Evolving Knowledge of Women and Heart Disease

Evolving Knowledge of Women and Heart Disease

Jo-Ann Eastwood PhD, RN, CCNS, ACNP-BC, FAHA

Magnitude of the ProblemMagnitude of the Problem

Leading cause of death, mostly due to ischemic heart disease and stroke Angina is a more common presentation of coronary heart disease

in women than in men

Ischemic heart disease in women versus men Present at older age Less likely to be diagnosed and treated Higher cardiovascular mortality

Estimated annual cost for cardiovascular disease in men and women: $400 billion

CVD & Other Causes of Death CVD & Other Causes of Death

More than More than 1 in 4 1 in 4 women will die of heart disease women will die of heart disease 1 in 30 1 in 30 women will die of breast cancerwomen will die of breast cancer

Women are getting the messageWomen are getting the message

What is the leading cause of death in women?What is the leading cause of death in women?We know the answer: Heart Disease!We know the answer: Heart Disease!

In 1997, In 1997, only 30% only 30% (less than 1 out of 3) women (less than 1 out of 3) women knew the right answer.knew the right answer.

In 2010, In 2010, 57% 57% of women knew the right answer.of women knew the right answer.This realization was shared by fewer Black &This realization was shared by fewer Black &

HispanicHispanic

Majority of women believed they couldreduce their Majority of women believed they couldreduce their risk with multivits, antioxidants or ASArisk with multivits, antioxidants or ASA

Only Only 53%53% said they would call said they would call 911 if they had 911 if they had symptomssymptomsMosca, L Circ. Cardiovasc Qual Outcomes 2010;3(2):120-7Mosca, L Circ. Cardiovasc Qual Outcomes 2010;3(2):120-7

Cardiovascular Disease Deathsin the United States (1980-2009)Cardiovascular Disease Deathsin the United States (1980-2009)

Dea

ths

(in t

hous

ands

Dea

ths

(in t

hous

ands

))

1980 1985 1990 1995 2000 2005 20091980 1985 1990 1995 2000 2005 2009

WomenWomen

MenMen

Go AS, et al. Go AS, et al. Circulation.Circulation. 2013;127:e6-e-245. 2013;127:e6-e-245.

Gender Differences in Sudden Cardiac Death, Symptoms, and Quality of Life

Gender Differences in Sudden Cardiac Death, Symptoms, and Quality of Life

Sudden cardiac death before arrival at a hospital Women: 42% Men: 25%

Symptomatic women versus men More often have recurrent symptoms requiring

hospitalizations Lower ratings of general well-being and limitations in

ability to perform activities of daily living

Shaw LJ, et al. Shaw LJ, et al. J Am Coll Cardiol. J Am Coll Cardiol. 2009;54:1561-1571.2009;54:1561-1571.

Aftermath of CHDAftermath of CHD

Survivors of ACS have 1.5 – 15 x greater risk of illness and death than general population

Within 6 years of MI: % Men % Women

Recurrent MI: 18 35 SCD 6 7 HF 22 46 Stroke 8 11

ACC National Cardiovascular Data Registry: In-Hospital Mortality

ACC National Cardiovascular Data Registry: In-Hospital Mortality

Chest PainChest Pain

In-H

osp

ital

In-H

osp

ital

Mo

rta

lity

Ra

te

Mo

rta

lity

Ra

te (%

)(%

)

BlackBlack(n=24,998)(n=24,998)

HispanicHispanic(n=3562)(n=3562)

NativeNativeAmericanAmerican(n=1251)(n=1251)

AsianAsian(n=7823)(n=7823)

WhiteWhite(n=338,252)(n=338,252)

..

PP<0.0001<0.0001

WomenWomen

MenMen

PP=0.89=0.89

PP=0.14=0.14PP=0.23=0.23

In-hospital mortality after coronary angiography.In-hospital mortality after coronary angiography.Among patients with stable chest pain, white women with 1- to 3-vessel CAD hadAmong patients with stable chest pain, white women with 1- to 3-vessel CAD had 1.67- to 2.02-fold higher in-hospital mortality than white men (1.67- to 2.02-fold higher in-hospital mortality than white men (PP=0.013).=0.013).

SEX MATTERSSEX MATTERS

In light of these epidemiologic data, common misunderstandings and a growing awareness of potentially relevant sex differences, the AHA has updated CVD Prevention Guidelines for Women.

