women die normally of CAD
 Although virtually all women can readily quote lifetime
incidence of breast cancer (1in 9), few realise that 50%
(1 in 2) all women will die of CVD.
 Whereas the death rate from CVD in men has declined
steadily during last 20 years. The rate has remained relatively
the same for woman.
Despite the magnitude of the problem in women, much less
Information about optimal primary & secondary. Presentation
strategies, diagnostic modalities and responses to medical & surgical
Treatment is available for women than for men.
This lack of data reflects several factors, exclusion of women
From many older clinical trials
•Lower prevelance of symptomatic CAD in women than
in man until age 70.
• Hormonal effects of gender differences in presenting symptoms
* Relaive effects of various risk factors
Gender difference versus gender bias
clear gender difference has been identified in epidiomology
of presentation of disease,Risk factor prevalence, phyioslogy
& response to diagnostic test & interventions.
Although there are several factors that solely or predominately
Effect women, including menopause status, hormone replacement
therapy.
Oral controceptives & pregnancy related heart diease
During last decade, several studies have noted important
Gender differences as in clinical outcomes and the use of
Diagnostic and therapeutic drugs and informations, especially
In evaluation and Rx of Treatment woman with CP and MI
The concern has been raised that women are evaluated less
Intensively, under referred and not treated as aggressively
as man for comparative presentation and disease
Ischemic Heart Disease
Framingham group reported that more women than man
(56% vs. 46%) have angine as their presenting symptom
Of cardiac disease. But more men who have angina go on to
have MI 25% vs 14%).
This led to erroneous conclusion that angina is benign condion
In women.
This misconception was clarified with publications (CASS)
Which showed that even in women with classical angina symptoms.
Rate of normal coronary arteries on angiography is approximately
50% compared with less than 20% in men.
In Framingham study angina has defined clinically without
Angiography, (women are more likely to have non Ischaemic
cause of chest pain that has benign prognosis.
Reexamining date, showed prognosis for older women with
Probably true ischemic was activity worse than for man in
Framingham study.
Presenting Symptoms
On average, women with CAD present with symptoms cardiac
Events or sudden death 10 years later than man. It is largely
Protective effects & endogenous oestrogen in premenopaul in men.
Most men & women present with typical symptoms CAD however
Disproportinately more women present atypically with dyspnea,
Fatigue and referred pain.
Because of late presentation, women are less likely to be eligible
For emergency PTCA – Thrombolysis for acute MI & often have
Advanced anatomical disease on coronary angiography
Stress Test
Standard stress ECG testing is less activate in women than in man.
Numrous studies high false positive rate in women compared to
Men (Lower prevalence (CAD) until 70 years.
Lower specificity is related to gender specific autonomic and sex
Hormone effects for ECG.
In older women, failure to achieve an adequate stress level due to
Deconditioning or orthopaedic limitation may adversely affect
Sensitivity of exercise test.
Normal finding of stress ECG at adequate work load in women
Are a good indication that flow limiting CAD is unlikley.
•Because of these limitation imaging stress have gained popolarity
for women.
•Gender specific antifacts and physiological responses have been
described in both nuclear and stress echo standard diagnostic
criteria used for interpreting exercise radionuclide angriographic
Finding have not proved accurate in women. Abnormal result is
Defined as a lack of increase in ejection fraction with exercise.
In men increase stroke volume in response to exercise is caused
By an increase in ejection fraction.
Whereas in women, it is caused by an increase in end-diastolic
Volume so 1/3 of women with normal coronary arteries do not
Have an increase in ejection fraction.
Stress Thallium Scintegraphy Improres
Diagnostic accuracy in women
-Breast tissue attenuates radioactivity and may produce a false
positive study as a result of artifactual defects in anterior wall
and septum.
-Use of technetium 99m (Tc99)sestamibi imaging higher energy
radioactivity, reduce breast tissue attenuation artifact.
-Limited studies suggested that thallium and sestamibi have similar
test sensitivity by specificity may be enhanced by sestamibi
imaging.
-Pharmacologic stress using dypyridamole, adenosine, or
dobutamine is limited but suggests that diagnostic accuracy is
similar for men and women.
