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Cardiovascular Research 2002 53(3):558-567; doi:10.1016/S0008-6363(01)00511-9
© 2002 by European Society of Cardiology
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Copyright © 2002, European Society of Cardiology

Clinical characteristics of coronary heart disease in women: emphasis on gender differences

Nanette K Wenger*

Emory University School of Medicine, Division of Cardiology, Grady Memorial Hospital, 69 Butler Street, S.E., Atlanta, GA 30303, USA

* Tel.: +1-404-616-4420; fax: +1-404-616-3093

Received 31 May 2001; accepted 15 October 2001

KEYWORDS Coronary disease; Gender


   1. Epidemiology
Top
 1. Epidemiology
2. Diagnostic evaluation of...
 3. Angina pectoris
 4. Sudden coronary death
 5. Acute coronary syndromes
 6. Myocardial infarction
 7. Myocardial revascularization:...
 8. Summary
 9. Coronary heart disease...
 References
 
Coronary heart disease (CHD) is the leading cause of mortality for adult women in most industrialized nations [1,2]. Internationally there is substantial variation in the rates of age-standardized CHD incidence and mortality; countries with high rates of CHD among men also have high rates for women [3]. That environmental/lifestyle factors may exert major importance compared with gender is highlighted by the fact that women in countries with high prevalence of CHD have greater CHD rates than men in countries with low CHD prevalence. Changes in age-standardized CHD mortality rates for men and women between 1981 and 1983 and 1991–1993 show prominent declines in Western European countries, the United Kingdom and the US for both genders, in contrast to increases in mortality rates for both women and men in Eastern European countries, highlighting the potential impact of environmental/lifestyle changes [3]. Within this favorable trend, the percentage decline in mortality rates in the US, the UK and Sweden has been far greater for men than women [4,5].

Although rates of CHD mortality increase prominently with age both for women and men, there is a consistent substantially greater CHD mortality for men at all ages, with the difference most marked at younger ages. The greater age-dependency of CHD for women than men has been known since the early reports of the Framingham Heart Study; any initial manifestation of CHD was delayed about 10 years in women compared with their male counterparts, with initial myocardial infarction (MI) occurring as much as 20 years later [6,7]. Convincing explanations for the CHD gender–age disparities remain elusive. There is not an abrupt increase in CHD rates for women at the time of menopause. By contrast coronary risk factor prevalence in women both in the US and the UK shows lower rates of hypertension, hypercholesterolemia, and diabetes in younger women compared with younger men, and a reversal of this pattern at older age [2,8].

In the United States whereas one in five men has had a coronary event by 60 years of age, this has occurred in only one of 17 US women. Nonetheless, with aging of the US population and a greater representation of women at elderly age, more women than men have died from CHD annually since 1984, with the gender gap in mortality rates continuing to widen. However CHD is not solely a disease of elderly women. Twenty thousand US women younger than 65 years of age die annually from MI, with a third of these women younger than 55 years of age. The adverse prognosis of CHD among younger women is addressed subsequently. Within the population of women in the United States, African American women have higher mortality rates from both CHD and stroke than white women. The age-adjusted CHD death rate is 25–50% higher for African American than white women in the US, with the death rate from MI for African American women double that for white women.

CHD is a major cause of disability for women as well; among US women aged 55–64 years with clinical manifestations of CHD, 36% are disabled by CHD symptoms, with disability rates increasing to 55% for women over 75 years of age [9].

Gender differences in coronary risk factors are not examined in detail in this review. For women in the US alarming trends in coronary risk factors show that smoking rates have decreased less for women than men; the prevalence of obesity is increasing; about 25% of US women report no regular physical activity; 52% of women older than 45 years of age have hypertension; and 40% of women older than age 55 have elevated cholesterol levels. Despite these observations, a 1998 Centers for Disease Control (CDC) National Ambulatory Medical Care Survey showed that, in office practice, 18% of women as compared with 23% of men were counseled about exercise, 21% of women versus 26% of men were counseled about nutrition, and 10% of women versus 12% of men were counseled about weight reduction [10]. Diabetes mellitus, a far more powerful coronary risk factor for women than men, is associated with a less favorable outcome of clinical coronary events for women [11–13]. The coronary prognosis is substantially worse for diabetic women than diabetic men compared with their nondiabetic counterparts. Diabetic women with MI have a doubled risk of reinfarction and fourfold greater likelihood of developing heart failure. Among patients who undergo myocardial revascularization procedures, both catheter-based revascularization and coronary artery bypass graft surgery, more women than men are diabetic; diabetes likely contributes to the less favorable outcome of women from such procedures.

