Treatment and outcome in acute myocardial infarction in a community in relation to gender

International Journal of Cardiology 135 (2009) 315 – 322 www.elsevier.com/locate/ijcard

Treatment and outcome in acute myocardial infarction in a community in relation to gender Johan Herlitz a,⁎, Mikael Dellborg b , Thomas Karlsson a , Maria Haglid Evander a , Marianne Hartford a,e , Elisabeth Perers a , Kenneth Caidahl c,d a b

Institute of Medicine, Department of Molecular and Clinical Medicine/Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden Institute of Medicine, Department of Emergency and Cardiovascular Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden c Clinical Physiology, Sahlgrenska University Hospital, Göteborg, Sweden d Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden e AstraZeneca R&D, Mölndal, Sweden Received 2 October 2007; received in revised form 11 March 2008; accepted 29 March 2008 Available online 10 July 2008

Abstract Aim: To describe treatment and outcome in all patients in a community with acute myocardial infarction (AMI) in relation to gender. Methods: All patients discharged from hospital between 2001 and 2002 in Göteborg, Sweden, with a diagnosis of AMI underwent a survey to find possible gender differences. All p-values are age adjusted. Results: Among 1423 admissions, women comprised 41% and were older than men (mean 79 versus mean 72 years). Women were admitted to a coronary care unit less frequently than men (49% versus 67%; p = 0.005). Women underwent coronary angiography less frequently (21% versus 40%; p = 0.02). Percutaneous coronary intervention (PCI) was performed in 10% of the women and 18% of the men (p = 0.36). Coronary artery bypass grafting (CABG) was performed in 2% of the women and in 9% of the men (p b 0.0001). Female gender was associated with a lower risk of reinfarction during first year after hospital discharge (12% versus 16%; p = 0.003). The cumulative three-year mortality was 49% in women and 41% in men. However, when adjusting for age, admittance to CCU, coronary angiography and coronary revascularisation, risk of death during 3 years was lower in women than men (odds ratio 0.72; 95% confidence interval 0.60–0.85; p = 0.0001). Conclusion: In the community of Göteborg women (mean age 79 years) with AMI are prioritised differently than men (mean age 72 years), prior to admission to a CCU. This results in a less invasive strategy in women, particularly with regard to CABG. When adjusting for difference in age, admittance to CCU and coronary revascularisation female gender was associated with a low risk of death during the subsequent 3 years. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Acute myocardial infarction; Gender; Prognosis

1. Introduction There is an ongoing debate about the gender perspective in the treatment and outcome of patients who suffer from acute myocardial infarction (AMI). A number of studies

⁎ Corresponding author. Tel.: +46 31 342 1000. E-mail address: [email protected] (J. Herlitz). 0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.03.065

have suggested that women are given lower priority than men in various respects [1–5] and that this might jeopardise the outcome for women. The clinical benefit of an invasive strategy is also less marked in women. In fact, a more aggressive revascularisation policy has not been shown to confer any benefit in women with unstable coronary artery disease, as opposed to the situation in men [6,7]. However, recent data indicate that, among patients below 80 years of age who reach the coronary care unit and fulfil

