cad in women
TRANSCRIPT
2016
Phoebe A. Ashley, MD, FACC
VCU Pauley Heart Center
CAD in Women:
Is There Really a
Difference?
Disclosures
• None
Mrs. J.. J56 year old woman• Diabetes
• High Blood Pressure
• High Cholesterol
• Depression
Presents with throat tightness at 1:30 pm
“You have a cold, wait here”
In Radiology at 8:00 pm . . .
The Resuscitation Room . . .
The Rest of the Story . . .
• Status-post a successful intervention of
the right coronary artery.
• Moderately reduced ventricular function
with chronic congestive heart failure
Agenda
• The Truths
• Women Are Not Simply Small Men
• Pathophysiology
• Risk Factors
• Clinical Presentation
The Truths
1.
Coronary Artery Disease in
Women: More to Think About
The Risk
• Coronary Artery Disease:
#1 cause of death
in women and men
in America and in most
industrialized nations
• Stroke:
#4 cause of death
of Americans
The Magnitude of the Problem
• CVD is the leading cause of mortality, morbidity for US women– 1 of 4 US women die from CVD
– Annual CVD morality 2x that of all forms of cancer combined
• An estimated 43 million women in the U.S. are affected by heart disease
• 90% of women have one or more risk factors for developing heart disease
• Despite increases in awareness over the past decade, only 54% of women recognize that heart disease is their number 1 killer
Mosca L, Circulation: Cardiovascular Quality Outcomes 2010
Women and Heart Disease
• Coronary heart disease remains understudied, under diagnosed, and undertreated in women
• Equal prevalence of this disease between the sexes by the age of 40; by the age of 60 more women than men are affected
• Since 1984, the annual CVD mortality rate has remained greater for women than for men
• Almost two-thirds (64%) of women who die suddenly of coronary heart disease have no previous symptoms
Mozaffarian, et al Circulation 2015
Gholizadeh, et al Health Care Women Int 2008
Roger Vl, et al. Circulation 2012
Sex Differences
• Regardless of age, more women than men
die in the first year following an MI (26% vs
19%)
• Within 5 years of a first MI more women will
die (47% vs 36%)
• More women suffer from heart failure
following their first MI (46% vs 22%)
• Women have a higher prevalence of DM, HF,
HTN, depression, and renal dysfunctionMozaffarian, et al Circulation 2015
Cardiovascular Disease Mortality
Trends U.S. 1979-2011
Mozaffarian D et al. Circulation. 2015;131:e29-e322
Our Risk
• Risk of death increases progressively in
older women . . .
Especially after the age of 45 !
• Many heart attacks go unrecognized,
particularly in younger women
Risk Factors at Presentation
0% 20% 40% 60% 80% 100%
Diabetes
Dyslipidemia
Smoking
Obesity
HTN
Men
Women
Dreyer, et al Eur Heart J ACC 2015
Co-morbidities on Presentation
0% 10% 20% 30% 40% 50% 60%
CHF
Renal dysfunction
Lung Disease
CVA/TIA
Cancer
Depression
Men
Women
Dreyer, et al, Eur Heart J, ACC 2015
Young Women with Acute
Myocardial Infarction
• Have more risk factors and more serious
disease than men
• Have more stress, poorer functioning, and
more depression than men
Dreyer, et al Eur Heart J ACC 2015
The Presentation
• Women more commonly present with
NSTEMI and non-obstructive CAD
• Women are more likely to have an unusual
pathophysiologic mechanism of CAD
– Spontaneous coronary artery dissection
(SCAD)
– Coronary artery spasm
Hochman, et al NEJM 1999, Hochman, et al JACC 1997, Hasdai, et al AJC 2003,
Bellasi, et al Cleve Clin J Med 2007, Merz, et al JACC 1999, Basso, et al Heart
1996, Demaio, et al AJC 1989, Thompson, et al J Inv Cardiol 2005, Selzer, et al
NEJM 1976
After Revascularization . . .
