Summary
Background
Gender differences in presentation, management and outcome in patients with ST-segment elevation myocardial infarction (STEMI) have been reported.
Aim
To determine whether female gender is associated with higher inhospital mortality.
Methods
Data from ORBI, a regional STEMI registry of 5 years’ standing, were analysed. The main data on presentation, management, inhospital outcome and prescription at discharge were compared between genders. Various adjusted hazard ratios were then calculated for inhospital mortality (women versus men).
Results
The analysis included 5000 patients (mean age 62.6 ± 13 years), with 1174 women (23.5%). Women were on average 8 years older than men, with more frequent co-morbidities. Median ischaemia time was 215 minutes (26 minutes longer in women; P < 0.05). Reperfusion strategies in women less frequently involved fibrinolysis, coronary angiography, radial access and thrombo-aspiration. Female gender, especially in patients aged < 60 years, was associated with poorer inhospital prognosis (including higher inhospital mortality: 9% vs. 4% in men; P < 0.0001), and underutilization of recommended treatments at discharge. Moreover, excess female inhospital mortality was independent of presentation, revascularization time and reperfusion strategy (hazard ratio for women 1.33, 95% confidence interval 1.01–1.76; P = 0.04).
Conclusions
One in four patients admitted for STEMI was female, with significant differences in presentation. Female gender was associated with less-optimal treatment, both in the acute-phase and at discharge. Efforts should be made to reduce these differences, especially as female gender was independently associated with an elevated risk of inhospital mortality.
Résumé
Contexte
Des différences liées au sexe sont signalées dans la présentation, la gestion et le pronostic des patients hospitalisés pour infarctus du myocarde avec élévation du segment ST (IDM ST+).
Objectif
Déterminer si le sexe féminin est associé à une mortalité intra-hospitalière plus élevée.
Méthodes
Nous avons analysé les données d’ORBI, un registre régional de 5 ans concernant les IDM ST+. Les principales données concernant la présentation, la gestion, le devenir intra-hospitalier et le traitement à la sortie ont été comparées en fonction du sexe. Ensuite, nous avons analysé la mortalité intra-hospitalière (femmes vs hommes), avec différentes variables d’ajustement.
Résultats
L’analyse a inclus 5000 patients (âge moyen 62,6 ± 13 ans), dont 1174 femmes (23,5 %), qui présentaient des co-morbidités plus fréquentes et étaient 8 ans plus âgées que les hommes. Le temps d’ischémie médian était de 215 minutes (26 minutes de plus chez les femmes). Comparativement aux hommes, les stratégies de reperfusion chez les femmes comportaient moins de fibrinolyse, de coronarographie, d’accès radial et de thrombo-aspiration. Le sexe féminin, en particulier chez les moins de 60 ans, était associée à un mauvais pronostic intra-hospitalier (y compris une plus forte mortalité intra-hospitalière : 9 % contre 4 % chez les hommes ; p < 0,0001), et une sous-utilisation des traitements recommandés à la sortie. Par ailleurs, la surmortalité intra-hospitalière observée chez les femmes était indépendante de la présentation, des délais de revascularisation et des stratégies de reperfusion ( hasard ratio 1,33, intervalle de confiance 95 % 1,01–1,76 ; p = 0,04).
Conclusions
Une personne sur 4 patients admis pour un IDM ST+ est une femme, avec des différences significatives dans la présentation. Le sexe féminin est associé à un traitement moins optimal, tant à la phase aiguë qu’à la sortie d’hôpital. Un effort particulier devra être effectué afin de réduire ces différences, d’autant plus que le sexe féminin semble constituer dans cette analyse un risque indépendant de surmortalité intra-hospitalière.
Background
Several studies have reported increased inhospital mortality in myocardial infarction (MI) with persistent ST-segment elevation (STEMI) in women when compared with men . Several hypotheses have been put forward to account for this excess female mortality, including more serious co-morbidity, longer time to revascularization or use of ‘less-optimal’ reperfusion strategies. It is, however, not yet clearly established whether female gender is in itself a risk factor for inhospital death in the case of STEMI. The present study is an update on gender-linked differences in the characteristics, means of treatment, mortality and inhospital prognosis of patients admitted for STEMI.
Methods
We used the data from the Brittany Regional Infarction Observatory (Observatoire Régional Breton sur l’Infarctus: ORBI) . Brittany is an administrative Region with a population of 3.2 million and nine interventional cardiology centres (see list in Appendix A ), covering an area of 34,023 km 2 . ORBI prospectively includes all patients admitted to any of the nine centres for STEMI (final diagnosis) within 24 hours of symptom onset. Demographic and electrocardiographic data, treatments, time intervals and inhospital events are recorded prospectively. Overall ischaemia time is defined as the time between symptom onset and initiation of reperfusion: balloon inflation, in the case of primary angioplasty, or administration of fibrinolytic treatment. All patients registered by ORBI between 01 July 2006 and 31 August 2011 were included in the present analysis.
