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Gender Differences in Presentation, Coronary Intervention, and Outcomes of 28,985 Acute Coronary Syndrome Patients in Victoria, Australia

      Abstract

      Background

      Differences in demographics, presenting characteristics, and treatment of heart disease in women may contribute to adverse outcomes. The purpose of this paper was to describe gender differences in the epidemiology, treatment, and outcomes of all admissions for acute coronary syndrome (ACS) in Victoria that occurred between June 2007 and July 2009.

      Methods

      We undertook a retrospective cohort study of all patients admitted to Victorian hospitals with a first time diagnosis of ACS. Use of angiograms, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), and adverse outcomes (death and/or unplanned readmission) were compared by gender and hierarchical logistic regression models were used to account for confounding variables.

      Results

      Of a total of 28,985 ACS patients, 10,455 (36%) were women. Compared with men, women were older (aged ≥75 years: 54% vs 31%; p < .001), more likely to present with multiple comorbidities (>1 comorbidity: 53% vs 46%; p < .001), and more likely to be diagnosed with non–ST-segment elevation ACS (86% vs 80%; p < .001). Women were less likely to receive coronary interventions (angiogram: adjusted odds ratio [aOR], 0.71; 95% CI, 0.66–0.75; PCI: aOR, 0.73; 95% CI, 0.66–0.80; CABG: aOR, 0.58; 95% CI, 0.53–0.64). Adverse outcomes were similar in women and men after accounting for confounding variables.

      Conclusions

      Our results show that women in Victoria were less likely to receive coronary interventions after an admission for ACS. Clinicians should be wary of inherent gender bias in decisions to refer patients for angiography.
      Myocardial infarction and unstable angina, collectively described as acute coronary syndrome (ACS), are the major clinical forms of coronary heart disease (CHD), which is the largest single cause of death in Australia and around the world (
      Australian Institute of Health and Welfare (AIHW)
      Australia’s health 2012 Australia’s Health Series No. 13. (Vol. Cat. no. AUS 156).
      ,
      • Sharma K.
      • Gulati M.
      Coronary artery disease in women: A 2013 update.
      ). In 2009, CHD accounted for 15% of all female deaths in Australia, compared with 4% from breast cancer (
      Australian Institute of Health and Welfare (AIHW)
      Monitoring acute coronary syndrome using national hospital data: An information paper on trends and issues.
      ). ACS occurs when an atherosclerotic plaque ruptures or erodes causing thrombosis and distal embolization resulting in a reduction in coronary blood flow (
      • Hamm C.W.
      • Bassand J.
      • Agewall S.
      • Bax J.
      • Boersma E.
      • Bueno H.
      • Widimsky P.
      ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).
      ). The diagnosis of ACS is based on presenting symptoms such as changes detected by electrocardiogram and, depending on the site and severity of the ischemia, may involve the presence of cardiac biomarkers indicating myocardial necrosis (
      National Heart Foundation of Australia, & Cardiac Society of Australian and New Zealand
      Guidelines for the management of acute coronary syndromes 2006.
      ). Strategies for the treatment of ACS require the determination of presence or absence of persistent ST-segment elevation on electrocardiogram and classification into ST-segment elevation myocardial infarction (STEMI) or non–ST-segment elevation ACS (NSTEACS;
      National Heart Foundation of Australia, & Cardiac Society of Australian and New Zealand
      Guidelines for the management of acute coronary syndromes 2006.
      ). Contemporary data indicate that there are close to 100,000 hospitalizations for ACS in Australia per year, with just over one-third (35%) being women (
      Australian Institute of Health and Welfare (AIHW)
      Monitoring acute coronary syndrome using national hospital data: An information paper on trends and issues.
      ,
      Australian Institute of Health and Welfare (AIHW)
      Australia’s health 2012 Australia’s Health Series No. 13. (Vol. Cat. no. AUS 156).
      ). Although ACS is less common in women than in men, the relative risk of in-hospital death after an ACS admission is higher for women than for men (
      Australian Institute of Health and Welfare (AIHW)
      Australia’s health 2012 Australia’s Health Series No. 13. (Vol. Cat. no. AUS 156).
      ). Yet, despite these statistics, the impact of CHD on women is often overlooked (
      • deGoma E.M.
      • Karlsberg R.P.
      • Judelson D.R.
      • Budoff M.J.
      The underappreciated impact of heart disease.
      ).
      Historically, CHD has been considered a man's disease and it has been shown that this stereotypical belief can influence the diagnostic and clinical decision making process (
      • Bonte M.
      • von dem Knesebeck O.
      • Siegrist J.
      • Marceau L.
      • Link C.
      • Arber S.
      • McKinlay J.B.
      Women and men with coronary heart disease in three countries: Are they treated differently?.
      ,
      • Wenger N.K.
      Women and coronary heart disease: A century after Herrick: Understudied, underdiagnosed, and undertreated.
      ). Over the last few years, it has been recognized that underestimation of CHD risk among women may have resulted in more conservative treatment and contributed to poorer outcomes (
      • Poon S.
      • Goodman S.G.
      • Yan R.T.
      • Bugiardini R.
      • Bierman A.S.
      • Eagle K.A.
      • Yan A.T.
      Bridging the gender gap: Insights from a contemporary analysis of sex-related differences in the treatment and outcomes of patients with acute coronary syndromes.
      ,
      • Shehab A.
      • Al-Dabbagh B.
      • Al Habib K.F.
      • Alsheikh-Ali A.A.
      • Almahmeed W.
      • Sulaiman K.
      • Amin H.
      Gender disparities in the presentation, management and outcomes of acute coronary syndrome patients: Data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2).
      ). Consequently, the issue of gender disparities in the diagnosis, treatment, and outcomes of ACS has started to be examined more closely (
      • Wenger N.K.
      Women and coronary heart disease: A century after Herrick: Understudied, underdiagnosed, and undertreated.
      ) with a view to understanding how differences in the demographics, presenting characteristics, pathophysiology, and treatment of heart disease in women may have contributed to adverse outcomes (
      • Sharma K.
      • Gulati M.
      Coronary artery disease in women: A 2013 update.
      ,
      • Worrall-Carter L.
      • Ski C.
      • Scruth E.
      • Campbell M.
      • Page K.
      Systematic review of cardiovascular disease in women: Assessing the risk.
      ). A number of differences in terms of the presentation and treatment of ACS in women have been well-described, whereas others are the subject of ongoing research. For example, women tend to experience ACS at an older age than men and are more likely to have hypertension, diabetes, and/or hypercholesterolemia but less likely to have a history of smoking (
      • Claassen M.
      • Sybrandy K.C.
      • Appelman Y.E.
      • Asselbergs F.W.
      Gender gap in acute coronary heart disease: Myth or reality?.
      ,
      • Worrall-Carter L.
      • Ski C.
      • Scruth E.
      • Campbell M.
      • Page K.
      Systematic review of cardiovascular disease in women: Assessing the risk.
      ). Women also tend to have lower rates of obstructive coronary artery disease (CAD), but a greater prevalence of microvascular dysfunction that, if not detected and well-managed with appropriate pharmacotherapy, results in adverse outcomes in terms of symptoms, hospitalizations, and mortality (
      • Gulati M.
      • Shaw L.J.
      • Bairey Merz C.N.
      Myocardial ischemia in women: Lessons from the NHLBI WISE study.
      ). Nevertheless, a substantial number of women with ACS present with “male-pattern” CAD, for which cardiac catheterization and reperfusion with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) are highly effective strategies in both men and women (
      • Anderson J.L.
      • Adams C.D.
      • Antman E.M.
      • Bridges C.R.
      • Califf R.M.
      • Casey Jr., D.E.
      • Wright R.S.
      2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction Foundation/American Heart Association Task Force on Practice Guidelines.
      ). In response to calls to better track the impact of ACS on women (
      Australian Institute of Health and Welfare (AIHW)
      Monitoring acute coronary syndrome using national hospital data: An information paper on trends and issues.
      ), the aim of this study was to examine gender differences in the epidemiology, treatment, and outcomes of patients admitted to hospitals in Victoria, Australia, with a primary diagnosis of ACS.

