The effects of cholesterol accumulation on Achilles tendon biomechanics: A cross-sectional study

Abstract

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, in vivo. 16 participants (10 men, 6 women; 37±6 years) with familial hypercholesterolemia, diagnosed with tendon xanthoma, and 16 controls (10 men, 6 women; 36±7 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±20 N/mm; controls: 111±18 N/mm; p = 0.001), which appeared to be linked to Achilles loading rate rather than an increased strain (FH: 5.27±1.2%; controls: 4.95±0.9%; p = 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±7.3%; controls: 43.8±10%; p<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.

Hyperlipidemia in tendon injury: chronicles of low-density lipoproteins

“…Interestingly, the LDL level had a direct impact on patellar tendon stiffness independently of body mass index. Similarly, hyperlipidemia and cholesterol accumulation were the major contributing factors to Achilles’ tendon injury in patients with familial hypercholesterolemia and tendinous xanthomas (Squier et al 2021 ).…”

“…Decreased stiffness can be possible be linked to different loading rate, rather than an increase in tendon strain. Concluding that increased cholesterol and lipid levels alter tendon structure and predispose tendinous injury (Squier et al 2021 ) N = 1208 familial hypercholesterolemia patients Analyzed genetic variants in LDL oxidation pathways Higher number of risk alleles were found in the oxLDL pathway in association with presence of tendon xanthomas (Oosterveer et al 2010 ) N = 14 heterozygous FH patients Measured Achilles tendon diameter on sonography, total RNA pools and also intracellular lipid contents It was shown that macrophages in patients with Achilles xanthomas present had differential gene expression in the presence of oxLDL, proposing that xanthoma formation in tendons is associated with increased levels of lipids and oxLDL (Artieda, et al 2005 ) N = 80 patients with heterozygous FH Measured levels of oxLDL, autoantibodies against oxLDL and LDL associated Phospholipase A2 Antibodies formed against oxLDL are independently associated with Achilles tendon thickness suggesting that they may play a role in Achilles tendon xanthomas in FH patients (Tsouli et al 2006 ) Literature review Compiled articles discussing the pathogenesis, detection and treatment Achilles tendon is the most common site for xanthoma formation. LDL is deposited into the tissues where it is converted into oxLDL by macrophages within tendon tissue (Tsouli et al 2005 ) …”

Minimally invasive excision and reconstruction of Achilles tendon xanthoma using free autologous semitendinosus tendon transfer: a surgical technique

“…Xanthomas have also been reported in the plantar fascia, fascia and periosteum overlying the lower tibia, the peroneal tendons, the triceps tendon and the patellar tendon [ 6 ]. Mechanical stress and neovascularization are considered as predisposing factor for xanthomas growth [ 7 ]. In addition to tendinous xanthomas, several types of xanthomas can be found such as tuberous and eruptive xanthoma, eyelid xanthelasma and xanthoma planum [ 6 ].…”

“…In addition to tendinous xanthomas, several types of xanthomas can be found such as tuberous and eruptive xanthoma, eyelid xanthelasma and xanthoma planum [ 6 ]. Xanthomas are frequently associated with hyperlipidemia, and high levels of triglycerides and total cholesterol: within families affected by familial hypercholesterolemia and type II hyperlipoproteinemia Achilles tendon xanthomas are frequent, probably because of the low-density lipoprotein storage in the tendon [ 7 ]. Furthermore, the presence of endothelial cells and macrophages is the main factors contributing to the pathogenesis of tendon xanthomas [ 8 ].…”

Does Additional Dietary Supplementation Improve Physiotherapeutic Treatment Outcome in Tendinopathy? A Systematic Review and Meta-Analysis

“…Tendinopathy is a common tendon disorder accounting for around 30% of complaints related to musculoskeletal pain and functional limitations [ 1 ]. The aetiology of this tendon pathology is multifactorial, including mechanical overuse [ 1 , 2 ] and metabolic disorders [ 3 , 4 , 5 ]. Usually, tendinopathies are characterized by tendon pain and impaired function, which also leads to a reduction in exercise participation in tendinopathic patients [ 6 ].…”