American College of Physicians: Internal Medicine — Doctors for Adults ®

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Special Focus: Coronary artery disease in women

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From the May ACP Observer, copyright 2007 by the American College of Physicians.

Women are less likely than men to develop heart disease, but their outcomes are often worse. As a result, internists should be highly suspicious when women present with several risk factors, such as smoking, diabetes, obesity or a family history of heart disease, said Rita F. Redberg, MD, director of Women's Cardiovascular Services at the University of California, San Francisco Medical Center's division of cardiology.

Dr. Redberg also emphasizes that heart disease, while a leading cause of death, is still very preventable. "You can certainly delay the onset, and so it's important to emphasize lifestyle factors, such as eating a heart-healthy diet, getting exercise and not smoking," she said.

A colored angiogram of the coronary arteries of a patient with heart disease reveals extensive areas of stenosis.


A colored angiogram of the coronary arteries of a patient with heart disease reveals extensive areas of stenosis.



Dr. Redberg is also a co-author of the updated American Heart Association's "Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women: 2007 Update" published in the AHA's Circulation and the Journal of the American College of Cardiology. Last revised in 2004, the guidelines cover the primary and secondary prevention of chronic atherosclerotic vascular diseases. An evaluation and treatment algorithm is also included. That update can be found here.

Most recommendations remain unchanged, but the authors removed the recommendation for women younger than age 65 to take aspirin routinely for prevention of myocardial infarction (although recently published data support a role for aspirin for prevention of stroke in women). The guidelines also recommend against the use of folic acid, with or without B6 and B12 supplements, for the primary or secondary prevention of cardiovascular disease.

The guidelines also advised physicians to look at several factors in addition to the short-term absolute Framingham global risk score when deciding on preventive therapy. Those factors include:

  • medical history and lifestyle,
  • family history of cardiovascular disease, and
  • genetic conditions such as familial hypercholesterolemia.

Additional recommendations deal with exercise, diet, use of dietary supplements, alcohol and smoking, and weight.

This issue of ACP Observer Special Focus is designed to help optimize your ability to diagnose, treat and manage coronary artery disease (CAD) in women.

PREVENTION

Smoking

Counsel all smokers about cessation and support continued abstinence in those who have quit. The risk for MI is three times higher in cigarette smokers than in non-smokers. Cessation decreases the risk for CAD by an estimated 36%, making it the single most important lifestyle modification.

Hypertension

Screen all women for hypertension by checking blood pressure at all patient visits and treat aggressively with lifestyle modification and medication, if needed. The goal blood pressure in patients with hypertension without diabetes is <140/85 mm Hg, and the goal blood pressure in patients with diabetes is <130/80 mm Hg.

Hypertension, particularly diastolic hypertension, is associated with a 1.6- to 3-fold increased risk for cardiovascular events in women and a tenfold higher increase in death from CAD. In elderly women, in particular, the presence of hypertension is a stronger indicator for CAD than it is in men.

Dyslipidemia

Dyslipidemia is a modifiable risk factor for CAD in women age 45 or older. Studies of lipid reduction in the primary and secondary prevention of cardiovascular events have included relatively few women. However, estimates of the relative benefit of lipid-lowering therapy for women have generally corresponded to estimates of benefit for men.

Low levels of HDL cholesterol (<35 mg/dL) may be particularly predictive of CAD in women. Perform a total cholesterol screen and obtain fasting total cholesterol, LDL, HDL and triglyceride levels if the initial total cholesterol level is elevated and/or if there are multiple risk factors for CAD. Although statins have not been shown to reduce cardiac events or mortality in women when used for primary prevention, current AHA guidelines recommend them when dyslipidemia is present.

Obesity and inactivity

Obesity has been associated with an increased risk for MI, death from coronary events and reinfarction rates in women in several large-cohort studies. The risk for CAD and death is lower in women who exercise regularly and who are more physically fit. Brisk walking or vigorous exercise (2.5 hrs/wk) was associated with a 30% reduced risk of cardiovascular events.

Diet

A balanced diet rich in whole grains, fresh vegetables and fruits, with regular intake of fish is recommended for optimal cardiovascular health. Recommend a diet that is low in saturated fats and oils, low in processed starches and simple sugars, and rich in fiber. Epidemiologic studies suggest that diets high in saturated fat and trans fatty acids found in vegetable shortening, stick margarine and many commercial baked goods are associated with increased rates of cardiovascular disease.