      Material and Methods

      This retrospective cohort study analyzed a database maintained by the Victorian State government. The Victorian Admitted Episodes Data Set comprises demographic, clinical, and administrative details for every admitted episode of care occurring in Victorian hospitals, rehabilitation centers, extended care facilities, and day procedure centers (
      Department of Health
      Victorian Admitted episodes data set (VAED) manual.
      ). Clinical information is coded in the format of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian modification (ICD-10-AM;
      • Roberts R.F.
      • Innes K.C.
      • Walker S.M.
      Introducing ICD-10-AM in Australian hospitals.
      ). Data for all patients admitted to hospital with a first time primary diagnosis of ACS between June 2007 and July 2009 were extracted, including any subsequent ACS admissions during the same 2-year period. ICD codes I210 through I213 were classified as STEMI; I214 as non-STEMI (NSTEMI); and I200 as unstable angina. I214 and I200 were grouped together as NSTEACS. With reference to national guidelines for the stratification of risk in NSTEACS (
      National Heart Foundation of Australia, & Cardiac Society of Australian and New Zealand
      Guidelines for the management of acute coronary syndromes 2006.
      ), the following comorbidities were classified as high-risk: congestive heart failure, cardiac arrhythmias, renal failure, and diabetes (uncomplicated and complicated). Consequently, high-risk NSTEACS were defined as all NSTEMI plus any unstable angina with high-risk comorbidities.
      Variables were created for coronary interventions and outcomes that occurred for the patient during any admission across the 2-year period (e.g., angiogram any admission). Coronary interventions analyzed were angiogram, PCI, and CABG. Outcomes were in-hospital death (defined using the variable ‘sepMode’ coded as death for that patient during the 2-year study period) and unplanned second ACS admission (no intention to readmit recorded on first admission, but patient had a second ACS admission). Socioeconomic status (SES) was based on the Australian Bureau of Statistics Socio-Economic Indexes for Areas Index of Relative Socio-Economic Advantage and Disadvantage (
      ABS
      Socio-economic indexes for areas. SEIFA. 2014.
      ). For analysis purposes the deciles were regrouped into low SES (1–2), middle SES (3–8), or high SES (9–10).
      Data were analyzed using SPSS V21 with comparisons between demographic or diagnostic subgroups (e.g., aged 15–59 vs aged ≥60; STEMI vs NSTEACS) calculated using χ2 tests, odds ratios (OR), and 95% CI. Multivariate logistic regressions were performed to assess predictors for using coronary interventions and for adverse outcomes in females versus males. Dependent variables associated with the independent variable (e.g., angiogram any admission) with at least 80% significance (i.e., p < .2) were included in the multivariate model and these varied for different interventions and outcomes.
      The research has been approved by the Human Research Ethics Committee at St Vincent's Hospital Melbourne, Australia.

