28-day mortality rates after first or recurrent Q-wave or non Q-wave AMI.

Transcription

1 Short-Term (28 Days) Prognosis Between Genders According to the Type of Coronary Event (Q-Wave Versus Non Q-Wave Acute Myocardial Infarction Versus Unstable Angina Pectoris) Jaume Marrugat, MD, María García, MD, Roberto Elosua, MD, Elena Aldasoro, MD, María José Tormo, MD, Oscar Zurriaga, MD, Fernando Arós, MD, Rafael Masiá, MD, Ginés Sanz, MD, Vicente Valle, MD, Esteban López De Sá, MD, Joan Sala, MD, Antonio Segura, MD, Catalina Rubert, MD, Concepción Moreno, MD, Adolfo Cabadés, MD, Lluís Molina, MD, José Luís López-Sendón, MD, and Miguel Gil, MD, for the IBERICA, PRIAMHO, RESCATE, PEPA, and REGICOR Investigators The type of acute coronary syndrome may account for different prognoses between men and women after myocardial infarction. This study assessed gender differences in 28-day mortality rates for first or recurrent Q-wave and non Q-wave myocardial infarctions and unstable angina by using data from 5 registries that included 20,836 patients (24.8% women). Mortality rates were higher in women with first Q-wave myocardial infarction but not in the other patients after adjusting for confounding variables by Excerpta Medica, Inc. (Am J Cardiol 2004;94: ) omen who are hospitalized with acute myocar- infarction (AMI) have been found to have Wdial higher adjusted risks of short-term mortality than men. 1 5 There is considerable variability in the type of acute coronary syndrome reported in published studies. In most instances, the analyses refer to a mixture of patients who have incident and recurrent Q-wave and non Q-wave AMI. 2,5,6 Unstable angina pectoris (UAP) has rarely been examined. These expressions of coronary disease have substantially different prognoses and do not affect men and women with the same frequency. 7 This study assessed gender differences in 28-day mortality rates after first or recurrent Q-wave or non Q-wave AMI. In this study, data from 5 registries were used: Recursos Empleados en el Síndrome Coronario Agudo y Tiempos de Espera (RESCATE), a study that included a registry of consecutive patients who had first AMI or UAP without previous AMI and were admitted to 4 hospitals 8,9 ; the Registre Gironí de COR (REGICOR) study, which included consecutive patients who had first or recurrent Q-wave AMI in a single hospital 10,11 ; the Investigación, Búsqueda Específica y Registro de Isquemia Coronaria Aguda (IBERICA), a study that included consecutive patients who had AMI in 100 hospitals 12 ; and the Proyecto de Estudio del Pronóstico de la Angina (PEPA) study, which included consecutive patients who had UAP in 18 hospitals. 13 In the Proyecto de Registro de Infarto Agudo de Miocardio Hospitalario (PRIAMHO) study, approximately 80% of patients who had first and recurrent Q-wave and non Q-wave AMI who had been admitted consecutively to the coronary care units in 24 hospitals were registered over 1 year. 14 Together these patient samples provided sufficient statistical power to analyze the role of gender in the prognosis of each acute coronary syndrome. All these registries operated between 1992 and 1998, and no important differences From the Institut Municipal d Investigació Mèdica, Barcelona; the Universitat Autónoma de Barcelona, Barcelona; the Departamento de Sanidad, Gobierno Vasco, Vitoria-Gasteiz; the Consejería de Sanidad y Consumo, Murcia; the Generalitat Valenciana, Valencia; the Hospital Txagorritxu, Vitoria; the Hospital Universitari Dr. Josep Trueta, Gerona; the Hospital Clinic, Barcelona; the Hospital Germans Trias i Pujol, Badalona; the Hospital Gregorio Marañón, Madrid; the Consejería de Sanidad de Castilla-La Mancha, Talavera de la Reina; the Hospital Son Dureta, Palma de