MATTERS OF THE HEART
| WOMEN’S CARDIAC HEALTH —Erminia M. Guarneri, MD, ABHM, Associate Clinical Professor, University of California,
San Diego, School of Medicine, Co-Founder and Medical Director, Scripps Center of Integrative Medicine, and Attending
Cardiologist, Cardiovascular Disease, Scripps Clinic, La Jolla, CA
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| Sex differences: chest pain and shortness of breath (SOB) with exertion red flags for angina and underlying cardiovascular
disease (CVD); men more likely to present with chest discomfort and diaphoresis when having myocardial infarction
(MI); women more likely to have jaw, neck, or back discomfort (particularly when lifting arms), SOB, and fatigue;
women treated less aggressively than men; less likely to receive stress testing or to be referred for angiography; less
likely to receive aspirin and β-blockers after MI; less likely to receive thrombolytics; in-hospital mortality worse for
women than men; deaths within 1 yr of MI, 38% (25% for men); deaths after MI in previously asymptomatic patient,
63% (50% for men)
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| Cholesterol: data show coronary events increased with cholesterol level >200 mg/dL; blood cholesterol not best predictor
of CVD—Framingham Heart Study showed same blood cholesterol values among 80% of people having MI as those
who did not have MI; 35% of cardiovascular (CV) events occur in people with total cholesterol <200 mg/dL; major clinical
trials show morbidity and mortality improve with use of statin therapy, but CV events continue to occur despite statin
therapy; lowering low-density lipoprotein (LDL) only one factor involved in halting CVD; emerging risk factors—
inflammation; lipoprotein a (Lp[a]); low high-density lipoprotein (HDL; particularly low HDL2b, subfraction that pulls
plaque out of vessels); high triglycerides; small dense LDL
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| Determinants of health: hormone status; vasoreactivity (common in menopause); CV events (increase after menopause;
occur earlier in women with diabetes and women who smoke); obesity; 70% to 90% of chronic disease related to
environment and lifestyle; US Surgeon General states 7 in 10 leading causes of illness and death in United States could
be significantly reduced by modifications in lifestyle (eg, alcohol abuse, lack of exercise, poor diet, tobacco smoking,
maladaptive responses to stress and tension)
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| Obesity: 300,000 Americans die annually from poor diet and inactivity; prevalence increasing in United States; causes
lipid abnormalities, diabetes, and inflammation; Nurses’ Health Study showed CV risk increases as body mass index
(BMI) increases; metabolic syndrome—≈43% of US population between ages 60 and 69 yr meet diagnostic criteria (ie,
central obesity, low HDL, high triglycerides, high LDL, hypertension, insulin resistance); diabetes—23 million people
with diabetes expected in United States by 2025; negates protective effect of estrogens in premenopausal women; worsens
effects of hypertension and dyslipidemia; associated with inflammation (important risk factor for women); as risk
factor, equivalent to having had coronary event (speaker believes same true for metabolic syndrome); woman with diabetes
has 3 to 7 times risk for heart disease and MI as woman who does not have diabetes; also, 2 to 4 times risk of having
cerebrovascular accident (CVA); if current trend continues, 1 in 3 children born in 2000 will be diagnosed with diabetes
in their lifetime
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| Diet: fat—average fat consumption in 1990s ≈34% of total calories, compared to 42% in 1960s; simple carbohydrates—
account for significant increase in calorie consumption; women’s daily intake of calories increased 22% between 1970s
and 2000 (now ≈1800 vs ≈1500 30 yr ago); food volume—speaker recommends food consumption be cut in half for patient
needing to lose weight; soda, alcohol, and fruit juice liquid calories; 54% of Americans clean plate even when full;
39% eat when they see food; 20% eat when depressed; 19% keep eating until stuffed; visceral fat—different from subcutaneous
fat; adipokines secreted by adipose tissue produce angiotensin II (raises blood pressure [BP]), tumor necrosis factor
(TNF)-α, interleukin 6, C-reactive protein (CRP); leads to hypertension, dyslipidemia, and inflammation; oxidized
LDL, vascular cell adhesion molecule-1 (VCAM-1) molecules, monocytes, macrophages, and breakdown of endothelial
lining part of inflammatory process; CRP, arachidonic acid, and TNF markers for inflammation; inflammation associated
with conditions of aging (eg, heart disease, Alzheimer’s disease, cognitive decline)
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| Dyslipidemia: decreased level of HDL and increased triglycerides independently stronger predictors of risk for CVD in
women than in men; 1-mg/dL increase in HDL associated with 3% decrease in incidence of CV events in women; different
types of HDL; HDL2b (measured by Berkeley or vertical auto profile [VAP] testing) associated with reverse cholesterol
transport (aids efflux of lipid from artery wall); HDL carrier for antioxidant enzymes that break down