      Results

      Data for 28,985 patients admitted to hospital for the first time with a primary diagnosis of ACS during the specified period were included, of whom 10,455 (36%) were female, 178 (1%) were Indigenous Australians, and 7,855 (27%) preferred to speak a language other than English. In total, there were 3,8126 ACS admissions during the 2-year period; close to one in four patients (23%) were admitted to hospital with ACS on more than one occasion. Approximately one-half (46%) of those second admissions were unplanned. Further analyses were conducted either at the patient level or first admission diagnosis level (i.e., n = 28,985).
      Women were more likely than men to be aged 75 or older across all ACS types. Women were also more likely to present with multiple comorbidities (>1 comorbidity: STEMI, 53% vs 40% [p < .001]; NSTEACS, 53% vs 48% [p < .001]) and had greater prevalence of all commonly occurring (i.e., ≥7% of patients) comorbid conditions. They were less likely than men to have a history of smoking (Table 1). Women were more likely than men to be diagnosed with NSTEACS (86% vs 80%; p < .001); within NSTEACS, there was no gender difference in the proportion classified as high risk.
      Table 1Gender Differences in Demographics, Interventions, and Outcomes by Type of ACS
      Total, n (%)Diagnosis on First Admission
      All ACSSTEMINSTEACSHigh-Risk NSTEACSLower-Risk NSTEACS
      Female, n (%)Male, n (%)Female, n (%)Male, n (%)Female, n (%)Male, n (%)Female, n (%)Male, n (%)Female, n (%)Male, n (%)
      Total28,98510,45518,5301,4603,6628,99514,8686,33810,4332,6574,435
      Age (y)
       15–597,555 (26)1,700 (16)5,855 (32)314 (22)1,602 (44)1,386 (15)4,253 (29)768 (12)2,687 (26)618 (23)1,566 (35)
       60–749,962 (34)3,103 (30)6,859 (37)447 (31)1,303 (36)∗∗2,656 (30)5,556 (37)1,648 (26)3,679 (35)1,008 (38)1,877 (42)
       ≥7511,468 (40)5,652 (54)5,816 (31)699 (48)757 (21)4,953 (55)5,059 (34)3,922 (62)4,067 (39)1,031 (39)992 (22)
      Indigenous178 (1)82 (1)96 (1)∗∗13 (1)26 (1)69 (1)70 (0)∗∗40 (1)44 (0)29 (1)26 (1)∗∗∗
      Socioeconomic status
       Low4,221 (15)1,536 (15)2,685 (14)224 (15)555 (15)1,312 (15)2,130 (14)926 (15)1,482 (14)386 (15)648 (15)
       Middle20,625 (71)7,412 (71)13,213 (71)1,041 (71)2,621 (72)6,371 (71)10,592 (71)4,460 (70)7,385 (71)1,911 (72)3,207 (72)
       High4,139 (14)1,507 (14)2,632 (14)195 (13)486 (13)1,312 (15)2,146 (14)952 (15)1,566 (15)360 (14)580 (13)
      Language other than English7,885 (27)2,857 (27)5,028 (27)341 (23)750 (20)∗∗∗2,516 (28)4,278 (29)1,707 (27)2,799 (27)809 (30)1,479 (33)∗∗∗
      Smoking (current/past)11,941 (41)2,823 (27)9,118 (49)379 (26)1,525 (42)2,444 (27)7,593 (51)1,714 (27)5,397 (52)730 (27)2,196 (50)
      Comorbidities
       05,120 (18)1,541 (15)3,579 (19)213 (15)850 (23)1,328 (15)2,729 (18)604 (10)1,420 (14)724 (27)1,309 (30)∗∗∗
       19,825 (34)3,399 (33)6,426 (35)480 (33)1,352 (37)∗∗2,919 (32)5,074 (34)∗∗1,574 (25)2,869 (27)1,345 (51)2,205 (50)
       26,170 (21)2,411 (23)3,759 (20)344 (24)741 (20)∗∗2,067 (23)3,018 (20)1,651 (26)2,406 (23)416 (16)612 (14)
       ≤37,870 (27)3,104 (30)4,766 (26)423 (29)719 (20)2,681 (30)4,047 (27)2,509 (40)3,738 (36)172 (6)309 (7)
      Hypertension19,148 (66)7,228 (69)11,920 (64)944 (65)2,060 (56)6,284 (70)9,860 (66)4,536 (72)7,050 (68)1,748 (66)2,810 (63)∗∗∗
      Cardiac arrhythmias7,678 (26)2,915 (28)4,763 (26)430 (29)896 (24)2,485 (28)3,867 (26)∗∗2,485 (39)3,867 (37)∗∗0 (0)0 (0)
      Fluid and electrolyte disorders6,107 (21)2,630 (25)3,477 (19)402 (28)715 (20)2,228 (25)2,762 (19)1,956 (31)2,410 (23)272 (10)352 (8)
      Renal failure3,982 (14)1,574 (15)2,408 (13)162 (11)273 (7)1,412 (16)2,135 (14)∗∗1,412 (22)2,135 (20)∗∗0 (0)0 (0)
      Peripheral vascular disorders1,936 (7)625 (6)1,311 (7)81 (6)195 (5)544 (6)1,116 (8)439 (7)887 (9)105 (4)229 (5)∗∗∗
      Chronic pulmonary disease1,895 (7)697 (7)11,98 (6)98 (7)146 (4)599 (7)1,052 (7)515 (8)913 (9)84 (3)139 (3)
      Coronary intervention (any admission)
       Angiogram16,566 (57)4,771 (46)11,795 (64)989 (68)3,036 (83)3,782 (42)8,759 (59)2,706 (43)6,419 (62)1,076 (40)2,340 (53)
       PCI3,400 (12)862 (8)2,538 (14)266 (18)900 (25)596 (7)1,638 (11)402 (6)1,164 (11)194 (7)474 (11)
       CABG2,657 (9)628 (6)2,029 (11)75 (5)302 (8)553 (6)1,727 (12)441 (7)1,373 (13)112 (4)354 (8)
       No intervention11,456 (40)5,429 (52)6,027 (33)453 (31)553 (15)4,976 (55)5,474 (37)3,479 (55)3,594 (34)1,497 (56)1,880 (42)
       Outcomes in-hospital death938 (3)449 (4)489 (3)155 (11)161 (4)294 (3)328 (2)279 (4)316 (3)15 (1)12 (0)
       Unplanned readmission3,109 (11)1,046 (10)2,063 (11)∗∗111 (8)312 (9)935 (10)1,751 (12)∗∗713 (11)1,303 (12)∗∗∗222 (8)448 (10)∗∗∗
      Abbreviations: ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; NSTEACS, non–ST-segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.
      Note. High-risk NSTEACS defined as unstable angina with comorbid arrhythmias, congestive heart failure, diabetes or renal failure plus all non-STEMI. Chi-square tests performed for female vs male within each subgroup.
      *p < .001. **p < .01. ***p < .05.
      On univariate analysis, women were less likely than men to undergo invasive coronary intervention (angiogram, PCI, CABG) across all types of ACS (Table 2). Other variables significantly associated with use of coronary interventions in univariate analysis were younger age and fewer comorbid conditions. In terms of ACS type, there was greater use of angiography and PCI for patients diagnosed with STEMI compared with NSTEACS. There was greater use of CABG for patients with high-risk NSTEACS than other types of ACS. Higher socioeconomic status was associated with increased use of angiography and PCI but not CABG (Table 2). Lower rates of coronary intervention in women persisted across STEMI and NSTEACS after adjusting for potential confounders (Table 3).
      Table 2Use of Coronary Interventions and Prevalence of Outcomes—All ACS