PresentationEvaluation and Treatment

Benefits and Risks

PresentationEvaluation and Treatment

Benefits and Risks

VIRGO Study: Gender Differences in Symptom Presentation and Perception

VIRGO Study: Gender Differences in Symptom Presentation and Perception

Younger patients with MI from 104 US hospitals, 2008-2012 (n=2990)

Age: 18 to 55 years 2:1 female to male enrollment

90% of men and 87% of women presented with chest pain, pressure, tightness, or discomfort

Women presented more additional symptoms

More women waited >1 day to seek care than men (55% versus 49%; P<0.05)

At time of hospitalization 24% of women said health care

provider did not think symptoms were heart related compared with 12% of men (P<0.001)

Symptoms atSymptoms atMI PresentationMI Presentation

Patients (%)Patients (%)

Women (n=2012)Women (n=2012)

Men (n=978)Men (n=978)

Lichtman JH, et al. Lichtman JH, et al. Circulation. Circulation. 2012;126(suppl). Abstract 17831.2012;126(suppl). Abstract 17831.

Chest Pain/Chest Pain/

DiscomfortDiscomfort

RadiatingRadiating

PainPain

Indigestion/Indigestion/

NauseaNausea

Shortness of Shortness of BreathBreath

Weakness/Weakness/

FatigueFatigue

PalpitationsPalpitations

**PP<0.05 and <0.05 and ††PP<0.01 versus men.<0.01 versus men.

††

**

††

††

††

**

Women’s Ischemia Syndrome Evaluation (WISE) StudyWomen’s Ischemia Syndrome Evaluation (WISE) Study

NHLBI-sponsored 4-center study Women (>18 years of age) undergoing clinically ordered coronary angiography for

suspected myocardial ischemia (n=936) Myocardial ischemia at non-invasive testing

Exclusion criteria Emergency referral, pregnancy, cardiomyopathy, NYHA class IV CHF, recent acute MI or

unstable angina, recent coronary revascularization, significant valvular or congenital heart disease, any contraindication to provocative myocardial stress testing, and any condition likely to affect study retention

Objectives Optimize symptom evaluation and diagnostic testing for ischemic heart disease Explore mechanisms for symptoms and myocardial ischemia in the absence of epicardial

coronary artery stenoses Evaluate the influence of reproductive hormones on symptoms and diagnostic test

response

Merz CN, et al. Merz CN, et al. J Am Coll Cardiol. J Am Coll Cardiol. 1999;33:1453-1461.1999;33:1453-1461.

WISE Study: Estimated Lifetime Costs for Women With AnginaWISE Study: Estimated Lifetime Costs for Women With Angina

0

200000

400000

600000

800000

1000000

1200000

Direct Cardiovascular Costs/PatientDirect Cardiovascular Costs/Patient

Pro

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ted

Lif

eti

me

Co

sts

P

roje

cte

d L

ife

tim

e C

os

ts (U

S$)

(US

$)

NonobstructiveNonobstructiveCADCAD

1 Vessel1 VesselCADCAD

2 Vessel2 VesselCADCAD

3 Vessel3 VesselCADCAD

Shaw LJ, et al. Shaw LJ, et al. Circulation. Circulation. 2006;114:894-904.2006;114:894-904.

$767,288$767,288

$1,001,493$1,001,493$1,051,302$1,051,302

$1,008,780$1,008,780

Evolving Understanding of Angina in Women Evolving Understanding of Angina in Women

Typical versus atypical angina diagnosis by gender 3225 patients referred to Duke University for evaluation of chest pain with median of 5

episodes of chest pain weekly

Angina equivalents Fatigue Lightheadedness Weakness Diaphoresis

Coronary patients with angina rate their quality of life lower than those without angina

**PP<0.05 for comparison across gender. No angina: males (11%) and females (19%).<0.05 for comparison across gender. No angina: males (11%) and females (19%).

Male (n=2249) Female (n=967)

Typical angina (%) 55 28

Atypical angina (%) 34* 53

− Shortness of breathShortness of breath

− NauseaNausea

− IndigestionIndigestion

Abrams J.Abrams J. N Engl J Med. N Engl J Med. 2005;352:2524-2533; Alexander KP, et al. 2005;352:2524-2533; Alexander KP, et al. J Am Coll Cardiol. J Am Coll Cardiol. 1998;32:1657-1664;1998;32:1657-1664;Fang JC.Fang JC. Braunwald’s Heart Disease. 9 Braunwald’s Heart Disease. 9 thth Edition Edition. 2012. Bandu I, et al. . 2012. Bandu I, et al. Chest.Chest. 1994;105:1009-1012; Stern S. 1994;105:1009-1012; Stern S.Circulation.Circulation. 2002;106:1906-1908; Marquis P, et al. 2002;106:1906-1908; Marquis P, et al. Eur Heart JEur Heart J. 1995;16:1554-1560.. 1995;16:1554-1560.

