Coronary Artery Disease Prevention: What's Different for Women?

Author: Joan Bedinghaus, Sabina Diehr
Date: April 1, 2001

Cardiovascular disease is the leading cause of death in women, as well as an important cause of disability, although many women and their physicians underestimate the risk. Exercise, hypertension treatment, smoking cessation and aspirin therapy are effective measures for the primary prevention of coronary artery disease in women. The roles of lipid-lowering agents and hormone replacement therapy in primary prevention are not well established. In secondary prevention, hormone replacement therapy has not been effective in lowering the risk of recurrent myocardial infarction, but several lipid-lowering agents have been shown to reduce this risk and to lower mortality rates in women with known coronary artery disease. Other secondary prevention measures, including aspirin, beta blockers, angiotensin-converting enzyme inhibitors, revascularization and rehabilitation, have proven benefits in women but are underused, especially in minority women. Family physicians should emphasize the use of proven treatments, with particular attention given to underserved populations. (Am Fam Physician 2001;63:1393-400,1405-6.)

Coronary artery disease has been widely considered a "man's disease" and not a major concern for women. Yet cardiovascular disease is the leading cause of death in adult women in the United States. A 1995 Gallup poll found that one in three primary care physicians in this country, as well as four out of five women, was unaware of this fact.(1(p3))

Women's age-adjusted mortality rates from heart disease are four to six times higher than their mortality rates from breast cancer. Yet, because public campaigns have emphasized breast cancer risks in the effort to promote screening mammography, many women are more afraid of breast cancer than of coronary artery disease.

Over the past two decades, public education efforts related to cardiovascular disease prevention have been aimed primarily at male populations. As a result, the prevalence of coronary risk factors and the number of cardiovascular deaths have decreased in men--but not in women.(1(pp4,6))

Lipid-lowering medications and hormone replacement therapy have raised great hopes for primary prevention of coronary artery disease (i.e., prevention of a first myocardial infarction or the onset of symptomatic coronary artery disease). However, in caring for women, physicians await evidence from randomized, controlled trials to support the effectiveness of these measures, while sorting among conflicting sets of recommendations. In secondary prevention, which includes measures to prevent reinfarction and cardiovascular death, there is good evidence for the effectiveness of many therapies. However, studies indicate that women may not be prescribed beneficial therapies as frequently as men.

This article reviews the characteristics of coronary artery disease, the prevalence and significance of coronary risk factors, and the evidence for the effectiveness of preventive strategies in women. Approaches to targeting preventive efforts to women's special needs are also addressed.

Characteristics of Coronary Disease in Women

When women present with myocardial infarction, they are more likely than men to be misdiagnosed, and they are also more likely to die of their first infarction(2) (Table 1).(1-9) Chest pain in perimenopausal women is often difficult to diagnose because it may present atypically. Shoulder or neck pain, nausea, fatigue or dyspnea are more likely to signal myocardial infarction in women than in men.(1) Classic substernal pressure symptoms are comparatively less predictive of myocardial infarction in women.(2-4)

Because studies have shown that women with coronary artery disease present with a mix of typical and atypical symptoms, it is important that physicians consider risk factors when evaluating chest pain syndromes in women.(4) An approach that uses risk-factor scoring to guide an appropriate assessment of chest pain in women without known coronary artery disease is presented in Figure 1.(4)

Chest Pain in Women Without Known Coronary Artery DiseaseAssign appropriate points for each of the patient's risk factors.Add the points to obtain the total score, which guides the diagnosticstrategy.Risk determinantsMajor risk factors (3 points each)Typical anginal pain ____Postmenopausal status without hormone replacement therapy ____Diabetes ____Peripheral vascular disease ____Intermediate risk factors (2 points each)Hypertension ____Smoking ____Total cholesterol level [greater than] ____ 265 mg per dL (6.85 mmol per L)Minor risk factors (1 point each)Patient age [greater than] 65 years ____Obesity ____Sedentary lifestyle ____Family history of coronary artery disease ____Stress ____Total score: ____Diagnostic strategy[less than Low likelihood of coronary artery diseaseor equal]2 ([less than] 20%): no tests indicatedpoints3 or 4 Moderate likelihood of coronary artery disease (20% to 80%):points exercise tolerance test or imaging study[greater than Strong likelihood of coronary artery diseaseor equal]5 ([greater than] 80%): exercise tolerance test, withpoints cardiac catheterization performed if test is inconclusive or positiveFIGURE 1. Approach to the assessment of chest pain in women not known tohave coronary artery disease.Information from Douglas PS, Ginsburg GS. The evaluation of chest pain inwomen. N Engl J Med 1996;334:1311-5.