Exercise echo may improve accuracy of exercise testing for
Diagnosis dobutamine echo is safe in women.
Until more studies, no firm guidelines can be offered about
Specific stress testing modalities in women, because no approach
Or technique has been shown to be clearly superior. As in men,
Pretest probability of disease is likely more important in deterMining diagnosis accuracy than specific type of test. If likelihoood
Of CAD is low, no stress test is very accurte. Women with
Intermediate probability of CAD and normal ECG standard test
ECG has acceptable sensitivity and specificity. If result are normal,
There is a high negative predictive value regarding absence of
CAD and prognosis is good.
Women with worrisome symptoms and high pretest probability
Of CAD argument can be made to proceed directly to angiography.
Coronary Angiography is safe in women
Most studies have demonstrated despite gender differences of
Rates of referral to angiography, after anatomy is defined women
Are revascularized at a rate similar to men.
Myocardial Infarction
•Numerous studies have demonstrated greater early and late
mortality and more compliclations in women than in men after
Myocardial infarction. However, analysis of several studies
(GUSTO-I, ISIS-11, TIMI IIIB)
•After baselise differences have been accounted for especially
age and cardiac risk factors, gender is no longer an independent
risk factor for death.
•Women with MI are older and have more comorbid conditions
and have increase of all cardiac risk factors except smoking.
•DM is more common in women and may account for
increased frequency of silent ischaemic
Women may be slightly less likely to present with sudden death
But more likely than men to have non-Q-myocardial infarction.
Also, women are morel likely to delay receiving Rx.
Risk of inhospital complications (reinfarction, stroke and
Myocardial rupture) has been reported to be higher in women.
But some of these differences may be related to older age.
Women have more heart failure despite better residual left
Ventricular systolic function, presumably because of diastolic
Abnormalities.
Women are less likely to be referred to cardiac rehabilitation
All therapies and interventions for RX of MI have been
Beneficial revascularization by thrombolysis, direct angioplasty
Or surgery ASA, Blocker, ACE.
More less likely to have invasive & therapeutic procedures when
Hospitalized with ACS. This relative “undertreatment” is not
Benign.
Women in these studies who have revascularization procedure
Had a better prognosis than those who did not.
Coronary Angiography
Female gender is independent predictor of a lower likelihood
Of receiving coronary angiography.
After little difference found in subsequent use of angiography
And bypass surgery, decisions made primarily on severity of
Disease and not gender.
Thrombolysis decreased 30% overall reduction in mortality.
No difference in fundamental mechanism of action of
Thrombolysis agents. After adjustment for age and comorbid
Conditions, women have same rate of vessel patency, LVEF and
Short - and long term martality as men. Women receive
Thrombolysis much less frequently at least partly because they
Are more likely to be ineligible at the time of evaluation, because
Of age, comorbid conditions and late presentation.
Intracerebral hemorrhage is more common in women than in men,
Smaller size and lack of dose adjustment.
CETHETER BASED REVASCUAFSTIN
Early in interventional era procedural success for PTCA in women was
lower then man because large non stearable catheters and balloons and
generaly smaller coronaly alteries in women currently no gender difference
in the procedure success or restenosis date have been document all report
series show that women more severe angina and more contaminant illness
including DM, Hypertention, Heart failer at the time of persentation
When age and these base lines charteristics are consider there minmal or no
genger difference in short or long term servival or rate of MI CABG wheter
interventional proccdure is perform for UA, acute MI, Elective stable
angina
Women more likely to have residual angina and to take anti angina
medication after PTCA this difference observed also after CABG
Microsvasculaer disease and abnormalities in coronary flow reseved
associated with LVH or DM may contribute this observation
Coronaryartery and Surgery
Earlear women who had CABG have greative operative short and long
mortality then man (smaller body size more advanced desisae at the time of
operation and refferial bias) however studies cass, bari trials reported
similar graft patency and loge term servival benefit.
Rate of the peri operative death and compications (MI, Strocks and heart
failer) are greater for women this disparty disappear when the base line
factors such as age heart falier are considered
Women are more likely to have residual angina that requires theropy also
women have more likely to have emergency by pass which is lndepently
assoated higher morbiatity and mortality CABE proides Excellent Relief of
symptomes and comprarable survival benefits in women.
