1 we’ve come a long way-prevention of cardiovascular disease in women ned ferguson, m.d....

1We’ve Come A Long Way-Prevention of

Cardiovascular Disease in Women

Ned Ferguson, M.D.University of Wisconsin Hospital and ClinicsSection of Cardiovascular MedicinePreventive CardiologyJanuary 2005

Faculty, National WATCH Program-Women’s AgendaTargeting Cholesterol in Heart DiseaseSpeaker, WATCH ProgramSpeaker, AHA Go Red for Women campaign

3

Cardiovascular Disease Prevention in Women

Scope of the problemLipids and CVDClinical trial evidenceThe new evidence-based AHA guidelines

4Deaths Due to Cardiovascular Diseases

United States 1979–2001

380

400

420

440

460

480

500

520

79 81 83 87 89 95 99Years

91 9785 93

Women

Men

De

ath

s (i

n T

ho

usa

nd

s)

01

American Heart Association. Heart Disease and Stroke Statistics -- 2004 Update. Dallas, Texas: American Heart Association; 2003.

5Cardiovascular Disease in Women: The Stats

• 1 in 5 women has some form of CVD • 1 in 2.5 women will die of heart disease

or stroke, compared with 1 in 30 from breast cancer

• Heart disease and stroke are the No. 1 and 3 causes of death in women

• In 2001, CVD– caused the deaths of 498,863 women

– was the first listed diagnosis of 3,168,000 women discharged from hospitals

American Heart Association. 2004 Heart and Stroke Statistical Update.

Dallas, Texas: AHA, 2003.

6Leading Causes of Death for WomenUnited States: 2001

A - Diseases of the Heart, and Stroke B - Cancer

F - Diabetes Mellitus

C - Accidents

G - Nephritis, Nephrotic Syndrome

Black or African-American

A - Diseases of the Heart, and Stroke

B - Cancer

D - Chronic Lower Respiratory

Diseases

F - Alzheimer’s Disease

G - Influenza and Pneumonia

White Hispanic or Latino

A - Diseases of the Heart, and Stroke

B - Cancer

E - Diabetes Mellitus

C - Accidents

F -Influenza and Pneumonia

Source: CDC/NCHS.



A B F C G

36.5

20.5

5.12.9 2.8

A B D F G

37.6

21.7

5.52.3 2.9

A B E C F

32.6

21.1

6.14.2 2.8

Percent of Total Deaths

7Prevalence of Cardiovascular Diseases in AmericansAge 20 and Older by Age and SexNHANES III: 1988-94

Source: CDC/NCHS. These data include CHD, CHF, stroke and hypertension.



20-24 25-34 35-44 45-54 55-64 65-74 75+Ages

01020304050607080

Per

cen

t o

f P

op

ula

tio

n MenWomen

5.54.6

10.4

4.2

17.413.6

34.228.9

51.048.1

65.2 65.270.7

79.0

8Age-Adjusted Death Rates for Coronary Heart Disease, Stroke, Lung and Breast Cancer for White and Black Females - United States: 2000

American Heart Association. Heart Disease and Stroke Statistics -- 2004 Update. Dallas, Texas: American Heart Association; 2003.

9

Annual Number of American Women Having Diagnosed Heart Attack by Age: ARIC: 1987-2000

Source: Extrapolated from rates in the NHLBI’s ARIC surveillance study, 1987-2000. These data don’t include silent MIs.



10,0000

100

200

300

400

500

29-44

New

and

Rec

urre

nt A

ttack

sIn

Tho

usan

ds

45-64 65+

88,000

372,000

Ages

10Coronary Disease More Often Presents Atypically in Women

• Chest pain/pressure/tightness is still common-but many may present with:

Back, jaw, neck, or shoulder discomfort Vague, flu-like symptoms Dizziness Fatigue, exhaustion Dyspnea GI Symptoms-Nausea, Indigestion Syncope

11Women Often Have a Worse Prognosis Than Men

• 38% of women will die within 1 year after having a first MI, compared with 25% for men

• 64% of women who died suddenly of CHD had no previous symptoms of this disease, compared with 50% for men

Source: Framingham Heart Study, National Heart Lung Blood Institute.

