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Circulation. 1995;92:1133-1140

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(Circulation. 1995;92:1133-1140.)
© 1995 American Heart Association, Inc.

Articles

Influence of Sex on the Short-term Outcome of Elderly Patients With a First Acute Myocardial Infarction

Héctor Bueno, MD; M. Teresa Vidán, MD; Aureliano Almazán, MD; José L. López-Sendón, MD; Juan L. Delcán, MD

From the Department of Cardiology, Hospital General Universitario "Gregorio Marañón," Madrid, Spain.

Correspondence to Héctor Bueno, MD, Department of Cardiology, Hospital General Universitario "Gregorio Marañón," Dr Esquerdo, 46, 28007 Madrid, Spain.


*    Abstract
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 *Abstract
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Background Sex seems to affect the course of acute myocardial infarction (AMI) in the general population. Although the epidemiological importance of female sex among patients with AMI is more important from the sixth decade of life, little is known about the impact of sex on the outcome of AMI in the elderly.

Methods and Results To determine the differences between sexes in the outcome of AMI in the elderly, we compared the clinical history and evolution of 204 consecutive patients (99 men, 105 women) >=75 years of age admitted with a first AMI. Women had a higher prevalence (P<.01) of hypertension (60% versus 32%) and diabetes (41% versus 18%), whereas men were more frequently smokers (41% versus 4%, P<.0001); these factors were associated with higher rates of congestive heart failure. Women showed lower ejection fractions and higher rates of congestive heart failure (odds ratio [OR], 2.32; 95% CI, 1.32 to 4.12) and shock (OR, 2.78; 95% CI, 1.29 to 6.40). Mortality rate was higher in women (40% versus 23%, P=.01; OR, 2.29; 95% CI, 1.26 to 4.26); however, sex was excluded as an independent predictor of in-hospital mortality in every regression model tested (OR, 0.75; 95% CI, 0.25 to 2.21).

Conclusions After a first AMI, elderly women experience a more complicated hospital course than men. The increase in mortality risk seems to be related to the impact of cardiovascular risk factors on left ventricular function more than to sex itself.


Key Words: myocardial infarction • heart failure • mortality • aging • women


*    Introduction
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 *Introduction
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down arrowDiscussion
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The clinical course and prognosis of patients with acute myocardial infarction (MI) have been studied extensively. Numerous studies demonstrated that age is strongly associated with morbidity and mortality after AMI,1 2 3 4 5 6 7 8 9 10 even after thrombolytic therapy.11 Thus, more attention has been paid recently to the study of the specific characteristics of the elderly population with AMI. On the other hand, the impact of sex on the clinical course and mortality of AMI is more controversial. Despite early studies that showed that women had prognoses similar to or even better than men,12 13 14 15 several studies found that after an AMI, women have higher unadjusted mortality rates than men.16 17 18 19 20 21 However, after adjustment for baseline differences, the sex disparities in the outcomes are not at all certain. Therefore, there is a substantial controversy concerning the determination of the causes of the worse prognoses for women in the general population. Whether this is due to intrinsic sex-related differences, their older age, or a different clinical profile with respect to men has still to be ascertained. Because of the loss of hormonal protection after menopause and the higher life expectancy of women with respect to men, the proportion of women among patients with MI rises from the sixth to the eighth decade of life to equal that of men. Thus, the epidemiological significance of MI in women is greater as age advances. Despite this fact, little is known about the particularities and prognosis of AMI in elderly women.22 We selected patients with first MIs to obtain a more homogeneous population sample and to facilitate our understanding of the prognostic factors. To the best of our knowledge, this is the first study to address the outcome of elderly women after a first AMI.


*    Methods
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Patients
The population studied consisted of 204 consecutive patients 75 years of age or older admitted from December 1988 to March 1992 to the coronary care unit (CCU) of our institution with a first AMI.

Definitions
AMI was defined as the presence of any two of the following criteria: (1) chest discomfort for at least 30 minutes compatible with myocardial ischemia (dyspnea of rapid onset was also accepted)1 23 24 ; (2) elevation of serum creatine kinase (CK) level to at least twice the upper normal limit (195 IU/L in our institution), with an MB fraction (MB) higher than 6% of the total level; and (3) characteristic ECG changes. Non–Q wave infarcts were diagnosed by typical ST-segment and T-wave changes accompanied by the two other criteria. Q-wave infarcts were classified according to the Q-wave location into anterolateral (I, aVL, and V1 through V8) or inferoposterior (II, III, aVF, and R wave in V1 to V2 >40 milliseconds). An infarction was considered of indeterminate location when intraventricular conduction defects such as left bundle-branch or bifascicular blocks precluded localization.

Exclusion Criteria
All patients with clinical or ECG evidence of previous MIs were excluded.