PHARMACOLOGIC THERAPY
ASA, B-blcoker, ACEI under utilized ineligible patients
With acute MI or left venticular dysfunction.
ISIS I & ISIS II, demonstrated that improved survival in women
Receiving b-blocker & ASA was comparale to that of men.
Trials involving ACEI & generally have sown beneficial
effects in women, but less than those in men so should be
used
NONCORONARY CARDIOVASCULAR
DISEASE (CVD)
Framingham and other reported markedly prevalence of MVP
Diagnosed clinically or by M-mode. In women but men with
MVP more likely to develop progressive MR and other
Complications.
More recent studies with two-dimensional echocardiography
(which may be less likely to overcall the diagnosis of MVP have
Not found any gender difference in prevalence of mitral valve
Prolapse.
AORTIC VALVE DISEASE
Calcific AS is disease of elderly
Women with aortic stenosis have different pattern of LV
Adaptation to pressure load of AS then man, with better
preservation of LV systolic function and concentric pattern
of LVH. Men more frequently have eccentric hypertrophy
And lower systolic function.
The classic criteria (LV EDD >70, LV ESD >50 for timing
AVR for severe AR has been questioned recently. Women
With even advanced severe AR rarely meet established LVD
Surgical criteria (which traditionally has not been adjusted for
Body size.
Even after sgnificant symptoms develop, ventricular
Dimension tend to be smaller than those of the criteria.
Thus, using these criteria for women results in operating
Late in the clinical course, with poor outcomes. Female gender
Appears independent risk factor for poor outcome and optimal
Criteria is not clear for surgical timing for asymptomatic chronic
Aortic regurgitation.
Surgery should be considered in men and women with more than
mild symptoms or with an ejection fraction less than 55%.
CONGESTIVE HEART FAILURE
Rate of hospitalization for CHF has increased steadily in
Last 20 years. CHF affects 20% of population over 45.
Framingham study found incidence rate of CHF are higher
In men but that of prevalence of CHF is nearly equal except
In very elderly.
•5 year suvival was better in women than in men.
• Hypertension, DM and valvular heart disease tend to be more
common in women with CHF whereas CAD and smoking
are more common in men.
Women are more likely to have better LV systolic function
Than men with similar heart failure symptoms. In women
Have been ascribed to higher rate of diastolic dysfunction
(more symptomatic with similar EF) Many of major heart failure
Trials did not include women or so conclusion must be interpreted
Carefuly, CONSENSUS, SOLVD, and SAVE heart failure
Trials women received less benefit from ACE than men.
Fewer than 20% of cardiac transplantation operations are
Performed on women, and there appears to be a gender effect
On outcome after cardiac transplantation.
Women may be at increased risk of death and rejection spisodes,
(small date) one possible cause frequency of autoimmune
Disease for in women and multiparity, which exposes women to
Additional antibodies to foreign material.
Arrhythmias, Syncope, and Sudden Death
Women presenting with syncope tend to be older, have fewer
Premonitory symptoms, have better LVF, and are less likely
To have cardiac cause of syncope identified subsequently
Have fewer cardiac events.
Female survivors of cardiac arrest tend to have better LV
Function and are less likely to have CAD as underlying cause.
They are more likely to have dilated cardiomyopathy, valvular
Heart disease, long QT syndrome, RV dysplasia, Coronary vasospasms
or structurally Normal heart. Despite these differences, long-term
survival appears to be similar.
Benefit of defibrillator therapy are less well defined mainly because
Of small number.
Prevalence of atrial fib is higher at all ages in men than in women.
It has been estimated athat 50% to 55% of all persons and 60%
Of those older than 75 years who have atrial fibrillation are
Women.
More women than men have atrial because of greater number
Of elderly women.
Paroxysmal SVT more common in women than men. Some
Investigations have described cyclical variation in the frequency
And duration of PSVT in premenopausal women, with highest
Frequency occurring in the luteal phase of the menstrual cycle
When estrogen levels are lowest. Mechanism may be cyclic body
Temperature changes, direct or indirect actions of estrogen or
Progesterone effects.
RISK FACTORS
Men & women have the same risk factors for CAD, but relative
Weight of a given risk may be more or less significant in women.