American Heart Association. 2004 Heart and Stroke Statistical Update. Dallas, Texas: AHA, 2003.

12

• Women with coronary syndrome (ACS) are less commonly diagnosed with ACS: more women have unstable angina (UA) and less ST elevation with acute MI (STEMI) than men.• If recognized early, women with UA have a better

prognosis than men, though a worse outcome with acute STEMI.

• Women with non-STEMI have greater hospital mortality than men, but receive fewer diagnostic tests, fewer cardiology consultations, less percutaneous interventions and fewer beneficial discharge medications.

13

• Women younger than 50 years of age have twice the MI hospital mortality than comparably aged men. Women are more likely to have MI complications of shock, heart failure, recurrent chest pain, cardiac rupture, and stroke.

• Antiplatlet therapy, thrombolysis, acute angioplasty, and CABG. All entail greater bleeding

risk for women than men.

14

• Post-CABG mortality rates in women are twice those in men.

• Post-MI survival is influenced to a large extent by age and diabetes in women.

15

• Anginal chest pain in women is less likely to be associated with flow-limiting obstructive coronary lesions than anginal chest pain in men.

• Anginal chest pain in women without flow-limiting coronary lesions may be associated with endothelial dysfunction and impaired coronary flow reserve.

• Such coronary microvascular dysfunction is associated with an increased rate of hospitalization for chest pain, a poor quality of life, and increased ongoing health care costs.

• Women’s Ischemic Syndrome Evaluation, Executive Summary.Circulation 2004;109:805-807.www.circulationaha.org e44-e63.

16

• Women have been underrepresented in many major clinical hypertension and dyslipidemia trials.

• In ALLHAT, there were 15,000 women and 17,000 men in this major hypertension trial.• However, men had better BP control and more

men received two drugs to reach goal than women.

• Women and men who achieved the same degree of BP control had the same clinical outcome.

17

• Personal observation: The metabolic syndrome with its attendant greatly increased cardiovascular

risk is taken less seriously in women than men.

• Established clinical evidence: Framingham scoring tables seriously underestimate cardiovascular risk with women with the metabolic syndrome.

18

• From 1997 to 2003, women have become more aware of CVD as leading cause of death

• <50% of women continue to list CVD as leading cause of death in 2003

• Young women feel least informed• Women at highest risk of CVD are the least

likely to be aware they are at risk

Mosca L et al. Circulation 2004; 109:573-579.

19Women’s Awareness1997, 2000, 2003:Women’s Perception of Leading Cause of Death

%


05

101520253035404550

BreastCancer

Cancer(general)

HeartDisease

Unsure

1997

2000

2003

20Women’s Awareness 2003:Perceived Leading Cause of Death by Ethnic Group


%

0

10

20

30

40

50

60

BreastCancer

Cancer(general)

HeartDisease

Unsure

White

Black

Hispanic

African-American and Latino/Hispanic women, who are at higher risk for heart disease, were least likely to be aware.

21

Behavioral Risk Factor Surveillance System, Centers for Disease Control and Prevention.

1991 1995

2002

Obesity Trends* Among U.S. AdultsBRFSS, 1991-2002

No Data <10% 10%–14% 15%–19% 20%–24% >25%

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

22NCEP ATP III: Clinical Identification of the

Metabolic Syndrome*

*Diagnosis is established when 3 of these risk factors are present.

Risk Factor

Waist circumference Men Women

Triglycerides

HDL-C Men

Women

Blood Pressure

Fasting glucose

Defining Level

> 102 cm (> 40 inches)> 88 cm (> 35 inches)

≥ 150mg/dL

< 40 mg/dL

< 50 mg/dL

≥ 130 / ≥ 85 mm Hg

≥ 110 mg/dL

National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.

23NHANES III: Age-Adjusted Prevalence of ≥3 Risk Factors for the

Metabolic Syndrome*

*Criteria based on ATP III; diabetics were included in diagnosis; overall unadjusted prevalence was 21.8%.