Variables
Data were obtained in a retrospective (until December 1989) and a prospective manner from histories, physical examinations, serial laboratory studies, chest x-ray films, ECGs, echocardiographies, and hemodynamic studies. Variables analyzed were (1) baseline characteristics—history of previous systemic hypertension, diabetes mellitus, cigarette smoking (if present in the last 12 months before infarct), dyslipemia, angina (more than 2 weeks before admission), congestive heart failure (CHF), stroke, and peripheral arterial disease; (2) infarct features—time from symptom onset to CCU admission, ECG presentation (anterolateral, inferoposterior, non–Q wave, and indeterminate), Killip class on admission, and infarct size (CK and MB peak values): (3) diagnostic procedures—echocardiography, predischarge stress test, and coronary angiography; (4) treatment—medical management, thrombolytic therapy, coronary angioplasty, and cardiac surgery; (5) clinical course—CHF, shock (persistent hypotension with signs of low cardiac output), mechanical complications (ventricular septal rupture, free-wall rupture, and massive acute mitral regurgitation), rhythm disturbances (third-degree AV block, ventricular fibrillation, ventricular tachycardia, and supraventricular arrhythmias), reinfarction, postinfarction angina, and noncardiac complications; and (6) in-hospital mortality—mortality rate and causes and predictors of death. The causes of death were classified into five groups: shock (caused by left or right ventricular failure or both but not by mechanical complications); mechanical complications (free-wall rupture, interventricular septal rupture, or acute mitral regurgitation determined by echocardiography or with surgical or postmortem verification; electromechanical dissociation (when a definite cause was not established and autopsy was not performed), arrhythmia/sudden death, and other causes. In patients who were operated on to treat mechanical complications and died in the perioperative period, death by any cause was included in the mechanical complications group.

Statistical Methods
All continuous variables are expressed as median (25th to 75th percentiles) because they did not fit a normal distribution. Fisher's exact and {chi}2 tests were used to determine the significance of the differences between proportions, and unpaired t tests were used for comparisons between means. Shapiro-Wilk's test was used to assess the normality of distribution of continuous variables, and Levene's test was used to assess the homogeneity of variances in different groups; when differences between variances were found, unequal-variance t tests were used. Ordinal variables were compared with the Mantel-Haenszel test. Multiple logistic regression analysis was performed among variables correlated with adverse outcomes (P<.1 in the appropriate univariate analysis) after exclusion of factors with high collinearity with other predictive variables. The odds ratios (ORs) of the continuous variables are relative to the increase in units of measure that we established as per 1 or 5 years of increase for age, 100 IU/L of increase for MB peak value, and 1000 IU/L of increase for CK peak value. All analyses were performed with the JMP statistical program, version 3.0.1 (SAS Institute Inc, 1994), except the Mantel-Haenszel tests, which were performed with SPSS version 4.0 software (SPSS Inc, 1990). Because the end point of the multivariate analysis was to ascertain the independent effect of sex on mortality, the regression model was selected with the criterion of obtaining the narrowest CI for the sex variable. All probability values were two-tailed, and a probability value of <=.05 was considered significant.


*    Results
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*Results
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Baseline Characteristics
Female patients made up 51% of the population. The median age was 78 and 79 years for men and women, respectively (P=NS). The clinical cardiovascular history showed no differences between sexes (Table 1Down). Men more often had an AMI without any previous known cardiovascular risk factor than women. Women had higher proportions of hypertension and diabetes mellitus, whereas men were more likely to have been smokers in the last 12 months. When the infarct occurred, none of the women were under estrogen replacement therapy.


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  		Table 1. Baseline Characteristics

Infarct features
The median elapsed time from symptom onset to CCU admission was 1 hour longer for women than for men (5 versus 4 hours), although this difference did not reach statistical signification. After grouping time delays into intervals, we found a trend toward a later admission of women (P=.08 by the Mantel-Haenszel test), who also arrived in a worse clinical status evaluated by the Killip class. There were no differences between groups in the ECG presentation of the infarcts or in CK and MB peak values (Table 2Down).


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  		Table 2. Infarct Features

Diagnostic Procedures
Echocardiography was performed in 155 patients, 77 men (78%) and 78 women (74%, P=NS). Most survivors (87% in both groups) but only 52% of nonsurvivors (48% of men and 56% of women, P=NS) were studied. Women presented a similar proportion of left ventricular (LV) hypertrophy (37% versus 39%, P=NS) and dilatation (26% versus 30%, P=NS) than men but a lower LV ejection fraction (Fig 1Down). The Mantel-Haenszel test showed that Q-wave infarctions (P=.018), diabetes mellitus (P=.072), a history of previous CHF (P=.073), and dyslipemia (P=.086) were also associated with lower LV ejection fractions. Among patients studied, a higher incidence of postinfarction mitral regurgitation was found in women (59% versus 35%, P=.007; OR, 2.67; 95% CI, 1.3 to 5.6). If only moderate to severe regurgitations were considered, the difference was of borderline statistical significance (13.5% versus 4.4%, P=.07; OR, 3.4; 95% CI, 0.9 to 16.1).



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  		Figure 1. Bar graph comparing left ventricular ejection fraction determined by two-dimensional echocardiography in both groups. *Mantel-Haenszel test.

Predischarge stress test was recommended whenever possible, except when contraindications for future interventions were present. Despite this general rule, the individual indication was stated by each particular physician based on his or her own clinical criteria. Stress test was performed less frequently in women than in men (13% versus 43% of survivors, P=.0001) and was positive in 27% of men and 11% of women (P=NS).