This review addresses the evidence for gender differences in the clinical manifestations of CHD: angina pectoris, sudden death, acute coronary syndromes, MI and myocardial revascularization procedures. Because of the under-representation of both women and elderly individuals in randomized clinical trials in the published literature [14], data bases, registries and case series provide much of the information. This under-representation is comparable in US and non-US randomized clinical trials.


   2. Diagnostic evaluation of chest pain in women
Top
 1. Epidemiology
 2. Diagnostic evaluation of...
3. Angina pectoris
 4. Sudden coronary death
 5. Acute coronary syndromes
 6. Myocardial infarction
 7. Myocardial revascularization:...
 8. Summary
 9. Coronary heart disease...
 References
 
Because women at all ages are less likely to have obstructive coronary artery disease and in particular triple vessel and left main coronary artery disease than their male counterparts, pretest probability of CHD is lower in women with chest pain presenting for a diagnostic evaluation. The lower prevalence of severe obstructive CHD gives the exercise ECG a slightly lower sensitivity for women than for men, which is compounded by the inability of many women to exercise to adequate intensity. Nonetheless, a true negative exercise ECG has high predictive accuracy for the absence of clinically significant CHD [15]. The lower prevalence of CHD in women leads to more false-positive exercise ECGs.

Myocardial perfusion imaging improves the diagnostic accuracy of exercise testing, with particular benefit of technetium 99m sestamibi SPECT imaging [16,17]. Stress echocardiography in women for whom an adequate echocardiographic image can be obtained shows comparable sensitivity and specificity to studies in men and is a valuable test [18,19]. The most cost-effective diagnostic strategy is a sequential approach to testing [20].


   3. Angina pectoris
Top
 1. Epidemiology
 2. Diagnostic evaluation of...
 3. Angina pectoris
4. Sudden coronary death
 5. Acute coronary syndromes
 6. Myocardial infarction
 7. Myocardial revascularization:...
 8. Summary
 9. Coronary heart disease...
 References
 
Angina pectoris is the predominant initial and subsequent presentation of CHD in women, in contrast to MI and sudden coronary death as the most frequent presentations for men [7]. Appropriate risk stratification of women with chest pain syndromes thus has the potential to identify the high-risk subset of women and to intervene prevent MI and sudden cardiac death. Data from the Coronary Artery Surgery Study (CASS) [21–23] Registry define that many women with chest pain clinically indistinguishable from angina pectoris have no significant atherosclerotic obstruction of their coronary arteries, 50% of women as contrasted with 17% of men. This highlights that the clinical history alone is inadequate to diagnose CHD and coronary risk in women and that objective confirmatory testing is required. However, in patients older than 65 years of age, there is a gender-neutral risk for coronary death associated with classical exertional chest pain relieved by rest; the relative risk is 2.7 for women and 2.4 for men and the association is independent of other coronary risk factors [24]. Exertional angina in the Established Populations for Epidemiologic Studies of the Elderly (EPESE) was also equally predictive of coronary death for both genders, emphasizing the importance of risk stratification for elderly women with exertional angina.

In the TIDES investigation, women who presented with angina, compared with their male counterparts, tended to be older and to more frequently have associated hypertension, diabetes, and heart failure; by contrast, they were less likely to have had either prior MI or a myocardial revascularization procedure [25].

Retrospective examination of the clinical characteristics of women and men prior to the index MI that determined their eligibility for the Survival and Ventricular Enlargement (SAVE) trial reveals gender disparities [26]. Although histories of angina pectoris were similar and 50% of women versus 31% of men reported physical activity limitation from anginal symptoms, men were twice as likely as women to be referred for coronary arteriography and coronary artery bypass graft surgery.

Although in prior years, predominantly based on US data, abnormal noninvasive test results in women were less likely to result in referral for coronary angiography, this pattern has substantially changed [27]. There is currently comparable referral to coronary angiography after abnormal results of exercise thallium testing [28]. Once coronary angiography has been undertaken, there is currently comparable referral to myocardial revascularization for both genders in the US and the UK [29,30], based on coronary anatomy.


