Familial hypercholesterolemia (FH) markedly increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). Despite available therapies, FH remains underdiagnosed and undertreated. The Show more
Familial hypercholesterolemia (FH) markedly increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). Despite available therapies, FH remains underdiagnosed and undertreated. The aim of this study is to characterize FH patients and to evaluate treatment response specifically in those with a confirmed pathogenic mutation. We retrospectively analysed 189 adults with clinical suspicion of FH seen at a cardiology department of a Belgian hospital between 2018 and 2024. Clinical, biochemical, and treatment data were retrieved from electronic records, and the Dutch Lipid Clinic Network (DLCN) score was calculated. Genetic testing was performed in 181 patients. Patients were stratified into primary and secondary prevention groups. The cohort comprised 116 patients (61%) in primary prevention and 73 (39%) in secondary prevention; the latter were older, predominantly male, and had more comorbidities. Genetic mutations were identified in 91 patients, most frequently in the LDL receptor gene (74%), followed by the ApoB gene (19%). Twenty-one patients had a DLCN score > 8, of whom four had no detectable pathogenic mutation. In genetically confirmed FH, mean LDL-cholesterol decreased from 267 ± 82 mg/dL at baseline to 100 ± 57 mg/dL at last follow-up, with greater reductions in secondary prevention. PCSK9 inhibitor use increased significantly during follow-up. Nevertheless, only 43% of secondary prevention patients achieved LDL-C < 55 mg/dL, and 24% of primary prevention patients reached < 70 mg/dL. FH lipid management in this real-world cohort achieved substantial LDL-C reductions, but target attainment remained suboptimal. Show less
DNA methylation changes in peripheral blood DNA have been shown to be associated with solid tumors. We sought to identify methylation alterations in whole blood DNA that are associated with breast can Show more
DNA methylation changes in peripheral blood DNA have been shown to be associated with solid tumors. We sought to identify methylation alterations in whole blood DNA that are associated with breast cancer (BC). Epigenome-wide DNA methylation profiling on blood DNA from BC cases and healthy controls was performed by applying Infinium HumanMethylation450K BeadChips. Promising CpG sites were selected and validated in three independent larger sample cohorts via MassARRAY EpiTyper assays. CpG sites located in three genes (cg06418238 in RPTOR, cg00736299 in MGRN1 and cg27466532 in RAPSN), which showed significant hypomethylation in BC patients compared to healthy controls in the discovery cohort (p < 1.00 x 10-6) were selected and successfully validated in three independent cohorts (validation I, n =211; validation II, n=378; validation III, n=520). The observed methylation differences are likely not cell-type specific, as the differences were only seen in whole blood, but not in specific sub cell-types of leucocytes. Moreover, we observed in quartile analysis that women in the lower methylation quartiles of these three loci had higher ORs than women in the higher quartiles. The combined AUC of three loci was 0.79 (95%CI 0.73-0.85) in validation cohort I, and was 0.60 (95%CI 0.54-0.66) and 0.62 (95%CI 0.57-0.67) in validation cohort II and III, respectively. Our study suggests that hypomethylation of CpG sites in RPTOR, MGRN1 and RAPSN in blood is associated with BC and might serve as blood-based marker supplements for BC if these could be verified in prospective studies. Show less