Coronary angiography was usually restricted to patients with evidence of postinfarction myocardial ischemia and an active preinfarction way of life. We studied 14 women (13%) and 13 men (14%, P=NS). Multivessel disease was found in 54% of females and 46% of males studied (P=NS).

Treatment
Aspirin, heparin, intravenous nitroglycerin, and angiotensin-converting enzyme inhibitors were used in a similar proportion of women (79%, 77%, 62%, and 17%, respectively) and men (83%, 74%, 63%, and 11%, respectively). Women were more frequently treated with diuretics (42% versus 23%, P=.005), inotropic agents (29% versus 11%, P=.002), and digitalis (25% versus 16%, P=.12) and were treated less often with calcium antagonists (37% versus 53%, P=.02) and oral ß-blockers (7% versus 13%, P=.18). Thrombolytic therapy was used in 8 women and 7 men (P=NS). Twenty patients, 11 women (10%) and 9 men (9%, P=NS), required a temporary pacemaker. Six patients with postinfarction angina (3 women and 3 men) were treated by coronary angioplasty. Twelve patients (6%) were operated on, 8 (5 women and 3 men) as treatment for mechanical complications and 4 (2 women and 2 men) for coronary artery bypass grafting (P=NS).

Hospital Course
Women experienced a substantially worse in-hospital clinical outcome (Table 3Down). They had a higher incidence of total complications and a higher mortality rate. Clinical LV dysfunction was not only more common in women but also more severe. Shock was more frequent among women, and the trend was for women to present mechanical complications more frequently. A similar incidence of other complications between sexes was found.


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  		Table 3. Hospital Course

We tried to determine which other factors were responsible for cardiac complications in our population. The oldest patients and those with diabetes mellitus, histories of previous CHF, or infarcts of indeterminate ECG location had a twofold to threefold higher incidence of having a Killip class higher than I/IV on admission. Fig 2Down shows the factors related to the development of CHF, shock, and mechanical complications after the infarction. Among these factors, logistic regression analysis selected the peak level of CK (OR, 1.54; 95% CI, 1.15 to 2.07), the antecedent of previous CHF (OR, 5.8; 95% CI, 1.3 to 40.3), and diabetes mellitus (OR, 2.1; 95% CI, 0.98 to 4.5) as independent predictors of CHF development during hospitalization. The occurrence of shock was independently associated with the peak level of CK (OR, 2.0; 95% CI, 1.4 to 3.0), infarcts of indeterminate ECG location (OR, 9.6; 95% CI, 2.2 to 44.7), older age (OR per 5-year interval of increase, 2.3; 95% CI, 1.2 to 4.5), and female sex (OR, 3.0; 95% CI, 0.99 to 10.4). Finally, only marginal predictors of mechanical complications were obtained: the peak level of CK (OR, 1.4; 95% CI, 0.97 to 2.0) and female sex (OR, 2.9; 95% CI, 0.94 to 9.9).



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  		Figure 2. Graph showing clinical univariate predictors of intermediate events after acute myocardial infarction in the whole population. CHF indicates congestive heart failure; CK, creatine kinase. *Odds ratio (OR) related to each 100 IU/L of increase. {dagger}OR related to each 1000 IU/L of increase. {ddagger}OR related to each 5-year interval of increase. §Independent predictors.

The in-hospital mortality rate for the female group was 40%, nearly twice the rate (23%) of the male group (OR, 2.29; 95% CI, 1.26 to 4.26). No statistically significant differences were found between the two groups in cause of death. The highest mortality rate occurred in the first 48 hours after admission (49% of women's deaths versus 35% of men's deaths, P=NS). Table 4Down shows the univariate predictors of in-hospital mortality. The multiple logistic regression analysis performed among these variables excluded in every model female sex as an independent predictor (adjusted OR relative to men in the selected model, 0.75; 95% CI, 0.25 to 2.21). Killip class, mechanical complications, higher peak levels of CK, older age, and complete AV block were selected as independent predictors of in-hospital mortality in our population (Table 5Down).


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  		Table 4. Factors Related to In-Hospital Mortality


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  		Table 5. Predictors of In-Hospital Mortality


*    Discussion
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up arrowResults
*Discussion
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The results of the present study indicate that elderly women suffering a first AMI have worse profiles of known cardiovascular risk factors and experience a more complicated hospital course, including a higher incidence and severity of LV failure and a higher in-hospital mortality rate, than men do. After considering the association of sex with other prognostic indexes, the increase in in-hospital mortality risk related to female sex was not apparent in our population.