• Longer hospitalizations
• Higher in-hospital mortality
• More bleeding complications
• 30% more readmissions within 30 d
following their index hospitalization
• Women fail to participate in cardiac rehab
due to significant patient-oriented
biopsychosocial barriersDolor, et al Effective Health Care Program: Comparative Effectiveness Review 2012, Anderson, et al
Circulation 2012, Ahmed, et al Circulation 2013, Poon, et al Am Heart J 2012
The Research
• Women were not enrolled in cardiovascular trials until 1993
• Today women comprise only 24% of participants in all heart related research studies
• Gender specific research is needed to optimize the recognition and treatment of women with heart disease
Challenges in Women
• Delays in symptom recognition and delays in treatment
• Misdiagnoses
• Lower use of angiography, revascularization, aspirin, beta blockers,
statins, and ACE inhibitors*
• Less counseling on risk factor control
• Fewer referrals to cardiac rehab and more “drop-outs”
• Lower adherence to proven guidelines (ACC/AHA, JNC VII, NCEP,
etc)
*Associated with 90% reduction in recurrent major adverse cardiac
events
MORTALITY
Women Are Not Simply
Small Men
2.
The Size Difference
• Our hearts and arteries are proportionately
smaller
Plaque Development in Women is
Often Different
Smooth Lumpy
Coronary Artery Disease
WOMEN• Unstable angina/NSTEMI
• Plaque Erosion
• Microvascular Disease*
• Endothelial Dysfunction*
• Fewer Collaterals
• Single vessel Disease
• More:
• Diabetes
• Dyslipidemia
• Metabolic Syndrome
MEN• MI/Sudden Cardiac Death
• Plaque Explosion
• Epicardial Disease
• Collaterals
• Multi-vessel Disease
• More:
• Smokers
• Hypertension
Pregnancy: A Woman’s First Stress
Test
• Detailed pregnancy history is integral component of risk
assessment for women
• Pregnancy complications: pre-eclampsia, gestational
DM, pregnancy-induced HTN, preterm delivery=early
indicators of CV risk
• Pre-eclampsia, gestational HTN CVD risk
– 3-6x subsequent HTN
– 2x ischemic heart disease, CVA
– Residual endothelial dysfunction, association with CAC
Mosca, Circulation 123:1243, 2011, Fraser, Circulation 125:1367, 2012, Wenger, Am J Cardiol 113:406, 2014, Bellamy, BMJ 335:974, 2007
Ahmed, J Am Coll Cardiol 63:1815, 2014
Pregnancy: A Woman’s First Stress
Test
• Cardiovascular, metabolic stress of
pregnancy potential for early prediction
of future CV risk
• Gestational DM 7x risk of Type 2 DM
Mosca, Circulation 123:1243, 2011, Fraser, Circulation 125:1367, 2012, Wenger, Am J Cardiol 113:406, 2014, Bellamy, BMJ 335:974, 2007 Ahmed, J Am Coll Cardiol
63:1815, 2014
As We Age
• Women’s hearts shrink with age
• Men’s hearts typically grow with age with
increasing ventricular mass
• Ventricular volume decreases in both
sexes, but more precipitously in women
• Increased LV mass associated with higher
blood pressure, increased BMI, and lower
HDL levels
Lima, et al Radiology 2015
Pathophysiology
3.
