Increased CX3CL1/CX3CR1 Axis Is Related to Atherosclerosis in Subjects with Familial Combined Hyperlipidaemia, Which Is Modulated by Insulin Resistance but Not by Sex

<b>Background</b>: A major factor in the development of atherosclerosis is the presence of a chronic inflammatory state. The CX₃CL1/CX₃CR1 axis has been implicated in the development of atherosclerosis and cardiovascular disease, but until now, scarce data are available regarding the influence of the CX₃CL1/CX₃CR1 axis in familial combined hyperlipidaemia (FCH). Since FCH is associated with a high risk of cardiovascular disease, the objective of the present study was to assess the presence of alterations in the CX₃CL1/CX₃CR1 axis in patients with FCH and to evaluate the influence of insulin resistance (IR) and sex. <b>Methods</b>: A cohort of 47 subjects with FCH and 38 control subjects was included. We measured the lipid profile, glucose, and insulin levels in plasma, circulating blood CX₃CL1 levels, and CX₃CR1 mRNA expression. Carotid IMT and the presence of atheroma plaques were also evaluated. <b>Results</b>: FCH subjects showed significantly higher activation of the CX₃CL1/CX₃CR1 axis than controls. In addition, FCH individuals with IR showed the worst profile of inflammation status, higher carotid IMT, and a higher prevalence of atherosclerotic plaque compared to controls and FCH patients without IR. However, sex did not influence the CX3CL1/CX3CR1 axis. <b>Conclusions</b>: FCH patients showed an increased CX₃CL1/CX₃CR1 axis, which was positively correlated with IR, but not with sex. These data could partially explain the increased risk of cardiovascular events in primary dyslipidemic patients.