Heart Disease in Women: New Concepts in Prevention and Management Nathan D. Wong, PhD, FACC Professor and Director Heart Disease Prevention Program Division of Cardiology University of California, Irvine
Jan 20, 2016
Heart Disease in Women: New Concepts in Prevention
and Management
Nathan D. Wong, PhD, FACC
Professor and Director
Heart Disease Prevention Program
Division of Cardiology
University of California, Irvine
HeartDisease
The leadingkiller ofwomenat allages
So how long have we known that So how long have we known that women are just not small men???women are just not small men???
Cardiovascular Disease in WomenCardiovascular Disease in Women
• 38.2 million women (34%) are living with 38.2 million women (34%) are living with cardiovascular disease and a much larger cardiovascular disease and a much larger population is at risk.population is at risk.
• Heart disease and stroke are the no. 1 and no. 3 Heart disease and stroke are the no. 1 and no. 3 killers of women over age 25killers of women over age 25
• 1 in 30 die of breast cancer, but 1 in 2.5 die of 1 in 30 die of breast cancer, but 1 in 2.5 die of cardiovascular disease or stroke.cardiovascular disease or stroke.
• 66,000 more women than men die per year of 66,000 more women than men die per year of cardiovascular disease; represents 54% of deaths cardiovascular disease; represents 54% of deaths in women compared to 46% in men.in women compared to 46% in men.
AHA Heart Disease and Stroke Statistics 2004 Update, and Mosca et al., Circulation 2007; 115: 1481-1501.
CHD: Differences in Presentation and Findings in Women Compared to Men–Lower prevalence of MI–More severe CHF–More severe angina–Less angiographic CAD–More ostial lesions–More microvascular dysfunction?–Abnormal vasomotor tone?–More endothelial dysfunction?
Source: Jacobs 2003
Diagnosis of Coronary Artery Disease in Women
• Chest pain is experienced by most women with CHD, but non-chest pain presentations are more common in women than men
• Other Presenting Symptoms– Upper abdominal pain, fullness, burning sensation– Shortness of breath– Nausea– Neck, back, jaw pain
• Associations– Precipitated by exertion– Precipitated by emotional distress
Source: Charney 2002, Goldberg 1998
Women have smaller coronary Women have smaller coronary arteriesarteries
• After correcting for After correcting for body surface area, body surface area, womens’ arteries are womens’ arteries are smallersmaller
• This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter– StenosisStenosis– Endothelial dysfunctionEndothelial dysfunction
Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: 585-594
Endo-thelium
Smallerarteries
Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling
• Plaque erosion and Plaque erosion and thrombus formation 2x thrombus formation 2x likely in women (men likely in women (men have more plaque have more plaque rupture)rupture)
• Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward than protrudes outward than impinging on the lumenimpinging on the lumen
Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: 585-594
Thrombus Formation
Lumen
Plaqueerosion
Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below), leading to more acute coronary syndromes(unstable angina) and non-Q MI in women,making diagnosis more difficult and leading to delays in treatment.
Gender Differences in Atherosclerosis
NEJM 1999
NIH-NHLBI-sponsored Women’s Ischemia NIH-NHLBI-sponsored Women’s Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE
• About 50% of women sent home with “normal About 50% of women sent home with “normal coronaries” continue to experience disabling coronaries” continue to experience disabling symptomssymptoms
• Possibly d/t coronary microvascular or macrovascular Possibly d/t coronary microvascular or macrovascular endothelial dysfunctionendothelial dysfunction
• 673/936 enrolled in WISE had persistent chest pain 673/936 enrolled in WISE had persistent chest pain (PChP)(PChP)
• PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign conditioncondition– 2x the number of CV events (MIs, strokes,CHF and 2x the number of CV events (MIs, strokes,CHF and
CV deaths) than those w/o PChP.CV deaths) than those w/o PChP.– Johnson,D, etal EurHeart Journal 2006Johnson,D, etal EurHeart Journal 2006
Assessing Ischemic DiseaseAssessing Ischemic Disease
• Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia– Guidelines still support for women with normal resting Guidelines still support for women with normal resting
12 lead EKG12 lead EKG
• Decreased functional capacity may predict poor Decreased functional capacity may predict poor outcomesoutcomes– WISE showed that women who could not achieve 4.7 WISE showed that women who could not achieve 4.7
METS of work had a risk of death or nonfatal MI 3.7x METS of work had a risk of death or nonfatal MI 3.7x higher that others with better functional capacityhigher that others with better functional capacity
• Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen
Mortality Rates in WomenMortality Rates in WomenAt Every Age, More Women Die From Heart Disease Than From CancerAt Every Age, More Women Die From Heart Disease Than From Cancer
National Center for Health Statistics. 1999:164-167.National Center for Health Statistics. 1999:164-167.