proinflammatory lipids; evidence from Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol
(ARBITER) 2 trial—triglycerides lowered when niacin added to statin therapy; carotid intima-media thickness and coronary
calcium score noninvasive tests useful in determining whether to use lipid-lowering therapy in asymptomatic patient;
statin and niacin beneficial in halting progression of CVD
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| Food as medicine: data show fat intake twice as high in United States as in rest of world; fiber intake 3 times lower; intake
of animal protein 90% higher in United States; heart disease 16-fold greater for men and 5.6-fold greater for women
in United States than in rural China; United States leads world in cancer, osteoporosis, diabetes, and hypertension; effect
of Indo-Mediterranean diet—decreased CV events by 50%, compared to National Cholesterol Education Program step 1
diet (not a CV diet); Ornish showed high levels of saturated fat in beef, pork, and lamb; Lyon heart study—showed 70%
reduction in CV events in participants (with history of CV event) who followed Mediterranean diet (eg, fruits, beans, vegetables,
fish); also reduction in late cancers; studies in Greenland Eskimos—showed CV mortality 7% among Greenland
Eskimos (45% in United States); arachidonic acid 26% in United States, compared to 8% in Greenland Eskimos; ratio of
omega-6 to omega-3 50 to 1 in United States, compared to 1 to 1 in Greenland Eskimos; anti-inflammatory properties in
fish oil lower triglycerides; omega-3 fatty acids lead to production of prostaglandin E3 (anti-inflammatory; prostaglandin
E2 proinflammatory); benefits of fish oil—improves BP; dietary supplement of 3.6 g and exercise can decrease systolic
BP 13 points; data show 20% decrease in total mortality with 1 g daily; patients with CVD should consume 1 g eicosapentaenoic
acid (EPA) daily from fish or supplements, 2 to 4 g if triglycerides high
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| Exercise: reduces heart disease deaths by 50%; Nurses’ Health Study showed CV events reduced by almost 50% in
women who exercised at highest quintile; decreases BP, weight, triglycerides and improves sense of well-being; American
College of Cardiology recommends 40 min to 1 hr of aerobic exercise daily, combined with strength training 3 times/
wk
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| Stress: precursor for disease; stress-related disorders account for 75% to 95% of all health care visits; stress response—
how patient perceives and responds to initiating event important to health; stress causes release of cortisol and elevation
of blood glucose, leading to accumulation of visceral fat; release of epinephrine and norepinephrine leads to increase in
cholesterol level and BP; risk for arrhythmias
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| Risk assessment: high risk—patients who have CVD, have had prior event or CVA, peripheral vascular disease, abdominal
aortic aneurysm, diabetes, or chronic renal insufficiency; speaker considers patient who smokes at high risk;
Framingham risk scoring obsolete; hypertension, dyslipidemia, smoking, metabolic syndrome, diabetes, obesity, stress,
and hostility and anger risk factors that can be controlled; lowering of BP <140/90 mm Hg important, as well as smoking
cessation (1-4 cigarettes daily increases risk for fatal or nonfatal MI; risk for MI decreases by 50% 1 yr after smoking
cessation)
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| Lipid-lowering studies: Heart Protection Study showed 27% reduction in major CV events, regardless of person’s
LDL level; data show 19% reduction in coronary mortality for every 39 mg/dL decrease in LDL; Incremental Decrease
in End Points through Aggressive Lipid Lowering (IDEAL) study showed benefit in reducing CVD; Adult
Treatment Panel (ATP) III trial supports lowering LDL to <70 mg/dL; A Study to Evaluate the Effect of Rosuvastatin
on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID) showed progression of disease prevented
with LDL 60 mg/dL; LDL 60 to 70 mg/dL target for high-risk patients
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| Treating high LDL: statin therapy—combination of diet and statin therapy recommended; statin therapy can reduce
LDL 55%; ≈18% reduction with ezetimibe (Zetia) alone; 46% reduction with 10 mg simvastatin and 10 mg ezetimibe
(27% reduction with 10 mg simvastatin alone, 36% reduction with 20 mg); bile acid sequestrants—last choice for treatment;
associated with gastrointestinal problems; shown to reduce LDL ≈15% to 30%; niacin—can lower triglycerides
50% and raise HDL 35%; contraindications gout, liver disease, and peptic ulcer disease; soluble fiber—≈15% reduction
in cholesterol with 15 g daily (increase by 5-g increments per week); plant sterols—2 to 3 g daily can lower cholesterol
15%; work in combination with statin therapy for further reduction of LDL; flax seed—ground and sprinkled on food;
studies show ≈10% reduction in LDL; soy protein—substitute for animal protein; red yeast rice—data show ≈16% reduction
in total cholesterol with 2.4 g daily; fish oil—lowers triglycerides in dose-dependent fashion
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| Conclusion: women may present with vague symptoms; if exercise treadmill test positive, follow with nuclear imaging,
