Akbar Shafiee

Hamidreza Goodarzynejad

Mahmood Sheikh Fathollahi

Frontiers in Cardiovascular Medicine

Directory of Open Access Journals

TYPE EditorialPUBLISHED 22 May 2023| DOI 10.3389/fcvm.2023.1220439EDITED AND REVIEWED BYTommaso Gori,Johannes Gutenberg University Mainz,Germany*CORRESPONDENCEHamidreza Goodarzynejadhamidreza.goodarzynejad@gmail.comRECEIVED 10 May 2023ACCEPTED 12 May 2023PUBLISHED 22 May 2023CITATIONGoodarzynejad H, Sheikh Fathollahi M andShafiee A (2023) Editorial: The role of sex incoronary artery disease.Front. Cardiovasc. Med. 10:1220439.doi: 10.3389/fcvm.2023.1220439COPYRIGHT© 2023 Goodarzynejad, Sheikh Fathollahi andShafiee. This is an open-access articledistributed under the terms of the CreativeCommons Attribution License (CC BY). The use,distribution or reproduction in other forums ispermitted, provided the original author(s) andthe copyright owner(s) are credited and that theoriginal publication in this journal is cited, inaccordance with accepted academic practice.No use, distribution or reproduction ispermitted which does not comply with theseterms.Frontiers in Cardiovascular MedicineEditorial: The role of sex incoronary artery diseaseHamidreza Goodarzynejad1,2*, Mahmood Sheikh Fathollahi3and Akbar Shafiee21Family Medicine Teaching Unit, North York General Hospital, Toronto, Canada, 2Tehran Heart Center,Tehran University of Medical Sciences, Tehran, Iran, 3Rajaei Cardiovascular, Medical and Research Center,Iran University of Medical Sciences, Tehran, IranKEYWORDScoronary artery disease, gender, sex, ischemic heart disease, coronary atherosclerosis,coronary heart disease, myocardial infarctionEditorial on the Research TopicThe Role of Sex in Coronary Artery DiseaseIntroductionAlthough coronary artery disease (CAD) has been primarily considered as a man’sdisease and for long time women were underrepresented in CAD clinical trials, women,as compared to men, have shown far worse clinical outcomes following CAD-relatedevents (1). Sex constitutes an easily available and cost-free biological variable thatfrequently acts as a disease modulator; however, investigators and reviewers are often at aloss about the issue of sex differences (2). The present Frontiers Research Topic aimed toanalyze the differences between men and women in awareness, risk factors,pathophysiology, prevention, clinical presentation, diagnostic evaluation, and managementof CAD. In this regard, an international selection of investigators contributed originaldata and up to date reviews to increase our current understanding on the role of sex in CAD.Seven articles included in our special issue that cover the main themes of the topic.Helman et al. offer an overview of sex differences within the mammalian stress responseand the interactions between sex, stress and CAD. The authors assume that the biology ofstress (and its influences on health and disease) must be viewed as distinct in men andwomen. They suggest that not only does repetitive or continued stress promote thedevelopment of chronic diseases including CAD, acute mental stress also acts as a potenttrigger and is strongly associated with cardiovascular events with greater propensity tomicrovascular dysfunction and ischemia in women. There is evidence that a relationbetween mental stress with major adverse cardiac events exists only in women but notmen (3). Chronic forms of psychosocial stress also appear to have greater effects onwomen compared to men. For example, a 2- to 4-fold higher risk of stress-dependentmyocardial infarction in women (4, 5), and up to 10-fold higher risk of Takotsubosyndrome—a stress-dependent coronary-myocardial disorder most prevalent in post-menopausal women—(6) has been reported. By discussing the multiple mechanisms bywhich chronic stress can influence pathophysiological aspects of cardiovascular disorders01 frontiersin.orgGoodarzynejad et al. 10.3389/fcvm.2023.1220439and the effects of sex on them, the authors highlighted how a moredetailed exploration into the mechanisms of sex and stress biologyis essential to develop targeted approaches to CAD prevention andtherapy in men and women separately. They also emphasized thatapart from clear sex-related biological differences, stress responsesare similarly influenced by external determinants such as socio-cultural and economic factors. Therefore, significantimprovements in the prevention of chronic diseases includingCAD in women can be made at fundamental socio-economiclevels.Despite receiving growing attention in recent years, healthdisparities in women presenting with CAD still exist causingworse clinical outcomes in women than in men (7, 8). Higherpatient and system delays are still experienced by women andthey continue to receive less aggressive drugs and less invasivetreatments. Using data analytics of electronic medical records of∼32,000 patients with CAD treated at the UCSF Medical Centerover an 8-year period, Panahiazar et al. studied