Prognosis of AMI in Elderly Women
The impact of sex on the outcome of AMI is still controversial. Although early studies suggested similar or even better prognoses for women than for men,12 13 14 15 most of the latest studies concluded that women have higher unadjusted mortality and morbidity rates after AMI in both short-term and long-term follow-ups.16 17 18 19 20 21 25 26 27 However, when differences in baseline characteristics are taken into account, analyses often reveal relatively similar outcomes in men and women. Therefore, the independent role of sex on the outcome after AMI remains unclear. While some studies found that female sex is an independent predictor of short-term mortality,25 26 others indicate that the higher mortality observed in women is due to differences in baseline characteristics.16 17 18 19 20 21 27 All previous investigations observed that the women studied were older than the men, and some of the studies attributed the worse prognoses observed in women to their older ages.17 18 28 These studies were performed in groups of wide ranges of ages, some of them excluding patients older than 75 years,19 20 21 26 whereas others reported their results stratified by age subgroups.5 16 17 18 25 The present study shows two major differences with respect to previous works: the circumscription of the population to older patients and the selection of patients with the first episode of AMI. The prognostic factors may change from the first infarction to subsequent events; therefore, the selection of first MI confers on the results a higher homogeneity and permits a more precise use of predictive factors. The selection of elderly patients also reduces the evident difference in age between men and women at the time when first infarction occurs in nonselected populations, restraining the impact of one of the most important prognostic factors. In our group, no difference was found in age between the male and female subgroups; therefore, older age does not account for the higher mortality of women in our population.

The only previous study addressing the outcome of women >=75 years of age with AMI22 surprisingly did not find a significant difference in mortality rates between men and women. Their results were obtained by a retrospective analysis of the database of the Myocardial Infarction Triage and Intervention (MITI) Registry, a multicenter study that included 19 CCUs in metropolitan Seattle, Ore. The relatively low mortality rate (18.6%) reported by Maynard et al22 for a population of such a high risk (very advanced age, history of prior MI in 32% of patients) compared with our results and with previous reports1 2 4 9 29 is also noteworthy. Maynard et al observed that women had a higher proportion of baseline risk factors and were older than men, but they also had some favorable characteristics such as a lower prevalence of previous MI and coronary artery bypass surgery and a shorter time delay from symptom onset to hospital arrival. Differences in the methodology, selection of patients, and management may explain the differences in outcomes. Their results were obtained by a retrospective survey of a multicenter study in which 8% of patients had more than one admission during the study and approximately 33% had histories of previous MIs. Patients who had resuscitated cardiac arrest before or at the time of admission were excluded. Our population enrolled only patients with first-time MIs admitted to a single CCU, and no selection according to the clinical status on admission was made. Our institution is a tertiary care hospital that attends a population of 750 000 and is also a reference center for other institutions. This suggests that the population at risk might have been a more unhealthy group than that of the MITI Registry. A somewhat more aggressive approach was also performed in Seattle; the proportion of patients treated with thrombolysis was similar in both studies, but coronary angiography, angioplasty, and coronary artery bypass graft surgery were performed approximately twice as frequently in Seattle than in Madrid. Finally, different patterns among centers in the admission criteria for the elderly might have influenced the findings. These disparities make comparisons between the results of both studies difficult.

Why Do Elderly Women Fare Worse Than Men After a First AMI?
The in-hospital mortality rate of women was very high, virtually twice that of men. Despite that difference, we failed to find an independent relation between sex and in-hospital mortality; therefore, differences in clinical features or their management must account for most of the increase in mortality risk.

A recent report from Israel indicated that late arrival is the first cause of ineligibility for thrombolytic therapy in women, and this accounts for more than half of female exclusions, whereas fewer than 40% of men are not treated with thrombolytics for that reason.30 Hence, a sex bias in admission has to be ruled out. We detected a trend toward later admission of women, who also presented clinical signs of LV failure more frequently than men did at that moment. It was reported that women with AMI seek medical care and are referred to CCUs later than men.27 31 Diabetes mellitus alters the perception of myocardial ischemia–related symptoms and might contribute to a delay in seeking medical care owing to the difficulty in recognizing the acute event.31 32 33 This difficulty might be aggravated in elderly patients in whom atypical presentations of MI are also more frequent.23 24 Physicians might be more likely to admit women only after complications have arisen. Actually, 12% of women and only 5% of men were admitted >24 hours after symptom onset. The fact that the vast majority of staff members of our department are men might also have played a role. On the other hand, if there had been a definite sex bias in admission,34 a change in the sex proportion of patients could be expected. According to the literature,1 35 a man to woman ratio of 0.95 in a group of such age is very likely to be proximal to reality. Hence, although a large sex bias in admission may be reasonably excluded, women may have had longer delays in arrival and/or in emergency room stay. We failed to find a direct association between admission time delay and mortality, probably because of the predominantly conservative therapeutic approach, but it is likely that admission time delay will be more clinically relevant because reperfusion therapies were used more often in the elderly.

Except for the predischarge stress test, performed less frequently in women, the sex-related differences in diagnostic and therapeutic procedures reported in previous studies28 30 36 37 38 39 40 were not found in our population. Because most high-risk patients died before the seventh day, the period after which the stress test is performed in our institution, we do not consider that this difference contributed significantly to the more adverse course for women. The differences found in medical treatment seem to be more a consequence than a cause of the different clinical outcomes.