   4. Sudden coronary death
Top
 1. Epidemiology
 2. Diagnostic evaluation of...
 3. Angina pectoris
 4. Sudden coronary death
5. Acute coronary syndromes
 6. Myocardial infarction
 7. Myocardial revascularization:...
 8. Summary
 9. Coronary heart disease...
 References
 
Recent information about sudden coronary death in women represents preliminary data likely to be expanded over time, because the pathoanatomic mechanisms of sudden coronary death appear to differ in older and younger women [31]. Younger women who die suddenly of coronary thrombosis are very often cigarette smokers, with smoking constituting the major coronary risk factor for younger women. They tend to have plaque erosion; they have relatively little coronary arterial narrowing and less plaque calcium at autopsy, which may constitute a potential limitation of calcium-based screening tests for CHD in younger women. Older women who die suddenly of coronary thrombosis are typically hypercholesterolemic, have plaque rupture in contrast to plaque erosion, and have severe coronary arterial narrowing and far more plaque calcium. Given this initial delineation, there is need to learn more about detailed mechanisms that underlie sudden coronary death in women across the life span, in addition to the prominent differences cited above.


   5. Acute coronary syndromes
Top
 1. Epidemiology
 2. Diagnostic evaluation of...
 3. Angina pectoris
 4. Sudden coronary death
 5. Acute coronary syndromes
6. Myocardial infarction
 7. Myocardial revascularization:...
 8. Summary
 9. Coronary heart disease...
 References
 
Since acute coronary syndrome is a term popularized in the 1990s, gender differences in acute coronary syndromes were not previously characterized. In an initial report from the TIMI IIIB study [32] poorer outcomes in women were associated with older age and higher rates of associated comorbidities.

A number of gender differences were elucidated in the GUSTO IIb cohort, comprised of 3662 women and 8480 men [33]. Women were more likely to have unstable angina than enzyme- or ECG-documented acute MI; among those with MI, fewer women than men had ECG-ST elevation MI, the subset appropriate for coronary thrombolysis. In this cohort, women were older than men; and were more likely to have diabetes, hypertension, and prior heart failure; and less likely to have had prior MI. During the hospitalization for MI women had an excess of complications and a higher 30-day mortality rate, but similar rates of reinfarction. Although women had an increase in overall mortality compared with men, the outcomes were similar after adjustment for age and baseline characteristics, except that women with unstable angina did better than men. This should not be construed as indicating more favorable outcomes for women. The GUSTO IIb data demonstrate that although women with acute coronary syndromes have increased mortality compared with men, the reason for the increased mortality appears age-dependent and baseline characteristic-dependent rather than gender-dependent. The authors also raise consideration of pathophysiologic and anatomic differences.

Among women with acute coronary syndromes, outcomes differ in subgroups of women. The women with ECG-ST elevation acute MI fared marginally worse than age-adjusted men. Because women with unstable angina did better than men this potentially affords the ability to intervene in this subset before MI occurs. MI without ECG-ST elevation, the subset not appropriate for coronary thrombolysis, had gender parity in outcomes. Among the total GUSTO IIb group, coronary angiography was undertaken in fewer women than men, 53% versus 59%. Although this gender disparity was less prominent than in prior years, at coronary angiography more women than men were described to have clinically insignificant obstructive disease. Clinically insignificant, in this report, meant not appropriate for intervention; the disease, however, was significant in that it occasioned a hospitalization for an acute coronary syndrome. For women with the totality of acute coronary syndromes, there was a delay in presentation to hospital after symptom onset compared with men.


   6. Myocardial infarction
Top
 1. Epidemiology
 2. Diagnostic evaluation of...
 3. Angina pectoris
 4. Sudden coronary death
 5. Acute coronary syndromes
 6. Myocardial infarction
7. Myocardial revascularization:...
 8. Summary
 9. Coronary heart disease...
 References
 
The predominant symptomatic presentation of MI in both genders is chest pain, but women are more likely to have atypical symptoms, particularly abdominal, neck and shoulder pain; and there is a greater frequency of painless dyspnea and extreme fatigue in older women and in diabetic women. However, in the Myocardial Infarction Triage and Intervention Registry, the clinical presentation of MI was indistinguishable by gender, with comparable numbers of women and men with typical and atypical pain presentations [34]. The delay in seeking care predominates in women.

