Heart Disease in Women

Women and Heart Disease:
What we know,
What we think we know, and
What we know we don’t know
Janice Preslar BS, NCT
Manager of Nuclear Cardiology

Why is Women’s Health Important?
• Women make up 51% of the population
• 58% of persons 65 years and older are women
• Women in the middle years (ages 45-64)
comprise the largest population
• 40% of the total American population
• 75% of all caregivers are women
• 2.3 M grandparents raising grandchildren
• 63% are women

Heart Disease is the No.1 Killer in
Women
• 1 in 4.6 women died of cancer vs. 1 in 2.6 died of CVD
• CVD caused about 1 death a minute among females
• >460,000 female lives in 2004
Chronic Lower
Respiratory
Diseases
Diabetes
Mellitus
Influenza and
Pneumonia
Cancer
Cardiovascular
Diseases

Awareness Gap
• 31% identified heart disease or stroke as the leading
cause of death
• 73% -- risk of developing HD by age 70 was

CV Mortality Trends

Why the Disparity?

Time to Treatment
• Women wait longer than men to go to the ED
when having an ACS
• Physicians are slower in recognizing ACS in
women than in men
• 66% of ED and critical care clinicians
• Primarily assessed for CP in persons with
suspected AMI

Different communication patterns
• Women are more likely to give full account of
symptoms whereas men tend to focus on what
is problematic
PAIN
Fatigue, dyspnea,
weakness, upset stomach,
hip pain, chest ache, etc.

Definitions are Faulty
• Normative standards for symptoms
of ACS were set in men

Chest pain symptoms
are less accurate and less precise
predictors of
obstructive CAD in women

Women and ACS
• Minority present with chest pain symptoms
• 30% of women with ACS reported CP
• More women present with constitutional symptoms
rather than chest pain
Milner et al, Am J Cardiol 1999; 84: 396.

Women with ACS
• 95% reported prodromal symptoms
• Unusual fatigue
• Sleep disturbance
• Shortness of breath
• Indigestion
• Anxiety
• Prodromal symptoms were the most important
predictor of acute coronary syndrome

67 yr. old female: Atypical CP
• Risk Factors:
DM,
FH of CAD,
Sedentary
Overweight

Rest
Stress
Lateral
Inferior Septal Anterior

Before
After

Implications
• More women are misdiagnosed and discharged
from ER
• More women have unrecognized AMI

Mortality after Unrecognized MI
Unrecognized MI
Recognized MI
Sheifer et al, Ann Intern Med 2001.

Chest pain symptoms
are less accurate and less precise
predictors of
obstructive CAD in women

Coronary Atherosclerosis
Bostrom et al, J Clin Invest 1993.

Obstructive Angiographic CAD

Nonobstructive CAD Rates in ACS Trials
Prevalence
Rate (%)
Anderson et al, Circulation 2007.

Nonobstructive Angiographic CAD
Escolar et al, Can Med Assoc J 2006.

Gender Differences in
Arterial Remodeling
Constrictive Remodeling
Expansive Remodeling

Gender Differences in
Arterial Remodeling
Nissen & Yock, Circulation 2001.

Women and CAD
• >50% of women (vs. 15% men) with chest
pain undergoing coronary angiography are
found to have normal or near normal
coronaries
• MPI false positive or real ?

“False-positive” myocardial perfusion scintigraphy findings
in patients with angiographically normal coronary arteries: 1
• 20 patients studied with chest pain, abnormal
exercise ECG, abnormal MPI, and normal
angiographic findings to examine the differences in
disease detection between three modalities
1. Verna E, et al. J Nucl Med. 2000;41(12):1935–1940.

False-Positive? 1
Reprinted with permission from Journal of Nuclear Medicine
1. Verna E, et al. J Nucl Med. 2000;41(12):1935–1940.

Event Rate in Patients with
“Nonobstructive CAD”
Bugiardini et al, Arch Intern Med 2006.

Event-free Survival from CV Events
by CAD and Persistent Chest Pain
*CAD defined as coronary stenosis ≥50%
in at least 1 major epicardial coronary artery
Johnson et al, Eur Heart J 2006.

