A L P E S H S H A H M D , F A C C , F S C A IT H E M E T H O D I S T D E B A K E Y H E A R T A N D V A S C U L A R C E N T E R
A P , W E I L L C O R N E L L M E D I C A L C O L L E G EA P , B A Y L O R C O L L E G E O F M E D I C I N E
D I R E C T O R , B R H S C A R D I A C C A T H L A B
CARDIO VASCULAR DISEASE IN WOMEN
FINANCIAL DISCLOSURE
• Medical Advisory Board: Abbott Vascular
• Consultant: Medtronic Inc
• Research grants: Abbott Vascular,
Medtronic Inc, GE imaging
CVD IS # 1 KILLER IN WOMEN
• Rates increasing in women between
30 and 54 years of age
• Obesity increasing (2 out of every 3 women>20 years overweight or obese)
GENDER BASED MORTALITY DIFFERENCE
Cardiovascular mortality among US women
has decreased dramatically each year since
2000; the 2007 cardiovascular mortality rate
in women represents a 43% reduction from
the 1997 rate
WOMEN ARE UNAWARE OF THE PROBLEM
STROKES
• Women have more strokes than men and
more strokes than CHD
• Hormone replacement, pregnancy etc.
contribute
• Women have more hypertension than
men at older age
• Risk factors are similar, outcomes however are worse in women
• Late referrals and delayed presentation
• Physicians not aggressive
• Atypical presentation
• more advanced CAD, older patients with more co morbidities
• Metabolic/ anatomical differences
• more urgent/emergent procedures
• Women comprise only 25% of participants in all heart-related research studies.
• More women than men die of heart disease each year, yet women receive only: • 33% of angioplasties/stents• 28% of implantable defibrillators• 36% of open-heart surgeries
MEDICAL CHALLENGES
RISK STRATIFICATION
NCEP ATP III guidelines:Age
HTN
Dyslipidemia
DM
Family history
smoking
• Classifies individuals into low, intermediate
(?indeterminate), high risk
• Uses Framingham risk score
• 2011 update recognized potential value of
hsCRP, CC score, CIMT
NON HDL-C/ TG
• LDL-C, VLDL-C, IDL-C,
Lp(a)cholesterol
• Non-HDL-C = Total cholesterol- HDL
cholesterol
• Non HDL-C goal is < 30mg above
LDL-C goal
• TG <150 mg
HDL-C
Current HDL-C Cut points
• NCEP ATP III: 40 mg/dL
• Metabolic syndrome criteria
(ATP III, IDF)
– Men <40 mg/dL
– Women <50 mg/dL
• AHA Women’s Cardiovascular Health
Guidelines:
50 mg/dL
• No treatment target for HDL-C as for
LDL-C
TREATMENT FOR LIPIDS
• Women with CHD, goals of treatment
LDLC<100 mg/dL, HDL-C >50 mg/dL, triglycerides<150 mg/dL,
and non-HDL-C <130 mg/dL;
• similar goals in women with other CVD or DM
• Aggressive control in women with recent ACS or
mulitple CV risk factors with CHD may require
LDL-C < 70.
• Drugs:
Statins
Fibrates
Niacin
Omega-3 fatty acids
Ezetimibe
Bile acid resins
HORMONES
CV risk is very low for women until
after menopause
Estrogen levels decrease at
menopause
Lipoprotein profile deteriorates after
menopause
HDL decreases
LDL increases
HRT improves lipoprotein profile
HRT lowers fibrinogen (surrogate
marker for CVD
HERS
observational studies had found lower rates of CHD in
women who take postmenopausal estrogen
2,763 postmenopausal women
average age 67
treated for approximately 4 years
estrogen/progestin combination or placebo
LDL cholesterol was reduced by 11%
HDL cholesterol was increased by 10%
HERS
the use of estrogen plus progestin in postmenopausal women with heart disease
did not prevent further heart attacks or death from CHD
HRT regimen was associated with increased the risk of DVT & PE
the results suggested an early acceleration of CV risk from HRT in these older
postmenopausal women with established CHD
The authors speculated that the HERS results may be explained by differences
in the effect of therapy over time
When they examined the results by year, they found that there was a trend
towards a higher risk for CHD events such as MI during the 1st year of therapy
but that this trend was reversed during the final two years.
