Evidence-Based Guidelines for Cardiovascular Disease

Prevention in Women

Objectives

To present strategies to assess and stratify women into high risk, at risk, and optimal risk categories for cardiovascular disease

To summarize lifestyle approaches to the prevention of cardiovascular disease in women

Objectives

To review evidence-based approaches to cardiovascular disease prevention for patients with hypertension, lipid abnormalities, and diabetes

To review an evidence-based approach to pharmacological risk intervention for women at risk for cardiovascular events

Objectives

To summarize commonly used therapies that shouldnot be initiated for the prevention or treatment ofheart disease, because they lack benefit, or becauserisks outweigh benefits

CVD and Other Major Causes of Death for Women in the United States: 2004

0

100,000

200,000

300,000

400,000

500,000

Total CVD CHD Cancer Stroke Asthma +COPD

Source: Adapted from Rosamond 2008

Annual Numbers of U.S. Adults Diagnosed with Myocardial Infarction and Fatal CHD by Age and Sex Categories: 1987-2004

0

100,000

200,000

300,000

35-44 45-64 65-74 75+

MenWomen

Source: Adapted from Rosamond 2008

Age in Years

Cardiovascular Disease Mortality: U.S. Males and Females 1980-2004

400,000

450,000

500,000

550,000

1980 1985 1990 1995 2000 2004

MenWomen

Source: Adapted from Rosamond 2008

Racial and Ethnic Groups

Cardiovascular disease is the leading cause of death for African Americans, Latinos, Asian Americans, Pacific Islanders, and American Indians

African American women are at the highest risk for death from heart disease among all racial, ethnic, and gender groups

Source: Rosamond 2008

Evidence-based Guidelines for Cardiovascular Disease Prevention

in Women: 2007 UpdateMosca L, et al. Circulation 2007; 115:1481-501.

http://www.circ.ahajournals.org

Cardiovascular Disease Prevention in Women: Current Guidelines A five-step approach

Assess and stratify women into high risk, at risk, and optimal risk categories

Lifestyle approaches recommended for all women Other cardiovascular disease interventions:

treatment of HTN, DM, lipid abnormalities Highest priority is for interventions in high risk

patients Avoid initiating therapies that have been shown

to lack benefit, or where risks outweigh benefits

Source: Adapted from Mosca 2004

Risk Stratification: High Risk

Diabetes mellitus Documented atherosclerotic disease

Established coronary heart disease Peripheral arterial disease Cerebrovascular disease Abdominal aortic aneurysm

Includes many patients with chronic kidney disease, especially ESRD 10-year Framingham global risk > 20%, or high risk based on another population-adapted global risk assessment tool

Source: Mosca 2007

Risk Stratification: At Risk:

> 1 major risk factors for CVD, including: Cigarette smoking Hypertension Dyslipidemia Family history of premature CVD (CVD at < 55 years

in a male relative, or < 65 years in a female relative) Obesity, especially central obesity Physical inactivity Poor diet

Metabolic syndrome Evidence of subclinical coronary artery disease (eg coronary

calcification), or poor exercise capacity on treadmill test or abnormal heart rate recovery after stopping exercise

Source: Mosca 2007

Definition of Metabolic Syndrome in Women

Abdominal obesity - waist circumference > 35 in. High triglycerides ≥ 150mg/dL Low HDL cholesterol < 50mg/dL Elevated BP ≥ 130/85mm Hg Fasting glucose ≥ 100mg/dL

Source: AHA/NHLBI 2005

Risk Stratification:

Optimal risk: No risk factors Healthy lifestyle Framingham global risk < 10%

Source: Mosca 2007

Lifestyle Interventions

Smoking cessation Physical activity Heart healthy diet Weight reduction/maintenance

Source: Mosca 2007

Relative Risk of Coronary Events for Smokers Compared to Non-Smokers

3.12

5.48

1

0

1

2

3

4

5

6

Never Smoked 1-14 Cigarettes perday

15 Cigarettes perday

Relative Risk

Source: Adapted from Stampfer 2000

Smoking

All women should be consistently encouraged to stop smoking and avoid environmental tobacco The same treatments benefit both women and men Women face different barriers to quitting

Concomitant depression Concerns about weight gain

Provide counseling, nicotine replacement, and other pharmacotherapy as indicated in conjunction with a behavioral program or other formal smoking cessation program

Source: Fiore 2000, Mosca 2007

Five A’s

Ask about tobacco use at every visit Advise in a clear and personalized message Assess willingness to quit Assist to quit Arrange follow-up

For more information: http://www.surgeongeneral.gov/tobacco/treating_tobacco_use.pdf

Source: Fiore 2000

Risk Reduction for CHD Associated with Exercise in Women

00.10.20.30.40.50.60.70.80.9

1

1 2 3 4 5Quintile Group for Activity (MET - hr/wk)

Walking

Any PhysicalExercise

Source: Manson 1999

Modifiable Risk Factors: Sedentary Lifestyle 40% of women report no leisure time physical activity

Exercise is less prevalent among white women compared to white men

African American and Hispanic women have the lowest prevalence of leisure time physical activity