the gender-basedtime discrepancy in diagnosis of CAD. Of patients whoeventually diagnosed with severe CAD, there was a greater delayin the time between prescribing aspirin and/or any othercardiovascular medications and prescribing beta-blockers—aknown drug to reduce cardiovascular risk—or ordering theelectrocardiogram test for women. Women, compared to men,also showed a significantly longer interval between their firstphysician encounter indicative of CAD and their first diagnosticcardiac catheterization, while the time difference from diagnosticCardiac Catheterization to coronary artery bypass graft (CABG)was not statistically significant. In another article in thecollection, using data of female patients assigned to the primarypercutaneous coronary intervention (pPCI) arms of threerandomized studies, Motovska et al. compared the combinedcohort of patients (n = 159) enrolled in the PRAGUE-1 (studyperiod: 1997–1999; female/male ratio = 29/72) and the PRAGUE-2 (1999–2002; 130/299) with those of the PRAGUE-18 study(2013–2016; 299/921). The results showed that the risk of deathwithin 30-days after the index event altered significantly from 8.2% in women undergoing pPCI in the PRAGUE-1 and -2 studiesto 3.3% in women enrolled to the PRAGUE-18 study. However,the proportion of women with time to reperfusion more than 6 hafter the onset of symptoms remained unacceptably high. Theauthors concluded that progress in the management of STelevation myocardial infarction (STEMI), includingadvancements in procedural instrumentation and technique, andadjuvant antiplatelet therapy, have brought about favorableprognoses for women with acute MI. Despite this, delayeddiagnosis and medical care-related delays make the outcomeworse in a large proportion of women.Myocardial infarction with non-obstructive coronary arteries(MINOCA) is a syndrome often overlooked. In this topic,Yildiz et al. comprehensively reviewed its prevalence,characteristics, prognosis, diagnosis, and treatment. Theydiscussed that this syndrome typically affects women with aheterogenous working diagnosis that is understudied,underdiagnosed, and undertreated, and that it has bad prognosissimilar to patients with MI and obstructive CAD. They providedFrontiers in Cardiovascular Medicine 02evidence that a wide variety of underlying pathophysiologicmechanisms can lead to MINOCA and MINOCA-mimickers.Thus, to guide treatment, it is essential to detect the underlyingmechanism using diagnostic workup including multimodalityadvanced imaging. Further researches are required to guide thespecific treatment of the underlying mechanism.Notably, non-obstructive CAD is linked to coronarymicrovascular dysfunction (CMD) that is more often seen inwomen compared to men (9). As women with chest pain andnon-obstructive CAD have a two-fold increased risk to developobstructive CAD events in the next 5–8 years (10), the earlydiagnosis of CMD, by measuring coronary blood flow reserve,and a better understanding of underlying contributors to sexdifferences in CMD is warranted. In this context, sexdifferences in contributors to CMD were investigated byKwan et al., comparing relations between myocardial perfusionreserve index (MPRI), semi-quantitative measure of perfusionvalidated as a measure of CMD (11), vs. traditionalcardiovascular risk factors and markers of cardiac structure/function in sex-stratified populations. The underlyingpathophysiology of CMD was intriguingly proposed by theauthors to differ between men and women, as MPRI showed anassociation with T1 times and LVMI in women vs. T1 timesand aortic diameter in men. In addition, reductions in MPRI inmen was associated with diabetes and hyperlipidemia while itwas not associated with any of traditional cardiovascular riskfactors in women.In a meta-analysis of systematic reviews, Leng et al., for thefirst time, explored the sex-dependent association of periodontaldiseases with CVD. It was observed that there is a significantassociation between periodontal disease and the risk of CVDindependent of sex, with a summary odds ratio of 1.22 forwomen and 1.11 for men. However, sex differences were foundin the CAD subgroup analysis where men with periodontaldisease in comparison with women, showed a higher risk ofCAD. The authors proposed that the sex-specific associationbetween periodontal disease and CVD may be different invarious types of CVDs indicating the need for further analysis inthe future. Finally, given that heart failure (HF) is a commoncomplication in patients with acute coronary syndrome (ACS),particularly in women, Yan et al. examined the risk predictorsfor new-onset HF after ACS by developing a simple nomogramto optimize the clinical management for women. They statedthat the novel nomogram can help identify female individualswith ACS who are at high risk of developing HF after dischargeand facilitate communication between female patients andphysicians.Overall, the present Research Topic