In the Nurses' Health Study, a prospective study of 80,000 women followed from 1980 to 1994, each increase of 5% in energy intake from saturated fat, as compared with equivalent energy intake from carbohydrates, was associated with a 17% increase in the risk of coronary disease. Researchers concluded that replacing saturated fat and trans fatty acids with monounsaturated and polyunsaturated fats is more effective in preventing coronary heart disease in women than reducing overall fat intake.

Antioxidants

Although oxidized lipids, particularly LDL cholesterol, are believed to be atherogenic, available randomized controlled trials have not shown any reduction in cardiovascular risk with use of antioxidant vitamins. Do not recommend antioxidant vitamins for the primary or secondary prevention of CAD. Instead, recommend abundant fresh vegetables and fruits as a source of micronutrients, based on U.S. Preventive Services Task Force research published in the July 2003 Annals of Internal Medicine.

Hormone replacement therapy

The Women's Health Initiative (WHI) randomized more than 16,000 healthy postmenopausal women to hormone therapy (HT) vs. placebo. This study showed a small but statistically significant excess of major cardiovascular events (nonfatal MI and coronary death) in women treated with HT over five years of follow-up. Largely due to these findings, the AHA now recommends against HT for cardiovascular risk reduction in postmenopausal women.

Randomized, controlled trials show that HRT does not protect against cardiovascular events in women with established CAD, and even increases short-term risk of thromboembolic complications.

Aspirin and vitamin E

Although numerous observational studies have shown a benefit of aspirin in both men and women with established CAD, there is no conclusive evidence of benefit from every-other-day aspirin use for primary prevention, according to results from the Women's Health Study, a randomized 2 x 2 factorial trial of 39,876 U.S. women using aspirin and vitamin E conducted between September 1992 and March 2004.

For high-risk women, AHA guidelines state that aspirin therapy (75 to 325 mg/d) should be used for primary prevention, unless contraindicated, when the following criteria are present:

  • abdominal aortic aneurysm,
  • end-stage or chronic renal disease,
  • diabetes mellitus, and
  • 10-year Framingham global risk >20%. The 10-year Framingham risk estimates can be found here.

AHA guidelines further state that all women should consider aspirin therapy (81 mg daily or 100 mg every other day) if their blood pressure is controlled and if the benefit for ischemic stroke and MI prevention is likely to outweigh the risk of gastrointestinal bleeding and hemorrhagic stroke.

Data from the Women's Health Study did not confirm a benefit from vitamin E supplementation on cardiac disease in men or women. In fact, a meta-analysis found increased mortality in vitamin E users at doses over 400 IU daily.

DIAGNOSIS

Perform a thorough history and physical exam, including a careful description of symptoms and evaluation for cardiac risk factors.

Classify the type of chest discomfort and the specific nature of associated symptoms in the patient with possible CAD. Although anginal pain is a strong predictor of CAD, women are more likely than men to present with atypical symptoms, such as pain with emotional stress and during rest or sleep. They are also more likely to experience radiation of pain to the neck and shoulder and to develop associated nausea, vomiting, and shortness of breath with MI.

Some studies have shown a tendency by physicians to treat women with chest pain differently from their male counterparts. In one study, for example, women who assumed a businesslike manner were more likely to be investigated further than women who presented with the same symptoms but assumed a more emotional attitude. A physician's assessment may also be influenced by a tendency among women to attribute ischemic symptoms to other causes because they do not consider themselves to be at risk for CAD.

Menopause is associated with increased levels of LDL cholesterol, decreased levels of HDL cholesterol, decreased insulin sensitivity, increased body mass, decreased fibrinolytic activity, and impaired endothelium-dependent vasodilatation. The incidence of morbidity and mortality due to CAD increases with age, and surgical menopause increases the risk for CAD over that of natural menopause, regardless of whether a woman takes hormonal therapy.

Use clinical evaluation of risk factors and symptoms to estimate the pretest probability of CAD and determine when and what further testing is necessary. One such evaluation, "The Probability of Coronary Artery Disease in Women according to Age and Character of Symptoms," can be found here. Further testing is most useful in women with an intermediate probability of having CAD (between 10% to 20% and 80% to 90%).