In contrast to other workers,18 19 26 we did not find significant differences between men and women in the prevalence of preinfarction CHF. The exclusion of patients with previous MIs may contribute to this particularity. There were no differences between sexes in the CK and MB peak values, suggesting similar infarct sizes, but larger infarcts in women cannot be definitely excluded because no normalization to the body mass was performed. As reported previously, women had a higher prevalence of diabetes mellitus and hypertension than men, whereas more men than women smoked.16 17 18 19 20 21 25 26 27 Although diabetes mellitus in our population was not directly associated with mortality, all the clinical manifestations of LV failure were more frequent among diabetic patients. They were admitted in higher Killip classes, had higher rates of CHF and shock during hospitalization, and had worse LV ejection fractions than nondiabetics. Hypertension was a borderline predictor of in-hospital CHF development, and cigarette smoking correlated with lower rates of CHF. Smoking is associated with the progression of arteriosclerosis, mainly in epicardial coronary arteries. Diabetic and hypertensive patients present not only epicardial involvement but also small vessel and myocardial interstitium disease, which lead to an increase in LV stiffness and a relaxation dysfunction in early stages,41 42 43 particularly if both diseases are present.44 45 Systolic dysfunction may develop later.46 Diabetes mellitus, even with small infarcts, is known to be associated with worse short-term and long-term prognoses after AMI, related to the greater risk of developing CHF.47 48 The increased risk of in-hospital death is more evident in diabetic women.48 49 The higher CHF incidence in diabetics is thought to be caused largely by diastolic dysfunction.49 Two multicenter studies18 26 demonstrated that women had higher postinfarction LV ejection fractions but higher mortality rates and higher incidences of CHF and shock after AMI. Diastolic dysfunction was again thought to play an important role in the worse outcome of women. We found that women had more reduced LV systolic function compared with men. This difference, along with the aforementioned results,18 26 might be explained by the longer effect of risk factors on LV function in a group of only elderly patients. Diabetes mellitus and hypertension probably contributed to the worse outcome through more extensive myocardial damage in the aged females that caused a higher degree of systolic and possibly diastolic dysfunction. LV diastolic function was not routinely evaluated in our patients; therefore, we could not assess its role on patients' prognoses.

In contrast to what could have been expected because of the higher prevalence of risk factors, two-dimensional echocardiography did not disclose a higher proportion of LV hypertrophy or dilatation in women. Nevertheless, these data should be regarded with caution because half of the nonsurvivors died before the echocardiographic study was performed, and although this subgroup was not very large, it had a special clinical relevance. This circumstance is also the most likely reason for the lack of correlation between the LV ejection fraction and the in-hospital mortality in our group.

Men had a 10-fold higher prevalence of cigarette smoking than women. We found that smokers had lower rates of CHF and tended to have higher in-hospital survival rates than nonsmokers. A "protective" effect of smoking in patients suffering an AMI has been reported.27 50 51 52 It is thought to be caused by an association with better risk profiles. MIs in smokers would occur at earlier stages of coronary artery disease and in patients without significant LV functional impairment. That is the most likely reason for the lower incidence of LV dysfunction–related complications and the lower mortality rates observed in smokers.

Women had a tendency to suffer mechanical complications more often than men. The higher prevalence of hypertension might have contributed to this fact, particularly to the higher occurrence of cardiac rupture,53 although conflicting results about this relation have been published.54 We failed to find an association between the antecedent of hypertension and cardiac rupture or mechanical complications, but the incidence of high arterial pressure during the acute phase of MI was not evaluated.55 56 Finally, the reason why women had a higher incidence and severity of postinfarction mitral regurgitation remains obscure to us. It might be related to the higher incidence of LV dysfunction and CHF in females.

Study Limitations
The results of this study were obtained from patients admitted to the CCU; therefore, information about sex differences in patients with unrecognized or silent infarcts57 and in patients who died before admission is missing. The small sample size may influence some of the statistical results because of either an inability to detect differences in low-prevalence factors or the generation of wide CIs in the ORs of the predictive factors. The criterion used to select the regression model was chosen to avoid the latter limitation, but it may restrict its predictive value somewhat in different populations.

Clinical Implications
Elderly women have significantly worse prognoses than men during the course of first AMIs. This adverse outcome seems to be related, at least in part, to the effects of a more unfavorable profile of cardiovascular risk factors, particularly the higher prevalence of diabetes mellitus, whereas sex itself may not have such an important independent effect. The deleterious effect of risk factors might be mediated by several mechanisms that finally end in a higher incidence of heart failure. Further investigation is needed into the role of risk factors on systolic and diastolic LV dysfunction and on MI course in the elderly. Elderly women with AMIs constitute a particular high risk subgroup and probably should be given priority in admission; physicians should be aware of the habitual longer delay in their admission to CCU.

Received December 28, 1994; revision received March 13, 1995; accepted March 19, 1995.


