Article

Inequalities in the early treatment of women and men with acute chest pain?

Unlabelled imageAmerican Journal of Emergency Medicine (2012) 30, 1515-1521

Original Contribution

Inequalities in the early treatment of women and men with acute chest pain??

Annica Ravn-Fischer MD a,?, Thomas Karlsson MSc a, Marco Santos MSc b,

Bo Bergman PhD b, Johan Herlitz MD, PhD c, Per Johanson MD, PhD a

aInstitution of Medicine, Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Goteborg, Sweden bCentre for Healthcare Improvement, Division of Quality Sciences, Chalmers University of Technology, Goteborg, Sweden cThe Centre of Prehospital Research in Western Sweden, University College of Boras and Sahlgrenska University Hospital, Goteborg, Sweden

Received 15 August 2011; revised 20 December 2011; accepted 20 December 2011

Abstract

Purpose: The aim of this study was to identify sex differences in the Early chain of care for patients with chest pain.

Design: This is a retrospective study performed at 3 centers including all patients admitted to the emergency department because of chest pain, during a 3-month period in 2008, in the municipality of Goteborg. Chest pain or discomfort in the chest was the only inclusion criterion. There were no exclusion criteria.

Data Sources: Data were retrospectively collected from ambulance and medical records and electrocardiogram (ECG), echocardiography, and laboratory databases.

Main Findings: A total of 2588 visits (1248 women and 1340 men) made by 2393 patients were included. When adjusting for baseline variables, female sex was significantly associated with a prolonged delay time (defined as above median) between (a) admission to hospital and admission to a hospital ward (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.25-2.03), (b) first physical contact and first dose of aspirin (OR, 2.22; 95% CI, 1.30-3.82), and (c) admission to hospital and coronary angiography (OR, 2.50;

95% CI, 1.29-5.13).

Delay time to the first ECG recording did not differ significantly between women and men.

Principal Conclusions: Among patients hospitalized due to chest pain, when adjusting for differences at baseline, female sex was associated with a prolonged delay time until admission to a hospital ward, to administration of aspirin, and to performing a coronary angiography. There was no difference in delay to the first ECG recording.

(C) 2012

? This study was supported by grants from the Laerdal Foundation in Acute Medicine in Norway and from the research program VINNVARD jointly funded by Vardalstiftelsen, VINNOVA, Sveriges Kommuner och Landsting (SKL), and Social departementet.

* Corresponding author. Department of Cardiology, Sahlgrenska

University Hospital, SE 413 45 Goteborg, Sweden.

E-mail address: [email protected] (A. Ravn-Fischer).

Introduction

Cardiovascular disease is a major cause of death among women and men worldwide [1]. In Sweden, the incidence of acute myocardial infarction (AMI) in 2008 for men and women was 619 per 100 000 and year, and 440 per 100 000 and year, respectively [2]. This incidence is decreasing over

0735-6757/$ – see front matter (C) 2012 doi:10.1016/j.ajem.2011.12.020

time: as compared with 2001, age-standardized incidence was 20% lower for men and 15% lower for women in 2008 [2]. This change has been seen despite new definitions of myocardial infarction and the use of new sensitive bio- markers [3]. Mortality has also decreased considerably during the last decade, and for 2008, the 28-day mortality rate for myocardial infarction in Sweden was 29% among men and 32% among women [2]. Our experience indicates that sex differences in the treatment of acute coronary syndromes (ACSs) are minor or even nonexistent if the patient was admitted to a coronary care unit (CCU) [4,5]. In contrast, recent scientific reports from China, France, Germany, and the United States still describe the underuti- lization of reperfusion therapy in ACS among women as compared with men [6-9].