Novel Risk Factors in WomenNovel Risk Factors in Women

Traditional risk factors and the Framingham risk score may underestimate risk in women

Novel risk markers may improve risk detection Abdominal obesity Metabolic syndrome Low estrogen levels Elevated testosterone levels and polycystic ovary syndrome Elevated C-reactive protein

Postmenopause Clustering of risk factors is common (obesity, hypertension, dyslipidemia)

These risk factors also predict early menopause

Shaw LJ, et al. Shaw LJ, et al. J Am Coll CardiolJ Am Coll Cardiol. . 2006;47(suppl):4S-20S.2006;47(suppl):4S-20S.Shaw LJ, et al. Shaw LJ, et al. J Am Coll CardiolJ Am Coll Cardiol. . 2009;54:1561-1575.2009;54:1561-1575.SWAN Study. http://www.swanstudy.org. SWAN Study. http://www.swanstudy.org. Greenland P, et al. Greenland P, et al. J Am Coll Cardiol. J Am Coll Cardiol. 2010;56:e50-e103.2010;56:e50-e103.

Reclassification of Risk in Women Using the Reynolds Risk ScoreReclassification of Risk in Women Using the Reynolds Risk Score

Ridker PM, et al. Ridker PM, et al. JAMAJAMA. . 2007;297:611-619.2007;297:611-619.Reynolds Risk Score calculator: http://www.reynoldsriskscore.org/.Reynolds Risk Score calculator: http://www.reynoldsriskscore.org/.

Assessment of Myocardial Ischemia and Obstructive Coronary Disease in Women

Assessment of Myocardial Ischemia and Obstructive Coronary Disease in Women

Symptoms suggestive of myocardial ischemia Women have lower rates of obstructive CAD at angiography

Early work by Diamond and Forrester Women with typical or atypical chest pain symptoms have calculated

obstructive CAD probabilities substantially less than men Typical exertional angina in a 55-year-old man has a probability of

obstructive CAD of approximately 90% as compared with wide range from 55% to 90% for a 55-year-old woman

This does not address angina equivalents

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

Shaw LJ, et al. Shaw LJ, et al. J Am Coll Cardiol. J Am Coll Cardiol. 2006;47(suppl):4S-20S.2006;47(suppl):4S-20S.Diamond GA, et al. Diamond GA, et al. N Engl J MedN Engl J Med. 1979;300:1350-1358.. 1979;300:1350-1358.

Gender Differences in Ischemic Heart Disease in WomenGender Differences in Ischemic Heart Disease in Women

Smaller size Increased stiffness (fibrosis,

remodeling, etc) More diffuse disease More plaque erosion versus

rupture Microemboli, rarefaction (drop

out), disarray, etc

Structural FeaturesStructural Features(macro- and microvessels)(macro- and microvessels)

Functional FeaturesFunctional Features(macro- and micro -vessels)(macro- and micro -vessels)

Wenger NK. Wenger NK. Curr Cardiol Rep. Curr Cardiol Rep. 2010;12:307:314.2010;12:307:314.Kramer MC, et al. Kramer MC, et al. J Am Coll Cardiol. J Am Coll Cardiol. 2010;55:122-132.2010;55:122-132.Shaw LJ, et al. Shaw LJ, et al. J Am Coll Cardiol. J Am Coll Cardiol. 2009;54:1561-1575.2009;54:1561-1575.

Endothelial dysfunctionEndothelial dysfunction

Smooth muscle dysfunction Smooth muscle dysfunction (Raynaud’s, migraine, coronary (Raynaud’s, migraine, coronary artery spasm) artery spasm)

InflammationInflammation

− Plasma markersPlasma markers

− Vasculitis (Takayasu’s, Vasculitis (Takayasu’s, rheumatoid, SLE, CNSV, rheumatoid, SLE, CNSV, giant cell, etc)giant cell, etc)

Model of Microvascular Angina in WomenModel of Microvascular Angina in Women

Shaw LJ, et al. Shaw LJ, et al. J Am Coll Cardiol. J Am Coll Cardiol. 2009;54:1561-1571.2009;54:1561-1571.

Overarching Working Model of Ischemic Heart Disease Pathophysiology in Women

Overarching Working Model of Ischemic Heart Disease Pathophysiology in Women

Shaw LJ, et al. Shaw LJ, et al. J Am Coll Cardiol. J Am Coll Cardiol. 2009;54:1561-1571.2009;54:1561-1571.