Mallorca; the Instituto de Salud Pública de Navarra, Pamplona; the Hospital la Fe, Valencia; and the Hospital del Mar, Barcelona, Spain. The Investigación, Búsqueda Específica y Registro de Isquemia Coronaria Aguda was funded by grants FIS 96/ to 05, FIS 97/1270, and FIS 98/1535 from the Fondo de Investigación Sanitaria, Madrid, Spain, a research grant from AstraZeneca, Madrid, Spain, and the health care administrations of the following Spanish autonomous governments: Baleares, Castilla La Mancha, Catalunya, Murcia, Navarra, País Vasco, and Valencia, Spain. The Proyecto de Registro de Infarto Agudo de Miocardio Hospitalario study was funded by the Sección de Cardiopatía Isquémica of the Sociedad Española de Cardiología, Madrid, Spain. The Registre Gironí de COR Study was funded by grants FIS 93/ 0568, FIS 96/ , and FIS 94/0539 from the Fondo de Investigación Sanitaria, Madrid, Spain. The Recursos Empleados en el Síndrome Coronario Agudo y Tiempos de Espera project was funded in part by grant FIS 92/0009 from the Fondo de Investigación Sanitaria, Madrid, Spain. The present study was funded in part by the Generalitat de Catalunya, Barcelona, Spain (CIRIT/2001/SGR/ 00408). The Proyecto de Estudio del Pronóstico de la Angina was funded by a research grant from Pfizer, Madrid, Spain. This study was also funded in part by the Red de Centros en Epidemiología y Salud Pública del Fondo de Investigación Sanitaria, Madrid, Spain (C03/09). Dr. Marrugat s address is: Unitat de Lípids i Epidemiologia Cardiovascular. Institut Municipal d Investigació Mèdica, Carrer Dr. Aiguader 80, E Barcelona, Spain. jmarrugat@ imim.es. Manuscript received April 13, 2004; revised manuscript received and accepted July 14, by Excerpta Medica, Inc. All rights reserved /04/$ see front matter The American Journal of Cardiology Vol. 94 November 1, 2004 doi: /j.amjcard

2 were observed among them in main clinical and patient characteristics (data not shown). All consecutive patients who had UAP without previous AMI (667 from RESCATE Study and 2,014 from PEPA), first Q-wave AMI (360 from REGICOR, 1,316 from RESCATE, 3,356 from PRIAMHO, and 7,481 from IBERICA), recurrent Q-wave AMI (57 from REGICOR, 78 from RESCATE, 593 from PRI- AMHO, and 1,458 from IBERICA), or first or recurrent non Q-wave AMI (84 from REGICOR, 266 from RESCATE, 1,293 from PRIAMHO, and 1,649 from IBERICA) were included (20,836 patients in total) regardless of survival period after admission and of the hospital department where they had been admitted, except in the PRIAMHO Study. AMI was diagnosed when abnormal new Q waves appeared on serial electrocardiograms or when 2 of the following criteria were present: sequential ischemic ST-T changes on electrocardiogram; creatine phosphokinase levels 2 the upper limit of normal, myocardial fraction of total creatine phosphokinase 10%, or the 2 conditions at the same time; and typical chest pain lasting 20 minutes. When only the last 2 criteria were met, the diagnosis was non Qwave AMI. Patients who had typical chest pain, regardless of duration, and did not meet the criteria for AMI (with or without Q wave) were classified as having UAP. This diagnosis was made only with a positive result on coronary angiogram or when ischemic electrocardiographic changes occurred while pain persisted at any time during hospitalization or at exercise testing. The end point of this study was 28-day mortality rate for all acute coronary syndromes. Patients were followed in the outpatient clinic or by telephone call. The cause of death was ascertained by reviewing clinical records. History and clinical characteristics were prospectively recorded in all registries. Demographic characteristics, smoking status, history of hypertension, diabetes, previous