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Our aim was to analyze the association of<jats:italic>APOE e4<\/jats:italic>with carotid atherosclerosis and the association of CRF with atherosclerosis in<jats:italic>APOE e4<\/jats:italic>carriers. A cross-sectional analysis based on a subsample of 90 participants in the Aragon Workers\u2019 Health Study was carried out. Ultrasonography was used to assess the presence of plaques in carotid territory; the submaximal Chester Step Test was used to assess CRF; and behavioral, demographic, anthropometric, and clinical data were obtained by trained personnel during annual medical examinations.<jats:italic>APOE e4e4<\/jats:italic>participants were categorized into Low-CRF (VO<jats:sub>2max<\/jats:sub>\u2009&lt;\u200935\u00a0mL\/kg\/min) and High-CRF (VO<jats:sub>2max<\/jats:sub>\u2009\u2265\u200935\u00a0mL\/kg\/min) groups. After adjusting for several confounders, compared with<jats:italic>APOE e3e3<\/jats:italic>, those participants genotyped as<jats:italic>APOE e3e4<\/jats:italic>and<jats:italic>APOE e4e4<\/jats:italic>showed an OR\u2009=\u20091.60 (95% CI 0.45, 5.71) and OR\u2009=\u20094.29 (95% CI 1.16, 15.91), respectively, for carotid atherosclerosis. Compared to Low-CRF<jats:italic>APOE e4e4<\/jats:italic>carriers, the odds of carotid plaque detection were 0.09 (95% CI 0.008, 0.98) times lower among High-CRF<jats:italic>APOE e4e4<\/jats:italic>carriers. The<jats:italic>APOE e4e4<\/jats:italic>genotype was associated with increased carotid atherosclerosis. However, CRF is a modifiable factor that may be targeted by<jats:italic>APOE e4e4<\/jats:italic>to decrease the elevation of atherosclerotic risk due to this genetic condition.<\/jats:p>","DOI":"10.1038\/s41598-022-23075-2","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T13:03:04Z","timestamp":1668085384000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiorespiratory fitness decreases the odds for subclinical carotid plaques in apolipoprotein e4 homozygotes"],"prefix":"10.1038","volume":"12","author":[{"given":"Jose Luis","family":"Perez-Lasierra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 A.","family":"Casaj\u00fas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Gonzalez-Ag\u00fcero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Miguel","family":"Arbones-Mainar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 A.","family":"Casasnovas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Laclaustra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bel\u00e9n","family":"Moreno-Franco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,11,10]]},"reference":[{"key":"23075_CR1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1161\/CIRCRESAHA.115.307611","volume":"118","author":"W Herrington","year":"2016","unstructured":"Herrington, W., Lacey, B., Sherliker, P., Armitage, J. & Lewington, S. 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