Ford ES et al. JAMA. 2002;287:356-359.

24.8

16.4

28.3

22.825.7

35.6

%%

0

5

10

15

20

25

30

35

40

White African-American Mexican-American

MenWomen

24WISE (Women’s Ischemia Syndrome Evaluation) Study:Obesity vs. Metabolic Syndrome in CV Risk

• 780 women referred for angiography for suspected myocardial ischemia

• 596 women (76%) overweight or obese by BMI

• 451 women (58%) with metabolic syndrome

• Prevalence of significant angiographic CAD (>50% stenosis)

• Metabolic syndrome but not BMI associated with:– Significant CAD

– 3-yr risk of MACE

• Metabolic syndrome conferred 2-fold adjusted risk of death and MACE

• Metabolic syndrome associated with elevated levels of hs-CRP

Kip KE, et al. Kip KE, et al. CirculationCirculation.. 2004;109:706-713.2004;109:706-713.

25WISE (cont’d): Relationship Between BMI, Metabolic Status, and Prevalence of Significant Angiographic CAD

Kip KE, et al. Kip KE, et al. CirculationCirculation.. 2004;109:706-713.2004;109:706-713.

0

10

20

30

40

50

60

Normal BMI Overweight Obese

Normal

Dysmetabolic

Pre

vale

nc

e o

f C

AD

, %P

reva

len

ce

of

CA

D, %

PP=0.002=0.002PP=0.0004=0.0004

PP=0.01=0.01

26Increasing US Prevalence of Diabetes

19911991

No dataNo data 4%–6%4%–6% 7%–8%7%–8% 9%–10%9%–10% >10%>10%<4%<4%

Mokdad AH et al. JAMA. 2003;28:76–79.

National Prevalence 7.9%

20012001

27

0

5

10

15

20

25

30

35

Mor

talit

y pe

r 10

00

Per

son-

Yea

rs*

*Age-adjustedAdapted from Gu K et al. Diabetes Care 1998;21:1138-1145.

Mortality Due to Heart Disease in Men and Women With or Without Diabetes (US)

29.9

19.2

Men Women

DiabetesDiabetes

No DiabetesNo Diabetes

All heart disease Ischemic heart diseaseMen Women

11.5

6.3

23.0

7.1

11.0

3.6

28Framingham Heart Study 30-Year Follow-Up:CVD Events in Patients With Diabetes (Ages 35-64)

Age-Adjusted Annual Rate/1000

109

20

11

9 63819

3*

30

0

2

4

6

8

10

Men Women

Total CVD CHD Cardiac Failure

Intermittent Claudication

Stroke

Ris

k R

atio

Vs.

Non

diab

etic

P<.001 for all values except *P<.05.

Wilson PWF, Kannel WB. In: Hyperglycemia, Diabetes and Vascular Disease.Ruderman N et al, eds. Oxford; 1992.

29



30CVD Prevention in Women:Why a Focus on Lipid Management?

• LDL predicts CVD in women similar to men

• HDL and triglycerides are stronger predictors in women

• Women are less likely than men to receive optimal lipid management

• Minority women are less likely to receive optimal preventive care compared to white women

• Evidence supports that women receive equal benefit from lipid management although less likely to receive than men

31Age-adjusted Cardiovascular Disease Mortality in Women by LDL-C and HDL-C (LRC Study)

At all levels of LDL-C, CVD mortality rates in women with low HDL-C levels were 3 to 4 times greater compared with women with high HDL-C levels

Bass KM et al. Arch Intern Med 1993;153:2209-16.