DM is more powerful risk factor for CAD and heart failure in
Women than in men and completely negates the protective effect
Of female gender, even in premenopausal women.
Metabolic derangements accompanying diabetes adversely
Contribute to obesity, lower levels of high-density lipoprotein
And TG abnormal endothelial and coagulation function and
Increased risk of hypertension. DM acts synergistically with
Other risk factors especially smoking, increase cardiac risk.
DM is independent risk for subsequent cardiac events and
Poor outcome after PTCA in women.
TOBACCO
Cigarette smoking is a significantly stronger risk factor in
Women than in men. Even women who smoke fewer than
5 cigarette per day have double the risk of CAD than nonSmokers
Smoking cessation is associated with a significant reduction
Of risk.
Women with CAD who continue to smoke have significant
Progression of atherosclerosis and are at risk for recurrent
Events and repeat revascularization.
HYPERTENTION
Women make up 60% of all those in the US who have hyperTention. Prevalence of hypertension is greater in men than
Women until age 60.
In Black and Hispanic persons older than 60 and white people
Older than 70. Age specific hypertension rate is higher in women
Tha in man. With women older than 80 have rates 14% higher
Than men.
BP tend to increase throughout life in men and women, but before
Age 60, women have lower systolic and diastolic BP than men.
Subsequently systolic BP increases more steeply in women and
Surpasses that of men.
As result older women more likely to have isolated systolic
hypertention.
SEVERAL TYPES OF HYPERTENSION
AFFECT WOMEN
Renal artery stenosis caused by fibromuscular dysplasia has a
Strong female preponderance (8:1) and should be considered
When hypertension occurs in women less than 40 difficult
To control or occurs in pregnancy complicated by severe
Hypertension.
Ingestion of currently available oral contraceptive agents is
Associated with and increase in BP, although not commonly
As first generation agents.
Hypertension and LVH both are stronger risk factors for stroke
And CHF in women than in men. Framingham (LVH removes
survival advantage of female gender.
No real gender differences exist in relative risk reduction for
Stroke and CHF from the treatment of hypertension. Absolute
Risk reduction are lower in women because the baseline risk
Of events is lower.
Current guidelines from the Joint National Committee on the
Treatment of Hypertenstion VI (JNC-VI) are not gender
Specific and it appears that women with hypertension benefit
From therapy and should e treated as aggressively as men.
HYPERLIPIDEMIA
Serum levels of toal cholesterol in women increase steadily
From mid-30s to age 55 – 60.
LDL remain lower than in men until 50 age, which levels in men
stabilize and are surpassed by those in women.
This coincides with the average age of menopause and likely
Contributes to observed increase in cardiac events in older
Women.
Women younger than 65 with T-cholesterol level greater
240mg/dL LDL greater 160mg/dL have relative risk of cardiac
Event is 2-3 times that of women without hyperlipidemia
HDL cholesterol remains a strong risk factor in women older
than 65.
Relationship of total cholesterol and LDL Ch. & CAD in older
Women is not as strong.
Conflicting data about triglyceride as independent risk factors.
This appear similar to those of men.
Primary prevention hyperlipidemia trials excluded women
And elderly; therefore little information on which to base
Therapeutic decisions.
1993 NCEP, ATP II acknowledged gender differences and
Estrogen status in calculating the risk for CAD for premenoPausal women with out CAD, there are insufficient data to
Recommend early or aggressive pharmacologic therapy unless
Multiple risks are present.
Postmenopausal women without CAD and hypercholesterolemia
Or a low HDL cholesterol may be considered for estrogen
Replcement therapy, which may obviate additional pharmacologic
Therapy.
AFCAPS / TEXT CAPS)
1000 postmenopausal women with no known vascular disease
Average TC, Low average HDL Ch. to placebo or treatment
With lovastatin and found 46% reduction in CV events in
Treated women. Study not powered to detect treatment differences
In mortality but showed similar or greater reduction events in
Women than in men and demonstrated risk reduction from
Lipid modification in relatively low risk group that otherwise
Not treated in current NCEP- ATP-II guidelines.