Obtain an ECG in all women presenting with possible ischemic chest pain to look for evidence of ischemic heart disease or previous MI. Baseline ECG abnormalities, such as ST segment depression, T-wave flattening, bundle branch blocks, arrhythmias, left ventricular hypertrophy and ischemic findings, are associated with increased cardiovascular disease and CAD mortality in women.

A normal ECG does not rule out the presence of CAD. In the Coronary Artery Surgery Study (CASS), 29% of patients with symptomatic, angiographically proven CAD had normal resting ECGs. On an ECG taken during chest pain, look for ischemic changes as important diagnostic information that may preclude the need for further stress testing and support direct cardiac catheterization. A normal ECG taken when the patient is having chest pain virtually excludes ischemia.

Obtain noninvasive stress testing and/or cardiac catheterization in women requiring evaluation for CAD, depending on the clinical circumstances. Obtain a treadmill exercise tolerance test as the first-line test in women with a normal baseline ECG, and reserve imaging tests for women at higher risk with abnormal baseline ECGs.

Imaging studies include exercise, radionuclide myocardial perfusion scanning and stress echocardiography. Recognize that there is a higher false-positive rate of exercise ECG and radionuclide cardiac imaging in women than in men.

Consider proceeding directly to cardiac catheterization in women with a high pretest probability for CAD (90%) without obtaining prior stress testing. Cardiac catheterization confirms the presence of CAD and delineates the extent of disease in high-risk patients. A negative stress test in a woman with a high pretest probability for CAD has a high likelihood of being a false negative. In this circumstance, cardiac catheterization is necessary, regardless of the result of stress testing.

Strongly consider CAD in the broad differential diagnosis for women with chest pain, particularly if they have multiple risk factors. However, also consider the possibility of other cardiac, pulmonary, gastrointestinal, musculoskeletal, neurologic and vascular processes. Although there is an increased incidence of nonischemic causes of chest pain, such as mitral valve prolapse, in women as compared to men, there is also an increased incidence of vasospastic and microvascular cardiac ischemia in women.

TREATMENT

Non-drug therapy

Lifestyle changes

Counsel all women about regular exercise and diet to maintain an ideal weight. Advise smoking cessation and reinforce continued abstinence in those who have already quit.

Treat hypertension, diabetes and hyperlipidemia with lifestyle changes and medication as needed.

All women with known CAD require lipid management for secondary prevention and should begin a diet low in saturated fats and trans fatty acids with more carbohydrates of the complex type coming from grains, fruits and vegetables. If LDL remains >100 mg/dL, drug therapy should be added to achieve LDL <100 mg/dL. A lower target LDL of <70 mg/dL is reasonable. In patients with an HDL <35 mg/dL, encourage exercise to increase HDL.

Invasive procedures

Revascularization procedures improve outcomes in women with unstable angina, significant angina interfering with lifestyle despite maximal medical therapy and those with high-risk findings on noninvasive testing.

Consider percutaneous transluminal coronary angioplasty (PTCA) in patients with single- or two-vessel disease who are not candidates for medical management alone. However, keep in mind that women are three times more likely than men to experience increased morbidity and mortality with PTCA. This is due, in part, to the fact that women who undergo PTCA are typically older and have more cardiac risk factors than men who undergo the procedure.

Consider coronary artery bypass surgery in patients with significant left main coronary artery stenosis; three-vessel disease, especially with left ventricular dysfunction; and two-vessel disease that includes a stenosis of more than 75% in the proximal left anterior descending artery and is accompanied by abnormal left ventricular function. Women who undergo coronary artery bypass surgery have more cardiac risk factors than men and are also more likely to experience complications such as death, heart failure, bleeding and infarction.

Drug Therapy

Aspirin. Aspirin decreases the short- and long-term risk for MI in patients with established CAD. Aspirin use in patients with angina is associated with approximately a 33% decrease in cardiovascular events. Patients should take aspirin 75 to 325 mg daily if there are no contraindications. Consider the use of clopidogrel if there is an absolute contraindication to aspirin, although there are no randomized controlled trials that support its benefit in this setting. Do not use the antiplatelet agent dipyridamole in the treatment of CAD. Dipyridamole can increase exercise-induced ischemia in patients with stable angina.