25

20

15

10

5

0

HDL-C <50 mg/dLHDL-C >50 mg/dL

< 130 mg/dL 130-159 mg/dL ≥160 mg/dL LDL-Cholesterol

Car

diov

ascu

lar

Dis

ease

Mor

talit

ype

r 10

00 P

erso

n-Y

ears

32Low HDL Low HDL

CholesterolCholesterolPostprandial Postprandial

HyperlipidemiaHyperlipidemiaSmall, Small,

Dense LDLDense LDL

HYPERTRIGLYCERIDEMIAHYPERTRIGLYCERIDEMIA

Procoagulant StateProcoagulant StateInsulin ResistanceInsulin ResistanceTriglyceride-RichTriglyceride-Rich

LipoproteinLipoproteinRemnantsRemnants

Figure 2. Association of elevated serum triglyceride levels and Figure 2. Association of elevated serum triglyceride levels and atherogenic risk factors. Modified from Brewer HB Jr. atherogenic risk factors. Modified from Brewer HB Jr. Hypertriglyceridemia: changes in the plasma lipoproteins Hypertriglyceridemia: changes in the plasma lipoproteins associated with an increased risk of cardiovascular disease. Am J associated with an increased risk of cardiovascular disease. Am J Cardiol 1999;83:3F-12F, with permission from Excerpta Medica Cardiol 1999;83:3F-12F, with permission from Excerpta Medica Inc.Inc.

33

163 150 110143 137

6010474 61

0

50

100

150

200

<50 50-59 >59

<80

80-119

>119

Women

Trigly

cerid

es (m

g/dL)

HDL Cholesterol (mg/dL)

CH

D/1

00

0/1

0 y

r

Coronary Heart Disease in Relation to HDL-C and Triglyceride Levels in Women

Framingham Heart Study — National Heart, Lung, and Blood Institute

Castelli WP. Can J Cardiol. 1988;4:5A-10A.

163 150

143

60

34

0.0

0.5

1.0

1.5

2.0

2.5

3.0

50 100 150 200 250 300 350 400

MenWomen

Re

lativ

e R

isk

Triglycerides (mg/dL)

Castelli WP. Can J Cardiol. 1988;4:5A-10A.

Impact of Triglyceride Levels on Relative Risk

of CHD: Framingham Heart Study

35Estimated 10-Year CHD Risk in 55-Year-Old Adult Women According to Levels of Various Risk FactorsFramingham Heart Study

Blood Pressure (mm Hg) 120/80 140/90 140/90 140/90Total Cholesterol (mg/dL) 200 240 240 240HDL Cholesterol (mg/dL) 50 50 40 40Diabetes No No Yes YesCigarettes No No No Yes

Wilson PWF, et al. Circulation. 1998;97:1837-1847.

58

27

20

0

5

10

15

20

25

30

A B C D

Est

imat

ed 1

0-Y

ear

Rat

e (%

)

36

Per

cen

t/10

yr

Men and Women, 55 yr

BP systolic 120 160 160 160 160 180 160

Cholesterol 220 220 260 260 260 260 260

HDL-C 50 50 50 35 35 35 35

Diabetes + + +

Cigarettes + +

LVH-ECG + +

Wilson PWF. Am J Hypertens. 1994;7(7 pt 2): 7S-12S.

MenWomen

Multiple Risk Factors Tend to Occur Together

Framingham Heart Study — National Heart, Lung, and Blood Institute57.5

38

23.428.8

8.713.7 16.5

5.5 9.2 11.3 1727.7

36.856.4

0

10

20

30

40

50

60

*

BEN: I couldn't find this article online, and I'm not sure that the slide adds a lot to this particular module. Delete?

37Does a Low HDL Matter as a Risk Factor?

100 160 2200.0

1.0

2.0

3.0

Ris

k o

f C

HD

Low HDL - C is an Independent Predictor of CHD Risk Even When LDL – C is Low

HDL-C(mg/dL)

LDL- C (mg/dL)

25

Gordon T et al. Am J Med.1977;62:707-714.

4565

85

38Lipid Profiles in Diabetic and Nondiabetic Women

Siegel RD et al. Metabolism. 1996;45:1267-1272.

*P*P0.0010.001

*

*

*

*

HDL-C <35HDL-C <35 TG >250TG >250 HDL-C <35HDL-C <35 LDL-C LDL-C 160160 LDL-C <100LDL-C <100 LDLLDL

TG >250TG >250 Pattern BPattern B

Framingham Offspring StudyFramingham Offspring Study

mg/dLmg/dL

0

10

20

30

40

50

Wom

en (

%)

Nondiabetic (n = 1879))Diabetic (n = 120)

39

Change in Lipids After Menopause

90

100

110

-24 6-18 -12 -6 0

% o

f le

vel a

t -6

mon

ths

befo

re m

enop

aus

e

Jensen J et al. Maturitas 1990;12:321-31.

