Key words: age; angiography; gender; myocardial infarction; noninvasive studies

Transcription

1 Influence of Age on Gender Differences in the Management of Acute Inferior or Posterior Myocardial Infarction* Manuel Martínez-Sellés, MD, PhD; Ramón López-Palop, MD, PhD; Esther Pérez-David, MD, PhD; and Héctor Bueno, MD, PhD Study objectives: To assess the effect of gender on the in-hospital management of patients with acute inferior or posterior myocardial infarction (MI). Design: Retrospective analysis of clinical records. Gender differences in management and prognosis were assessed by stepwise multiple logistic regression analysis. Setting: University, large-volume, tertiary hospital. Patients: We studied 1,178 consecutive patients admitted to our coronary care unit with an acute inferior or posterior MI, and evaluated the influence of gender on clinical management and outcome. Interventions: None. Measurements and results: Women were older (73 years vs 66 years), had a higher prevalence of diabetes and hypertension, presented later (8 h vs 6 h after symptom onset), and had a higher in-hospital mortality rate (26% vs 9%) [all p values < 0.01]. Women underwent reperfusion therapy (45% vs 61%, p < 0.01), noninvasive studies (30% vs 62%, p < 0.001), and coronary angiography (34% vs 48%, p < 0.01) less often than men. Multivariable analysis revealed that female gender was an independent predictor of a lower use of noninvasive studies (odds ratio [OR], 0.41; 95% confidence interval [CI], 0.24 to 0.63; p < 0.005) and coronary angiography (OR, 0.59; 95% CI, 0.37 to 0.93; p 0.02). A significant interaction between age and gender was found (p 0.002); therefore, women > 75 years old had a much lower probability of undergoing noninvasive tests and coronary angiography than men of the same age. Conclusion: Despite their worse prognosis, women undergo noninvasive studies and coronary angiography less frequently than men after an acute inferior or posterior MI. The gender gap increases in patients > 75 years old. (CHEST 2005; 128: ) Key words: age; angiography; gender; myocardial infarction; noninvasive studies Abbreviations: AV atrioventricular; CI confidence interaval; CK creatine kinase; MI myocardial infarction; OR odds ratio; PCI percutaneous coronary intervention Previous studies 1 4 have reported that the beneficial effects of fibrinolytic therapy and invasive cardiac procedures on morbidity and mortality of acute myocardial infarction (MI) are similar in *From the Department of Cardiology (Drs. Martínez-Sellés, Pérez-David, and Bueno), Hospital General Universitario Gregorio Marañón, Madrid; and Hospital Universitario Virgen de la Arrixaca (Dr. López-Palop), Murcia, Spain. Drs. Martínez-Sellés and López-Palop contributed equally to this article. Presented in part at XXIII Congress of the European Society of Cardiology. Stockholm, Sweden, August 1 5, Manuscript received February 18, 2004; revision accepted March 2, Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( org/misc/reprints.shtml). Correspondence to: Héctor Bueno, MD, PhD, Department of Cardiology, Hospital General Universitario Gregorio Marañón, Dr. Esquerdo, , Madrid, Spain; hecbueno@jet.es women and in men. However, women with acute MI receive less aggressive treatment than men, and differences related to gender in the use of fibrinolytic therapy, coronary angiography, and percutaneous coronary interventions (PCIs) have been reported. 5 7 Despite the lower rates of use of diagnostic and therapeutic interventions reported in women, there is disagreement as to whether this difference is due to an independent effect of gender on healthcare delivery or results from the association of female gender with other variables such as a more advanced age. 4 8 Inferior/posterior-wall infarcts represent nearly half of all ST-segment elevation MIs. Although the prognosis of inferior/posterior MI is believed to be more benign than that of anterior MI, it is more heterogeneous as there are patients with a very good 792 Clinical Investigations

