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Advances in Cardiovascular Health for Women over the Past Decade:

Guidelines Recommendations for Practice

Amparo C. Villablanca, MD

Professor, Cardiovascular Medicine

Director, Women’s Cardiovascular Medicine Program

Frances Lazda Endowed Chair, Women’s Cardiovascular Medicine

Objectives Epidemiology of CVD in Women (ACS/CHD,

stroke, valve disease, CHF)

Seven Areas of Progress (Evidence Base) 1. Primary Prevention and Community Care 2. Secondary Prevention of CVD 3. Stroke in Women 4. Heart Failure and Cardiomyopathies 5. Ischemia with Non-obstructive CAD 6. SCAD 7. Arrhythmias and Device Therapies

Summary of Guidelines

Leading Causes of Death for All Males and Females (NCHS)

(A) CVD (C) Accidents (E) DM (B) All Cancers (D) Lung Disease (F) Alzheimer’s

Cardiovascular Disease Mortality Trends for Males and Females: 2004-2014 (NCHS)

Heart Disease Death Rates, in women remain overall high (2011-2013, CDC)

CVD in Women (AHA): More Progress Needed

Knowledge: Most women, some health professionals, lack knowledge (24% 1997> 56% 2012), and for gender-specific aspects of CVD

Prevention: Failure to link CVD risk to need for prevention

Under-utilization: of evidence-based guidelines by health professionals

Under-treatment: of women with proven therapies

Lack of comfort: Only 20% of heath professional report feeling ‘comfortable’ treating CVD in women

Objectives

Epidemiology of CVD in Women

Seven Areas of Progress 1. Primary Prevention and Community Care 2. Secondary Prevention of CVD 3. Stroke in Women 4. Heart Failure and Cardiomyopathies 5. Ischemia with Non-obstructive CAD 6. SCAD 7. Arrhythmias and Device Therapies


Primary Prevention New risk factors for CVD:

- gestational diabetes and hypertension - pre-eclampsia, eclampsia - autoimmune disorders - obstructive sleep apnea, and - radiation-induced myocardial injury

Comprehensive preventive health care screening and interventions increase awareness, improve prevention, reduce CV risk factors in women

A systems approach to community engagement can increase awareness, modify risk behaviors, improve clinical risk profiles and reduce serum inflammatory CV risk markers in high-risk women

AHA/ACC sex specific guidelines (last updated 2011); AHA HTN guidelines (2017)

Recommendations for Practice DO’s (class I)

∗ Lifestyle therapies (Life’s Simple 7’s):

∗ Use ASCVD risk score to predict risk, guide statin therapy use and HTN Rx

∗ Avoid interventions without proven

benefit/potential harm (class III) ∗ Use guidelines for non-invasive testing (minimize

radiation exposure)

ASCVD Risk Calculator [Intended for use if there if no ASCVD and LDL-cholesterol is <190]

Gender: Male/Female

Age (40 to 75 year range)

Race: White/African-American/Other

Total Cholesterol

HDL-Cholesterol

Systolic Blood Pressure

Treatment for Hypertension: Yes/No

Diabetes: Yes/No

Smoker: Yes/No

Recommendations for Practice

DON’Ts (Class III)

∗ Hormone therapy or selective estrogen-receptor modulators for prevention of CVD

∗ Antioxidant vitamin supplements (A, E, C) for

CVD prevention ∗ Aspirin for primary prevention of myocardial

infarction (or stroke) in low risk women age <65

Lifestyle Therapy

�1. avoid smoking and tobacco smoke �2. engage in aerobic activity (150 min/wk) �3. eat heart healthy foods

� - fruits, vegetables � - avoid processed foods � - whole-grains, high fiber � - more fish, less meat

�4. control blood pressure � - goal <120/80 mmHg � - reduce sodium (<1,500 mg/dy) � - increase dietary potassium

�5. maintain target lipid profile �6. control diabetes (A1C <7.0) �7. manage weight (BMI <25)

Lipids: 4 statin therapy groups (age 40-75)

Known ASCVD

Known DM (use risk score for intensity)*

Heritable HLP: LDL >190

ASCVD 10-yr risk >7.5%

Statin Intensity

High intensity

Clinical ASCVD/age <75

LDL >190

DM and 10 yr risk >7.5%

Moderate intensity

Clinical ASCVD/age >75

--

DM and 10 yr risk <7.5%

10 yr risk >7.5%

New HTN Guidelines - Goals

Goals:

1. Reduce target organ damage

2. Reduce CV risk

3. Reduce CV morbidity and mortality

New HTN Guidelines: Cut Points

HTN Management

HTN and Women

• Pregnancy: - Gestational HTN and Pre-Eclampsia are not benign and confer higher lifetime risk of ASCVD and HTN - First line agents: methyldopa, nifedipine, and/or labetalol - Avoid: ACEi, ARBs