Because antecedent angina is more common among women with an initial MI, the challenge remains whether earlier diagnostic testing of women during the stable phase of angina pectoris and intervention for the high-risk subset may avert MI. In the Worcester Heart Study [35] more women than men had a history of angina pectoris prior to the initial MI. As well, existing angina in patients hospitalized for MI in the Israel SPRINT Study [36] was associated with an increased risk of both hospital and post-hospital mortality.

Most published studies describe a greater severity of MI in women. At presentation to hospital women with MI are more likely to have a higher Killip class, tachycardia, atrioventricular block, and pulmonary rales. Complications including shock, heart failure, recurrent chest pain, cardiac rupture and stroke are more common in women; although these gender differences lessen with correction for comorbidity and older age, they do not disappear [37–40]. In the US MILIS study [41], women had an excess of post-hospital deaths as well as more frequent angina and heart failure among survivors, with a particularly adverse prognosis for African American women. Although more men than women died prior to hospitalization in the Scottish MONICA study, women had higher mortality rates after hospital admission.

Although application of coronary thrombolysis significantly decreased the early mortality rate for acute MI, it did not abolish the gender differences. In the GUSTO-I trial [42] comparable survival benefit was evident for women and men who received coronary thrombolysis (despite an excess of bleeding complications, particularly intracranial hemorrhage, in women). It remains uncertain whether this is thrombolytic therapy bleeding or heparin-related bleeding or both. Most data antedate the weight-based heparin protocols and many of the weight-based thrombolytic therapy protocols. In the absence of weight-based therapies, women likely receive higher drug dosages than men. The unadjusted 30-day mortality rates for women were more than twice those for men, 13% versus 4.8%. Women in GUSTO-I also had a greater risk of nonfatal complications of MI including shock, heart failure, and reinfarction [43,44]. The median time from onset of chest pain both to admission and to thrombolysis was longer for women than for men [43]. In addition to their lesser eligibility for coronary thrombolysis due to late arrival at hospital, women may not undergo appropriate rapid triage owing to less severe chest pain or atypical pain presentations. Whether these mortality differences reflect the contribution of gender per se or of the comorbidities that characterize women: older age and greater prevalence of hypertension, diabetes, and hypercholesterolemia, remains to be ascertained. The gender difference in 30-day mortality in GUSTO-I remains unexplained, in that there was comparable patency of the infarct-related artery and comparable response of the ventricular myocardium to ischemia and reperfusion for women and men. Women with acute MI in the Thrombolysis and Myocardial Ischemia II (TIMI-II) trial treated with thrombolysis also had higher rates of 6-week morbidity and mortality than their male counterparts [45]. In the GISSI trial [46], although coronary thrombolysis decreased the overall mortality rates, the gender differences were not altered, with 1-year mortality rates for women being double those for men, 29.8% versus 15.2%.

Registry data from the US and surveillance data from other countries provide important information on the contemporary mortality from acute MI for women. The Myocardial Infarction Triage and Intervention (MITI) Registry represents outcomes of contemporary therapy with coronary thrombolysis but antedates the use of glycoprotein IIb/IIIa antiplatelet agents and the routine application of acute coronary angioplasty [34,47]. Hospital mortality was greater for women than men, 16% versus 11%; there was an excess first year mortality for women and, among survivors, a greater and earlier recurrence of myocardial infarction than for men. Although in this Registry the symptomatic presentation for MI, time at arrival to hospital, and hemodynamic and electrocardiographic findings were comparable for both genders, women were not as aggressively treated; they were 50% less likely to undergo acute interventions including coronary thrombolysis, coronary angiography, coronary angioplasty or coronary artery bypass graft surgery. There was also less use of beta blocking drugs and of aspirin [47]. Therefore it remains uncertain whether the greater 1 year mortality following MI, as well as the earlier and more frequent reinfarction among survivors, reflected gender differences or differences in therapy. With analysis controlling for older age and comorbidity, the gender differences lessened but did not disappear.

Women, and particularly older women, with MI in the Cooperative Cardiovascular Project were less likely to undergo coronary angiography and had somewhat less aggressive treatment but had comparable 30-day mortality rates to men [48]. A recent national survey in the UK [49] found no important gender differences in the hospital management of acute ischemic syndromes in patients under 70 years.