Sex discrepancies in patients with myocardial infarction do exist. Women are 4 to 10 years older than men when having their first myocardial infarction [10,11]. They more often have a previous history of hypertension and diabetes but are less likely to have a history of previous myocardial infarction or revascularization [11]. Female coronary artery vessels have smaller dimensions, and the atherosclerosis is often more diffuse than in men. Chest pain due to spasm in the coronary arteries and cardiac syndrome X seem to be more common in women, as is stress-induced or takotsubo cardiomyopathy [12,13]. Among patients with AMI, women more frequently report nausea, vomiting, and dyspnea, and there is also a difference in localization of symptoms where women have more pain in the neck, back, and abdomen as compared with men [14-17].

The purpose of this study was to identify differences in the chain of care for women and men with chest pain. Our primary hypothesis was that there is a difference in delay time to a hospital ward between men and women with chest pain. The secondary objective measures were delay time to

(1) electrocardiogram (ECG) recording, (2) administration of aspirin, and (3) coronary angiography. Our primary objective reflects the capacity of the health care system in handling the large volumes of patients with chest pain in our community. The secondary objective measurements are chosen because of their diagnostic and therapeutic importance to reduce myocardial damage when given early in the ACS event.

We also wanted to descriptively compare investigations and treatments to highlight any differences between sexes, with the intention to generate future hypotheses for studies focusing on equitable cardiac care.

Methods

Study design

This is a retrospective chart review performed at 3 centers including all patients admitted to the emergency department (ED) because of chest pain, during a 3-month period in 2008,

in the municipality of Gothenburg. This study was approved by the Goteborg Ethical Review Board.

Study population

From mid-September to mid-December in 2008, all patients with chest pain visiting one of the 3 hospitals (Sahlgrenska, Ostra or Molndal) in the Sahlgrenska Univer- sity Hospital organization were included in this study. The patients were retrospectively found through the ED’s database where they were coded and triaged as “chest pain or discomfort in the chest.” Patients were included regardless of being hospitalized or discharged after visiting the ED. Chest pain or discomfort in the chest was the only inclusion criterion. There were no exclusion criteria.

Data sources

Data were retrospectively collected from ambulance and medical records and ECG, echocardiography, and laboratory databases. For included patients, an extensive formulary comprising more than 200 variables was developed and used for collecting data. Age, sex, previous history of illness, smoking and alcohol habits, body mass index, symptoms, time to treatments and investigations, laboratory parameters, mortality, medications at discharge, and follow-up after discharge were collected and entered into a database for subsequent statistical analysis. The data sampling was performed by different coworkers, and all the collaborators were clearly instructed how to record data with strict definitions for each variable that was assessed. However, no measures were implemented to compare and increase the interdata collector validity. All ECG variables were reviewed by an independent cardiologist.

Outcome measures

The primary outcome measure in this study was delay time to presentation to a hospital ward. Secondary outcome measures were delay time to the first ECG recording, to administration of aspirin, and to coronary angiography.

Definition of variables

We estimated that about half of the population with chest pain would use emergency medical service (EMS) as transport system for hospital admission. In the ambulance, the paramedics, when there is a suspicion of ACS, often initiate treatment with anti-ischemic drugs. When we analyzed the data, we, therefore, used the first physical contact as a reference for time delay to first ECG recording and administration of aspirin. Electrocardiogram registra- tion time was defined as the interval between the first physical contact with health care providers (in the ambulance or at the ED) and the time of the initial ECG. Time to aspirin

Age (y), mean +- SD

62 +- 19

58 +- 19

b.0001

69 +- 15

65

+- 16

b.0001

Previous history (%)

Diabetes

13 b

14 b

.25

18

16

.55

Hypertension

41 b

30 c

b.0001

49

37

.0005

Heart failure

9 b

10 b

.007

14

14

.10

Myocardial infarction

16 b

26 b

b.0001

23

36

b.0001

Angina pectoris

21 b

22 c

.002

31

33

.007

PCI

8 b

15 b

b.0001

11

21

b.0001

CABG

4 b

12 b

b.0001

6

17

b.0001

Stroke

7 b

8 b

.05

10

10

.28

Peripheral vascular disease

1 b

2 b

.08

1

3

.01

Depression/Psychiatric disease

16 b

10 c

b.0001

16

11

.0004

Need of interpreter (%)