Universal Classification of MI
Thygesen et al. Third Universal Definition of Myocardial Infarction Circ 2012
Underlying Etiologies of MI
Thygesen et al. Third Universal Definition of Myocardial Infarction Circ 2012
Thrombotic Coronary Occlusions
1. Plaque Rupture
Most common
76% of men 55% of women with fatal MI1
Rare in premenopausal women2
2. Plaque Erosion
Common in younger women3
3. Calcific Nodule
Accounts for ~2-7% of thrombosis in STEMI4
7-32% of women with MI have no angiographicallydemonstrable obstructive CAD (>50%)5, 6, 7, 8
1 Falk, et al EurHeart J 2013, 2 Davies Heart 2000, 3 Farb, et al Circulation 1996,
4Virmani, et al Arterioscler Thromb Vasc Biol 2000,5 Hochman, et al JACC 1997,
6Chokshi, et al Clin Cardiol 2010, 7Berger, et al JAMA 2009, 8Gehrie, et al Am Heart J
2009
Ischemic Heart Disease
Different Types of Vulnerable
Plaque
Scientific Figure on ResearchGate. Available from:
https://www.researchgate.net/figure/259447500 accessed 1/29/16
Plaque Erosions
• Absent or denuded endothelium overlying a plaque
• Downstream microembolization focal myocardial necrosis
• More smooth muscle and proteoglycans, no necrotic core, denuded endothelium leading to thrombosis
• Common cause of ACS
• More likely to be fatal in young women in autopsy studies of MI and SCD
Jia H et al, JACC 2013; Farb A et al, Circulation 1996, Guagliumi et al JACC Intv 2014
Cited in Yamashita A, Asada Y -
J. Biomed. Biotechnol. (2010),
with permission from Sato et al
Coronary Microvascular Disease
• NOT just a small vessel disease problem
• Diffuse atherosclerosis
– Non-obstructive plaque in epicardial vessels
– Abnormal coronary vasoreactivity
– Subendocardial and epicardial ischemia
• More common in women
• Prognosis is poor in women and men
• Multimodality imaging is often required for diagnosis and to guide management
Shaw, LJ, ACC 2013
Ms. F
• 39 y/o female waitress with no known CRFs aside
from stress presents with substernal chest pressure
which developed while at work and was associated
with n/v
• Exam: (-)
• ECG: Normal
• Troponin T: 0.03, 0.09, 0.06
• Angiography: “Ulcerated RCA plaque”
• Severe coronary vasospasm
• Complicated PCI with DES placed in the RCA
3 months later . . .
• Recurrent chest pressure and diaphoresis
• ECG: normal
• Coronary angiography
Coronary Angiography
Spontaneous Coronary Artery Dissection
SCAD
• Should be suspected in any young women without typical atherosclerotic risk factors
• Prevalence– 0.2-4% of patient’s undergoing cardiac cath
– 10.8% in women <50 with ACS or AMI
– ~ 80% women
– ~20% peripartum
• Associated with:– Pregnancy and postpartum status
– Oral contraceptive use
– Exercise
– Connective tissue disorders and vasculitides (including fibromusculardysplasia)
• Familial cases
• STEMI 49%, multi-vessel disease 23%
Vanzetto, et al Eur J Cardiothorac Surg 2009, Nishiguchi, et al Eur Heart J Acute Cardiovasc
Care 2015, Alfonso, et al JACC Cardiovasc Interv 2012, Tweet, et al Circulation 2012,
Michelis JACC 2014, Saw, et al JACC Cardiovasc Interv 2013
SCAD Management
• Diagnosis challenging
• Index of suspicion: young women with no risk factors and no plaque
• Tortuous coronary arteries
• Excess complications with intervention
• Dissection: healing without intervention 60%
• Recurrence: 21% in 10 years
• Survival: >atherosclerotic ACS: 93% at 10 years
Tweet, et al, Circulation 2012; Lettieri, AJC 2015
Coronary Spasm
• May contribute to MI
with or without
atherosclerosis
• Thrombosis likely
plays a role
• With or without
antecedant
vasospastic angina
• Difficult to prove
Coronary Artery Spasm
Medical Treatment Varies
Dependent Upon the ACS Type
ACS
• Plaque Rupture
• Erosion
• Dissection
• Spasm
TREATMENT
• DAPT + statin
• DAPT + statin (?)
• DAPT, no statin
• DAPT + statin + CCB
+ Nitrate
Beta Blocker and ACEI/ARB, dependent upon left
ventricular function
DAPT = Dual antiplatelet therapy CCB= Calcium channel blocker
Risk Factors
4.
Risk Factors
Non-modifiable versus Modifiable
Your #1 Risk Factor:
Family History of Premature Heart Disease
Father with
Heart Disease < age 55
Mother with
Heart Disease < age 65
Need comparable
photo of a man
Non-modifiable Risk Factors
SEX
Non-modifiable Risk Factors
AGE
What About Menopause?
Estrogen
Weight &
Blood
Pressure
HDL
LDL &
Triglycerides
Risk Factors That Can Be Modified
• Diabetes/Glucose Intolerance
• Tobacco
• High Blood Pressure
• Hyperlipidemia
• Obesity
• Metabolic Syndrome
• Obstructive Sleep Apnea
• Lack of Exercise
• Drug Use
• Dental Disease
• Newer Modifiable Risks
– Hostility/Anger
– Stress
– Anxiety/Depression
What’s the Risk of Heart Disease
for People with Diabetes?
