# Comorbidities and Molecular Genetics Status in Familial and Nonfamilial Hypercholesterolemia: A Single-Center Study

## TL;DR

This study compares comorbidities and genetic factors in patients with familial and non-familial hypercholesterolemia, highlighting differences in disease profiles and genetic testing outcomes.

## Contribution

The study shows that expanding genetic testing to possible FH cases could improve diagnosis and management.

## Key findings

- Patients with non-FH had higher cardiometabolic comorbidities, including chronic pancreatitis.
- Genetic testing identified pathogenic variants in over 70% of probable or definite FH cases, mainly in the LDLR gene.
- Genetic testing in possible FH cases had a 46.7% yield, suggesting broader testing could be beneficial.

## Abstract

The aim of the study was to characterize the prevalence of comorbidities and molecular genetic status in patients with familial hypercholesterolemia (FH) and non-familial hypercholesterolemia (non-FH). This cross-sectional observational study included 323 patients. Assessments comprised personal and family histories, physical examination, fasting lipid profiling, and molecular genetic testing. Patients with FH were not characterized by an increased prevalence of type 2 diabetes mellitus. In contrast, the non-FH group demonstrated a pronounced cardiometabolic comorbidity profile with a high prevalence of recurrent chronic pancreatitis. Patients with probable or definite FH had a higher prevalence of coronary heart disease and peripheral atherosclerosis, whereas myocardial infarction (MI) was common across all studied groups. Among patients with definite and probable FH, pathogenetic variants were identified in 78.2% and 71.4%, respectively, predominantly in the LDLR gene, with one variant in the APOB gene. In the possible FH group, pathogenic variants were identified in 46.7% of cases (LDLR gene in 64.3% and APOB gene in 28.6%). Patients with FH were characterized by a lower prevalence of concomitant cardiometabolic diseases. The high diagnostic yield of genetic testing in the possible FH category (figured Clinic Network score 3–5) suggests that expanding indications for molecular genetic testing to include this patient group should be considered.