9

8

.22

10

9

.40

Admitted to hospital (%)

Via emergency ward

96

95

.17

97

95

.04

Directly to CCU

1

3

.009

3

5

.04

Already hospitalized d

3

3

.65

Transported by ambulance (%)

42

38

.62

54

50

.53

Hospitalized (%)

53

56

.0003

ECG (%)

ST changes

5.5 b

6.5 b

.0002

9.2

8.6

.13

ST elevation

1.9 b

4.3 b

b.0001

2.9

5.2

.01

ST depression

4.4 b

3.0 b

.66

7.6

4.6

.55

a Age adjusted (except for age).

b Five percent to 10% missing.

c Ten percent to 25% missing.

d Including those transferred from another hospital, family doctor, nursing home, and others.

administration was defined as the interval between the first physical contact and the registration of Aspirin administration (either by paramedics in the ambulance or by the nurse at the ED). Time to coronary angiography was defined as the interval between arrival to the ED (or hospital ward for those bypassing the ED) and to registered needle time/start of procedure at the intervention laboratory. The primary objective measure, time to presentation to a hospital ward, was defined as the interval from arrival to ED and arrival registration by the nurse at the ward.

Table 1 Baseline characteristics in all patients and in patients who were hospitalized

All patients

Women (n = 1248) Men (n = 1340)

P a

Hospitalized patients

Women (n = 629) Men (n = 721)

P a

The definition of AMI was based on the following diagnostic criteria: (1) laboratory parameters (minimum 1 troponin value, I or T, above the upper reference level, and another troponin value 6 hours later indicating dynamic changes) and at least 1 of the 2 conditions: (2a) symptoms raising suspicion of myocardial infarction (such as pain or discomfort in the chest, arms, neck, jaw, back, or abdomen), dyspnea, nausea, and cold sweat or (2b) ECG findings suggesting ischemia: ST-segment elevation/de- pression in at least 2 contiguous leads (ST-segment elevation of >=0.1 mV in leads aVL, aVF, I, II, III, and V5-V6 or >=0.2 mV in leads V1-V4; ST-segment depression of >=0.1 mV) or Left bundle-branch block [3]. The definition of ACS was a final diagnosis of AMI including

ST-elevation myocardial infarction , or non- STEMI, or unstable angina pectoris.

Statistical analyses

Mann-Whitney U test was used to test for the difference in age between women and men. All other P values are age adjusted using the Cochran-Mantel-Haenszel statistic for proportions and a stratum-adjusted Kruskal-Wallis test for continuous/ordered variables. For the primary and secondary objectives, using multiple logistic regression with delay time dichotomized by the median as dependent variable, all baseline characteristics were also adjusted (ie, all variables in Table 1), with a univariate P b .20 for association both with sex and with the delay time in question. All tests are 2 sided, and a P value below .01 was regarded as statistically significant.

Results

A total of 2588 visits (1248 women and 1340 men) made by 2393 patients were included. Of these visits, 1350

Delay variable Women (n = 629) Men (n = 721) P a OR b (95% CI) P b

Arrival in hospital to admission: PCI–laboratory or ward 236 (88, 550) 200 (67, 502) b.0001 1.59 (1.25-2.03) .0002

(median, 215)

1st physical contact to 1st ECG (median, 13) 15 (0, 76) c 13 (0, 75) c .07 1.14 (0.89-1.47) .31

1st physical contact to 1st aspirin (median, 79) 138 (6, 1356) d 60 (5,1119) c .002 2.22 (1.30-3.82) .004

Arrival in hospital to coronary angiography (median, 1815) 2717 (24, 9866) d 1517 (19, 7260) d .01 2.50 (1.29-5.13) .007

a Age adjusted.

b Adjusted for all baseline variables with univariate P b .20 for association with both sex and delay. Baseline variables used are as follows: for arrival in hospital to arrival in PCI laboratory/ward: age, previous PCI, depression/psychiatric disease, and ST-elevation; for 1st physical contact to first ECG: age, previous diabetes, previous hypertension, previous myocardial infarction, peripheral vascular disease, and ST elevation; for 1st physical contact to aspirin: age, previous hypertension, previous CABG, and ST elevation; and for arrival in hospital to coronary angiography: previous myocardial infarction, previous PCI, and previous CABG.

c Ten percent to 25% missing.

d Five percent to 10% missing.

resulted in hospitalization (in 1266 patients). Of all visits, 42% of women and 38% of men (P = .62) were transported by the EMS.

