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Canadian Journal of Cardiology

Clinical Outcomes in Younger Women Hospitalized With an Acute Myocardial Infarction: A Contemporary Population-Level Analysis

Published:October 04, 2022DOI:https://doi.org/10.1016/j.cjca.2022.06.023

      Abstract

      Background

      For younger women with acute myocardial infarction (AMI), little is known regarding their contemporary care pathways and clinical outcomes.

      Methods

      We studied AMI patients aged 18-55 years, hospitalized from April 1, 2009, to March 31, 2019, in Ontario, Canada. We compared trends in comorbidities, angiographic findings, and revascularisation rates in men and women. The primary outcome was 1-year all-cause mortality or readmission for unstable angina, AMI, heart failure, or stroke. Inverse probability of treatment weighting was used to account for differences in baseline clinical characteristics between men and women.

      Results

      Among the 38,071 AMI patients included, 8,077 (21.2%) were women. Over the study period, women had increasing rates of diabetes (24.8% to 34.9%; Ptrend < 0.001), and declining rates of smoking (53.2% to 41.7%; Ptrend < 0.005). Although most patients received coronary angiography (96%), coronary revascularisation was less frequent among women than men (percutaneous coronary intervention: 61.9% vs 78.8% [P < 0.001]; surgery: 4.1% vs 6.0% [P < 0.001]). Women had more normal coronary anatomy (5.8% vs 1.7%; P < 0.001) and nonobstructive disease (22.8% vs 9.3%; P < 0.001) than men. Compared with men, the primary composite end point was significantly increased among women (10.0% vs 7.9%, adjusted HR 1.11; P = 0.02) and related to increased readmission rates for cardiovascular events. All-cause readmission was significantly increased among women (25.8% vs 21.1%, adjusted HR 1.34; P < 0.0001).

      Conclusions

      Coronary angiography is performed almost universally in younger women with AMI; however, coronary revascularisation is less frequent, perhaps reflecting less obstructive disease. Although mortality rates after AMI were similar between sexes, cardiovascular readmission rates and all-cause readmissions were significantly increased among women.

      Résumé

      Contexte

      La trajectoire actuelle de soins et les résultats cliniques des jeunes patientes ayant subi un infarctus aigu du myocarde (IAM) sont mal connus.

      Méthodologie

      Nous avons mené une étude portant sur les patients de 18 à 55 ans ayant subi un IAM et hospitalisés entre le 1er avril 2009 et le 31 mars 2019 en Ontario (Canada). Nous avons comparé les tendances entre les hommes et les femmes pour les troubles concomitants, les observations à l’angiographie et les taux de revascularisation. Le paramètre d’évaluation principal était la mortalité toutes causes confondues ou la réadmission à hôpital en raison d’une angine instable, d’un IAM, d’une insuffisance cardiaque ou d’un accident vasculaire cérébral après un an. La pondération par probabilité inverse de traitement a été utilisée pour tenir compte des différences initiales dans les caractéristiques cliniques entre les hommes et les femmes.

      Résultats

      Parmi les 38 071 patients ayant subi un IAM admis à l’étude, 8 077 (21,2 %) étaient des femmes. Pendant la période visée, le taux de diabète chez les femmes a augmenté (de 24,8 % à 34,9 %; Ptendance < 0,001), et le taux de tabagisme a diminué (de 53,2 % à 41,7 %; Ptendance < 0,005). Bien qu’une angiographie coronarienne ait été effectuée dans presque tous les cas (96 %), la revascularisation coronarienne était moins fréquente chez les femmes que chez les hommes (intervention coronarienne percutanée : 61,9 % vs 78,8 % [P < 0,001]; intervention chirurgicale : 4,1 % vs 6,0 % [P < 0,001]). Les femmes avaient plus fréquemment que les hommes une anatomie normale des artères coronaires (5,8 % vs 1,7 %; P < 0,001) ou une coronaropathie non obstructive (22,8 % vs 9,3 %; P < 0,001). Par rapport aux hommes, la fréquence du critère d’évaluation principal regroupé était significativement plus élevée chez les femmes (10,0 % vs 7,9 %, RRI ajusté de 1,11; P = 0,02), accompagnée d’un taux de réadmission plus élevé pour des événements cardiovasculaires. La réadmission toutes causes confondues était significativement plus élevée chez les femmes que chez les hommes (25,8 % vs 21,1 %, RRI ajusté de 1,34; P < 0,0001).