Coronary artery diseaseCoronary artery disease
StrokeStroke
Lung cancerLung cancer
Breast cancerBreast cancer
Colon cancerColon cancer
Endometrial cancerEndometrial cancer
Age (years)Age (years)
Mo
rtal
ity
Rat
e p
er 1
00,0
00M
ort
alit
y R
ate
per
100
,000
65006500
45004500
25002500
16001600
12001200
800800
400400
004545––49 5049 50––54 5554 55––59 6059 60––64 6564 65––69 7069 70––74 7574 75––79 8079 80––84 85+84 85+
50% of women (1 in 2) will 50% of women (1 in 2) will die from CVD compared die from CVD compared with 4% with 4% (1 in 25) who will die from (1 in 25) who will die from breast cancerbreast cancer
Women Experience Women Experience Menopause…..Menopause…..• Changes with MenopauseChanges with Menopause• LipidsLipids• Total-CholesterolTotal-Cholesterol • HDL-CholesterolHDL-Cholesterol
• Prevalence DifferencesPrevalence Differences• HypertensionHypertension • Metabolic Syndrome Metabolic Syndrome
• Risk Factor, Disease, or Outcome RiskRisk Factor, Disease, or Outcome Risk• TriglyceridesTriglycerides
Diabetes Mellitus Diabetes Mellitus
• Obesity (BMI Obesity (BMI >>30)***30)***
Waist Circumference >35” Waist Circumference >35” – ******ObesityObesity ~25% of women - BMI ~25% of women - BMI >>30, 30, Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --
Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: 585-594
Menopause and Menopause and the Risk of Coronary Heart Disease the Risk of Coronary Heart Disease
(modified data from “Menopausal status as a risk for coronary artery disease”(modified data from “Menopausal status as a risk for coronary artery disease”Arch Intern Med 1995;155:57-61Arch Intern Med 1995;155:57-61
0
0.5
1
1.5
2
2.5
3
3.5
4
40 - 45 45 - 49 50 - 54
Before menopauseAfter menopause
Age (in years)
An
nu
al O
ccu
ren
ce o
f H
eart
Att
ack
/100
0
Chest pain or AnginaChest pain or AnginaTypical Angina:Typical Angina: heaviness, pressure or squeezing sensation behind the breastboneheaviness, pressure or squeezing sensation behind the breastbone with with
radiation across the chest, up the neck or down the left armradiation across the chest, up the neck or down the left arm or “strangling” or “suffocating” sensation. or “strangling” or “suffocating” sensation.
caused or worsened by exercise and eased by restcaused or worsened by exercise and eased by rest usually lasts two to five minutesusually lasts two to five minutes
Atypical AnginaAtypical Angina (frequently encountered in women):(frequently encountered in women):shortness of breathshortness of breathextreme fatigueextreme fatiguelightheadedness or faintinglightheadedness or faintingnausea and/or indigestionnausea and/or indigestion
Women’s Early Warning Signs of a Women’s Early Warning Signs of a Heart Attack Heart Attack
• Weeks before Heart Attack (95% of women)Weeks before Heart Attack (95% of women) Unusual fatigue (70.7%)Unusual fatigue (70.7%) Sleep disturbance (47.8%)Sleep disturbance (47.8%) Shortness of breath (42.1%)Shortness of breath (42.1%) Indigestion (39.4%)Indigestion (39.4%) Chest pain (29.7 %)Chest pain (29.7 %)
• At time of Heart AttackAt time of Heart Attack Shortness of breath (57.9%)Shortness of breath (57.9%) Weakness (54.8%)Weakness (54.8%) Fatigue (42.9%)Fatigue (42.9%) Chest pain (57%)Chest pain (57%)
McSweeney, JC et al. Circulation 2003; 2619-2623
Tracking women's awareness of heart disease: an American Heart Association national study
Mosca L, et al. Circulation. 2004 Feb 10;109(5):573-9 • Telephone survey of a nationally representative
random sample of women; 1024 respondents age > or =25 years
• 46% identified heart disease as the leading cause of death in women, up from 30% in 1997 and 34% in 2000
• Black, Hispanic, and younger women (<45 years old) had lower awareness of heart disease
• Only 38% of women reported that their doctors had ever discussed heart disease with them.
Major Risk Factors
• Cigarette smoking (passive smoking?)• Elevated total or LDL-cholesterol• Hypertension (BP 140/90 mmHg or on
antihypertensive medication)• Low HDL cholesterol (<40 mg/dL)† • Family history of premature CHD
– CHD in male first degree relative <55 years– CHD in female first degree relative <65 years
• Age (men 45 years; women 55 years)† HDL cholesterol 60 mg/dL counts as a “negative” risk factor; its
presence removes one risk factor from the total count.