316

J. Herlitz et al. / International Journal of Cardiology 135 (2009) 315–322

the criteria for acute coronary syndrome, there is no marked gender difference in the allocation of therapeutic resources [8]. As the current study did not include patients older than 80 years of age or patients suffering from AMI who did not reach the CCU, the situation in these groups is unknown. The present survey aims to bridge the gap in knowledge by evaluating the treatment strategies and outcome among all patients in the Municipality of Göteborg, Sweden, who were discharged from hospital with a diagnosis of AMI (dead or alive), in relation to gender. 2. Material and methods 2.1. Place of study Göteborg is the second largest city in Sweden. In 2002, Göteborg had a population of 475,000 inhabitants. The total population in Sweden at this time was 8,940,000 million people. There are two large hospitals in the city, one with and one without facilities for revascularisation. 2.2. Patients All the patients were screened from the diagnosis register at the two city hospitals. All the patients in the municipality are admitted to one of these two hospitals. All the patients who were given a discharge diagnosis of acute myocardial infarction or unstable angina pectoris were evaluated for inclusion. 2.3. Inclusion criteria The following three conditions had to be met: 1. Living in the city of Göteborg 2. Hospitalised alive at one of the two city hospitals in Göteborg between 1 July 2001 and 30 June 2002 3. Given a discharge diagnosis of either acute myocardial infarction or unstable angina pectoris in combination with the elevation of a biochemical marker of myocardial necrosis (CKMB N 5 µg/l or troponin T N 0.05 µg/l or an equivalent rise in troponin I).

Previous myocardial infarction: documented previous infarction or previous silent myocardial infarction according to ECG Previous angina pectoris: angina pectoris with a duration of three weeks or more prior to the actual hospitalisation Peripheral vessel disease: (any of the following were included) Claudicatio intermittens, peripheral bypass surgery, abdominal or thoracic aortic aneurysm, carotid stenosis or previous carotid endarterectomy, previous peripheral vessel angioplasty, extremity gangrene, acute artery insufficiency, any non-invasive or invasive vascular study documenting peripheral vessel disease Cerebrovascular disease: a history of a transitory ischemic attack (TIA) or stroke TIA: a neurological deficit with a duration of less than 24 h with a total regression Stroke with minor residual deficit: permanent neurological defect caused by cerebrovascular disease but not function limiting Stroke with major residual deficit: patients with a permanent neurological defect caused by cerebrovascular disease limiting normal function. Connective tissue disease: such as systematic lupus erythematosus disseminatus, scleroderma, dermatomyositis, rheumatic diseases etc. Renal disease: known previous renal disease or a creatinine value of more than 375 mMol/l. 2.6. Complications in hospital Congestive heart failure: according to physician's diagnosis Cardiogenic shock: cardiogenic shock was regarded as being present if any of the following three criteria was met: 1. Systolic blood pressure below 80 mm Hg in the ambulance or on admission to hospital 2. If cardiogenic shock was mentioned in the case record forms 3. If patients required inotropic medication in order to maintain systolic blood pressure above 80 mm Hg. 2.7. In-hospital events

2.4. Exclusion criteria

2.5. Definitions

Hypotension: systolic blood pressure below 80 mm Hg on two occasions or more with at least a five-minute interval or need for an aortic balloon pump or inotropic medication due to hemodynamic instability.

No suspicion of heart attack on admission: this included elective admissions and patients who were admitted to a hospital ward due to a preliminary diagnosis other than heart attack. Previous history of: Current smoking: regular smoking or stopped smoking less than 30 days prior to hospital admission

2.7.1. Arrhythmias and ECG criteria Sinus bradycardia: below 60 beats/min Sinus tachycardia: N 100 beats/min High-degree AV block: AV block II (Mobitz Type II or AV block III) Ventricular tachycardia was recorded if noted in the case record form.

None.

J. Herlitz et al. / International Journal of Cardiology 135 (2009) 315–322

The presence of arrhythmias, sinus bradycardia, sinus tachycardia and high-degree AV block (Mobitz Type II and third-degree AV block) was identified through ECG abstraction, a review of telemetry and a review of nursing and physician documentation. ST elevation was defined as the presence of ≥ 2 mm ST elevation in leads V1 or V2 or ≥ 1 mm ST elevation in two continuous leads (I, II, III, aVL, aVF, V3, V4, V5 and V6). 2.8. Definitions of ECG localisation Anterior leads: V2–V4 Inferior leads: II, III or aVF Lateral leads: I, aVL, V5, V6

317

adjusted for age. For long-term mortality analysis, the Kaplan–Meier method was used for unadjusted mortality estimation and the Cox proportional hazards model for calculations of age-adjusted hazard ratio. Only the first admission for those individuals with multiple admissions during the study period was included in the analyses of mortality and morbidity after discharge; otherwise all admissions were included in the analyses. All p-values are two sided and, due to the large number of comparisons, they are considered significant if below 0.01. 2.10. Results A total of 1423 admissions fulfilled the inclusion criteria. The proportion of women was 41% (n = 588).