By the end of the study, there was no significant difference in CHD risk
between the two groups
CURRENT HRT RECOMMENDATION
• Hormone therapy after menopause does not reduce the risk of
CHD and should not be used for primary or secondary CHD
Prevention
Hormone therapy after menopause increases rates of stroke
and venous thromboembolism
screening for stroke risk factors is advised before initiating hormones in all
postmenopausal women.
CHD events are increased by estrogen plus progestin
treatment in women with an intact uterus
the CV risk within the first 10 years after menopause is minimal
so one could consider HRT for postmenopausal vasomotor
symptoms, at the lowest effective dose for the least amount of
time
METABOLIC SYNDROME
GENDER DIFFERENCES IN METABOLIC DISEASE.
Central adiposity
• Prevalence of extreme obesity is increased in women compared with men
• Increased waist circumference in women increases risk of metabolic syndrome to a
greater degree than in men
Dyslipidemia
• Associated with a greater risk for coronary artery disease in women than in men
• Elevated triglyceride levels have a greater impact on coronary artery disease risk in
women than in men, especially when combined with low HDL levels
Hypertension
• Congestive heart failure is more commonly seen as a consequence of hypertension
in women than in men
• 'White coat hypertension' is more commonly reported in women than in men
Hyperglycemia
• Glucose levels after a glucose load are more commonly elevated than fasting
blood glucose in women; the opposite is found in men
EFFECTS OF HTN
SECONDARY HTN
DRUGS INDUCED HTN
TREATMENT OF BLOOD PRESSURE
• Therapy is indicated when BP ≥ 140/90 or ≥
130/80 in the setting of CKD and DM
• Initial therapy should include thiazide diuretics
unless special populations indicate special
therapies (Class I, Level of evidence A)
• *ACEI contraindicated in women who are
pregnant or may become pregnant
RENAL ARTERY SYMPATHETIC DENERVATION FOR REFRACTORY HTN CONTROL (SIMPLICITY)
Radiofrequency ablation BP change
-18 -23 -23 -25 -27-11 -10 -11 -12 -13
-40
-30
-20
-10
0
10
1 month(n=70)
3 months(n=64)
6 months(n=56)
9 months(n=40)
12 months(n=34)
Systolic
Diastolic
ASPIRIN
• Aspirin (75 mg to 325 mg) in women with CHD
• Aspirin (75 mg to 325 mg) in women with DM
• Can be used in women ≥ 65 yrs (81 mg daily or
100 mg every other day) if BP is controlled for
ischemic stroke and MI prevention (as long as
benefit outweighs risk of GI bleed or
hemorrhagic stroke) and may be reasonable for
stroke prevention (but not MI) in women < 65 yrs
PREGNANCY: CONTRAINDICATIONS
Pulmonary hypertension ~25%
mortality
Severe ventricular dysfunction
SVEF <30%, NYHA III/IV; residual PPCM
Severe Left Heart Obstruction
Symptomatic AS, MS, coarc
Dilated aortic root
Marfan (equivalents) AAo > 45 mm
BAV with Aao >50 mm (27/m2)
* Cyanotic heart disease: 85/90 Rule
Stress ECG
NONINVASIVE TESTING OPTIONS
Stress ECHOStress MPI/PET
EBCT/CTA MRI
DIAGNOSTIC ACCURACY OF EXERCISE ECG TESTING IN WOMEN
• Altered prevalence of disease1,2
• Reduced predictive accuracy in younger women2
• Potential factors affecting diagnostic accuracy1:• Hormonal influences
• Reduced functional capacity
• Resting ST-T wave abnormalities
• Comorbidities
1. Isaac D, et al. Can J Cardiol. 2001;17(suppl D):38D-48D.
2. Shaw LJ, et al. In: Charney P, ed. Coronary Artery Disease in Women: What All
Physicians Need to Know. Philadelphia, Pa: American College of Physicians.
1999:327-350.
Courtesy of Howard Lewin, MD, of San Vicente Cardiac Imaging Center.
Ultrasound performed
both at rest and during
peak stress
Exercise or other stress
Ischemia defined by
development of wall-motion abnormalities
STRESS ECHO
Courtesy of Jennifer H. Mieres, MD, NYU Medical Center.
Exercise or pharmacologic stress
vs rest
Myocardial accumulation of
radioactivity in proportion to
blood flow
Ischemia defined by diminished
perfusion during stress vs rest
Stress
Rest
Stress
Rest
Stress
Rest
Stress
Rest
NUCLEAR STRESS TEST
HOW IS CARDIOVASCULAR DISEASE PRESENTATIONDIFFERENT IN WOMEN?