Statistical analysis
Qualitative data are expressed as percentages and quantitative data as means ± standard deviations, except for times, which are expressed as medians (range). Multiple imputation was performed to take into account missing data . As a first step, univariate analysis according to gender, clinical characteristics, time to revascularization, revascularization strategy, inhospital prognosis and discharge prescription was performed. Student’s (or Wilcoxon’s, as appropriate) and Chi 2 tests were used for quantitative and qualitative data, respectively. In a second step, inhospital mortality was analysed according to gender, using a Cox model. The association is presented as a hazard ratio (HR) (95% confidence interval [CI]). Various models were constructed according to adjustment strategy: model 1, unadjusted; model 2, adjusted for patient characteristics (age, diabetes, arterial hypertension, active smoking, anterior STEMI location, three-vessel or common left main coronary disease); model 3, adjusted for the variables of model 2 and for overall ischaemia time; and model 4, adjusted for the variables of model 3 and for revascularization variables (coronary angiography, primary angioplasty, radial arterial approach, thrombo-aspiration, glycoprotein IIb/IIIa inhibitor administration, fibrinolysis).
The significance threshold was systematically set at 5%. Statistical analysis used SAS ® software, version 9.1 (SAS Institute Inc., Cary, NC, USA).
Results
Over the study period, 5000 patients (mean age 62.6 ± 13 years) were included in ORBI; 1174 (23.5%) were female. The main patient characteristics, coronary disease and MI data are presented according to gender in Table 1 . Emergency myocardial revascularization was performed in 4344 patients (87%): 3583 (71%) by primary angioplasty and 761 (15%) by fibrinolysis.
| Male ( n = 3826) | Female ( n = 1174) | P | |
|---|---|---|---|
| Age (years) | 60.8 ± 12 | 68.8 ± 14 | < 0.001 |
| Arterial hypertension | 1377 (36) | 634 (54) | < 0.001 |
| Dyslipidaemia | 1989 (52) | 528 (45) | < 0.001 |
| Diabetes | 420 (11) | 152 (13) | 0.06 |
| Active smoking | 1568 (41) | 305 (26) | < 0.001 |
| Body mass index (kg/m 2 ) | 26.8 ± 3 | 25.5 ± 5 | < 0.001 |
| Known coronary disease | 734 (19) | 208 (18) | 0.2 |
| History of myocardial infarction | 306 (8) | 47 (4) | < 0.001 |
| Anterior STEMI location | 1606 (42) | 537 (45) | 0.02 |
| Three-vessel or common left main coronary disease | 700 (18) | 183 (15) | 0.03 |
| Killip class III or IV at admission | 182 (5) | 92 (8) | < 0.001 |
The initial emergency call was made using the dedicated emergency telephone number 15 (emergency medicalized ambulance service [Service d’Aide Médicale Urgente ; SAMU]) for 40% of female versus 44% of male patients ( P = 0.004). Electrocardiography, when performed before hospital admission, showed significant ST-segment elevation in 88% of female versus 95% of male patients ( P = 0.03). The SAMU provided preadmission treatment in 55% of female versus 61% of male patients ( P < 0.001). Finally, direct access to the catheterization laboratory in the case of primary angioplasty was available for 57% of female versus 66% of male patients ( P < 0.0001).
Median overall ischaemia time was 215 minutes (63–1530 minutes) and was significantly longer for female patients (235 vs. 209 minutes for male patients; P < 0.05), with delayed treatment at all stages: median pain onset-to-call time, 60 vs. 44 minutes ( P < 0.0001); call-to-door, 130 vs. 125 minutes ( P < 0.05); and door-to-balloon (or thrombo-aspiration) in primary angioplasty, 45 vs. 40 minutes ( P < 0.05). Thus, the median time from first medical contact to balloon inflation or thrombo-aspiration was 95 minutes: 100 minutes in female versus 94 minutes in male patients ( P < 0.05), and < 120 minutes in 65% of female versus 72% of male patients ( P < 0.0001). Table 2 presents revascularization strategies according to gender, showing lower rates of use of the various reperfusion techniques in women.
| Male ( n = 3826) | Female ( n = 1174) | P | |
|---|---|---|---|
| Primary strategy | |||
| Fibrinolysis | 618 (16) | 143 (12) | 0.0009 |
| Primary angioplasty | 2754 (72) | 829 (70) | 0.36 |
| No acute-phase reperfusion | 454 (12) | 203 (18) | < 0.0001 |
| No acute-phase coronary angiography | 229 (6) | 107 (9) | |
| Acute-phase coronary angiography without angioplasty | 178 (5) | 90 (8) | |
| Acute-phase coronary angiography with delayed angioplasty | 47 (1) | 5 (< 1) | |
| Glycoprotein IIb/IIIa inhibitor | 2269 (59) | 628 (53) | 0.0004 |
| Coronary angiography (at admission or otherwise) | 3772 (98) | 1122 (95) | < 0.0001 |
| Radial approach a | 1348 (51) | 303 (40) | < 0.0001 |
| Thrombo-aspiration b | 1433 (52) | 388 (46) | < 0.0001 |
| Stent b | 2188 (79) | 649 (78) | 0.4 |
| Drug-eluting stent b | 319 (12) | 99 (12) | 0.8 |
| TIMI 3 flow (spontaneous, after fibrinolysis or at end of angioplasty) c | 2555 (91) | 758 (82) | 0.02 |
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