      Conclusions

      L’angiographie coronarienne est pratiquement systématique chez les jeunes patientes ayant subi un IAM; toutefois, la revascularisation coronarienne est moins fréquente, ce qui pourrait s’expliquer par le plus faible taux de coronaropathies obstructives. Malgré des taux de mortalité similaires entre les sexes après un IAM, les taux de réadmission pour des événements cardiovasculaires et de réadmission toutes causes confondues étaient significativement plus élevés chez les femmes.
      Despite improvements in the management and outcomes of patients with ischemic heart disease, large numbers of young women are hospitalized with an acute myocardial infarction (AMI).
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      that included limited numbers of women, and others may not be representative of contemporary AMI care.
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      • Vaccarino V.
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      • Barron H.V.
      • Krumholz H.M.
      Sex-based differences in early mortality after myocardial infarction. National Registry of Myocardial Infarction 2 participants.
      ,
      • Bucholz E.M.
      • Strait K.M.
      • Dreyer R.P.
      • et al.
      Editor’s choice—Sex differences in young patients with acute myocardial infarction: a VIRGO study analysis.
      ,
      • Pelletier R.
      • Humphries K.H.
      • Shimony A.
      • et al.
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      • DeVon H.A.
      • et al.
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      ,
      • Vaccarino V.
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      • Krumholz H.M.
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      • Otten A.M.
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      • et al.
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      To understand whether disparity continues to exist in processes of care and clinical outcomes, we studied the population of younger AMI patients hospitalized from 2009 to 2019 in Ontario, Canada.

      Methods

      Data sources

      Ontario is Canada’s largest province, with a population of around 14 million, all of whom are provided universal health care provided by a single third-party payer, the Ministry of Health and Long-Term Care.
      We conducted an observational study using population-linked clinical and administrative data in Ontario, Canada. We used the CorHealth Ontario Cardiac Registry, which is a prospective clinical database that collects demographic, clinical, and procedural characteristics on all patients undergoing cardiac catheterisation and percutaneous coronary intervention (PCI) in Ontario, Canada. This clinical registry was then linked to several administrative databases with the use of unique encoded identifiers and analysed at ICES (formerly known as the Institute for Clinical Evaluative Sciences). The Canadian Institute for Health Information’s Discharge Abstract Database (CIHI-DAD) was used to capture additional clinical comorbidities as well as ascertain admission status. The Ontario Health Insurance Plan physician claims database was used to determine physician follow-up. Statistics Canada census data were used to assess neighbourhood income information. The Registered Persons Database was used to determine the vital status of patients. The use of data in this study was authorized under section 45 of Ontario’s Personal Health Information Protection Act, which does not require review by a research ethics board.

      Study population

      The study cohort included patients aged 18-55 years, with a valid health card number and who were hospitalized with AMI in Ontario from April 1, 2009, to March 31, 2019. A diagnosis of AMI was identified by the International Classification of Diseases, 10th revision, Canada (ICD-10-CA) codes I21 and I22 in the CIHI-DAD. Patients who had a death date before the index date, left hospital against medical advice, were flagged as a nonurgent admission, or left hospital within 24 hours of admission were excluded. For patients with multiple AMI admissions to hospital in a given year, the first AMI was considered as the index event for study inclusion. An age threshold of 55 years or less to denote younger patients is consistent with previous studies.
      • Arora S.
      • Stouffer G.A.
      • Kucharska-Newton A.M.
      • et al.
      Twenty year trends and sex differences in young adults hospitalized with acute myocardial infarction.
      • Bucholz E.M.
      • Strait K.M.
      • Dreyer R.P.
      • et al.
      Editor’s choice—Sex differences in young patients with acute myocardial infarction: a VIRGO study analysis.
      • Pelletier R.
      • Humphries K.H.
      • Shimony A.
      • et al.
      Sex-related differences in access to care among patients with premature acute coronary syndrome.

      Angiographic data

      Angiographic data obtained within 30 days of AMI hospitalization characterised the extent of coronary artery disease (CAD) as 0-3 vessels with ≥ 70% stenosis. Normal coronary arteries was defined as the absence of CAD on coronary angiography. Nonobstructive disease was defined as the presence of coronary artery disease with no significantly diseased vessels ≥ 70%. Significant left main CAD was defined as a stenosis of ≥ 50% involving the left main coronary artery.

      Outcomes

      The primary outcome of this study was a composite end point composed of 1-year all-cause mortality or hospitalization for unstable angina, AMI, heart failure, or stroke. Secondary outcomes included the individual components of the primary outcome and all-cause readmission at 30 days and 1 year. We also reported trends in the prevalence of cardiac risk factors over time, utilisation rates of invasive procedures (coronary angiography, PCI, or surgical revascularisation), and access to primary and speciality care after AMI.

