9/24/2019 Overview Women and Heart Disease Cardiovascular Health - - PDF document

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Cardiovascular Health 101

Chrisandra Shufelt MD, MS

Associate Director, Barbra Streisand Women’s Heart Center & Preventive and Rehabilitative Cardiac Center Director, Women’s Hormone and Menopause Program Associate Professor, Cedars‐Sinai Medical Center

Disclosures

• No disclosures related to this topic.
• Funding: NIH/ NHLBI

Overview

• Women and Heart Disease

– Facts – Sex-specific risk factors – What is the impact of menopause on CVD risk

• CVD Prevention and Menopause, when to recommend:

– Statins – Aspirin – Blood pressure

Alarming Facts: Cardiovascular Disease in Women

• CVD remains the leading killer of women in US

– Only half of women know CVD is their #1 killer

• Nearly every 80 seconds, a woman dies from heart disease

– 1 in 8 prior to menopause – 1 in 3 after menopause

• Heart disease and stroke kill more women each year than all cancers

combined

CDC.gov – Heart Disease Facts Benjamin et al. Circulation 2017;135(10):e146‐e603

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Is this optimal for women? Go Red awareness campaign Education, Women’s CVD trials

0.6 0.6 2.0 3.6 2.2 3.6 4.0 6.5

1 2 3 4 5 6 7 <40 40–44 45–49 50–54

Premenopausal Postmenopausal

Incidence (per 1000 women) Age (years)

Kannel WB, et al. Ann Intern Med. 1976;85:447-52.

The Framingham Study

Incidence of CVD: Relation to Menopause Status

Symptoms – Heart Disease

Typical in both sexes

• Pain, pressure, squeezing, or stabbing pain in

the chest

• Pain radiating to neck, shoulder, back, arm, or

jaw

• Pounding heart, change in rhythm
• Difficulty breathing
• Heartburn, nausea, vomiting, abdominal pain
• Cold sweats or clammy skin
• Dizziness

Typical in Women

• Milder symptoms

(without chest pain)

• Sudden onset of weakness, shortness of

breath, nausea/ vomiting, indigestion, fatigue, body aches, or overall feeling

• f illness (without chest pain)
• Unusual feeling or mild discomfort in the back,

chest, arm, neck, or jaw (without chest pain)

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Milner KA et al. Am J Cardiol. 1999;84:396-399.

Gender Differences in Heart Attack Symptoms

• Women have more symptoms overall
• Women also have more atypical symptoms

20 30 40 50 60 10

Dyspnea Indigestion Nausea/ vomiting Dizziness/ fainting Fatigue Sweating Arm/shoulder pain

Men n=127 Women n=90 Patients (%)

P=0.032 P=0.012 P=0.040 P=0.581 P=0.071 P=0.235 P=0.085

Traditional CVD Risk Factors & Women

Aggarwal, NR et al. Circ Cardiovasc Qual Outcomes. 2018;11:e004437.

Aggarwal et al. Circ Cardiovasc Qual Outcomes; Feb 2018.

Who should take a statin for CVD prevention?

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Prevalence of High Serum Cholesterol 2005-2006

American Heart Association. Heart Disease and Stroke Statistics2018 Update.

Population (%) Total 20- 39y/o > 40-59 y/o > 60 and older

High serum total cholesterol = serum total cholesterol > 240mg/dl * Significant difference from men

* *

Change in Lipids After Menopause

Jensen et al. Maturitas. 1990;12:321‐331. 90 100 110

• 24

6

• 18 -12
• 6

% of Mean Level During Premenopause Total-C

• 24

6

• 18
• 12
• 6

HDL-C % of Mean Level During Premenopause Months 90 100 110

• 24

6

• 18 -12
• 6

LDL-C Months 90 100 110 Triglycerides 90 100 110

• 24 -18
• 12
• 6

6 Menopause Menopause

ACC Risk Calculator Plus to Assess Risk Category

Use the new AHA/ACC Blood Cholesterol Guideline Algorithm for Primary Prevention to guide management

ACC/AHA Guidelines: Risk-Enhancers for ASCVD

• Family history of premature ASCVD
• Persistently elevated LDL-C ≥160 mg/dL
• Chronic kidney disease
• Metabolic syndrome
• Conditions specific to women (e.g., gestational diabetes, preeclampsia,

premature menopause, post-menopausal state)

• Inflammatory disease (generally more common in women)
• Ethnicity (e.g., South-Asian ancestry)