Other Recognized Risk Factors• Obesity: Body Mass Index (BMI)
– Weight (kg)/height (m2)– Weight (lb)/height (in2) x 703
• Obesity BMI >30 kg/m2 with overweight defined as 25-<30 kg/m 2
• Abdominal obesity involves waist circumference >40 in. in men, >35 in. in women
• Physical inactivity: most experts recommend at least 30 minutes moderate activity at least 4-5 days/week
BMI and Relative Risk of CHD Over 14 Years: Nurse’s Health Study
• Relative risk of CHD increases for BMI > 23, diabetes risk increases for BMI > 22.
• Risk also significantly increases for weight gain after age 18 years of 5 kg or more. 0
0.5
1
1.5
2
2.5
3
3.5
<21 21-22.9 23-24.9 25-28.9 >29
Diabetes as a CHD Risk Equivalent
• 10-year risk for CHD 20%• High mortality with established CHD
– High mortality with acute MI– High mortality post acute MI
Prevalence has increased over 25% in past 15 years in California, paralleling 50% increase in overweight/obesity
Probability of Death From CHD in Patients With NIDDM and in Nondiabetic Patients,
With and Without Prior MI
Kaplan-Meier estimatesHaffner SM et al. N Engl J Med 1998;339:229–234
0 1 2 3 4 5 6 7 80
20
40
60
80
100
Nondiabetic subjects without prior MI
Diabetic subjects without prior MI
Nondiabetic subjects with prior MI
Diabetic subjects with prior MI
Years
Surv
ival (%
)
Framingham Heart Study 30-Year Follow-Up:CVD Events in Patients With Diabetes
(Ages 35-64)10
9
20
11
9 63819
3*
30
0
2
4
6
8
10
Age-adjusted annual rate/1,000
Men Women
Total CVD
CHD Cardiac failure
Intermittent claudication
Stroke
Riskratio
P<0.001 for all values except *P<0.05.
Wilson PWF, Kannel WB. In: Hyperglycemia, Diabetes and Vascular Disease.Ruderman N et al, eds. Oxford; 1992.
Adapted from Ballantyne CM. Am J Cardiol. 1998;82:3Q-12Q.
Primary and Secondary Prevention Trials With Statins
2° prevention placebo
2° prevention statin
1° prevention placebo
1° prevention statin
0
5
10
15
20
25
30
80 90 100 110 120 130 140 150 160 170 180 190 200
LDL-C Achieved (mg/dL)
AFCAPS
AFCAPS
WOSCOPS
WOSCOPS
CARECARE
LIPID LIPID
4S
4S
Eve
nt
Rat
e (%
)
HPSHPS
CHD Events: Results of Secondary Prevention CHD Events: Results of Secondary Prevention Studies in WomenStudies in Women
PP value for heterogeneity=.35 value for heterogeneity=.35Walsh et al. Walsh et al. JAMAJAMA. 2004;291:2243-2252.. 2004;291:2243-2252.
0 1 2
Placebo No.Placebo No.Events/WomenEvents/Women
Intervention No.Intervention No.Events/WomenEvents/Women
RR RR (95% CI)(95% CI)
4S4S 91/42091/420 60/40760/4070.68 (0.51-0.68 (0.51-
0.91)0.91)
CARECARE 80/29080/290 46/28646/2860.60 (0.37-0.60 (0.37-
0.97)0.97)
LIPIDLIPID 104/760104/760 90/75690/7560.87 (0.67-0.87 (0.67-
1.13)1.13)
HPSHPS 282/1638282/1638 237/1628237/16280.85 (0.72-0.85 (0.72-
0.99)0.99)
Total and Total and summarysummary 557/3108557/3108 433/3077433/3077
0.80 (0.71-0.80 (0.71-0.91)0.91)
Testing for Ischemic Heart Diseasein Women and Factors to Consider
Technique Assessment Issues in Women
Angiography Coronary anatomy
Less focal disease
Coronary CT Coronary calcification
Less well-validated than other techniques
Echocardiography
Regional wall motion
Reader expertise variable
Nuclear Cardiology
Regional blood flow
Attenuation issues
Source: Charney 2002, Greenland 2007
Drawbacks of Diagnostic Imaging in Women
• Low exercise capacity – likelihood of reaching adequate pressure rate product– Solution: Pharmacologic stress testing
• Breast attenuation artifact – higher false positive imaging studies– Solution: Gated acquisition; attenuation correction for nuclear
imaging– Solution: Echocardiography
• Lower pretest probability of CAD – higher false positive rate– Solution: Integrate clinical variables, risk factors, into
decision-making process
Source: Duvernoy, personal communication
Women and CHD: What Test to Order When
• For women at high or intermediate risk of coronary artery disease, consider treadmill echocardiogarphy or nuclear perfusion imaging
• For women unable to exercise, consider dobutamine stress echocardiography or adenosine or dipyridamole nuclear imaging
• In high risk women with typical symptoms of coronary artery disease, consider referral to a cardiologist
• For high risk women, consider cardiac catheterization if symptoms persist despite negative non-invasive imaging
Source: Anderson 2007, Klocke 2003, Douglas 2008, Duvernoy 2005
Women and CHD: What Test to Order When
• A stepwise approach beginning with conventional exercise testing may be considered for women who:– Are at low or intermediate risk for coronary artery disease– Are able to exercise– Have an electrocardiogram that can
be interpreted during stress testing• An image-enhanced test may be more predictive in women than
conventional electrocardiogram stress testing, and may also be more cost effective in women at intermediate risk for CHD
Source: Anderson 2007, Klocke 2003, Douglas 2008,Mieres 2005
Mosca L et al. Mosca L et al. CirculationCirculation. 2004;109:672-693 and Circulation 2007; 115: 1481-1501.. 2004;109:672-693 and Circulation 2007; 115: 1481-1501.
Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen
• AA – Assess your risk: high, intermediate, or low? – Assess your risk: high, intermediate, or low?
• LL – Lifestyle recommendations are first priority – Lifestyle recommendations are first priority
• OO – Other interventions prioritized according to – Other interventions prioritized according to expert panel rating scaleexpert panel rating scale
• HH – Highest priority for therapy is for women at – Highest priority for therapy is for women at highest riskhighest risk
• AA – Avoid medical therapies called Class III – Avoid medical therapies called Class III where evidence is lackingwhere evidence is lacking
Mosca L. Circulation 2004
A - Assessment of CHD RiskFor persons without known CHD, other forms of
atherosclerotic disease, or diabetes:• Count the number of risk factors.• Use Framingham scoring if 2 risk factors* to determine the
absolute 10-year CHD risk.• Determine risk status: high (>20% 10-year risk or CHD risk
equivalents), intermediate (10-20% 10-year risk), or low (<10% risk)
*For persons with 0–1 risk factor, Framingham calculations are not necessary.
Expert Panel on Detection, Evaluation, and Treatment ofHigh Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. © 2001, Professional Postgraduate Services®
www.lipidhealth.org
Point Total 10-Year Risk Point Total 10-Year Risk
<9 <1% 2011%
9 1% 2114%
10 1% 2217%
11 1% 2322%
12 1% 2427%
13 2% 25 30%
14 2%15 3%16 4%17 5%18 6%19 8%
Assessing CHD Risk in Women
Note: Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian population in Massachusetts, USA.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
Step 1: Age
YearsPoints
20-34 -735-39 -340-44 045-49 350-54 655-59 860-64 1065-69 1270-74 1475-79 16
TC Points at Points at Points at Points atPoints at(mg/dL) Age 20-39 Age 40-49 Age 50-59 Age 60-69
Age 70-79 <160 0 0 0 0
0160-199 4 3 2 1
1200-239 8 6 4 2
1240-279 11 8 5 3
2280 13 10 7 4
2
HDL-C(mg/dL) Points
60 -1
50-59 0
40-49 1
<40 2
Step 3: HDL-Cholesterol
Systolic BP PointsPoints
(mm Hg) if Untreated if Treated
<120 0 0120-129 1 3130-139 2 4140-159 3 5160 4 6
Step 4: Systolic Blood Pressure
Step 5: Smoking StatusNonsmoker 0 0 0 0
0Smoker 9 7 4 2
1
Age
Total cholesterol
HDL-cholesterol
Systolic blood pressure
Smoking status
Point total
Step 6: Adding Up the Points
Step 7: CHD Risk
Step 2: Total Cholesterol
ATP III Framingham Risk Scoring
© 2001, Professional Postgraduate Services®
www.lipidhealth.org
AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al., Circ 2007)Classification of CVD Risk in Women (Mosca et al., Circ 2007)
• High Risk:High Risk:– Established coronary heart diseaseEstablished coronary heart disease– Cerebrovascular diseaseCerebrovascular disease– Peripheral arterial diseasePeripheral arterial disease– Abdominal aortic aneurysmAbdominal aortic aneurysm– End-stage or chronic renal diseaseEnd-stage or chronic renal disease– Diabetes mellitusDiabetes mellitus– 10-year Framingham global risk >20%10-year Framingham global risk >20%
Classification of CVD Risk in Women (Mosca et al., Circ 2007)Classification of CVD Risk in Women (Mosca et al., Circ 2007)
• At RiskAt Risk::– Evidence of subclinical vascular disease (e.g., coronary calcium)Evidence of subclinical vascular disease (e.g., coronary calcium)– Metabolic SyndromeMetabolic Syndrome– Poor exercise capacity on treadmill and/or abnormal heart rate recoveryPoor exercise capacity on treadmill and/or abnormal heart rate recovery– >=1 major risk factor for CVD including:>=1 major risk factor for CVD including:
• Cigarette smokingCigarette smoking• Poor dietPoor diet• Physical inactivityPhysical inactivity• Obesity (esp central obesity)Obesity (esp central obesity)• Family history of premature CVD (<55 male or <65 female relative)Family history of premature CVD (<55 male or <65 female relative)• HypertensionHypertension• DyslipidemiaDyslipidemia