      Total, nAngiogram, n (%)Intervention (Any Admission)No Intervention, n (%)Outcome
      PCI, n (%)CABG, n (%)In-Hospital Death (Any Admission), n (%)Unplanned Readmission, n (%)
      Gender
       Female10,4554,771 (46)*862 (8)*628 (6)*5,429 (52)*449 (4)*1,046 (10)**
       Male18,53011,795 (64)*2,538 (14)*2,029 (11)*6,027 (33)*489 (3)*2,063 (11)**
      Age (y)
       15–597,5555,424 (72)*1,279 (17)*640 (8)***1,914 (25)*45 (1)*663 (9)*
       60–749,9626,577 (66)*1,307 (13)*1,306 (13)*2,908 (29)*181 (2)*1,073 (11)
       ≥7511,4684,565 (40)*814 (7)*711 (6)*6,634 (58)*712 (6)*1,373 (12)*
      Indigenous17897 (54)16 (9)11 (6)77 (43)1 (1)***12 (7)
      Socioeconomic status
       Low4,2212,263 (54)*452 (11)***399 (9)1,809 (43)*158 (4)***481 (11)
       Middle20,62511,696 (57)***2,372 (12)1,865 (9)8,237 (40)***653 (3)2,218 (11)
       High4,1392,607 (63)*576 (14)*393 (9)1,410 (34)*127 (3)410 (10)
      Language other than English7,8855,273 (67)*983 (12)***872 (11)*2,280 (29)*207 (3)*907 (12)**
      Smoking (current/past)11,9417,260 (61)*1,338 (11)***1,361 (11)*4,203 (35)*254 (2)*1,631 (14)*
      Comorbidities
       05,1203,192 (62)*835 (16)*159 (3)*1,851 (36)*76 (1)*217 (4)*
       19,8256,136 (62)*1,529 (16)*594 (6)*3,427 (35)*186 (2)*795 (8)*
       26,1703,467 (56)576 (9)*752 (12)*2,440 (40)230 (4)***720 (12)**
       ≥37,8703,771 (48)*460 (6)*1,152 (15)*3,738 (47)*446 (6)*1,377 (17)*
      Diagnosis on first admission
       STEMI5,1224,025 (79)*1,166 (23)*377 (7)*1,006 (20)*316 (6)*423 (8)*
       High-risk NSTEACS16,7719,125 (54)*1,566 (9)*1,814 (11)*7,073 (42)*595 (4)*2,016 (12)*
       Lower-risk NSTEACS7,0923,416 (48)*668 (9)*466 (7)*3,377 (48)*27 (0)*670 (9)*
      Abbreviations: ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; NSTEACS, non–ST-segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.
      Note. High-risk NSTEACS defined as unstable angina with comorbid arrhythmias, congestive heart failure, diabetes or renal failure plus all non-STEMI. Chi-squared tests performed for each subgroup vs. others (e.g., 15–39 vs. ≥40).
      *p < .001. **p < .01. ***p < .05.
      Table 3Gender Differences for Coronary Interventions and Outcomes by ACS Type
      Female n (%)Male n (%)pUnadjustedAdjusted
      OR95% CIOR95% CI
      All ACS10,45518,530
       Angiogram any admission4,771 (46)11,795 (64).0000.480.46–0.500.710.66–0.75
       PCI any admission862 (8)2,538 (14).0000.570.52–0.610.730.66–0.80
       CABG any admission628 (6)2,029 (11).0000.520.47–0.570.580.53–0.64
       No intervention any admission5,429 (52)6,027 (33).0002.242.13–2.351.511.42–1.61
       In-hospital death any admission449 (4)489 (3).0001.661.45–1.890.940.81–1.08
       Unplanned readmission1,046 (10)2,063 (11).0030.890.82–0.960.900.83–0.98
      STEMI1,4603,662
       Angiogram any admission989 (68)3,036 (83).0000.430.38–0.500.730.62–0.86
       PCI any admission266 (18)900 (25).0000.680.59–0.800.850.72–1.00
       CABG any admission75 (5)302 (8).0000.600.46–0.780.590.44–0.77
       No intervention any admission453 (31)553 (15).0002.532.19–2.921.471.24–1.73
       In-hospital death any admission155 (11)161 (4).0002.582.05–3.251.230.95–1.58
       Unplanned readmission111 (8)312 (9).2820.880.71–1.120.980.77–1.25
      NSTEACS8,99514,868
       Angiogram any admission3,782 (42)8,759 (59).0000.510.48–0.530.680.64–0.72
       PCI any admission596 (7)1,638 (11).0000.570.52–0.630.680.62–0.76
       CABG any admission553 (6)1,727 (12).0000.500.45–0.550.580.52–0.64
       No intervention any admission4,976 (55)5,474 (37).0002.132.02–2.241.571.48–1.67
       In-hospital death any admission294 (3)328 (2).0001.501.28–1.760.830.70–0.99
       Unplanned readmission935 (10)1,751 (12).0010.870.80–0.950.900.82–0.98
      Abbreviations: ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; NSTEACS, non–ST-segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.
      Note. Bold text represents a statistically significant relationship.
      ALL ACS: Variables with p < .2 were included in the model: Angiogram, PCI and No intervention: sex, age, socioeconomic status, preferred language, smoking history, number of comorbidities, ACS type; CABG: sex, age, indigenous status, smoking history, number of comorbidities, ACS type; Died: sex, age, preferred language, smoking history, number of comorbidities, ACS type; Unplanned readmission: sex, age, preferred language, smoking history, number of comorbidities, ACS type.
      STEMI: Variables with p < .2 were included in the model: Angiogram and No intervention: sex, age, socioeconomic status, smoking history, number of comorbidities; PCI and CABG: sex, age, socioeconomic status, preferred language, smoking history, number of comorbidities; Died and unplanned readmission: sex, age, smoking history, number of comorbidities.
      NSTEACS: Variables with p < .2 were included in the model: Angiogram, No intervention, Died and unplanned readmission: sex, age, indigenous, socioeconomic status, preferred language, smoking history, number of comorbidities; PCI: sex, age, indigenous, socioeconomic status, preferred language, number of comorbidities; CABG: sex, age, preferred language, smoking history, number of comorbidities.
      In terms of adverse outcomes, the overall rate of in-hospital death was 4% and varied according to ACS type (STEMI vs. high-risk NSTEACS: 6.2% vs, 3.5% [p < .001]; high-risk vs lower risk NSTEACS: 3.5% vs 0.4% [p < .001]). In-hospital death was higher amongst patients who did not receive coronary intervention than those who did (5.7% vs. 1.6%; p < .001). Interestingly, unplanned second admission was higher for those initially diagnosed with high-risk NSTEACS than for those diagnosed with STEMI (12.0% vs. 8.3%; p < .001), with this pattern being consistent for both genders. After adjusting for potential confounding factors, the odds of death for those with STEMI was similar in men and women whereas for those with NSTEACS women had lower adjusted odds of death and unplanned readmission than men (Table 3).