      Statistical analysis

      We compared demographics and clinical characteristics of women and men by means of χ2 test for categoric variables and analysis of variance for continuous variables as appropriate. To examine trends in risk factors, we stratified the patient cohort by fiscal year (April 1 to March 31) of the index hospitalization. Temporal changes in the prevalence of diabetes, hypertension, dyslipidemia, and current smoking were evaluated with linear regression.
      The comparison of outcomes among men and women was performed using an inverse probability of treatment weighting (IPTW) approach to account for baseline differences between men and women.
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      An introduction to propensity score methods for reducing the effects of confounding in observational studies.
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      Variables considered in the weighting are presented in Tables 1 and 2, including demographic variables (age, neighbourhood income quintile), cardiac risk factors, comorbidities, and admission characteristics (ST-segment elevation myocardial infarction, left ventricular ejection fraction, extent of coronary artery disease). Standardised differences were used to compare characteristics in the weighted sample, where differences of less than 0.1 indicated good balance.
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      with men as the reference group. Adjusted Kaplan-Meier survival curves were estimated for men and women separately in the IPTW sample. A weighted log-rank test was used to compare group differences in survival functions.
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      Table 1Baseline characteristics, cardiac evaluations, revascularisation, and physician follow-up
      Total (n = 38,071)Women (n = 8077)Men (n = 29,994)P value
      Demographics
       Mean age, y48.7 ± 5.648.9 ± 5.548.6 ± 5.60.002
       Rural residency5385 (14.1)1300 (16.1)4085 (13.6)< 0.001
      Mean length of stay, d4.2 ± 4.64.5 ± 4.94.1 ± 4.5< 0.001
      Socioeconomic status< 0.001
       Lowest income quintile8853 (23.3)2203 (27.3)6650 (22.2)
       Highest income quintile5975 (15.7)1081 (13.4)4894 (16.3)
      Presentation
       STEMI17,296 (45.4)2898 (35.9)14,398 (48.0)< 0.001
      Cardiac risk factors
       Diabetes8605 (22.6)2452 (30.4)6153 (20.5)< 0.001
       Hypertension15,748 (41.4)3823 (47.3)11,925 (39.8)< 0.001
       Dyslipidemia18,877 (49.6)3650 (45.2)15,227 (50.8)< 0.001
       Current smoker17,843 (46.9)3673 (45.5)14,170 (47.2)0.005
       Former smoker5108 (13.4)960 (11.9)4148 (13.8)< 0.001
      Comorbidities
       Previous MI3340 (8.8)751 (9.3)2589 (8.6)0.06
       Previous PCI5020 (13.2)882 (10.9)4138 (13.8)< 0.001
       Previous CABG888 (2.3)193 (2.4)695 (2.3)0.702
       Heart failure1424 (3.7)460 (5.7)964 (3.2)< 0.001
       Renal disease1567 (4.1)537 (6.6)1030 (3.4)< 0.001
       COPD4661 (12.2)1426 (17.7)3235 (10.8)< 0.001
       Cancer536 (1.4)193 (2.4)343 (1.1)< 0.001
       Peripheral vascular disease1393 (3.7)488 (6.0)905 (3.0)< 0.001
       Cerebrovascular disease384 (1.0)145 (1.8)239 (0.8)< 0.001
      Echocardiography during index hospitalization25,857 (67.9)5430 (67.2)20,427 (68.1)0.14
      Left ventricular function
      Left ventricular function data was available for a subset of 36,368 patients: 7518 female, and 28,850 male.
      < 0.001
       < 20%511 (1.4)103 (1.4)408 (1.4)
       20%-34%2917 (8.0)586 (7.8)2331 (8.1)
       35%-49%9715 (26.7)1702 (22.6)8013 (27.8)
       ≥ 50%17,035 (46.8)3946 (52.5)13,089 (45.4)
      Coronary angiography during index hospitalization36,523 (95.9)7549 (93.5)28,974 (96.6)< 0.001
      Extent of disease
       ≥ 50% lesion in left main artery906 (2.5)156 (2.1)750 (2.6)0.009
       No. of diseased vessels ≥ 70%< 0.001
      04399 (12.1)1711 (22.8)2688 (9.3)
      119,270 (53.0)3856 (51.3)15,414 (53.4)
      28547 (23.5)1315 (17.5)7232 (25.1)
      34152 (11.4)636 (8.5)3516 (12.2)
       Normal coronary arteries967 (2.5)470 (5.8)497 (1.7)< 0.001
      Revascularisation during index hospitalization
       PCI28,622 (75.2)4999 (61.9)23,623 (78.8)< 0.001
       CABG2133 (5.6)329 (4.1)1804 (6.0)< 0.001
      Outpatient follow-up within 90 days
       Cardiology follow-up28,050 (74.5)5668 (71.1)22,382 (75.4)< 0.001
       Primary care follow-up34,564 (91.8)7450 (93.4)27,114 (91.4)< 0.001
      Data are presented as mean ± SD or n (%).
      CABG, coronary artery bypass graft surgery; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.
      Left ventricular function data was available for a subset of 36,368 patients: 7518 female, and 28,850 male.
      Table 2Weighted baseline characteristics, and cardiac evaluations
      WomenMenWeighted standard difference
      Demographics
       Mean age, y48.748.70.003
       Rural residency14.814.20.017
      Socioeconomic status
       Lowest income quintile23.623.30.006
       Highest income quintile15.515.70.005
      Presentation
       STEMI46.446.20.005
      Cardiac risk factors
       Diabetes23.322.80.012
       Hypertension42.041.50.010
       Dyslipidemia49.949.60.005
       Current smoker48.047.00.021
       Former smoker13.413.40.0003
      Comorbidities
       Previous MI9.38.90.015
       Previous PCI13.513.20.009
       Previous CABG2.42.30.004
       Heart failure4.03.90.008
       Renal disease4.44.20.009
       COPD12.712.40.009
       Cancer1.01.00.001
       Peripheral vascular disease4.03.80.011
       Cerebrovascular disease1.01.00.001
      Left ventricular function
       < 20%1.51.40.008
       20%-34%7.77.70.001
       35%-49%25.225.50.007
       ≥ 50%44.444.70.006
      Extent of disease at angiography
       No. of diseased vessels ≥ 70%
      011.411.40.0001
      150.249.90.006
      221.421.70.007
      3 or left main artery ≥ 50%12.312.40.005
      CABG, coronary artery bypass graft surgery; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.

