Prevalence of familial hypercholesterolemia and coronary heart disease in a tertiary referral hospital in Lithuania

Abstract Introduction Cascade screening and genetic testing have become one of the most effective methods for early detection of familial hypercholesterolemia (FH) identification and early prevention of coronary artery disease (CAD) 1. FH is usually caused by variants in the genes coding for the low-density lipoprotein receptor (LDLR). Variants in the genes for apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) have also been associated with FH 2. The results of our pilot study showed that APOB was widespread in our population. Purpose To estimate the prevalence of APOB variants in FH patient’s cohort. Methods This is a retrospective cohort study of patients with a suspected diagnosis of FH who were treated at a tertiary center between February 2022 and June 2023. Patients were included in the study according to the criteria of the Dutch Lipid Clinic (DLC). Patients were divided into three groups according to the results of the genetic tests: 1. patients with APOB variant; 2. patients without previously described variants causing FH; 3. patients with the LDLR variant. Next generation sequencing was used to sequence the coding regions. Statistical analysis was performed using SPSS 29.0.1. statistical software. Results A total of 45 patients were enrolled in this study, including 27 (60%) men and 18 (40%) women, with a mean age of 47.93 years (SD=9.391). After genetic sequencing evaluation, 7 (16%) patients were diagnosed with APOB rs5742904 variant causing FH. In addition, 2 (4%) patients were found to have an LDLR rs879254754 variant. As the patients with an LDLR variant had no CHD symptoms, no further screening was performed. No statistically significant demographic and clinical differences were found between the groups. The distribution of DLC network scores is shown in Figure 1. The only significant difference between the groups was found in the patients with the APOB rs5742904 variant, where more patients had the highest DLC score. The most frequently affected segments in both groups were: S1, S6 and S7. Conversely, the least affected segments were: S10, S14, S15 (Figure 2). A remarkable result was seen in the S2 segment, where complete occlusion occurred significantly more frequently in patients with an APOB rs5742904 variant than in patients without this variant. Conclusion Contrary to what is mentioned in the literature, there were more people with APOB rs5742904 mutation than with LDLR in our study. We also found that patients with the APOB rs5742904 mutation had statistically significantly more occlusions in the right coronary artery.