2.9. Statistical methods 2.11. Age and previous history Unless otherwise stated, all p-values are age adjusted, using logistic regression for dichotomous variables and a stratumadjusted Kruskal–Wallis test for continuous variables. All proportions/means are presented as crude results, i.e. not

Women were significantly older than men. They tended to have a higher prevalence of previous hypertension. On the other hand, they had a lower prevalence of previous myocardial

Table 1 Age and previous history.

Age (mean ± SD; years) Past medical history (%) Risk factors for AMI Hypertension On medication Diabetes Smoking at the time of arrival Previous heart disease Acute myocardial infarction Angina pectoris Cardiac arrest CABG PCI Congestive heart failure Atrial fibrillation Other vascular disease Peripheral vascular disease Cerebrovascular disease Transitory ischemic attack Stroke with no residual deficit Stroke with minor residual deficit Stroke with major residual deficit Stroke but uncertain about deficit Other disease Chronic obstructive pulmonary disease Connective tissue disease Liver disease Non-metastatic tumour Metastatic tumour Renal disease Ulcer disease Paralysis

Women (n = 588)

Men (n = 835)

p⁎

79.2 ± 10.2

72.7 ± 12.5

b0.0001

56 53 a 21 16 b

46 43 24 22 a

0.01 0.01

33 44 a b1 7 5 34 20

42 43 a 1 10 7 32 20

b0.0001

12 a 22 a 7a 7a 5a 2a b1 a

17 18 4 6 5 3 b1

0.001

12 4 b1 a 8a 4a 5a 10 3a

10 2 1 10 6 11 14 3

⁎ All p-values (except for age) are age adjusted and denoted if b0.10. ⁎⁎ More among men. a 1–5% missing information. b 5–10% missing information.

0.06 0.32 0.02 ⁎⁎ 0.02 ⁎⁎

0.03 0.07 0.04 b0.0001 0.03

318

J. Herlitz et al. / International Journal of Cardiology 135 (2009) 315–322

infarction, peripheral vascular disease and renal disease (Table 1).

Table 3 Initial ECG changes and arrhythmias. Women (n = 588)

2.12. Presentation There were no major differences between genders. Women tended to have more elevated blood pressure and heart rate on admission to hospital (Table 2). 2.13. Initial ECG changes and arrhythmias We did not observe any major differences between genders in terms of ECG changes or arrhythmias. However, women had a lower frequency of right bundle branch block and tended to have a lower frequency of left bundle branch block on admission to hospital (Table 3). 2.14. In-hospital procedures and events A much lower percentage of women than men were admitted to the CCU. Among patients with ST elevation, 66% of women and 79% of men (p = 0.92) were admitted to the CCU. A coronary angiography tended to be performed less frequently among women. Treatment with PCI did not differ significantly between men and women, but CABG was less frequently performed in women, among patients with Table 2 Presentation. Women (n = 588) Elective admission (%) Admitted for reason other than a heart attack (%) Originating location (%) Emergency department in the hospital Emergency department in other hospital Ward in other hospital Mobile coronary care unit Other ward within the hospital Other Transport by ambulance (%) Symptoms (%) Chest pain/pressure/discomfort Loss of consciousness Pulmonary oedema or cardiogenic shock Other at presentation (%) First recorded SBP b100 mm Hg First recorded SBP N180 mm Hg First recorded HR b60 beats/min First recorded HR N100 beats/min Cardiogenic shock Congestive heart failure

Men (n = 835)