• Chest tightness, pressure,
burning and squeezing of the
chest
• Discomfort in one or both
arms, shoulders, neck, jaw,
stomach or back
• Shortness of breath
• Fatigue, cold sweats, nausea,
weakness
• Pain in upper back, jaw or
neck
• Shortness of breath
• Flu- like symptoms, nausea
or vomiting, cold sweats
• Fatigue or weakness
• Feeling of anxiety, loss of
appetite, discomfort
Typical Heart Attack
Warning Signs
Less Typical Symptoms Of
Heart Disease In Women
GAPS IN DIAGNOSIS AND TREATMENT
Prevalence of Coronary Heart Disease (CHD)
M 52%: W 48%
Diagnostic Procedures
(Diag. catheterizations & Non-invasive Tests)
M 55%: W 45%
CABG
M 73%: W 27%PCI
M 61%: W 39%
Medical Management
Only
M 47%: W 53%
PCI / STENTS
Expandable metal mesh tubes that buttresses the dilated segment, limit
restenosis.
Drug eluting stents: further reduce cellular proliferation in response to
the injury of dilatation.
STENT
Bare metal stent Drug eluting stent
32
STENT FEATURE MATRIX
Bare-Metal
Stents
Drug-eluting
Stent
Bioabsorbable
drug- eluting
Stent
Reduced Dual-
Antiplatelet Therapy
No neointimal
hyperplasia
Restoration of
Vasomotion
Material
(Biocompatible)
• Only 33% of PCI are performed in women annually
• Delayed treatment with PCI in women is common
• Often >24 hours after presentation
• Women continue to be underrepresented in clinical
trials of percutaneous coronary intervention
• They don’t meet inclusion criteria!!!• Get there late
• More risk factors: older, worse renal function
• Sicker on presentation
Blomkalns AL et al. J Am Coll Cardiol 2005;45:832-37, Lee et al. JAMA.
2001;286:708-713, Harris DJ et al. N Engl J Med 2000;343(7):475-480, Simon V. Science 2005;308(5728):1517.
PCI
PCI PROCEDURE RELATED CHALLENGE
• Higher bleeding complication , especially access site
• Contemporary subacute or late thrombosis rates are similar between genders, 1.3% vs 1.2%, p=NS
• Women are 61% more likely to present with in-stent restenosis following stents, particularly diffuse in-stent restenosis
• 1.9x more women will return to the ER within 30 days of their intervention even after successful interventions
• 38% of women and 25% of men will die within one year of a first recognized heart attack.
• Complex anatomy, small vessels
• More recent data suggests no difference in death, MI, and emergent CABG but continued increased risk of morbidity, particularly bleeding
• Improved PCI mortality over time in both men and women
CLINICAL OUTCOMES DURING PCI BY GENDER (ACUITY TRIAL)
Women
(N=2091)
Men
(N=5698)P-value
30-Day Major Bleeding
10.7% 4.2% <0.0001
1-Year Composite Ischemia
19.6% 18.5% 0.27
1-Year Mortality 3.5% 3.1% 0.31
PERCUTANEOUS ACCESS(FEMORAL, RADIAL, BRACHIAL)
37
RADIAL APPROACH IS STILL ASSOCIATED WITH MORE BLEEDING IN WOMEN
• 1348 ACS patients pretreated with ASA, clopidogrel→ radial PCI using 70 u/kg uFH and abciximab
(EASY trial of early discharge)
Women Men p valueSheath size – 5F
– 6F
57%
43%
44%
55%
0.0003
Hb drop 1.7% 0.4% 0.059
Hematoma 22% 5.8% 0.001
Final ACT (sec) 322 308 0.003
AHJ 2009; 157:740
TREATMENT OF WOMEN WITH ACUTE CORONARY SYNDROME
• Less likely to have an ECG done within 10 minutes of presentation
• Less likely to be cared for by a cardiologist during their inpatient admission
• Less likely to acutely be given appropriate pharmacotherapy such as heparin, aspirin, statins, ACE-I
• longer DTB times in STEMI cases
LESS OFTEN RECEIVE GUIDELINE RECOMMENDED THERAPY BUT WOULD SIGNIFICANTLY BENEFIT FROM AN EARLY
AGGRESSIVE INVASIVE STRATEGY
AMI in Women: Later Presentation and Delay in Treatment
- CADILLAC Primary PCI Trial-
Men Women
P
Value
N
Chest pain to ER (hrs)
ER to procedure (hrs)
Stent use
Abciximab use
1520
2.6 ± 2.5
1.9 ± 2.2
57%
54%
562
3.0 ± 2.6
2.1 ± 2.3
57%
51%
-
< 0.001
< 0.001
NS
NS
PRIMARY PCI IS SUPERIOR TO LYTICS IN WOMENMETA-ANALYSIS - 23 RANDOMIZED TRIALS (PCAT-2)
9.6
14.4
5.3
7.17.7
8.5
3.5
4.9
0
2
4
6
8
10
12
14
16
≤ 2 hrs > 2 hrs ≤ 2 hrs > 2 hrs
30
-Da
y M
ort
ali
ty
Lytic
Primary PCI
Women Men
Singh M et al. J Am Coll Cardiol 2008; 51:2313-2320.