There is strong evidence from well-designed randomized
Trials to support aggressive treatment of increased cholesterol
Levels in women with CAD.
CARE randomized men and women with recent myocardial
Infarction and normal LDL cholesterol levels (115-174 m/dL)
To treatment pravastatin or placebo.
Treated men and women both had a significant reduction in all
end points including cardiac death, MI & revascularization.
Subgroup analysis demonstrated an even greater reduction
In risk for coronary events in women than in men (46% vs. 20%)
and benerfit was observed much earlier the follow-up period.
4 S Study randomly assigned hyperlipidemic patients wth CAD
to treatment a placebo. The risk reduction for major coronary
Events were similar in men and women (34% vs. 35%,
Respectively).
These studies provide evidence to support the use of the
Current NCEP-ATP-II guidelines for secondary prevention
Of CAD with goal LDL cholesterol of less than 100mg/dL.
No study has suggested significant gender differences in dietary
Intervention or lipid lowering drugs.
RISK FACTORS UNIQUE TO WOMEN
Oral Contraceptives
One of the most effective methods for pregnancy prevention
But women who took first generation high-dose agents has
Increased rate of MI and thrombotic events.
There was a clear synergy with cigarette smoking believed
Thrombotic rather than atherosclerotic currently oral contraCeptives with markedly lower estrogen content have been
Lower rates MI and appears that there is little or no increased
In nonsmoking women taking oral contraceptive and no inceased
Risk in those who previously took them.
Small excess risk of ischemic stroke cannot be excluded
Large risk appears unlikely
Smokers specially older than 35 years shout quit smoking, and
If unable to do so, should use an alternative birth control method.
Oral contraceptives are associated with increased BP, some
Become overtly hypertensive (if happened should discontinue).
Increased incidence of DVT & PE has been associated with
Taking oral contraceptive (less with current pills with relatives
Risk.
The risk of pregnancy related thromboembolic events and stroke
Is as much as 3 times than that associated with oral contaceptives.
Menopause and Hormone Replacement Therapy
Estrogen at menopause associated with several adverse effects
On cardiac risk factors, include:
 TC
 LDL Ch.
 LP9a) LP (a)
 Circulating procoagulants
And homocysteine
Decreased HDL cholesterol
These changes responsible at least partly for the observed
Acceleration of cardiovascular events afer menopause.
Premenopausal women who have had bilaeral oophonatomy
And do not receive estrogen have more than twice the risk of
MI than those receive estrogen replacement has been associated
With cardiovascular risk.
Primary epidemiological data and meta-analysis, including
Lipid Research Clinic and Nurse Health Study. Indicate risk
Reductions of 40% - 50% for CAD in women who choose to
Take postmenopausal HRT.
The data for stroke reduction by estrogen is less but similar risk
Reduction has been showb. These data are observational and not
from prospective randomized trials but has remarkable uniformity
and consistency in results
Estroen reverses many of the unfavorable physiologic changes
That occur at menopause.
Lipid effects are prominent, but the mechanism are incompletely
Understood.
Oral administered estrogen decreased LDL cholesterol by
10%-20%, increased HDL cholesterol by 10%-30%
And lowers LP(a) by 25% - 50%
Triglycerides are increased 20% or more
Transdermal administration of estrogen has little or no effect
On lipoprotein levels, suggesting that the liver effects of
Estrogen absorbed through the gut are responsible for these
Changes.
These favorable effects are also seen when estrogen is combined
With progestational agents, but increase in HDL levels is often
Blunted. Limited data suggest that the use of micronized proGesterone, comapred with medroxyprogesterone, blunts the
Estrogen induced increase in HDL cholesterol less, while
Maintaining protection against endometrial hyperplasia.
Balance of the effects estrogen is likely due to several
Direct and indirect vascular and hemostatic effects.
Despite the impressive benefits reported for coronary artery
Disease risk in these observational trials,.
The first randomized, blinded, placebo-controlled trial of
Estrogen for secondary prevention of coronary events did not
Show any significant reduction in cardiac risk
The Heart and Estrogen/Progesterone Replacement
Study( HERS)
Enrolled 2763 postmenopausal women younger than 80 years
With definite coronary artery disease and intact uterus to receive
Continuous-combined estrogen and medroxyprogesterone or
Placebo.