Total Cholesterol

90

100

110

-24 6-18 -12 -6 0

HDL-C

Months

90

100

110

-24 6-18 -12 -6 0

% o

f le

vel a

t -6

mon

ths

befo

re m

enop

aus

e

LDL-C

Months

90

100

110

-24 6-18 -12 -6 0

Triglycerides

40WHI Estrogen+Progesterone Study

Absolute and Relative Risk or Benefit of Combo HRT

Coronary Heart Disease (CHD)1

Strokes

Breast cancer

VTEs

Colorectal cancer

Hip fractures

Total fractures

Relative Riskvs. Placeboat 5.2 Years

Increased Absolute Risk

per 10,000Women/YrHealth Event

1.24

1.41

1.26

2.11

0.63

0.66

0.76

6

8

8

18

6

5

44

Increased Absolute Benefit

per 10,000Women/Yr

1Manson JE et al. N Engl J Med. 2004;349:523-534.Writing Group for the Women’s Health Initiative Investigators. JAMA. 2002;288:321-333.

Nominal95%

1.00-1.54

1.07-1.85

1.00-1.59

1.58-2.82

0.43-0.92

0.45-0.98

0.69-0.85

Adjusted95%

0.97-1.60

0.86-2.31

0.83-1.92

1.26-3.55

0.32-1.24

0.33-1.33

0.63-0.92

Confidence Interval

Nominal = variability based on simple trial for single outcome; Adjusted = corrects variability for multiple analyses over time.

41WHI Estrogen Alone Trial: Primary CHD Outcomes

CHD † 177 (0.49%) 199 (0.54%) 0.91 (0.75,1.12)(0.72,1.15)

CHD Death 54 (0.15%) 59 (0.16%) 0.94 (0.65,1.36)(0.54,1.63)

Non-fatal MI 132 (0.37%) 153 (0.41%) 0.89 (0.70,1.12)(0.63,1.26)

Stroke 158 (0.44%) 118 (0.32%) 1.39 (1.10-1.77)(0.97-1.99)

Average follow-up was 6.8 years.

* Adjusted for multiple comparisons across time (OBF procedures). A Bonferroni adjustment for 6 outcomes was applied to all outcomes other than CHD, Breast Cancer and the global Index.

† CHD includes acute MI requiring hospitalization, silent MI determined from serial electrocardiograms and coronary deaths. There were 14 silent MIs.

Conjugated 95% CIEquine Estrogen Placebo Hazard Ratio Nominal Adjusted*

The Women’s Health Initiative Steering Committee. JAMA 2004;291:1701-12.

42



43Meta-Analysis of Effects of Statins from Major Clinical Trials

-20

-35

-30

-25

-20

-15

-10

-5

0

5TC

-28

LDL-C

-13

TG

-31

CoronaryEvents

-29

FatalCHD

-21

TotalMortality

5

HDL-C

Change%

10

LaRosa JC et al. JAMA. 1999;282:2340-2346.

44Risk Reduction for Major Coronary Events by Gender in Statin Trials

504540353025201510

50

Pro

po

rtio

nal

Ris

k R

edu

ctio

n (

%)

4S CARE LIPID AFCAPS

Women 427 576 1516 997

Men 1803 3583 7498 5608

LaRosa JC et al. JAMA.1999;282:2340-2346.

37 38

4346

22

15

27 37

45Major Vascular Event Rates by Gender and LDL Cholesterol: Heart Protection Study

Event Rate ratio & 95% CI

STATIN better PLACEBO better

Baseline LDL cholesterol (mg/dL)

282 358(16.4%) (21.0%)< 100

668 871(18.9%) (24.7%)

1083 1356(21.6%) (26.9%) 130

24% SE 3reduction(2P<.00001)

2033 2585(19.8%) (25.2%)ALL PATIENTS

0.4 0.6 0.8 1.0 1.2 1.4

Available at: http://www.ctsu.ox.ac.uk/~hps/hps_slides.shtml. Accessed June 15, 2004.

