{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T08:05:25Z","timestamp":1792051525116,"version":"4.4.0"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"crossref","award":["704333"],"award-info":[{"award-number":["704333"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-166129"],"award-info":[{"award-number":["PJT-166129"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Familial hypercholesterolemia, a common genetic metabolic disorder characterized by high cholesterol levels, is involved in the development of atherosclerosis and other preventable diseases. Familial hypercholesterolemia can also cause tendinous abnormalities, such as thickening and xanthoma (tendon lipid accumulation) in the Achilles, which may impede tendon biomechanics. The objective of this study was to investigate the effect of cholesterol accumulation on the biomechanical performance of Achilles tendons, <jats:italic>in vivo<\/jats:italic>. 16 participants (10 men, 6 women; 37\u00b16 years) with familial hypercholesterolemia, diagnosed with tendon xanthoma, and 16 controls (10 men, 6 women; 36\u00b17 years) underwent Achilles biomechanical assessment. Achilles biomechanical data was obtained during preferred pace, shod, walking by analysis of lower limb kinematics and kinetics utilizing 3D motion capture and an instrumented treadmill. Gastrocnemius medialis muscle-tendon junction displacement was imaged using ultrasonography. Achilles stiffness, hysteresis, strain and force were calculated from displacement-force data acquired during loading cycles, and tested for statistical differences using one-way ANOVA. Statistical parametric mapping was used to examine group differences in temporal data. Participants with familial hypercholesterolemia displayed lower Achilles stiffness compared to the control group (familial hypercholesterolemia group: 87\u00b120 N\/mm; controls: 111\u00b118 N\/mm; <jats:italic>p<\/jats:italic> = 0.001), which appeared to be linked to Achilles loading rate rather than an increased strain (FH: 5.27\u00b11.2%; controls: 4.95\u00b10.9%; <jats:italic>p<\/jats:italic> = 0.413). We found different Achilles loading patterns in the familial hypercholesterolemia group, which were traced to differences in the centre of pressure progression that affected ankle moment. This finding may indicate that individuals with familial hypercholesterolemia use different Achilles loading strategies. Participants with familial hypercholesterolemia also demonstrated significantly greater Achilles hysteresis than the control group (familial hypercholesterolemia: 57.5\u00b17.3%; controls: 43.8\u00b110%; <jats:italic>p<\/jats:italic>&lt;0.001), suggesting that walking may require a greater metabolic cost. Our results indicate that cholesterol accumulation could contribute to reduced Achilles function, while potentially increasing the chance of injury.<\/jats:p>","DOI":"10.1371\/journal.pone.0257269","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T17:42:09Z","timestamp":1631814129000},"page":"e0257269","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["The effects of cholesterol accumulation on Achilles tendon biomechanics: A cross-sectional study"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6293-8270","authenticated-orcid":true,"given":"Kipling","family":"Squier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8648-1591","authenticated-orcid":true,"given":"Michael A.","family":"Hunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3686-3807","authenticated-orcid":true,"given":"Liam R.","family":"Brunham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazel","family":"Screen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3090-046X","authenticated-orcid":true,"given":"Charlie M.","family":"Waugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"issue":"11","key":"pone.0257269.ref001","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1161\/CIRCULATIONAHA.115.018791","article-title":"Prevalence of familial hypercholesterolemia in the 1999 to 2012 United States national health and nutrition examination surveys (NHANES).","volume":"133","author":"SD De Ferranti","year":"2016","journal-title":"Circulation"},{"issue":"45","key":"pone.0257269.ref002","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.1093\/eurheartj\/eht273","article-title":"Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: Guidance for clinicians to prevent coronary heart disease","volume":"34","author":"BG Nordestgaard","year":"2013","journal-title":"European Heart Journal"},{"issue":"Feb.","key":"pone.0257269.ref003","first-page":"1544","article-title":"Hyperlipidemia in Coronary Heart Disease","volume":"52","author":"JL Goldstein","year":"1973","journal-title":"J Clin Invest"},{"issue":"9","key":"pone.0257269.ref004","first-page":"39","article-title":"An overview of cholesterol management.","volume":"1","author":"RAB Schaiff","year":"2008","journal-title":"American Health & Drug Benefits."},{"issue":"6","key":"pone.0257269.ref005","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1007\/s11999-009-1151-9","article-title":"The effect of hypercholesterolemia on rotator cuff disease","volume":"468","author":"JA Abboud","year":"2010","journal-title":"Clinical Orthopaedics and Related Research"},{"key":"pone.0257269.ref006","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s004020050410","article-title":"Serum cholesterol is elevated in patients with Achilles tendon ruptures","volume":"119","author":"G Mathiak","year":"1999","journal-title":"Archives of Orthopaedic and Trauma Surgery"},{"issue":"1\u20132","key":"pone.0257269.ref007","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0009-8981(03)00075-5","article-title":"Is high concentration of serum lipids a risk factor for Achilles tendon rupture?","volume":"331","author":"T Ozgurtas","year":"2003","journal-title":"Clinica Chimica Acta"},{"issue":"2","key":"pone.0257269.ref008","first-page":"311","article-title":"Lipid Deposition in Human Tendon Xanthoma","volume":"121","author":"HS Kruth","year":"1985","journal-title":"Am J Pathol"},{"issue":"4","key":"pone.0257269.ref009","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/rheumatology\/kes395","article-title":"Occurrence of tendon pathologies in metabolic disorders.","volume":"52","author":"M Abate","year":"2013","journal-title":"Rheumatology"},{"issue":"7","key":"pone.0257269.ref010","first-page":"251","article-title":"The pathogenesis of tendolipomatosis; 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