Gender-Specific Short and Long-Term Mortality in Diabetic Versus Nondiabetic Patients With Incident Acute Myocardial Infarction in the Reperfusion Era (the MONICA/KORA Myocardial Infarction Registry)
2010; Elsevier BV; Volume: 106; Issue: 12 Linguagem: Inglês
10.1016/j.amjcard.2010.08.009
ISSN1879-1913
AutoresChrista Meisinger, Margit Heier, Wolfgang von Scheidt, Inge Kirchberger, Allmut Hörmann, Bernhard Kuch,
Tópico(s)Heart Failure Treatment and Management
ResumoThe aim of this study was to investigate gender-specific short- and long-term mortalities after a first acute myocardial infarction (AMI) in patients with and without diabetes mellitus (DM). The study was based on 505 men and 196 women with DM and 1,327 men and 415 women without DM consecutively hospitalized with a first-ever AMI from January 1998 to December 2003 recruited from a population-based MI registry. Patients were followed until December 31, 2005 (median follow-up time 4.3 years). In men and women, no significantly independent association between DM and short-term mortality was observed. After multivariable adjustment odds ratios (95% confidence intervals [CIs]) for 28-day case fatality were 1.45 (95% CI 0.90 to 2.34) in men with DM compared to men without DM and 1.44 (95% CI 0.66 to 3.15) in women with DM compared to women without DM. Conversely, in 28-day AMI survivors DM was significantly associated with long-term mortality in age-adjusted analyses, in which men with DM had a hazard ratio (HR) of 1.57 (95% CI 1.18 to 2.10) for all-cause mortality compared to non-DM men; the corresponding HR in women with DM was 2.91 (95% CI 1.82 to 4.65). After multivariable adjustment the strong association in women with DM remained significant (HR 2.56, 95% CI 1.53 to 4.27); however, in men with DM it became borderline significant (HR 1.36, 95% CI 1.00 to 1.85). In conclusion, short-term mortality was not significantly increased in men and women with DM after a first-ever AMI, although estimates were relatively high, indicating a possible relation. However, long-term mortality was higher in patients with AMI and DM, particularly in women. The aim of this study was to investigate gender-specific short- and long-term mortalities after a first acute myocardial infarction (AMI) in patients with and without diabetes mellitus (DM). The study was based on 505 men and 196 women with DM and 1,327 men and 415 women without DM consecutively hospitalized with a first-ever AMI from January 1998 to December 2003 recruited from a population-based MI registry. Patients were followed until December 31, 2005 (median follow-up time 4.3 years). In men and women, no significantly independent association between DM and short-term mortality was observed. After multivariable adjustment odds ratios (95% confidence intervals [CIs]) for 28-day case fatality were 1.45 (95% CI 0.90 to 2.34) in men with DM compared to men without DM and 1.44 (95% CI 0.66 to 3.15) in women with DM compared to women without DM. Conversely, in 28-day AMI survivors DM was significantly associated with long-term mortality in age-adjusted analyses, in which men with DM had a hazard ratio (HR) of 1.57 (95% CI 1.18 to 2.10) for all-cause mortality compared to non-DM men; the corresponding HR in women with DM was 2.91 (95% CI 1.82 to 4.65). After multivariable adjustment the strong association in women with DM remained significant (HR 2.56, 95% CI 1.53 to 4.27); however, in men with DM it became borderline significant (HR 1.36, 95% CI 1.00 to 1.85). In conclusion, short-term mortality was not significantly increased in men and women with DM after a first-ever AMI, although estimates were relatively high, indicating a possible relation. However, long-term mortality was higher in patients with AMI and DM, particularly in women. The purpose of the present population-based study was to compare short- and long-term mortalities after an incident acute myocardial infarction (AMI) in patients with and without diabetes mellitus (DM), taking into account advances in noninvasive and invasive therapy, such as percutaneous coronary intervention. In particular, we examined whether there are different results in men and women. As part of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) project, the population-based Augsburg Coronary Event Registry was implemented in 1984.1Meisinger C. Hörmann A. Heier M. Kuch B. Löwel H. Admission blood glucose and adverse outcomes in non-diabetic patients with myocardial infarction in the reperfusion era.Int J Cardiol. 