• Optimal risk:Optimal risk: Framingham global risk <10% and a healthy Framingham global risk <10% and a healthy lifestyle with no risk factorslifestyle with no risk factors
Priorities for Prevention in Practice According to Priorities for Prevention in Practice According to Risk AssessmentRisk Assessment
High-Risk WomenHigh-Risk Women
(>20% Risk)(>20% Risk)
Intermediate-Risk Intermediate-Risk WomenWomen
(10% to 20% Risk)(10% to 20% Risk)
Lower-Risk WomenLower-Risk Women
(10% Risk)(10% Risk)
Class I Class I recommendationsrecommendations
Smoking cessation Phys Smoking cessation Phys activity/card rehabactivity/card rehab
Diet therapyDiet therapyWeight maint/reductWeight maint/reductBP controlBP controlCholest control/RxCholest control/RxAspirin therapyAspirin therapy
-Blocker therapy-Blocker therapy
ACE inhibitor (ARBs)ACE inhibitor (ARBs)
Mgmt/control of DMMgmt/control of DM
Smoking cessationSmoking cessation
Physical activityPhysical activity
Heart-healthy dietHeart-healthy dietWeight maint/reductWeight maint/reductBP controlBP control
Cholesterol controlCholesterol control
Smoking cessationSmoking cessation
Physical activityPhysical activity
Heart-healthy diet Heart-healthy diet Weight maint/reductWeight maint/reduct
Treat individual Treat individual heart risk factors as heart risk factors as indicatedindicated
Class IIa Class IIa recommendationrecommendation
Treatment for Treatment for depressiondepression
Aspirin therapyAspirin therapy
Class IIb Class IIb recommendationsrecommendations
Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation
Folic acid Folic acid supplementationsupplementation
Mosca, L “Heart Disease Mosca, L “Heart Disease Prevention in Women” Prevention in Women” Circulation, 2004Circulation, 2004
L – Lifestyle Change: First Line of Defense L – Lifestyle Change: First Line of Defense Against Heart DiseaseAgainst Heart Disease
• The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendations:recommendations:
– Stop cigarette smoking and avoid secondhand tobacco smokeStop cigarette smoking and avoid secondhand tobacco smoke
– Get at least 30 minutes of physical activity most or preferably all Get at least 30 minutes of physical activity most or preferably all days (60-90 minutes for those needing to lose or sustain weight)days (60-90 minutes for those needing to lose or sustain weight)
– Start a risk-reduction or cardiac rehabilitation program if recent Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event acute coronary syndrome or cardiovascular event
– Eat a heart-healthy diet (consistent with NCEP/ATP III TLC)Eat a heart-healthy diet (consistent with NCEP/ATP III TLC)
– Maintain healthy weight by balancing caloric intake with caloric Maintain healthy weight by balancing caloric intake with caloric expenditure to achieve BMI between 18.5-24.9 kg/mexpenditure to achieve BMI between 18.5-24.9 kg/m22
Mosca et al. Circulation 2004 and 2007
Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)
• Decrease in saturated fats (<7% of total calories) and trans fatty acids1
• Increased dietary and supplemental fiber1
– High-fiber breakfast cereals, supplements, and so forth
• Plant sterols and stanols (2 g/d)1
– Spreads, pills, added to yogurt or other foods, or combined with aspirin
• Soy protein2
• Flavonoids (nuts)3
• Weight loss1
• Exercise1
1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285(19):2486-2497. • 2. Sacks FM, et al; American Heart Association Nutrition Committee. Circulation. 2006;113(7):1034-1044. • 3. Kelly JH Jr and Sabaté J. Br J Nutr. 2006;96(suppl 2):S61-S67.
Aspirin in Primary Prevention:Aspirin in Primary Prevention:Effective Gender DifferencesEffective Gender Differences
Ridker, P. et al.,Ridker, P. et al., N Engl J Med N Engl J Med 2005; 352:1293-204. 2005; 352:1293-204.