For Men:
2-3 times greater
For Women:
4-6 times greater
Tobacco Use
• > 50% of heart attacks in middle-aged women are attributed to tobacco use– Cigarette smoking triples
the MI risk in women
– 25% increased coronary risk among women smokers than men smokers
• Even minimal use elevates risk
• Leads to early menopause
Huxley, et al Lancet 2011
Mrs. B
46 year old woman
Cardiac Risk Factors:
• None
Symptoms:
• Intermittent chest discomfort
– Mid to left side
– Occurs with exertion and at rest
90% Blocked
with Plaque
Mrs. B’s
Coronary Angiogram
• Status post single vessel coronary artery
bypass grafting
• Subsequently diagnosed with high
cholesterol
The Rest of the Story . . .
Hyperlipidemia:
High Cholesterol
The “GOOD” (HDL)
The “BAD” (LDL)
The “UGLY” (Triglycerides)
High Density Lipoprotein:
HDL = Good Cholesterol
Low HDL is BAD
Low Density Lipoprotein:
LDL = Bad Cholesterol
• Better predictor of coronary
artery disease in men than
in women
• Plateaus in men after age 50,
continues to rise in women until at least
age 65
Triglycerides=Ugly
• Underestimation of the association between TG and
disease in a multivariate analysis
• Individual genetic susceptibility may play an important
role in the relationship between plasma TG levels and
CVD
• 76% increase in CVD risk in women
• 31% increased CVD risk in men
(Associated with 1 mmol/L increase in TG levels)
Austin Can J Cardiol. 1998
Ms. P.
• 40 y/o female with hyperlipidemia,
impaired fasting glucose, and elevated
blood pressure is referred for atypical
chest pain.
• SHx: single mother, working fulltime,
nonsmoker, no alcohol or drug use
• ECG: lateral TW inversions
The Rest of the Story . . .
• 95% left circumflex
lesion
• 40% LAD disease
• Small RCA
Characteristics of Metabolic Risk
• Central Obesity
• Insulin Resistance
• Dysproteinemia
• Hypertension
Metabolic Syndrome and CV Risk
• Even in the absence of CVD and diabetes,
individuals with metabolic syndrome have
a significantly higher risk of CAD and all
cause mortality Hu, et al 2004
Ms. Z
• 48 y/o PMP female with RA
• Meds: Prednisone, MTX, Plaquenil
• ECG: RBBB, cannot rule out IMI
• BNP 54, RA 596
• CXR: lung nodule
• CT: incidental coronary artery calcification
Female:Male Ratios in Autoimmune
Diseases• Hashimoto’s thyroiditis 10:1
• Systemic lupus erythematosus 9:1
• Sjogren’s syndrome 9:1
• Antiphospholipid syndrome-secondary 9:1
• Primary biliary cirrhosis 9:1
• Autoimmune hepatitis 8:1
• Graves’ disease 7:1
• Scleroderma 3:1
• Rheumatoid arthritis 2.5:1
• Antiphospholipid syndrome-primary 2:1
• Autoimmune thrombocytopenic purpura 2:1
• Multiple sclerosis 2:1
• Myasthenia gravis 2:1
What is Ms. Z’s risk for Acute MI?
• The odds ratio for AMI:
• RA 1.48
• SLE 2.67
• RA patients have a 59% increase in CAD mortality
• Other disorders to consider:
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Giant Cell ArteritisAARDA, American Autoimmune and Related Diseases Association
Others: Psoriatic Arthritis Ankylosing Spondylitis Giant Cell Arteritis
https://www.aarda.org/autoimmune-information/autoimmune-disease-in-women/ Accessed Nov 29, 2015
Avina-Zubieta JA, Ann Rheum Dis 2012;71:1524-9 Fischer LM, Am J Cardiol. 2004;93(2):198
Cardiac Involvement in
Inflammatory Joint Disease
Nurmohamed, M. T. et al. (2015) Rheumatol. doi:10.1038/nrrheum. Manzi, S. et al. Am. J. Epidemiol. 145, 408–415 (1997)
Paradoxic Effect of Traditional RFs
in RA
• The higher the BMI, the better the survival
• Active inflammation in RA decline in
levels of TC, LDL-C, and HDL-C
compared to individuals without RA
– Lower lipid levels
– Altered lipid structure and function
– Antiatherogenic effects of HDL-C become
proatherogenic
The Emotional Side of
Heart Disease
5.
