Cardiovascular disease is the leading cause of death in women in this country, claiming the lives of over half a million women each year. Women present with coronary heart disease (CHD) events on average 10 years later than men, but have a steady rise in the incidence of myocardial infarction (MI) or “heart attacks” as they reach and go through menopause. In fact, cardiovascular disease death rates for women have outstripped rates for men every year since 1984, with continued widening of the gap each year. some of the reasons for this increase are tobacco addiction, untreated hypertension (high blood pressure), obesity, high dietary fat intake, and lack of regular exercise. Furthermore, new evidence suggests that in addition to continued differences in the way men and women are treated after an MI, differences exist in the basic structure of the arterial walls and “clot formation” when compared to men. These differences may be especially grave in younger women; mortality rates after acute MI are twice as high in women less than 50 when compared to men in the same age group. Women greater than 75 years show mortality rates equal to their male counterparts.
Cholesterol-rich particles are deposited inside arterial walls. The arteries become occluded due to the progressive buildup of plaque (cholesterol and blood particles such as platelets) inside artery walls. This plaque can then rupture and erode, compromising blood flow to the heart muscle and resulting in acute MI. Plaque erosion has been more commonly found in women younger than 50 years, and is highly associated with cigarette smoking. In contrast, plaque rupture has been found to be more common in older women, and is associated with significantly higher total cholesterol levels than in patients dying with plaque erosion. Along with plaque rupture and erosion, vascular spasm is more common in women than in men, and can result in heart attacks and chest pain.
Risk factors for coronary heart disease
The significant risk factors for coronary heart disease include tobacco smoking, hypertension, diabetes mellitus, high LDL (“bad cholesterol”), low HDL (“good cholesterol”), and also family history of premature coronary heart disease (<55 years of age). Female patients are more likely than men to have a history of hypertension, diabetes, angina, and congestive heart failure.
Tobacco smoking remains the most common reversible cause of coronary heart disease. There is evidence for a relative estrogen deficiency in female smokers, as documented by earlier onset of menopause, higher rates of osteoporosis, and lower endometrial cancer risk. The majority of infarcts, which occur in middle-aged women, can be attributed to tobacco use.
Female diabetics have a threeto sevenfold increase in heart disease risk, compared with a twoto threefold elevation in risk in men with diabetes. The deadly interplay between diabetes and other risk factors in women is particularly important; diabetics have more unfavorable lipid profiles, with higher LDL, triglycerides, and lower HDL levels. Diabetics are more likely to be hypertensive and obese than nondiabetic women. One possible explanation for this excess risk is that diabetes may impair estrogen binding in the vasculature. The presence of diabetes as a risk factor greatly magnifies the adverse effects of other factors such as cigarette smoking, elevated cholesterol levels, and hypertension.
Common symptoms suggesting acute MI are chest pain, along with shortness of breath, nausea, and diaphoresis. several factors make accurate recognition of MI more difficult in women than in men. While the majority of women presenting with acute MI do complain of chest pain, other more nonspecific complaints such as upper abdominal pain, dyspnea, fatigue, and nausea occur more frequently in female than in male patients. significantly fewer women present to emergency rooms in less than 2 hours—the golden time period for reperfusion therapy—underscoring the need for education of both patients and providers.
There are also conflicting data with respect to treatment strategies for women diagnosed with acute MI.
While some authors have suggested that the gender gap for mortality is due to underutilization of proven strategies such as acute coronary intervention, more recent data have shown no difference in rates of cardiac catheterization and intervention after diagnosis.
Proven treatment strategies during acute MI for women are similar to those for men.
Aspirin has been shown to be of benefit in females. Other agents shown to be of benefit in a female as well as male population include beta-blockers, cholesterollowering medication, clopidogrel (potent clot inhibitor at the level of the platelet), and angiotensin converting enzyme (ACE) inhibitors. Acute treatment of MI includes thrombolytic agents (these agents dissolve the clot) as well as primary angioplasty (trying to open the diseased artery immediately in the cardiac catheterization laboratory). Both strategies have shown benefit in women and men.
