1 We’ve Come A Long Way-Prevention of Cardiovascular Disease in Women Ned Ferguson, M.D. University of Wisconsin Hospital and Clinics Section of Cardiovascular Medicine Preventive Cardiology January 2005 Faculty, National WATCH Program-Women’s Agenda Targeting Cholesterol in Heart Disease Speaker, WATCH Program Speaker, AHA Go Red for Women campaign
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1 We’ve Come A Long Way-Prevention of Cardiovascular Disease in Women Ned Ferguson, M.D. University of Wisconsin Hospital and Clinics Section of Cardiovascular.
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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.
American Heart Association. 2004 Heart and Stroke Statistical Update.
Dallas, Texas: AHA, 2003.
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.
American Heart Association. 2004 Heart and Stroke Statistical Update.
Dallas, Texas: AHA, 2003.
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.
American Heart Association. 2004 Heart and Stroke Statistical Update.
Dallas, Texas: AHA, 2003.
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 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
%
Mosca L et al. Circulation 2004; 109:573-579.
05
101520253035404550
BreastCancer
Cancer(general)
HeartDisease
Unsure
1997
2000
2003
20Women’s Awareness 2003:Perceived Leading Cause of Death by Ethnic Group
Mosca L et al. Circulation 2004; 109:573-9.
%
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
Cardiovascular Disease Prevention in Women
Scope of the problemLipids and CVDClinical trial evidenceThe new evidence-based AHA guidelines
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
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
* 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
Cardiovascular Disease Prevention in Women
Scope of the problemLipids and CVDClinical trial evidenceThe new evidence-based AHA guidelines
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,
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
Cardiovascular Disease Prevention in Women
Scope of the problemLipids and CVDClinical trial evidenceThe new evidence-based AHA guidelines
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.
Mosca L et al. Circulation 2004; 109:573-9.
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
Mosca L et al. Circulation 2004; 109:672-93.
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)
*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
Mosca L, et al. Circulation 2004; 109:672-93.
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%.
Mosca L, et al. Circulation 2004; 109:672-93.
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
Mosca L, et al. Circulation 2004; 109:672-93.
62
Clinical Recommendations
• Lifestyle interventions
• Major risk factor interventions
• Preventive drug interventions
• Atrial fibrillation/stroke prevention
• Class III interventions
Mosca L et al. Circulation 2004; 109:672-93.
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
Mosca L, et al. Circulation 2004; 109:672-93.
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
Mosca L, et al. Circulation 2004; 109:672-93.
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
Mosca L, et al. Circulation 2004; 109:672-93.
66Major Risk Factor Interventions: Lipids and Lipoproteins
• 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
Mosca L, et al. Circulation 2004;109:672-93.
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.
69Lipids and Lipoproteins: Pharmacotherapy
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
Mosca L, et al. Circulation 2004;109:672-93.
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
– 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
Mosca L, et al. Circulation 2004;109:672-93.
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.
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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
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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