Additional recent information (1990–1994) is available from the United States National Registry of Myocardial Infarction (NRMI), encompassing data from 354435 patients in 1234 United States hospitals [50]. This Registry identified that one-third of all MIs occur in women; that women are older than men at presentation, 70 versus 63 years; that women have more time from symptom onset to presentation to hospital; and have greater mortality with acute MI than men, even when matched for age and both with and without coronary thrombolysis, 9.3% compared with 4.5% and 16% compared with 10.9%, respectively. Women in NRMI were less likely to receive coronary thrombolysis than men, but more likely to have major bleeding when they did. Stroke, major bleeding and recurrent infarction predominated in women. In the Emergency Department, women were not only less likely to receive coronary thrombolysis but also heparin, beta blockers, and aspirin; likely they were not recognized initially as having acute MI. Women were less likely to undergo coronary angiography, coronary angioplasty and coronary artery bypass graft surgery. Women were more likely to die of cardiac rupture than men, but less likely than men to die of a cardiac arrhythmia.

Additional information, from NRMI 2 examining gender differences in short-term MI mortality addresses age differentials in the 155565 women and 229313 men aged 30–89 years enrolled between 1994 and 1998. Younger women, defined as below 70 years of age, had higher death rates during hospitalization than their male counterparts [51]. The younger the age, the higher the risk of mortality for women versus men. Only at older age was there gender parity, and, in the very oldest age group, women had better outcomes. Only women under age 50 in the National Acute Myocardial Infarction Register in Sweden had a worse prognosis than men, with much of the excess mortality associated with diabetes [52]. The Worcester Heart Study [53] examined 6826 patients who survived the hospitalization for acute MI between 1975 and 1995. Younger (<60 years) women had higher two year mortality rates than men of similar age. Although in both genders mortality rates increased with increasing age; in the below 60-year age group, there was an excess mortality for women; there was gender comparability at ages 60–69; and greater mortality for men at ages over 70 years. By contrast, the higher 28 day mortality rate of women than men with an initial Q wave MI in Spain [54] was attributed to the large number of 65–74 year old patients in whom the risk was greater for women than men; women younger than 65 years did not have special risk.

The RESCATE investigators in Catalonia, Spain examined consecutive patients younger than age 80 hospitalized for an initial MI between 1992 and 1994 [55]. The RESCATE women compared with men were older; had more diabetes, hypertension, and prior angina pectoris; and twice as frequent pulmonary edema and cardiogenic shock, 24.8% versus 10.5% for men. Women not only had greater delay in arriving at the Emergency Room, but greater delay in transfer to the Coronary Care Unit. Women received less coronary thrombolysis than men (23.9 versus 41.3%). Even though the numbers of revascularization procedures were comparable by 6 months, men received revascularization earlier. The women had an increased mortality risk at 28 days and at 6 months, but had almost double the readmission rate for men (23.3 versus 12.2%) within the initial 6 months following MI. During these readmissions women received revascularization procedures that allowed them to assume parity revascularization with their male counterparts by 6 months. The RESCATE investigators attributed the more adverse outcomes in women to an increased severity of MI; these outcomes were independent of age, comorbidity, and use of thrombolytic therapy.

A sizeable number randomized controlled clinical trials of therapies for MI, including antiplatelet drugs, beta blocking drugs, calcium channel blocking drugs, fibrinolytic drugs, and ACE inhibitors have provided summary data that confirm a comparable reduction in mortality rates for treated as compared with control male and female patients. Because the rates of risk reduction are similar in the men and women so treated, there is no empiric evidence supporting different pharmacologic treatments based on gender. The less frequent use of standard therapies documented to improve survival in women with suspected acute MI, offers the potential for improved clinical outcomes [56]. The paucity of information regarding efficacy and safety of many therapeutic interventions for women and elderly persons with MI [14] was considered by the authors to influence undertreatment of these populations, even with evidence-based beneficial drugs.

In the Primary Coronary Angioplasty for Acute Myocardial Infarction (PAMI) trial, primary percutaneous transluminal coronary angioplasty (PTCA) was compared with coronary thrombolysis for ST-elevation acute MI. Coronary thrombolysis was more likely to be associated with early mortality and life-threatening hemorrhagic complications for women than men. Primary PTCA was associated with a lesser risk of intracranial bleeding and improved survival for women, with evidence of gender parity, i.e., an in-hospital prognosis of women and men equally favorable following primary PTCA [57].