2006; 113: 229-235Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar After termination of MONICA in 1995, the registry became part of the framework of the Cooperative Health Research in the Region of Augsburg (KORA). Methods of case finding, diagnostic classification of events, and data quality control have been described elsewhere.1Meisinger C. Hörmann A. Heier M. Kuch B. Löwel H. Admission blood glucose and adverse outcomes in non-diabetic patients with myocardial infarction in the reperfusion era.Int J Cardiol. 2006; 113: 229-235Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar, 2Kuch B. Heier M. von Scheidt W. Kling B. Hoermann A. Meisinger C. 20-Year-trends in clinical characteristics, therapy and short-term prognosis in acute myocardial infarction according to presenting electrocardiogram—results of the MONICA/KORA Augsburg Myocardial Infarction Registry (1985–2004).Am J Cardiol. 2007; 100: 1056-1060Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Up to December 31, 2000, diagnosis of a major nonfatal AMI was based on symptoms, cardiac enzymes, and typical electrocardiographic changes according to the MONICA manual.2Kuch B. Heier M. von Scheidt W. Kling B. Hoermann A. Meisinger C. 20-Year-trends in clinical characteristics, therapy and short-term prognosis in acute myocardial infarction according to presenting electrocardiogram—results of the MONICA/KORA Augsburg Myocardial Infarction Registry (1985–2004).Am J Cardiol. 2007; 100: 1056-1060Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Since January 1, 2001, all patients with AMI diagnosed according to European Society of Cardiology and American College of Cardiology criteria have been included.3Alpert J.S. Thygesen K. Antman E. Bassand J.P. Myocardial infarction redefined—a consensus document of the Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction.J Am Coll Cardiol. 2000; 36: 959-969Abstract Full Text Full Text PDF PubMed Scopus (3818) Google Scholar Briefly, patients are interviewed during their hospital stay using a standardized questionnaire and further data are recorded by chart review. Demographic data, data on cardiovascular risk factors, medical history, co-morbidities including DM, and medication before and during hospital stay and at discharge are collected from each patient. Laboratory parameters, electrocardiogram, and in-hospital course are also determined. Rate of reperfusion (lysis, percutaneous coronary intervention, and coronary artery bypass grafting) was documented. Moreover, in-hospital adverse events, including ventricular fibrillation, cardiogenic shock, cardiac arrest, recurrent MI, and pulmonary edema, were recorded. In the present analysis, all registered patients with and without DM with an incident AMI from January 1, 1998 to December 31, 2003 were included. Of 2,737 men and women with an incident AMI during the study period, all subjects with incomplete data on any of the covariables (n = 294) were excluded. Therefore the present analyses concerned 1,327 men and 415 women without DM and 505 men and 196 women with DM 25 to 74 years of age with an incident AMI. Informed consent was obtained from each patient and the study was approved by the appropriate ethics committee. End points used in this study were case fatality within 28 days and all-cause long-term mortality. Death certificates were obtained from local health departments. Continuous data were expressed as means and categorical variables as percentages. Chi-square test was used to test differences in prevalences. The t test was used to compare means. Distributions of length of hospital stay and peak creatinine phosphokinase levels were markedly skewed and therefore log-transformed in analyses where normality was required. Multiple logistic regression models were performed to assess the relation between known DM and 28-day case fatality. Significance at the 15% level in univariate analysis was used as the criterion for entry in the multivariable model. The first model included DM and age (continuously). The second model included age; any reperfusion therapy (yes/no); treatment with angiotensin-converting enzyme (ACE) inhibitor (yes/no), β blocker (yes/no), lipid-lowering drug (yes/no), and antiplatelets during hospital stay (yes/no); cardiac arrest before hospitalization (yes/no); and any complication during hospital stay (recurrent infarction or ventricular fibrillation or pulmonary edema). For investigation of the association between known DM and long-term mortality in 28-day surviving patients, relative risks were computed by Cox proportional hazards models. Proportional hazards assumption was valid for all factors used in Cox models shown by parallel lines of log(−log[event]) versus log of event times. Significance at the 15% level in