Table 2 All hospitalized patients: median (10th, 90th percentile; in minutes), odds ratio (OR), and corresponding 95% confidence interval (CI) for women in relation to men having a delay above median

Baseline characteristicsall patients and hospitalized patients

In our study population, women were older than men (mean age, 62 years vs 58 years; P b .0001). They had a significantly higher prevalence of previous hypertension and depression or psychiatric disease than did men. These differences were also present in the subgroup of hospitalized patients (Table 1).

Men had a significantly higher prevalence of previous heart failure, myocardial infarction, and angina pectoris and higher rates of previously performed percutaneous coronary intervention (PCI) and Coronary artery bypass grafting (CABG). Men also had more frequent ST elevation on the first ECG recorded as compared with women.

Women were less frequently directly admitted to a hospital ward (bypassing the ED) and were overall less frequently hospitalized.

Delay times in all patients hospitalized

In our setting, women had a significantly longer delay time from arrival to hospital to admission to a hospital ward as compared with men (median, 236 minutes vs 200 minutes), even when adjusting for differences in baseline characteristics. The adjusted odds ratio for women in relation to men having a delay time exceeding 215 minutes (ie, the median in the entire group) was 1.59 (95% confidence interval, 1.25-2.03; P = .0002) (Table 2).

Echocardiography performed

25

36

b.0001

EF b50% c

15

27

b.0001

EF b30% c

2

5

.03

Similarly, the adjusted odds ratios showed that women, significantly more often than men, had longer delay times from the first physical contact until the first dose of aspirin. Women also had a prolonged delay compared

with men from admission to hospital until undergoing a coronary angiography.

However, delay from the first physical contact until the first ECG did not differ significantly between sexes.

Table 3 Diagnosis and findings in hospital and secondary preventive activities

All hospitalized patients

Secondary preventive activities (%) d

Lipid analysis b24 h after onset of symptoms

Discharged alive from hospital (%) d

a Age adjusted.

55 e

49

.05

94

95

.58

b Of those where angiography was performed.

c EF, Ejection Fraction; Of those where echocardiography was performed.

d Only patients with ACS as first final diagnosis.

e Ten percent to 10% missing.

Women (n = 629)

Men

(n = 721)

P a

First position final diagnosis (%)

AMI

11

18

b.0001

ST-elevation AMI

5

8

.01

Non-ST-elevation AMI

6

11

.0002

Unstable angina pectoris

3

5

.09

Final diagnosis, any position (%)

AMI

12

19

b.0001

Unstable angina pectoris

4

6

.05

Findings (%)

Coronary angiography

13

23

b.0001

performed

Main stem stenosis b

5

9

.14

Triple vessel disease b

28

30

.25

2-Vessel disease b

30

35

.36

1-Vessel disease b

19

26

.35

No coronary artery disease b

24

9

b.0001

Diagnoses and findings in hospital and secondary preventive activities

Among all hospitalized patients with chest pain, a final diagnosis of AMI was more common in men as compared with women, and a coronary angiography was more often performed in men. A normal angiography was more common in the female group. Echocardiography was more often performed in men, and a normal echocardiography was more common in women (Table 3).

Use of various treatments among patients with ACS

In the ACS group, we could not identify any differences in medication therapy between sexes. In this patient group, there was a high prescription among both men and women of aspirin, clopidogrel, ?-blockers, angiotensin-converting en- zyme (ACE) inhibitors/A2-blockers, and lipid-lowering drugs at hospital discharge (Table 4).