1 23

2 18

94

90

b1

b1

b1 1 3 b1 84 a

b1 3 4 b1 78 b

84 c 6c 6

90 c 7c 7

8c 16 c 8c 27 c b1 37

9 12 10 c 20 c 1 32

⁎ All p-values are age adjusted and denoted if b0.10. a 5–10% missing information. b 10–25% missing information. c 1–5% missing information.

p⁎

0.06

On admission ST elevation (%) 382 Diagnostic ST elevation (%) 332 Location if ST elevation (%) # Anterior 60 Inferior 35 Lateral 28 Number of leads with ST 3.4 ± 1.5 elevation (mean ± SD) # Maximum ST elevation in any 3.2 ± 2.41 lead (mean ± SD) # ST depression (%) 492 Maximum ST depression in 2.3 ± 1.41 any lead (mean ± SD) ## Q-wave (%) 262 Left bundle branch block (%) 91 Not known before (%) 51 Known before (%) 51 Right bundle branch block (%) 41 T-wave inversion (%) 431 Non-specific ST/T changes (%) 182 Arrhythmias on admission (%) Sinus bradycardia 5 Sinus tachycardia 16 High-degree AV block 1 Atrial flutter 2 Atrial fibrillation 19 Ventricular fibrillation 1 Ventricular tachycardia b1 Asystole 0 Other 3 Arrhythmias during hospital stay (%) Sinus bradycardia 26 Sinus tachycardia 20 High-degree AV block 2 Atrial flutter 4 Atrial fibrillation 27 Ventricular fibrillation 1 Ventricular tachycardia 3 Asystole 9 Other 4

Men (n = 835)

p⁎

392 342 60 42 33 3.8 ± 1.6 3.1 ± 2.2 512 2.4 ± 1.61 272 111 52 71 82 442 142

0.04 0.02 0.0002

9 13 2 2 15 1 b1 0 3

0.06

36 18 3 4 24 3 5 7 8

0.03 0.09

0.09 0.002

⁎All p-values are age adjusted and denoted if b0.10. = 1–5% missing information; 2 = 5–10% missing information. # = of those with diagnostic ST elevation; ## = of those with ST depression.

1

0.08

0.02 0.02 0.03

both STEMI and non-STEMI. Among patients who underwent coronary angiography, 46% of women and 44% of men underwent PCI (p = 0.52) and 11% of women and 21% of men underwent CABG (p = 0.003). Despite these observations, a recurrent AMI tended to occur less frequently in women (Table 4). Pneumonia was also observed less frequently in women. There was no difference in the occurrence of heart failure or death. 2.15. Medication Some differences were observed. Aspirin was used less frequently by women prior to hospital admission. A similar

J. Herlitz et al. / International Journal of Cardiology 135 (2009) 315–322

319

Table 4 In-hospital procedures and events. Women Men p⁎ (n = 588) (n = 835) Treated in CCU (%) 49 Thrombolysis (%) 8 Procedures and treatment (%) Echocardiography 43 Exercise bicycle test 12 Coronary angiography 21 PCI 10 Primary 7 Rescue 2 Elective b1 CABG 2 Events (%) Extension of AMI 3 Recurrent AMI 2 Pulmonary embolism b1 Pneumonia 8 Stroke 5 Deep vein thrombosis b1 Acute renal failure 2 Haemorrhage requiring transfusion 3 Hypotension 11 Pericarditis 0 Cardiogenic shock 2 Congestive heart failure 45 Death (%) 14

67 10 58 23 40 18 15 2 b1 9 3 4 b1 11 4 b1 3 4 12 b1 2 41 12

0.005

0.05 0.02

b0.0001

0.02 0.009

STEMI patients

p⁎

Non-STEMI patients

p⁎

Women (n = 180) Men (n = 267)

Women (n = 372) Men (n = 511)