angina pectoris, AMI location, development of acute pulmonary edema or cardiogenic shock, presence of severe arrhythmia (defined as 1 episode of ventricular fibrillation or sustained ventricular tachycardia that required immediate medical intervention) within the first 72 hours, recurrent AMI and/or angina, use of thrombolytic and antiplatelet agents, and diagnostic and coronary angiograms, percutaneous transluminal coronary angioplasty, and coronary artery bypass grafting were recorded. All variables had similar definitions in all studies. Differences between men and women and between deceased and surviving subjects were assessed by chisquare test for categorical variables and Student s t test for continuous variables. The level of significance used was 5%. The adjusted odds ratios and 95% confidence intervals of 28-day mortality rates for women were estimated by a logistic model that included demographic, co-morbidity, and clinical factors that met preliminary biologic plausibility and confounding variable criteria, i.e., those that differed statistically in bivariate analysis between men and women and were associated with 28- day mortality rate but could not be considered mechanisms of death. Age was entered into the model as a continuous variable. Adjustment variables were included manually 1 by 1 in the models and retained if they produced a 10% change in the coefficient of female gender. Calculations were made with SPSS (SPSS, Inc., Chicago, Illinois). Between 1992 and 1998, 15,666 men (75.2%) and 5,170 women (24.8%) ages 23 to 94 years (mean SD ) admitted with a first Q-wave AMI (9,571 men, 2,942 women), a recurrent Q-wave AMI (1,784 men, 402 women), a non Q-wave AMI (2,410 men, 882 women), or UAP (1,826 men, 855 women 80 years) had been entered into the RESCATE, REGICOR, PRIAMHO, IBERICA, and PEPA registries. Women were older, more frequently had histories of diabetes and hypertension, and more often developed acute pulmonary edema or cardiogenic shock, angina, or recurrent AMI during admission compared with men, regardless of whether the event was recurrent or whether it involved a Q wave. In contrast, women were less often smokers and less often developed severe ventricular arrhythmias. Anterior location of AMI was more frequent in women who had first Q-wave AMI. Delay in reaching a hospital after symptom onset was longer in women for all coronary syndromes (Table 1). Thrombolysis was used more frequently among men than among women who had Q-wave AMI and among those patients who had non Q-wave AMI and presented initially with ST elevation. Antiplatelet drugs were used similarly in men and women, although somewhat less in women (in particular those who had first Q-wave AMI). Other interventions, including coronary angiography and percutaneous transluminal coronary angioplasty, were used more frequently in men than in women for all coronary syndromes (Table 1). Raw mortality rate was significantly higher in women for all coronary syndromes (Table 1). Follow-up rates at 28 days were 99.9% for incident Q-wave AMI, 99.7% for recurrent Q-wave AMI, 99.8% for non Q-wave AMI, and 95.4% for UAP. The number of deaths during the 28-day period was 2,741 (13.1%). The crude mortality rate in women was 2 times that of men who had first Q-wave AMI (p 0.001) and higher in women who had the other coronary syndromes (all p 0.001; except UAP p 0.065). Compared with survivors, deceased subjects were older, more often women, nonsmokers, diabetic and hypertensive, had worse clinical features, and received fewer antiplatelet and thrombolytic drugs for all coronary syndromes. They also had significantly fewer angiograms for Q-wave and non Q-wave coronary syndromes (Table 2). Women who had first Q-wave AMI (odds ratio 1.54, 95% confidence interval 1.34 to 1.76) had a higher adjusted risk of 28-day mortality than did men, but those who had recurrent Q-wave AMI, non Qwave AMI, or UAP did not. Further adjustment for severity variables (i.e., pulmonary edema, cardiogenic 1162 THE AMERICAN JOURNAL OF CARDIOLOGY VOL. 94 NOVEMBER 1, 2004