More recent data on primary PTCA [58] for acute MI show that gender is not an independent predictor of 30-day and 7-month survival after control for baseline characteristics, but absolute survival data are less favorable for women. Acute procedural success rates were similar, 92 versus 97%, but women had greater mortality at 30 days and at 7 months, 10 versus 0.9%, and 15 versus 4.4%, respectively, than their male counterparts. Outcome differences are likely due to baseline characteristics rather than gender per se, in that women were older, had more cardiogenic shock and had smaller reference vessel diameters.

A case series from Italy [59] described similar benefit of primary PTCA for both genders, with decreased restenosis with stenting.

Coronary angiography and myocardial revascularization data after documented acute MI [60] contrast with the results in acute coronary syndromes [33]. Although women were older and had more diabetes and hypertension than men, post-infarction women and men were equally likely to meet the ACC/AHA class I and class IIa criteria for post-infarction angiography and angiographic rates were nearly identical by gender. Significant coronary disease was equally prevalent in post-infarction women and men, they were equally likely to undergo myocardial revascularization procedures and mortality rates were comparable for women and men.

Fewer women than men following MI are referred to cardiac rehabilitation programs, with the gender disparity accentuated at older age. The exercise training component of cardiac rehabilitation can improve functional status comparably for women and men and coronary risk reduction has been documented [61].


   7. Myocardial revascularization: coronary artery bypass graft surgery and transcatheter revascularization procedures
Top
 1. Epidemiology
 2. Diagnostic evaluation of...
 3. Angina pectoris
 4. Sudden coronary death
 5. Acute coronary syndromes
 6. Myocardial infarction
 7. Myocardial revascularization:...
8. Summary
 9. Coronary heart disease...
 References
 
7.1. Coronary artery bypass graft surgery
Case series or registry data, rather than randomized clinical trials, provide the basis for most gender comparisons of myocardial revascularization procedures. Because of the paucity of randomized trial data, baseline differences between women and men assume substantial importance. In most reported series women are older and have more frequent comorbidity, particularly diabetes and hypertension. As well, they report greater functional impairment prior to coronary artery bypass graft (CABG) surgery and have more severe symptoms of chest pain [62,63].

The randomized trial data from the Coronary Artery Surgery Study (CASS) describe a perioperative mortality rate of 4.5% for women compared with 1.9% for men [21]. A comparable doubled hospital mortality rate was evident for women in the Myocardial Infarction Triage Intervention Registry, 13 versus 6% for women and men, respectively [64]. In reports from the 1980s women were described to have lower rates of graft patency, were less likely to receive an internal mammary artery graft, had more frequent perioperative MI and heart failure, and had less symptomatic relief postoperatively; they were more likely to require reoperation within the initial 5 years following CABG surgery. Nonetheless, the greatest risk appeared to be perioperative, in that women who survived the operative hospitalization had a comparable 15-year survival to men [65]. In many earlier studies, postoperative coronary risk factor control was suboptimal for women [66] but likely was equally suboptimal for men. Less favorable psychosocial outcomes following CABG surgery were also described for women [67]; with more frequent depression, delayed resumption of preoperative activities save for household tasks, and a lesser and later return to remunerative employment. The relationship of these adverse outcomes to older age, greater comorbidity, lesser social support, widowhood, financial constraints and the like have not been adequately evaluated. More recent survey data suggest that after adjustment for older age and severity of disease, women and men have comparable physical and psychosocial functioning at 6 months post-operatively.

Contemporary CABG surgery information derives from the US Society of Thoracic Surgeons database [68] involving 344913 CABG patients, 26% women, operated during the middle of the last decade. Women were older; more likely to have diabetes, hypertension, and peripheral vascular disease; and more likely to undergo nonelective procedures. Men had more left ventricular dysfunction, likely due to prior MI; were more likely to be smokers; and had a greater need for reoperation. The CABG operative mortality for women was 4.5%, for men 2.6%. The women had a greater operative mortality for every risk factor examined univariately including subgroups with and without internal mammary artery grafting and including consideration of body surface area, a surrogate for coronary artery size. In multivariate analysis, women were significantly more likely to have increased mortality compared with equally-matched men in the low and medium risk groups. The women in the highest risk group did not have excess mortality compared with men; the highest risk group was defined as elderly patients and those with nonelective procedures and with reoperation. The authors concluded that female gender independently predicted greater CABG operative mortality except in the highest risk category.