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

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

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

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

Thrombus Thrombus FormationFormation

LumenLumen

What to Tell a Woman When She Doesn’t Want to be a Statistic?

What to Tell a Woman When She Doesn’t Want to be a Statistic?

AHA Impact Goal For All Americans AHA Impact Goal For All Americans

20% by 2020 : Improvement CV health Reduction in CVD/stroke deaths

Primordial prevention (at all levels of risk) CVD & associated risk factors develop early in life

Health promotion & disease prevention require all approaches: Population-level Individual high risk

Focus on WomenFocus on Women

“..defining a women’s risk status and then improving adherence to preventive lifestyle behaviors is the most effective way to lower CVD in women.”

Wenger, NK. Clin Cardilol. 2011

Targeting Education - Awareness AND. . .Targeting Education - Awareness AND. . .

Ideal Health Behaviors such as:Ideal Health Behaviors such as:

CVD Risk in Women CVD Risk in Women

Mosca, Circulation 123:1243, 2011 Mosca, Circulation 123:1243, 2011

Female – Specific IssuesFemale – Specific Issues

• Gender differences in CVD risk factors

• Tobacco• Diabetes and Met Syn• Dyslipidemia• HTN• Fitness

• Autoimmune diseases with ↑ CVD risk

• Rheumatoid Arthritis• SLE

• Female specific issues • Pregnancy induced HTN• Pre-eclampsia• Gestational diabetes• PCOS

• Other Issues for Women

• Breast cancer therapy effects,

• Chest radiation

Counseling All Women: Recommended Lifestyle ChangesCounseling All Women: Recommended Lifestyle Changes

For all women: Smoking cessation and avoidance of secondhand

smoke Physical activity

Moderate activity at least 6-7 days a week Strength training x2/week

DASH-like low-sodium diet Weight Management

2011 Guidelines: Evidence-based to Effectiveness-based

2011 Guidelines: Evidence-based to Effectiveness-based

Benefits and risks observed in clinical practice

Therapies that may have potential benefit

Ex. Screening for depression- indirectly may impact CVD risk through adherence to prevention therapies or other mechanisms.

Acknowledgement that 10 year risk is not efficacious in women

Targeting Women Throughout the LifespanTargeting Women Throughout the Lifespan

PremenopausalPremenopausal

Initial assessment: Detailed medical and pregnancy-complications hx

Pregnancy: Early “stress test”? Unique opportunity to assess

lifetime CVD risk “Metabolic syndrome of pregnancy” Preeclampsia

Postpartum referral for CVD risk assessment

Pregnancy: A Stress Test for Life Pregnancy: A Stress Test for Life

Pregnancy stresses maternal carbohydrate, lipid, inflammatory pathways, Pregnancy stresses maternal carbohydrate, lipid, inflammatory pathways, vascular function vascular function

● ● Unmasks underlying metabolic, vascular disease Unmasks underlying metabolic, vascular disease ••? Pregnancy a screen for later hypertension, diabetes ? Pregnancy a screen for later hypertension, diabetes

••? Preeclampsia induces damage to vascular endothelium; ? pathway for ? Preeclampsia induces damage to vascular endothelium; ? pathway for microvascular dysfunction microvascular dysfunction

••? Preeclampsia triggers inflammatory, autoimmune responses ? Preeclampsia triggers inflammatory, autoimmune responses

••? How can/should preeclampsia, hypertensive disorders of pregnancy ? How can/should preeclampsia, hypertensive disorders of pregnancy (HDP) be incorporated into CV risk assessment for women(HDP) be incorporated into CV risk assessment for women Williams, Curr Opin Obstet Gynec 15:465, 2003 Williams, Curr Opin Obstet Gynec 15:465, 2003 Ness, Ann Epidemiol 15:726, 2005 Ness, Ann Epidemiol 15:726, 2005 Mosca, Circulation 123:1243, 2011 Mosca, Circulation 123:1243, 2011

HDP and Subsequent CV Disease HDP and Subsequent CV Disease

Compelling evidence for association HDP and future CVDCompelling evidence for association HDP and future CVD Hypertension Hypertension Ischemic heart disease Ischemic heart disease Ischemic stroke Ischemic stroke Thromboembolic disease Thromboembolic disease Heart failure Heart failure Chronic kidney disease Chronic kidney disease Diabetes mellitus Diabetes mellitus Arrhythmias Arrhythmias Hypertension in adolescent life in offspring Hypertension in adolescent life in offspring Mannisto, Circulation 127:681, 2013 Mannisto, Circulation 127:681, 2013 88