66 24

79 27

44 b1

63 2

0.0006

54 16 28 16 10 5 1 2

70 28 57 30 22 6 2 10

40 12 0.03 20 7 7 0 b1 0.01 3

55 22 34 13 12 b1 b1 10

0.09 0.06

5 1 2 4 6 b1 2 3 13 0 3 45 14

3 3 01 81 51 01 21 21 111 01 31 32 9

2 2 b1 0.05 9 5 0 2 3 9 0 2 43 12

3 4 b1 10 3 b1 3 4 11 b1 2 43 12

0.002

⁎All p-values are age adjusted and denoted if b0.10. 1 = 1–5% missing information.

trend was found for anticoagulants. ACE inhibitors tended to be used less frequently among women and similar trends were found for nitrates in hospital (Table 5). 2.16. Events after discharge CABG tended to be performed less frequently among women than men. However, male gender was associated with an increased risk of reinfarction and there was a trend towards the same finding for death (Table 6). 2.17. Long-term mortality In Table 7 it is shown that, unadjusted, women had a higher risk of death during the subsequent 3 years as compared with men (49.0% versus 40.7%). However, when adjusting for age and when adjusting for admittance to CCU, coronary angiography and coronary revascularisation respectively, the risk of death was lower in women than men. When simultaneously adjusting for both, the risk of death was markedly lower in women than men. 3. Discussion 3.1. Study population The study population is unique as it includes all patients hospitalised within a community and discharged from hospital

(dead or alive) with a diagnosis of AMI, regardless of where in hospital the patient was treated, regardless of whether there was a suspicion of AMI on admission to hospital and regardless of whether AMI was the primary diagnosis. This is a notable difference in comparison with both randomised studies and registry data, both of which frequently select patients with a lower risk [9–11]. The mean age in this representative survey was 75 years, considerably higher than in previous reported surveys. There are two possible explanations for this: 1) Patients who suffer from AMI are older in Göteborg than the other parts of the western world or 2) The study population is more representative than previous surveys. Patients were included in the survey regardless whether they were treated in CCU. About 40% of patients were never admitted to CCU. 3.2. Treatment differences between women and men The most important finding was that a markedly lower percentage of women than men were admitted to the CCU. This finding is in agreement with a previous report indicating that female gender was an independent predictor of not being admitted to the CCU among patients with acute chest pain [12]. Previous studies have also shown that female gender is independently associated with an increased risk of inappropriate discharge from the emergency department among

320

J. Herlitz et al. / International Journal of Cardiology 135 (2009) 315–322

Table 5 Medication (only those discharged alive included in at-discharge calculations).

Statins (%) Pre-arrival In hospital At discharge Anti-platelets (%) Pre-arrival In hospital At discharge Anti-arrhythmics (%) Pre-arrival In hospital At discharge Anti-coagulants (%) Pre-arrival In hospital At discharge Beta-blockers (%) Pre-arrival In hospital At discharge Calcium channel blockers (%) Pre-arrival In hospital At discharge Diuretics (%) Pre-arrival In hospital At discharge ACE inhibitors (%) Pre-arrival In hospital At discharge Nitrates (%) Pre-arrival In hospital At discharge Digitalis (%) Pre-arrival In hospital At discharge

Women (n = 588)

Men (n = 835)

14 30 34

20 46 51

54 87 89

55 88 89

b1 3 b1

b1 4 2

6 73 11

8 79 15

53 86 86

47 88 87

18 19 16

16 18 15

45 67 60

38 57 49

17 33 34

20 39 41

0.006 0.04 0.01

30 44 38

25 47 35

0.01

11 21 14

8 15 9

Table 6 Events after hospital discharge during first year (of those discharged alive) — first admission only.

p⁎

0.002

Death (%) Reinfarction (%) Stroke (%) Coronary angiography (%) PCI (%) CABG (%)

Women (n = 469)

Men (n = 658)

p⁎

22 12 a 5a 8 5 4

18 16 3 12 7 10

0.04 ⁎⁎ 0.003

0.02

⁎ All p-values are age adjusted and denoted if b0.10. ⁎⁎ More among men. a 1–5% missing information. 0.04 0.04 0.07

⁎All p-values are age adjusted and denoted if b0.10.