Discussion

In the Goteborg region, there are 3 hospitals that provide emergency and basic care to approximately 620 000

Table 4 Use of various treatments among patients with ACS

Women (n = 83)

Men (n =

161)

P a

Before arrival in hospital b (%)

Aspirin

34

39

.70

Clopidogrel

8

15

.25

Nitroglycerin

57

58

.73

?-Blocker

6

4

.40

In hospital (%)

Aspirin

93

94

.93

Clopidogrel

79

84

.79

Heparin or LMWH

66 c

68 c

.66

Nitroglycerin

84

68 c

.01

?-Blocker

91

96

.48

Lipid-lowering drug

71

87 c

.09

ACE inhibitor/A2-blocker

66 c

72

.85

Coronary angiography

63

80

.67

PCI

44

57

.97

CABG

5 d

5 c

.49

At hospital discharge e (%)

Aspirin

90

95

.58

Clopidogrel

68

79 c

.51

Warfarin

11

6 c

.21

?-Blocker

86

91

.80

Lipid-lowering drug

75

88 c

.52

ACE inhibitor/A2-blocker

67

73 c

.65

a Age adjusted.

b Only Ambulance transported patients (55 + 97).

c Ten percent to 10% missing.

d Ten percent to 25% missing.

e Of patients not documented as death in hospital (78 + 153).

residents and also provide highly Specialized care for 1.6 million inhabitants living in western Sweden (December 31, 2010). Patients with chest pain are common at the EDs, and these 3 hospitals are taking care of nearly 10 000 patients with chest pain every year. Therefore, it is of greatest importance to optimize and improve the quality of care for this group of patients.

Research on sex differences on delay times to treatments and investigations in ACS is scant. In an era when there is focus on equal care and equality between sexes, we wanted to investigate this area.

In this study, we could confirm our primary hypothesis that there is a sex difference regarding delay time to finally reaching a hospital ward. In general, we found long delays before the patient reached a ward. It could certainly be questioned to leave a patient with chest pain in need of further in-hospital assessment, waiting for more than 3 hours in the ED while having a possible myocardial infarction or at least chest pain of uncertain etiology.

The probably strongest contributing factor to these long delay times is a shortage of Hospital beds. Over time, the number of hospital beds per capita in Sweden has been reduced to a level of 2.8 per 1000 inhabitants, leaving us at the lower end when comparing with other OECD (Organi- sation for Economic Co-operation and Development) countries [18]. Such shortage of beds might even become a threat to quality of care.

The secondary hypotheses suggesting differences in delay Time to administration of aspirin and time to coronary angiography between sexes were also confirmed. To minimize the risk of excessive myocardial damage and subsequent complications in patients with ACS, it is important to speed up investigations and treatments in both female and male patients with a presumed ACS.

The sex differences in this study are in accordance with what previous studies have shown: for example, difference in age [10,11] and previous history of illness [11], differences in ECG findings [3], and difference in prevalence of atherosclerosis in coronary vessels [19].

In our study and in former studies, women with chest pain undergoing a coronary angiography seem to have a higher probability of a normal angiogram, and women are less likely to develop an AMI as compared with men [19]. Furthermore, there are studies indicating that female sex is not an independent risk factor of increased short-term mortality in ACS [4,20]. However, these trials were all conducted on men and women actually admitted to a CCU or a similar ward. In this study, women were less frequently directly admitted to the CCU than men. This finding is in concordance with previous studies and, thus, indicates that men are given priority over women before admission to the CCU but that only minor sex differences are seen thereafter [21].

In the municipality of Goteborg and probably in many other communities, a large percentage of patients with ACS are treated outside a dedicated CCU. Among those patients, sex differences possibly constitute larger problems, with

lower frequencies of coronary angiography and revascular- ization in the female group [21]. Several surveys have shown that women with AMI have more nonspecific symptoms including pain in the neck, back, and abdomen, and this is in accordance with our findings [14-17].