Coronary risk factors are more prevalent in women who are older, poor, African American, Hispanic or Native American. Primary and secondary prevention in these underserved populations requires particular attention to the context of these women's lives. There is evidence that several preventive measures can reduce the risk of coronary disease (Table 2).(10-17)

PHYSICAL INACTIVITY, OBESITY AND DIABETES

Sedentary lifestyle is the most common risk factor for coronary artery disease in women. Data from the National Center for Health Statistics indicate that 39 percent of white women and 57 percent of women of color do not get enough physical exercise.(18) Rates of physical inactivity are highest among poor women.

Physical inactivity contributes to obesity and is an independent risk factor for myocardial infarction.(13) Conversely, modest exercise has been strongly associated with risk reduction in observational studies. Investigators in the Nurses' Health Study(19) found that 30 to 45 minutes of walking three times weekly reduces the risk of myocardial infarction by 50 percent in women (even older women). Exercise has also been found to reduce the risk of type 2 diabetes (formerly known as non-insulin-dependent diabetes, and also a risk factor for coronary artery disease), even in women with obesity and a family history of diabetes.(20)

Obesity is an independent risk factor for all-cause mortality. It is highly associated with diabetes, hyperlipidemia and hypertension.(21) According to the National Center for Health Statistics,(18) 33 percent of African American women and 17 percent of white women are obese (i.e., body mass index [BMI] greater than 30). The risk of cardiovascular disease becomes higher with increasing weight, even at lower BMIs. Central obesity (a waist-to-hip ratio greater than 0.8) is associated with a disproportionate increase in coronary risk. The most effective treatment for obesity in women has not been determined, and exercise appears to be less effective in promoting weight loss in women than in men.(22)

Obesity is also a major risk factor for the development of type 2 diabetes, which is the most important risk factor for coronary disease in women. Coronary artery disease generally presents at an older age in women than in men, but diabetes wipes out this gender-protective effect. Furthermore, coronary disease is more likely to be fatal in women with diabetes.(5) Native Americans and African Americans have higher rates of diabetes and its cardiovascular sequelae.

Although there is a dose-response relationship between the level of hyperglycemia and the incidence of coronary artery disease, studies have not clearly shown that tight control of type 2 diabetes reduces the risk of cardiovascular disease. However, secondary prevention trials have found that aggressive control of hypertension and hyperlipidemia does reduce the risk of reinfarction in women with diabetes.(17)

(31.) Sorensen G, Pechacek TF. Attitudes toward smoking cessation among men and women. J Behav Med 1987;10:129-37.

(32.) Killen JD, Fortmann SP, Newman B, Varady A. Evaluation of a treatment approach combining nicotine gum with self-guided behavioral treatments for smoking relapse prevention. J Consult Clin Psychol 1990;58:85-92.

(33.) Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999; 340:685-91.

(34.) Manson JE, Stampfer MJ, Colditz GA, Willet WC, Rosner B, Speizer FE, et al. A prospective study of aspirin use and primary prevention of cardiovascular disease in women. JAMA 1991;266:521-7.

(35.) Krumholz HM, Radford MJ, Ellerbeck EF, Hennen J, Meehan TP, Petrillo M, et al. Aspirin for secondary prevention after acute myocardial infarction in the elderly: prescribed use and outcomes. Ann Intern Med 1996;124:292-8.

(36.) Gan S, Beaver S, Houck PM, MacLehose RF, Lawson HW, Chan L. Treatment of acute myocardial infarction and 30-day mortality among women and men. N Engl J Med 2000;343:8-15.

Members of various medical faculties develop articles for "Practical Therapeutics." This article is one in a series coordinated by the Department of Family and Community Medicine at the Medical College of Wisconsin, Milwaukee. Guest editors of the series are Linda N. Meurer, M.D., M.P.H., and Douglas Bower, M.D.

JOAN BEDINGHAUS, M.D., is assistant professor in the Department of Family and Community Medicine at the Medical College of Wisconsin, Milwaukee. Dr. Bedinghaus graduated from Harvard Medical School, Boston, and completed a family practice residency at MetroHealth Medical Center, Cleveland.

LOREN LESHAN, M.D., is associate professor in the Department of Family and Community Medicine at the Medical College of Wisconsin and director of the family practice residency program at St. Mary's Hospital, Milwaukee. Dr. Leshan received her medical degree from Tufts University School of Medicine, Boston, and completed a family practice residency at MetroHealth Medical Center, Cleveland.

SABINA DIEHR, M.D., is assistant professor in the Department of Family and Community Medicine at the Medical College of Wisconsin and medical director of the Family Medicine Clinic at Curative Rehabilitation Services, Milwaukee. Dr. Diehr graduated from Temple University School of Medicine, Philadelphia, and completed a family practice residency at Sacred Heart Hospital, Allentown, Pa.