univariate Cox proportional hazards analysis was used as the criterion for entry in the multivariable model. The first model included DM and age. The second model included age, any reperfusion therapy (yes/no), treatment with antiplatelets during hospital stay (yes/no), history of hypertension (yes/no), history of hyperlipidemia (yes/no), body mass index (BMI), cardiac arrest before hospitalization (yes/no), and any complication during hospital stay (recurrent infarction or ventricular fibrillation or pulmonary edema). Univariate survival analysis was performed using Kaplan-Meier curves. Comparisons between survival curves were performed using log-rank test. Results are presented as odds ratios or hazard ratios (HRs) and 95% confidence intervals (CIs). Significance tests were 2-tailed and p values <0.05 were accepted as statistically significant. All analyses were performed using SAS 9.1 (SAS Institute, Cary, North Carolina). There were 76 deaths of men without DM, 46 of men with DM men, 26 of women without DM, and 22 of women with DM within 28 days. Up to December 31, 2005 (median follow-up time 4.3 years) there were 199 deaths of men without DM and 122 of men with DM who survived 28 days; corresponding numbers in women were 58 and 62 deaths. Baseline characteristics of men and women according to DM status are listed in Table 1. Men and women with DM were significantly older, were more often hypertensive, were less often smokers, and had a significantly higher BMI than men and women without DM. In men and women no significant differences with regard to proportions of anterior infarction, cardiac arrest before admission, and history of lipid disorders between patients with and without DM could be observed.Table 1Clinical characteristics and in-hospital treatment of nondiabetic and diabetic men and women with incident acute myocardial infarctionMenWomenNo DMDMp ValueNo DMDMp Value(n = 1,327)(n = 505)(n = 415)(n = 196)Clinical characteristics Age (years)58.6 ± 10.261.8 ± 8.6<0.000162.6 ± 9.164.7 ± 8.00.006 Anterior wall infarction533 (40%)209 (41%)0.63200 (48%)97 (50%)0.76 Peak creatinine phosphokinase⁎Geometric mean ± geometric SD.448.7 ± 3.1401.3 ± 3.10.06371.6 ± 3.3324.2 ± 3.60.20 Cardiac arrest before hospitalization64 (5%)26 (5%)0.7718 (4%)11 (6%)0.49 Length of stay (days)⁎Geometric mean ± geometric SD.13.3 ± 1.915.1 ± 1.90.000113.6 ± 2.015.0 ± 2.10.11 Smoker543 (41%)155 (31%)<0.0001147 (35%)39 (20%)<0.0001 Hypertension813 (61%)388 (77%)<0.0001312 (75%)169 (86%)0.002 Lipid disorders989 (75%)365 (72%)0.33315 (76%)143 (73%)0.43 Body mass index (kg/m2)†Based on 1,670 men (1,226 without diabetes and 444 with diabetes) and 551 women (385 without diabetes and 166 with diabetes).26.8 ± 3.627.9 ± 4.6<0.000126.6 ± 5.029.1 ± 5.1<0.0001Treatment in hospital Percutaneous coronary intervention709 (53%)218 (43%)<0.0001195 (47%)67 (34%)0.003 Coronary artery bypass grafting206 (16%)91 (18%)0.2054 (13%)32 (16%)0.27 Thrombolysis376 (28%)120 (24%)0.05111 (27%)33 (17%)0.007 Any reperfusion therapy1,066 (80%)358 (71%)<0.0001297 (72%)118 (60%)0.005 β Blockers1,248 (94%)478 (95%)0.62391 (94%)181 (92%)0.38 Antiplatelets1,293 (97%)483 (96%)0.05402 (97%)187 (95%)0.37 Angiotensin-converting enzyme inhibitors999 (75%)412 (82%)0.004317 (76%)164 (84%)0.04 Lipid-lowering drug1,023 (77%)363 (72%)0.02316 (76%)140 (71%)0.21Recommended discharge medications‡Based on 28-day surviving patients (1,251 nondiabetic and 459 diabetic men and 389 nondiabetic and 174 diabetic women). β Blockers1,157 (93%)420 (92%)0.50363 (93%)164 (94%)0.67 Antiplatelets1,183 (95%)420 (92%)0.02364 (94%)158 (91%)0.24 Angiotensin-converting enzyme inhibitors797 (64%)342 (75%)<0.0001270 (69%)128 (74%)0.32 Lipid-lowering drug940 (75%)325 (71%)0.07291 (75%)125 (72%)0.46Data are expressed as mean ± SD or number of patients (percentage). Geometric mean ± geometric SD.† Based on 1,670 men (1,226 without diabetes and 444 with diabetes) and 551 women (385 without diabetes and 166 with diabetes).