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Age 0–19 y

• Lifestyle to prevent or

reduce ASCVD risk

• Diagnosis of Familial

Hyper-cholesterolemia → statin

Age 20–39 y

• Estimate lifetime

risk to encourage lifestyle to reduce ASCVD risk

• Consider statin if

family history premature ASCVD and LDL-C ≥160 mg/dL

Age 40–75 y &

LDL-C 70 to <190 mg/dL without diabetes mellitus

• 10-year ASCVD risk

percent begins risk discussion

2018 AHA/ACC Guideline on the Management of Blood Cholesterol: Primary Prevention

Primary Prevention: Assess ASCVD Risk in Each Age Group Emphasize Adherence to Health Lifestyle LDL-C 190 mg/dL No risk assessment; High-intensity statin Diabetes mellitus and age 40-75 y Moderate-intensity statin Diabetes mellitus and age 40-75 y Risk assessment to consider high-intensity statin Age >75 y Clinical assessment, Risk discussion

Class I (Strong). Benefit >>> Risk. Class IIa (Moderate). Benefit >> Risk. Class IIb (Weak). Benefit  Risk. Grundy SM et al. Circulation. 2019;139:e1082-e1143. Although high TG was noted as a CVD risk factor, treatment of HTG was covered only briefly and prescription omega-3 was not mentioned. (Published simultaneously with REDUCE-IT.) Continued on next slide

2018 AHA/ACC Guideline on the Management of Blood Cholesterol: Primary Prevention (con’t)

≥7.5% to <20% “Intermediate Risk” ≥20% “High Risk” Risk discussion:

If risk estimate + risk enhancers favor statin, initiate moderate-intensity statin to reduce LDL-C by 30% – 49%

Risk discussion:

Initiate statin to reduce LDL-C ≥50%

Risk discussion: Emphasize lifestyle to reduce risk factors Risk discussion:

If risk enhancers present then risk discussion regarding moderate- intensity statin therapy

<5% “Low Risk” 5% to <7.5% “Borderline Risk”

Grundy SM et al. Circulation. 2019;139:e1082-e1143. Class I (Strong). Benefit >>> Risk. Class IIa (Moderate). Benefit >> Risk. Class IIb (Weak). Benefit  Risk.

If risk decision is uncertain: Consider measuring CAC in selected adults:

• CAC = zero (lower risk; consider no statin, unless diabetes, family history of

premature CHD, or cigarette smoking are present)

• CAC = 1–99 favors statin (especially after age 55)
• CAC = 100+ and/or ≥75th percentile, initiate statin therapy

Available Statins

High-Intensity Statin Therapy Moderate-Intensity Statin Therapy Low-Intensity Statin Therapy Daily dose lowers LDL- C by approximately ≥50% Daily dose lowers LDL-C by approximately 30% to <50% Daily dose lowers LDL- C by <30% Atorvastatin 40-80 mg Rosuvastatin 20(40) mg Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin 20-40 mg Simvastatin 80 mg* Pravastatin 40(80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2-4 mg Simvastatin 10 mg Pravastatin 10-20 mg Lovastatin 20 mg Fluvastatin 20-40 mg Pitavastatin 1 mg

Stone NJ, et al. ACC/AHA 2013 Blood Cholesterol Guidelines. J Am Cardiol Coll. 2014;63(25):2889-2934.

Who should take an Aspirin for CVD prevention?

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Membrane Phospholipids Arachadonic Acid Prostaglandin H2 COX-1 Thromboxane A2  Platelet Aggregation Vasoconstriction Prostacyclin  Platelet Aggregation Vasodilation Aspirin

Aspirin: Mechanism of Action

Husain S, et al. Circulation. 1998;97:716‐20. Vane JR. Nature. 1971;231:235‐5. Patrono C. NEJM 1994;330:1287‐94.

Irreversibly inhibits platelet function

Source: Steering Committee of the Physicians’ Health Study Research Group. NEJM 1989;321:129-135 CI=Confidence interval, CV=Cardiovascular

Physician’s Health Study (PHS)

22,071 male participants randomized to aspirin (325 mg every

• ther day) followed for an average of 5 years

Aspirin reduces the risk of myocardial Infarction among men

Aspirin Evidence: Primary Prevention

Women’s Health Study

Ridker PM, Cook NR, Lee IM, et al. N Engl J Med. 2005;352:1293‐1304.

• 39,876 healthy women  100 mg/d aspirin on

alternate days or placebo

• average age at 55 yrs for 10 yrs
• Aspirin did not lower the risk of MI or

cardiovascular death but instead, significantly lowered the risk of total stroke by 17% and risk of ischemic stroke by 24%

• women 65+ years had a significant benefit from

aspirin with reductions in major CVD events by 25%, MI by 35%, and ischemic stroke by 30%

But then came 2018…

ARRIVE

ASPREE

ASCENT

Aspirin vs placebo, n=12,546, Moderate risk of CVD

• men >55 yrs with >2

CVD risk factors

• women>60 yrs with >3

CVD risk factors

Aspirin + omega 3 or placebo, n=15,480 diabetes but no CVD, age 40 yrs and older

• 40% women

Aspirin vs placebo, n=19,114, one or more CVD risk factor, 70yrs and older,

• 56% women

Gaziano et al. Lancet. 2018 Aug. //doi.org/10.1016/S0140-6736(18)31924-X McNeil JJ, et al. NEJM. 2018;379(16):1509-1518. Zheng SL, et al. JAMA. 2019;321(3):277-287.

