WOMENS HEARTS ARE DIFFERENT

Cardiovascular disease accounts for nearly 500,000 deaths in American women each year, half of which may be attributed to coronary heart dis ease (CHD). However, most women and many primary care physicians are n ot aware that cardiovascular disease is the leading cause of death of women in the United States. This misperception may have contributed to the relative exclusion of women from early cardiovascular clinical tr ials; however, the results of these trials have been routinely general ized to women. It is unclear whether cardiovascular diagnostic and the rapeutic strategies studied in men may be applied to women, because ge nder discrepancies may exist in the pathophysiology of cardiovascular symptoms, accuracy of diagnostic testing, efficacies of therapies, and outcomes after cardiac events. Atherosclerosis, the underlying pathop hysiologic abnormality in patients with CHD, may, cause ''typical'' an gina by limiting coronary blood flow during periods of increased myoca rdial oxygen demand (e.g., exertion or emotional stress). The presenta tion of CHD differs between men and women. The predominant initial man ifestation of CHD in women is angina, which occurs in 47% of women wit h CHD compared with only 32% of men. The predominant presentation of m en with CHD is myocardial infarction (MI), which occurs in 46% of men compared with 32% of women. Although angina is the predominant initial manifestation of CEH) in women, 58% of women versus 88% of men with ' 'typical'' exertional angina have angiographically defined coronary at herosclerosis. ''Atypical'' angina is associated with CHD in only 35% of women versus 67% of men. Therefore the pathophysiology of chest pai n is gender-dependent. Indeed, women are more likely to have chest pai n caused by abnormal coronary vasomotor tone causing large vessel spas m or inadequate vasodilatation of the coronary microvasculature. Chest pain resulting from coronary atherosclerosis is associated with an in creased frequency of adverse cardiac events. Although premenopausal wo men have a low incidence of CHD, postmenopausal women are at increased risk, suggesting that aggressive atherosclerotic risk factor analysis and treatment is warranted. In addition to gender and menopausal stat us, traditional atherosclerotic risk factors include hypertension, dia betes, dyslipidemia, cigarette use, and a family history of premature CHD. However, many of these are not independent risk factors because o f their associations with gender. The magnitude of the effects of thes e risk factors also differs between men and women. Because both pathop hysiologic mechanisms of chest pain and prevalences of significant CHD are gender-related, it is to be expected that the sensitivities and s pecificities of cardiovascular tests differ by gender. Indeed, women h ave higher false-positive rates and lower sensitivities of the treadmi ll exercise electrocardiographic stress test. Similar findings have be en reported for Thallium-201 exercise stress tests, The low specificit y of noninvasive evaluations of chest pain in women may contribute to a bias in the clinical evaluation of women. Several studies have demon strated that women with chest pain or cardiovascular syndromes receive diagnoses and are treated less aggressively than their male counterpa rts, as manifested by a lower likelihood of referral for diagnostic co ronary angiography and percutaneous and surgical coronary revasculariz ation. The underuse of invasive diagnostic and therapeutic cardiovascu lar procedures in women may be related to gender discrepancies in card iac outcomes. For instance, women who have a myocardial infarction are more likely than men to die in-hospital or within 1 year and to have post-myocardial infarction congestive heart failure and stroke. After being referred for coronary angioplasty or bypass surgery, women fare worse as manifested by increased in-hospital mortality and less relief from angina. These gender discrepancies are at least in part related to older age, increased prevalences of comorbid diseases, and smaller caliber coronary arteries in women. Women may reduce their CHD risk by using postmenopausal hormone replacement therapy. Meta-analyses of cl inical studies suggest that postmenopausal hormone replacement is asso ciated with a 35% to 50% decrease in cardiovascular risk. Favorable al teration of the lipid profile accounts for less than half of estrogen' s clinical; cardioprotective effect. Other proposed mechanisms include direct inhibition of arterial intimal hyperplasia, inhibition of low- density lipoprotein oxidation, and prevention of abnormal coronary vas oconstriction. The latter mechanism suggests that estrogen therapy may be effective in decreasing Symptoms of chest pain in postmenopausal w omen with coronary vasospasm or microvascular angina. In summary, wome n continue to be treated by strategies based on clinical trials that p redominantly focused on men despite the identification of gender discr epancies in the presentation of CHD, mechanism of chest pain, risk fac tor profiles, diagnosis and treatment of CHD, and outcomes after cardi ac events and invasive therapies. Practitioners should alter their pra ctice patterns to incorporate both the implications of these gender di screpancies and the results of ongoing clinical trials that are studyi ng gender-specific cardiovascular diagnostic and therapeutic strategie s.