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Understudied, Under-Recognized, Underdiagnosed, and Undertreated: Sex-Based Disparities in Cardiovascular Medicine

2022; Lippincott Williams & Wilkins; Volume: 15; Issue: 2 Linguagem: Inglês

10.1161/circinterventions.121.011714

1941-7632

Sonya Burgess,

Cardiovascular Issues in Pregnancy

HomeCirculation: Cardiovascular InterventionsVol. 15, No. 2Understudied, Under-Recognized, Underdiagnosed, and Undertreated: Sex-Based Disparities in Cardiovascular Medicine Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBUnderstudied, Under-Recognized, Underdiagnosed, and Undertreated: Sex-Based Disparities in Cardiovascular Medicine Sonya N. Burgess, PhD, MBChB Sonya N. BurgessSonya N. Burgess Correspondence to: Sonya N. Burgess, PhD, MBChB, Department of Cardiology, Nepean Hospital, Derby St, Kingswood, Sydney, New S Wales, Australia 2747. Email E-mail Address: [email protected] https://orcid.org/0000-0001-5262-3064 Department of Cardiology, Nepean Hospital, Sydney. University of Sydney, NSW, Australia. Originally published23 Jan 2022https://doi.org/10.1161/CIRCINTERVENTIONS.121.011714Circulation: Cardiovascular Interventions. 2022;15:e011714This article is a commentary on the followingSex Differences in Health Status and Clinical Outcomes After Nonprimary Percutaneous Coronary InterventionOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 24, 2022: Ahead of Print Outcome disparities for women with cardiovascular disease have not yet been adequately addressed. We are far from achieving this goal. Multiple contemporary studies indicate suboptimal treatment and outcomes for women with heart disease when compared with men.1–5 The Lancet women and cardiovascular disease commission succinctly describe the scale of this problem stating "cardiovascular disease in women remains understudied, under-recognized, underdiagnosed, and undertreated" in their 2021 annual report.1See Article by Hiremath et alStartling examples of the magnitude of this problem are easy enough to find. In cardiovascular trials, women are underrepresented with participation to prevalence ratio in acute coronary syndrome trials of only 0.6.6 For women, significant sex differences persist in time to presentation, and revascularization, with concerning underestimation of risk by patients and by health care workers and an average total mean delay to revascularization in ST-segment–elevation myocardial infarction of 30 minutes for women compared with men.2 Despite the fact that the leading cause of death for women globally is cardiovascular disease,1 which was responsible for 35% of all deaths in women in 2019,1 young women with myocardial infarction are significantly more likely than men to be told by their health care provider that their prodromal symptoms are not cardiac (53% versus 37%, P<0.001).3 Women with ST-segment–elevation myocardial infarction are less likely to receive angiography (adjusted odds ratio, 0.53 [95% CI, 0.41–0.69]), revascularization (adjusted odds ratio, 0.42 [95% CI, 0.34–0.52]), timely revascularization (adjusted odds ratio, 0.72 [95% CI, 0.63–0.83]), or primary percutaneous coronary intervention (adjusted odds ratio, 0.76 [95% CI, 0.61–0.95]).4 For women, incomplete revascularization is common4,5 and is associated with a poorer prognosis when compared with men (at short- and long-term follow-up, and pre and post risk multivariable risk adjustment).4,5 Adjusted rates of death, and cardiac death or myocardial infarction are 2-fold higher for women post-ST-segment–elevation myocardial infarction than they are for men.2,4,5Meaningfully, addressing these disparities has been more challenging and remains a work in progress. Well powered equity focused studies are important. We must understand what drives outcome differences to successfully decrease them.In the current issue of Circulation: Cardiovascular Interventions, Hiremath et al7 present research exploring sex-based differences in clinical outcomes and health status of patients treated with nonprimary percutaneous coronary intervention. The authors provide post hoc analysis of the CPORT-E (Cardiovascular Patient Outcomes Research Team Non-Primary Percutaneous Coronary Intervention) trial and focus on health outcome and symptom burden. They provide important equity focused research investigating outcomes of more stable ischemic heart disease (IHD) cohort in a large US population. Hiremath et al7 found health status and symptom burden improved for both men and women post-percutaneous coronary intervention but also demonstrated major sex-based differences in health status both pre and post referral for percutaneous coronary intervention.The study's primary outcome and major finding was that fewer women were angina free than men at the time of referral for angioplasty 26.2% versus 29.8%, at 6 weeks (71.6% and 78.7%) and at 9 months (78.1% and 83.0%; P<0.001 for all). These differences persisted post risk adjustment, freedom from angina in women compared with men was 34% less likely