1.01.0 5.05.00.50.50.20.2 0.20.2
BDT, 1988BDT, 1988
CombinedCombined
PPP, 2001PPP, 2001
HOT, 1998HOT, 1998
TPT, 1998TPT, 1998
PHS, 1989PHS, 1989
RR of MI Among MenRR of MI Among Men
2.02.0
RR = 0.68 (0.54RR = 0.68 (0.54––0.86)0.86)PP = .001 = .001
RR of Stroke Among MenRR of Stroke Among Men
RR = 1.13 (0.96RR = 1.13 (0.96––1.33)1.33)P P = .15= .15
1.01.00.20.2 2.02.0 5.05.00.50.5
HOT, 1998HOT, 1998
CombinedCombined
WHS, 2005WHS, 2005
PPP, 2001PPP, 2001
RR of MI Among WomenRR of MI Among Women
Aspirin BetterAspirin Better Placebo BetterPlacebo Better
RR = 0.99 (0.83RR = 0.99 (0.83––1.19)1.19)PP = .95 = .95
2.02.0
Aspirin BetterAspirin Better Placebo BetterPlacebo Better
1.01.0
RR of Stroke Among WomenRR of Stroke Among Women
5.05.00.50.50.20.2
RR = 0.81 (0.69RR = 0.81 (0.69––0.96)0.96)P P = .01= .01
0.50.5 1.01.0 2.02.0 5.05.0
Blood Pressure RegulationBlood Pressure Regulationin Womenin Women
• 3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it
• Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it
• All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure
NIH Web site. Your guide to lowering high blood pressure: issues for women.NIH Web site. Your guide to lowering high blood pressure: issues for women.Available at: http://www.nhlbi.nih.gov/hbp/issues/issues.htm.Available at: http://www.nhlbi.nih.gov/hbp/issues/issues.htm.
AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women: Blood PressureWomen: Blood Pressure
• Encourage an optimal blood pressure of Encourage an optimal blood pressure of <120/80 <120/80 mm Hg through lifestyle approachesmm Hg through lifestyle approaches (Class I, (Class I, Level B)Level B)
• Pharmacotherapy when BP is Pharmacotherapy when BP is 140/90 mm Hg140/90 mm Hg
• Get BP even lower whenGet BP even lower when– Target-organ damageTarget-organ damage
– Diabetes Diabetes
(Class I, Level A)(Class I, Level A)
Mosca L et al. Mosca L et al. J Am Coll CardiolJ Am Coll Cardiol. 2004;43:900-921.. 2004;43:900-921.
CHD Risk Equivalents• > 20% 10-year risk of CHD
(Framingham projections) (downloadable risk algorithms at www.nhlbi.nih.gov)
• Diabetes
• Other forms of clinical atherosclerotic disease
– Peripheral arterial disease (ABI <0.90)
– Abdominal aortic aneurysm
– Carotid artery disease (>=1mm CIMT?)
NCEP ATP III. JAMA. 2001;285:2486-2497.
Other Modalities for Measuring Atherosclerotic Burden
• Carotid B-mode ultrasonography: intimal medial thicknesses
• Ankle-Brachial Index (ABI) for assessment of peripheral vascular disease
• CT (EBT or multislice detectors): coronary calcium score or volume
• Magnetic resonance imaging of carotid plaques: vessel wall area
• Intravascular ultrasound (invasive)
Recommendations for Noninvasive Screening
• AHA Prevention V (Greenland et al., Circ. 2000) indicated persons at intermediate risk may be suitable for screening by noninvasive tests, including ABI and carotid US for those over age 50 years, and coronary calcium screening.
• ATP III has suggested CAC scores above 75th percentile indications for more aggressive treatment (e.g., as CHD risk equivalent).
Cardiovascular Health Study: Combined intimal-medial thickness
predicts total MI and stroke
Cardiovascular Health Study (CHS) (aged 65+): MI or stroke rate 25% over 7 years in those at highest quintile of combined IMT (O’Leary et al. 1999)
Significant Coronary Artery Calcium (Score >400)
Risk of Total Mortality by Calcium Category in 10,377 Asymptomatic IndividualsShaw LJ et al., Radiology 2003; 228: 826-33
L – Lifestyle Change: First Line of Defense Against Heart Disease
• The AHA expert panel rated the following as Class I recommendations:– Stop cigarette smoking and avoid secondhand tobacco
smoke– Get at least 30 minutes of physical activity each day– Start a cardiac rehabilitation program if recently
hospitalized for heart disease– Eat a heart-healthy diet – Maintain healthy weight by balancing caloric intake
with caloric expenditureMosca et al. Circulation 2004
ATP III: Nutritional Components of the TLC Diet
Expert Panel on Detection, Evaluation, and Treatment ofHigh Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
*Trans fatty acids also raise LDL-C and should be kept at a low intake.Note: Regarding total calories, balance energy intake and expenditure tomaintain desirable body weight.