stress echocardiography, and dobutamine echocardiography; rubidium myocardial perfusion imaging gold standard for
testing; <1% event rate within next 3 yr if single-photon emission computed tomography (SPECT) studies or rubidium
imaging normal; women with diabetes or metabolic syndrome more sensitive to high triglycerides and low HDL; women
with diabetes twice as likely as men with diabetes to have recurrent MI (requires aggressive treatment); smoking stronger
risk factor for MI in women of middle age than for men
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| PREGNANCY AND THE HEART —Elyse Foster, MD, Professor of Clinical Medicine, and Director, Adult Echocardiography
Laboratory and Adult Congenital Heart Disease Service, University of California, San Francisco, School of Medicine
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| Incidence of heart disease in pregnancy: 1% to 4% of all pregnancies; expected to increase as older women with
risk factors for heart disease become pregnant; congenital heart disease and cardiomyopathy more common in developed
countries; rheumatic heart disease more common in developing nations; rare coronary anomalies can present as pericardial
cardiomyopathy, ischemia, MI, and coronary artery dissection
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| Physiologic changes during pregnancy: 30% to 50% increase in cardiac output; increase in blood volume increases
preload (larger blood volume at beginning of systole); decrease in systemic vascular resistance decreases afterload; pulmonary
vascular resistance decreases; left ventricular (LV) ejection fraction unchanged; hemodynamics further altered
during labor and delivery; stroke volume begins to rise at fifth week of pregnancy, and continues to rise during second
and early third trimesters; stroke volume falls during third trimester, due to decreased venous return
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| Prenatal history: critical; symptoms before pregnancy (eg, SOB, syncope, palpitations, chest pains, peripheral edema);
New York Heart Association classification—useful in risk stratification; class I, asymptomatic; class II, symptoms occur
only with more than usual activity; class III, symptoms during usual activity; class IV, symptoms at rest (highest risk); severity
of disease; review findings of most recent diagnostic testing and consult with patient’s cardiologist; previous surgical
and nonsurgical interventions; ventricular function key in stratifying risk; pulmonary artery pressure (pulmonary
hypertension one of most severe and fatal diseases in pregnancy); review current medications; preexisting arrhythmias or
unexplained syncope; risk for thromboembolic complications; presence of prosthetic valve; assess for atrial fibrillation
(risk for stroke); risk for endocarditis
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| Physical examination: BP and heart rate (mild tachycardia normal in pregnancy); jugular venous distention (mild elevation
common in pregnancy, especially late stages); pulmonary crackles and bibasilar rales may be heard in late stages
of pregnancy and may be normal (abnormal in early pregnancy); digital clubbing, cyanosis, and edema signs of congenital
heart disease with right to left shunting; auscultatory findings during pregnancy—>90% of women have systolic murmur;
best heard at base of heart in pulmonic area; usually peaks in early systole and ends before second heart sound; S1
may be split (can be normal, especially in younger patient); S2 physiologically split (becomes dual heart sound at end of
inspiration); diastolic heart murmur uncommon; early diastolic sound heard in young women (ST gallop); S4 (late diastolic
sound) likely to be heard in older women, especially those with hypertension and diabetes; when to refer patient for
electrocardiography (ECG) and echocardiography—diastolic murmur (usually indicates mitral stenosis or aortic insufficiency);
grade 4 systolic murmur (usually palpable and associated with thrill) or grade 3 or less if patient symptomatic;
ECG—minor ST segment changes common, especially in late pregnancy; concerning if arrhythmias present (other than
premature atrial contractions); LV hypertrophy could be sign of aortic stenosis, hypertrophic cardiomyopathy, or hypertensive
heart disease; right ventricular hypertrophy and right atrial enlargement could be signs of pulmonary hypertension
and pulmonary valve stenosis; right ventricular hypertension and left atrial enlargement usually indicates mitral
stenosis; normal structural changes on echocardiography—left ventricular mass increases by ≈10% in pregnancy; cavity
dilates (eccentric hypertrophy); left atrial and ventricular volume increases; aortic root dilates slightly; mild physiologic
valve regurgitation common in absence of any structural valve disease; small pericardial effusions may be present in late
pregnancy
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| Valvular and other heart diseases: severe obstructive lesions carry highest risk; regurgitant lesions, aortic insufficiency,
and mitral regurgitation better tolerated as long as patient asymptomatic and ventricular function normal; mitral
stenosis—most common form of valvular heart disease in pregnancy; mitral valve area (MVA) <1 cm2 (symptoms possible