3 TABLE 1 Characteristics of 20,836 Patients Who Had an Acute Coronary Syndrome and Were Consecutively Included in a Study by Gender and Type of Coronary Syndrome First Q-Wave AMI Recurrent Q-Wave AMI Non Q-Wave AMI UAP Variable Men Women Men Women Men Women Men Women (n 9,571) (n 2,942) (n 1,784) (n 402) (n 2,410) (n 882) (n 1,826) (n 855) Age (yrs), mean SD * * * * Hypertension 39.3% 61.6%* 44.6% 67.4%* 46.6% 65.9%* 48.8% 71.2%* Diabetes mellitus 21.4% 42.3%* 30.0% 54.6%* 25.3% 46.7%* 23.0% 38.2%* Current smoker 75.9% 12.1%* 70.7% 9.3%* 72.2% 9.5%* 76.1% 8.9%* Previous angina pectoris 32.1% 36.5%* 53.2% 59.8% 44.2% 47.4% 63.1% 73.2% Previous myocardial infarction % 100% 25.8% 20.9% 0 0 Anterior myocardial infarction 35.1% 40.7%* 40.4% 39.3% 16.4% 15.1% 0 0 Acute pulmonary edema/cardiogenic 13.9% 29.1%* 29.2% 46.6%* 15.8% 24.3%* 0 0 shock Angina during admission 11.2% 13.8%* 15.2% 17.8%* 12.1% 16.0% 0 0 Recurrent myocardial infarction 2.6% 4.3%* 3.2% 6.6% 2.6% 4.1% 0 0 Severe arrhythmia 15.3% 12.1%* 19.3% 10.4%* 7.0% 6.2% 0 0 Thrombolysis 53.5% 40.4%* 39.4% 23.5%* 13.3% 8.2%* 0.8% 0.5% Antiplatelet drug use 92.8% 88.9%* 87.9% 86.4% 93.1% 91.2% 95.6% 93.5% Delay from symptom onset to 120 (60, 300) 180 (90, 418) 120 (60, 240) 195 (120, 406) 120 (79, 360) 158 (80, 360) 165 (60, 450) 163 (60, 360) admission 28-day coronary angiograms 28.2% 21.2%* 32.1% 22.2%* 26.7% 21.2% 58.9% 45.1%* 28-day coronary angioplasty 13.9% 9.9%* 12.3% 8.2% 9.0% 5.1%* 22.0% 9.2%* 28-day coronary bypass 4.0% 3.4% 5.7% 4.5% 5.3% 4.8% 15.1% 9.2%* 28-day mortality rate 10.9% 24.3%* 22.5% 32.8%* 10.1% 15.8%* 2.2% 3.5% *p ; p 0.001; p Median (25th, 75th quartiles) (minutes). Data were available only for patients in the PRIAMHO, IBERICA, and RESCATE studies. Data were available for all patient in all studies and in a sample of 750 patients in the PRIAMHO study. BRIEF REPORTS 1163

4 1164 THE AMERICAN JOURNAL OF CARDIOLOGY VOL. 94 NOVEMBER 1, 2004 TABLE 2 Characteristics of 20,836 Patients Consecutively Admitted According to Survivorship and Type of Acute Coronary Syndrome First Q-wave AMI Recurrent Q-wave AMI Non Q-wave AMI UAP Deceased Alive Deceased Alive Deceased Alive Deceased Alive Variable (n 1,757) (n 10,749) (n 533) (n 1,651) (n 382) (n 2,907) (n 69) (n 2,562) Age (yrs), mean SD * * * * Women 40.7% 20.7%* 24.8% 16.4%* 36.4% 25.5%* 45.5% 32.6% Hypertension 51.7% 43.4%* 50.5% 48.3% 56.2% 51.2% 55.1% 56.1% Diabetes 37.6% 24.5%* 44.6% 31.4%* 42.1% 29.5% 53.6% 27.2%* Current smoker 40.7% 64.1%* 48.3% 63.0%* 40.6% 57.2%* 49.3% 50.7% Previous angina 35.8% 32.7% 61.7% 52.1%* 56.4% 43.6%* 72.7% 66.3% Previous AMI % 100% 33.6% 23.3%* 0 0 Anterior AMI 44.9% 35.0%* 43.8% 39.1%* 18.6% 15.7% 0 0 Acute pulmonary 68.0% 9.5%* 75.9% 19.1%* 71.1% 11.1%* 0 0 edema/cardiogenic shock Angina after AMI 7.4% 12.5%* 11.2% 17.1% 19.1% 12.4%* 0 0 Recurrent myocardial infarction 6.6% 2.4%* 6.1% 3.2% 11.1% 2.0%* 0 0 Severe arrhythmia 33.5% 11.6%* 38.8% 11.2%* 22.2% 5.6%* 0 0 Thrombolysis 32.6% 53.3%* 24.9% 40.3%* 5.0% 12.9%* 1.4% 0.7% Antiplatelet drug use 72.3% 95.0%* 66.4% 94.3%* 78.2% 94.5%* 98.3% 94.8% 28-day coronary angiogram 9.8% 29.3%* 11.3% 36.3%* 15.1% 26.6%* 52.2% 55.3% 28-day coronary angioplasty 4.3% 14.3%* 4.9% 13.6%* 4.5% 8.5% 14.5% 19.7% 28-day coronary bypass 2.7% 4.0%* %* 2.1% 5.6% 13.1% 27.5% *p ; p 0.001; p Data were available for all patient in all studies and in a sample of 750 patients in the PRIAMHO study.

