Evidence based management of cardiovascular disease in women

Evidence Based Management of Evidence Based Management of Cardiovascular Disease in WomenCardiovascular Disease in Women

Karol E. Watson, MD, PhD, FACCKarol E. Watson, MD, PhD, FACC

Co-director, UCLA Program in Preventive CardiologyCo-director, UCLA Program in Preventive CardiologyAssociate Professor of Medicine/Cardiology Associate Professor of Medicine/Cardiology

David Geffen School of Medicine at UCLADavid Geffen School of Medicine at UCLA

Karol E. WatsonKarol E. Watson

Disclosure of Financial RelationshipsConsultant: Genentech, Genzyme

Clinical Trials Adjudication Committee: Merck

CV disease: Leading cause of death CV disease: Leading cause of death in Americansin Americans

0

100

200

300

400

500

A Total CVD*B Cancer D Chronic lower respiratory diseases

C Accidents

433,825

288,768

69,257 60,71334,301

493,623

268,503

64,10338,94841,877

Deaths(1000s)

*CHD, stroke, HF, hypertension, arterial diseasesData compiled for 2002

Men

Women

F Alzheimer’s Disease E Diabetes

CDC/NCHS and NHLBI.

A B C D E A B C F E

Cardiovascular Disease: Leading Cause of Cardiovascular Disease: Leading Cause of Death in WomenDeath in WomenCardiovascular Disease: Leading Cause of Cardiovascular Disease: Leading Cause of Death in WomenDeath in Women

0000

100100100100

200200200200

300300300300

400400400400

500500500500

600600600600

Total CVDTotal CVDTotal CVDTotal CVD Chronic Chronic Obstructive Obstructive Pulmonary Pulmonary

DiseaseDisease

Chronic Chronic Obstructive Obstructive Pulmonary Pulmonary

DiseaseDisease

Diabetes Diabetes MellitusMellitusDiabetes Diabetes MellitusMellitus

CancerCancerCancerCancer Pneumonia Pneumonia and Influenzaand InfluenzaPneumonia Pneumonia

and Influenzaand Influenza

502,938502,938502,938502,938

258,467258,467258,467258,467

53,04553,04553,04553,045 47,16547,16547,16547,165 34,44934,44934,44934,449

Breast cancerBreast cancer41,94341,943

Breast cancerBreast cancer41,94341,943

Deaths in Deaths in ThousandsThousandsDeaths in Deaths in

ThousandsThousands

United States: 1997 MortalityUnited States: 1997 MortalityUnited States: 1997 MortalityUnited States: 1997 Mortality

2000 2000 Heart and Stroke Statistical UpdateHeart and Stroke Statistical Update , American Heart Association., American Heart Association.2000 2000 Heart and Stroke Statistical UpdateHeart and Stroke Statistical Update , American Heart Association., American Heart Association.

Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women--2011 Update: A Guideline

From the American Heart Association

L. Mosca et al. Circulation. 2011 Feb 16.

• Reducing atherosclerosis

• Preventing plaque rupture

• Limiting thrombosis

Prevention of CHD:Prevention of CHD:

Severe obstruction (angina, no rupture) vs Severe obstruction (angina, no rupture) vs mild obstruction (no angina, likely to rupture)mild obstruction (no angina, likely to rupture)

RevascularizationAnti-anginal Rx

Exertional angina• (+) ETT

Severe fibrotic plaque• Severe obstruction• No lipid• Fibrosis, Ca2+

Pharmacologic stabilizationEarly identification of high-risk?

Plaque rupture• Acute MI• Unstable angina• Sudden death

Vulnerable plaque•Minor obstruction•Large lipid pool•Thin fibrous cap

Courtesy of PH Stone, MD.

Typical Angina Atypical Angina

Age Women Men Women Men<40 13 21 4 4

40-49 20 42 7 15

50-59 32 60 12 31

60-69 42 72 18 38

70-79 53 77 31 48

>80 65 84 35 50

Women n=19,761Men n=23,868

ACC – NCDR: ACC – NCDR: CAD Prevalence in Diagnostic CatheterizationCAD Prevalence in Diagnostic Catheterization

WISE: Landmark study in womenWISE: Landmark study in women

Goals:• Improve diagnostic testing for ischemic heart

disease in women• Study pathophysiologic mechanisms for ischemia in

the absence of epicardial coronary artery stenoses• Evaluate the influence of menopausal status and

reproductive hormone levels on diagnostic testing results

Bairey Merz CN et al. J Am Coll Cardiol. 1999;33:1453-61.

