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We aimed to assess sex differences in the association of ML-FFR<jats:sub>CT<\/jats:sub> and incident cardiovascular outcomes. We studied a retrospective cohort of consecutive patients who underwent clinically indicated CCTA and single photon emission computed tomography (SPECT). Obstructive stenosis was defined as\u2009\u2265\u200970% stenosis severity in non-left main vessels or\u2009\u2265\u200950% in the left main coronary. ML-FFR<jats:sub>CT<\/jats:sub> was computed using a machine learning algorithm with significant stenosis defined as ML-FFR<jats:sub>CT<\/jats:sub>\u2009&lt;\u20090.8. The primary outcome was a composite of death or non-fatal myocardial infarction (D\/MI). Our study population consisted of 471 patients with mean (SD) age 65 (13) years, 53% men, and multiple comorbidities (78% hypertension, 66% diabetes, 81% dyslipidemia). Compared to men, women were less likely to have obstructive stenosis by CCTA (9% vs. 18%; p\u2009=\u20090.006), less multivessel CAD (4% vs. 6%; p\u2009=\u20090.25), lower prevalence of ML-FFR<jats:sub>CT<\/jats:sub>\u2009&lt;\u20090.8 (39% vs. 44%; p\u2009=\u20090.23) and higher median (IQR) ML-FFR<jats:sub>CT<\/jats:sub> (0.76 (0.53\u20130.86) vs. 0.71 (0.47\u20130.84); p\u2009=\u20090.047). In multivariable adjusted models, there was no significant association between ML-FFR<jats:sub>CT<\/jats:sub>\u2009&lt;\u20090.8 and D\/MI [Hazard Ratio 0.82, 95% confidence interval (0.30, 2.20); p\u2009=\u20090.25 for interaction with sex.]. In a high-risk cohort of symptomatic patients who underwent CCTA and SPECT testing, ML-FFR<jats:sub>CT<\/jats:sub> was higher in women than men. There was no significant association between ML-FFR<jats:sub>CT<\/jats:sub> and incident mortality or MI and no evidence that the prognostic value of ML-FFR<jats:sub>CT<\/jats:sub> differs by sex.<\/jats:p>","DOI":"10.1038\/s41598-022-17875-9","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T12:05:34Z","timestamp":1660651534000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Sex differences in machine learning computed tomography-derived fractional flow reserve"],"prefix":"10.1038","volume":"12","author":[{"given":"Mahmoud","family":"Al Rifai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Ibrahim","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushui","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Michel","family":"Saad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talal","family":"Alnabelsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Nabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Min","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myra","family":"Cocker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Schwemmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Ramirez-Giraldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Zoghbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Mahmarian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouaz H.","family":"Al-Mallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"17875_CR1","doi-asserted-by":"publisher","first-page":"2602","DOI":"10.1016\/j.jacc.2020.03.060","volume":"75","author":"L Cho","year":"2020","unstructured":"Cho, L. et al. 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Drs Cocker, Schwemmer and Ramirez-Giraldo are employed by Siemens. All other authors have nothing to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"13861"}}