Age is most probably a contributory factor, but this was adjusted for in the p-value calculation [12]. Once patients are admitted to the CCU, recent data indicate that differences are less marked between genders with regard to various treatment aspects [8,11,16]. At the time of this survey, most decisions on the use of an invasive strategy were taken in the CCU and our finding of a lower admission rate to the CCU in women can therefore to some extent explain the tendency towards a lower rate of coronary angiography in women and the lower rate of CABG in women. However, even among patients who underwent coronary angiography, women tended to be revascularised less frequently than men. This is in line with a less severe coronary artery disease in women than in men as reported from earlier studies [6]. In terms of age and previous history, most results were expected. Many previous studies have reported that, among patients with AMI, women have a lower prevalence of previous AMI and a higher prevalence of previous hypertension [15,16]. Moreover, a lower prevalence of peripheral vascular disease in women was expected [15]. However, contrary to previous studies, we did not find a higher prevalence of previous heart failure and diabetes among women [11,15,16]. We have no clear explanation for this finding. It is possible that the high age of the participants influenced our results. 3.3. Presentation on admission

patients with acute coronary syndromes [13]. A recent large survey indicated that females with potential acute coronary syndrome receive fewer catheterizations than male patients [14]. Finally, it has been shown that, among patients with acute coronary syndrome admitted to the CCU, women have to wait longer in the emergency department than men [15]. All these data indicate that women with acute coronary syndrome and AMI are prioritised differently than men prior to admission to the CCU. The mechanism behind this information is not known. It is tempting to suggest that the initial degree of suspicion of AMI was lower in women. However, previous studies have indicated that, even after adjusting for the initial degree of suspicion of AMI, female gender is associated with a lower admission rate to the CCU [12].

In terms of presentations on admission to hospital, no major difference was found between genders. As has been shown many times before [17,18], women tended to report Table 7 Unadjusted and adjusted odds ratio for death during 3 years (women versus men) when considering age, admittance to CCU and various aspects of revascularisation.

Unadjusted: Adjusted for age: Adjusted for CCU, coronary angiography, PCI, CABG, thrombolysis Adjusted for age, CCU, coronary angiography, PCI, CABG, thrombolysis

OR 95% confidence limit

p-value

1.25 (1.06, 1.47) 0.79 (0.67, 0.94) 0.84 (0.71, 0.99)

p = 0.008 p = 0.006 p = 0.04

0.72 (0.60, 0.85)

p = 0.0001

J. Herlitz et al. / International Journal of Cardiology 135 (2009) 315–322

symptoms from the chest less frequently, but there was no significant difference. The observation of a tendency towards higher blood pressure among women is in agreement with a higher prevalence of hypertension among women [11,15,16]. We did not find any difference in ECG pattern on admission to hospital, with the exception of a slightly lower rate of bundle branch block in women. This is in agreement with a previous report [15]. It has previously been suggested that, for anatomic reasons, women should present with less ST deviation than men [19]. However, this has not been confirmed by others [20]. On the other hand, previous studies have suggested that, among patients with AMI, STEMI is less frequent among women than men [21]. We found a similar degree of ST deviation in women and men. The percentage of patients with ST elevation who were revascularised was low and tended to be lower in women than in men. The mechanism behind this observation is unclear. One strong contributory factor was most probably the high age and co-morbidity in this representative study population. 3.4. Outcome Despite a lower admission rate to the CCU and a lower revascularisation rate in women, female gender was associated with a lower risk of recurrence during the first year. However a higher proportion of women died during 3 years as compared with men. An important question is what the outcome would have been if women were admitted to CCU to a similar extent as men and if women underwent coronary angiography and coronary revascularisation to a similar extent as men. According to our results this should have lead to a lower risk of death among women than among men. Indeed when adjusting for age as well as various aspects of early treatment the odds for death among women was 28% lower than men and highly significant. Contributing factors might be a more extensive coronary artery disease in men, a higher occurrence of previous AMI in men and a higher prevalence of renal disease in men. Our data are in agreement with one previous Swedish survey which only included patients admitted to intensive or coronary care unit [10] when patients were followed for 1 year. Other surveys did not find any major difference in prognosis between genders neither short time [22] nor long time [23]. However, our findings are only valid if we know that the effect of early revascularisation is similar in women and men. Unfortunately, there is a lack of clear evidence of clinical benefit for early revascularisation among women suffering from unstable coronary artery disease [6,7]. Results from other studies have, however, indicated similar results in men and women [24,25]. Overall the mortality was, as compared with other studies, very high. A hospital mortality of 12 and 14% is much higher than reported by others [26,27]. This should be related to the high age in our study population probably reflecting the representativeness of the cohort.