2 prognosis such as those with isolated posterior infarcts and high-risk subgroups, such as patients showing right ventricular involvement, 9 particularly if they are older, 10 have ST-segment depression in anterolateral leads, 11 or have high-degree atrioventricular (AV) block. 12 Therefore, the absolute benefit of reperfusion therapy differs to a larger extent among the subgroups of inferior/posterior MI than among patients with infarcts of anterior location. 13,14 This heterogeneous prognosis could lead to an increased variability in the clinical management of patients with inferior/posterior MI. It has been described that women with acute MI are, as a group, subjected to greater variations in the use of diagnostic and therapeutic resources than men. 5 This gender-related variability may be increased in a group of patients with a heterogeneous prognosis and response to treatment such as those with inferior or posterior MI. Thus, the present study was designed to assess the influence of gender on the clinical management of patients with acute inferior or posterior MI and their hospital outcome. Materials and Methods A detailed description of the population and methods has been published elsewhere. 15 Briefly, all consecutive patients with an acute inferior or posterior MI admitted to our coronary care unit within 48 h from symptom onset during the years 1990 to 1995 were studied. To the original data set, 376 patients admitted during the years 1996 and 1997 were added. The final population consisted of 1,178 consecutive patients with a definite diagnosis of acute inferior or posterior MI. A definite diagnosis was established when the following criteria were met: ST-segment elevation 0.1 mv or Q-waves in two or more inferior leads in the admission ECG and/or development of an R wave in V 1 or V s with an R/S voltage ratio 1; and at least one of the following: (1) chest discomfort 30 min compatible with myocardial ischemia, or (2) elevation of serum creatine kinase (CK) level to at least twice the upper normal limit (195 U/L in our institution), with an MB fraction 10% of the total CK level. The study was approved by the hospital ethics committee. Statistical Analysis Means ( SD) are reported for continuous variables. The 2 test was used to assess the significance of the differences between proportions, and Student t test was used for comparisons between means. Gender differences in the use of reperfusion therapy (fibrinolytic therapy and primary PCI) were assessed in a stepwise multivariate logistic regression analysis that included all prognostic factors available at the time of hospital admission: age, risk factors, shock at hospital admission, previous MI, and delay to hospital admission. The independent association of gender with the use of noninvasive tests and coronary angiography was evaluated in patients not treated with primary PCI who survived hospitalization, also considering other variables obtained during admission (left ventricular ejection fraction, complete AV block). The influence of gender on in-hospital outcome was adjusted for all the variables previously mentioned. The presence of increasing gender differences with age was tested by including a sex-age interaction in all models. All probability values are two tailed. As patients admitted during years 1996 and 1997 were added to the original data set, a subanalysis was performed with these patients, showing a slight increase in the use of reperfusion therapy in both genders, compared with patients included during the years 1990 to However, as gender-related differences and in-hospital mortality remained similar in both populations, the analyses were performed with the whole group. All analyses were performed using statistical software (Version 11.0; SPSS; Chicago, IL). Table 1 Demographic and Clinical Characteristics of Patients Admitted With Acute Inferior MI, According to Sex* Characteristics Women (n 257) Men (n 921) p Value Age, yr 73 (66 81) 62 (53 70) Age 75 yr 127 (49) 135 (15) Delay on arrival, h 4 (2 12) 3 (2 6) Risk factors Hypertension 157 (61.1) 304 (33.1) Left ventricular hypertrophy 72 (28.2) 133 (14.4) Diabetes 99 (38.5) 179 (19.4) Current smoking 40 (15.6) 667 (72.4) Hyperlipemia 86 (33.5) 364 (39.5) 0.08 Previous diseases Stroke 25 (9.7) 43 (4.7) 0.02 Previous MI 25 (9.7) 116 (12.6) 0.2 COPD 17 (6.8) 134 (14.5) In hospital Systolic BP on hospital admission 129 ( ) 127 ( ) 0.51 Diastolic BP on hospital admission 76 (69 90) 77 (70 90) 0.77 Heart rate on hospital admission 77 (62 90) 74 (60 85) 0.05 Peak CK-MB values 225 (91 278) 223 ( ) 0.93 ST-segment depression 1mminV 4 V 6 75 (29.2) 345 (37.5) 0.01 Right ventricular infarction 111 (43.1) 362 (39.3) 0.23 *Data are presented as median (25th 75th percentile) or No. (%). CHEST / 128 / 2/ AUGUST,

3 Table 2 In-Hospital Stay, Adverse Events, and Interventions in Patients With Acute Inferior MI, According to Gender* Variables Women (n 257) Results Characteristics of the Patients Men (n 921) p Value In-hospital outcomes Adverse in-hospital events 156 (60.8) 370 (40.2) Congestive heart failure 81 (31.4) 80 (8.7) Cardiogenic shock 45 (17.6) 58 (6.3) Reinfarction 19 (7.5) 50 (5.4) 0.2 Mechanical complications 24 (9.5) 36 (3.9) Complete AV block 50 (19.6) 111 (12.1) Primary ventricular 13 (5.1) 64 (7.0) 0.29 fibrillation Length of stay, d In-hospital mortality 68 (26.5) 82 (8.8) yr 20 (15.4) 54 (6.9) yr 48 (37.8) 27 (20.0) Interventions Reperfusion therapy 116 (45.1) 558 (60.6) Age 75 yr 70 (53.8) 499 (63.5) 0.36 Age 75 yr 46 (36.2) 59 (43.7) 0.21 Delay 6 h 104 (65.4) 517 (74.2) 0.04 Delay 6 to 12 h 5 (10.9) 20 (18.5) 0.18 Delay 12 to 24 h 5 (12.8) 15 (17.9) 0.49 Fibrinolytic therapy 84 (32.6) 425 (46.1) Primary PCI 32 (12.5) 134 (14.5) 0.42 Noninvasive studies 69 (42.3) 530 (73.9) Age 75 yr 60 (64.5) 491 (78.1) Age 75 yr 9 (12.9) 39 (44.3) Coronary angiography 41 (25.0) 289 (40.3) Age 75 yr 36 (38.7) 265 (42.1) 0.53 Age 75 yr 5 (7.0) 24 (27.0) PCI 36 (14.1) 216 (23.4) Coronary artery bypass graft 8 (3.2) 41 (4.4) 0.4 *Data are presented as mean SD or No. (%). Female patients (n 257) were significantly older and had a higher prevalence of diabetes and hypertension (Table 1). A longer delay from onset of symptoms to hospital admission was found in women (8 h vs 6 h). Women also presented with cardiogenic shock on hospital admission more frequently than men. Reperfusion Therapy Women were significantly less likely to receive fibrinolytic therapy than men (Table 2). This difference was explained, at least in part, by their older age and a longer time delay (adjusted odds ratio [OR] for reperfusion therapy, 0.84; 95% confidence interval [CI], 0.59 to 1.24) [Table 3]. Medication During Hospitalization Medications used to prevent or treat heart failure (diuretics, inotropic agents, and angiotensin-converting enzyme inhibitors) were more frequently used in women (Table 4), whereas statins were prescribed less often. Aspirin, -blockers, and heparin were used similarly in both genders. Noninvasive Studies Noninvasive studies (97.6% exercise stress tests) were performed less frequently in women than in men, regardless of age (Table 2). This difference was particularly pronounced in patients 75 years old (p value for sex-age interaction, 0.002). Among hospital survivors who were not treated by primary PCI, noninvasive tests were performed in 8% of women 75 years old and in 33% of men 75 years old (adjusted OR, 0.17; 95% CI, 0.08 to 0.36; p ). Coronary Angiography Women had a lower chance than men to undergo coronary angiography during hospitalization. The gender difference persisted after adjustment for confounding variables (adjusted OR, 0.59; 95% CI, Table 3 Influence of Female Gender on the Use of Reperfusion Therapy, Coronary Angiography, Noninvasive Studies, and In-Hospital Mortality* Interventions Adjusted OR (95% CI) p Value Reperfusion therapy 0.84 ( ) NS Sex/age interaction for reperfusion therapy NS Coronary angiography 0.59 ( ) 0.02 Sex/age interaction for diagnostic catheterization 0.94 ( ) Noninvasive studies 0.17 ( ) Sex/age interaction for noninvasive studies 0.94 ( ) In-hospital mortality 1.40 ( ) 0.07 Sex/age interaction for in-hospital mortality NS *Patients who died during hospitalization and those treated with primary angioplasty were excluded from the analyses to explain the use of diagnostic coronary angiography and noninvasive studies. NS not significant. OR refers to the use of the intervention in women compared with men adjusted for age, risk factors, shock on hospital admission, previous MI, delay to hospital admission, complete AV block, and in the case of diagnostic catheterization, also by left ventricular ejection fraction. 794 Clinical Investigations