• Child-Bearing Age: - Avoid ACEi, ARBs - Consider role of OCPs as cause of HTN

• Side Effects: Higher incidence of cough with ACEi in women

Non Invasive Testing- General Rules

CHD risk increases with age and risk factor prevalence

Assess risk level (age, DM, PAD), symptoms, and FC

Low risk, young, asymptomatic- rarely testing indicated

Intermediate/high risk with symptoms- testing indicated

Objectives




Secondary Prevention

High prevalence of CVD risk factors in the US --Obesity 80M, HTN 75M, hyperlipidemia 37M, diabetes 10.5M--

Most secondary prevention involves the use of pharmacotherapy (ASA, statins, beta blockers, ACEi), in addition to lifestyle therapy

Women often receive less aggressive care, despite known benefits

Cardiac rehab is under utilized in women (MI, PCI, CABG, stable angina, PVD, CHF, transplant, valve surgery)

Secondary Prevention

Aspirin and statins reduce mortality in women with CVD

AHA 2016 scientific statement for the management of acute myocardial infarction in women (same treatment as men, ? dose adjust)

AHA/ACC 2014 guidelines for non-ST-elevation MI and acute coronary syndromes include sex-specific recommendations for use of early invasive strategy

Objectives




Stroke in Women

3rd leading cause of death in US for women

Impact: Women higher stroke disability, worse post stroke QOL, and greater stroke mortality (age-adjusted)

Symptoms: Women less likely to have traditional stroke symptoms (mental status changes)

Risk factors for stroke in women include: older age, HTN, Afib, CHF, metabolic syndrome, pre-eclampsia, and gestational HTN

Treatment: Women less likely to receive ASA, statin, thrombolytics; more likely to have delays in care

FAST (Face-Arm-Speech-Time): medical emergency and time to call 911


DO’s (class I) ∗ Low dose aspirin from 12th week of gestation until

delivery in pregnant women with hypertension ∗ Calcium supplementation during pregnancy to

prevent pre-eclampsia (calcium intake >600 mg/day) ∗ Severe hypertension in pregnancy should be

treated (methyldopa, labetalol, nifedipine) with consideration of maternal/ fetal side effects

∗ Blood pressure measurement prior to oral

contraceptives (OCs)


DONT’s (class III) ∗ OCs may be harmful with a history of

thromboembolic events or smoking ∗ Not useful to screen for pro-thrombotic mutations

prior to OC ∗ No hormone therapy in postmenopausal women for

stroke prevention

∗ No anticoagulation for AFib if low risk (anticoagulate if CHADS-Vasc>=2)

Objectives




Heart Failure and Cardiomyopathy

Almost 3M women with CHF

Prevalent risk factors for women: age, HTN (vs CAD for men)

Increasing prevalence of HFpEF; less likely to have CAD

More women than men have Takotsubo cardiomyopathy (broken-heart syndrome)

Unique pregnancy-associated (PPCM)

HFpEF and Diastolic Dysfunction: Pathophysiologic Stages

1. Impaired (slowed) relaxation (harder to ‘suck’ blood into the LV)

2. Increased diastolic stiffness (harder to ‘push’ blood

into the LV) 3. Increased restriction to filling (impaired filling of LV)

HFpEF

New HFpEF paradigm for pathophysiology: chronic inflammation from co-morbidities (DM, HLP, Obesity, HTN) causes endothelial dysfunction, myocardial fibrosis, and myocardial hypertrophy

Pathophysiology of HFpEF

Heart Disease in Pregnancy

Heart disease is leading cause of death in pregnancy: Peripartum cardiomyopathy and MPS (HTN)

Peripartum cardiomyopathy:

- Dx of exclusion; late gestation/early post partum - has better prognosis than in the past (72% recover EF) - Blacks more likely to have persistent cardiac dysfunction

- genetic mutations identified similar to other cardiomyopathies

MPS: Eclampsia, Pre-Eclampsia, Gestational HTN

Heart Failure and Cardiomyopathy

Mortality higher in women vs men awaiting heart transplantation

Similar survival in women as men with left ventricular assist devices

Reduced cardiovascular death/ HF hospitalization with: - sacubitril/valsartan (Entresto) - biventricular pacemakers in women with left

bundle branch block and QRS 130-149 msec - standard CHF therapy


Follow evidence-based guidelines for use of beta blockers and ACEi (increase survival)- caution with ACEi in reproductive age women, increased side effect of cough in women

Aldosterone receptor antagonists have EF/FC based indications and are contraindicated if serum creatinine is greater than 2.0 mg/dL in women (2.5 in men)

Some cardiomyopathies can reoccur: PPCM and Takatsubo’s. Don’t stop therapy! Cardiologist involvement.

Cardiac rehab referral

Objectives




Ischemia with normal cors or non-obstructive CAD (NOCA)

Angina in absence of CAD remains under- recognized & under-treated

Can present with SCD, STEMI, NSTEMI, UA, chronic angina

Up to 50% of women (17% of men) with anginal symptoms who undergo cardiac catheterization don’t have the obstructive type of CAD. Often dismissed from PCP or specialty practice.