      Results

      Creation of the study cohort

      There were 213,897 records for patients who were admitted to an acute care hospital in Ontario with a diagnosis of AMI from April 1, 2009, to March 31, 2019 (Fig. 1). After exclusions, the study cohort included 38,071 AMI hospitalizations involving 8,077 (21.2%) women. Notably, younger women accounted for approximately 11% of women of all ages admitted with AMI during the study period.
      Figure thumbnail gr1
      Figure 1Construction of the hospitalized acute myocardial infarction (AMI) cohort.

      Baseline characteristics

      The overall mean age at presentation with AMI was 48.7 ± 5.6 years, and the mean length of stay was 4.2 ± 4.6 days (Table 1). A greater proportion of younger women belonged to the lowest income quintile than did men (27.3% vs 22.2%). Overall, women had a significantly greater prevalence of cardiac and other comorbidities compared with men. Compared with men, women had a higher prevalence of diabetes (30.4% vs 20.5%), hypertension (47.3% vs 39.8%), chronic obstructive pulmonary disease (17.7% vs 10.8%), and renal failure (6.6% vs 3.4%). Rates of current smoking, dyslipidemia, and previous PCI were greater in men.
      Risk factors that changed the most over time were the prevalence of diabetes and current smoking in women (Table 3 and Fig. 2). In 2009, nearly 25% of women had diabetes, and by 2018 the rate of diabetes increased to 34.9%. In contrast, the rates of diabetes increased by 3.9% from 18.2% to 22.1% in men over the same time period. Current smoking significantly decreased in both women and men during this time period (women: 53.2% in 2009 to 41.7% in 2018; men: 52.7% to 43.3%).
      Table 3Temporal trends in the prevalence of cardiac risk factors
      Risk factorSex2009, %2018, %Annual % change (95% CI)P valuePinteraction
      DiabetesWomen24.834.90.99 (0.80 to 1.19)< 0.001< 0.001
      Men18.222.10.45 (0.25 to 0.65)< 0.001
      HypertensionWomen45.247.50.08 (−0.22 to 0.37)0.620.80
      Men38.740.80.13 (−0.17 to 0.42)0.39
      DyslipidemiaWomen44.946.70.04 (−0.29 to 0.38)0.810.04
      Men52.447.9−0.46 (−0.79 to −0.12)0.007
      Current smokingWomen53.241.7−0.93 (−1.45 to −0.40)< 0.0010.88
      Men52.743.3−0.87 (−1.40 to −0.34)0.0013
      Figure thumbnail gr2ac
      Figure 2Trends in cardiac risk factors. (A) Diabetes; (B) hypertension; (C) dyslipidemia; (D) current smoking.
      Figure thumbnail gr2d
      Figure 2Trends in cardiac risk factors. (A) Diabetes; (B) hypertension; (C) dyslipidemia; (D) current smoking.

      Cardiac evaluations and physician follow-up

      About two-thirds of patients had echocardiography for left ventricular function assessment during AMI hospitalization (Table 1). Of those assessed, proportionally more women had left ventricular ejection fraction ≥ 50% than men (52.5% vs 45.4%; P < 0.001). Overall, 93.5% of women received coronary angiography during hospitalization compared with 96.6% of men. The use of coronary angiography increased significantly during the study period (women: 90.4% in 2009 to 95.9% in 2018 [Ptrend < 0.001]; men: 94.0% in 2009 to 97.8% in 2018 [Ptrend < 0.001]). Coronary angiography revealed a significantly greater prevalence of normal coronary arteries (5.8% vs 1.7%; P < 0.001), no significantly diseased vessels ≥ 70% (22.8% vs 9.3%; P < 0.001), and less multivessel disease in women compared with men. Women underwent significantly less coronary revascularisation during the index hospitalization than men (PCI: 61.9% vs 78.8% [P < 0.001]; coronary artery bypass graft surgery [CABG]: 4.1% vs 6.0% [P < 0.001]). Rates of 90-day follow-up with a cardiologist were slightly lower for women than men (71.1% vs.75.4%; P < 0.001) while more than 90% of patients had primary care follow-up within 90 days of AMI hospitalization.

