Coronary Artery Calcium Is Independently Associated with Arterial Stiffness and LDL Cholesterol Burden in Patients with Familial Hypercholesterolemia

<b>Background:</b> Familial hypercholesterolemia (FH) is a genetic disorder characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) and exposing patients to higher risk of early cardiovascular (CV) atherosclerotic diseases. Though the estimated prevalence of heterozygous FH (HeFH) is about 1 in 200, FH is still underdiagnosed and undertreated. Coronary artery calcification (CAC) assessment and arterial stiffness measured as pulse wave velocity (PWV) have demonstrated their accuracy in CV risk assessment, but data on HeFH are lacking. This study aims to evaluate CAC and PWV in a population of HeFH patients to improve risk stratification and therapy timing and setting. <b>Methods:</b> One hundred genetically characterized HeFH patients, regularly followed up since diagnosis, were recruited at our outpatient clinic. In all patients, CAC, PWV measurement, and LDL-C burden calculation were assessed. <b>Results</b>: The mean age was 45 ± 16 years. A total of 25% of patients had hypertension, and 15% were in secondary prevention. Through univariate analysis, we found strong positive correlations between CAC and both PWV (r = 0.52 <i>p</i> > 0.0001) and total LDL-C burden (r = 0.52 <i>p</i> < 0.0001). No other associations with lipid parameters were found. Multivariate analysis showed that CAC was independently associated with PWV adjusted for sex, total LDL-C burden, systolic blood pressure, smoking, LDL-C, HDL-C, and statin treatment. <b>Conclusions</b>: Arterial stiffness is strongly associated with CAC in HeFH patients with similar total LDL-C burden and CV risk profiles. Personalized risk assessment based on arterial stiffness and CAC evaluation enhances the stratification and management of cardiovascular risk in FH patients, supporting individualized therapeutic approaches.