‡ Based on 28-day surviving patients (1,251 nondiabetic and 459 diabetic men and 389 nondiabetic and 174 diabetic women). Open table in a new tab Data are expressed as mean ± SD or number of patients (percentage). Treatment in men and women during hospital stay according to DM status is also presented in Table 1. During hospital stay, men and women with DM less likely received reperfusion therapy and more frequently were treated with ACE inhibitors. Although men with DM were less often treated with lipid-lowering drugs, there was no difference in treatment with lipid-lowering drugs in women with and without DM. At discharge, men with DM less often were recommended treatment with antiplatelets but more often with ACE inhibitors compared to men without DM, whereas there were no significant differences between women with DM and those without DM with regard to treatment recommendations. Frequency of major in-hospital complications cardiogenic shock and pulmonary edema was significantly higher in men with DM compared to men without DM. There were no significant differences with regard to complications during hospital stay between women with and without DM (Table 2).Table 2Complications during hospital stay in nondiabetic and diabetic men and womenVariableMenWomenNo DMDMp ValueNo DMDMp Value(n = 1,327)(n = 505)(n = 415)(n = 196)Ventricular fibrillation67 (5%)23 (5%)0.6617 (4%)11 (6%)0.40Cardiogenic shock45 (3%)36 (7%)0.00124 (6%)16 (8%)0.27Pulmonary edema33 (3%)27 (5%)0.00216 (4%)12 (6%)0.21Recurrent infarction47 (4%)22 (4%)0.4116 (4%)9 (5%)0.67Cardiac arrest in hospital136 (10%)68 (14%)0.0545 (11%)28 (14%)0.22Data are expressed as number of patients (percentage). Open table in a new tab Data are expressed as number of patients (percentage). As presented in Table 3, after adjustment for age DM in men or women was not significantly associated with 28-day case fatality. Compared to subjects without DM the age-adjusted odds ratios of 28-day case fatality associated with DM were 1.43 (0.97 to 2.10) for men and 1.69 (0.93 to 3.09) for women (model 1). Multivariable adjustment attenuated the association in men and women. In analyses of the entire study sample, p value for the interaction between gender and DM in the multivariable model was 0.9730.Table 3Risk of 28-day case fatality and long-term mortality in diabetic men and women with incident myocardial infarctionMenWomen28-day case fatality, OR (95% CI) Model 1⁎Model 1 adjusted for age.1.43 (0.97–2.10)1.69 (0.93–3.09) Model 2†Model 2 adjusted for age; reperfusion therapy; treatment with angiotensin-converting enzyme inhibitor, β blocker, lipid-lowering drug, and antiplatelets during hospital stay; cardiac arrest before hospitalization; and complications in hospital (recurrent infarction or ventricular fibrillation or pulmonary edema).1.45 (0.90–2.34)1.44 (0.66–3.15)Long-term mortality, HR (95% CI) Model 1⁎Model 1 adjusted for age.1.57 (1.18–2.10)2.91 (1.82–4.65) Model 2‡Model 2 adjusted for age, reperfusion therapy, treatment with antiplatelets during hospital stay, history of hypertension, cardiac arrest before hospitalization, history of hyperlipidemia, body mass index, and complications in hospital (recurrent infarction or ventricular fibrillation or pulmonary edema).1.36 (1.00–1.85)2.56 (1.53–4.27)OR = odds ratio. Model 1 adjusted for age.† Model 2 adjusted for age; reperfusion therapy; treatment with angiotensin-converting enzyme inhibitor, β blocker, lipid-lowering drug, and antiplatelets during hospital stay; cardiac arrest before hospitalization; and complications in hospital (recurrent infarction or ventricular fibrillation or pulmonary edema).‡ Model 2 adjusted for age, reperfusion therapy, treatment with antiplatelets during hospital stay, history of hypertension, cardiac arrest before hospitalization, history of hyperlipidemia, body mass index, and complications in hospital (recurrent infarction or ventricular fibrillation or pulmonary edema). Open table in a new tab OR = odds ratio. As presented in Table 3, of the 28-day surviving patients DM was strongly associated with long-term all-cause mortality in men and women—particularly in women—in age-adjusted analysis. After multivariable adjustment (model 2) the association in women remained highly significant (HR 2.56, 95% CI 1.53 to 4.27); however, in men it became borderline significant (HR 1.36, 95% CI 1.00 to 1.85). In analyses of the entire study sample, p value for the interaction between gender and DM was 0.0256 in the multivariable adjusted model. Figure 1 presents Kaplan-Meier curves for long-term mortality by DM status for men and women. Men and women without DM had an almost identical survival rate over the follow-up period. However, men and women with DM had a significantly lower survival rate compared to subjects without DM (p 2.5-fold higher risk for long-term mortality even after multivariable adjustment. Results from previous studies regarding differences in mortality between men and women with DM and those without DM and AMI are conflicting. The results of the present study including patients treated with modern therapy are in accordance with previous studies mainly conducted in the era before reperfusion, which also found no gender differences regarding the association between DM and short-term mortality.4Vaccarino V. Parsons L. Every N.R. Barron H.V. Krumholz H.M. Impact of history of diabetes mellitus on hospital mortality in men and women with first acute myocardial infarction The National Registry of Myocardial Infarction 2 participants.Am J Cardiol. 