      Discussion

      The main findings from this study included that women (who comprised just greater than one-third of all ACS patients) were more likely than men to have an initial diagnosis of NSTEACS. In line with well-documented epidemiology, we also found that women were older than men, more likely to have multiple comorbidities, and had a greater prevalence of most comorbid conditions, but were less likely to have smoked. The study further found that, for all ACS types, women were around one-half as likely to be treated with an invasive strategy. This disparity in the use of coronary interventions, although being somewhat attenuated by differences in female and male patient characteristics, remained significant after adjusting for potential confounders. However, the higher rate of in-hospital death among women than men was explained fully when data were analyzed to adjust for confounding factors such as ACS type, age, and number of comorbidities. In the multivariate model, female patients with NSTEACS were less likely to suffer adverse outcomes than their male counterparts, despite being less likely to receive a coronary intervention.
      These findings were consistent with those of many other recent international studies where the investigators similarly found that women comprised around a third of the ACS population (
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      • Chew D.P.
      • French J.
      • Briffa T.G.
      • Hammett C.J.
      • Ellis C.J.
      • Ranasinghe I.
      • Brieger D.B.
      Acute coronary syndrome care across Australia and New Zealand: The SNAPSHOT ACS study.
      ,
      • Shehab A.
      • Al-Dabbagh B.
      • Al Habib K.F.
      • Alsheikh-Ali A.A.
      • Almahmeed W.
      • Sulaiman K.
      • Amin H.
      Gender disparities in the presentation, management and outcomes of acute coronary syndrome patients: Data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2).
      ,
      • Yu H.T.
      • Kim K.J.
      • Bang W.D.
      • Oh C.M.
      • Jang J.Y.
      • Cho S.S.
      • Jang Y.
      Gender-based differences in the management and prognosis of acute coronary syndrome in Korea.
      ), and had more comorbidity than men at presentation (
      • Poon S.
      • Goodman S.G.
      • Yan R.T.
      • Bugiardini R.
      • Bierman A.S.
      • Eagle K.A.
      • Yan A.T.
      Bridging the gender gap: Insights from a contemporary analysis of sex-related differences in the treatment and outcomes of patients with acute coronary syndromes.
      ,
      • Yu H.T.
      • Kim K.J.
      • Bang W.D.
      • Oh C.M.
      • Jang J.Y.
      • Cho S.S.
      • Jang Y.
      Gender-based differences in the management and prognosis of acute coronary syndrome in Korea.
      ). The proportion of NSTEACS classified as high risk was similar to another Australian study that used the National Health Data Dictionary classification of high risk (
      • Chew D.P.
      • Amerena J.
      • Coverdale S.
      • Rankin J.
      • Astley C.
      • Brieger D.
      Current management of acute coronary syndromes in Australia: Observations from the acute coronary syndromes prospective audit.
      ). The identification of patients with high-risk NSTEACS is important in light of evidence-based guidelines that indicate the need for an evaluation of the coronary anatomy using angiography for all patients classified high risk, regardless of gender (
      • Anderson J.L.
      • Adams C.D.
      • Antman E.M.
      • Bridges C.R.
      • Califf R.M.
      • Casey Jr., D.E.
      • Wright R.S.
      2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction Foundation/American Heart Association Task Force on Practice Guidelines.
      ,
      • Hamm C.W.
      • Bassand J.
      • Agewall S.
      • Bax J.
      • Boersma E.
      • Bueno H.
      • Widimsky P.
      ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).
      ,
      National Heart Foundation of Australia, & Cardiac Society of Australian and New Zealand
      Guidelines for the management of acute coronary syndromes 2006.
      ). On the other hand, strategies employed in the treatment of lower-risk NSTEACS can be either early invasive or conservative, where the latter involves medical therapy and patients are referred for angiography only if their symptoms fail to abate with medical therapy or if they are reassessed as high risk. The underestimation of risk in women is thought to be one of the major factors leading to the underuse of guideline medications and coronary interventions amongst this population group (
      • Poon S.
      • Goodman S.G.
      • Yan R.T.
      • Bugiardini R.
      • Bierman A.S.
      • Eagle K.A.
      • Yan A.T.
      Bridging the gender gap: Insights from a contemporary analysis of sex-related differences in the treatment and outcomes of patients with acute coronary syndromes.
      ). Our recent systematic review and meta-analysis concluded that women had a 23% greater odds of being classified as high risk than men when stratified using guideline endorsed risk scoring methods (e.g., GRACE, TIMI, PURSUIT risk scores;

      Worrall-Carter, L., McEvedy, S., Kuhn, L., Scruth, E., MacIsaac, A., & Rahman, M. A. (In press). Systematic review and meta-analyses investigating whether risk stratification explains lower rates of coronary angiography among women with non-ST-segment-elevation acute coronary syndrome. Journal of Cardiovascular Nursing.