*    References
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 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
up arrowResults
up arrowDiscussion
*References
 

  1. Konu V. Myocardial infarction in the elderly: a clinical and epidemiological study with a one-year follow-up. Acta Med Scand. 1977;604(suppl):6-68.
  2. Latting CA, Silverman ME. Acute myocardial infarction in hospitalized patients over age 70. Am Heart J. 1980;100:311-318. [Medline] [Order article via Infotrieve]
  3. Hoit BD, Gilpin EA, Henning H, Maisel AA, Dittrich H, Carlisle J, Ross J Jr. Myocardial infarction in young patients: an analysis by age subsets. Circulation. 1986;74:712-721. [Abstract/Free Full Text]
  4. Yang XS, Willems JL, Pardaens J, De Geest H. Acute myocardial infarction in the very elderly: a comparison with younger age groups. Acta Cardiol. 1987;42:59-68. [Medline] [Order article via Infotrieve]
  5. Tofler GH, Muller JE, Stone PH, Willich SN, Davis VG, Poole WK, Braunwald E, for the MILIS Study Group. Factors leading to shorter survival after acute myocardial infarction in patients ages 65 to 75 years compared with younger patients. Am J Cardiol. 1988;62:860-867. [Medline] [Order article via Infotrieve]
  6. Goldberg RJ, Gore JM, Gurwitz JH, Alpert JS, Bardy P, Strohsnitter W, Chen Z, Dalen JE. The impact of age on the incidence and prognosis of initial acute myocardial infarction: the Worcester Heart Attack Study. Am Heart J. 1989;117:543-549. [Medline] [Order article via Infotrieve]
  7. Marcus FI, Friday K, McCans J, Moon T, Hahn E, Cobb L, Edwards J, Kuller L. Age-related prognosis after acute myocardial infarction (The Multicenter Diltiazem Postinfarction Trial). Am J Cardiol. 1990;65:559-566. [Medline] [Order article via Infotrieve]
  8. Smith SC, Gilpin E, Ahnve S, Dittrich H, Nicod P, Henning H, Ross J Jr. Outlook after acute myocardial infarction in the very elderly compared with that in patients aged 65 to 75 years. J Am Coll Cardiol. 1990;16:784-792.[Abstract]
  9. Montague TJ, Ikuta RM, Wong RY, Bay KS, Teo KK, Davies NJ. Comparison of risk and patterns of practice in patients older and younger than 70 years with acute myocardial infarction in a two year period (1987-1989). Am J Cardiol. 1991;68:843-847. [Medline] [Order article via Infotrieve]
  10. Rich MW, Bosner MS, Chung MK, Shen J, McKenzie JP. Is age an independent predictor of early and late mortality in patients with acute myocardial infarction? Am J Med. 1992;92:7-13. [Medline] [Order article via Infotrieve]
  11. Maggioni AP, Maseri A, Fresco C, Franzosi MG, Mauri F, Santoro E, Tognoni G, on behalf of the Investigators of the GISSI-2. Age-related increase in mortality among patients with acute myocardial infarction treated with thrombolysis. N Engl J Med. 1993;329:1442-1448. [Abstract/Free Full Text]
  12. Norris RM, Brandt PWT, Cughey DOE, Lee AJ, Scott PJ. A new coronary prognostic index. Lancet. 1969;1:274-278. [Medline] [Order article via Infotrieve]
  13. Norris RM, Caughey DE, Deeming LW, Mercer CJ, Scott PJ. Coronary prognostic index for predicting survival after recovery from acute myocardial infarction. Lancet. 1970;2:485-488. [Medline] [Order article via Infotrieve]
  14. Johansson S, Bergstrand R, Ulvenstam G, Vedin A, Wilhemsson C, Wedel H. Sex differences in preinfarction characteristics and long-term survival among patients with myocardial infarction. Am J Epidemiol. 1984;119:610-623. [Abstract/Free Full Text]
  15. Weinblatt E, Shapiro S, Frank CW. Prognosis of women with newly diagnosed coronary heart disease: a comparison with course of disease among men. Am J Public Health. 1973;63:577-593. [Free Full Text]
  16. Puletti M, Sunseri L, Curione M, Erba SM, Borgia C. Acute myocardial infarction: sex-related differences in prognosis. Am Heart J. 1984;108:63-66. [Medline] [Order article via Infotrieve]
  17. Robinson K, Conroy RM, Mulcahy R, Hickey N. Risk factors and in-hospital course of first episode of myocardial infarction or acute coronary insufficiency in women. J Am Coll Cardiol. 1988;11:932-936. [Abstract]
  18. Dittrich H, Gilpin E, Nicod P, Cali G, Henning H, Ross J Jr. Acute myocardial infarction in women: influence of gender on mortality and prognostic variables. Am J Cardiol. 1988;62:1-7. [Medline] [Order article via Infotrieve]
  19. Fiebach NH, Viscoli CM, Horwitz RI. Differences between women and men in survival after myocardial infarction: biology or methodology? JAMA. 1990;263:1092-1096. [Abstract]
  20. Lincoff AM, Califf RM, Elli SG, Sigmon KN, Lee KL, Leimberger JD, Topol EJ, for the Thrombolysis and Angioplasty in Myocardial Infarction Study Group. Thrombolytic therapy for women with myocardial infarction: is there a gender gap? J Am Coll Cardiol. 1993;22:1780-1787. [Abstract]