Contemporary Recommendations Contemporary Recommendations

Pregnancy history integral component of CV risk evaluation Pregnancy history integral component of CV risk evaluation for women for women

Women with prior preeclampsia, hypertensive disorders Women with prior preeclampsia, hypertensive disorders of pregnancy → early, intensive coronary risk intervention of pregnancy → early, intensive coronary risk intervention Counsel re ↑ CVD risk Counsel re ↑ CVD risk Counsel re effectiveness of CV risk assessment, reduction Counsel re effectiveness of CV risk assessment, reduction in primary prevention CV disease in primary prevention CV disease ? Screen as early as 1 year postpartum ? Screen as early as 1 year postpartum

Guidelines needed for structured follow-up, CV risk Guidelines needed for structured follow-up, CV risk management after HDP management after HDP

Smith, Am J Obstet Gynecol 200:58.e1, 2009 Smith, Am J Obstet Gynecol 200:58.e1, 2009 Mosca, Circulation 123:1243, 2011 Mosca, Circulation 123:1243, 2011

PerimenopausalPerimenopausal

Decrease in exercise > decrease in calorie intake Weight gain, waist circumference, increase BP

Decreased social interaction d/t: Mood disorders Sleep disturbance Vasomotor symptomsChanges in work patterns /stress

Alterations in lipid profiles

((ESHRE Capri Workshop Group 2011)ESHRE Capri Workshop Group 2011)

PostmenopausalPostmenopausal

Dyslipidemia Hypertension Metabolic Syndrome Lack of exercise Psychosocial function

Social support Dysphorias

Higher prevalence of stroke

Dispelling Myths: Confusion Among Women RemainsDispelling Myths: Confusion Among Women Remains

Observational studies reported HRT effective for symptoms & diseases ie CV and osteoporosis for menopausal women

2 large RCTS HERS and WHI reported no benefits prevention of CVD. WHI found increases Breast CA incidence & CV events in healthy women

Million Women Study- increase in Breast CA with HRT

Dispelling Myths: Confusion Among Women RemainsDispelling Myths: Confusion Among Women Remains

Hormone therapy should not be used for primary or secondary prevention of CVD

Supplements not useful in preventing CVD Vitamins E and C Beta carotene Folic acid

Aspirin not recommended for healthy women < 65 yrs

Health DisparitiesHealth Disparities

Higher prevalence of risk factors in racial/ethnic groups HTN → Black women Diabetes →Hispanic women

Additional socio-economic factors Inadequate access to healthcare Reduced access to fresh food/easy availability

of fast food Community characteristics

Challenges: Real WorldChallenges: Real World

“I want to eat 5 fruits a day but once I dole out the fruit to the kids there is nothing left”

“It’s not safe in my neighborhood to walk besides I can’t leave the kids”

“I have to use the money I have for healthy groceries to give to the kids to pay for lunch. If they stand in the free lunch line they are teased and embarrassed all day!”

Successes!Successes!

“This is the first time my husband’s blood pressure has been down to 120/80 since the 6th grade” (N’s husband was admitted for a BP of 210/100 last November)

“My daughter (14 yo and overweight) watched me choosing good foods to eat and said I want to eat what you’re eating Mommy”

“My BP is 138/88 and my doctor says lose 20 lbs! Then I got your message about getting to goal <120/80. I am going back!”

Lessons from the FieldLessons from the Field

Women may be the key to changing health habits in minority communities A message that resonates: “Take care of

yourself so you can take care of your family” If you treat the woman, the family changes Women need social support Go where the women are:

Churches, community organizations

Online Resources Online Resources

Thank-you for your attention! Thank-you for your attention!

AHA : Clinical Research Grant Award

& to the many LA women who have committed themselves to not becoming a statistic!

Additional ReferencesAdditional References

AHA. http://www.americanheart.org/downloadable/heart/1136818052118Females06.pdf.

Go AS, et al. Circulation. 2013;127:e6-e-245. Wenger NK. Prog Cardiovasc Dis. 2003;46:199-229. Hemingway H, et al. JAMA. 2006;295:1404-1411. Daly C, et al. Circulation. 2006;113:490-498 Merz CN, Kelsey SF, Pepine CJ, et al. The Women's Ischemia Syndrome

Evaluation (WISE) study: protocol design, methodology and feasibility report. J Am Coll Cardiol. 1999;33:1453-1461

Shaw LJ, et al. J Am Coll Cardiol. 2008;117:1787-1801