      in press). We acknowledge that results of that meta-analysis are contrary to the present findings, which found no gender difference in the proportion of NSTEACS patients who were high risk. We suggest that the inconsistency is owing to differences in the method of risk stratification. Specifically, risk scoring tools typically include age as a variable which increases risk, whereas the paradigm for risk stratification in the national guidelines does not include age as a high-risk feature (
      National Heart Foundation of Australia, & Cardiac Society of Australian and New Zealand
      Guidelines for the management of acute coronary syndromes 2006.
      ).
      Our finding of lower rates of coronary angiography in women is consistent with the findings of several other recent studies (
      • Bugiardini R.
      • Estrada J.L.
      • Nikus K.
      • Hall A.S.
      • Manfrini O.
      Gender bias in acute coronary syndromes.
      ,
      • Dey S.
      • Flather M.D.
      • Devlin G.
      • Brieger D.
      • Gurfinkel E.P.
      • Steg P.G.
      • Eagle K.A.
      Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: The Global Registry of Acute Coronary Events.
      ,
      • Poon S.
      • Goodman S.G.
      • Yan R.T.
      • Bugiardini R.
      • Bierman A.S.
      • Eagle K.A.
      • Yan A.T.
      Bridging the gender gap: Insights from a contemporary analysis of sex-related differences in the treatment and outcomes of patients with acute coronary syndromes.
      ,
      • Shehab A.
      • Al-Dabbagh B.
      • Al Habib K.F.
      • Alsheikh-Ali A.A.
      • Almahmeed W.
      • Sulaiman K.
      • Amin H.
      Gender disparities in the presentation, management and outcomes of acute coronary syndrome patients: Data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2).
      ). Importantly, we were able to show that lower rates of coronary intervention could not be explained by confounding factors such as ACS type or age. The current study also found that women were less likely to receive revascularization with PCI or CABG. The decision to revascularize is driven by angiographically assessed coronary anatomy and, as foreshadowed, it is well-known that women presenting with symptoms of ACS are less likely to have obstructive CAD, which is suitable for PCI or CABG; therefore, lower rates of revascularization in women are not surprising (
      • Gulati M.
      • Shaw L.J.
      • Bairey Merz C.N.
      Myocardial ischemia in women: Lessons from the NHLBI WISE study.
      ). However, while appreciating the risk of microvascular CAD in women, it is also important to remember that a substantial proportion of women with ACS symptoms do have male-pattern obstructive CAD (
      • Gulati M.
      • Shaw L.J.
      • Bairey Merz C.N.
      Myocardial ischemia in women: Lessons from the NHLBI WISE study.
      ), so it can be argued that the frequent decision not to refer women for angiography means that their underlying coronary anatomy is not assessed and that opportunities to revascularize eligible women may be missed (
      • Banks A.D.
      Women and heart disease: Missed opportunities.
      ). Recent systematic reviews have confirmed the benefit of an early invasive therapy in women with ACS, while noting the under-representation of women in many trials and the problem of limited reporting of results by gender (
      • Dolor R.J.
      • Melloni C.
      • Chatterjee R.
      • LaPointe N.M.A.
      • Williams J.B.
      • Coeytaux R.R.
      • Samsa G.P.
      Treatment strategies for women with coronary artery disease.
      ,
      • Lundberg G.
      • King S.
      Coronary revascularization in women.
      ).
      In-hospital mortality after ACS has been shown to vary across different countries and to depend on patients' baseline characteristics and clinical management (
      • Andre R.
      • Bongard V.
      • Elosua R.
      • Kirchberger I.
      • Farmakis D.
      • Hakkinen U.
      • Ferrieres J.
      International differences in acute coronary syndrome patients' baseline characteristics, clinical management and outcomes in Western Europe: The EURHOBOP study.
      ). However, the rate of in-hospital mortality in Victorian hospitals from our study was similar to that reported in other ACS registries (
      • Assiri A.S.
      Gender differences in clinical presentation and management of patients with acute coronary syndrome in Southwest of Saudi Arabia.
      ,
      • Chew D.P.
      • French J.
      • Briffa T.G.
      • Hammett C.J.
      • Ellis C.J.
      • Ranasinghe I.
      • Brieger D.B.
      Acute coronary syndrome care across Australia and New Zealand: The SNAPSHOT ACS study.
      ,
      • Mohanan P.P.
      • Mathew R.
      • Harikrishnan S.
      • Krishnan M.N.
      • Zachariah G.
      • Joseph J.
      • Prabhakaran D.
      Presentation, management, and outcomes of 25 748 acute coronary syndrome admissions in Kerala, India: Results from the Kerala ACS Registry.
      ). In univariate analysis, in-hospital mortality in our study was associated with female gender, advanced aged (≥75 years), low SES, more comorbidity, and having STEMI or high-risk NSTEACS. When these confounding factors were accounted for, women were no longer more likely to have adverse outcomes than men. In this regard, our results differ to several studies where female gender remained an independent predictor of in-hospital death (
      • Kuhn L.
      • Page K.
      • Rahman M.A.
      • Worrall-Carter L.
      Gender difference in treatment and mortality of patients with ST-segment elevation myocardial infarction admitted to Victorian public hospitals: A retrospective database study.