Prospective cohort study conducted at 4 US sites

AA BB

CC

AA BB

CC

V3016V3016

Source: WISE – Unpublished data – S. Nissen

Negative Remodeling

Positive Remodeling

WISE: Persistent chest pain in WISE: Persistent chest pain in women predicts future CV eventswomen predicts future CV events

Johnson BD et al. Eur Heart J. 2006;27:1408-15.

With CADHR 1.17 (0.76–1.80)P = 0.49

Without CADHR 1.89 (1.06–3.39)P = 0.03

Event-freesurvival (%)

Years from PChP diagnosis (at one year)

0.7

0.6

1

0.9

0.8

0 1 2 3 4 5 6

Neither PChPNo CAD

No PChPCAD

Both

n = 673 WISE participants with chest pain at baseline

PChP = persistent chest pain

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

• Plaque erosion and Plaque erosion and thrombus formation 2x thrombus formation 2x likely in women (men likely in women (men have more plaque have more plaque rupture)rupture)

• Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below), leading to more acute coronary syndromes(unstable angina) and non-Q MI in women,making diagnosis more difficult and leading to delays in treatment.

Gender Differences in Atherosclerosis

NEJM 1999

Panting JR. New Engl J Med 2002; 346: 1948-53.

Con

trol

Syn

dro

me -X

Rest Stress

Perfusion CMR in Cardiac Syndrome-XPerfusion CMR in Cardiac Syndrome-X

• Women with chest pain suggestive of myocardial ischemia yet no or nonobstructive CAD (i.e., cardiac syndrome x) may have subendocardial ischemia as demonstrated using cardiac MR perfusion


• Preventing plaque rupture / EROSION



• Tobacco Smoke

• High Blood Cholesterol

• High Blood Pressure

• Physical Inactivity

• Obesity and Overweight

• Diabetes Mellitus

• Age

Classic Cardiovascular Risk Factors

Diabetes and CV Risk in FraminghamAge 35-64 Years--30 Year Follow-up

CHD Stroke Claudication HeartFailure

Total CVD

Wilson Am J Kidney Dis 1998

0

2

4

6

8

10

Ris

k R

atio

MenWomen

P<0.001

P<0.001

P<0.05

P<0.001

P<0.001

P<0.001

P<0.001

P<0.001

P<0.001

Risk Factor Defining LevelAbdominal obesity(Waist circumference)

MenWomen

>102 cm (>40 in)

>88 cm (>35 in)

TG 150 mg/dlHDL-C

MenWomen

<40 mg/dl<50 mg/dl

Blood pressure 130/85 mm HgFasting glucose 110 mg/dl

The Metabolic SyndromeThe Metabolic SyndromeDiagnosis is established Diagnosis is established

when when 3 of risk factors are present3 of risk factors are present

Source: Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.

Metabolic Syndrome and CV MortalityMetabolic Syndrome and CV Mortality

• European cohort studies (6156 men and 5356 women):

• Modified WHO definition of Metabolic Syndrome• CV mortality

– 2.26 [1.61-3.17] in men – 2.78 [1.57-4.94] in women

Hu et al. Arch Intern Med 2004; 164: 1066-76Hu et al. Arch Intern Med 2004; 164: 1066-76

Elevated Triglycerides Increase CHD RiskElevated Triglycerides Increase CHD Risk

0.0

0.5

1.0

1.5

2.0

2.5

50 100 150 200 250 300 350 400

Rela

tive R

isk f

or

CH

D

Men

Women

Framingham Heart Study

For every increase in serum TG level of 89 mg/dL, risk of CHD increases 30% in men and 69% in women

Meta-Analysis of 17 Prospective Studies





Primary Pro-Inflammatory Cytokines (eg, IL-1, TNF-)

IL-6“Messenger” Cytokine

ICAM-1Selectins, HSPs, etc.

LiverEndotheliumand other cells

CRPSAA

Adapted from Libby P et al.Circulation. 1999;100:1148–1150.

Inflammatory Pathways in Inflammatory Pathways in AtherogenesisAtherogenesis

Circulation

Pro-inflammatory Risk Factors

0

1

2

3

4

5

6

7

Hs-CRP and Risk of Future Cardiovascular Hs-CRP and Risk of Future Cardiovascular Events in Apparently Healthy WomenEvents in Apparently Healthy Women

Source: Source: Ridker PM et al. Ridker PM et al. CirculationCirculation 1998;98:731-733. 1998;98:731-733.