-blockers. Use as a first-line treatment to decrease ischemic symptoms both at rest and with exertion, and to reduce mortality. Use -blockers only if patients have no contraindications and avoid abruptly discontinuing them. Titrate to a resting heart rate of 55 to 60 beats/min in women with stable angina. In both randomized trials and meta-analyses, -blockers improved survival in patients with recent MI. -blockers are not effective in the treatment of (and may even induce) vasospastic angina and therefore should not be used for this purpose. They may be combined with slow-release dihydropyridines or new generation, long-acting, dihydropyridine calcium-channel antagonists. Bradycardia or AV block may occur with -blockers and verapamil or diltiazem.

Calcium channel antagonists. Consider the use of slow-release or long-acting calcium-channel antagonists in patients who are unable to take -blockers or when the response to -blockers is suboptimal. Calcium channel antagonists are also useful in the treatment of vasospastic (Printzmetal's) angina. Slow-release or long-acting calcium-channel blockers are as effective as -blockers in reducing angina, whereas short-acting or immediate-release agents may increase post-MI mortality.

Nitrates. Use to control anginal symptoms. Nitrates decrease myocardial oxygen consumption and improve myocardial perfusion. Instruct patients to use short-acting sublingual nitrates as needed for ischemic symptoms or prophylactically in circumstances known to cause angina. Consider the use of long-acting nitrates as an alternative first-line therapy to -blockers in women who have contraindications or unacceptable side effects, or in addition to -blockers when a -blocker alone is insufficient. Nitrate tolerance develops to the antianginal, antiplatelet, and hemodynamic effects of the drug. A nitrate-free period of 8 to 12 hours each day is required to prevent nitrate tolerance. For this reason, many clinicians prefer calcium-channel antagonists to nitrates for maintenance treatment of CAD.

ACE-inhibitors. The use of ACE-inhibitors in patients with CAD reduces major cardiovascular events and reduces mortality in patients with reduced left ventricular function. In the HOPE trial, subjects with vascular disease or diabetes and at least one additional cardiovascular risk factor who were treated with ramipril had a significantly reduced risk of major cardiovascular events, total mortality, cardiovascular mortality, MI, stroke, heart failure, diabetic complications, revascularization procedures, and cardiac arrest. The recent EUROPA trial confirmed the results of the HOPE trial.

Dyslipidemia. Lipid-lowering therapy with statins or other drugs is recommended for all patients with CAD or CAD equivalents—diabetes or established non-coronary vascular disease. It should also be considered for all women with dyslipidemia and an estimated 10-year risk of major cardiovascular events of more than 20%.

FOLLOW-UP

Assess patients for signs and symptoms suggesting disease progression. Ask whether the patient has developed new or worsening chest discomfort, dyspnea or other anginal equivalent symptoms that may require an adjustment to the treatment regimen or further investigation, such as cardiac catheterization. Ask how often the patient is using sublingual nitroglycerin and determine if this is an increase over previous use.

Examine the patient for findings suggesting advancing atherosclerosis (e.g., newly decreased pulses) or for developing complications, such as heart failure. At each follow-up visit:

  • Assess adequacy of cardiac risk factor modification and the development of new risk factors.
  • Assess smoking status on each visit and counsel appropriately.
  • Assess physical activity and advise regular exercise.
  • Measure blood pressure on every visit and treat appropriately.
  • Weigh patients on each visit and treat appropriately.
  • Ensure that the patient is up to date on screening for diabetes mellitus and hyperlipidemia and that those patients already diagnosed with either or both are receiving adequate treatment.

In the absence of clinical change, there is no evidence that routine periodic ECGs are useful. When clinical changes occur, ECGs may identify new ischemic changes or MI. Obtain an ECG and stress test:

  • in women with known CAD who experience changes in their anginal symptoms.
  • when medication affecting cardiac conduction is begun or changed.
  • when there is a change in anginal pattern or there is concern about a dysrhythmia.

Consider obtaining periodic stress testing in high-risk patients. Stress testing stratifies patients with known or suspected CAD into low-, intermediate- and high-risk groups.

Review the patient's medication regimen at each visit. Determine whether the patient is taking each medication in the prescribed dose and manner, as well as whether she is experiencing side effects.

This information comes from the PIER module "Coronary Artery Disease in Women."


The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.

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