By Mary Beattie, M.D.
National Centers for Exvellence in Women’s Health
University of California, sanFrancisco, Medical Center
Assistant Professor of Medicine, University of California, San Francisco, School of Medicine
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By Mary Beattie, M.D. |
Nearly 300,000 women in the U.S. die of coronary artery disease (CAD) each year, which is more than the number of women who die from all types of cancers combined. By the age of 60, 1 in 17 women in the U.S. has had a coronary event, compared with 1 in 5 men. After the age of 60, however, 1 in 4 women, as well as 1 in 4 men, die of CAD. Although the rates of mortality from CAD have been falling since the 1960s, the rate of decline has been slower among women than among men. Women with CAD experience more symptoms and are more likely to die as a result of their disease than men. A 50-year-old woman has about a 50% chance of developing CAD during her lifetime, and about a 30% chance of dying of CAD.
Fewer women than men have been enrolled in randomized trials investigating the treatment of CAD; however, this situation is improving.
Coronary atherosclerosis is a disease of older women, and thus age is truly the greatest predictor of the development of CAD in women. Advanced age confers an increased risk of CAD in both women and men.
Other risk factors for CAD in women include smoking, diabetes, hypertension, family history of CAD, obesity, elevated cholesterol, and decreased estrogen levels (e.g., after menopause).
Individuals who smoke 25 or more cigarettes per day have a risk of CAD that is five times greater than that of nonsmokers. Even smoking 1 -4 cigarettes per day doubles the risk of CAD. When women quit smoking, their risk of CAD starts to drop, and after 3-5 years, their risk approaches that of women who have never smoked. The effect of cigarette smoking is substantially greater among women who have other risk factors. Despite a general trend toward decreased smoking, the percentage of female teenagers who smoke has increased to approximately 25%. Smoking cessation reduces the risk of CAD more than any other change in CAD risk factors (see Table 1).
Individuals who smoke 25 or more cigarettes per day have a risk of CAD that is five times greater than that of nonsmokers. Even smoking 1 -4 cigarettes per day doubles the risk of CAD. When women quit smoking, their risk of CAD starts to drop, and after 3-5 years, their risk approaches that of women who have never smoked. The effect of cigarette smoking is substantially greater among women who have other risk factors. Despite a general trend toward decreased smoking, the percentage of female teenagers who smoke has increased to approximately 25%. Smoking cessation reduces the risk of CAD more than any other change in CAD risk factors (see Table 1).
| Table 1: Achievable Reduction in Risk for Various Interventions | |
|---|---|
| Smoking Cessation | 50-70% |
| Reduce serum cholesterol by 10 % | 25% |
| Decrease DBP 5 mm Hg | 12% |
| Low-dose aspirin | 33% |
| HRT | 44% |
After smoking, diabetes is the next greatest contributor to CAD mortality in women; this association is more prevalent in women than in men. Mortality rates for CAD are 3-5 times higher among women with diabetes than among nondiabetic women, as compared with rates that are 2-4 times higher among men with diabetes than among nondiabetic men. Smoking, hypertension, and obesity act in synergy with diabetes to increase the risk of CAD. Smoking cessation and the control of high blood pressure and obesity yield greater reductions in the risk of myocardial infarction (MI)—heart attack—in patients with diabetes than in nondiabetic individuals.
Hypertension is another known and prevalent risk factor for CAD in both women and men. In women, the more severe the hypertension, the greater the risk of CAD. However, hypertensive women have a better prognosis than men, perhaps due to the benefits to the heart women receive from estrogen. Among men and women with the same blood pressure, women have a significantly lower risk of stroke, CAD, congestive heart failure, and sudden death. Women with a history of MI or stroke in their mother or a sibling before age 60 have a greater risk of CAD and MI than men with a similar history in their father.
The Framingham Study showed obesity to be an independent risk factor for CAD, especially for women. Truncal obesity (a waist to hip ratio greater than 0.8) was more important than the overall degree of obesity.
The presence of estrogen has significant positive effects on the lipid profile, raising HDL (good) cholesterol and lowering LDL (bad) cholesterol. Among women in particular, there is a significant inverse correlation between HDL levels and CAD, meaning the higher their HDL levels, the lower their risk of CAD. This female advantage diminishes gradually after menopause. However, most of the research on cholesterol and CAD has involved middle-aged men, and it is difficult to extrapolate these findings to women.
The incidence of CAD in women increases dramatically after menopause, which has led to die speculation that menopause, marks the end of a protective effect from ovarian hormones.
Indeed, women who had an early and abrupt menopause as a result of bilateral ovary removal and who did not receive estrogen replacement therapy (ERT) had a risk of CAD 2.2 times higher than that of premenopausal women of the same age. The combined results of over 30 studies on postmenopausal ERT and CAD have estimated that women who use hormone (estrogen and progestin) replacement therapy (HRT) have a 44% lower risk of CAD than nonusers. About one third of this effect is related to the positive effects of estrogen on cholesterol.
Estrogen has many other positive effects on the cardiovascular system which are also being investigated. These include possible interactions with the endothelium and smooth muscle in blood vessels and a possible role as an antioxidant. Studies have shown that the women who benefit most from ERT or HRT are women who already have CAD. A recent study-using coronary angiograms demonstrated an increase in 10 years' survival from 60-97% in women with CAD who took HRT compared to women with CAD who did not take HRT. There is no evidence that the use of low dose oral contraceptives increases the risk of CAD among women under the age of 30 or among nonsmoking women who are 30 to 50 years old.