4 0.37 to 0.93; p 0.02) [Table 3]. Age had an important effect on the relation between gender and the use of coronary angiography (p value for sex/age interaction, 0.002). While women 75 years old were referred for coronary angiography as frequently as men (adjusted OR, 0.93; 95% CI, 0.62 to 1.31; p 0.7), it was performed less frequently in older women (adjusted OR, 0.41; 95% CI, 0.23 to 0.72, p 0.002). In-hospital Mortality The crude in-hospital mortality rate was 26% for women and 9% for men (p ) [Table 2]. The higher mortality of women was observed in younger and older patients. However, after adjustment for clinical dissimilarities, we only found a nonsignificant trend toward a higher in-hospital death rate in women (Table 3). Discussion Women with acute inferior or posterior MI show higher in-hospital mortality and cardiac complications rates than men, but these differences are mostly explained by their older age and a worse clinical risk profile. When confounding factors were taken into account, women had a 80% lower probability of being studied by noninvasive tests, and a 40% lower chance of undergoing coronary angiography. This sex difference in the performance of noninvasive studies was small in patients 75 years old (65% in women vs 78% in men) and large in the elderly (13% vs 44%). The rate of use of coronary angiography was similar in younger men and women but much lower in women 75 years old compared with older men (7% vs 27%). Although in-hospital mortality rates were 26% in Table 4 Use of Pharmacologic Therapies During Hospitalization According to Sex* Variables Women (n 257) Men (n 921) p Value Aspirin 238 (92.7) 872 (94.7) Blockers 86 (33.3) 344 (37.3) 0.29 Calcium antagonists 79 (30.9) 277 (30.1) 0.85 Ticlopidine 44 (17.2) 197 (21.4) 0.19 Statins 25 (9.8) 144 (15.6) 0.02 Heparin 176 (68.5) 677 (73.5) 0.26 Nitrates 179 (69.9) 629 (68.3) 0.72 Diuretics 68 (26.5) 124 (13.5) Inotropic agents 59 (23.0) 119 (12.9) Angiotensin-converting enzyme inhibitors 104 (40.5) 262 (28.4) *Data are presented as No. (%). women and 9% in men, we found a nonsignificant trend toward a higher death rate in women after adjustment for confounding factors. However, we did not find a significant interaction between age and gender in mortality because there was a consistent increase in mortality across all age subgroups. These findings are in contrast to previous studies 16 that reported a higher hospital mortality in younger women but not in older women compared with men of the same age, but are concordant with others 17,18 that found a higher mortality in older women. The reasons for this discrepancy are unknown, but the type of MIs analyzed may play a role. In the present study, only patients with confirmed inferior or posterior infarcts were included. Our results are similar to those found by the studies 17,18 that only recruited patients with ST-segment elevation or Q-wave MIs, and differ from the study by Vaccarino et al, 16 in which roughly half of the patients presented with ST-segment elevation MIs. Inability to perform a stress test after an acute MI is a powerful predictor of long-term mortality, particularly in older patients. 19 In our study, noninvasive studies were performed in women less often. As women were on average 12 years older, it is likely that factors such as a poorer functional capacity and a lower degree of mobility influenced the rate of use of treadmill tests. Although the lower specificity of noninvasive tests in women reported previously may have also played a role, this would not explain the lower utilization of noninvasive tests in younger women or the lack of use of alternative studies such as pharmacologic stress tests, which are helpful in postinfarction risk stratification in older patients. 