Average follow-up 4.1 years and was 100% complete. No
Signifidant differnece were observed for any of the CV
Outcome.
That is combination hormone replacement therapy(HRT) did
Not reduce cardiovascular events as expected from result of
Previous observational trials.
Most previous studies, conjugated equine estrogen (Premarin)
Was only estrogen formulation used
•Doses was higher than currently recommended
• Use of progestational agent in women was not routine
(Not practice now)
•Addition of progestins antagonies part on the beneficial
of estrogen. Women in HERS, received continuous progestrone
Which blunts beneficial lipid effect
•Selection bias or healthy user.
Results trial should not be extropaleted to other patient poplation
Patient without CAD
Without uterus
Other HrT formulation
Several study are on going for bot Pri + Sec includes women
Health study.
NONCARDIAC RISK AND BENEFITS
OF HORMONE
All women with suspected CAD should have their hormonal
Status assessed as a risk factors. Decision to start hormone
Replacement therapy must be individdual and based on risk of
CAD breast cancer and fracture and on hysterectomy status,
Life expectancy, and side effects.
Non cardiac beneficial oesgtrogen replacement therapy
decreased postmenopausal symptoms
decreased osteoprotic fracture
decreased Colon Ca
decreased Urinary incontinence
of Alzheimer dieses
Cancer Breast
Estrogen therapy for more 5 – 10 years associated
With an increased relative risk 1.2 to 1.5 which is similar to early
Menanrche and mulliparity.
Breast cancer must be put into perspective because CVD kills
More women that breast cancer at all ages.
Unopposed estrogen is associated with significantly increased
Risk of endometrial hyperplasia and cancer. Excess risk of
Cancer is eliminated with addition of progestrin; therefore,
Unopposed estrogen is recommended only for women who had
A hysterectomy.
Venous thromboembolism and pulmonary embolus have
Been associated with estrogen replacement. The increae
In relative risk of various thromboembolism appears to be
2 to 4 (2.9 in HERS_. This risk appears higher during the
First year of treatment and affects those currently receiving
Treatment but not those who formerly received it. The
Women affected may have unidentified coagulapathies or
Other predisposing risk factors, because no consistent adverse
Effects on the clotting system have been identified. The
Absolute incidenc is low, but women experiencing venous
thromboembolism while receiving hormone replacement therapy
Should be evaluated for the presence of coagulapathy.
Selective estrogen receptor modulators (SERMS) are a class
Of synthetic tissue-specific estrogens(“designer estrogens”)
Formulated to provide the beneficial action of estrogen without
The risks and side effects Tarnoxifen (used for prevention and
Treatment of breast cance) and raloxifene (approved for the
treatment of osteoporosis) are the most commonly used SERMs,
And both of them have favorable effects on lipoprotein and
Homocysteine levels. These drugs do not have significant
Beneficial effects on HDL cholesterol, and the observed
Improvements in the lipid profile are less than those observed
with oral estrogen. Currently, the role of SERMs in preventing
Cardiovascular disease is unclear.
Hrmone Replacement Therapy Recommendations
Currently, no consensus exists about the role of postmenopausal
Hormone replacement therapy in the prevention of coronary artery
Disease. Recommendations are evolving as now data published.
Hypercholesterolemia
The National Choelsterol Education Program (NCEP II) gudelines
Now include postmenopausal status as CAD risk factor in the
Assessment for hyperlipidemia. Estrogen replacement therapy
Considered as athe initial/primariy therapy of hyperterolemia in
Postmenopausal women because of the efficacy and relatively low
Cost. It has complemented effects on the lipid profile when
Combined with statins statins should be given as initial therapy for hype
Lipdema in women with vascular disease.
Secondary Preventions
HRT should not be recommended to women with documented
CAD solely for cardio protection if noncardiac indications exist,
Hormone replacement may be prescribed but the inceased risk of
Venous trhomboembolism should be discussed. All other proved
Rx (aspirin, beta-blocker, statisn, ACE inhibitors used
Maximal.
Primary Preventions
Adeauate data to support widespreade use of estrogen replacement
Therapy in postmenopausal women for primary precaution of
CAD do not exist.