Women with CAD are more likely than men to experience angina (heart-related pain) as their first symptom. Angina in women is more likely to be associated with mental stress, sleep, and rest, as opposed to typical exertional angina. Fifty percent of men, compared with 34% of women, have a heart attack or MI as their first sign of CAD. Unfortunately, an initial MI is more likely to be fatal in women than in men (39% vs. 31%). There is also a higher proportion of silent MIs in women. Women who have an MI are less likely to show the classic electrocardiogram (EKG) criteria for MI (that is, to show a Q wave MI).
After an MI, women, especially black women, have a poorer prognosis. They are more likely to develop post MI angina or congestive heart failure, and they have a higher mortality rate than men. A recent study showed that 64% of women and 52% of black women, are alive four years after an MI, as compared to 79% of men. This may be due to other factors, such as differences in treatment, age, and diabetes. Men and women with diabetes have a poorer prognosis than nondiabetics. Compared with men, women with diabetes are twice as likely to die as a result of their MI. In one study of patients at the time of hospital discharge following an MI, 66% women with diabetes were alive compared with 87% of men with diabetes. After four years, these numbers dropped to 61% and 83% respectively.
Among diagnostic tools, the exercise treadmill test (ETT) has been used for decades to evaluate CAD in men and in some women, but only in recent years have studies been done to test its accuracy in women. The ETT has a high false positive rate in women (22-37% of positive results are falsely positive). The false negative rate is also high (estimated at 20-50%). When the resting EKG is abnormal and the history suggests angina, imaging with thallium or a newer radioisotope such as sestamibi can be done after exercise or stress testing to improve its accuracy.
Exercise or stress echocardiography is another noninvasive technique that can detect abnormalities in heart function in cases of myocardial ischemia. It has been reported to have a good predictive accuracy in single-vessel CAD, a common finding in women. This technique, however, requires an experienced echocardiographer, and there are concerns about its accuracy outside of university centers.
Invasive diagnostic testing with cardiac catheterization is done less frequently in women. Black women in particular—even those with histories similar to those of their white or male counterparts—are less likely to be referred for cardiac catheterization. Data from large registries suggest that women undergoing angiography have more total complications, arrhythmias, and hemorrhage. However, there is no difference in the incidence of death, MI, stroke, vascular complications, or contrast reactions between men and women.
Medical management of CAD in women is similar to that in men, with the notable exception ofHRT, which has been shown to significantly improve survival in women with CAD. HRT also has preventive effects for women with risk factors for CAD. HRT should be considered in all postmenopausal women who have CAD or who have significant risk factors for CAD. There is some evidence that nitrates are not as effective in reducing the frequency or intensity of anginal symptoms in women with chronic stable angina as they are in men. Women tend to have more symptoms of depression and fatigue with the routine use of beta blockers. Aspirin and beta blockers have comparable benefits in women and men for the prevention of reinfarction after MI. Aspirin probably also has preventive effects in women at risk for CAD, as it does for men. Treating an acute MI with thrombolytic therapy has been shown to be beneficial for women in terms of survival. Unfortunately, the benefit is not as great as it is for men, and serious bleeding complications are more frequent in women.
Percutaneous transluminal coronary angioplasty (PTCA) is a procedure that opens coronary vessels that have narrowed as a result of CAD. Women initially have less symptomatic and angiographic success and higher in-hospital death rates than men. This may be related to older age and the presence of more concurrent diseases or medical conditions. However, the long-term outcome for women is actually better, and restenosis (or renarrowing of the vessels) is less likely in women. Women have a significantly higher rate of angiographic and clinical complications with coronary atherectomy and following the insertion of devices such as stents. This may be due in part to the smaller coronary vessel size in older women.
Women who undergo coronary artery bypass grafting surgery (CABG) have roughly twice the postop death rate as men, but similar 5- and 10-year survival rates. There appear to be several reasons for this situation. Women are more likely to undergo emergency surgery, have more advanced disease, and are at a later, more symptomatic stage of disease when they undergo a CABG procedure. Smaller blood vessels in women may reduce the opportunity to obtain complete revascularization. Women referred for CABG are more likely to have diabetes, hypertension, and congestive heart failure and are less likely to have had an MI. Women are more likely to suffer from depression after MI and are less likely to be referred to cardiac rehabilitation programs that men.
Risk factor modification is very important in the management of CAD in women. As mentioned above, smoking cessation can lower the risk of CAD, as well as lower the risk of a second MI more than any other risk factor modification. Weight reduction and probably glycemic control in women with diabetes are important for lowering the risk of CAD. Controlling hypertension and hyperlipidemia, and following a low-fat diet and a regular exercise program should be encouraged.
Coronary artery disease is the leading cause of death in US women. It is a rare event in premenopausal women, but 15 to 20 years after menopause the incidence is equal among women and men. Risk factors for CAD in women include advanced age, smoking, diabetes, hypertension, family history, obesity, elevated cholesterol, and being postmenopausal without hormone replacement therapy. Unfortunately, the diagnosis can be difficult, because women often present with nonclassic angina, and diagnostic tests aren't as sensitive or specific in women. Medical treatment of CAD in women is similar to that in men, with the exception of HRT. Forms of interventional treatment such as angioplasty and surgery have higher postop complications in women than in men, but these treatments can be equally effective in the long run. Finally, risk factor modification should be attempted at all stages of treatment.