      Clinical outcomes

      The incidence of the primary composite end point was significantly increased among women (10.0% vs 7.9%, adjusted HR [aHR] 1.11, 95% CI 1.02-1.21; P = 0.02) (Table 4; unadjusted clinical outcomes presented in Supplemental Table S1). This finding was driven by significantly higher rates of 1-year readmission for unstable angina or AMI, heart failure, and stroke experienced by women. Mortality rates were not significantly different between women and men at 1 year (2.9% vs 2.8%, aHR 1.03, 95% CI 0.88-1.20; P = 0.70). The incidence of 1-year all-cause readmission was significantly greater among women than men (25.8% vs 21.1%, aHR 1.34, 95% CI 1.27-1.42; P < 0.0001).
      Table 4Clinical outcomes after inverse probability of treatment weighting adjustment
      Adjusted outcomeWomen, %Men, %HR (95% CI)P value
      Primary end point
       30 days3.73.41.11 (0.97-1.28)0.13
       1 year10.07.91.11 (1.02-1.21)0.02
      Mortality
       30 days1.51.60.98 (0.79-1.21)0.83
       1 year2.92.81.03 (0.88-1.20)0.070
      Unstable angina or AMI readmission
       30 days1.61.41.16 (0.93-1.44)0.19
       1 year5.44.21.34 (1.18-1.52)< 0.0001
      Heart failure hospitalization
       30 days0.50.41.62 (1.13-2.32)0.008
       1 year1.51.21.40 (1.13-1.75)0.002
      Stroke
       30 days0.10.10.92 (0.42-2.03)0.83
       1 year0.50.31.69 (1.15-2.47)0.008
      Revascularisation (PCI or CABG) after discharge
       30 days1.52.30.77 (0.60-0.97)0.03
       1 year5.86.71.03 (0.90-1.18)0.66
      All-cause readmission
       30 days9.48.21.26 (1.15-1.38)< 0.0001
       1 year25.821.11.34 (1.27-1.42)< 0.0001
      AMI, acute myocardial infarction; CABG, coronary artery bypass graft surgery; PCI, percutaneous coronary intervention.

