HDL cholesterol as an associate of prevalent coronary artery disease in heterozygous Familial hypercholesterolemia beyond LDL cholesterol.

PURPOSE: Low high-density lipoprotein cholesterol (HDL-C) levels have been associated with increased risk of coronary artery disease (CAD) in the general population. We examined the association between HDL-C levels and CAD prevalence in adult patients with heterozygous familial hypercholesterolemia (HeFH) in the HELLAS-FH registry. METHODS: Adult patients with HeFH were categorized into quartiles based on baseline (i.e., before any treatment) HDL-C levels. Patient demographics, lipid profile, CAD risk factors and CAD prevalence were analyzed. RESULTS: Patients (n = 1867; 960 males; mean age 51 ± 14 years) were divided into quartiles based on baseline HDL-C levels: Q1 (35 ± 5 mg/dL), Q2 (45 ± 2 mg/dL), Q3 (54 ± 3 mg/dL) and Q4 (70 ± 10 mg/dL). Lower HDL-C quartiles were associated with increased prevalence of CAD risk factors i.e. hypertension, type 2 diabetes (T2D), smoking and body mass index ≥ 25 kg/m2 compared with higher ones. The lowest HDL-C quartile was associated with the highest prevalence of established total (47.6%) and premature CAD (39.7%) among HeFH patients (p < 0.01 compared with all other quartiles). Multivariate logistic regression indicated 5% lower odds of prevalent CAD for each 1 mg/dL higher HDL-C after adjusting for major ASCVD risk factors, including triglycerides. This association of HDL-C was linear and persisted across patient subgroups based on sex, age, hypertension, smoking and T2D as well as across low-density lipoprotein cholesterol quartiles. CONCLUSION: An independent inverse linear association was observed between HDL-C concentrations and CAD prevalence in patients with HeFH. These findings emphasize the importance of considering HDL-C levels in CAD risk stratification of patients with HeFH.