No to minimal benefits seen for CVD, with increased risk for major bleeding

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2019 AHA Recommendations for ASA

• For primary prevention, low dose aspirin should be considered in

women age 40-70 years with a 10-year cardiovascular risk >20%

• In women with diabetes and a 10-year cardiovascular risk > 10%
• The risk of bleeding outweighs the benefits in low-risk women and

in women above age 70 years.

Arnett Donna K et al. Circulation.2019 0(0):CIR.0000000000000678.

What blood pressure should I recommend?

Estimated Prevalence of Hypertension in US Adults by Age and Sex NHANES 1999-2004

10 20 30 40 50 60 70 80 90 Percent

20-34 35-44 45-54 55-64 65-74 75+

Ages

Men Women

H

Heart Disease and Stroke Statistics – 2018 Update, AHA

BP Rises After Menopause Risk of HTN Triples

*P ≤.05; †P = .07. ‡Baseline SBP: Pre = 121.4 ± 1.3 mm Hg; Peri = 122.0 ± 1.8 mm Hg; Post = 126.5 ± 1.7 mm Hg. Controls were men matched by age and BMI. Staessen JA, et al. J Hum Hypertens. 1997;11:507–514.

Changes in SBP From Baseline to Follow-Up (Mean 5.2 y) 6 5 4 3 2 1 –1 –2 –3 –1.9 .4 3.3 3.8 .2 –.1

†

* Women Controls Pre (n = 166) Peri (n = 44) Post (n = 105) Change From Baseline‡ SBP (mm Hg)

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Postmenopausal Hypertension

• Estrogen is potent vasodilator

– Relaxes VSMC by increase NO

• Studies have shown that menopause increases salt-sensitivity,

leading to an increase in blood pressure

• Loss of Estrogen  RAAS activation

– Increased number of AT1 receptors – Increased expression and activity of ACE – Reduced plasma renin levels

Oparil S, Miller AP. J Clin Hypertension (Greenwich).2005; 7: 300-307. Reckelhoff JF. Hypertension. 2005: 45: 170-174. Nickenig G et al. Circulation. 1998; 97: 2197-2201.

136 121

Years Systolic BP (mm Hg) Standard Rx Intensive Rx

The SPRINT Research Group. N Engl J Med 2015; 373:2103‐2116

SPRINT STUDY: 5‐years of follow up

CVD Event Death*

Years of follow up

*Stopped early after mean follow up of 3.26 years.

SPRINT STUDY: Make BP great again!

2017 AHA/ACC BP Guidelines

• Hypertension is now defined as BP ≥

130/80 mm Hg

• High blood pressure should now be

treated earlier with lifestyle changes ± medication at a threshold of 130/80 mm Hg rather than 140/90 mm Hg

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JNC 7 vs. 2017 BP Guidelines

SBP DBP JNC 7 2017 ACC/AHA <120 and <80 Normal BP Normal BP 120-129 and <80 Prehypertension Elevated BP 130-139

• r

80-89 Prehypertension Stage 1 hypertension 140-159

• r

90-99 Stage 1 hypertension Stage 2 hypertension ≥160

• r

≥100 Stage 2 hypertension Stage 2 hypertension

High blood pressure now defined as 130/80 mm Hg compared to prior definition of 140/90 mm Hg High blood pressure now defined as 130/80 mm Hg compared to prior definition of 140/90 mm Hg

BP Thresholds and Recommendations for Treatment and Follow- Up

BP-lowering medications is recommended for patients with:

• Stage 1 hypertension with clinical ASCVD or

estimated 10-y CVD risk ≥10%

• Stage 2 hypertension
• Start 2 BP medications

Nonpharmacologic therapy recommended for patient with:

• Elevated BP
• Patients with Stage 1 hypertension with

no clinical ASCVD or estimated 10-y CVD risk <10%

Normal BP (BP<120/80 mm Hg) Elevated BP (BP 120-129/<80 mm Hg) Stage 1 hypertension (BP 130-139/<80-89 mm Hg) Promote optimal lifestyle habits

ABCDE of Primary Prevention Summary

• Emerging risk factors for women and CVD include

adverse pregnancy outcomes, autoimmune disorder, XRT and chemo for cancer, and low estrogen states, such as premature menopause.

• CVD risk factors such as hypertension, dyslipidemia

increase at the time of menopause

• Statin therapy recommendation is based on ASCVD

risk and risk enhancing modifiers in women

• Aspirin is used in primary prevention of CVD in high

ASCVD risk in women

• A blood pressure >130/80 is considered stage 1

hypertension and management is based on ASCVD risk in women

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Thank you