23 Moreover, if inability to perform were the cause of the lower rate of use of stress tests in women, a higher rate of coronary angiography would be expected among them. Previous studies 4 7 have shown that women are less likely than men to undergo coronary angiography after MI, and that failure to perform coronary angiography after MI is associated with an increased short-term mortality risk, particularly in the elderly. 7,24,25 Our study shows that older women with inferior or posterior MI are at the highest mortality risk but undergo coronary angiography less often than men. Gan et al 4 found that women 65 years old were significantly less likely than men to undergo catheterization. However, even in this elderly population, this difference was more pronounced at older ages. Alter et al 6 also found a lower rate of coronary angiography within the first 6 months after MI in women, particularly in the oldest patients. The reasons why older women are less frequently scheduled for invasive studies are unknown. Rathore et al 26 showed that the lower rates of cardiac catheteriza- CHEST / 128 / 2/ AUGUST,

5 tion in older women occur primarily in patients with equivocal diagnosis of ischemic heart disease, but that is not the case in our cohort, in which all patients had confirmed MI. Our study shows an age-related increase in the gender difference in the of noninvasive studies and coronary angiography, which is not explained by clinical characteristics. Although other reasons such as nonregistered comorbidities, 27 differences in quality of life, functional status, mental disorders, 28 and patient refusal to undergo invasive or noninvasive studies could have contributed to the disparity, it is unlikely that they explain the large gender gap in the use of these resources, particularly in the oldest. Therefore, we cannot formally exclude that a gender bias may be partially behind this gap, particularly among the oldest patients. Limitations This observational study shows the routine management of patients with acute inferior or posterior MI, so the ultimate causes for the use or nonuse of specific interventions are frequently unknown. Although we registered several clinical features, we could not account for factors such as quality of life, noncardiac comorbidity, functional status, and patient preferences, which may influence the process of decision making, particularly the use of coronary angiography, so the degree of appropriateness in the use of the diagnostic and therapeutic resources could not be calculated. Finally, although the research was conducted in a large-volume teaching hospital, it is a single center study where the vast majority of staff members are men in a country where coronary angiography after MI is not routine practice, and therefore our results may not be extrapolated. In conclusion, women with acute inferior or posterior MI have a worse prognosis than men but undergo noninvasive tests and coronary angiography less frequently during hospitalization. This gap is not explained by the differences in clinical characteristics, and increases with age. Our results should be interpreted as an opportunity to improve the care of women with acute MI, particularly the elderly. References 1 Fibrinolytic Therapy Trialists (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. [published erratum appears in Lancet 1994; 343:742]. Lancet 1994; 343: Woodfield SL, Lundergan CF, Reiner JS, et al. Gender and acute myocardial infarction: is there a different response to thrombolysis? J Am Coll Cardiol 1997; 29: Krumholz HM, Murillo JE, Chen J, et al. Thrombolytic therapy for eligible elderly patients with acute myocardial infarction. JAMA 1997; 277: Gan SC, Beaver SK, Houck PM, et al. Treatment of acute myocardial infarction and 30-day mortality among