Early Atherosclerosis in Familial Hypercholesterolemia Patients: Significance of Vascular Markers for Risk Stratification.

Background: Familial hypercholesterolemia (FH) is a genetic disorder that manifests as impaired low-density lipoprotein cholesterol (LDL-C) metabolism, resulting in lifelong exposure to high cholesterol levels and increased risk of cardiovascular disease (CVD). There is heterogeneity in cardiovascular risk for FH patients, so risk stratification is of utmost importance. The aim of this study was to evaluate the impact of increases in LDL-C and the impact of other CVD risk factors on vascular markers in the FH patient population.

Methods: A total of 428 patients were included in this study and divided into two groups according to age: ≤40 years in the first group and ≥41 years in the second group. Vascular markers of atherosclerosis included the common carotid artery (CCA) intima-media thickness (IMT), pulse wave velocity (PWV), flow-mediated dilation (FMD), ankle-brachial index (ABI), and cardio-vascular index (CAVI). The influence of traditional CVD risk factors on atherosclerotic changes in vascular markers was analyzed.

Results: A statistically significant difference in IMT was detected between the same sex and different age groups ( < 0.001), whereas no significant difference was detected between the sexes within each age group. In the ≤40-year-old group, the mean IMT among males was 612.5 μm (±88.2) and that among females was 580.6 μm (±77.7) ( > 0.05); in the ≥41-year-old group, the mean IMT was 697.4 μm (±138.4) for males and 700.3 μm (±114.4) for females ( > 0.05). Higher LDL-C was associated with greater IMT ( = 0.405; = 0.009) in the younger age group (≤40 years); however, in the older age group (≥41 years), this correlation was not evident ( = -0.07; = 0.596). Carotid plaque formation was more common among males (OR = 2.2; 95% CI: 1.2-4.0) and hypertensive patients (OR = 2.7; 95% CI: 1.6-4.7). Age was a mildly significant risk factor for increased ABI ( = 0.13, < 0.05). FMD was found to be impaired for all patients, and no risk factors were shown to have further influence. Age was a significant risk factor for increased arterial stiffness, as measured by both the CAVI and PWV.

Conclusions: Although vascular markers of atherosclerosis may provide a unique and valuable way to evaluate cardiovascular risk, the results of this study show that only increased IM thickness could be beneficial for risk stratification in young FH patients, whereas other vascular markers of atherosclerosis would be excessive, as they do not provide merit in risk evaluation in this population.