In a CCU, there are cardiologists responsible for patients with ACS/AMI, and they are probably more familiar with the diagnostic difficulties and atypical symptoms in women. Physicians working outside the CCU have various backgrounds and might be less familiar with such possible differences.

It is important to include patients with chest pain admitted to hospital wards outside the CCU in future studies, to compare and improve quality of care especially with regard to sex. It is also important that the whole chain of care in patients with chest pain is optimized for achieving optimal outcomes. This includes the dispatch center, EMS, Triage systems, ED, and the CCU [22]. Previous studies have shown that a prolonged time to ECG assessment is associated with an increased risk and adverse clinical outcomes in patients with STEMI [23]. Sex differences with longer delay times to ECG among women have been reported, although not reproduced in our study [24].

In the current study, a coronary angiography was performed less frequently in women with symptoms suspicious enough for hospitalization, as compared with men. One could argue that, among those patients, in whom a coronary angiography actually was performed, women still had less significant coronary disease even if they were meticulously scrutinized before referral to this investigation. Also, coronary artery disease is generally believed to be less common in women seeking care for chest pain or other symptoms of ACS. However, in our opinion, it is important to properly–and equally–examine, investigate, risk strat- ify, and, finally, treat this group of patients with symptoms and signs suggesting possible ACS, even if (post hoc) analyses from previous pivotal trials suggest that women might benefit less from early invasive treatment [25].

Our findings do indicate a lower use of diagnostic tools such as coronary angiography and echocardiography as well as lower direct access to a CCU among women. We know from previous research that the CCU offers the best evaluation for ischemic heart disease even if the Short-term outcome in patients with ACS admitted to a noncardiology service bed not always is worsened [26]. Perhaps, the CCU capacity ought to expand to prepare for larger volumes of patients. This will, however, be afflicted with costs that must be related to other priorities in our health care system. It is also important to recognize age perspectives in the discussion of chain of care in patients with chest pain. We know that the elderly more often have multiple illnesses and more severe heart problems. This group would probably benefit from a higher, instead of lower, attention and from being treated by geriatrically orientated cardiologists when having acute heart problems.

In the future, women and the elderly with a suspicion of myocardial infarction, hopefully more often and with shorter

delay time, can be directly admitted to a CCU to get the best treatment for their heart problems. An obvious goal ought to be to make chest pain triage and care as equal as possible despite age and sex.

Limitations

Our study is retrospective, and there is some amount of missing data for a few variables mainly because of the retrospective design of the study. Because different persons at each hospital were performing the data collection, we cannot entirely rule out the possibility of any bias regarding this, even if a standardized manner of collection was used. The data collectors were clearly instructed to maintain the data collection as uniform as possible; however, no measurement of interdata collector validity was done.

This study comprises a large amount of tests that might raise the risk for false statistical significances. To reduce this risk, a P level of b .01 was used.

Clinical implications

Our data suggest that when a final diagnosis of ACS is established, the differences in treatment of women and men might be minor. However, early in the triage system, our findings indicate differences between sexes. Here, we still need to educate the medical profession to approach women with acute chest pain as aggressively as men, despite the fact that the likelihood of myocardial damage is less in women.

Conclusion

Among patients hospitalized due to chest pain, a final ACS diagnosis in men is more common. Furthermore and maybe as a consequence of that, coronary angiographies were more often performed in men. Delay time to the appropriate level of care and delay to treatments and investigations such as administration of aspirin and time to coronary angiography did differ significantly between women and men, but there was no statistically significant difference in medication at hospital discharge.

Acknowledgments

Thanks to Eva Brandstrom, Soren Johansson, Henrik Eriksson, Asa Axelsson, and Annika Odell for fruitful discussions and good ideas during this project. I also want to thank Eva-Sofie Andreen, Angela Synnero, Renee Palmnas, Annika Dahllof, Anneli Linner, and Carina Gustafsson for their great support during data collection. Last but not least, I want to express my gratefulness to Nguyen Dang Thang for great support in ECG analysis.

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