      Discussion

      This population-based study evaluated the characteristics, care patterns, and clinical outcomes in a cohort of younger women and men hospitalized with AMI in Ontario, Canada, and adds several insights. First, we found that younger women hospitalized with AMI had a significantly higher prevalence of cardiac risk factors and comorbidities compared with younger men with AMI. Second, we found a steady increase in the prevalence of diabetes in women over time, such that 24.8% had diabetes in 2009 compared with 34.9% in 2019. The prevalence of diabetes increased more among women than men during this period (10% vs 4%). Third, we noted a high prevalence of current smoking among younger patients of both sexes (40%-50%) and much higher than rates noted among the general population (10%). A significant decline in current smoking rates occurred during the study period, somewhat more for women than for men. Fourth, we found that the use of coronary angiography was nearly universal for all younger patients; however, we observed much lower rates of PCI provided to women compared with men, suggesting sex differences in the pathophysiology of AMI. This assertion may be partially supported by the greater prevalence of normal coronary arteries and nonobstructive coronary artery disease observed at angiography among women compared with men. Finally, although 1-year mortality rates were similar among men and women, we observed significantly greater rates of 1-year rehospitalization for major adverse cardiovascular events and all-cause readmission among women.
      Our contemporary study adds to the current understanding of potential sex differences in AMI treatment and outcomes among younger patients. Most of the published literature on sex-based analyses of younger AMI patients used data collected before 2016.
      • Vaccarino V.
      • Parsons L.
      • Every N.R.
      • Barron H.V.
      • Krumholz H.M.
      Sex-based differences in early mortality after myocardial infarction. National Registry of Myocardial Infarction 2 participants.
      ,
      • Vaccarino V.
      • Parsons L.
      • Peterson E.D.
      • Rogers W.J.
      • Kiefe C.I.
      • Canto J.
      Sex differences in mortality after acute myocardial infarction: changes from 1994 to 2006.
      ,
      • Berg J.
      • Bjorck L.
      • Nielsen S.
      • Lappas G.
      • Rosengren A.
      Sex differences in survival after myocardial infarction in Sweden, 1987-2010.
      ,
      • Arora S.
      • Stouffer G.A.
      • Kucharska-Newton A.M.
      • et al.
      Twenty year trends and sex differences in young adults hospitalized with acute myocardial infarction.
      • Bucholz E.M.
      • Strait K.M.
      • Dreyer R.P.
      • et al.
      Editor’s choice—Sex differences in young patients with acute myocardial infarction: a VIRGO study analysis.
      • Pelletier R.
      • Humphries K.H.
      • Shimony A.
      • et al.
      Sex-related differences in access to care among patients with premature acute coronary syndrome.
      ,
      • Khera S.
      • Kolte D.
      • Gupta T.
      • et al.
      Temporal trends and sex differences in revascularisation and outcomes of ST-segment elevation myocardial infarction in younger adults in the United States.
      ,
      • Alkhouli M.
      • Alqahtani F.
      • Jneid H.
      • Al Hajji M.
      • Boubas W.
      • Lerman A.
      Age-stratified sex-related differences in the incidence, management, and outcomes of acute myocardial infarction.
      For example, the landmark 1999 study by Vaccarino et al. found 3%-3.5% higher mortality rates among younger women with AMI compared with men and challenged cardiologists to take action for this high-risk group.
      • Vaccarino V.
      • Parsons L.
      • Every N.R.
      • Barron H.V.
      • Krumholz H.M.
      Sex-based differences in early mortality after myocardial infarction. National Registry of Myocardial Infarction 2 participants.
      Some of the difference in outcomes between men and women in that early study may be explained by relatively low rates of prescribing evidence-based medications (aspirin, beta-blockers, and thrombolysis) and a 10% lower use of coronary angiography in women than men. The past decade has seen tremendous improvements in AMI care through both public and professional education campaigns (including the American Heart Association’s Go Red for Women, Get With The Guidelines, and Mission Lifeline), reorganisation of health care systems around ST-segment elevation myocardial infarction care offering primary PCI or pharmaco-invasive approaches, and better pharmacotherapy for AMI (eg, potent antiplatelet therapy). In this context, it is encouraging to see that by 2019 in Ontario, certain care gaps identified in earlier studies appear to have closed such that the use of coronary angiography is largely universal for both sexes, the rates of primary and specialist care are high, and mortality rates over our study period were similar among men and women and relatively low overall.
      Despite these aforementioned gains in the quality of AMI care, we observed that younger women continue to be readmitted for recurrent AMI, heart failure, and stroke to a significantly greater extent than younger men, and that all-cause readmissions rates are also significantly higher. Chest pain syndromes experienced after AMI hospitalization in women have a fairly broad differential diagnosis that includes stent thrombosis, loss of coronary side branches after PCI, extension of spontaneous coronary artery dissection (SCAD)–related dissection, coronary vasospasm, and microcirculatory dysfunction, in addition to noncardiac chest discomfort. The increased rate of all-cause readmission is an interesting finding given our angiographic data demonstrating higher rates of normal coronary arteries or nonobstructive disease among women. We expected that less angiographic disease may lead to fewer readmissions and less use of health care services in women, but this was not the case. A previous younger AMI cohort showed that women were more likely to be rehospitalized for all causes, but not cardiac causes.
      • Pelletier R.
      • Choi J.
      • Winters N.
      • et al.
      Sex differences in clinical outcomes after premature acute coronary syndrome.
      Social determinants of health have been shown to play an important role after AMI in younger patients in both the US and Canada, with unemployment being associated with lower quality of care and increased cardiac readmissions.
      • Raparelli V.
      • Pilote L.
      • Dang B.
      • et al.
      Variations in quality of care by sex and social determinants of health among younger adults with acute myocardial infarction in the US and Canada.
      Furthermore, greater symptom levels of depression, posttraumatic stress disorder, and perceived stress have been reported among younger women recovering from AMI compared with similarly aged men, as well as increased rates of mental stress–induced myocardial ischemia.
      • Bucholz E.M.
      • Strait K.M.
      • Dreyer R.P.
      • et al.
      Editor’s choice—Sex differences in young patients with acute myocardial infarction: a VIRGO study analysis.
      ,
      • Vaccarino V.
      Myocardial infarction in young women.
      ,
      • Xu X.
      • Bao H.
      • Strait K.
      • et al.
      Sex differences in perceived stress and early recovery in young and middle-aged patients with acute myocardial infarction.
      ,
      • Vaccarino V.
      • Sullivan S.
      • Hammadah M.
      • et al.
      Mental stress–induced myocardial ischemia in young patients with recent myocardial infarction: sex differences and mechanisms.
      As previously observed among patients recovering from SCAD, an adverse psychosocial profile could result in increased emergency room visits or readmissions for chest pain or related symptoms.
      • Edwards K.S.
      • Vaca K.C.
      • Naderi S.
      • Tremmel J.A.
      Patient-reported psychological distress after spontaneous coronary artery dissection: evidence for post-traumatic stress.
      Some readmissions could also be related to bleeding complications after AMI, given that more women than men are typically characterised as having high bleeding risk status,
      • Urban P.
      • Mehran R.
      • Colleran R.
      • et al.
      Defining high bleeding risk in patients undergoing percutaneous coronary intervention.
      ,
      • Chandiramani R.
      • Cao D.
      • Claessen B.E.
      • et al.
      Sex-related differences in patients at high bleeding risk undergoing percutaneous coronary intervention: a patient-level pooled analysis from 4 postapproval studies.