  21. Marrugat J, Antó JM, Sala J, Masiá R, for the REGICOR Investigators. Influence of gender in acute and long-term cardiac mortality after a first myocardial infarction. J Clin Epidemiol. 1994;47:111-118. [Medline] [Order article via Infotrieve]
  22. Maynard C, Litwin PE, Martin JS, Weaver WD. Treatment and outcome of acute myocardial infarction in women 75 years of age and older: findings from the Myocardial Infarction Triage and Intervention Registry. Cardiol Elderly. 1993;1:121-125.
  23. Pathy MS. Clinical presentation of myocardial infarction in the elderly. Br Heart J. 1967;29:190-199. [Free Full Text]
  24. Day JJ, Bayer AJ, Pathy MSJ, Chadha JS. Acute myocardial infarction: diagnostic difficulties and outcome in advanced old age. Age Ageing. 1987;16:239-243. [Abstract/Free Full Text]
  25. Greenland P, Reicher-Reiss H, Goldbourt U, Behar S, for the Israeli SPRINT Investigators. In-hospital and 1-year mortality in 1524 women after myocardial infarction: comparison with 4315 men. Circulation. 1991;83:484-491. [Abstract/Free Full Text]
  26. Tofler GH, Stone PH, Muller JE, Willich SN, Davis VG, Poole WK, Strauss HW, Willerson JT, Jaffe AS, Robertson T, Passamani E, Braunwald E, for the MILIS Study Group. Effects of gender and race on prognosis after myocardial infarction: adverse prognosis for women, particularly black women. J Am Coll Cardiol. 1987;9:473-482. [Abstract]
  27. Jenkins JS, Flaker GC, Nolte B, Price LA, Morris D, Kurz J, Petroski GF. Causes of higher in-hospital mortality in women than in men after acute myocardial infarction. Am J Cardiol. 1994;73:319-322. [Medline] [Order article via Infotrieve]
  28. Maynard C, Litwin PE, Martin JS, Weaver WD. Gender differences in the treatment and outcome of acute myocardial infarction: results from the Myocardial Infarction Triage and Intervention Registry. Arch Intern Med. 1992;152:972-976. [Abstract]
  29. Lew AS, Hod H, Cercek B, Shah PK, Ganz W. Mortality and morbidity rates of patients older and younger than 75 years with acute myocardial infarction treated with intravenous streptokinase. Am J Cardiol. 1987;59:1-5. [Medline] [Order article via Infotrieve]
  30. Behar S, Gottlieb S, Hod H, Narinsky R, Benari B, Rechavia E, Pauzner H, Rougin N, Kracoff OH, Katz A, Roth A, Goldhammer E, Rudnik L, Faibel HE, Lotan C, Shapira C, Jafari J, Freedberg NA, Daka F, Kanetti M, Weiss T, Barasch E, Klutstein N, Blondheim D, Mahul N, Gelvan A, Barbash G, for the Israeli Thrombolytic Survey Group. Influence of gender in the therapeutic management of patients with acute myocardial infarction in Israel. Am J Cardiol. 1994;73:438-443. [Medline] [Order article via Infotrieve]
  31. Meischke H, Eisenberg MS, Larsen MP. Prehospital delay interval for patients who use emergency medical services: the effect of heart-related medical conditions and demographic variables. Ann Emerg Med. 1993;22:1597-1601. [Medline] [Order article via Infotrieve]
  32. Soler N, Bennet M, Pentecost B, Fitzgerald M, Malins J. Myocardial infarction in diabetics. Q J Med. 1975;173:125-132.
  33. Uretsky BF, Farquhar D, Berezin A, Hood W. Symptomatic myocardial infarction without chest pain: prevalence and clinical course. Am J Cardiol. 1977;40:498-503. [Medline] [Order article via Infotrieve]
  34. Wiklund I, Herlitz J, Johansson S, Bengtson A, Karlson BW, Persson NG. Subjective symptoms and well-being differ in women and men after myocardial infarction. Eur Heart J. 1993;14:1315-1319. [Abstract/Free Full Text]
  35. Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham population. Am Heart J. 1986;111:383-390. [Medline] [Order article via Infotrieve]
  36. Chiriboga DE, Yarzebski J, Goldberg RJ, Chen Z, Gurwitz J, Gore JM, Alpert JS, Dalen JE. A community-wide perspective of gender differences and temporal trends in the use of diagnostic and revascularization procedures for acute myocardial infarction. Am J Cardiol. 1993;71:268-273. [Medline] [Order article via Infotrieve]
  37. Khan SS, Nessim S, Gray R, Czer LS, Chaux A, Matloff J. Increased mortality of women in coronary artery bypass surgery: evidence for referral bias. Ann Intern Med. 1990;112:561-567.
  38. Krumholz HM, Douglas PS, Lauer MS, Pasternak RC. Selection of patients for coronary angiography and coronary revascularization early after myocardial infarction: is there evidence for a gender bias? Ann Intern Med. 1992;116:785-790.
  39. Steingart RM, Packer M, Hamm P, Coglianese ME, Gersh B, Geltman EM, Sollano J, Katz S, Moyé L, Basta LL, Lewis SJ, Gottlieb SS, Bernstein V, McEwan P, Jacobson K, Brown EJ, Kukin ML, Kantrowitz NE, Pfeffer MA, for the Survival and Ventricular Enlargement Investigators. Sex differences in the management of coronary artery disease. N Engl J Med. 1991;325:226-230. [Abstract]