Address correspondence to Joan Bedinghaus, M.D., Department of Family and Community Medicine, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226 (e-mail: jbmd@mcw.edu). Reprints are not available from the authors.

TABLE 1Coronary Artery Disease: What's Different for Women?PresentationWomen present at a later age.(1(p3)-3)In women, typical angina is less predictive of coronary artery disease (pretest probability is 50 to 60 percent in women versus 80 to 99 percent in men).(3,4)Women may present with shoulder or jaw pain, dyspnea or nausea.(1(p316),4)Risk factorsDiabetes has a stronger influence in women.(3,5)High HDL cholesterol levels, which lower the risk of coronary artery disease, are more common in women.(6)The roles of total cholesterol, LDL cholesterol and lipoprotein(a) in women are unclear.(7)The risk of coronary artery disease increases after menopause.PrognosisWomen are more likely to die of a first myocardial infarction.(2)Women experience more long-term disability.(1(p25))Women have more comorbidity (because they are usually older on presentation).Primary preventionThere is insufficient evidence for the benefits of cholesterol-lowering drugs in women.There is insufficient evidence for the benefit of estrogen replacement therapy.Secondary preventionWomen are less likely to undergo angioplasty or bypass surgery.(8)Fewer women receive cardiac rehabilitation.(1(p213))Fewer women receive therapy with aspirin, beta blockers or angiotensin-converting enzyme inhibitors.(9)HDL = high-density lipoprotein; LDL = low-density lipoprotein.Information from references 1 through 9.TABLE 2Measures for Primary and Secondary Prevention of Coronary Artery DiseasePrimary preventionProven benefit in controlled trials(10,11) Hypertension control Beta blockers Thiazide diuretics Aspirin(12)Benefit in observational studies Exercise(13) Smoking cessation(14)Proven benefit in men but controversial in women Drug therapy to lower cholesterol levels(15)Insufficient evidence of benefit Estrogen replacement therapySecondary preventionProven benefit in controlled trials Hypertension control Beta blockers Aspirin Angiotensin-converting enzyme inhibitors(16) Aggressive cholesterol-lowering therapy(17) Angioplasty Coronary artery bypass surgeryBenefit in observational studies Smoking cessation Exercise rehabilitation[*][*]--Functional improvement; no studies on mortality reduction.Information from references 10 through 17.TABLE 3Recommendations on Cholesterol Screening and Treatment for Women:Primary Prevention of Coronary Artery Disease[*] ScreeningGroup Normal riskUSPS Task Total cholesterol level in womenForce(24) 45 to 65 years of ageACP(25) Total cholesterol level "appropriate but not mandatory" in women 45 to 65 years of age Unknown value in women 65 to 75 years of age Not recommended in women older than 75 yearsNCEP(6) Total and HDL cholesterol levels in all persons 20 years and older ScreeningGroup High risk[]USPS Task Total cholesterol levelForce(24) obtained earlier in women at high riskACP(25) Total cholesterol level obtained earlier in women at high risk Not recommended in women older than 75 yearsNCEP(6) Consider obtaining total and HDL cholesterol levels in children and adolescents. Treatment TreatmentGroup Normal risk High risk[]USPS Task Low-fat diet Consider drug therapy.Force(24) ExerciseACP(25) Drug therapy not No recommendation necessary in premenopausal womenNCEP(6) Drug therapy if LDL Drug therapy if LDL cholesterol cholesterol level level is higher than 160 mg per is higher than dL (4.15 mmol per L). The goal 190 mg per dL is an LDL cholesterol level below (4.90 mmol per L) 130 mg per dL (3.35 mmol per L).USPS = U.S. Preventive Services; ACP = American College of Physicians;NCEP = National Cholesterol Education Program; HDL = high-densitylipoprotein; LDL = low-density lipoprotein.[*]--These recommendations apply to women with no history ofmyocardial infarction, angina pectoris or known coronary artery disease(primary prevention). Women with a previous myocardial infarction orknown coronary artery disease should be treated aggressively to achievean LDL cholesterol level below 100 mg per dL (2.60 mmol per L) tolower their risk of a second cardiac event (secondary prevention).[]--Women should be considered at high risk if they have diabetes or othermacrovascular disease, a family history of premature coronary arterydisease or two of the following: a family history of coronary arterydisease, smoking, hypertension, older than 55 years, severehyperlipidemia or an HDL cholesterol level below 35 mg per dL(0.90 mmol per L).Information from references 6, 24 and 25.

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