2000; 85: 1486-1489Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 5Koek H.L. Soedamah-Muthu S.S. Kardaun J.W. Gevers E. de Bruin A. Reitsma J.B. Bots M.L. Grobbee D.E. Short- and long-term mortality after acute myocardial infarction: comparison of patients with and without diabetes mellitus.Eur J Epidemiol. 2007; 22: 883-888Crossref PubMed Scopus (46) Google Scholar, 6Behar S. Boyko V. Reicher-Reiss H. Goldbourt U. Ten-year survival after acute myocardial infarction: comparison of patients with and without diabetes.Am Heart J. 1997; 133: 290-296Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar However, other studies showed higher early mortality only in women with DM7Miettinen H. Lehto S. Salomaa V. Mahonen M. Niemela M. Haffner S.M. Pyorala K. Tuomilehto J. Impact of diabetes on mortality after the first myocardial infarction The FINMONICA myocardial infarction register study group.Diabetes Care. 1998; 21: 69-75Crossref PubMed Scopus (610) Google Scholar, 8Maier B. Thimme W. Kallischnigg G. Graf-Bothe C. Rohnisch J.U. Hegenbarth C. Theres H. Berlin Myocardial Infarction RegistryDoes diabetes mellitus explain the higher hospital mortality of women with acute myocardial infarction? Results from the Berlin Myocardial Infarction Registry.J Investig Med. 2006; 54: 143-151Crossref PubMed Scopus (16) Google Scholar, 9Chun B.Y. Dobson A.J. Heller R.F. The impact of diabetes on survival among patients with first myocardial infarction.Diabetes Care. 1997; 20: 704-708Crossref PubMed Scopus (91) Google Scholar or a stronger effect of DM on short-term mortality in men.10Cooper R.S. Pacold I.V. Ford E.S. Age-related differences in case-fatality rates among diabetic patients with myocardial infarction.Diabetes Care. 1991; 14: 903-908Crossref PubMed Scopus (30) Google Scholar In addition, further studies reported a weak association between DM and short-term mortality after an AMI in men or women.11Donahue R.P. Goldberg R.J. Chen Z. Gore J.M. Alpert J.S. The influence of sex and diabetes mellitus on survival following acute myocardial infarction: a community-wide perspective.J Clin Epidemiol. 1993; 46: 245-252Abstract Full Text PDF PubMed Scopus (78) Google Scholar Discrepancies between these former studies and the present study may be due to different causes. Previous studies did not identify first AMI, and so the index AMI may represent a recurrent event. Recurrent events are more frequent in patients with DM, especially in women,12Lundberg V. Stegmayr B. Asplund K. Eliasson M. Huhtasaari F. Diabetes as a risk factor for myocardial infarction: population and gender perspectives.J Intern Med. 1997; 241: 485-492Crossref PubMed Scopus (116) Google Scholar leading to the higher mortality in women with DM observed in some studies. Furthermore, differences in study design, case definition, and study population may have contributed to discrepancies among studies. Although a large percentage of men and women in the present study were treated with invasive therapy, an increased risk of long-term mortality for patients with DM compared to those without DM was found. This was particularly true for women with DM. Weitzman et al13Weitzman S. Wang C. Rosamond W.D. Chambless L.E. Cooper L.S. Shahar E. Goff D.C. Is diabetes an independent risk factor for mortality after myocardial infarction? The ARIC (Atherosclerosis Risk in Communities) Surveillance Study.Acta Diabetol. 2004; 41: 77-83Crossref PubMed Scopus (10) Google Scholar reported a significantly higher 1-year mortality in men with DM (odds ratio 1.5, 95% CI 1.2 to 1.9) but no significant association in women. Data from the Onset Study, conducted from 1989 to 1994, showed that women with DM had a significantly higher risk to die during a mean follow-up of 3.7 years (HR 2.7, 95% CI 1.8 to 4.2); the corresponding HR in men with DM was 1.3 (95% CI 1.0 to 1.8).14Mukamal K.J. Nesto R.W. Cohen M.C. Muller J.E. Maclure M. Sherwood J.B. Mittleman M.A. Impact of diabetes on long-term survival after acute myocardial infarction.Diabetes Care. 2001; 24: 1422-1427Crossref PubMed Scopus (209) Google Scholar Our finding that DM is associated with a greater risk of long-term mortality particularly in women after AMI is in accordance with other previous studies conducted in the era before reperfusion.11Donahue R.P. Goldberg R.J. Chen Z. Gore J.M. Alpert J.S. The influence of sex and diabetes mellitus on survival following acute myocardial infarction: a community-wide perspective.J Clin Epidemiol. 