Women considered candidates for CABG surgery who either refuse surgery or who, for other reasons, are treated medically have less favorable outcomes than their counterparts who undergo CABG. Clinical and angiographic characteristics are the major determinants of the indications and recommendations for CABG surgery for women, but the higher CABG operative mortality for women than men must be appreciated.

7.2. Transcatheter revascularization procedures
Registry data provided most of the early information regarding PTCA in women, rendering gender differences in baseline characteristics important in evaluating these data. As with CABG surgery, women referred for PTCA were more likely to be older than men and to have comorbidities, particularly a history of heart failure, unstable angina, hypertension, hypercholesterolemia and diabetes; they were less likely to have had either prior MI or prior revascularization procedures [69,70]. With comparable angiographic disease, women were more likely to have severe stable angina and unstable angina. Women had better left ventricular function than men despite greater reporting of heart failure, likely representing ventricular diastolic dysfunction.

In the initial NHLBI PTCA Registry, 1985–1986 [71], twice as many women as men referred for PTCA were considered either inoperable or at high surgical risk, and more women than men had unstable angina. Although at 4-year follow up more women than men had died following PTCA, both MI and the need for CABG surgery was comparable for women and men. However, women in the Registry not only had more residual angina, but had more severe angina and consequently received more maintenance antianginal medications.

In the National Heart, Lung, and Blood Institute's 1993–1994 PTCA Register [72], comparison is made with the 1985–1986 data, where women were considered under-represented. The 1993–1994 Registry reported data only for women; these women were older and had more diabetes and comorbidity than the 1980s women. Despite their higher risk profiles, they had greater angiographic and clinical success rates; comparable mortality, MI, and need for emergency CABG surgery rates; and a decrease in the combined endpoint of death, MI, and the requirement for CABG surgery. Thus higher risk women who undergo PTCA today have better angiographic and clinical success rates and decreased rates of major complications, i.e., improved clinical outcomes. In the 1985–1986 Registry, the angiographic and clinical success rates were 85 and 79%, respectively, compared with 90 and 89%, respectively, in the 1993–1994 Registry. The combined endpoint of mortality, nonfatal MI and the requirement for emergency CABG surgery was 9.7% in the 1985–1986 Registry versus 4.4% in the 1993–1994 Registry. This improvement likely reflects both increased operator experience and the currently available smaller catheters suitable for the smaller coronary artery size of women.

The Bypass Angioplasty Revascularization Investigation (BARI) [73] randomized patients eligible for either procedure to CABG surgery or PTCA; 27% of the 1829 patients were women. Unadjusted hospital 5-year mortality rates for CABG surgery were comparable in both genders, with hospital mortality rates of 1.3 and 1.4% in women and men, respectively, and rates of Q-wave MI 4.7 and 4.6%, respectively. Women were more likely to have heart failure and pulmonary edema, 9.8% as compared with 1.8% for men. Five-year CABG survival was comparable, 87% for women and 87% for men. The hospital mortality rates for patients randomized to PTCA were 0.8% and 1.2% for women and men, respectively, with rates of Q-wave MI of 1.2 and 2.4%, respectively. As with CABG surgery, there was an excess of heart failure and pulmonary edema in women, 4.8% as compared with 1.4% for men. However, 5-year survival was comparable, 75% for women and 77% for men.

There were baseline differences between genders, in that BARI women were older and were more likely to have heart failure, hypertension, diabetes, hypercholesterolemia, and unstable angina [73]; left ventricular function and multivessel coronary disease were comparable to that for men. There were also differences in the interventions: women received the same number of total grafts but fewer internal mammary artery grafts at CABG surgery (72 versus 85% for men), but those randomized to PTCA had more lesions successfully dilated (76% compared with 71% for men). After adjustment for baseline risk characteristics, women had a significantly decreased 5-year mortality risk, and no difference in the 5-year risk of mortality plus nonfatal MI. The investigators concluded that female sex independently predicted increased 5-year survival, after adjustment for baseline risk characteristics. This should not be construed to mean that women do not have an increased procedural risk; it means only that gender, per se, does not impart increased risk; the increased risk for women is due to their higher baseline risk profile. Comparison among women in BARI undergoing CABG surgery and PTCA procedures showed similar hospital mortality rates; with CABG surgery compared with PTCA, there was an excess of Q-wave MI, of heart failure, and of pulmonary edema.