at 6 weeks (odds ratio, 0.66 [95% CI, 0.61–0.71]; P<0.001) and 32% less likely at 9 months (odds ratio, 0.68 [95% CI, 0.62–0.74]; P<0.001). Detailed assessment of potential contributing factors was included, and Hiremath et al concluded that women in this 18 867-patient cohort had poorer health status before and after treatment.Poor health status, including angina free status, is important and has previously been associated with poor clinical outcomes such as major adverse cardiac events.7 While Hiremath et al acknowledge their study was not powered to detect significant differences in major adverse cardiac events in this low-risk cohort, and significant differences in major adverse cardiac events post risk adjustment were not evident, this data does provide multiple other insights.Hiremath et al found poorer prescriber adherence to guideline recommended drugs for women with IHD with respect to dual anti-platelet therapy and statins. These finding echo those of other research investigating sex-based prescribing disparities in acute coronary syndrome cohorts.1,4,5Hiremath et al's data also suggests clinicians may have a higher threshold for initiating investigation and treatment for IHD in women compared with men, 1 in 3 men were angina free at first referral compared with 1 in 4 women (P<0.001). This disparity in angina free status became larger post treatment, suggesting rather than closing the gap current management decisions are making it wider.Early detection and successful management of cardiovascular disease in women is essential to address outcome disparities including symptom burden. Underestimation of risk and under treatment continues to contribute to poor outcomes for women with cardiovascular disease, particularly in well powered studies of higher risk acute coronary syndrome cohorts.1,2,4,5 Hiremath et al7 have demonstrated even in more stable IHD cohorts significant differences are evident. Innovative solutions are needed.Health care equity issues extend well beyond those related to sex. Importantly in the CPORT-E cohort, women were likely to be Black than men. Outcome disparities for women of non-European descent can become logarithmic in their magnitude. Appropriate solutions are desperately needed, particularly for Black or African American women, Indigenous women, American Indian women, Latinx women, Spanish women, Alaskan Native women, Pasifika women, Australian Aboriginal and Torres Strait Islander women, and Maori women.8 All are underrepresented in our workforces and over-represented in our adverse outcome data.8 All have barriers to optimal cardiovascular health that begin with barriers to access, models of care, inclusion, and self-determination.8 Transgenerational trauma also continues to contribute to contemporary health care inequities for many women and their families.Hiremath et al by studying a contemporary nonprimary percutaneous coronary intervention population demonstrate sex differences for more stable IHD patients are also evident pre and post revascularization and need to be addressed. The authors call for additional investigation into therapies that address pathophysiologic and psychosocial causes of poor health status in women with coronary artery disease.New innovations are undoubtably important, but we must also apply the evidence-based medicine we do have in a more systematic manner, for women and patients less likely to receive guideline-based care. Including more consistent referral and treatment thresholds, better use of radial access, potent P2Y12 inhibitors, referral to cardiac rehab, statin therapy, and more aggressive management of cardiac risk factors particularly hypertension and body mass index. It is critically important to use well the established tools we already have and consistently treat patients in accordance with accepted guidelines.Nondiverse workforces frequently observed in cardiology may also have an impact. A large observational study (n=581 797) found the poorer outcomes observed for female AMI patients were not evident when female patients were treated by female doctors.9 Data demonstrating female physicians and cardiologists adhere more closely to guidelines and evidence-based practice, spend more time communicating with their patients, and have lower patient mortality and readmission rates provide insights into the factors that contribute to improved outcomes for female patients treated by female doctors.8,10Comorbidities and advanced age are frequently hypothesized to play a primary role in sex-based outcome disparities, however Hiremath et al7 found significant sex-based differences persist following risk adjustment. These are not new findings they are findings in keeping with a large number of contemporary high-quality studies reporting significant inequities which persist following careful multivariate risk analysis.1–5 Inaccurate assumptions regarding causality limit our ability to address inequity. Data disaggregated by sex until recently has been lacking, and major trials have historically included a disproportionately low number of women.6 This limits our ability to meaningfully address gender-associated outcome differences, or to identify what drives these outcome disparities.6Hiremath et al's7 study is equity focused, timely and relevant, it serves as a reminder that we are far from closing the gender gap for women with cardiovascular disease and is a call to action to keep working toward better evidence-based solutions and to more consistent and equitable management strategies.Article InformationDisclosuresDr Burgess has previously received speakers honoraria from Astra Zeneca, Novartis, and Women as One. She has in 2021 received a research award and grant from Women as One.