Screening for subclinical atherosclerosis in patients clinically diagnosed with familial hypercholesterolemia and determination of imaging-guided patient management strategy

Introduction: Familial hypercholesterolemia (FH) is a monogenic dyslipidemia characterized by elevated plasma LDL-C levels, leading to early cardiovascular disease. The Dutch Lipid Clinic Network (DLCN) score is the most widely used clinical scoring system in current practice. Subclinical atherosclerosis is defined as the detection of atheromatous plaques in arterial territories, such as coronary, carotid or iliofemoral, before a symptom or event occurs. It is an early indicator of atherosclerotic burden. In this study, we investigated the presence of subclinical atherosclerosis and in FH patients with a definite or probable clinical diagnosis according to DLCN score. We also tried to identify independent predictors of subclinical atherosclerosis. Additionally, we aimed to demonstrate how the presence of subclinical atherosclerosis affects treatment strategies. Methods: This study is a single-center, prospective, and cross-sectional investigation involving a cohort of 215 FH patients. These patients categorized as primary prevention patients. Among them, 120 patients received a definite clinical diagnosis, while 95 patients received a probable clinical diagnosis based on the DLCN score. Carotid USG and Femoral USG were performed to screen for subclinical atherosclerosis and CAC score was calculated by non- contrast CT. Apo A-I, Apo B and Lp (a) measurements were analyzed by nephelometric method. Results: The study population consisted of 136 (63%) women and 79 (37%) men. The mean age was 54 years (43-62) and the stigmata rate was 18%. Initially, 17% of patients were on aspirin, and 32% were receiving statin treatment; however, following subclinical atherosclerosis screening, these proportions significantly increased (aspirin rate: %32 and statin rate %96). Within the population 148 patients (69%) had subclinical atherosclerosis in at least one site. Upon regional analysis, subclinical atherosclerosis rates were 48% in the coronary arteries, 47.5% in the carotid bifurcation region, and 40.5% in the femoral bifurcation region. Additionally, 25% of patients had atherosclerosis at one site, 27% at two sites, and 17% at all three sites. Age, male gender, pretreatment LDL-C level, Apo A-I/Apo B ratio and DM were identified as independent predictors of the presence of subclinical atherosclerosis in the FH patients. Furthermore age, male gender, pretreatment nonHDL-C level, Lp (a) ≥ 30 mg/dl and presence of femoral plaque were identified as independent predictors of coronary atherosclerosis. Conclusion: Subclinical atherosclerosis is prevalent among FH patients, and this study has identified independent predictors associated with presence of subclinical atherosclerosis. However, despite this heightened risk, medication utilization among these patients remains below optimal levels and only a small proportion of the population has achieved their treatment goals. Our study underscores the impact of subclinical atherosclerosis on treatment strategies, as evidenced by the significant increase in statin and aspirin utilization observed post-screening.