      ,
      • Poon S.
      • Goodman S.G.
      • Yan R.T.
      • Bugiardini R.
      • Bierman A.S.
      • Eagle K.A.
      • Yan A.T.
      Bridging the gender gap: Insights from a contemporary analysis of sex-related differences in the treatment and outcomes of patients with acute coronary syndromes.
      ), although there have also been studies that have found no gender difference in mortality after ACS (
      • Assiri A.S.
      Gender differences in clinical presentation and management of patients with acute coronary syndrome in Southwest of Saudi Arabia.
      ,
      • Yu H.T.
      • Kim K.J.
      • Bang W.D.
      • Oh C.M.
      • Jang J.Y.
      • Cho S.S.
      • Jang Y.
      Gender-based differences in the management and prognosis of acute coronary syndrome in Korea.
      ).
      Reasons for older age at the onset of ACS in women compared with men are thought to relate to the protective features of female sex hormones, which act as potent modulators of cardiac risk (
      • Worrall-Carter L.
      • Ski C.
      • Scruth E.
      • Campbell M.
      • Page K.
      Systematic review of cardiovascular disease in women: Assessing the risk.
      ). Thus, ACS is relatively rare in women of reproductive age, but increases after menopause (
      • Choi J.
      • Daskalopoulou S.S.
      • Thanassoulis G.
      • Karp I.
      • Pelletier R.
      • Behlouli H.
      • Pilote L.
      Sex- and gender-related risk factor burden in patients with premature acute coronary syndrome.
      ). Advanced age and postmenopausal status are also associated with a higher rate of comorbidity and greater risk factor load. Women are susceptible to traditional, non-traditional, and gender-specific risk factors for heart disease, including high cholesterol, obesity, lack of physical activity, diabetes, depression, psychosocial risks associated with gender role, the metabolic syndrome, menopause, ovulation dysfunction, polycystic ovarian syndrome, issues that arise during pregnancy, and therapies used to treat breast cancer (
      • Gulati M.
      • Shaw L.J.
      • Bairey Merz C.N.
      Myocardial ischemia in women: Lessons from the NHLBI WISE study.
      ,
      • Worrall-Carter L.
      • Ski C.
      • Scruth E.
      • Campbell M.
      • Page K.
      Systematic review of cardiovascular disease in women: Assessing the risk.
      ). Although women tend to be older than men at presentation, the risk of CHD in younger women should not be underestimated (
      • deGoma E.M.
      • Karlsberg R.P.
      • Judelson D.R.
      • Budoff M.J.
      The underappreciated impact of heart disease.
      ). A recent study found that young women had a greater traditional and non-traditional risk factor burden than men (
      • Choi J.
      • Daskalopoulou S.S.
      • Thanassoulis G.
      • Karp I.
      • Pelletier R.
      • Behlouli H.
      • Pilote L.
      Sex- and gender-related risk factor burden in patients with premature acute coronary syndrome.
      ). An analysis of trends in the annual incidence of ACS in Western Australia found that incidence had increased by 2.3% in 35- to 54-year-old women between 1996 and 2007, whereas it declined in all other groups (
      • Nedkoff L.J.
      • Briffa T.G.
      • Preen D.B.
      • Sanfilippo F.M.
      • Hung J.
      • Ridout S.C.
      • Hobbs M.
      Age- and sex-specific trends in the incidence of hospitalized acute coronary syndromes in Western Australia.
      ). Mortality rates also tend to be higher among young women with ACS, which means that women's health physicians need to remain vigilant regarding risks in this group (
      • Claassen M.
      • Sybrandy K.C.
      • Appelman Y.E.
      • Asselbergs F.W.
      Gender gap in acute coronary heart disease: Myth or reality?.
      ).
      This study has a number of strengths. The population-based data that inform the study findings came from all Victorian hospitals, including public and private and, therefore, represent the whole state of Victoria in Australia. The large sample size facilitated extensive subgroup analyses and adjustment for confounding variables. The limitations of this study are similar to the restrictions encountered in any research using a secondary database. The data were retrospective, and as such were collected at the study hospitals as part of routine procedure and it was not possible to collect further information. Therefore, we were unable to generate risk scores for each case, which may have resulted in different risk stratification profiles for men and women with NSTEACS. Variables regarding the use of noninvasive imaging techniques were not available nor were we able to include patients' angiographically assessed disease severity (which guides decisions around revascularization) in our analyses. The quality of diagnostic coding in the Victorian Admitted Episodes Data Set is maintained through routine, external audit every 3 years. We tried to limit inclusions to patients experiencing a first ACS; however, there is the possibility that misclassification could occur if a patient experienced a first event in another state or country. Restricting the time period to 2 years eliminated any unplanned readmission beyond the study period from our analyses. The classification of comorbidity was based on a coded diagnosis in the hospital record and there may be a potential for under-reporting. However, risk of missed classification applies equally to men and women and is unlikely to introduce bias into the results of the present study.