5 TABLE 3 Odds Ratio (95% Confidence Interval) of 28-Day Mortality Risk for Women Among 20,836 Patients Consecutively Hospitalized for Each Acute Coronary Syndrome Model* First Q-wave AMI Recurrent Q-wave AMI Non Q-wave AMI UAP (n 12,513) (n 2,186) (n 3,292) (n 2,681) ( ) 0.98 ( ) 1.04 ( ) 1.53 ( ) ( ) 0.97 ( ) 1.25 ( ) *Model 1 for first Q-wave AMI was adjusted for age, diabetes, thrombolysis, and smoking status, and model 2 was adjusted for hypertension, aspirin, anterior location of AMI, previous angina, pulmonary edema, cardiogenic shock and severe arrhythmia (i.e., sustained ventricular tachycardia of fibrillation) in addition to the adjustment of model 1. Model 1 for non Q-wave and recurrent Q-wave AMI was adjusted for age, diabetes, thrombolysis, aspirin, previous angina, and smoking status. Model 2 for recurrent Q-wave AMI was adjusted for anterior location of AMI, pulmonary edema, cardiogenic shock, and severe arrhythmia in addition to the adjustment of model 1. Model 2 for non Q-wave AMI was adjusted for hypertension, anterior location of AMI, pulmonary edema, cardiogenic shock, and severe arrhythmia in addition to the adjustment of model 1. Model 1 for UAP was adjusted for age, diabetes, and smoking status. shock, and sustained ventricular tachycardia or fibrillation) and other variables that met preliminary confounding criteria (i.e., were associated with gender and mortality rate) but did not change the gender coefficient when entered into the models did not substantially change the risk estimates for women with any coronary syndrome (Table 3). No interaction between gender and any adjustment variable including hospital was statistically significant. In particular, interaction of gender with dataset by study was not observed for any acute coronary syndrome. This study shows that early prognosis between genders differs depending on the type of acute coronary syndrome. Women fare worse than men after a first AMI. With respect to the other acute coronary syndromes, the difference was due to differences in age, co-morbidity, and clinical characteristics. Women developed more severe AMI syndromes than did men, as reflected by their larger proportion of anterior locations for AMI, pulmonary edema, and cardiogenic shock. This severity greatly increases their risk of death in the acute phase of AMI. 15 However, after a recurrent Q-wave AMI, women had an adjusted 28-day mortality risk similar to that of men. This suggests that factors other than severity alone may be involved in the difference observed in these subjects. The interaction between gender and age observed in other studies 6,15,16 was not observed in this study. There was no significant interaction between gender and dataset by study for any coronary syndrome. The cumulative incidence rates of AMI in Spain are 25% and 33% those in Finland and 50% and 33% those in the United States for women and men, respectively. 14,17 It has been observed that the initial form of coronary artery disease presents as angina more often in women than in men. 7 Apparently, not only do women present milder symptoms of AMI than do men, but they also develop more atypical symptoms, which often consist of abdominal discomfort and dyspnea. 5,18 Approximately 13% to 25% of myocardial ischemic episodes are symptomless owing to diabetes and older age. APPENDIX A list of REGICOR, RESCATE, PRIAHMO, IBERICA, and PEPA investigators can be found at 1. Greenland P, Reicher-Reiss H, Goldbourt U, Behar S. In-hospital and 1-year mortality in 1,524 women after myocardial infarction. Comparison with 4,315 men. Circulation 1991;83: Marrugat J, Sala J, Masia R, Pavesi M, Sanz G, Valle V, Molina L, Seres L, Elosua R. Mortality differences between men and women following first myocardial infarction. JAMA 1998;280: Ceniceros I, Gastaldo R, Cabades A, Cebrian D. El