321

3.4.1. Limitation There was missing information in a number of patients in some of the variables. 3.4.2. Conclusion In the community of Göteborg women with AMI are prioritised differently than men, prior to admission to a CCU. This results in a less invasive strategy in women, particularly with regard to CABG. When adjusting for difference in age, admittance to CCU and coronary revascularisation female gender was associated with a low risk of death during the subsequent 3 years. References [1] Gottlieb S, Harpaz D, Shotan A, et al. Sex differences in management and outcome after acute myocardial infarction in the 1990s: a prospective observational community-based study. Israeli thrombolytic survey group. Circulation 2000;102:2484–90. [2] Hanratty B, Lawlor DA, Robinson MB, Sapsford RJ, Greenwood D, Hall A. Sex differences in risk factors, treatment and mortality after acute myocardial infarction: an observational study. J Epidemiol Community Health 2000;54:912–6. [3] Mahon NG, McKenna CJ, Codd MB, O'Rorke C, McCann HA, Sugrue DD. Gender differences in the management and outcome of acute myocardial infarction in unselected patients in the thrombolytic era. Am J Cardiol 2000;85:921–6. [4] Heer T, Schiele R, Schneider S, et al. Gender differences in acute myocardial infarction in the era of reperfusion (the MITRA registry). Am J Cardiol 2002;89:511–7. [5] Kaplan KL, Fitzpatrick P, Cox C, Shammas NW, Marder VJ. Use of thrombolytic therapy for acute myocardial infarction: effects of gender and age on treatment rates. J Thromb Thrombolysis 2002;13:21–6. [6] Lagerqvist B, Säfström K, Ståhle E, Wallentin L, Swahn E. Is early invasive treatment of unstable coronary artery disease equally effective for both women and men? J Am Coll Cardiol 2001;38:41–8. [7] Fox KA, Poole-Wilsson PA, Henderson RA, et al. Interventional versus conservative treatment for patients with unstable angina or nonST-elevation myocardial infarction: the British Heart Foundation RITA3 randomised trial. Randomised Intervention Trial of unstable Angina. Lancet 2002;360:743–51. [8] Perers E, Caidahl K, Herlitz J, Karlson BW, Karlsson T, Hartford M. Treatment and short-term outcome in women and men with acute coronary syndromes. Int J Cardiol 2005;103:120–7. [9] Bjorklund E, Lindahl B, Stenestrand U, et al. Swedish ASSENT-2; RIKS-HIA Investigators. Outcome of ST-elevation myocardial infarction treated with thrombolysis in the unselected population is vastly different from samples of eligible patients in a large-scale clinical trial. Am Heart J Oct 2004;148(4):566–73. [10] Alfredsson J, Stenestrand U, Wallentin L, Swahn E. Gender differences in management and outcome in non-ST-Elevation acute coronary syndrome. Heart 2007;93:1357–62. [11] Montalescot G, Dallongeville J, Van Belle E, et al. STEMI and NSTEMI: are they so different? 1 year outcomes in acute myocardial infarction as defined by the ESC/ACC definition (the OPERA registry). Eur Heart J 2007;28:1409–17. [12] Herlitz J, Karlson BW, Karlsson T, Svensson L, Zehlertz E, Kalin B. A description of the characteristics and outcome of patients hospitalized for acute chest pain in relation to whether they were admitted to the coronary care unit or not in the thrombolytic era. Int J Cardiol 2002;82:279–87. [13] Pope JH, Aufderheide TP, Ruthazer R, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 2000;342:1163–70.

