Lipoprotein-Specific Fatty Acid Profiles in Familial Hypercholesterolemia: Associations with Cardiovascular History and Dietary Patterns

<b>Background/Objectives</b>: Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease characterised by lifelong LDL cholesterol levels and premature presentation of cardiovascular disease if left untreated. Whether fatty acid (FA) composition in lipoproteins is modified in FH patients is not known. This study aimed to identify FA differences in low- and high-density lipoprotein (LDL and HDL, respectively) among young Spanish individuals with FH, treated as per guidelines recommendations, compared to their unaffected relatives with similar LDL concentrations in plasma. We also evaluated associations between the occurrence of cardiovascular event (CVE), dietary patterns, and the lipoprotein FA profile in FH. <b>Methods</b>: Lipoprotein FA profiles were determined by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). <b>Results</b>: In comparison to their non-FH relatives, FH patients showed changes in the FA profile, predominantly in LDL particles while HDL particles were only modestly changed. FH individuals exhibited higher concentrations of poly- and monounsaturated FAs, oleic, γ-linoleic, α-linoleic, arachidonic, and eicosapentaenoic acids (<i>p</i> < 0.05). Interestingly, FH individuals showed greater adherence to the Mediterranean diet than their non-FH relatives, with no significant differences between those with and without previous CVE. The most pronounced changes in FA profile were observed in FH patients with a history of CVE, although the event itself did not significantly modify lipoprotein FA profiles. <b>Conclusions</b>: Well treated FH patients showed a FA profile that responded to a healthier diet than their relatives with similar plasma LDL levels. The strict lifestyle and pharmacological treatment affected positively the lipoproteins of FH patients and needs to be recommended.