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.
Methods
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. 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. 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. Since January 1, 2001, all patients with AMI diagnosed according to European Society of Cardiology and American College of Cardiology criteria have been included.
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).
Results
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.
| Men | Women | |||||
|---|---|---|---|---|---|---|
| No DM | DM | p Value | No DM | DM | p Value | |
| (n = 1,327) | (n = 505) | (n = 415) | (n = 196) | |||
| Clinical characteristics | ||||||
| Age (years) | 58.6 ± 10.2 | 61.8 ± 8.6 | <0.0001 | 62.6 ± 9.1 | 64.7 ± 8.0 | 0.006 |
| Anterior wall infarction | 533 (40%) | 209 (41%) | 0.63 | 200 (48%) | 97 (50%) | 0.76 |
| Peak creatinine phosphokinase ⁎ | 448.7 ± 3.1 | 401.3 ± 3.1 | 0.06 | 371.6 ± 3.3 | 324.2 ± 3.6 | 0.20 |
| Cardiac arrest before hospitalization | 64 (5%) | 26 (5%) | 0.77 | 18 (4%) | 11 (6%) | 0.49 |
| Length of stay (days) ⁎ | 13.3 ± 1.9 | 15.1 ± 1.9 | 0.0001 | 13.6 ± 2.0 | 15.0 ± 2.1 | 0.11 |
| Smoker | 543 (41%) | 155 (31%) | <0.0001 | 147 (35%) | 39 (20%) | <0.0001 |
| Hypertension | 813 (61%) | 388 (77%) | <0.0001 | 312 (75%) | 169 (86%) | 0.002 |
| Lipid disorders | 989 (75%) | 365 (72%) | 0.33 | 315 (76%) | 143 (73%) | 0.43 |
| Body mass index (kg/m 2 ) † | 26.8 ± 3.6 | 27.9 ± 4.6 | <0.0001 | 26.6 ± 5.0 | 29.1 ± 5.1 | <0.0001 |
| Treatment in hospital | ||||||
| Percutaneous coronary intervention | 709 (53%) | 218 (43%) | <0.0001 | 195 (47%) | 67 (34%) | 0.003 |
| Coronary artery bypass grafting | 206 (16%) | 91 (18%) | 0.20 | 54 (13%) | 32 (16%) | 0.27 |
| Thrombolysis | 376 (28%) | 120 (24%) | 0.05 | 111 (27%) | 33 (17%) | 0.007 |
| Any reperfusion therapy | 1,066 (80%) | 358 (71%) | <0.0001 | 297 (72%) | 118 (60%) | 0.005 |
| β Blockers | 1,248 (94%) | 478 (95%) | 0.62 | 391 (94%) | 181 (92%) | 0.38 |
| Antiplatelets | 1,293 (97%) | 483 (96%) | 0.05 | 402 (97%) | 187 (95%) | 0.37 |
| Angiotensin-converting enzyme inhibitors | 999 (75%) | 412 (82%) | 0.004 | 317 (76%) | 164 (84%) | 0.04 |
| Lipid-lowering drug | 1,023 (77%) | 363 (72%) | 0.02 | 316 (76%) | 140 (71%) | 0.21 |
| Recommended discharge medications ‡ | ||||||
| β Blockers | 1,157 (93%) | 420 (92%) | 0.50 | 363 (93%) | 164 (94%) | 0.67 |
| Antiplatelets | 1,183 (95%) | 420 (92%) | 0.02 | 364 (94%) | 158 (91%) | 0.24 |
| Angiotensin-converting enzyme inhibitors | 797 (64%) | 342 (75%) | <0.0001 | 270 (69%) | 128 (74%) | 0.32 |
| Lipid-lowering drug | 940 (75%) | 325 (71%) | 0.07 | 291 (75%) | 125 (72%) | 0.46 |
⁎ 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).
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 ).
| Variable | Men | Women | ||||
|---|---|---|---|---|---|---|
| No DM | DM | p Value | No DM | DM | p Value | |
| (n = 1,327) | (n = 505) | (n = 415) | (n = 196) | |||
| Ventricular fibrillation | 67 (5%) | 23 (5%) | 0.66 | 17 (4%) | 11 (6%) | 0.40 |
| Cardiogenic shock | 45 (3%) | 36 (7%) | 0.001 | 24 (6%) | 16 (8%) | 0.27 |
| Pulmonary edema | 33 (3%) | 27 (5%) | 0.002 | 16 (4%) | 12 (6%) | 0.21 |
| Recurrent infarction | 47 (4%) | 22 (4%) | 0.41 | 16 (4%) | 9 (5%) | 0.67 |
| Cardiac arrest in hospital | 136 (10%) | 68 (14%) | 0.05 | 45 (11%) | 28 (14%) | 0.22 |
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