<200 mg/dCholesterol
~15% of total caloriesProtein
20–30 g/dFiber
50%–60% of total caloriesCarbohydrate (esp. complex carbs)
25%–35% of total caloriesTotal fat
Up to 20% of total caloriesMonounsaturated fat
Up to 10% of total caloriesPolyunsaturated fat
<7% of total caloriesSaturated fat*
Recommended IntakeNutrient
© 2001, Professional Postgraduate Services®
www.lipidhealth.org
Possible Benefits From Other Therapies
Therapy Result
• Soluble fiber in diet (2–8 g/d) (oat bran, fruit, and vegetables)
• Soy protein (20–30 g/d)
• Stanol esters (1.5–4 g/d) (inhibit cholesterol absorption)
• Fish oils (3–9 g/d) (n-3 fatty acids)
LDL-C 1% to 10%
LDL-C 5% to 7%
LDL-C 10% to 15%
Triglycerides 25% to 35%
Jones PJ. Curr Atheroscler Rep. 1999;1:230-235.Lichtenstein AH. Curr Atheroscler Rep. 1999;1:210-214.Rambjor GS et al. Lipids. 1996;31:S45-S49.Ripsin CM et al. JAMA. 1992;267:3317-3325.
Nuts, Soy, Phytosterols, Garlic• Nurses’ Health Study: five 1oz servings of nuts per week
associated with 40% lower risk of CHD events; 2-4 servings/wk 25% lower risk
• Metaanalysis of 38 trials of soy protein showed 47g intake lowered total, LDL-C, and trigs 9%, 13%, and 11%, respectively; no effect on HDL-C.
• Phytosterol-supplemented foods (e.g., stanol ester margarine) lowers LDL-C avg. 10%
• Meta-analysis of garlic studies showed 9% total cholesterol reduction from 1/2-1 clove consumed daily for 6 months.
Health Benefits of Weight Loss
• Decreased cardiovascular risk
• Decreased glucose and insulin levels
• Decreased blood pressure
• Decreased LDL and triglycerides, increased HDL
• Decrease in severity of sleep apnea
• Reduced symptoms of degenerative joint disease
• Improved gynecological conditions
National Obesity Education Initiative Treatment
Algorithm
Patient Encounter
Hx of 25 BMI?
•Measure weight, height, and waist circumference •Calculate BMI
Examination
Brief reinforcement/ educate on weight management
Periodic weight check
Advise to maintain weight/address other risk factors
Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control
Assess reasons for failure to lose weight
Maintenance counseling: Dietary therapy Behavior therapy Physical activity:
Treatment
Assess risk factors
No
Yes
1
2
14
15 13
12
11 1016
3
4 6
5 7
8
9
Yes
No
Yes
No
Hx BMI 25?
No
Yes
Yes
No
Does patient want to lose weight?
Yes
No
Progress being made/goal
achieved?
BMI 25 OR waist circumference
> 88 cm (F) > 102 cm (M)
BMI 30 OR
{[BMI 25 to 29.9 OR waist circumference
>88 cm (F) >102 cm (M)] AND 2 risk
factors}
BMImeasured in past
2 years?
Whenever possible, weight loss therapy should employ the combination of
• Low-calorie/low-fat diets
• Increased physical activity
• Behavior modification
Weight Loss Therapy
O – Other Interventions with Class I Recommendations
• Blood pressure – encourage optimal levels of <120/80 mmHg
• Cholesterol levels – optimal cholesterol levels <200 mg/dl, LDL-C< 100 mg/dl, HDL >50 mg/dl, triglycerides <150 mg/dl
• Diabetes – recommend control to HgbA1c < 7%
Evidence-based Guidelines for CVD Prevention in Women – Major Risk Factor Interventions
(Mosca et al., Arterioscler Throm Vasc Biol 2004; 24: e29-e50)
I have some bad news for you. While your cholesterol has remained the same, the research
findings have changed.
When LDL-lowering drug therapy When LDL-lowering drug therapy
is employed in high-risk or is employed in high-risk or
moderately high risk patients, moderately high risk patients,
intensity of therapy should be intensity of therapy should be
sufficient to achieve a 30–40% sufficient to achieve a 30–40%
reduction in LDL-C levels.reduction in LDL-C levels.
JNC-7 New Features and Key Messages
Thiazide-type diuretics should be initial drug therapy for most, either alone or combined with other drug classes.
Certain high-risk conditions are compelling indications for other drug classes.
Most patients will require two or more antihypertensive drugs to achieve goal BP.
If BP is >20/10 mmHg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic.