expand our knowledge onsex differences in the CAD. Obviously, the articles collected hererepresent only a small glimpse of the many lines of research thatare ongoing on this topic. As recently illustrated in acomprehensive review, sex and gender can both impact onalmost every organ and every disease (12). Not only is itessential to include sex or gender as a variable in the design ofstudies, but also is of importance to perform sex/gender stratifiedanalyses, as these can reveal other influences. In fact, in Mayfrontiersin.orgGoodarzynejad et al. 10.3389/fcvm.2023.12204392014, the National Institutes of Health (NIH) announced theintention to “require applicants to consider sex as a biologicalvariable (SABV) in the design and analysis of NIH-fundedresearch involving animals and cells.” (13) To provide morereliable evidence for CAD diagnosis and treatment with the goalof personalized therapeutics in both men and women, morewomen of all age groups must be included in future randomizedcontrolled trials.Author contributionsHG led the editorial preparation. MS and AS provided criticalfeedback. All authors contributed to the article and approved thesubmitted version.Frontiers in Cardiovascular Medicine 03Conflict of interestThe authors declare that the research was conducted in theabsence of any commercial or financial relationships that couldbe construed as a potential conflict of interest.Publisher’s noteAll claims expressed in this article are solely those of theauthors and do not necessarily represent those of their affiliatedorganizations, or those of the publisher, the editors and thereviewers. Any product that may be evaluated in this article, orclaim that may be made by its manufacturer, is not guaranteedor endorsed by the publisher.References1. Maas AH, Appelman YE. Gender differences in coronary heart disease. NethHeart J. (2010) 18(12):598–602. doi: 10.1007/s12471-010-0841-y2. Bhargava A, Arnold AP, Bangasser DA, Denton KM, Gupta A, Hilliard KrauseLM, et al. Considering sex as a biological variable in basic and clinical studies: anendocrine society scientific statement. Endocr Rev. (2021) 42(3):219–58. doi: 10.1210/endrev/bnaa0343. Widmer RJ, Prasad M, Gomaa M, Sara JDS, Reriani MK, Lerman LO, et al.Vascular reactivity to mental stress is associated with poor cardiovascular diseaseoutcomes in females following acute coronary syndrome. Coron Artery Dis. (2020)31(3):300–5. doi: 10.1097/MCA.00000000000008314. Vaccarino V, Wilmot K, Al Mheid I, Ramadan R, Pimple P, Shah AJ, et al. Sexdifferences in mental stress-induced myocardial ischemia in patients with coronaryheart disease. J Am Heart Assoc. (2016) 5(9):e003630. doi: 10.1161/JAHA.116.0036305. Vaccarino V, Sullivan S, Hammadah M, Wilmot K, Al Mheid I, Ramadan R, et al.Mental stress-induced-myocardial ischemia in young patients with recent myocardialinfarction: sex differences and mechanisms. Circulation. (2018) 137(8):794–805.doi: 10.1161/CIRCULATIONAHA.117.0308496. Lyon AR, Citro R, Schneider B, Morel O, Ghadri JR, Templin C, et al.Pathophysiology of takotsubo syndrome: JACC state-of-the-art review. J Am CollCardiol. (2021) 77(7):902–21. doi: 10.1016/j.jacc.2020.10.0607. Haider A, Bengs S, Luu J, Osto E, Siller-Matula JM, Muka T, et al. Sex and genderin cardiovascular medicine: presentation and outcomes of acute coronary syndrome.Eur Heart J. (2020) 41(13):1328–36. doi: 10.1093/eurheartj/ehz8988. Khamis RY, Ammari T, Mikhail GW. Gender differences in coronary heartdisease. Heart. (2016) 102(14):1142–9. doi: 10.1136/heartjnl-2014-3064639. Kothawade K, Bairey Merz CN. Microvascular coronary dysfunction in women:pathophysiology, diagnosis, and management. Curr Probl Cardiol. (2011) 36(8):291–318. doi: 10.1016/j.cpcardiol.2011.05.00210. EUGenMed T, Group CCS, Regitz-Zagrosek V, Oertelt-Prigione S, Prescott E,Franconi F, et al. Gender in cardiovascular diseases: impact on clinicalmanifestations, management, and outcomes. Eur Heart J. (2015) 37(1):24–34.doi: 10.1093/eurheartj/ehv59811. Bakir M, Wei J, Nelson MD, Mehta PK, Haftbaradaran A, Jones E, et al. Cardiacmagnetic resonance imaging for myocardial perfusion and diastolic function-referencecontrol values for women. Cardiovasc Diagn Ther. (2016) 6(1):78–86. doi: 10.3978/j.issn.2223-3652.2015.09.0312. Mauvais-Jarvis F, Bairey Merz N, Barnes PJ, Brinton RD, Carrero JJ, DeMeo DL,et al. Sex and gender: modifiers of health, disease, and medicine. Lancet. (2020) 396(10250):565–82. doi: 10.1016/S0140-6736(20)31561-013. Arnegard ME, Whitten LA, Hunter C, Clayton JA. Sex as a biological variable: a5-year progress report and call to action. J Women Health. (2020) 29(6):858–64.doi: 10.1089/jwh.2019.8247frontiersin.org

Editorial: The role of sex in coronary artery disease

https://www.frontiersin.org/articles/10.3389/fcvm.2023.1220439/pdf

Editorial: The role of sex in coronary artery disease

Abstract

Similar works

Full text

Available Versions

Directory of Open Access Journals