PCI MORTALITY COMPARISONS BY ERA AND GENDER
Group 30-d mortality,
1979–1995 (%)
30-d mortality,
1996–2004 (%)
P value
Women 4.4 2.9 0.002
Men 2.8 2.2 0.04
ABSORB III
EXCEL (LEFT MAIN STENT VS. CABG)
Demonstrating in subjects with ULMCA disease
(either isolated to the left main trunk or associated with
disease in other coronary arteries)
that compared to CABG, treatment of the left main stenosis other significant coronary lesions with the XIENCE PRIME or XIENCE V
stent will result in
non-inferior or superior rates of the composite measure of all-cause mortality, MI or stroke at an anticipated
median follow-up duration of 3 years
MANY WOMEN WITH ANGINA HAVE NON-OBSTRUCTIVE CAD
• 57% of women presenting with chest pain or suspected myocardial ischemia had non-obstructive CAD (<50% stenosis)
• An analysis of 673 WISE patients showed 46% with non-obstructive CAD had persistent chest pain (PChP) at 1 year follow-up
• More intense symptoms at baseline
• Younger (mean 54 years)
• Lower functional capacity
• More comorbidities
• Depression and lower QOL
% of Patients with Persistent
Chest Pain (PChP) at 1 Year
WHAT IS MICROVASCULAR DISEASE?
• Dysfunction in small coronary arterioles <500 microns in diameter
• Main determinants of vascular resistance
• Major etiological factor for ischemic heart disease in women
• Potential precursor of obstructive CAD
• 2-3 million women with microvascular coronary dysfunction in the U.S.
• ~90,000 new cases annually
INDICATIONS FOR SURGERY(GENERAL)
• Left main disease
• three-vessel disease
• two-vessel disease with proximal LAD
lesion
• significant left ventricular impairment
with
multi-vessel disease
• Diabetes?
• Failure of medical/PTCA
management
WOMEN AND CABG
• Increased transfusion rate
• Increased need for urgent surgical
intervention
• Older age at operation
• Diffuse disease process?
• More advanced symptoms of CHF
• More postop admissions for CHF and
unstable
angina
SURGICAL OPTIONS
ALOHA: SAY FAREWELL TO HEART DISEASE
Assess and stratify women into high, intermediate, lower, or optimal risk categories.
Lifestyle approaches (smoking cessation, regular exercise, weight management, and heart-healthy diet) to prevent CVD—should be recommended for all women and a top priority in clinical practice.
Other CVD risk-reducing interventions should be prioritized on the basis of strength of recommendation. Lifestyle, which is a top priority for all women.
Highest priority for risk intervention in clinical practice is based on risk stratification (high risk > intermediate risk > lower risk > optimal risk).
Avoid interventions designated as Class III: antioxidants, hormone replacement, and aspirin for women at low risk.
AHA Guidelines: CV Prevention in Women
Mosca et al. Circulation. 2004;109:158-160.
“NO DIFFERENCE? R U KIDDING ME?”
A L P E S H S H A H M D , F A C C , F S C A IT H E M E T H O D I S T D E B A K E Y H E A R T A N D V A S C U L A R C E N T E R
A P , W E I L L C O R N E L L M E D I C A L C O L L E G EA P , B A Y L O R C O L L E G E O F M E D I C I N E
D I R E C T O R , B R H S C A R D I A C C A T H L A B
CARDIO VASCULAR DISEASE IN WOMEN