322

J. Herlitz et al. / International Journal of Cardiology 135 (2009) 315–322

[14] Chang AM, Mumma B, Sease KL, Robey JL, Shofer FS, Hollander JE. Gender bias in cardiovascular testing persists after adjustment for presenting characteristics and cardiac risk. Acad Emerg Med 2007;14:599–605. [15] Perers E, Caidahl K, Herlitz J, et al. Spectrum of acute coronary syndromes: history and clinical presentation in relation to sex and age. Cardiology 2004;102:67–76. [16] Hochman JS, McCabe CH, Stone PH, et al. Outcome and profile of women and men presenting with acute coronary syndromes: a report from TIMI IIIB. TIMI investigators. Thrombolysis in myocardial infarction. J Am Coll Cardiol 1997;30:141–8. [17] Goldberg RJ, O'Donnell C, Yarzebski J, Bigelow C, Savageau J, Gore JM. Sex differences in symptom presentation associated with acute myocardial infarction: a population-based perspective. Am Heart J 1998;136:189–95. [18] Canto JG, Shlipak MG, Rogers WJ, et al. Prevalence, clinical characteristics and mortality among patients with myocardial infarction presenting without chest pain. JAMA 2000;283:3223–9. [19] Dellborg M, Herlitz J, Emanuelsson H, Swedberg K. ECG-changes during myocardial ischemia. Differences between men and women. J Electrocardiol 1994:42–5 27 Suppl. [20] Raitt MH, Litwin PF, Martin JS, Weaver WD. ECG findings in acute myocardial infarction. Are there sex-related differences? J Electrocardiol 1995;28:13–6.

[21] Hochman JS, Tamis JE, Thompson TD, et al. Sex, clinical presentation, and outcome in patients with acute coronary syndromes. Global use of strategies to open occluded coronary arteries in acute coronary syndromes IIb investigators. N Engl J Med 1999;341:226–32. [22] Rosengren A, Spetz CL, Koster M, Hammar N, Alfredsson L, Rosén M. Sex differences in survival after myocardial infarction in Sweden; data from the Swedish National Acute Myocardial Infarction Register. Eur Heart J 2001;22:314–22. [23] Perers E, Caidahl K, Herlitz J, Karlsson T, Hartford M. Impact of diagnosis and sex on long-term prognosis in acute coronary syndromes. Am Heart J 2007;154:482–8. [24] Glaser R, Herrmann HC, Murphy SA, et al. Benefit of an early invasive management strategy in women with acute coronary syndromes. JAMA 2002;288:3124–9. [25] de Winter RJ, Windhausen F, Cornel JH, et al. Early invasive versus selectively invasive management for acute coronary syndromes. N Engl J Med 2005;353:1095–104. [26] Magid DJ, Wang Y, Herrin J, et al. Relationship between time of day, day of week, timeliness of reperfusion, and in-hospital mortality for patients with acute ST-segment elevation myocardial infarction. JAMA 2005;294:803–12. [27] Liew R, Sulfi S, Ranjadayalan K, Cooper J, Timmis AD. Declining case fatality rates for acute myocardial infarction in South Asian and white patients in the past 15 years. Heart 2006;92:1030–4.