Impact
• Many women with angina are told that they do
not have significant heart disease
• May lead to worse adverse outcomes as
diagnostic and treatment strategies are focused on
identification of “obstructive” CAD
• Offered no specific treatment other than
reassurance

Women and Coronary Symptoms
Ischemic mechanism
related to coronary microvascular or macrovascular
endothelial dysfunction

Abnormal Vascular Function
• Seen in 47% of women with “normal” or “near
normal” angiograms
• 59% who had abnormal vasomotor response to ACh
continued to have CP and developed CAD on follow-up
• Women with normal vasomotor response had complete
resolution of symptoms at follow-up

Abnormal Vascular Function
• Not well understood
• Plays a central role in genesis of symptoms and
ischemia in women
• More prevalent in women and so places a woman
at relatively higher risk than her male counterpart
for any amount of CAD

Mental Stress-Induced
Myocardial Ischemia
• Young et al (1991) -- mental stress - paradoxical
arterial vasoconstriction in diseased arteries.
• Patients with CAD often show an exaggerated
systemic response to stress.
• Hemodynamic changes with mental stress occur
suddenly as opposed to exercise.

Mental Stress-Induced
Myocardial Ischemia
• Known CAD, normal exercise or
adenosine stress nuclear test
• Hemodynamic Changes
• SBP: 130.1 ± 13mmHg to 190 ± 26mmHg
• DBP: 76.8 ± 5mmHg to 103.2 ± 12mmHg
• HR: 64.3 ± 9 bpm to 86 ± 14 bpm
• N=21 – 29% had mental-stress induced
reversible perfusion defect
Ramachandruni S et al, J Am Coll Cardiol 2006.

Women and Coronary Symptoms
• How can vascular dysfunction be tested?
Quantitative heart
blood flow at rest and
stress

Cardiac P.E.T.

Women and Coronary Symptoms
• Is vascular dysfunction in the absence of
flow limiting stenosis a treatment target?
• What treatment?

Aggressive Risk
Factor Modification
+
Exercise Training

Aggressive Risk
Factor Modification
Further Define Risks

• Framingham
Risk Stratification
Risk Scores
• Age
• LDL/Cholesterol
• HDL
• BP
• DM
• Smoker
= 10 year risk
Wilson et al, Circulation 1998.

Risk Stratification
• Limitations of Framingham score
• Based on white population
• Did not take family history into account
• 40% of women with a family history of early CAD
classified as low risk but had detectable coronary
calcium
• 12% had CAC >100, and 6% had CAC ≥ 400
• 32% had significant subclinical atherosclerosis and
17% ranked above the 90 th percentile

Risk Stratification
• Reynolds Risk Score
• Web based calculator that uses 6 questions relating to:
• Age
• Smoking status
• Systolic BP
• Total cholesterol
• High-density lipoprotein cholesterol (HDL)
• C-reactive protein
• Family history (mother or father having a myocardial infarction
before age 60 years)
• Similar for low and high risk groups but faired better
for intermediate risk groups.

10 Year Risk vs. Lifetime Risk
Lloyd-Jones et al, Arch Intern Med 2003.

Lifetime Risk
• Provide absolute risk assessment
• May be more easily understood by patients and
clinicians
• Help motivate lifestyle changes or behaviors

Lifetime Risk

Need to Consider Lifetime Risk
in addition to Short-Term Risk

Exercise
1/36.5 M hrs

How many miles would I have to
run ?
Sudden Death

Functional Capacity
• Exercise capacity is an independent predictor of the
risk of death and cardiac events among women and
men
• Functional capacity correlated well with outcomes
• 67% of deaths or MI in women occurred with DASI
scores

Exercise ECG Testing
• Developed and validated
using a male population

Nomogram of the Percentage of
Predicted Exercise Capacity for Age
Gulati et al, NEJM 2005.