H – Highest Priority for Therapy is for Women at Highest Risk
• Those at highest risk, who already have pre-existing CVD, diabetes, or chronic kidney disease are most likely to benefit from preventive therapy involving the following Class I recommendations:– ACE inhibitor therapy (if coughing, subst. ARB)– Aspirin therapy (baby aspirin or maximum dose of 162 mg)
unless contraindicated– Beta-blocker therapy in those with prior MI or current angina– Statin therapy – Niacin or fibrate therapy if low HDL present– Fibrates to lower triglycerides and improve HDL– Warfarin in those with atrial fibrillation unless
contradindicated
H H – Highest Priority for Therapy is – Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk
• Those at highest risk, who already have pre-existing Those at highest risk, who already have pre-existing CVD, diabetes, or chronic kidney disease are most CVD, diabetes, or chronic kidney disease are most likely to benefit from preventive therapy involving the likely to benefit from preventive therapy involving the following Class I recommendations:following Class I recommendations:– ACE inhibitor therapy (if coughing, subst. ARB)ACE inhibitor therapy (if coughing, subst. ARB)– Aspirin therapy (baby aspirin or maximum dose of 162 mg) Aspirin therapy (baby aspirin or maximum dose of 162 mg)
unless contraindicatedunless contraindicated– Beta-blocker therapy in those with prior MI or current anginaBeta-blocker therapy in those with prior MI or current angina– Statin therapy Statin therapy – Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present– Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL– Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless
contradindicatedcontradindicated
AA – Avoid “Class III” Interventions – Avoid “Class III” Interventions(Not proven useful or effective / may be harmful)(Not proven useful or effective / may be harmful)
• Combined estrogen and progestin therapy, and *estrogen Combined estrogen and progestin therapy, and *estrogen monotherapy since associated with increased risk of CVDmonotherapy since associated with increased risk of CVD
• Selective estrogen-receptor modulators (SERMs) also not Selective estrogen-receptor modulators (SERMs) also not recommendedrecommended
• Antioxidant supplements including vigtamin E, C, and beta-Antioxidant supplements including vigtamin E, C, and beta-carotene carotene
• Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation
• Aspirin for MI prevention in women aged <65 yearsAspirin for MI prevention in women aged <65 years
Vitamins: Major Vascular Events
Vascular Event
Major coronary 1063 1047
Any stroke 511 518
Revascularization 1058 1086
Any of the above 2306 (22.5%)
2312 (22.5%)
Heart Protection Study Collaborative Group. Lancet. 2002;360:23–33.
Risk Ratio and 95% CIRisk Ratio and 95% CI
Vitamin BetterVitamin Better Vitamin WorseVitamin Worse
0.40.4 0.60.6 0.80.8 1.01.0 1.21.2 1.41.4
1.00 (0.94–1.06)P > 0.9
Vitamins (n = 10,269)
Placebo (n = 10,267)
Does Hormone Replacement Therapy Prevent Heart Disease?
• Epidemiologic studies over the past several decades together have shown approximately a 50% lower risk in women randomized to estrogen replacement therapy vs. placebo
• Even the Nurses’ Health Study showed those on estrogen/progestin to have approximately a 60% lower risk of heart disease events
Heart and Estrogen/Progestin Replacement Study (HERS): Secondary Prevention of CHD in
Women
• Randomized, placebo-controlled trial of E/P therapy vs. placebo in 2763 women with CHD; average age 67 years
• Treatment was 0.625 mg CEE + 2.5 mg medroxyprogesterone daily for 4 years
• Primary endpoint: nonfatal MI and CHD death• Secondary endpoints: CABG, PTCA, unstable
angina, CHF, PVD, TIAJAMA 1998;280:605-613
JAMA 1998;280:605-613
HERS Results• No statistically significant difference between HRT
and placebo in both primary and secondary endpoints after 4 years.
• Within first year, greater incidence in CHD events in HRT group. In years 3 and 4, lower CHD events in HRT group compared to placebo.
• HRT lowered LDL 11% and increased HDL 10% compared to placebo.
• Approximately 50% of randomized women were on lipid-lowering drugs.
• Higher incidence of VTE and cholelithiasis in HRT group.
More Bad News: The Women’s Health Initiative
• Over 160,000 women nationwide, aged 50-79 and postmenopausal have participated in various components (observational, dietary modification, and HRT clinical trials)—over 3,000 at UCI
• The Estrogen/Progestin component of the HRT clinical trial involving 16,608 women nationwide was discontinued prematurely in Spring 2002 after 5.2 years of follow-up (instead of 8.5 years).
WHI Estrogen/Progestin and Estrogen Only Results
• Those randomized to estrogen/progestin compared to placebo and statistically significant increased risks:– Breast cancer 26% (8/10,000 person years)– Total coronary heart disease 29% (7/10,000 person years)– Stroke 41% (8/10,000 person years)– Pulmonary emobolism 2.1 X (8/10,000 person years)– Protective for colorectal cancer (37% lower) and hip fracture
(34% lower): no effect endometrial cancer or total mortalityJAMA. 2002 Jul 17;288(3):321-33.
• Estrogen-only arm was also recently discontinued in December 2003 and was associated with a 39% increased risk of stroke (12 excess strokes per 10,000 person years) and 12% significant increased risk of cardiovascular events. JAMA. 2004 Apr 14;291(14):1701-12.
Women Making a ChangeWomen Making a Change
For More Information about Preventing Heart Disease:
Preventive Cardiology, 2nd ed.from McGraw-Hill …..
For more information, see the UCI Heart Disease Prevention Website at www.heart.uci.edu