However, procedural complications and mortality rates are significantly higher in women, according to data from 1985 to 1986 National Heart, Lung and Blood Institute Coronary Angioplasty Registry. Complications occurred at a rate of 29% in women versus 20% in men, while procedural mortality was 2.6% for women and 0.3% for men. Some authors have related the gender difference in outcomes after both angioplasty and coronary artery bypass surgery to smaller vessel size in women, greater age of female patients, greater number of comorbid conditions, and generally poorer functional status.
Mortality for women may be higher after thrombolytic therapy due to intracranial bleeding, a relatively more frequent event in female patients. Women continue to show higher death rates, higher transfusion rates, and higher rates of vascular complications after percutaneous intervention. Furthermore, women were less frequently given intravenous blood thinning agents such as GP IIb/IIIa inhibitors as adjunctive therapy during interventional procedures, despite data showing benefit for their use. Furthermore, women less frequently received stents than their male counterparts.
Lifestyle change, regular exercise, weight loss, and quitting cigarette smoking are very important in preventing heart attacks. An aspirin a day has been proven to be of benefit in patients with risk factors for coronary artery disease and in those with coronary artery disease.
Hormone replacement therapy (HRT)
Finally, no benefit for primary or secondary prevention has been demonstrated for HRT in postmenopausal women. In fact, recently published randomized, placebo-controlled trials including the Heart and Estrogen/Progestin Replacement Study (HERS) and Women’s Health Initiative (WHI) found either no benefit or slight increase in risk of CHD events for women taking HRT versus those on placebo.
In women with known heart disease, taking hormones after menopause does not protect against heart attack or stroke, and increases the risk of dangerous blood clots and gallbladder disease. Furthermore, longterm HRT also does not appear to prevent cardiovascular events in healthy women. Basic research suggests that younger, nondiseased vascular tissue may be more likely to respond to the effects of HRT, and future clinical studies may address this. HRT is very effective in the amelioration of menopausal symptoms such as hot flashes and vaginal dryness; current knowledge favors short-term, targeted use of HRT only for women with troubling menopausal symptoms who do not have contraindications to their use.
Pregnancy and Coronary heart disease
While cholesterol plaque accounts for the vast majority of heart attacks in women, there are a few rare etiologies that may cause CHD in pregnant women. Acute MI during pregnancy occurs at a rate of 1 in 10,000 pregnancies, with slightly less than half the cases being caused by cholesterol plaque. Spontaneous coronary thrombosis (clot formation) without underlying plaque does occur. Possible mechanisms include the presence of a relative hypercoagulable (tendency to clot easily) state during pregnancy, with decreased availability of factors which dissolve blood clots. Increased vascular reactivity during pregnancy may also be a factor, with a greater propensity toward vascular spasm and constriction. Use of oxytocin (Pitocin), which is used to induce labor, may play a role as well. Spontaneous coronary dissection occurred in 16% of the cases described. This ominous complication of pregnancy is thought to occur because of hormonally mediated biochemical and vascular changes occurring in arterial walls during pregnancy. These same factors may also play a role in rare cases of acute MI that have occurred in young women taking oral contraceptives.
Rare causes of MI in young women, such as pregnancy or oral contraceptive, must not be ignored. Diagnosis of MI in a female requires heightened suspicion because of the often nonspecific nature of the presenting complaint. Clinicians should strive toward aggressive, early treatment of MI in women just as in men, with accepted strategies including thrombolytic therapy and primary angioplasty or stent implantation. Primary percutaneous revascularization may be especially efficacious as an initial treatment strategy in females because of the increased risk of hemorrhagic stroke associated with thrombolytic therapy in women. Secondary prevention after MI should include proven medical therapy such as aspirin, beta-blockers, ACE inhibitors, and lipid-lowering therapy with statins; HRT no longer has a meaningful role to play.