Physical Inactivity
• Ranks second as the most important contributor to
population ill-health
• Ranks first as leading contributor to preventable illness and
morbidity in women and second in men
•Women are more likely
to lead sedentary lifestyles
than men
Population Prevalence (%)
40
35
30
25
20
15
10
Men
Women
5
0
2000 2003

Physical Inactivity
• Inactivity increases with age
• Physical activity declines rapidly with age during
adolescence, especially among females
• Among women age 18 and older, 40.6%
sedentary (have no leisure-time physical activity)
National Center for Health Statistics. Health 2006.

Risk Factors
Predictive Power Varies by Sex

Depression and CAD
45
40
35
Men
Women
30
Percent
25
20
15
10
5
0
or=60 years
Malik et al, Arch Int Med 2006.

Depression and CAD
• Strong predictor of adverse outcomes after ACS
• Associated with worse patient health status and higher
cost of care
• Direct mechanism vs. behavioral
• Physiology of depression (high sympathetic tone and high
platelet aggregability)
• Noncompliance with medications and lifestyle interventions

Rate of depression among
women with AMI under
the age of 60 was 40%

Social Support
• Associated with better survival after an AMI
• Does marital status confer similar social support
to men and women after AMI?

Marital Status ≠ Social Support
in Women

Marital Status and Survival after AMI

Women with CAD
• Depression screening is important, particularly
among young women
• Need to evaluate whether psychosocial
interventions for women after AMI can reduce
observed disparities in outcomes

AHA 2007 Guidelines for
CVD Prevention in Women

The Good News

Awareness of CVD in Women
50
45
40
Population (%)
35
30
25
20
15
Heart Disease/Heart Attack
Cancer (General)
Breast Cancer
10
5
0
1997 2000 2003
Year of Survey

Awareness of CVD in Women
• Suggest that efforts
to educate women
have been successful
Improved general awareness is associated with
greater personal awareness and increased
actions to lower CVD risk

Recent CV Mortality Trends
Rosamond et al, Circulation 2007.

AHA 2011 Guidelines for
CVD Prevention in Women
• Lowered threshold for “High Risk”-20% to 10%
• “Real World” vs. Clinical Trials
• Pregnancy complication
• Aspirin in DM
• DM control
• Statins / C-reative protein

Clinical Trials
• Many early trials mainly focused on men
• Now more women, oversampling of women,
mandating inclusion of specific % women by
NIH
• Get more sex-specific data and evidence-based
information
• Heart for Women Act – requiring gender
information

The Bad News

Translation of Knowledge
to Positive Behavior
• AHA-GWTG and CRUSADE Database
• Time from symptom onset to hospital presentation
Diercks et al, Am Heart J 2010; 160: 80-87.

Cardiac Rehabilitation
• Underused, particularly in women and the elderly
• Women were 55% less likely than men to
participate in cardiac rehabilitation

Physician Awareness
Fewer than 1 in 5 physicians knew that more
women than men die each year from CVD

Frequency of Use of Evidence-Based Medical
Therapy After Presentation to a Cardiologist
Medication Overall Male Female P
Antiplatelet 81% 84% 76%

CAD and Women
The Myth Still Exists

Sex Matters
• Every cell has a sex, so sex does matter
• Sex affects behavior and perception
• Sex affects health – different patterns of illness and
different life spans
• Dissimilar exposures, susceptibilities and responses to
initiating agents, variable responses to pharmacologic agents
Sex is an important basic human variable that
should be considered when designing and
analyzing studies in all areas and at all levels of
biomedical and health-related research

Gender-Based Disparities
• Since 1984, more women than men have died annually
from ischemic heart disease
• Women with IHD have more adverse outcomes
• Traditional disease management approaches that focus
on obstructive coronary stenosis often fail to identify
those women who are at risk

Gender-Based Disparities
• Expanding definition of the “typical” female
coronary disease pathophysiology and presentation
• Modify normative standards
• Educate patients and healthcare professionals

• Further Study is Needed to Define Sex
Differences in Atherosclerosis
• Poor understanding of the gender-specific
differences in presentation and prognosis of heart
disease
• Studies for Gender Based Management
Strategies
• Future research should publish both efficacy and
ADR by gender

Application of proven interventions
in day to day practice

Her Future

The New Face of Heart Disease