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Disclosures, see page 129.Correspondence to: Sonya N. Burgess, PhD, MBChB, Department of Cardiology, Nepean Hospital, Derby St, Kingswood, Sydney, New S Wales, Australia 2747. Email sonya.[email protected]nsw.gov.auReferences1. Vogel B, Acevedo M, Appelman Y, Bairey Merz CN, Chieffo A, Figtree GA, Guerrero M, Kunadian V, Lam CSP, Maas AHEM, et al. The Lancet women and cardiovascular disease commission: reducing the global burden by 2030.Lancet. 2021; 397:2385–2438. doi: 10.1016/S0140-6736(21)00684-XCrossrefMedlineGoogle Scholar2. Stehli J, Martin C, Brennan A, Dinh DT, Lefkovits J, Zaman S. Sex differences persist in time to presentation, revascularization, and mortality in myocardial infarction treated with percutaneous coronary intervention.J Am Heart Assoc. 2019; 8:1–9. doi: 10.1161/JAHA.119.012161LinkGoogle Scholar3. Lichtman JH, Leifheit EC, Safdar B, Bao H, Krumholz HM, Lorenze NP, Daneshvar M, Spertus JA, D'Onofrio G. Sex differences in the presentation and perception of symptoms among young patients with myocardial infarction.Circulation. 2018; 137:781–790. doi: 10.1161/CIRCULATIONAHA.117.031650LinkGoogle Scholar4. Khan E, Brieger D, Amerena J, Atherton JJ, Chew DP, Farshid A, Ilton M, Juergens CP, Kangaharan N, Rajaratnam R, et al. Differences in management and outcomes for men and women with ST-elevation myocardial infarction.Med J Aust. 2018; 209:118–123. doi: 10.5694/mja17.01109CrossrefMedlineGoogle Scholar5. Burgess SN, Juergens CP, Nguyen TL, Leung M, Robledo KP, Thomas L, Mussap CJ, Zaman SJ, Lo STH, French JK. Comparison of late cardiac death and myocardial infarction rates in women vs men with st-elevation myocardial infarction.Am J Cardiol. 2020; 128:120–126. doi: 10.1016/j.amjcard.2020.04.044CrossrefMedlineGoogle Scholar6. Scott PE, Unger EF, Jenkins MR, Southworth MR, McDowell TY, Geller RJ, Elahi M, Temple RJ, Woodcock J. Participation of women in clinical trials supporting FDA approval of cardiovascular drugs.J Am Coll Cardiol. 2018; 71:1960–1969. doi: 10.1016/j.jacc.2018.02.070CrossrefMedlineGoogle Scholar7. Hiremath PG, Aversano T, Spertus JA, Lemmon CC, Naiman D, Czarny M. Sex differences in health status and clinical outcomes after nonprimary percutaneous coronary intervention.Circ Cardiovasc Interv. 2022; 15:e011308. doi: 10.1161/CIRCINTERVENTIONS.121.011308LinkGoogle Scholar8. Burgess S, Morice M-C, Alasnag M, Grines C, Mehran R, Zaman S. Women and cardiology: the value of diversity.Hear Lung Circ. 2021; 30:3–5. doi: 10.1016/j.hlc.2020.06.027CrossrefMedlineGoogle Scholar9. Greenwood BN, Carnahan S, Huang L. Patient–physician gender concordance and increased mortality among female heart attack patients.Proc Natl Acad Sci. 2018; 201800097. doi: 10.1073/pnas.1800097115Google Scholar10. Burgess S, Shaw E, Ellenberger K, Thomas L, Grines C, Zaman S. Women in medicine.J Am Coll Cardiol. 2018; 72:2663–2667. doi: 10.1016/j.jacc.2018.08.2198CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Fritzsche M, Akyüz K, Cano Abadía M, McLennan S, Marttinen P, Mayrhofer M and Buyx A (2023) Ethical layering in AI-driven polygenic risk scores—New complexities, new challenges, Frontiers in Genetics, 10.3389/fgene.2023.1098439, 14 Gauci S, Cartledge S, Redfern J, Gallagher R, Huxley R, Lee C, Vassallo A and O'Neil A (2022) Biology, Bias, or Both? The Contribution of Sex and Gender to the Disparity in Cardiovascular Outcomes Between Women and Men, Current Atherosclerosis Reports, 10.1007/s11883-022-01046-2, 24:9, (701-708), Online publication date: 1-Sep-2022. Samaei M, Jenkins M and McGregor A (2022) Closing the gap: How women can benefit more from science, research, policies, and health services, Med, 10.1016/j.medj.2022.04.012, 3:5, (302-308), Online publication date: 1-May-2022. Related articlesSex Differences in Health Status and Clinical Outcomes After Nonprimary Percutaneous Coronary InterventionPranoti G. Hiremath, et al. Circulation: Cardiovascular Interventions. 2022;15 February 2022Vol 15, Issue 2 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCINTERVENTIONS.121.011714PMID: 35067073 Originally publishedJanuary 23, 2022 KeywordswomensexEditorialsangioplastycardiovascular diseasedeathPDF download Advertisement SubjectsDisparitiesHealth EquityPercutaneous Coronary InterventionRevascularizationTreatment