With the newer transcatheter revascularization procedures, particularly those utilizing stent implantation [74] gender outcomes are comparable, although there is a greater requirement for vascular repair in women and increased rates of coronary dissection, need for transfusion, and hypotension. One year outcomes of coronary stenting in 1001 women and 3263 men with symptomatic CHD treated between 1992 and 1998 at two tertiary referral institutions in Germany showed that women were older, and were more likely to have diabetes, hypertension, and hypercholesterolemia. They had less extensive coronary disease, less prior MI, and better left ventricular function. Their 30-day rate of death or nonfatal MI was marginally increased compared with men, but 1-year outcomes were similar. Saphenous vein graft stenting in women [75] entailed a higher risk of early mortality, vascular complications and post-procedural renal failure, but one year outcomes were similar to men.

Despite the doubling of coronary arteriography among US women during the past decade, and an almost threefold increase in the rates of both CABG surgery and transcatheter revascularization procedures, concerns remain about the delayed referral of women for myocardial revascularization. Potential contributors to the higher risk of adverse outcomes of myocardial revascularization for women include the greater likelihood of severe and unstable angina, which may require urgent or emergency intervention. Because of less favorable outcome data, referral of women appears delayed until their presentation is more severe and less stable, with a resultant vicious circle. It remains uncertain whether earlier and better control of risk factors, particularly diabetes, hypertension, and hyperlipidemia may exert a favorable effect. As with MI, fewer women than men, and particularly fewer elderly women, are referred for cardiac rehabilitation following myocardial revascularization; such rehabilitation enables improvement in functional capacity as well as a structured format for encouraging coronary risk reduction [61].


   8. Summary
Top
 1. Epidemiology
 2. Diagnostic evaluation of...
 3. Angina pectoris
 4. Sudden coronary death
 5. Acute coronary syndromes
 6. Myocardial infarction
 7. Myocardial revascularization:...
 8. Summary
9. Coronary heart disease...
 References
 
The vulnerability of women to CHD currently remains poorly recognized both by women and by their treating physicians, presenting a challenge to provide information and education and to reshape and alter practice patterns.

CHD in women is not only an equal opportunity killer but often disadvantages women. Over time the increased application of appropriate diagnostic, therapeutic, and interventional managements seems to favorably alter the prognosis for women, particularly when adjusted for baseline characteristics. Clinician education is the key to insuring that comparable therapies are provided for coronary patients of both genders for this extraordinarily threatening health problem.


   9. Coronary heart disease in women: key points
Top
 1. Epidemiology
 2. Diagnostic evaluation of...
 3. Angina pectoris
 4. Sudden coronary death
 5. Acute coronary syndromes
 6. Myocardial infarction
 7. Myocardial revascularization:...
 8. Summary
 9. Coronary heart disease...
References
 

  • Clinical manifestations of CHD present 10–20 years later than in men
  • Radionuclide or echocardiographic imaging improves diagnostic accuracy of exercise testing
  • Angina is predominant initial and subsequent CHD presentation
  • Pathoanatomy of sudden cardiac death differs in younger and older women – ? clinical implications
  • With an acute coronary syndrome, women more likely to have unstable angina than MI
  • Women more likely to have atypical MI symptoms: dyspnea, abdominal neck and shoulder pain
  • Increased MI mortality and reinfarction women vs. men
  • Thrombolysis does not abolish gender difference
  • Improved outcomes with primary PTCA vs. thrombolysis
  • Comparable gender benefit of MI pharmacologic therapies
  • Less aggressive diagnosis and therapy a likely contributor to adverse outcomes
  • Increased CABG mortality women vs. men
  • Increased PTCA mortality women vs. men relates substantially to less favorable baseline risk characteristics

Time for primary review 57 days.


   References
Top
 1. Epidemiology
 2. Diagnostic evaluation of...
 3. Angina pectoris
 4. Sudden coronary death
 5. Acute coronary syndromes
 6. Myocardial infarction
 7. Myocardial revascularization:...
 8. Summary
 9. Coronary heart disease...
 References
 

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