1<0.15

Rela

tive R

isk

Quartile of hs-CRP (range, mg/dL)

20.15–0.37

30.37–0.73

4>0.73

PP Trend <0.002 Trend <0.002Any Event

MI or Stroke

Risk Factors for Future Cardiovascular Risk Factors for Future Cardiovascular Events: Women’s Health StudyEvents: Women’s Health Study

IL, interleukin; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; sICAM, serum intercellular adhesion molecule; SAA, serum amyloid A; ApoB, Apolipoprotein B; HDL-C, high-density lipo-protein cholesterol; hs-CRP, high-sensitivity C-reactive protein.Ridker PM, et al. N Engl J Med. 2000;342:836-843.

0 1.0 2.0 4.0 6.0

Lipoprotein(a)HomocysteineIL-6TCLDL-CsICAM-1SAAApo BTC: HDL-Chs-CRPhs-CRP + TC: HDL-C

High-Sensitivity C-Reactive Protein High-Sensitivity C-Reactive Protein (hsCRP)(hsCRP)

• hsCRP should not be used for routine screening of all women, but should be reserved for refining risk estimates in intermediate risk patients when there is uncertainty regarding the need to start drug therapy

• Consider statins in women over 60 years of age if, after lifestyle modification, hsCRP remains elevated above 2 mg/dL and no acute inflammatory process is present (Class IIb; Level of Evidence B)

Source: Mosca 2011, Ridker 2009

0 1 2 3 4 50

2

4

6

8C

-rea

ctiv

e P

rote

in (

mg

/L)

Number of Components of the Metabolic Syndrome

Ridker PM, et al. Circulation. 2003;107:391-397. (with permission)

Metabolic Syndrome and CRP Metabolic Syndrome and CRP LevelsLevels

• Increased body fat

• Smoking

• Low physical activity

• Poor aerobic fitness

• Low fruit and vegetable intake

• Low omega-3 fatty acid intake

Behavioral factors associated with elevated biomarkers of inflammation

Nicklas BJ, You T, Pahor M. Behavioral treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training. Can Med Assoc J 2005; 172:1199-1209




• Recognizing Presence of CHD in women


Aspirin Evidence: Secondary PreventionAspirin Evidence: Secondary Prevention

Antithrombotic Trialist Collaboration. BMJ 2002;324:71–86

Acute MI

Acute CVA

Prior MI

Prior CVA/TIA

Other high risk

CVD(e.g. unstable angina, heart failure)

PAD(e.g. intermittent claudication)

High risk of embolism (e.g. Afib)

Other (e.g. DM)

All trials

1.00.50.0 1.5 2.0

Control better Antiplatelet better

Effect of antiplatelet treatment* on vascular events**

End points (mean, 10.1 yrs):● Combined end point of nonfatal MI, nonfatal stroke, or total cardiovascular death

● Incidence of total malignant neoplasms of epithelial cell origin

Women's Health Study: Women's Health Study: Low-Dose Aspirin in Primary Prevention TrialLow-Dose Aspirin in Primary Prevention Trial

Ridker PM. Presented at: 54th Annual Scientific Session of the American Collegeof Cardiology; March 7, 2005; Orlando, Fla. Ridker PM, et al. N Engl J Med. 2005;352.

39,876 initially healthy† women, aged 45 yrsRandomized, blinded, factorial

Low-Dose Aspirin100 mg on alternate days

n=19,934

Placebo

n=19,942

Aspirin : Primary Prevention in WomenAspirin : Primary Prevention in WomenWomens’ Health Study (WHS)Womens’ Health Study (WHS)

0.00

0.01

0.02

0 2 4 6 8 10

Cum

ulat

ive

Inci

denc

e of

MI

Placebo

Aspirin

P=0.83

Ridker P et al. NEJM 2005;352:1293-304

Years

39,876 women randomized to aspirin (100 mg every other day) or placebo for an average of 10 years

Aspirin does not reduce the risk of MI in low risk womenAspirin does not reduce the risk of MI in low risk women