even with moderate stenosis; most rheumatic in origin; patients tend to underestimate symptoms; opening snap and
diastolic rumble best heard at apex of heart; echocardiography may overestimate MVA; pulmonary pressure and valve
gradient (poor sign when elevated) more reliable; mean gradient >10 mm Hg and/or pulmonary artery systolic pressure
>40 mm Hg of concern in early pregnancy; evaluate morphology of valve to determine suitability for balloon valvuloplasty;
treatment—judicious use of diuretics; β-blockers to slow heart rate; anticoagulation if patient in atrial fibrillation
or has history of embolus or stroke; percutaneous mitral balloon valvotomy best performed in second trimester; avoid
surgery if possible; aortic stenosis—mostly congenital; severe aortic stenosis defined as aortic valve area ≤1 cm2 or peak
gradient >64 mm Hg; symptoms include dyspnea, chest pain, and syncope; late peaking systolic murmur associated with
soft or diminished A2; increase in aortic valve gradient with increase in cardiac output; patient with severe aortic stenosis
(even with mild symptoms) should avoid pregnancy until treated; treatment—avoid excessive diuresis; bed rest may be
necessary; percutaneous balloon valvotomy; surgical valvotomy or valve replacement; anticoagulation—necessary for
patients with prosthetic heart valves, venous thromboembolic disease, and atrial fibrillation; highest risk for embryopathy
with warfarin between 6 and 12 wk of gestation (risk low with <5 mg); adjusted dose of subcutaneous heparin not completely
protective in patients with tilting disk and older prostheses; continuous heparin impractical and associated with
complications (probably safe to use low-molecular-weight heparin [LMWH]); aspirin and clopidogrel considered safe;
aspirin optional in management of preexisting prosthetic valve during pregnancy; continuous anticoagulation indicated
for patients with mechanical valves; continue warfarin until pregnancy documented; use LMWH or heparin until term;
adjust dose, maintaining anti-factor Xa levels at 4 hr post dose ≈1 U/mL; peripartum cardiomyopathy—angiotensin-converting
enzymes and angiotensin receptor blockers contraindicated in pregnancy; hydralazine, low-dose diuretics, β-
blockers, and metoprolol (instead of atenolol) and digoxin considered safe; furosemide more potent than thiazides; anticoagulate
patient only if they have thromboembolism; good prognosis, compared to other forms of cardiomyopathy; no
definite answer about subsequent pregnancy; dobutamine echocardiography recommended before next pregnancy; recurrent
heart failure and mortality high in patients with LV dysfunction and ejection fraction <50%; Marfan syndrome—
genetic counseling; aortic insufficiency and mitral valve prolapse; aortic root dimension >4.5 cm highest risk; β-blocker
therapy indicated throughout pregnancy
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Suggested Reading
de Lorgeril M, Salen P: Mediterranean diet and n-3 fatty acids in the prevention and treatment of cardiovascular disease.
J Cardiovasc Med Suppl 1:S38, 2007; Libby P: Inflammation in atherosclerosis. Nature 420:868, 2002; Moreyra
AE et al: Effects of combining psyllium fiber with simvastatin in lowering cholesterol. Arch Intern Med 165:1161, 2005;
Presbitero P et al: Pregnancy in cyanotic congenital heart disease. Outcome of mother and fetus. Circulation 89:2673,
1994; Siu SC et al: Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation
104:515, 2001.
Educational Objectives
| The goal of this program is to improve the care of women at risk for heart disease and pregnant women with heart disease.
After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Recognize sex differences in symptom presentation associated with myocardial infarction in women.
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| 2. Discuss factors other than blood cholesterol that cause cardiovascular disease (CVD).
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| 3. Counsel patients about lifestyle modifications that prevent CVD and other diseases of aging.
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| 4. Distinguish normal physiologic changes in pregnancy from abnormal changes.
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| 5. Provide prenatal care for pregnant women with heart disease.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee members
to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified
conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business
or commercial interest. For this program, the following has been disclosed: Dr. Foster has received grant support from Guidant-
Boston Scientific and Evalve. Dr. Guarneri and the planning committee reported nothing to disclose.
Acknowledgements
Dr. Guarneri was recorded at Primary Care Medicine: A Practical Approach, sponsored by Scripps Clinic, held on August 10-12,
2007, in San Diego, CA. Dr. Foster was recorded at Antepartum & Intrapartum Management, sponsored by the University of California,
San Francisco, School of Medicine, and held on June 7-9, 2007, in San Francisco. The Audio-Digest Foundation thanks
the speakers and the sponsors for their cooperation in the production of this program.
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