Not benign: Higher rate of MI, CVA, CHF than asymptomatic women (25% vs 6%)

Pathophysiology: microvascular disease (MVD), endothelial dysfunction, micro embolization, high plaque burden (diffuse vs focal)

Need additional evaluation (cMR) and treatment

Ischemia and Non-obstructive CAD

Higher mortality in symptomatic women with ischemia and non-obstructive coronary artery disease than asymptomatic

Most women had significant

atheroma detectable by IVUS

Risk factors same as those for obstructive CAD


No guidelines-recommended therapy is available (except for symptom relief and CVD risk factor management) because of insufficient research in this field.

Experts recommend traditional anti-anginal therapy and drugs to reduce oxidative stress, improve endothelial dysfunction, and manage ischemia: - angiotensin converting enzyme inhibitors - Aspirin - Statins - Nitrates, Amlodipine, BB

Consider adding TCAs to improve chest pain control

Objectives




SCAD

Non atherosclerotic cause of ACS due to dissection (not plaque rupture)

LAD most common vessel

SCAD

Suspect if MI in young women with no risk factors

Risk factors: extreme emotional stress/exertion, pregnancy

Conservative therapy best

Associated with other vascular

abnormalities (fibromuscular dysplasia, vascular aneurysms)

In-hospital mortality low


No guideline directed therapies for SCAD patients exist.

Experts recommend conservative therapy; possible PCI for ACS. - PCI has a high failure rate with risk of

propagation of the coronary artery dissection - CABG has high failure rate with only 24% of

patients having patent graft vessels 3.5 years following revascularization

Risk of recurrence and major adverse cardiac events (MACE)

Objectives




Arrhythmias in Women Women under-treated for arrhythmias

EKG in women: higher resting HR, longer QTc (450 males, 460 femalesincreased likelihood of drug-induced TdP VT)

Over 60% of AFib occurs in women age >75

Thus, CHADS-Vasc stroke scoring system includes female gender (1) and age >75 (2) as risks

Women more Asymptomatic from Afib than men

CHADS-Vasc Score for AFib stroke risk

Age: <65 = 0, 65-74 = 1, >75 = 2

Female = 1

CHF = 1

HTN = 1

prior CVA/TIA = 2

vascular disease = 1

DM = 1

Score >=2: Anticoagulate!

Arrhythmias and Device Therapy in Women

AFib: - Higher risk of stroke and death with Afib - Similar safety and benefit with N/DOACS for non

valvular AF - Superior efficacy of ablation therapy for AFib

controversial

VT: - Lower risk of SCD in women vs men - AICD less survival benefit and under-utilized - High recurrence rate of VT after ablation in women vs

men - Inappropriate ICD therapy more likely in women vs men


2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation

2016 ACC/AHA updated guidelines on arrhythmias and device therapy - recommend guidelines based clinical

management irrespective of sex

Objectives




Key ACC/AHA Guidelines Statements

(2011) Effectiveness-based guidelines for the prevention of cardiovascular disease in women (2013) Guidelines on the assessment of cardiovascular risk: A report of the ACC/AHA task force on practice guidelines (2014) Role of non-invasive testing in the clinical evaluation of women with suspected ischemic heart disease (consensus statement) (2014) Acute myocardial infarction in women (Scientific statement) (2014) Guidelines for the management of patients with non-ST-elevation acute coronary syndromes (2014) Guidelines for the prevention of stroke in women: A statement for healthcare professionals from the AHA/ASA (2013) Guidelines for the management of heart failure (2013) An update of the 2013 ACCF/AHA 2013 guidelines for the management of heart failure: A report of the ACC/AHA task force on clinical practice guidelines and the heart failure society of America (2016) Toward Sex-Specific Guidelines for Cardiac Resynchronization Therapy? (2017) Guidelines for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults (AHA)

Conclusions Many significant advances including sex specific research,

utilization of therapy, and management guidelines Understanding of CV conditions occurring mainly in

women/more prevalent in women propelled by unique resources (e.g., Mayo registry for PPCM and SCAD; WISE study)

New risk factors for CVD identified for women: autoimmune disorders, OSA, pregnancy-associated conditions

Sex/gender specific research stimulated by Congressional mandates to NIH to include women, female animals/cells as a variable in research

Since 2014 FDA collecting and analyzing data from studies by sex

Powerful partnerships (academic/private, academic/community, others) improving CV health for women

Unresolved Issues

Available data limited in women age >80

Impact of culture, ethnicity, race

Gaps in knowledge for pathophysiology

Ongoing quest for therapeutic options

Quiz 1. Heart disease is the leading killer of women

True or False?

2. Deaths from heart disease are increasing in younger women

True or False?

3. Evidence-based guidelines are under-utilized in women

True or False?

4. Gestational DM, HTN and pre-eclampsia are not CVD risk factors

True or False?

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