But…But…

Aspirin Placebo RR 95% CI P

Primary endpoint:Major cardiovascular event* 477 522 0.91 0.80-1.31 .13

Secondary endpoints:Stroke 221 206 0.83 0.69-0.99 .04

Ischemic 170 221 0.76 0.63-0.93 .009

Hemorrhagic 51 41 1.24 0.82-1.87 .31

Transient ischemic attack 186 238 0.78 0.64-0.94 .01

Myocardial infarction (MI) 198 193 1.02 0.84-1.25 .83

revascularization 389 374 1.04 0.90-1.20 .61

Cardiovascular death 120 129 0.95 0.74-1.22 .68

All-cause mortality 609 642 0.95 0.85-1.06 .32

Womens’ Health Study (WHS)Womens’ Health Study (WHS)


Womens’ Health Study (WHS)Womens’ Health Study (WHS)


Aspirin Placebo RR 95% CI P

Smoking status

Current (n = 5235) 157 127 1.30 1.03-1.64 .03

Past/never (n = 34,605) 319 392 0.80 0.69-0.93 .003

Age (yrs)

45-54 (n = 24,025) 163 161 1.01 0.81-1.26 .92

55-64 (n = 11,754) 183 186 0.98 0.80-1.20 .84

65+ (n = 4097) 131 175 0.74 0.59-0.92 .008

Men ages 45-79Men ages 45-79Encourage aspirin use when potential CVD benefit (MIs prevented) outweighs potential harm of GI hemorrhage

Women ages 55-79 Encourage aspirin use when potential CVD benefit (strokes prevented) outweighs potential harm of GI hemorrhage.

10-year CHD risk 10-year stroke risk

Age 45-59 years ≥4% Age 55-59 years ≥3%



USPSTF: Risk level at which CVD events prevented (benefit) exceeds GI harms

Men Age <45 Years and Women Age <55 Years : Do not encourage aspirin use Men & Women Age ≥80 Years: No Recommendation (Insufficient Evidence) AHRQ Publication No. 09-05129-EF-3

Current as of March 2009

Women have strokes too Women have strokes too

0.6961 0.6218 - 2.0376 1.1256 3.4/3.0 55 - 64

0.0040 1.3205 - 4.3267 2.3903 2.5/1.0 45 - 54

0.6876 0.4715 - 3.1268 1.2142 1.2/1.0 35 - 44

P 95% CI OR Women/Men (%)

Age group (y)

NHANES data from 17,061 individuals older than 18 years between 1999 and 2004

Stroke StatisticsU.S. StatisticsStroke StatisticsU.S. Statistics

• The risk stroke doubles each decade after the age of 55. – ~25% of strokes occur in people < 65 years of age.

• Stroke death rates are higher for African Americans than for whites, even at younger ages.

• Each year, about 55,000 more women than men have a stroke.

• The risk of ischemic stroke in current smokers is about double that of nonsmokers

• High blood pressure is the most important risk factor for stroke.

U.S. Centers for Disease Control and Prevention and the Heart Disease and Stroke Statistics - 2010 Update

Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women--2011 Update: A Guideline

From the American Heart Association

L. Mosca et al. Circulation. 2011 Feb 16.

Lifestyle InterventionsLifestyle Interventions

• Cigarette smoking DON’T! (Class I; LOE B )

• Physical activity– 150 min/wk of moderate exercise or 75 min/wk of vigorous

exercise, performed in episodes of at least 10 min, (Class I; LOE B)

– Muscle strengthening activities on ≥2 d per week (Class I; LOE B)

• Cardiac rehabilitation YES (Class I; LOE B)

• Dietary intake– Diet rich in fruits, vegetables, and whole grains. Limit saturated

fat, cholesterol, alcohol, salt, and sugar. Avoid trans-fatty acids (Class I LOE B)

Lifestyle Interventions (cont.)Lifestyle Interventions (cont.)

• Weight maintenance/reduction– Maintain or lose weight through physical activity and appropriate

caloric intake to achieve appropriate body weight (BMI <25 kg/m2, waist size <35 inches) (Class I; LOE B).

• Omega-3 fatty acids– Consumption of omega-3 fatty acids in the form of fish or in

capsule form for women with hypertriglyceridemia or for primary or secondary prevention of CHD (Class IIb; LOE B).

Major Risk Factor InterventionsMajor Risk Factor Interventions

• Blood pressure management– Pharmacotherapy when blood pressure is ≥140/90 mm Hg

(≥130/80 mm Hg in the setting of chronic kidney disease and diabetes. (Class I; LOE B).

• Lipid Management– LDL-C–lowering drug therapy is recommended (along

with lifestyle) in women with CHD, other atherosclerotic CVD, diabetes mellitus or 10-year absolute risk >20% to achieve an LDL-C <100 mg/dL (Class I; LOE A)

– LDL-C–lowering with lifestyle therapy in all others, even if LDL > 190 mg/dL. (Class I LOE B).