  40. Tobin JN, Wassertheil-Smoller S, Wexler JP, Steingart RM, Budner N, Lense L, Wachspress J. Sex bias in considering coronary bypass surgery. Ann Intern Med. 1987;107:19-25.
  41. Riggs TW, Transue D. Doppler echocardiographic evaluation of left ventricular diastolic function in adolescents with diabetes mellitus. Am J Cardiol. 1990;65:899-902. [Medline] [Order article via Infotrieve]
  42. Hiramatsu K, Ohara N, Shigematsu S, Aizawa T, Ishihara F, Niwa A, Yamada T, Naka M, Momose A, Yoshizawa K. Left ventricular filling abnormalities in NID diabetes mellitus and improvement by a short-term glycemic control. Am J Cardiol. 1992;70:1185-1189. [Medline] [Order article via Infotrieve]
  43. Uusitupa M, Mustonen JN, Laakso M, Vainio P, Lansimies E, Talwar S, Pyorala K. Impairment of diastolic function in middle-aged type 1 (insulin dependent) and type 2 (non-insulin-dependent) diabetic patients free of cardiovascular disease. Diabetologia. 1988;31:783-791. [Medline] [Order article via Infotrieve]
  44. Venco A, Grandi A, Barzizza F, Finardi G. Echocardiographic features of hypertensive-diabetic heart muscle disease. Cardiology. 1987;74:28-34. [Medline] [Order article via Infotrieve]
  45. Danielson R. Factors contributing to left ventricular diastolic dysfunction in long-term type I diabetic subjects. Acta Med Scand. 1988;224:249-256. [Medline] [Order article via Infotrieve]
  46. Mustonen JN, Uusitupa MIJ, Tahvanainen K, Talwar S, Laakso M, Lansimies E, Kuikka JT, Pyorala K. Impaired left ventricular systolic function during exercise in middle-aged insulin-dependent and noninsulin-dependent diabetic subjects without clinical evident cardiovascular disease. Am J Cardiol. 1988;62:1273-1279. [Medline] [Order article via Infotrieve]
  47. Jaffe AS, Spadaro JJ, Schetchman K, Roberts R, Geltman EM, Sobel BE. Increased congestive heart failure after myocardial infarction of modest extent in patients with diabetes mellitus. Am Heart J. 1984;108:31-37. [Medline] [Order article via Infotrieve]
  48. Savage MP, Krolewski AS, Kenien GG, Lebeis MP, Christlieb AR, Lewis SM. Acute myocardial infarction in diabetes mellitus and significance of congestive heart failure as a prognostic factor. Am J Cardiol. 1988;62:665-669. [Medline] [Order article via Infotrieve]
  49. Stone PH, Muller JE, Hartwell T, York BJ, Rutherford JD, Parker CB, Turi ZG, Strauss HW, Willerson JT, Robertson T, Braunwald E, Jaffe AS, for the MILIS Study Group. The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. J Am Coll Cardiol. 1989;14:49-57. [Abstract]
  50. Mueller HS, Cohen LS, Braunwald E, Forman S, Feit F, Ross A, Schweiger M, Cabin H, Davison R, Miller D, Solomon R, Knatterud GL, for the TIMI Investigators. Predictors of early morbidity and mortality after thrombolytic therapy of acute myocardial infarction: analyses of patients subgroups in the thrombolysis in myocardial infarction (TIMI) trial, phase II. Circulation. 1992;85:1254-1264. [Abstract/Free Full Text]
  51. Molstad P. First myocardial infarction in smokers. Eur Heart J. 1991;12:753-759.
  52. Kelly TL, Gilpin E, Ahnve S, Henning H, Ross J Jr. Smoking status at the time of acute myocardial infarction and subsequent prognosis. Am Heart J. 1985;110:535-541. [Medline] [Order article via Infotrieve]
  53. Pollak H, Diez W, Spiel R, Enenkel W, Mlczoch J. Early diagnosis of subacute free wall rupture complicating acute myocardial infarction. Eur Heart J. 1993;14:640-648. [Abstract/Free Full Text]
  54. Reddy SG, Roberts WC. Frequency of left ventricular free wall or ventricular septum among necropsy cases of fatal acute myocardial infarction since introduction of coronary care units. Am J Cardiol. 1989;63:906-911. [Medline] [Order article via Infotrieve]
  55. Pohjola-Sintonen S, Muller JE, Stone PH, Willich SN, Antman EN, Davis VG, Parker CB, Braunwald E, for the MILIS Study Group. Ventricular septal and free wall rupture complicating acute myocardial infarction: experience in the Multicenter Investigation of Limitation of Infarct Size. Am Heart J. 1989;117:809-816. [Medline] [Order article via Infotrieve]
  56. Shapira I, Isakov A, Burke M, Almog C. Cardiac rupture in patients with acute myocardial infarction. Chest. 1987;92:219-223. [Abstract/Free Full Text]
  57. Murabito JM, Evans JC, Larson MG, Levy D. Prognosis after the onset of coronary heart disease: an investigation of differences in outcome between the sexes according to initial coronary disease presentation. Circulation. 1993;88:2548-2555. [Abstract/Free Full Text]



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