      or perhaps the presence of increased comorbidities at baseline among women may contribute to increased risk for rehospitalization after AMI. While we do not fully understand all the reasons for increased rates of all-cause readmissions among women compared with men, we suspect that differing pathophysiology for AMI (CAD, SCAD, coronary vasospasm, or microvascular dysfunction), new heart failure due to reduced ejection fraction, and varying comorbidities and psychosocial needs may be contributory factors. Possible strategies to avoid early readmissions among women could include increased referral rates to cardiac rehabilitation programs, including home-based programs, and those programs offering access to peer support groups. Furthermore, increasing the number of follow-ups and ensuring an early follow-up (2 weeks) after discharge for AMI may reduce the number of early readmissions or emergency room visits. Leveraging virtual care and physician extenders or other allied health professionals may make this a viable strategy to address unmet care needs among younger women recovering from AMI.
      Consistent with other studies, we also found that younger women with AMI had a greater burden of cardiac risk factors and other comorbidities compared with younger men.
      • Berg J.
      • Bjorck L.
      • Nielsen S.
      • Lappas G.
      • Rosengren A.
      Sex differences in survival after myocardial infarction in Sweden, 1987-2010.
      ,
      • Arora S.
      • Stouffer G.A.
      • Kucharska-Newton A.M.
      • et al.
      Twenty year trends and sex differences in young adults hospitalized with acute myocardial infarction.
      ,
      • Otten A.M.
      • Maas A.H.
      • Ottervanger J.P.
      • et al.
      Is the difference in outcome between men and women treated by primary percutaneous coronary intervention age dependent? Gender difference in STEMI stratified on age.
      ,
      • Hao Y.
      • Liu J.
      • Liu J.
      • et al.
      Sex differences in in-hospital management and outcomes of patients with acute coronary syndrome.
      The Atherosclerosis Risk in Communities (ARIC) surveillance study reported 20-year trends (1995 to 2014) and sex differences in 8737 young AMI patients aged 34 to 54 years in 4 communities in the United States.
      • Arora S.
      • Stouffer G.A.
      • Kucharska-Newton A.M.
      • et al.
      Twenty year trends and sex differences in young adults hospitalized with acute myocardial infarction.
      Over this period, among young women with AMI, the prevalence of hypertension increased by 9% (66% to 75%, vs 12% increase in younger men), diabetes increased by 2% (34% to 36%, vs 8% increase in younger men), and smoking declined by 10% (56% to 46% vs 6% decrease in younger men). In our study, the prevalence of diabetes in women increased by 10% in just 10 years, and that was greater than the increase of diabetes in men. By 2018, more than 1 in 3 young women with AMI had diabetes, almost one-half had hypertension, and dyslipidemia, and more than 2 in 5 were current smokers. Although it is encouraging to see a declining prevalence of current smoking in this cohort, we still observed that > 40% of patients were current smokers in 2018-2019. These estimates are consistent with other published reports in younger AMI populations.
      • Biery D.W.
      • Berman A.N.
      • Singh A.
      • et al.
      Association of smoking cessation and survival among young adults with myocardial infarction in the Partners YOUNG-MI Registry.
      ,
      • Yandrapalli S.
      • Nabors C.
      • Goyal A.
      • Aronow W.S.
      • Frishman W.H.
      Modifiable risk factors in young adults with first myocardial infarction.
      Biery et al. reported lower socioeconomic status, increased rates of mental illness, alcohol use, and illicit drug use among current smokers with AMI at a younger age.
      • Biery D.W.
      • Berman A.N.
      • Singh A.
      • et al.
      Association of smoking cessation and survival among young adults with myocardial infarction in the Partners YOUNG-MI Registry.
      The increased burden of cardiovascular risk factors among younger women with AMI confirms the ongoing need for aggressive primary prevention measures that could potentially reduce the development of AMI in these vulnerable patients. In the postpandemic era, renewed attention to public education and primary prevention measures by national cardiovascular organisations would be worthwhile. Such initiatives would highlight the importance of healthy lifestyle choices, regular exercise, and the maintenance of normal body weight to prevent the development of hypertension, dyslipidemia, diabetes, and cardiovascular diseases.
      Despite prior studies showing that women receive invasive angiography less often than men, we found that almost all young patients with AMI, regardless of sex, received coronary angiography. The increasing rates of angiography over time for both men and women is also consistent with increasing capacity for cardiac services within the Canadian health care system. Interestingly, we saw a large gap in the use of coronary revascularisation such that the PCI rate was lower by 16.9% and CABG rate by 1.9% for women compared with men. Previous studies have speculated that women with AMI had a lower rates of coronary revascularisation because of older age, comorbidities, smaller coronary arteries, or less obstructive plaques.
      • Mehta L.S.
      • Beckie T.M.
      • DeVon H.A.
      • et al.
      Acute myocardial infarction in women: a scientific statement from the American Heart Association.
      ,
      • Aggarwal N.R.
      • Patel H.N.
      • Mehta L.S.
      • et al.
      Sex differences in ischemic heart disease: advances, obstacles, and next steps.
      Although we were unable to distinguish all the reasons underlying these differences, we think, for several reasons, that the difference may not be a result of undertreatment of women. First, patients in our cohort were young and had fewer comorbidities overall compared with those studied in the prior literature, and therefore, concerns of risks associated with PCI are unlikely a reason to explain the observed sex difference. Second, selection bias would tend to occur at the time of selection of patients for coronary angiography and less likely to occur when obstructive lesions were identified. Third, there are increasingly recognised sex differences in the pathophysiology of AMI such that women are more likely to have AMI presentations due to coronary artery spasm, microvascular dysfunction, SCAD, or takotsubo stress–induced cardiomyopathy, for which conservative approaches with medical therapy are preferred over coronary revascularisation. The angiographic data available from our cohort support this assertion, with more women having normal coronary arteries (4.1% higher in women than men) and nonobstructive coronary artery disease (13.5% higher) among women.
      Several potential limitations of our study merit discussion. First, we were unable to assess for potential sex differences in the use of evidence-based medications, because the Ontario drug benefit program only medication coverage provides for patients older than 65 years. Second, our study focused on harder outcomes such as mortality and repeated hospitalizations as the main clinical outcomes. We acknowledge that other measures, such as health-related quality of life, may be equally important in comparing outcomes between women and men but were unable to examine such outcomes owing to the lack of data. Third, although we observed a higher prevalence of preserved left ventricular function after AMI among women, suggesting smaller infarcts in women compared with men, we did not have access to cardiac enzyme data to further explore this finding.
      In conclusion, we report that sex-based care gaps are gradually closing in Ontario on several fronts. Over the study period, we found similar adjusted mortality rates for young women and men after AMI hospitalization; however, rehospitalization rates for adverse cardiovascular events and all-cause readmission rates were significantly higher in women compared to men. By 2018, the use of coronary angiography was largely universal for both sexes, and high levels of primary and specialist care were taking place after hospitalization. The lower rate of PCI among younger women may reflect increasing recognition of alternative pathophysiology for AMI among women in this age group. Our study also underscores the need for ongoing intensive primary prevention strategies directed at younger women.