Major Risk Factor Interventions Major Risk Factor Interventions (cont.)(cont.)

• Lipid Management (cont.)– In women >60 years of age and with an estimated CHD risk

>10%, statins could be considered if hsCRP >2 mg/dL after lifestyle modification and no acute inflammatory process is present (Class IIb; LOE B)

– Niacin or fibrate therapy can be useful when HDL-C is low (<50 mg/dL) or non–HDL-C is elevated (>130 mg/dL) in high-risk women after LDL-C goal is reached (Class IIb; LOE B)

• Diabetes Management– Lifestyle and/or pharmacotherapy to achieve HbA1C <7

(Class IIa LOE B).

Preventive Drug InterventionsPreventive Drug Interventions• Aspirin• Aspirin (75–325 mg/d) in women with CHD unless

contraindicated (Class I; LOE A).

• Aspirin (75–325 mg/d) is reasonable in women with diabetes (Class IIa; LOE B).

• Aspirin (81 mg daily or 100 mg every other day) can be useful in women ≥65 years of age, if … benefit for ischemic stroke and MI prevention is likely to outweigh risk of GI bleeding and hemorrhagic stroke (Class IIa; LOE B)

• Aspirin (81 mg daily or 100 mg every other day) may be reasonable for women <65 years of age for ischemic stroke prevention (Class IIb; LOE B).

Class III Interventions (Not Useful/Effective and May Be Harmful)

• Menopausal therapy– Hormone therapy … should not be used for the primary or

secondary prevention of CVD (Class III, LOA A).

• Antioxidant Supplements– Antioxidant vitamin supplements (eg, vitamins A, C, E) should

not be used for the primary or secondary prevention of CVD (Class III, LOA A).

• Folic Acid– Folic Acid, with or without B6 and B12, should not be used for the

primary or secondary prevention of CVD (Class III, LOA A).

• Aspirin for MI prevention in women <65– Routine use of aspirin in healthy women 65 years of age is not

recommended to prevent MI (Class III, LOA B).

24% Increase Breast Cancer

Also: DVTs

Fracture Reduction (Hip 23%)

STOPPED Early, Clear Harm

24% Increase CHD31% Increase

Stroke

RisksBenefits

JAMA. 2002;288:321-333

Stopped 3.3 yrs early

111% Increase Pulmonary Emboli

39% Reduction Colorectal Cancer

WHI E+P Trial Findings, July 2002 (avg 5.2 y)

105% Increase Dementia

Also: DVTs

Fracture Reduction (Hip 39%)

STOPPED Early, suggestion of harm

Neutral for CHDNeutral for breast cancer

39% Increase Stroke

Risks

Benefits

JAMA 2004;291:2947-58

Stopped 1.7 yrs early

34% Increase Pulmonary Emboli

WHI E Alone Trial Findings, 2004 (avg 6.8 y)

49% Increase Dementia

0 6 12 18 24 30 36 42 48

Months

70

75

80

85

90

95

100% Surviving (free of MI, stroke, death)

Vitamin E

Placebo

GISSI-Prevenzione Investigators. Lancet 1999;354:447-55

RR 0.95, P=0.293

Vitamin E: Secondary PreventionVitamin E: Secondary Prevention(GISSI)-Prevenzione Trial

Prim

ary

End

Poi

nt (

%)*

Months

11,324 patients with a recent MI randomized to Vitamin E (300 mg) or placebo for 3.5 years

*Includes freedom from death, nonfatal MI, and stroke

Bonna KH et al. NEJM 2006;354:1578-1588

Folic Acid and B-Vitamins: Secondary PreventionFolic Acid and B-Vitamins: Secondary Prevention

NORVIT: 3,749 patients with a NORVIT: 3,749 patients with a recent myocardial infarction recent myocardial infarction randomized to 4 treatment arms randomized to 4 treatment arms for 40 monthsfor 40 months

• Vitamin B6 (40 mg), Vitamin B12 (0.4 mg), and Folic acid (0.8 mg)†

• Vitamin B12 (0.4 mg) and Folic acid (0.8 mg)‡

• Vitamin B6 (40 mg)^

• Placebo

†HR=1.22, P=0.05 compared to placebo‡HR=1.08, P=0.31 compared to placebo^HR=1.14, P=0.09 compared to placebo