Ballantyne CM. Am J Cardiol.2003;92(suppl):3K-9K.

1666 2135(21.6%) (27.6%)Male (n=15,454)

367 450(14.4%) (17.7%)Female (n=5,082)

Sex

46Gender-Specific Effects of Statins on Lipids

CARE 4S

Lewis SJ et al, J Am Coll Cardiol 1998; 32:140.Miettinin TA et al, Circulation 1997; 96:4211.

-40-35-30-25-20-15-10-505

10

Total LDL HDL TG-40

-30

-20

-10

0

10

Total LDL HDL TG

Women Men

47

0%

6%

-31%

-22% -22%

-29%

-40%

-30%

-20%

-10%

0%

10%

20%

% Change (Gemfibrozilvs Placebo)

VA-HIT: Benefit of Gemfibrozil in Male Patients With Coronary Heart Disease

LDL-C HDL-C TG Nonfatal CHD Stroke† MI or CHD Death

Death

* *

***

*

* P0.05; ** P=0.07; † Investigator designated

2,531 men with coronary heart disease, HDL ≤ 40 mg/dL, and LDL ≤ 140 mg/dL were randomized to gemfibrozil (1200 mg/day) or or placebo, and followed for a mean of 5.1 years. Rubins HR et al. N Engl J Med. 1999;341:410-418.

48

Ev

ent

Ra

te %

- 27%*

- 14%*

- 26%*

Placebo (n=1119)

Niacin (n=2789)

- 47%*†

†5-year rate

*P<0.05

Coronary Drug Project:5-Year Events

Coronary Drug Project Research Group. JAMA. 1975;231:360-381.

0

5

10

15

20

25

30

35

Nonfatal MI/CHDdeath

Nonfatal MI Stroke/TIA CV Surgery

49HDL-Atherosclerosis Treatment Study (HATS)

Niacin and Statin Regression Trial

Brown BG et al. N Engl J Med 2001;345:1583-1592.

Placebo S + N + AVS + N

Com

posi t

e E

ven

t R

ate

, %

Com

posi t

e E

ven

t R

ate

, %

AV

Coronary Death, MI, Stroke, or Revascularization

89%Reduction

21.4

2.6*

14.3

*P<.05 vs Placebo

23.7

0

5

10

15

20

25

50Dose-Related Lipid Level Changes in Women by Monotherapy Niacin

LDL-C, low density lipoprotein-cholesterol; HDL-C, high density lipoprotein-cholesterol; TG,

Triglycerides. NIASPAN® [package insert]. Miami, Fla: Kos Pharmaceuticals, Inc.; 2003.

Mean Change From Baseline (%)

-11

20

-20-16

24

-28

-18

26

-36-40

-30

-20

-10

0

10

20

30

LDL-C HDL-C TG

1000 mg qhs (n=52)

1500 mg qhs (n=59)

2000 mg qhs (n=53)

51

The CVD Prevention Paradox

Risk factors for CVD, including lifestyle, hypertension, dyslipidemia, and diabetes, have been established for decades.

Substantial data supports the statement that appropriate management of CVD risk factors saves lives, yet substantial numbers of patients don’t get lifesaving interventions.

Why?

52



53Evidence-Based Guidelines for CVD

Prevention in Women

Mosca L et al. Circulation. 2004;109:672-693.

54Evidenced-Based Guidelines or CVD Prevention in Women: Rationale

• Significant advances in science base needed to be translated into clinical recommendations

• Women were excluded from many early CVD trials and lack of data may be an obstacle to prevention in women

• In the wake of HERS and WHI there was a heightened need to clarify what prevention strategies are based on the highest quality evidence

• Recent survey showed women confused about prevention strategies

Mosca L, et al. Circulation. 2004; 109:672-93.