      Acknowledgements

      ICES is an independent nonprofit research institute whose legal status under Ontario’s health information privacy law allows it to collect and analyse health care and demographic data, without consent, for health system evaluation and improvement. This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health ( MOH ) and the Ministry of Long-Term Care (MLTC). Parts of this material are based on data and information compiled and provided by the MOH and CIHI. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred The authors acknowledge that the clinical registry data used in this publication are from participating hospitals through CorHealth Ontario, which serves as an advisory body to the Minister of Health and Long-Term Care (MOHLTC), is funded by the MOHLTC, and is dedicated to improving the quality, efficiency, access, and equity in the delivery of the continuum of adult cardiac, vascular, and stroke services in Ontario, Canada.

      Funding Sources

      This study was funded in part by an Innovation in Quality Award from the Division of Cardiology, University of Toronto, Toronto, Ontario, Canada, and in part by a Foundation Grant (FDN-154333) from the Canadian Institutes of Health Research. Dr Madan is supported by the Heart and Stroke Foundation Polo Chair in Cardiology at the University of Toronto. Dr Austin is supported by a Mid-Career Award from the Heart and Stroke Foundation. Dr Ko is supported by the Jack Tu Chair of Cardiovascular Outcomes Research.

      Disclosures

      The authors have no conflicts of interest to disclose.

      Supplementary Material

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      Linked Article

      • Sex Differences in Acute Myocardial Infarction: Good News and Bad News
        Canadian Journal of CardiologyVol. 38Issue 11
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          Although mortality caused by cardiovascular disease has declined over the past few decades,1 the incidence of hospitalization for acute myocardial infarction (AMI) is showing a concerning increase among young women < 55 years of age.2 Higher mortality in young women compared with young men hospitalized with AMI has been documented in numerous studies. In addition, lower rates of coronary angiography and the use of evidence-based medication in female patients with AMI have persisted for decades.1-3
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