women and men. N Engl J Med 2000; 343: Ayanian JZ, Epstein AM. Differences in the use of procedures between women and men hospitalized for coronary heart disease. N Engl J Med 1991; 325: Alter DA, Naylor CD, Austin PC, et al. Biology or bias: practice patterns and long-term outcomes for men and women with acute myocardial infarction. J Am Coll Cardiol 2002; 39: Yarzebski J, Col N, Pagley P, et al. Gender differences and factors associated with the receipt of thrombolytic therapy in patients with acute myocardial infarction: a community-wide perspective. Am Heart J 1996; 131: Maynard C, Litwin PE, Martin JS, et al. 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: Zehender M, Kasper W, Kauder E, et al. Right ventricular infarction as an independent predictor of prognosis after acute inferior myocardial infarction. N Engl J Med 1993; 328: Bueno H, López-Palop R, Bermejo J, et al. In-hospital outcome of elderly patients with acute inferior myocardial infarction and right ventricular involvement. Circulation 1997; 96: Berger PB, Ryan TJ. Inferior myocardial infarction: high-risk subgroups. Circulation 1990; 81: Nicod P, Gilpin E, Dittrich H, et al. Long-term outcome in patients with inferior myocardial infarction and complete atrioventricular block. J Am Coll Cardiol 1988; 12: Berger PB, Ruocco NAJ, Ryan TJ, et al. Incidence and prognostic implications of heart block complicating inferior myocardial infarction treated with thrombolytic therapy: results from TIMI II. J Am Coll Cardiol 1992; 20: Wellens HJJ. Right ventricular infarction. N Engl J Med 1993; 328: Bueno H, López-Palop R, Perez-David E, et al. Combined effect of age and right ventricular involvement on acute inferior myocardial infarction prognosis. Circulation 1998; 98: Vaccarino V, Parsons L, Every NR, et al. Sex-based differences in early mortality after myocardial infarction. National Registry of Myocardial Infarction 2 Participants. N Engl J Med 1999; 341: Bueno H, Vidan MT, Almazan A, et al. Influence of sex on the short-term outcome of elderly patients with a first acute myocardial infarction. Circulation 1995; 92: Malacrida R, Genoni M, Maggioni AP, et al. A comparison of the early outcome of acute myocardial infarction in women and men: the Third International Study of Infarct Survival Collaborative Group. N Engl J Med 1998; 338: Deckers JW, Fioretti P, Brower RW, et al. Ineligibility for predischarge exercise testing after myocardial infarction in the elderly: implications for prognosis. Eur Heart J. 1984; 5(suppl): Gibbons RJ, Balady GJ, Timothy BJ, et al. ACC/AHA 2002 guideline update for exercise testing: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). J Am Coll Cardiol 2002; 40: Kwok Y, Kim C, Grady D, et al. Meta-analysis of exercise 796 Clinical Investigations

6 testing to detect coronary artery disease in women. Am J Cardiol 1999; 83: Arruda-Olson AM, Juracan EM, Mahoney DW, et al. Prognostic value of exercise echocardiography in 5,798 patients: is there a gender difference? J Am Coll Cardiol 2002; 39: de la Torre MM, San Roman JA, Bermejo J, et al. Prognostic power of dobutamine echocardiography after uncomplicated acute myocardial infarction in the elderly. Chest 2001; 120: Jenkins JS, Flaker GC, Nolte B, et al. Causes of higher in-hospital mortality in women than in men after acute myocardial infarction. Am J Cardiol 1994; 73: Stenestrand U, Wallentin L. Early revascularisation and 1-year survival in 14-day survivors of acute myocardial infarction: a prospective cohort study. Lancet 2002; 359: Rathore SS, Wang Y, Radford MJ, et al. Sex differences in cardiac catheterization after acute myocardial infarction: the role of procedure appropriateness. Ann Intern Med 2002; 137: Ghali WA, Faris PD, Galbraith PD, et al. Sex differences in access to coronary revascularization after cardiac catheterization: importance of detailed clinical data. Ann Intern Med 2002; 136: Druss BG, Bradford DW, Rosenheck RA, et al. Mental disorders and use of cardiovascular procedures after myocardial infarction. JAMA 2000; 283: CHEST / 128 / 2/ AUGUST,