55

Classification and Levels of Evidence

Strength of RecommendationClassification

Class I Intervention is useful and effectiveClass IIa Weight of evidence/opinion is in favor of

usefulness/efficacyClass IIb Usefulness/efficacy is less well established byevidence/opinionClass III Intervention is not useful/effective and may be harmful

Level of EvidenceA Sufficient evidence from multiple randomized trialsB Limited evidence from single randomized trial or other nonrandomized studiesC Based on expert opinion, case studies, standard of care

Generalizability Index1 Very likely that results generalize to women2 Somewhat likely that results generalize to women3 Unlikely that results generalize to women0 Unable to project if results generalize to women


56ALOHA to Heart Disease

Lay Guidelines

• A-Assess your risk and rank yourself

• L-Lifestyle interventions are top priority

• O-Other interventions prioritized by expert rating

• H-Highest priority for women at highest risk

• A-Avoid Class III interventions (HRT, antioxidant supplements, and aspirin in low-risk women)

Mosca, L Circulation Patient Page www.circulationaha.org (2004;109;e158-160).

57Framingham Risk AssessmentA Cholesterol Management Implementation Tool for the Palm Operating System

Based on ATP III

58

Spectrum of CVD Risk in Women

Framingham Global Risk Framingham Global Risk

Risk GroupRisk Group (10-y Absolute CHD Risk)(10-y Absolute CHD Risk)

High ≥ 20%

Intermediate 10% to 20%

Lower ≤10%

Optimal ≤10%

Mosca L, et al. Circulation 2004; 109:672-93.

59High CVD Risk in Women:

Clinical Examples

• Established CHD• Cerebrovascular disease*• Peripheral arterial disease• Abdominal aortic aneurysm• Diabetes mellitus• Chronic kidney disease†

*Cerebrovascular disease may not confer high risk for CHD if the affected vasculature is above the carotids. Carotid artery disease (symptomatic or asymptomatic with >50% stenosis) confers high risk.†As chronic kidney disease deteriorates and progresses to end-stage kidney disease, the risk of CVD

increases substantially


60Intermediate CVD Risk in Women: Clinical

Examples

• Subclinical CVD‡

• Metabolic syndrome• Multiple risk factors§

• Markedly elevated levels of a single risk factor**• 1st degree relative(s) with onset of atherosclerotic

CVD at ≤ 55 y in men and ≤ 65 y in women

‡Patients with subclinical CVD and >20% 10-year CHD should be elevated to the high-risk category.§Patients with multiple risk factors can fall into any of the 3 categories by Framingham scoring.**Most women with a single, severe risk factor will have a 10-year risk >10%.


61Lower/Optimal CVD Risk in Women:

Clinical Examples

• Lower• May include women with multiple risk factors,

metabolic syndrome, or ≤ 1 risk factors

• Optimal• Optimal levels of risk factors and heart-healthy

lifestyle


62

Clinical Recommendations

• Lifestyle interventions

• Major risk factor interventions

• Preventive drug interventions

• Atrial fibrillation/stroke prevention

• Class III interventions


63

Class I Lifestyle Interventions

• Cigarette smoking cessation

• Physical activity

• Cardiac rehabilitation (in women with recent MI)

• Heart-healthy diet/therapeutic diet

• Weight maintenance/reduction


64What’s New in the Guidelines

Concerning Lipid Management

• Initiate statin treatment for high-risk women regardless of their LDL levels

• Optimal level HDL-C > 50 mg/dl

• Initiating niacin or fibrate therapy for low HDL or elevated non-HDL in high-risk women is a Class I recommendation


65Major Risk Factor Interventions:

Lipid, Lipoproteins

Optimal levels of lipids and lipoproteins in women:

– LDL-C <100 mg/dL

– HDL-C >50 mg/dL

– Triglycerides <150 mg/dL

– Non–HDL-C (total cholesterol minus HDL-C) <130 mg/dL

Encourage lifestyle approaches (Class I, Level B)GI=1


66Major Risk Factor Interventions: Lipids and Lipoproteins

Heart-healthy diet– Consistently encourage overall healthy eating pattern

• Fruits, vegetables, grains, low-fat or nonfat dairy products, fish, legumes, and sources of protein low in saturated fat.