Stress and Your Heart
How Does Stress
Contribute to Heart Disease ?
Blood Pressure Increases
Cholesterol Increases
Tendency to Overeat
Exercise Less
Smoke, Drink, Take Drugs
Stress Makes
Other Factors Worse
Can cause persistently
elevated levels of
stress hormones
• Adrenaline
• Cortisol
Effects of
Chronic Stress
Changes the way
blood clots, increasing
risk of heart attack
Psychosocial Stress
• Women have higher levels of psychological risk factors such as – Early life adversity
– Post-traumatic stress disorder
– Depression.
• Women are more prone to develop mental problems as a result of stress
• Socioeconomic and psychosocial factors seem to have a higher impact on CAD in women
• Emotional or psychological stress potentially contributes to heart disease in many ways, from influencing heart disease risk factors, to affecting the development of atherosclerosis (hardening of the arteries), to triggering heart attacks
• Young women are especially vulnerable to the negative effects of stress on the heart, which may result in earlier onset of heart disease or more negative health outcomes if the disease is already present
Dreyer, et al Eur Heart J ACC 2015
Vaccarino, et al Psychomed Som 2014
Myocardial Infarction and Mental
Stress Study
• Women 50 years or younger had twice the rate of mental
stress induced myocardial ischemia (52 percent versus
25 percent)
– This gender difference was not seen in men and
women over age 50.
Vaccarino, et al Psychomed Som 2014
Marital Stress vs Work Stress
• Marital stress predicts poor prognosis in women aged 30
to 65 years with CHD
• Marital stress was associated with a 2.9-fold increased
risk of recurrent events after adjustment for age,
estrogen status, education level, smoking, diagnosis at
index event, diabetes mellitus, systolic blood pressure,
smoking, triglyceride level, high-density lipoprotein
cholesterol level, and left ventricular dysfunction
• Among working women (n = 200), work stress did not
significantly predict recurrent coronary events
Orth-Gomér, et al JAMA 2000
Depression
• Depression was shown to be an independent risk factor and consequence of CAD
• Depression may be a component of the increased risk of younger women following both MI and CABG procedures 32,44
• Depressive symptoms predicted CAD presence in women aged ≤ 55 years, but not in men aged ≤ 55 years or women aged >55 years.
• Depressive symptoms also predicted increased risk of death in women aged ≤ 55 years, but not in men aged ≤ 55 years and women aged >55 years
Möller-Leimkühler World J Biol Psychiatry2008
Shah, et al J Am Heart Assoc. 2014
Anxiety
• 2280 patients followed for 32 years
• Those with modest anxiety had a 5 fold increased incidence of sudden cardiac death
• Younger adults with ACS with feminine gender are at increased risk of recurrent ACS over 12 months independent of female sex, thought possibly related to increased anxiety
Kawachi et al, Circulation 1994
Pelletier, et al JACC 2016
Stress Mastery
• Change your environment
• Change how you respond to your
environment
Symptoms of Heart
Disease
6.
Professor D.
61 y/o woman
• Cardiac Risk Factors
– Hypertension
– Newly diagnosed high cholesterol
• Symptoms
– Shortness of breath with exertion
– Increasing fatigue
The Widow Maker
Angina Pectoris
Chest Discomfort Equivalents
• Shortness of breath
• Profound fatigue
• Weakness
• Lightheadedness
• Nausea
• Sweating
• Altered mental sensorium
• Fainting
In the absence of chest discomfort
50% of women do not
have typical symptoms
• Extreme Fatigue
• Shortness of Breath
• Indigestion/Nausea
• Dizziness
• Sleep Disturbance50%
Summary
• Heart disease is the #1 killer of women
• Pregnancy and menopause have significant cardiovascular implications
• Women may experience angina in the absence of significant epicardial coronary disease
• Stress is a significant risk factor in women; young women are especially vulnerable to the negative effects of stress on the heart
Be Sure to Stop and Smell the Roses
Thank You