      Implications for Practice and/or Policy

      Clinicians should be aware that female gender could bias decisions regarding referral for diagnostic angiography and that this may contribute to subsequent adverse outcomes in women. The literature suggests that possible reasons of reluctance to catheterize women are older age, more comorbidities, and increased risk of procedural complications (
      • Dolor R.J.
      • Melloni C.
      • Chatterjee R.
      • LaPointe N.M.A.
      • Williams J.B.
      • Coeytaux R.R.
      • Samsa G.P.
      Treatment strategies for women with coronary artery disease.
      ,
      • Wenger N.K.
      Women and coronary heart disease: A century after Herrick: Understudied, underdiagnosed, and undertreated.
      ). Although a number of noninvasive testing techniques exist that may be more appropriate in the detection of microvascular CAD in stable cases (
      • Mieres J.H.
      • Shaw L.J.
      • Wenger N.K.
      Noninvasive testing in women with suspected ischemic heart disease: Ten highlights to guide quality clinical care.
      ), catheterization remains the gold standard for acute cases involving STEMI or high-risk NSTEACS (
      • Hamm C.W.
      • Bassand J.
      • Agewall S.
      • Bax J.
      • Boersma E.
      • Bueno H.
      • Widimsky P.
      ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).
      ). That notwithstanding, owing to the prevalence of microvascular CAD in women, disease management approaches that fail to look beyond the detection of critical stenosis may fail to identify those women critically at risk (
      • Leuzzi C.
      • Modena M.G.
      Coronary artery disease: Clinical presentation, diagnosis and prognosis in women.
      ). Therefore, an angiogram that shows clear coronary arteries should not lead to an assumption that the patient is disease free, but rather that she should be referred for further testing and appropriate medical therapy (
      • Sharma K.
      • Gulati M.
      Coronary artery disease in women: A 2013 update.
      ).

      Conclusion

      Our results show that women in Victoria were less likely than men to receive coronary interventions after an admission for ACS. Clinicians should be wary of inherent gender bias in decisions to refer patients for angiography.

      Acknowledgments

      The authors acknowledge the contribution of Mr. David Reid, Clinical Data Analyst at St Vincent's Hospital Melbourne, for his assistance in data extraction.

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      Biography

      Professor Linda Worrall-Carter, PhD, BEd, Med(Prelim), RN, is Founder and CEO of Her Heart, a not-for-profit raising awareness of heart disease in women. Previously she was the director of the Centre for Nursing Research and academic director of The Cardiovascular Research Centre at St Vincent's Hospital/Australian Catholic University.
      Ms. Samantha McEvedy, LLB, worked as a Research Associate with St Vincent's Centre for Nursing Research (SVCNR) at Australian Catholic University.
      Associate Professor Andrew Wilson, MBBS, FRACP, PhD, is a Cardiologist at St Vincent's Hospital Melbourne; Reader and Principal Research Fellow at The University of Melbourne and Adjunct Professor at Australian Catholic University.
      Dr. Muhammad Aziz Rahman, MBBS, MPH, PhD, an epidemiologist and a medical doctor, worked as a Senior Research Fellow at St Vincent's Centre for Nursing Research (SVCNR) and The Cardiovascular Research Centre (CvRC) at Australian Catholic University.