sexo femenino es un factor pronóstico independiente de mortalidad en la fase aguda del infarto de miocardio. Med Clin (Barc) 1997;109: Malacrida R, Genoni M, Maggioni AP, Spataro V, Parish S, Palmer A, Collins R, Moccetti T, for the Third International Study of Infarct Survival Collaborative Group. A comparison of the early outcome of acute myocardial infarction in women and men. N Engl J Med 1998;338: Maynard C, Every NR, Martin JS, Kudenchuk PJ, Weaver WD. Association of gender and survival in patients with acute myocardial infarction. Arch Intern Med 1997;157: Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz HM. Sex-based differences in early mortality after myocardial infarction. National Registry of Myocardial Infarction 2 Participants. N Engl J Med 1999;341: Kannel WB, Abbot RD. Incidence and prognosis of myocardial infarction in women: the Framingham Study. In: Eaker ED, Packard B, Wenger MK, Clarkson TB, Tyroler HA, eds. Coronary Heart Disease in Women: Proceedings of the NIH Workshop. New York: Haymarket Doyma, 1987: Marrugat J, Sanz G, Masia R, Valle V, Molina L, Cardona M, Sala J, Seres L, Szescielinski L, Albert X, et al, for the RESCATE Investigators. Six-month outcome in patients with myocardial infarction initially admitted to tertiary and nontertiary hospitals. J Am Coll Cardiol 1997;30: Lupon J, Valle V, Marrugat J, Elosua R, Seres L, Pavesi M, Freixa R, Sanz G, Masia R, Molina L, et al, for the RESCATE Investigators. Six-month outcome in unstable angina patients without previous myocardial infarction according to the use of tertiary cardiologic resources. J Am Coll Cardiol 1999;34: Sala J, Marrugat J, Masia R, Porta M. Improvement in survival after myocardial infarction between and in the REGICOR study. (Registre GIroni del COR) registry. Eur Heart J 1995;16: Gil M, Marrugat J, Sala J, Masia R, Elosua R, Albert X, Pena A, Vila J, Pavesi M, Perez G, for the REGICOR Investigators. Relationship of therapeutic improvements and 28-day case fatality in patients hospitalized with acute myocardial infarction between 1978 and 1993 in the REGICOR study, Gerona, Spain. Circulation 1999;99: Fiol M, Cabades A, Sala J, Marrugat J, Elosua R, Vega G, Tormo Diaz MJ, Segura A, Aldasoro E, Moreno-Iribas C, et al, for the Investigators of IBERICA. Variability in hospitalized myocardial infarction patient management in Spain: the IBERICA (Investigación, Búsqueda Específica y Registro de Isquemia Coronaria Aguda) Study (in Spanish). Rev Esp Cardiol 2001;54: Bermejo Garcia J, Lopez de Sa E, Lopez-Sendon JL, Pabon Osuna P, Garcia-Moran E, Bethencourt A, Bosch Genover X, Roldan Rabadan I, Calvino Santos R, Valle Tudela V. Unstable angina in the elderly: clinic profile, management and 3-month mortality. Data from the PEPA Registry (in Spanish). Rev Esp Cardiol 2000;53: Cabades A, Lopez-Bescos L, Aros F, Loma-Osorio A, Bosch X, Pabon P, Marrugat J, for the PRIAMHO Investigators. Variability in myocardial infarction patient management and short- and middle-term prognosis in Spain: the PRIAMHO Study (in Spanish). Rev Esp Cardiol 1999;52: Demirovic J, Blackburn H, McGovern PG, Luepker R, Sprafka JM, Gilbertson D. Sex differences in early mortality after acute myocardial infarction (the Minnesota Heart Survey). Am J Cardiol 1995;75: Marrugat J, Gil M, Masia R, Sala J, Elosua R, Anto JM, for the REGICOR Investigators. Role of age and sex in short-term and long term mortality after a first Q wave myocardial infarction. J Epidemiol Community Health 2001;55: Perez G, Pena A, Sala J, Roset P, Masia R, Marrugat J. Acute myocardial infarction case fatality, incidence and mortality rates in a population registry in Gerona, Spain, Int J Epidemiol 1998;27: Wenger NK. Clinical characteristics of coronary heart disease in women: emphasis on gender differences. Cardiovasc Res 2002;53: BRIEF REPORTS 1165