CONGRESS ABSTRACT

Background:Familial hypercholesterolemia (FH) is a major risk factor for cardiovascular disease (CVD),due to chronically elevated levels of low-density lipoprotein cholesterol (LDL-C).The objective of this report was to assess the impact of clinical and genetic factors in FH,with particular attention to cumulative LDL-C exposure,on the coronary artery calcium (CAC) score obtained by coronary computed tomography and carotid ultrasound. Methods:In this real-world cohort,CAC scores were obtained in 15 genetically confirmed FH patients, including 14 heterozygotes (LDLR variants)and one homozygote (LDLRAP1variant).None of the patients had a history of cardiovascular events at clinical evaluation. Associations between CAC score and clinical features, maximum LDL-C levels,cumulative LDL-C exposure and genetic variables was therefore investigated. Results: CAC scores were distributed as follows: 0 (N=4, 26.6%), 1–99 (N=5,33.3%), and ≥100 (N=8, 53.3%). Patients with CAC>0 showed a higher prevalence of xanthomas (N=10, 67%)and a family history of coronary artery disease(CAD) (N=12,80%).Carotid ultrasound findings showed a discordant pattern compared with CAC scores in the intermediate group. Specifically,patients with CAC scores between 1 and 99 did not exhibit significant carotid stenosis (<30%), despite evidence of coronary calcification. In contrast, patients with CAC ≥100 consistently showed more rilevant carotid stenoses (range 35-55%), indicating a more advanced atherosclerotic burden.The CAC ≥100 group exhibited the highest maximum LDL-C levels (405.1 mg/dL vs. 265.2 mg/dL in the CAC=0 group). Age at genetic diagnosis was similar between groups (41.8 years in CAC ≥100vs. 40.0 years in CAC=0 group).However, patients with CAC ≥100 started lipid-lowering therapy (LLT) later than those with CAC=0 (30.2 vs. 23.7 years), resulting in a significantly higher lifetime cumulative LDL-C exposure (17,293.0 mg/dL for CAC ≥100 vs. 11,376.5 mg/dL for CAC=0). Conclusions:Early diagnosis and timely LLT are essential for reducing lifelong cholesterol burden in FH patients.The observed heterogeneity in vascular involvement and the discordance between coronary and carotid imaging in patients with intermediate CAC scores underscore the need for an integrated imaging approach.High CAC values (≥100) identify patients with more advanced and systemic atherosclerosis, supporting the role of CAC scoring combined with carotid ultrasound for improved cardiovascular risk stratification.