Source: U.S. Surgeon General 1996, Rosamond 2008

Physical Activity

Consistently encourage women to accumulate a minimum of 30 minutes of moderate intensity physical activity on most, or preferably all, days of the week

Women who need to lose weight or sustain weight loss should accumulate a minimum of 60-90 minutes of moderate-intensity physical activity on most, and preferably all, days of the week

Source: Mosca 2007

Body Weight and CHD Mortality Among Women

5.8

4.6

3.1

1.411

0

1

2

3

4

5

6

19.0-21.9 22.0-24.9 25.0-26.9 27.0-28.9 29.0-31.9 32

BMI

Relative Risk of CHD

Mortality Compared to

BMI<19

P for trend < 0.001

Source: Adapted from Manson 1995

Body Weight and CHD Mortality Among Women

7.4

2.6

0

1

2

3

4

5

6

7

8

Wt Gain 10-19kg Wt Gain 20kg

Weight Gain Since Age 18

Relative Risk of CHD

Mortality

P for trend < 0.001

≥

Source: Adapted from Manson 1995

1998

2006

1990

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Obesity Trends* Among U.S. AdultsBehavioral Risk Factor Surveillance SystemBRFSS, 1990-2006

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman)

Source: CDC

Weight Maintenance/Reduction Goals

Women should maintain or lose weight through an appropriate balance of physical activity, calorie intake, and formal behavioral programs when indicated to maintain: BMI between 18.5 and 24.9 kg/m² Waist circumference < 35 inches

Source: Mosca 2007

Body Mass Index: Definition

BMI = weight in kilograms divided by the square of the height in meters (kg/m2)

BMI chart showing BMI based on weight in pounds and height in inches available at: http://www.nhlbi.nih.gov/guidelines/obesity/ob_home.htm

Source: NHLBI

Low Risk Diet is Associated with Lower Risk of Myocardial Infarction in Women

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

1 2 3 4 5

Diet Score by Quintile (1= least vegetables, fruit, whole grains, fish, legumes)

RelativeRisk of MI*

*Adjusted for other cardiovascular risk factors

Source: Akesson 2007

P< .05 for quintiles 3-5 comparedto 1-2

Diet Consistently encourage healthy eating patterns

Healthy food selections: Fruits and vegetables Whole grains, high fiber Fish, especially oily fish, at least twice per week No more than one drink of alcohol per day Less than 2.3 grams of sodium per day

Saturated fats < 10% of calories, < 300mg cholesterol Limit trans fatty acid intake (main dietary sources are baked

goods and fried foods made with partially hydrogenated vegetable oil)

Source: Mosca 2007

Major Risk Factor Interventions

Blood Pressure Target BP<120/80 mmHg Pharmacotherapy if BP> 140/90, or > 130/80 in diabetics or

patients with renal disease Lipids

Follow NCEP/ATP III guidelines Diabetes

Target HbA1C<7%, if this can be accomplished without significant hypoglycemia

Source: Mosca 2007

Hypertension

Encourage an optimal blood pressure of < 120/80 mm Hg through lifestyle approaches

Pharmacologic therapy is indicated when blood pressure is > 140/90 mm Hg or an even lower blood pressure in the setting of diabetes or target-organ damage (> 130/80 mm Hg)

Thiazide diuretics should be part of the drug regimenfor most patients unless contraindicated, or unless compelling indications exist for other agents

For high risk women, initial treatment should be with a beta-blocker or angiotensin converting enzyme inhibitor or angiotensin receptor blocker

Source: Mosca 2007

Lifestyle Approaches to Hypertension in Women

Source: JNC VII 2004, Sacks 2001, Mosca 2007

Maintain ideal body weight Weight loss of as little as 10 lbs reduces blood pressure

DASH eating plan Even without weight loss, a diet rich in fruits, vegetables, and low

fat dairy products can reduce blood pressure

Sodium restriction to 2300 mg/d Further restriction to 1500 mg/d may be beneficial, especially in

African American patients

Increase physical activity

Limit alcohol to one drink per day Alcohol raises blood pressure One drink = 12 oz beer, 5 oz wine, or 1.5 oz liquor

DASH Eating Plan

7–8 servings of grains, grain products daily

4–5 servings of vegetables daily

4–5 servings of fruits daily

2–3 servings of low-fat or nonfat dairy foods daily

≤ 2 servings of meats, poultry, fish daily

4–5 servings of nuts, seeds, legumes weekly

Limited intake of fats, sweets

Source: NHLBI 1998

DASH Diet with Low Sodium Intake in Hypertensive Individuals Compared to Control Diet with Average U.S. Sodium Intake

-12.6

-9.5

-14

-12

-10

-8

-6

-4

-2

0

Change in BP

(mm Hg)

Systolic BP

African American Non-African American

* P<.001 from baseline*

Source: Sacks 2001

*

Lipids

Optimal levels of lipids and lipoproteins in women are as follows (these should be encouraged in all women with lifestyle approaches): LDL < 100mg/dL HDL > 50m/dL Triglycerides < 150mg/d Non-HDL (total cholesterol minus HDL) < 130mg/d