• Limit saturated fat intake to <10% of calories, limit cholesterol to <300 mg/d, and limit intake of trans fatty acids (Class I, Level B)GI=1

Diet therapy– In high-risk women or when LDL-C is elevated, reduce

saturated fat intake to <7% of calories, cholesterol to <200 mg/d, and trans fatty acid intake (Class I, Level B)GI=1

Mosca L, et al. Circulation 2004;109:672-93.

67Lipids and Lipoproteins: Pharmacotherapy

High risk women (10-year absolute CHD risk > 20%)– Initiate LDL-C–lowering (preferably statin) therapy with

lifestyle therapy when LDL-C >100 mg/dL (Class I, Level A)GI=1, and initiate statin therapy when LDL-C <100 mg/dL unless contraindicated (Class 1, Level B)GI=1

– Initiate niacin or fibrate therapy when HDL-C is low, or elevated non–HDL-C (Class I, Level B)GI=1


Class I Intervention is useful and effectiveLevel A Sufficient evidence from multiple randomized trials B Limited evidence from single randomized trial or other nonrandomized studies

68“Dietary supplement niacin must not be used as a substitute for prescription niacin…”

No-flush (inositol hexaniacinate)– Contains no free nicotinic acid– Should not be used to treat dyslipidemia

Sustained-release– Hepatotoxicity associated with several formulations

Immediate-release– Shown to prevent cardiovascular disease and death– TID dosing:

• increases flush• difficult to titrate• lessens compliance

Extended-release – Approved by the FDA available only by prescription– Once before bedtime dosing

Meyers CD et al. Ann Intern Med 2003;139:996-1002. HPS Collaborative Group. Lancet. 2002;360;7-22.


Intermediate Risk Women (10-yr absolute CHD risk 10%-20%)

• Initiate LDL-C–lowering therapy (preferably statin) if LDL-C level is > 130 mg/dL on lifestyle therapy (Class I, Level A), or niacin or fibrate therapy when HDL-C is low or non–HDL-C is elevated after LDL-C goal is reached (Class I, Level B)GI=1


Class I Intervention is useful and effectiveLevel A Sufficient evidence from multiple randomized trials B Limited evidence from single randomized trial or other nonrandomized studies


Lower Risk Women (10-yr absolute CHD risk <10%)• Consider LDL-C–lowering therapy:

– 0 or 1 risk factor when LDL-C level is > 190 mg/dL

– If multiple risk factors are present when LDL-C is >160 mg/dL (Class IIa, Level B)

– Niacin or fibrate therapy when HDL-C is low or non–HDL-C

elevated after LDL-C goal is reached (Class IIa, Level B)GI=1


Class I Intervention is useful and effectiveLevel A Sufficient evidence from multiple randomized trials B Limited evidence from single randomized trial or

other nonrandomized studies

71

• Combination therapy is generally safe– 1% incidence of CK (>3x) elevation with statin and fibrates

– Incidence CK (>3x) elevation is even less with statin and niacin

• CK and statins– Obtain baseline CK

– Obtain CKs if patient reports suggestive muscle symptoms

– Discontinue statin if CK > 10x in patients with muscle symptoms

– If muscle symptoms without CK or with moderate CK elevation, follow clinically

– Asymptomatic patients with moderate baseline CK elevation may still be safely treated with statins

ACC/AHA/NHLBI Clinical Advisory on Statins

Pasternak RC et al. J Am Coll Cardiol. 2002;40:567-572.

72

Bottom Line

• Can we identify women at risk? (yes)

• Do we have therapy to reduce risk? (yes)

• Do we uniformly apply this knowledge? (no)– Patient related– Physician barriers– Health system barriers– Societal issues– Compliance

73

Conclusions

• CVD is leading killer of women yet awareness is suboptimal

• Lipids are common and important risk factors in women

• Substantial data exists on reducing CV events by treating dyslipidemia in women

• If new guidelines are more uniformly implemented, the burden of CVD in women will be reduced

1 we’ve come a long way-prevention of cardiovascular disease in women ned ferguson, m.d....

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