1993; 46: 245-252Abstract Full Text PDF PubMed Scopus (78) Google Scholar, 15Abbott R.D. Donahue R.P. Kannel W.B. Wilson P.W. The impact of diabetes on survival following myocardial infarction in men vs women: the Framingham Study.JAMA. 1988; 260: 3456-3460Crossref PubMed Scopus (407) Google Scholar, 16Benderly M. Behar S. Reicher-Reiss H. Boyko V. Goldbourt U. Long-term prognosis of women after myocardial infarction SPRINT Study Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial.Am J Epidemiol. 1997; 146: 153-160Crossref PubMed Scopus (26) Google Scholar The strongly increased risk of dying during follow-up in women with DM in our study may be related to older age and a risk factor burden that was already higher at admission than that in men with DM. Compared to men with DM, women with DM and AMI more frequently had hypertension and a higher mean BMI at admission. Another possibility that may contribute to the poorer prognosis in women with DM may be that they were less frequently treated with any reperfusion therapy during hospital stay. There may be other factors responsible for the increased long-term mortality risk in women. For example, results from the 34-year follow-up of the Framingham Study showed that DM doubled the risk of recurrent AMI in women but not in men. In addition, type of acute coronary syndrome could account for different prognoses between men and women with AMI. Marrugat et al17Marrugat J. Garcia M. Elosua R. Aldasoro E. Tormo M.J. Zurriaga O. Aros F. Masia R. Sanz G. Valle V. De Sa E.L. Sala J. Segura A. Rubert C. Moreno C. Cabades A. Molina L. Lopez-Sendon J.L. Gil M. IBERICA, PRIAMHO, RESCATE, PEPA, and REGICOR InvestigatorsShort-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).Am J Cardiol. 2004; 94: 1161-1165Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar showed that mortality rates were higher in women with first Q-wave AMI but not in other patients. Furthermore, women with DM more frequently developed heart failure compared to women without DM.15Abbott R.D. Donahue R.P. Kannel W.B. Wilson P.W. The impact of diabetes on survival following myocardial infarction in men vs women: the Framingham Study.JAMA. 1988; 260: 3456-3460Crossref PubMed Scopus (407) Google Scholar Further studies are needed to investigate the underlying basis for gender differences in long-term mortality risk from DM after AMI. The present study has several limitations that need to be considered. Diagnosis of DM was made from self-report and review of data contained in medical records. A previous study showed that many patients with AMI have unrecognized DM at time of hospital admission.18Sala J. Masia R. Gonzalez de Molina F.J. Fernandez-Real J.M. Gil M. Bosch D. Ricart W. Senti M. Marrugat J. REGICOR Investigators Short-term mortality of myocardial infarction patients with diabetes or hyperglycaemia during admission.J Epidemiol Community Health. 2002; 56: 707-712Crossref PubMed Scopus (80) Google Scholar Furthermore, hyperglycemia on admission was found to be associated with higher short-term mortality regardless of previous diagnosis of DM.18Sala J. Masia R. Gonzalez de Molina F.J. Fernandez-Real J.M. Gil M. Bosch D. Ricart W. Senti M. Marrugat J. REGICOR Investigators Short-term mortality of myocardial infarction patients with diabetes or hyperglycaemia during admission.J Epidemiol Community Health. 2002; 56: 707-712Crossref PubMed Scopus (80) Google Scholar It was not possible to identify patients with undetected DM or impaired glucose tolerance or to take admission glucose into account in the present study. A further limitation is that only all-cause mortality was considered. Readmission for nonfatal recurrences (e.g., recurrent AMI or unstable angina pectoris) would have been important because DM and female gender are known to be related to these types of end points. Also, no information on cause-specific mortality was available in the present study. Although we adjusted for a variety of risk factors, residual confounding by unmeasured factors cannot be excluded. We studied 25- to 74-year-old German patients with AMI only and thus results might not be generalizable to other populations and age groups. Strengths of the present study are its population-based design, including all consecutive unselected patients of a general population presenting with an incident AMI registered according to a standardized protocol. Therefore, our population represents a real-world cross section of patients who have had a first AMI.
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