• Recognizing Presence of CHD in women


Clinical Recognition of CAD : Gender Clinical Recognition of CAD : Gender Differences in Heart Attack SymptomsDifferences in Heart Attack Symptoms

Typical in both sexes• Pain, pressure, squeezing, or

stabbing pain in the chest• Pain radiating to neck, shoulder,

back, arm, or jaw• Pounding heart• Difficulty breathing• Heartburn, nausea, vomiting,

abdominal pain• Cold sweats or clammy skin• Dizziness

More common in women• Milder symptoms • Sudden onset of weakness,

shortness of breath, fatigue, body aches, or overall feeling of illness (without chest pain)

• Unusual feeling or mild discomfort in the back, chest, arm, neck, or jaw (without chest pain)

Source: AHA &: WISE data JACC 2006

Women’s Early Warning Signs of Heart Women’s Early Warning Signs of Heart AttackAttack

• Weeks before Heart Attack (95% of women)Weeks before Heart Attack (95% of women) Unusual fatigue (70.7%)Unusual fatigue (70.7%) Sleep disturbance (47.8%)Sleep disturbance (47.8%) Shortness of breath (42.1%)Shortness of breath (42.1%) Indigestion (39.4%)Indigestion (39.4%) Chest pain (29.7 %)Chest pain (29.7 %)

• At time of Heart AttackAt time of Heart Attack Shortness of breath (57.9%)Shortness of breath (57.9%) Weakness (54.8%)Weakness (54.8%) Fatigue (42.9%)Fatigue (42.9%) Chest pain (57%)Chest pain (57%)

McSweeney, JC et al. Circulation 2003; 2619-2623

Shaw LJ, et al. Coronary Artery Disease in Women.1999:327-350.

Limited Numbers of Women in Research on Noninvasive Testing

0102030405060708090

100

ECG ECHO MPI

Women

Men

% o

f P

atie

nts

Diagnostic Tests in WomenDiagnostic Tests in Women

Treadmill exercise electrocardiogram is often

inaccurate

~ 33% false positive rate

~ 25% false negative rate

Addition of nuclear imaging or exercise

echocardiogram increases predictive

accuracy to ~ 90%

SOURCE: Crouse. The Fourth Chicago Women & Heart Disease Conference, 1997.

AHA Consensus Statement – Algorithm AHA Consensus Statement – Algorithm for Evaluation of Symptomatic Women for Evaluation of Symptomatic Women

Using Cardiac ImagingUsing Cardiac Imaging

Source: Mieres Circulation 2005; 111:682–696

Intermediate-high likelihood women with atypical or typical chest pain symptomsIntermediate-high likelihood women with atypical or typical chest pain symptoms

Risk factormodification +/-anti-ischemic Rx

Good Ex toleranceGood Ex tolerance+ normal 12-L ECG+ normal 12-L ECG

Diabetes, abnormal 12-L ECG, orDiabetes, abnormal 12-L ECG, orquestionable Ex capacityquestionable Ex capacity

Ex or pharmacologic stress imagingEx or pharmacologic stress imagingExercise TM

test

Int riskInt riskTMTM

LowLowPost-ETTPost-ETT

LKLK

Able to ExAble to Ex Unable to ExUnable to Ex

Exercisestress

Pharmacologicstress

Normal or mildlyNormal or mildlyabnormal withabnormal with

normal LV functionnormal LV function

Moderate-severelyModerate-severelyabnormal orabnormal or

depressed EFdepressed EF

Cardiaccath

Cardiaccath

Ischemia in women may occur from mental Ischemia in women may occur from mental stress more often than physical stressstress more often than physical stress

• 160 men and 24 women with known CHD underwent exercise stress test and mental stress tests

• Women had more EKG documented ischemia during mental stress; men more ischemia during physical stress

Journal of Health Psychology January 2000; 5:75-85

• 170 men and 26 women with known CHD evaluated during daily activities, exercise, and mental stress • Women reported chest pain more often during daily activities (P =0.04) and during laboratory mental stressors (P =0.01); men reported chest pain more often during exercise

Sheps et al. Am Heart J. 2001 Nov;142(5):864-71

CONCLUSIONSCONCLUSIONS

• CHD is the leading cause of death in women

• Risk Factor Modification cornerstone of CV risk reduction

• Pathophysiology of Angina and ACS may differ

• Preventive Strategies may differ

• Evidence-based therapies should be utilized and therapies of no proven benefit should be avoided

• As always…evidence continues to evolve

Health & Medicine

Evidence based management of cardiovascular disease in women