Source: Mosca 2007

Lipids

In high-risk women or when LDL is elevated: Saturated fat < 7% of calories Cholesterol < 200mg/day Reduce trans-fatty acids

Major dietary sources are foods baked and fried with partially hydrogenated vegetable oil

Source: Mosca 2007

Approximate and Cumulative LDL Cholesterol Reduction Achievable By Dietary ModificationDietary Component Dietary Change Approximate

LDL Reduction

MajorSaturated fat <7% of calories 8-10%Dietary cholesterol <200 mg/day 3-5%Weight reduction Lose 10 lbs 5-8%

Other LDL-lowering optionsViscous fiber 5-10 g/day 3-5%Plant/sterol 2g/day 6-15% stanol esters

Cumulative estimate 20-30%

Source: Adapted from ATP III 2002

Lipids

Treat high risk women aggressively with pharmacotherapy LDL-lowering pharmacotherapy (preferably a statin)

should be initiated simultaneously with lifestyle modification for women with LDL>100mg/dl

Source: Mosca 2007

Coronary Disease Mortality and Diabetes in Women

0

10

20

30

40

50

60

0 - 3 4 - 7 8 - 11 12 - 15 16 - 19 20 - 23

Duration of Follow-up (yrs)

DiabeticWomenNondiabeticWomen

Source: Krolewski 1991

Race/Ethnicity and Diabetes

At high risk: Latinas American Indians African Americans Asian Americans Pacific Islanders

Source: American Diabetes Association 2001

Preventive Drug Interventions

Aspirin – High risk women 75-325 mg/day, or clopidogrel if patient intolerant to aspirin,

should be used in high-risk women unless contraindicated

Aspirin- Other at-risk or healthy women Consider aspirin therapy (81 mg/day or 100 mg every other

day) if blood pressure is controlled and benefit is likely to outweigh risk of GI side effects and hemorrhagic stroke

Benefits include ischemic stroke and MI prevention in women aged > 65 years, and ischemic stroke prevention in women < 65 years

Source: Mosca 2007

Women’s Health Initiative Estrogen and Progestin Arm: Absolute Excess Risk

Excess CHD events: 7/10,000 woman-years

Excess stroke events : 8/10,000 woman-years

Excess pulmonary emboli: 8/10,000 woman-years

Excess invasive breast cancer: 8/10,000 woman-years

Source: Writing Group for the WHI Investigators 2002

Women’s Health Initiative Estrogen and Progestin Arm: Absolute Benefits

Fewer colorectal cancers: 6/10,000 woman-years

Fewer hip fractures: 5/10,000 woman-years

Source: Writing Group for the WHI Investigators 2002

Women’s Health Initiative: Estrogen Alone in Postmenopausal Women Compared to Placebo: Major Clinical Outcomes

0.61

0.77

0.91

1.04

1.08

1.39

0 0.5 1 1.5 2

Stroke

Colorectal Cancer

Total Mortality

CHD

Breast Cancer

Hip Fracture

Relative Risk Compared to Placebo

*

* P < .05*

Favors Treatment Favors Placebo

Source: Adapted from WHI Steering Committee 2004

Menopausal Hormone Therapy, SERMs and CVD: Summary of Major Randomized Trials Use of estrogen plus progestin associated with

a small but significant risk of CHD and stroke Use of estrogen without progestin associated with

a small but significant risk of stroke Use of all hormone preparations should be limited

to short term menopausal symptom relief Use of a selective estrogen receptor modulator

(raloxifene) does not affect risk of CHD or stroke, but is associated with an increased risk of fatal stroke

Source: Hulley 1998, Rossouw 2002, Anderson 2004, Barrett-Connor 2006

Interventions that are not useful/effective and may be harmful for the prevention of heart disease

Hormone therapy and selective estrogen-receptor modulators (SERMs) should not be used for the primary or secondary prevention of CVD

Source: Mosca 2007

Interventions that are not useful/effective and may be harmful for the prevention of heart disease Antioxidant supplements and folic acid

supplements No cardiovascular benefit in randomized trials of primary

and secondary prevention

Source: Mosca 2007

The NORVIT Trial: Homocysteine Lowering Did Not Reduce Cardiovascular Events in Women with Prior MI

0

0.2

0.4

0.6

0.8

1

1.2

Folic Acid and B12 Folic Acid, B12, and B6

RelativeRisk of CVD Event

*Compared to B12 alone

Source: Bonaa 2006

* **

**Compared to placebo

Reproductive Age Women and CHD

Over 10,000 reproductive age women suffer MI or fatal CHD each year

All women of reproductive age prescribed drug therapy should be counseled about preconception planning, as many recommended drugs are contraindicated during pregnancy

Reproductive age women with CHD who are pregnant or planning pregnancy should be cared for by health care providers with expertise in both cardiovascular disease and obstetrics (team approach)

Source: American Heart Association 2008, Pregler 2005

The Heart Truth Professional Education Campaign Website

http://www.womenshealth.gov/hearttruth

Conclusions

Gender differences exist in diagnosis, treatment, and prognosis of CHD

Knowledge of gender differences is essential for appropriate therapy

Evidence-based guidelines provide a framework for prevention and treatment of cardiovascular disease in women